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Fluocinolone acetonide topical is used to treat skin discomforts such as swelling, itching and redness by activating the natural substances in the skin. Several process-related impurities and degradation products are identified and reported. But hydroperoxide impurities in Fluocinolone acetonide topical solution are not reported anywhere. In this study, we identify two potential genotoxic isomeric hydroperoxide impurities in Fluocinolone acetonide topical solution by Liquid Chromatography Mass Spectrometry analysis. A possible mechanism for the formation of these two novel hydroperoxide impurities is based on the neighboring group participation effect of adjacent hydroxyl group (Internal SN2) which results in the loss of fluorine atom and formation of epoxide intermediate followed by the addition of the HOOH group. Since most of the hydroperoxide impurities are genotoxic in nature, one should eliminate these impurities from Active Pharmaceutical Ingredient (API) or protect the formulation product from these oxidative impurities., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: The aim of our prospective off-label, interventional clinical trial was to evaluate the efficacy and safety of the fluocinolone-loop-anchoring technique over two years in eyes with iris-lens diaphragm disruption and pseudophakic cystoid macular edema., Methods: In 10 eyes, scleral fixation of fluocinolone implant was performed. Main outcome measures were the development of best-corrected visual acuity (BCVA), central retinal thickness over 24 months, and general safety of the procedure., Results: A significant improvement to 0.57 ± 0.38 log MAR (Snellen 20/80) (range 0-1.30) was observed (P = 0.003) at 1 month. Further improvement to 0.45 ± 036 log MAR (Snellen 20/60) was observed until month 18 (P = 0.081). Mean central retinal thickness decreased by 22% from 601.6 ± 235.5 µm to 449.1 ± 128.9 µm at 1 month. In one patient, the implant has to be removed at Month 7 because of elevated intraocular pressure and one patient after globe rupture had a retinal redetachment at Month 4., Conclusion: In this study, we showed that the treatment of recalcitrant pseudophakic cystoid macular edema with scleral fixated fluocinolone implant in eyes with disruption of the iris-lens diaphragm provides good anatomical and functional results with a reasonable safety profile over 24 months in eyes where pseudophakic cystoid macular edema is otherwise difficult to treat and often left untreated., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Oral tranexamic acid (TXA) is a relatively new treatment option for melasma. It is thought to reduce hyperpigmentation through inhibition of the plasminogen/plasmin pathway with resulting decreases in epidermal melanocyte tyrosinase activity, inflammatory mediators, dermal neovascularization, and mast cell numbers.

Purpose : Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) are considered the gold standard for diabetic macular edema (DME). Despite adequate anti-VEGF treatments, many patients present persistent DME. The aim of this study is to identify systemic, ocular and anatomical characteristics influencing functional and anatomical outcomes in refractory DME patients treated with IVI of corticosteroid. Materials and Methods : Retrospective multicenter hospital-based cohort study including type 2 diabetic adult patients with refractory DME that switched from intravitreal anti-VEGF to intravitreal corticosteroid between January 2017 and September 2018. Sociodemographic, clinical data, DME and treatment characteristics were collected at baseline (visit before switch), as well as spectral domain OCT features. Results : A total of 101 eyes were included. The median number of anti-VEGF injections before switch was 5.0 (min-max: 4.0-9.0) and the median anti-VEGF treatment duration before switch was 33.2 (min-max: 19.5-50.3) months. More than half of the patients (56; 54.9%) were diagnosed with diffuse DME. At baseline, 80 (88%) patients had cystoid DME, 55 (62.5%) patients had disorganization of retinal inner layers (DRIL) and 16 (17.6%) had subretinal fluid. Dexamethasone was the corticosteroid more commonly used (71.4%), followed by triamcinolone (24.4%) and fluocinolone (4.2%). Regarding best corrected visual acuity (BCVA), post-switch results showed no statistically significant improvement at three-month follow-up ( p = .048/0.096), but the mean central macular thickness (CMT) decreased significantly from 486.3 (SD = 159) µm to 369.3 (SD = 129) µm at three-month follow-up ( p < .001). DRIL was the tomographic characteristic able to influence significantly both CMT and BCVA final results ( p = .02 and 0.012, respectively). Conclusions : Subfoveal DRIL on structural OCT was the DME factor influencing significantly clinical and imaging outcomes in refractory DME patients treated with intravitreal corticosteroid. Portuguese care trend towards DME shows preference for the use of dexamethasone implant after therapeutic failure with ranibizumab or bevacizumab injection.

Objective: Tympanic membrane (TM) fibroblast cytotoxicity of quinolone ear drops is enhanced by dexamethasone and fluocinolone. Hydrocortisone has not been evaluated. We aimed to assess the effects of these 3 steroids on mouse and human TM fibroblast survival., Study Design: In vitro., Setting: Academic laboratory., Subjects and Methods: Mouse and human TM fibroblasts were exposed to hydrocortisone, dexamethasone, or fluocinolone at concentrations in commercial ear drops (1%, 0.1%, or 0.025%, respectively) and at steroid potency equivalents (1%, 0.033%, or 0.0033%, respectively), or dilute ethanol (control), twice within 24 hours or 4 times within 48 hours for 2 hours each time. Cells were observed with phase-contrast microscopy until the cytotoxicity assay was performed., Results: Mouse and human TM fibroblasts treated with any of the steroids had lower survival after 24 and 48 hours compared to control (all P < .0001). After 24 hours, viability of mouse fibroblasts treated with the steroids was not different ( P > .05), while treatment with hydrocortisone decreased human TM fibroblast viability ( P < .0001). After 48 hours, at concentrations found in ear drops and at equivalent steroid potency, dexamethasone and fluocinolone had similar survival in mouse and human fibroblasts (all P > .05), but hydrocortisone had lower survival in both mouse ( P = .02 and P < .0001) and human ( P < .0001) fibroblasts. Phase-contrast images mirrored the cytotoxicity findings., Conclusion: Steroids found in commercial ear drops reduce survival of mouse and human TM fibroblasts. Hydrocortisone appears to be more cytotoxic than the more potent steroids, dexamethasone and fluocinolone. These findings should be considered when assessing clinical outcomes of ototopical preparations.

Silicosis is an occupational disease triggered by the inhalation of fine particles of crystalline silica and characterized by inflammation and scarring in the form of nodular lesions in the lungs. In spite of the therapeutic arsenal currently available, there is no specific treatment for the disease. Flunisolide is a potent corticosteroid shown to be effective for controlling chronic lung inflammatory diseases. In this study, the effect of flunisolide on silica-induced lung pathological changes in mice was investigated. Swiss-Webster mice were injected intranasally with silica particles and further treated with flunisolide from day 21 to 27 post-silica challenge. Lung function was assessed by whole body invasive plethysmography. Granuloma formation was evaluated morphometrically, collagen deposition by Picrus sirius staining and quantitated by Sircol. Chemokines and cytokines were evaluated using enzyme-linked immunosorbent assay. The sensitivity of lung fibroblasts was also examined in in vitro assays. Silica challenge led to increased leukocyte numbers (mononuclear cells and neutrophils) as well as production of the chemokine KC/CXCL-1 and the cytokines TNF-α and TGF-β in the bronchoalveolar lavage. These alterations paralleled to progressive granuloma formation, collagen deposition and impairment of lung function. Therapeutic administration of intranasal flunisolide inhibited granuloma and fibrotic responses, noted 28 days after silica challenge. The upregulation of MIP-1α/CCL-3 and MIP-2/CXCL-2 and the cytokines TNF-α and TGF-β, as well as deposition of collagen and airway hyper-reactivity to methacholine were shown to be clearly sensitive to flunisolide, as compared to silica-challenge untreated mice. Additionally, flunisolide effectively suppressed the responses of proliferation and MCP-1/CCL-2 production from IL-13 stimulated lung fibroblasts from silica- or saline-challenged mice. In conclusion, we report that intranasal treatment with the corticosteroid flunisolide showed protective properties on pathological features triggered by silica particles in mice, suggesting that the compound may constitute a promising strategy for the treatment of silicosis., (Copyright © 2020 Ferreira, Lima, Farias-Filho, Jannini de Sá, de Arantes, Guimarães, Carvalho, Hogaboam, Wallace, Martins and Silva.)

Background: Melasma is a pigmentary disorder affecting mainly face . Various treatment modalities available as topicals, superficial chemical peels and lasers but none till date gives promising results, until date quest for the best treatment modality is on., Aim: To study the effect of oral and topical Tranexamic acid (TXA) and modified Kligman's regimen in treatment of melasma., Method: Patients having melasma were enrolled after consent for voluntary participation. A detailed history and clinical examination was done. Total 60 patients were enrolled and randomized in three groups, 20 received oral TXA 250 mg twice daily, 20 topical TXA and 20 received modified Kligman's regimen for 8 weeks along with sunscreen MASI(Melasma area severity index) was calculated at baseline, at end of 4 & 8 weeks. MASI score was compared with that at the end of the study. Based on reduction in mean MASI the therapeutic response was graded. Pre and post treatment photographs was also compared. Statistical analysis done by using student square T test , ANOVA And TUKEY test., Results: Reduction in MASI score was observed in all the groups but greater reduction in MASI score with modified Kligman's regimen by 30% followed with oral TXA by 25% reduction and least with topical TXA by 5%., Conclusion: Although modified Kligman's regimen is comparatively more efficient but due to its side effects in long term usage oral tranexamic acid could be a promising therapeutic approach for melasma., (© 2020 Wiley Periodicals, Inc.)

A 42-year-old woman with phototype V, presented a 9-year history of refractory centrofacial melasma to topical bleaching agents and peelings, untreated for the last 90 days. One session of microneedling with 1.5 mm needles was performed with hydroquinone 4% sterile serum drug delivery; after 3 days, modified Kligman's formula (hydroquinone 4% + fluocinolone acetonide 0.01% + tretinoin 0.05%) and broad-spectrum sunscreen SPF 70 were introduced for daily use. After 30 days, a significant improvement was observed in the clinical outcome (Figure 1) and the quality of life of the patient. These parameters were measured using Melasma Area and Severity Index (MASI) scale, with an 82.5% decrease, and Melasma Quality of Life Scale - Brazilian Population (MELASQoL-BP), with a 60% decrease. Dermatoscopic analysis (polarized videodermatoscopy x20) of the glabellar region revealed lighting of the pseudoreticular pigment network, diffuse light to dark brown background, and reduction in vascularity and telangiectasias (Figure 2). At the 5-month follow-up, there had been no relapse. The patient continued to use a broad-spectrum sunscreen along with the topical regiment.

Purpose: To establish an in vivo-relevant Transwell dish-based dissolution test system for the "respirable" aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products., Methods: "Respirable" ≤ 5.8 or 6.5 μm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter membranes under the modified assembly of the cascade impactor. Their dissolution in 10 ml of the simulated lung lining fluid (sLLF) was determined over time in the Transwell dish at 37°C and ~100% relative humidity in the presence of subsequent diffusive permeation across the Transwell's supporting membrane., Results: While three ICSs with high-to-intermediate solubility enabled the first-order "sink" and complete dissolution in 6 h, 4 ICSs with poor solubility including fluticasone propionate (FP) resulted in the pseudo-zero-order "non-sink", slow and limited dissolution. The aerosol dissolution rate constants (k diss ) were derived, well-correlated with the solubility. For FP, but not for highly-soluble flunisolide (FN), dissolution was kinetically aerosol mass-dependent. However, for a given ICS, dissolution profiles were indistinguishable between the formulations and products upon comparable aerosol mass collection., Conclusions: The in vivo-relevant Transwell dish-based "respirable" aerosol dissolution test system was developed, kinetically discriminative in accordance with the ICS solubility, but indistinguishable for a given ICS between the marketed products.

Background: Melasma is an acquired, facial hyperpigmentation without a specific origin. It is regularly associated with multiple etiologic factors such as pregnancy, genetic, racial, and from estrogen administration. Among the methods to treat skin hyperpigmentation a series of skin bleaching agents have been used. At present, the most commonly used agent is known as hydroquinone. Nowadays, it is known that hydroquinone can cause cancer in animals with unknown relevance to humans., Material and Methods: In this work, Raman spectroscopy was used to observe the presence of hydroquinone in the skin of 18 patients who have been under treatment for melasma., Results: A significant increase in the Raman signal was observed in the six bands associated with hydroquinone after melasma treatment., Conclusion: The authors believe that monitoring the presence of hydroquinone may be useful for an optimal personalized treatment of melasma and to provide the specialist a support tool to control the administration of this type of bleaching agents., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Human immunodeficiency virus (HIV) continues to be a major contributor to morbidity and mortality worldwide, particularly in developing nations where high cost and logistical issues severely limit the use of current HIV therapeutics. This, combined HIV's high propensity to develop resistance, means that new antiviral agents against novel targets are still urgently required. We previously identified novel anti-HIV agents directed against the nuclear import of the HIV integrase (IN) protein, which plays critical roles in the HIV lifecycle inside the cell nucleus, as well as in transporting the HIV preintegration complex (PIC) into the nucleus. Here we investigate the structure activity relationship of a series of these compounds for the first time, including a newly identified anti-IN compound, budesonide, showing that the extent of binding to the IN core domain correlates directly with the ability of the compound to inhibit IN nuclear transport in a permeabilised cell system. Importantly, compounds that inhibited the nuclear transport of IN were found to significantly decrease HIV viral replication, even in a dividing cell system. Significantly, budesonide or its analogue flunisolide, were able to effect a significant reduction in the presence of specific nuclear forms of the HIV DNA (2-LTR circles), suggesting that the inhibitors work though blocking IN, and potentially PIC, nuclear import. The work presented here represents a platform for further development of these specific inhibitors of HIV replication with therapeutic and prophylactic potential., (© 2018 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.)

The objective of the present study was to design and develop drug-device combination product in particular flunisolide nasal spray (FNS) using quality by design (QbD) approach. Quality target product profile (QTPP) of FNS was defined and critical quality attributes (CQAs), i.e. viscosity (cp) ( Y 1 ) and D 50 droplet size distribution (DSD) (μm) ( Y 2 ) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tools. Plackett-Burman and Box-Behnken designs were used for screening the significant factors and optimizing the variables range, respectively. It was observed that viscosity (cp) ( Y 1 ) was significantly impacted by formulation variables X 1 : propylene glycol (PG) (%) and X 2 : polyethylene glycol (PEG) 3350 (%), while D 50 DSD (μm) ( Y 2 ) was significantly impacted by formulation variables X 1 : PG (%), X 2 : PEG 3350 (%) and device variable X 8 : delivery volume (μl). A design space plot within which the CQAs remained unchanged was established at laboratory scale. In conclusion, this study demonstrated how QbD based development approach can be applied to the development of drug-device combination products with enhanced understanding of the impact of formulation, process and device variables on CQAs of drug-device combination products.

Hypopigmented mycosis fungoides (HMF) is an uncommon form of cutaneous T-cell lymphoma. It can be seen in children and is usually mistaken for eczema, vitiligo, or progressive macular hypomelanosis, clinically and histopathologically. We present a boy with HMF confirmed by histopathology. The patient had a course with slow clinical progression without Sezary syndrome.

Objective Ciprofloxacin, commonly given as eardrops, has been shown to adversely affect tympanic membrane fibroblasts. Dexamethasone potentiates this effect. A newly available eardrop contains ciprofloxacin and fluocinolone, a more potent steroid. We evaluated the cytotoxic effects of this preparation on mouse tympanic membrane fibroblasts. Study Design Prospective, in vitro. Setting Academic laboratory. Subjects and Methods In experiment 1, fibroblasts were exposed to 1:10 dilutions of commercially available 0.3% ofloxacin, 0.3% ciprofloxacin, 0.3% ciprofloxacin + 0.1% dexamethasone, 0.3% ciprofloxacin + 0.025% fluocinolone, or dilute hydrochloric acid (control), twice within 24 hours. In experiment 2, cells were also treated with the dilutions of the pure form of dexamethasone 0.1% or fluocinolone 0.025%, alone and in combination with ofloxacin or ciprofloxacin. Cells were exposed to the solutions for 2 hours each time and were placed back in growth media after the treatments. Cells were observed with phase-contrast microscope until the cytotoxicity assay was performed. Results Survival of fibroblasts treated with ofloxacin was not different from the control. Fibroblasts treated with ciprofloxacin, ciprofloxacin + dexamethasone, or ciprofloxacin + fluocinolone had much lower survival (all P < .0001). Cells treated with ciprofloxacin + fluocinolone had lower survival than ciprofloxacin ( P < .0001) and ciprofloxacin + dexamethasone ( P = .0001). Steroids alone also decreased fibroblast survival compared to control ( P < .0001). The combination of dexamethasone or fluocinolone with ciprofloxacin, but not ofloxacin, further decreased fibroblast survival ( P < .0001). Phase-contrast images mirrored the cytotoxicity findings. Conclusion Tympanic membrane fibroblast cytotoxicity of ciprofloxacin is potentiated by corticosteroids. This effect may be deleterious when treating a healing perforation but beneficial when treating granulation tissue on the tympanic membrane.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To compare the intraocular pressure (IOP) outcomes of Ahmed glaucoma valve (AGV) surgery alone versus AGV with fluocinolone implant in uveitic glaucoma patients., Methods: We identified uveitic glaucoma patients with AGV surgery alone and AGV surgery combined with fluocinolone implant from the Massachusetts Eye and Ear Ocular Inflammation Database. Demographic information, visual acuity, and IOP were recorded at preoperative visits and 1, 6, and 12 months after surgery. Incidence of hypertensive phase, defined as an IOP of >21 mm Hg or use of additional treatment to lower IOP occurring any time between 7 days to 6 months postoperatively, was investigated. Multilevel mixed effects models were performed to compare the outcomes between groups., Results: Eighteen eyes of 13 uveitic glaucoma patients with 1-year follow-up data were included. There were 11 eyes of 9 patients (mean age, 56.5 years; 63.6% male) in the AGV group and 7 eyes of 4 patients (mean age, 61.3 years; 71.4% male) in the AGV + fluocinolone group. There was no significant difference in visual acuity change at 1 year after surgery between groups ( P = 0.25), although visual acuity improvement was significant in the AGV group ( P = 0.01). The hypertensive phase occurred in 91% of AGV patients and 43% of AGV + fluocinolone patients ( P = 0.30), with onset of 8-40 days (mean, 18 days) after surgery. IOP and number of glaucoma medications decreased at the 1-year postoperative visits in both the AGV group ( P < 0.0001, P < 0.0001) and the AGV + fluocinolone group ( P = 0.001, P < 0.0001). Compared to the AGV group, the AGV + fluocinolone group used fewer glaucoma medications (0.28 vs 1.30 [ P = 0.01]) and had better inflammation control ( P = 0.02). The surgical complication rates were similar between groups., Conclusions: In uveitic glaucoma, AGV with fluocinolone achieves a similar, desired IOP control but with fewer glaucoma medications than AGV alone.

Background: Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative., Objectives: To determine if administration of inhalation corticosteroids after the first week of life until 36 weeks PMA to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 4), MEDLINE via PubMed (1966 to 19 May 2017), Embase (1980 to 19 May 2017), and CINAHL (1982 to 19 May 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials., Selection Criteria: We included randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD. We excluded trials investigating systemic corticosteroids versus inhalation corticosteroids., Data Collection and Analysis: We collected data on participant characteristics, trial methodology, and inhalation regimens. The primary outcome was death or BPD at 36 weeks PMA. Secondary outcomes were the combined outcome death or BPD at 28 days PNA, the seperate outcomes of death and BPD at both 28 days PNA, and at 36 weeks PMA, and short-term respiratory outcomes, such as failure to extubate; total days of mechanical ventilation and oxygen use; and the need for systemic corticosteroids. We contacted the original trialists to verify the validity of extracted data and to provide missing data. We analysed all data using Review Manager 5. When possible, we performed meta-analysis using typical risk ratio (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). We analysed ventilated and non-ventilated participants separately.We used the GRADE approach to assess the quality of the evidence., Main Results: We included eight trials randomising 232 preterm infants in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. The meta-analyses of the studies showed a reduced risk in favor of inhalation steroids regarding failure to extubate at seven days (typical RR (TRR) 0.80, 95% CI 0.66 to 0.98; 5 studies, 79 infants) and at the latest reported time point after treatment onset (TRR 0.60, 95% CI 0.45 to 0.80; 6 studies, 90 infants). However, both analyses showed increased statistical heterogeneity (I 2 statistic 73% and 86%, respectively). Furthermore, inhalation steroids did not impact total duration of mechanical ventilation or oxygen dependency. There was a trend toward a reduction in the use of systemic corticosteroids in infants receiving inhalation corticosteroids (TRR 0.51, 95% CI 0.26 to 1.00; 4 studies, 74 infants; very low-quality evidence). There was a paucity of data on short- and long-term adverse effects. Our results should be interpreted with caution because the total number of randomised participants is relatively small, and most trials differed considerably in participant characteristics, inhalation therapy, and outcome definitions., Authors' Conclusions: Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiologic methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure and adverse effects, and thereby increase the efficiency and effectiveness of inhaled drug delivery. The availability of small-particle aerosols of corticosteroids, bronchodilators, or their combination enables a higher total lung deposition and better peripheral lung penetration and provides added clinical benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas, confusion, and misconceptions related to small airways directed therapy. To this end, we have reviewed all studies on small-particle aerosol therapy systematically to address the dilemmas, confusion, and misconceptions related to small airways directed therapy., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Acute generalized exanthematous pustulosis (AGEP) is a rare skin condition typically caused by medications. The objective of this study was to examine the clinical features, causes, and outcomes of AGEP at a sole tertiary care center., Methods: A retrospective review of patients with AGEP (European Study of Severe Cutaneous Adverse Reactions score of ≥ 5) seen at Mayo Clinic (Rochester, MN, USA) between January 1, 1996, and December 31, 2013, was conducted., Results: Of 28 patients (mean age at onset: 56 years), 17 (61%) were women. The development of AGEP was attributed to medications in 25 patients (89%), with clindamycin the most common culprit (six patients). Three patients (11%) had mucous membrane involvement, and 21 (75%) showed systemic involvement. Ten patients (36%) received systemic corticosteroids for treatment of AGEP. Skin findings resolved within 15 days in 26 patients (93%) (mean time to resolution: 7.6 days). In three patients (11%), generalized skin eruptions or dermatitis developed weeks to months after the resolution of AGEP. Twenty-four patients (86%) had a personal history of drug reactions before the development of AGEP., Conclusions: A previous history of drug reactions and clindamycin causation were more common in the present cohort than in prior reports. A small subset of patients experienced new-onset non-AGEP skin eruptions within a few months of the resolution of AGEP., (© 2017 The International Society of Dermatology.)

Importance: Acute otitis media with tympanostomy tubes (AOMT) in children commonly presents with otorrhea and negatively affects their daily activities., Objective: To evaluate the efficacy and safety of topical ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution relative to ciprofloxacin, 0.3%, otic solution alone and fluocinolone acetonide, 0.025%, otic solution alone in the treatment of AOMT in children., Design, Setting, and Participants: Two twin multicenter, randomized, double-blind clinical trials with identical designs were conducted from June 24, 2011, through June 23, 2014, at ear, nose, and throat pediatric practices, general practices, hospitals, and clinical research centers. The study population comprised 662 children (331 in each trial) with AOMT in at least 1 ear who presented with moderate or severe purulent otorrhea for 3 weeks or less. Data analyses were performed on an intention-to-treat basis., Interventions: Patients were randomly assigned to receive ciprofloxacin plus fluocinolone, ciprofloxacin alone, or fluocinolone alone twice daily for 7 days and were evaluated on days 1 (baseline), 3 to 5 (undergoing therapy), 8 to 10 (end of therapy), and 18 to 22 (test of cure)., Main Outcomes and Measures: The primary efficacy measure was time to cessation of otorrhea. The principal secondary end point was sustained microbiological cure, defined as eradication or presumed eradication at end-of-therapy and test-of-cure visits., Results: A total of 662 children participating in the 2 studies were randomized to receive ciprofloxacin plus fluocinolone (n = 223), ciprofloxacin alone (n = 221), or fluocinolone alone (n = 218). The median age was 2.5 years (range, 0.6-12.7 years). The median time to cessation of otorrhea was 4.23 days (95% CI, 3.65-4.95 days) in patients receiving ciprofloxacin plus fluocinolone compared with 6.95 days (95% CI, 5.66-8.20 days) in those receiving ciprofloxacin and not estimable findings in those receiving fluocinolone alone (P < .001). The clinical cure rate at the test-of-cure visit was 80.6% in the ciprofloxacin plus fluocinolone group, 67.4% in the ciprofloxacin group (difference, 13.2%; 95% CI, 5.0%-21.4%; P = .002), and 47.6% in the fluocinolone group (difference, 33.0%; 95% CI, 24.0%-42.0%; P < .001). The sustained microbiological cure rate was 79.7% in the ciprofloxacin plus fluocinolone group vs 67.7% in the ciprofloxacin group (difference, 12.0%; 95% CI, 0.8%-23.0%; P = .04) and 37.6% in the fluocinolone group (difference, 42.1%; 95% CI, 29.3%-54.8%; P < .001). Only 7 (3.1%) of the patients receiving ciprofloxacin plus fluocinolone, 8 (3.6%) of the patients receiving ciprofloxacin, and 10 (4.7%) of the patients receiving fluocinolone presented with adverse events related to study medication., Conclusions and Relevance: The combination of ciprofloxacin plus fluocinolone is more effective than treatment with ciprofloxacin or fluocinolone alone for AOMT, and it is safe and well tolerated in children., Trial Registration: clinicaltrials.gov Identifiers: NCT01395966 and NCT01404611.

Corticosteroids are unique in that they are the one class of agents that acts upon most of the multiple processes in the pathophysiology of macular edema. Corticosteroids are capable of inhibiting prostaglandin and leukotriene synthesis as well as interfering with intercellular adhesion molecule-1 (ICAM-1), interleukin-6, VEGF-A, and stromal cell derived factor-1 pathways. Triamcinolone, dexamethasone, and fluocinolone have been extensively used in the treatment of retinal and choroidal vascular diseases. Sustained release implants of steroids have reduced the burden of repeated intravitreal injections necessary in most of the retinal diseases. Complement factors play an important role in the pathogenesis of age-related macular degeneration (AMD). Inhibitors of complement could provide a breakthrough in the treatment of dry AMD. Complement factor inhibitors, such as POT-4, lampalizumab, and eculizumab, have been tested in clinical trials for dry AMD with promising results. However, results of phase 3 trials are awaited.

Introduction: Intraocular pharmacotherapy (vascular endothelial growth factor [VEGF] inhibitors and corticosteroids) has become first-line therapy for diabetic retinopathy (DR). A series of intraocular injections is usually required before disease modulation decreases the treatment burden in some patients, but others with chronic diabetic macular edema may require intensive longer-term therapy., Areas Covered: Recent studies showing successful pharmacologic treatment of proliferative DR will probably lead to increased use of pharmacotherapy, thereby further emphasizing the need for longer duration drugs. Recently approved anti-VEGF drugs (aflibercept) and corticosteroids (dexamethasone and fluocinolone inserts) provide extended durations of action. Longer action anti-VEGF molecules, sustained release devices and pumps, and encapsulated cell technology, may further decrease treatment burden, though regulatory approval may not occur for at least 5 years. Oral medications (danazol and minocycline) and modified topical drugs (loteprednol) will require daily administration but may decrease the frequency of visits to physicians' offices. Intravitreally administered drugs that target different biochemical pathways are being developed as monotherapy and combination therapy, and their effects on durability remains to be seen., Expert Opinion: The rich development pipeline promises to provide improved therapeutic options in addition to drugs and devices with longer duration of action.

Purpose: To determine whether long-term, slow-release exposure to corticosteroids with Retisert promotes better surgical outcomes after Ahmed valve implantation., Patients: This comparative retrospective cohort study included 17 study eyes (10 patients) with uncontrolled uveitis requiring Retisert and Ahmed implantation, and 55 control eyes (51 patients) with other types of medically uncontrolled glaucoma that only received Ahmed., Materials and Methods: Main outcome measures were intraocular pressure (IOP), glaucoma eye drops per day, best-corrected visual acuity, early complications, and late complications at 1, 3, 6, and 12 months. Linear mixed effects models were used to model IOP, glaucoma drops per day, and visual acuity at 1 year after surgery., Results: At 1 year, the study eyes had a mean IOP of 12.24, which was lower than that for control eyes at 15.17 (P=0.04). At 1 year, the average number of glaucoma eye drops used per day for study eyes was 1.4, which was lower than that for control eyes at 2.3 (P=0.03). At 1 year, there were no statistically significant differences in change in visual acuity, early complications, and late complications between study and control eyes., Conclusions: Patients who received a Retisert implantation had lower IOP and used fewer glaucoma eye drops compared with control eyes at 1-year post-Ahmed valve surgery. This study suggests that long-term, slow-release corticosteroid medication from Retisert (fluocinolone acetonide) may improve the surgical outcome for patients with an Ahmed valve implantation and/or Retisert helps control uveitis in patients with uveitic glaucoma receiving Ahmed valves.

Purpose: To assess French practice patterns in the treatment of diabetic macular edema (DME)., Methods: A 31-item survey investigating practice patterns in the diagnosis and management of DME was e-mailed in March 2015 to retina specialist members of the French-speaking Retina Specialist Society. During this time frame, only ranibizumab was reimbursed for this indication. For each question concerning the choice of treatments, respondents were asked to assume that all treatments having market approval were also reimbursed. Answers were analyzed anonymously by Evalandgo software., Results: Ninety-five specialists answered the survey. Two thirds of them initiated an intravitreal treatment for DME for a loss of vision greater than 0.5 (Monoyer scale). The three determining factors for treatment choice were potential VA improvement, expected retinal anatomic improvement, and patient availability for monthly follow-up. For central DME in phakic or pseudophakic eyes, the first choice of intravitreal (IVT) treatment was ranibizumab, even assuming that all drugs approved by French authorities (HAS) were reimbursed by the health care system. Eighty-five percent of retinal specialists propose bilateral intravitreal injections the same day for the same patient., Conclusion: Most of the specialists initiate DME treatment for a VA>0.5 in France. Eighty-five percent of them perform bilateral intravitreal injections on the same day in the case of bilateral DME., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Steroids have been extensively used to treat macular edema due to diabetic retinopathy, venous occlusive disease, ocular inflammation and, to a lesser extent, also in some cases of choroidal neovascularization. The various intraocular steroids that have been employed include dexamethasone, triamcinolone and fluocinolone. During the past few years, new drug delivery methods for corticosteroids have been developed and are now part of our therapeutic armamentarium. This chapter provides a brief description of the pharmacology, efficacy and adverse effects associated with the use of steroids in various retinal diseases., (© 2016 S. Karger AG, Basel.)

The external granule layer (EGL) is a proliferative region that produces over 90% of the neurons in the cerebellum but can also malignantly transform into a cerebellar tumor called the medulloblastoma (the most common malignant brain tumor in children). Current dogma considers Hedgehog stimulation a potent proliferative signal for EGL neural progenitor cells (NPCs) and medulloblastomas. However, the Hedgehog pathway also acts as a survival signal in the neural tube where it regulates dorsoventral patterning by controlling NPC apoptosis. Here we show that Hedgehog stimulation is also a potent survival signal in the EGL and medulloblastomas that produces a massive apoptotic response within hours of signal loss in mice. This toxicity can be produced by numerous Hedgehog antagonists (vismodegib, cyclopamine, and jervine) and is Bax/Bak dependent but p53 independent. Finally, since glucocorticoids can also induce EGL and medulloblastoma apoptosis, we show that Hedgehog's effects on apoptosis can occur independent of glucocorticoid stimulation. This effect may play a major role in cerebellar development by directing where EGL proliferation occurs thereby morphologically sculpting growth. It may also be a previously unknown major therapeutic effect of Hedgehog antagonists during medulloblastoma therapy. Results are discussed in terms of their implications for both cerebellar development and medulloblastoma treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: This study investigated the effect of different active pharmaceutical ingredients (API) on aerosol electrostatic charges and aerosol performances for pressurized metered dose inhalers (pMDIs), using both insulating and conducting actuators., Methods: Five solution-based pMDIs containing different API ingredients including: beclomethasone dipropionate (BDP), budesonide (BUD), flunisolide (FS), salbutamol base (SB) and ipratropium bromide (IPBr) were prepared using pressure filling technique. Actuator blocks made from nylon, polytetrafluoroethylene (PTFE) and aluminium were manufactured with 0.3 mm nominal orifice diameter and cone nozzle shape. Aerosol electrostatics for each pMDI formulation and actuator were evaluated using the electrical low-pressure impactor (ELPI) and drug depositions were analysed using high performance liquid chromatography (HPLC)., Results: All three actuator materials showed the same net charge trend across the five active drug ingredients, with BDP, BUD and FS showing positive net charges for both nylon and PTFE actuators, respectively. While SB and IPBr had significantly negative net charges across the three different actuators, which correlates to the ionic functional groups present on the drug molecule structures., Conclusions: The API present in a pMDI has a dominant effect on the electrostatic properties of the formulation, overcoming the charge effect arising from the actuator materials. Results have shown that the electrostatic charges for a solution-based pMDI could be related to the interactions of the chemical ingredients and change in the work function for the overall formulation.

Introduction: Inflammation plays a key role in the pathological processes leading to macular edema. Sustained release, low-dose intraocular corticosteroid delivery devices provide long-term anti-inflammatory therapy. Recently, a novel fluocinolone acetonide intravitreal insert (FAi, Iluvien), has been introduced with promising long-term results in the treatment of macular edema., Areas Covered: An extensive review of the literature in the English language was performed to provide comprehensive information on the pharmacological properties of FAi and its safety and efficacy data from various multi-center randomized clinical trials., Expert Opinion: The FAc, Retisert is a sustained-release device that is surgically implanted in the vitreous and has been approved by the US FDA for the treatment of non-infectious intermediate, posterior or panuveitis. FAi was developed after FAc and is an intravitreal corticosteroid delivery system that allows controlled release of therapeutic levels of fluocinolone acetonide (FA). Initial efficacy and safety data suggest that this delivery system maintains clinical effectiveness for up to 3 years after a single delivery of the device. This second-generation fluocinolone delivery device has shown superior safety results in clinical trials compared to the previous version of the higher dose FAc (0.59 mg). Sustained delivery preparations may help to reduce the treatment burden and its associated risks by decreasing the frequency of intravitreal injections. However, much needs to be learnt from additional clinical trials, post-marketing surveillance and results of extension studies. Concerns of intravitreal corticosteroids, such as cataract and increase in intraocular pressure, remain major challenges for this therapeutic strategy.

Flunisolide hydrofluoroalkane (HFA) with integrated spacer is the most recent reformulated inhaled corticosteroid (ICS) for asthma available in the United States. It is the only product that combines a corticosteroid extrafine aerosol with a built-in spacer. The potential clinical benefit of the flunisolide HFA formulation and its integrated spacer for treating persistent asthma was assessed through a comprehensive review of the published literature and data from the past 10 years focusing on (1) flunisolide, the molecule, and the impact of the HFA reformulation; (2) updated information on the anti-inflammatory response to flunisolide HFA, particularly in the distal airways; and (3) the usefulness of an integrated spacer. Flunisolide HFA was found effective and safe in clinical studies and comparable with the chlorofluorocarbon (CFC) formulation, but at about one-third the dose of flunisolide CFC, likely reflecting both the device and the particle size of the reformulated product. Compared with the CFC formulation, the extrafine aerosol and smaller particle size of flunisolide HFA substantially increased pulmonary deposition and decreased oropharyngeal deposition. The integrated spacer further enhanced the pulmonary/oropharyngeal deposition ratio. Examination of lung biopsy specimens indicated a favorable anti-inflammatory response to flunisolide HFA in peripheral airways. Pediatric studies showed no significant effects on growth. The data indicate that flunisolide HFA is a safe and effective maintenance therapy for asthma patients. The integrated spacer may provide an added advantage for patients, especially those who may be more likely to experience adverse effects of ICSs, both local and systemic, including children susceptible to adverse effects on growth.

Background: Treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern, especially the effects on linear growth., Objectives: To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments (molecule, dose, length of exposure, inhalation device) and of treated children (age, disease severity, compliance with treatment)., Search Methods: We searched the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO; we handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases to look for potential relevant unpublished studies. The literature search was conducted in January 2014., Selection Criteria: Parallel-group randomised controlled trials comparing daily use of ICS, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma., Data Collection and Analysis: Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0. We used the random-effects model for meta-analyses. We used mean differences (MDs) and 95% CIs as the metrics for treatment effects. A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls. We performed a priori planned subgroup analyses to explore potential effect modifiers, such as ICS molecule, daily dose, inhalation device and age of the treated child., Main Results: We included 25 trials involving 8471 (5128 ICS-treated and 3343 control) children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) [corrected] given at low or medium daily doses were used during a period of three months to four to six years. Most trials were blinded and over half of the trials had drop out rates of over 20%.Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period.Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment (Chi² = 26.1, degrees of freedom (df) = 5, P value < 0.0001). The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 μg/d hydrofluoroalkane (HFA)-beclomethasone. Subgroup analyses did not show a statistically significant impact of daily dose (low vs medium), inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period. However, head-to-head comparisons are needed to assess the effects of different drug molecules, dose, inhalation device or patient age. No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). Of two trials that reported linear growth velocity in the third year of treatment, one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups (5.34 cm/y vs 5.34 cm/y), and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group (MD -0.33 cm/y, 95% CI -0.52 to -0.14, P value 0.0005). Among four trials reporting data on linear growth after treatment cessation, three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation. One trial showed accelerated linear growth velocity in the fluticasone group at 12 months after treatment cessation, but there remained a statistically significant difference of 0.7 cm in height between the fluticasone and placebo groups at the end of the three-year trial.One trial with follow-up into adulthood showed that participants of prepubertal age treated with budesonide 400 μg/d for a mean duration of 4.3 years had a mean reduction of 1.20 cm (95% CI -1.90 to -0.50) in adult height compared with those treated with placebo., Authors' Conclusions: Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma. The effect size of ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose (low to medium dose range). ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. However, additional studies are needed to better characterise the molecule dependency of growth suppression, particularly with newer molecules (mometasone, ciclesonide), to specify the respective role of molecule, daily dose, inhalation device and patient age on the effect size of ICS, and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma.

Inhaled corticosteroids (ICSs) are recommended for treatment of persistent asthma. Several ICSs are available and delivered by a variety of devices. After the banning of chlorofluorocarbon (CFC), a formulation of hydrofluoroalkane (HFA)-flunisolide marketed with an in-built spacer has been developed, complying with the request of efficacy and safety for children and adults. It delivers an aerosol with mass median aerodynamic diameter smaller than that of the CFC-formulation (1.2 vs 3.8 m). The extrafine aerosol and the add-on spacer are peculiarities of HFA-flunisolide with respect to the traditional ICSs, assuring larger lung deposition, lower oro-pharyngeal dose and targeting small airways. HFA-flunisolide with the spacer is effective at one-third the dose of CFC-flunisolide delivered without spacer. HFA-flunisolide may be considered an effective alternative to currently available ICSs for asthma management of adult and pediatric patients 6 years of age and older.

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug-drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug-drug interaction in order to suggest options for the clinical management of HIV-positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids., (© 2013 British HIV Association.)

The use of intravitreal (IVT) corticosteroids for treatment of posterior segment diseases has increased significantly over the last decade. A commonly recognized complication of IVT steroids is secondary ocular hypertension (OHT) that can occur immediately secondary to direct intraocular volume increase or weeks to months later as a result of increased outflow resistance. We performed a meta-analysis and found 32% (95% confidence interval, 28.2-36.3) of individuals developed OHT following 4 mg IVT triamcinolone, 66% (50.2-78.8) and 79% (72.2-84.5) following 0.59 and 2.1 mg fluocinolone implant, respectively, and 11% (6.4-17.9) and 15% (9.2-24.3) following 0.35 and 0.7 mg dexamethasone implant, respectively. Risk factors included pre-existing glaucoma, higher baseline intraocular pressure (IOP), younger age, OHT following previous injection, uveitis, higher steroid dosage, and fluocinolone implant. Most cases of OHT can be controlled medically; up to 45% following fluocinolone implant require surgery, however. We suggest a protocol to monitor IOP after IVT steroid injection/implantation that includes checking IOP within 30 minutes after injection, followed by 1 week after IVT triamcinolone and 2 weeks after implant insertion, then every 2 weeks for the first month and monthly for up to 6 months after IVT triamcinolone and dexamethasone implantation and 9 months after fluocinolone implantation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To analyze the early spectral domain optical coherence tomography changes after fluocinolone implantation in eyes with baseline uveitic macular edema., Methods: Patients with uveitic macular edema and who received fluocinolone implantations by 2 surgeons (R.P.S. and J.E.S.) at the Cole Eye Institute (Cleveland Clinic, Cleveland, OH) from September 2009 to July 2010 were eligible for this study. Best-corrected visual acuity, intraocular pressure, central subfield thickness, cube volume, cube average thickness, and cystoid macular edema grade were recorded before implantation and in the early postoperative period (median: 3 months postimplantation). Changes in these variables were analyzed using the Wilcoxon signed-rank test for paired comparisons of clustered data. P values were 2 sided, and alpha was set at 0.05., Results: Twelve eyes of seven patients were included in the study. The median best-corrected visual acuity improved in the early postoperative period after implantation (20/80 before implantation and 20/50 after implantation), but this improvement was not found to be significant (P = 0.12). However, the spectral domain optical coherence tomography measurements-central subfield thickness, cube volume, cube average thickness, and cystoid macular edema grade-were all significantly reduced (median changes: -234 μm [P = 0.02], -1 mm [P = 0.04], -39 μm [P = 0.04], and -3 [P = 0.03], respectively)., Conclusion: Fluocinolone implantation is associated with a significant reduction in macular edema as measured by spectral domain optical coherence tomography in the early postoperative period, a result that is consistent with the proposed mechanism of the drug.

Asthma is one of the most prevalent diseases in the world, for which the mainstay treatment has been inhaled glucocorticoids (GCs). Despite the widespread use of these drugs, approximately 30% of asthma sufferers exhibit some degree of steroid insensitivity or are refractory to inhaled GCs. One hypothesis to explain this phenomenon is interpatient variability in the clearance of these compounds. The objective of this research is to determine how metabolism of GCs by the CYP3A family of enzymes could affect their effectiveness in asthmatic patients. In this work, the metabolism of four frequently prescribed inhaled GCs, triamcinolone acetonide, flunisolide, budesonide, and fluticasone propionate, by the CYP3A family of enzymes was studied to identify differences in their rates of clearance and to identify their metabolites. Both interenzyme and interdrug variability in rates of metabolism and metabolic fate were observed. CYP3A4 was the most efficient metabolic catalyst for all the compounds, and CYP3A7 had the slowest rates. CYP3A5, which is particularly relevant to GC metabolism in the lungs, was also shown to efficiently metabolize triamcinolone acetonide, budesonide, and fluticasone propionate. In contrast, flunisolide was only metabolized via CYP3A4, with no significant turnover by CYP3A5 or CYP3A7. Common metabolites included 6β-hydroxylation and Δ(6)-dehydrogenation for triamcinolone acetonide, budesonide, and flunisolide. The structure of Δ(6)-flunisolide was unambiguously established by NMR analysis. Metabolism also occurred on the D-ring substituents, including the 21-carboxy metabolites for triamcinolone acetonide and flunisolide. The novel metabolite 21-nortriamcinolone acetonide was also identified by liquid chromatography-mass spectrometry and NMR analysis.

Fox-Fordyce disease (FFD) is a rare inflammatory disorder that affects the apocrine sweat glands. Clinically, lesions are equidistant, smooth, uniform, firm, folliculocentric papules, which can range in color from flesh-colored to red-brown to slightly yellow. Whereas the axillae are most commonly involved, FFD also can involve the anogenital and periareolar areas, lips, umbilicus, sternum, perineum, and upper medial aspects of the thighs. The underlying etiology of FFD remains unclear although epidemiologic data support a hormonal component because women are more commonly affected than men. Moreover, symptoms initially present after the onset of puberty, flare perimenstrually, and often resolve during pregnancy and after menopause. Histopathologic findings include the obstruction of the apocrine duct by a hyperkeratotic plug in the follicular infundibulum, which is believed to represent the primary pathophysiologic process; subsequent ductal rupture and resulting inflammatory response produce the typical clinical picture. Treatment of FFD is difficult because no one agent has proven particularly effective. Topical and interlesional glucocorticoids are often considered the first-line pharmacologic agents, although use is often limited by concerns for atrophy. Other agents that have shown some success include topical and systemic retinoids, topical clindamycin, topical pimecrolimus cream, benzoyl peroxide, and oral contraceptives. For medication-refractory cases, mechanical destruction or removal of the apocrine glands has been efficacious in small case series.

Background: Psoriasis is among the top dermatologic diagnoses for older adult patients, and the number of older adult psoriasis patients is expected to rise., Purpose: To characterize trends in older adult psoriasis health care practices of US ambulatory physician offices from 1993 to 2009., Methods: We used data from the National Ambulatory Medical Care Survey to assess demographics, specialties seen, and treatment in visits by older adult patients, 55 years of age and older., Results: There were approximately 14.1 million outpatient visits for psoriasis among the older adult population during the study period. Older adult psoriasis patients were 52.4% female and 47.6% male. The most frequent older adult age group seen for psoriasis was the 55 to 64 year age group. Dermatologists saw 69.3% of patients, internists saw 14.5%, and general and family practitioners saw 11.6%. Topical corticosteroids were the most frequently prescribed medications. Dermatologists preferred clobetasol whereas non-dermatologists more commonly prescribed betamethasone. For both the 18 to 54 year age group and the 55 and older group, the leading 7 out of 10 medications prescribed were topical corticosteroids and calcipotriene. However, etanercept, coal tar, and fluocinolone were among the leading medications in the younger group but not in the 55 and older group., Conclusions: Treatment approach for older adult psoriasis patients showed some differences among medical specialties and among the younger and older age groups. Further research specific to older adult psoriasis patients is needed to determine optimal treatment strategies for this patient population.

Inhaled corticosteroids (ICSs) are the mainstay of anti-inflammatory treatment in subjects with asthma and COPD. This review evaluates the role of nebulizers as an alternative to inhalers for delivering ICSs in asthma and COPD. I selected 16 randomized, placebo-controlled, blinded, long-term studies, mostly carried out in asthma (n = 14) and COPD. Nebulized budesonide has been demonstrated to be effective and safe in children ages 1-8 years, and, with less evidence, in infants and adults with asthma. Other investigations, with the addition of in vitro and in vivo comparison studies, have shown that nebulized beclomethasone, fluticasone, and flunisolide are effective alternatives to nebulized budesonide in asthma and COPD. Efficient delivery of nebulized ICSs requires that the nebulizer system, the nebulized drug formulation, and the inhaling subject interact properly. The practices of mixing nebulized ICSs with bronchodilators and using nebulized ICSs in acute settings are promising, but require further confirmations, and at present cannot be recommended. I conclude that nebulizers may be considered as an effective alternative to inhalers for delivering ICSs and can be recommended to asthmatic and COPD subjects who are unwilling or unable to use inhalers. Newer formulations could possibly offer a relevant advance for a more efficient nebulization of ICSs.

Background: Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative., Objectives: To determine if administration of inhalation corticosteroids after the first week of life to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes., Search Methods: We identified randomised, controlled trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), PubMed (from 1966), EMBASE (from 1974), CINAHL (from 1982), references from retrieved trials and handsearches of journals, all assessed to February 2012., Selection Criteria: Randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD were included. Trials investigating systemic corticosteroids versus inhalation corticosteroids were excluded., Data Collection and Analysis: Data on patient characteristics, trial methodology, and inhalation regimens were collected. The primary outcomes were death or BPD, or both, at 28 days PNA or 36 weeks PMA. Secondary outcomes were short-term respiratory outcomes, such as failure to extubate, total days of mechanical ventilation and oxygen use, and the need for systemic corticosteroids. The original trialists were contacted to verify the validity of extracted data and to provide missing data. All data were analysed using RevMan 5.0.24. When possible, meta-analysis was performed using typical risk ratio (TRR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). Ventilated and non-ventilated participants were analysed separately., Main Results: Eight trials randomising 232 preterm infants were included in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. Furthermore, inhalation steroids did not impact short-term respiratory outcomes such as failure to extubate and total duration of mechanical ventilation or oxygen dependency. There was a trend to a reduced use of systemic corticosteroids in favour of inhalation corticosteroids (TRR 0.51; 95% CI 0.26 to 1.00). There was a paucity of data on short-term and long-term adverse effects. These results should be interpreted with caution because the total number of randomised patients is relatively small and most trials differed considerably in patient characteristics, inhalation therapy and outcome definitions., Authors' Conclusions: Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

Purpose: To evaluate the associations between visual acuity and self-reported visual function; visual acuity and health-related quality of life (QoL) metrics; a summary measure of self-reported visual function and health-related QoL; and individual domains of self-reported visual function and health-related QoL in patients with uveitis., Methods: Best-corrected visual acuity, vision-related functioning as assessed by the NEI VFQ-25, and health-related QoL as assessed by the SF-36 and EuroQoL EQ-5D questionnaires were obtained at enrollment in a clinical trial of uveitis treatments. Multivariate regression and Spearman correlations were used to evaluate associations between visual acuity, vision-related function, and health-related QoL., Results: Among the 255 patients, median visual acuity in the better-seeing eyes was 20/25, the vision-related function score indicated impairment (median, 60), and health-related QoL scores were within the normal population range. Better visual acuity was predictive of higher visual function scores (P ≤ 0.001), a higher SF-36 physical component score, and a higher EQ-5D health utility score (P < 0.001). The vision-specific function score was predictive of all general health-related QoL (P < 0.001). The correlations between visual function score and general quality of life measures were moderate (ρ = 0.29-0.52)., Conclusions: The vision-related function score correlated positively with visual acuity and moderately positively with general QoL measures. Cost-utility analyses relying on changes in generic healthy utility measures will be more likely to detect changes when there are clinically meaningful changes in vision-related function, rather than when there are only changes in visual acuity. (ClinicalTrials.gov number, NCT00132691.).