Adverse childhood experiences and alcohol use and misuse: Testing the impact of traditional and expanded adverse childhood experiences among racially/ethnically diverse youth transitioning into adulthood.

Objective: Traditional Adverse Childhood Experiences (T-ACEs), such as abuse and neglect, have been associated with an increased risk of youth alcohol use and misuse. This study aims to compare associations of T-ACEs and Expanded ACEs (E-ACEs), an expanded set of ACEs that encompass community-level adversities, with alcohol use and misuse by race/ethnicity. Method: Data came from a three-wave (1998-1999; 1999-2000; 2004-2005) community-based study in Houston, including youth transitioning into adulthood. We compared associations between ACEs at Wave 1 and past-year alcohol use, abuse, and dependence at Wave 3. Results: Participants (n = 2,391) included White (n =908), Black (n = 898) and Latinx (n = 585) youth (M (SD) = 14.00 (2.04)) transitioning into young adulthood (M (SD) = 19.77 (2.34)). T-ACEs were associated with higher odds of alcohol use, abuse, and dependence (OR = 1.15, OR = 1.18, OR = 1.24, respectively) while E-ACEs increased the odds of alcohol dependence (OR = 1.23) in the total sample. No significant differences by race/ethnicity were found. Racial/ethnic differences in increased alcohol risk were observed for some ACE items, such as bullying and use for Latinx youth (OR = 2.13) and poverty and dependence for White youth (OR = 2.01). Conclusions: T-ACES and E-ACEs increase the risk of alcohol use and misuse. Results highlight the importance of preventing ACEs exposure as a risk factor for youth alcohol use and misuse. Public policies must also focus on preventing ACEs through multi-level interventions aimed at reducing violence, bullying, and financial instability.

Proteomic research on new urinary biomarkers of renal disease in canine leishmaniosis: Survival and monitoring response to treatment.

The objective of our study was to search for survival biomarkers (SB) and treatment response monitoring biomarkers (TRMB) in the urinary proteome of dogs with renal disease secondary to canine leishmaniosis (CanL), using UHPLC-MS/MS. The proteomic data are available via ProteomeXchange with identifier PXD042578. Initially, a group of 12 dogs was evaluated and divided into survivors (SG; n = 6) and nonsurvivors (NSG; n = 6). A total of 972 proteins were obtained from the evaluated samples. Then, bioinformatic analysis reduced them to 6 proteins like potential SB increased in the NSG, specifically, Haemoglobin subunit Alpha 1, Complement Factor I, Complement C5, Fibrinogen beta chain (fragment), Peptidase S1 domain-containing protein, and Fibrinogen gamma chain. Afterwards, SG was used to search for TRMB, studying their urine at 0, 30, and 90 days, and 9 proteins that decreased after treatment were obtained: Apolipoprotein E, Cathepsin B, Cystatin B, Cystatin-C-like, Lysozyme, Monocyte differentiation CD14, Pancreatitis-associated precursor protein, Profilin, and Protein FAM3C. Finally, enrichment analysis provided information about the biological mechanisms in which these proteins are involved. In conclusion, this study provides 15 new candidate urinary biomarkers and an improved understanding of the pathogenesis of kidney disease in CanL.

Thoracic ultrasound alone or in combination with tracheal amylase as a tool predictor of ventilator-associated pneumonia in neurocritical patients.

In this study, we aim to evaluate whether thoracic ultrasound (TUS) and tracheal amylase (TA) alone or in combination can predict the development of ventilator-associated pneumonia (VAP) in neurocritical patients. Consecutive adult patients with neurocritical disease with normal chest radiographs who required intensive care unit admission and mechanical ventilation between March 2015 and July 2018 were included. TUS and Amylase levels were measured during the first 24 hours and repeated 48 hours after orotracheal intubation. Forty-three patients with a median age of 34 years (17-82) were included. TUS had a sensitivity of 100% and specificity of 96.3% as a predictor of VAP within the first 48 hours when nonpattern A was observed. TA levels > 200 UI/L in the first 48 hours had a sensitivity of 87.5%, and specificity of 63% as a predictor of VAP. Moreover, no benefit of TUS plus TA compared to TUS alone as a predictor of VAP was found. The identification of abnormal TUS patterns in the first 48 hours of orotracheal intubation is a significant predictor of VAP in neurocritical patients.

Urinary proteome of dogs with renal disease secondary to leishmaniosis.

Canine leishmaniosis is frequently associated with the development of renal disease. Its pathogenesis is complex and not fully understood. For this reason, this study aimed to describe the urinary proteome, and identify possible new biomarkers in dogs with kidney disease secondary to leishmaniosis. Urine samples were collected from 20 dogs, 5 from healthy dogs, and 15 from stages Leishvet III and IV. Urine samples were analyzed by UHPLC-MS/MS. The data are available via ProteomeXchange with identifier PXD029165. A total of 951 proteins were obtained. After bioinformatic analysis, 93 urinary proteins were altered in the study group. Enrichment analysis performed on these proteins showed an overrepresentation of the complement activation pathway, among others. Finally, 12 discriminant variables were found in dogs with renal disease secondary to leishmaniosis, highlighting C4a anaphylatoxin, apolipoprotein A-I, haptoglobin, leucine-rich alpha-2-glycoprotein 1, and beta-2-microglobulin. This study is the first to describe the urinary proteomics of dogs with renal disease caused by leishmaniosis, and it provides new possible biomarkers for the diagnosis and monitoring of this disease.

Electrospinning-Generated Nanofiber Scaffolds Suitable for Integration of Primary Human Circulating Endothelial Progenitor Cells.

The extracellular matrix is fundamental in order to maintain normal function in many organs such as the blood vessels, heart, liver, or bones. When organs fail or experience injury, tissue engineering and regenerative medicine elicit the production of constructs resembling the native extracellular matrix, supporting organ restoration and function. In this regard, is it possible to optimize structural characteristics of nanofiber scaffolds obtained by the electrospinning technique? This study aimed to produce partially degraded collagen (gelatin) nanofiber scaffolds, using the electrospinning technique, with optimized parameters rendering different morphological characteristics of nanofibers, as well as assessing whether the resulting scaffolds are suitable to integrate primary human endothelial progenitor cells, obtained from peripheral blood with further in vitro cell expansion. After different assay conditions, the best nanofiber morphology was obtained with the following electrospinning parameters: 15 kV, 0.06 mL/h, 1000 rpm and 12 cm needle-to-collector distance, yielding an average nanofiber thickness of 333 ± 130 nm. Nanofiber scaffolds rendered through such electrospinning conditions were suitable for the integration and proliferation of human endothelial progenitor cells.

Chimeric Antigen Receptor-T Cells: A Pharmaceutical Scope.

Cancer is among the leading causes of death worldwide. Therefore, improving cancer therapeutic strategies using novel alternatives is a top priority on the contemporary scientific agenda. An example of such strategies is immunotherapy, which is based on teaching the immune system to recognize, attack, and kill malignant cancer cells. Several types of immunotherapies are currently used to treat cancer, including adoptive cell therapy (ACT). Chimeric Antigen Receptors therapy (CAR therapy) is a kind of ATC where autologous T cells are genetically engineered to express CARs (CAR-T cells) to specifically kill the tumor cells. CAR-T cell therapy is an opportunity to treat patients that have not responded to other first-line cancer treatments. Nowadays, this type of therapy still has many challenges to overcome to be considered as a first-line clinical treatment. This emerging technology is still classified as an advanced therapy from the pharmaceutical point of view, hence, for it to be applied it must firstly meet certain requirements demanded by the authority. For this reason, the aim of this review is to present a global vision of different immunotherapies and focus on CAR-T cell technology analyzing its elements, its history, and its challenges. Furthermore, analyzing the opportunity areas for CAR-T technology to become an affordable treatment modality taking the basic, clinical, and practical aspects into consideration.

Olefin-Bridged Bidentate Adsorbates for Generating Self-Assembled Monolayers on Gold.

A series of custom-designed olefin-bridged bidentate adsorbates composed of an olefin group linking symmetrical hydrocarbon moieties of varying chain lengths was synthesized and used for the preparation of self-assembled monolayers (SAMs) on gold. The structures of the adsorbates are in the form Z-[CH3(CH2)m]2(C═C)[CH2SH]2 (OBCnSH) where m = 12-15 and n = m + 3 (OBC15SH, OBC16SH, OBC17SH, and OBC18SH). The influence of the olefin linker on the structural and interfacial properties of the SAMs was investigated and compared to SAMs formed from analogous n-alkanethiols. Characterization techniques included ellipsometry, X-ray photoelectron spectroscopy (XPS), polarization modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS), and contact angle measurements. The OBCnSH SAMs exhibited ellipsometric thicknesses that were similar to their monodentate counterparts, suggesting that the new olefin-bridged adsorbates pack similarly to the monodentate analogs. Characterization by PM-IRRAS revealed that the OBCnSH SAMs were as conformationally ordered as those derived from the reference n-alkanethiols with the exception of the adsorbate with the shortest chain length OBC15SH, which exhibited low coverage and a liquid-like structure. Unlike the SAMs derived from the n-alkanethiols, the OBCnSH SAMs failed to exhibit "odd-even" effects. However, the OBCnSH SAMs displayed similar hexadecane contact angles as their n-alkanethiol counterparts with the exception of OBC15SH, which exhibited markedly diminished hexadecane contact angles. The similar structural and interfacial properties of the OBCnSH SAMs, when compared to analogous n-alkanethiol SAMs, render the molecular architecture of the olefin-bridged dithiol as a robust platform for the synthesis of adsorbates with two chemically distinct tailgroups for use in the preparation and study of phase-incompatible "conflicted" interfaces.

Simultaneous Silencing of Xylanase Genes in Botrytis cinerea.

The endo-ß-1,4-xylanase BcXyn11A is one of several plant cell-wall degrading enzymes that the phytopathogenic fungus Botrytis cinerea secretes during interaction with its hosts. In addition to its enzymatic activity, this protein also acts as an elicitor of the defense response in plants and has been identified as a virulence factor. In the present work, other four endoxylanase coding genes (Bcxyn11B, Bcxyn11C, Bcxyn10A, and Bcxyn10B) were identified in the B. cinerea genome and the expression of all five genes was analyzed by Q-RT- PCR in vitro and in planta. A cross-regulation between xylanase genes was identified analyzing their expression pattern in the ΔBcxyn11A mutant strain and a putative BcXyn11A-dependt induction of Bcxyn10B gene was found. In addition, multiple knockdown strains were obtained for the five endoxylanase genes by transformation of B. cinerea with a chimeric DNA construct composed of 50-nt sequences from the target genes. The silencing of each xylanase gene was analyzed in axenic cultures and during infection and the results showed that the efficiency of the multiple silencing depends on the growth conditions and on the cross-regulation between them. Although the simultaneous silencing of the five genes was observed by Q-RT-PCR when the silenced strains were grown on medium supplemented with tomato extract, the endoxylanase activity measured in the supernatants was reduced only by 40%. Unexpectedly, the silenced strains overexpressed the Bcxyn11A and Bcxyn11C genes during the infection of tomato leaves, making difficult the analysis of the role of the endo-ß-1,4-xylanases in the virulence of the fungus.

The Effect of Excipients on the Permeability of BCS Class III Compounds and Implications for Biowaivers.

PURPOSE: Currently, the FDA allows biowaivers for Class I (high solubility and high permeability) and Class III (high solubility and low permeability) compounds of the Biopharmaceutics Classification System (BCS). Scientific evidence should be provided to support biowaivers for BCS Class I and Class III (high solubility and low permeability) compounds. METHODS: Data on the effects of excipients on drug permeability are needed to demonstrate that commonly used excipients do not affect the permeability of BCS Class III compounds, which would support the application of biowaivers to Class III compounds. This study was designed to generate such data by assessing the permeability of four BCS Class III compounds and one Class I compound in the presence and absence of five commonly used excipients. RESULTS: The permeability of each of the compounds was assessed, at three to five concentrations, with each excipient in two different models: Caco-2 cell monolayers, and in situ rat intestinal perfusion. No substantial increases in the permeability of any of the compounds were observed in the presence of any of the tested excipients in either of the models, with the exception of disruption of Caco-2 cell monolayer integrity by sodium lauryl sulfate at 0.1 mg/ml and higher. CONCLUSION: The results suggest that the absorption of these four BCS Class III compounds would not be greatly affected by the tested excipients. This may have implications in supporting biowaivers for BCS Class III compounds in general.

Best practices for the development, scale-up, and post-approval change control of IR and MR dosage forms in the current quality-by-design paradigm.

In this whitepaper, the Manufacturing Technical Committee of the Product Quality Research Institute provides information on the common, best practices in use today in the development of high-quality chemistry, manufacturing and controls documentation. Important topics reviewed include International Conference on Harmonization, in vitro-in vivo correlation considerations, quality-by-design approaches, process analytical technologies and current scale-up, and process control and validation practices. It is the hope and intent that this whitepaper will engender expanded dialog on this important subject by the pharmaceutical industry and its regulatory bodies.

Passive transdermal systems whitepaper incorporating current chemistry, manufacturing and controls (CMC) development principles.

In this whitepaper, the Manufacturing Technical Committee (MTC) of the Product Quality Research Institute has updated the 1997 Transdermal Drug Delivery Systems Scale-Up and Post Approval Change workshop report findings to add important new product development and control principles. Important topics reviewed include ICH harmonization, quality by design, process analytical technologies, product and process validation, improvements to control of critical excipients, and discussion of Food and Drug Administration's Guidance on Residual Drug in Transdermal and Related Drug Delivery Systems as well as current thinking and trends on in vitro-in vivo correlation considerations for transdermal systems.

Efficacy of a methylphenidate transdermal system versus t.i.d. methylphenidate in a laboratory setting.

OBJECTIVE: To test the efficacy and tolerability of the methylphenidate transdermal formulation (MTS) against immediate-release methylphenidate (IR MPH) and placebo in a 12-hr analog classroom setting. METHOD: A total of nine boys ages 6 to 9 years, medicated with MPH for ADHD, complete a within-subject, double-blind study. For the purpose of the study, the boys are administered a dose of 20 cm(2) MTS, a matched dose of IR MPH 10 mg TID, and placebo. ADHD symptoms and frequency counts of classroom rule violations and the number of math problems completed are assessed hourly, during three consecutive analog classroom sessions. RESULTS: Findings show that, across measures and throughout the day, both treatments significantly differentiated from placebo (p < .05) but not from each other. It is also observed that the MTS produced more consistent results across the day but had a delayed onset versus IR MPH. Both medications are well tolerated with only mild reductions in sleep onset. CONCLUSION: The MTS demonstrates comparable efficacy and tolerability to TID IR MPH.

Effects of application to two different skin sites on the pharmacokinetics of transdermal methylphenidate in pediatric patients with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study was conducted to quantify the rate and extent of methylphenidate (MPH) absorption from a transdermal system when applied to two different skin sites in pediatric subjects with attention-deficit/hyperactivity disorder (ADHD). METHODS: In an open-label, single-dose, randomized, two-way crossover study, children (6-12 years) with ADHD were randomized to wear one MPH transdermal system (MTS) on the hip area or on the scapular area for 16 hours. The following week, subjects were crossed over to the opposite application site. Serial blood samples were collected after each MTS application and pharmacokinetic (PK) parameters for d,l-MPH were calculated. Worn MTS units were assayed to calculate the Apparent Dose absorbed from MTS. RESULTS: PK analyses included 23 subjects. Hip and scapular application resulted in quantifiable levels of d,l-MPH, with approximately 31% higher bioavailability upon hip application. Logarithm transformed mean ratios for area under the curve (AUC) and C(max) indicated a lack of equivalence between the two sites. CONCLUSION: MTS applied to both hip and scapular areas resulted in quantifiable plasma levels of d,l-MPH. Bioavailability of MPH from the same transdermal delivery system appears to differ substantially when applied to two different skin surfaces in young children but with similar overall skin effects assessments.

Evolution of stimulants to treat ADHD: transdermal methylphenidate.

OBJECTIVE: The following comprehensive review describes the evolution of stimulant drug formulations used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Emphasis is placed on the basic and clinical pharmacology of the dl-methylphenidate (MPH) transdermal system (MTS). METHODS: The pharmacokinetic and pharmacodynamic literature pertaining to MPH and amphetamine enantiomers was reviewed in the context of ADHD therapy and MTS as a treatment option. RESULTS: MTS incorporates MPH into an adhesive monolithic matrix, using the free base form of the drug to facilitate transdermal absorption. MTS technology minimizes contact dermatitis by eliminating to need for percutaneous penetration enhancers. After a lag time of approximately 2 h, plasma concentrations of the therapeutic d-MPH isomer become detectable, then continuously rise over the course of the recommended 9 h wear time. Concentrations of l-MPH typically attain 40-50% that of d-MPH (vs. 1-2% following oral MPH). Unauthorized MTS removal poses some misuse liability and over 50% of MTS drug content remains in the discarded system. CONCLUSIONS: While liquid or chewable MPH formulations overcome potential swallowing difficulties, as do sprinkled once-daily extended-release (ER) MPH products, only MTS addresses swallowing difficulties while also offering a flexible individualized MPH exposure time in a once-daily MPH regimen.

Effect of the rate of niacin administration on the plasma and urine pharmacokinetics of niacin and its metabolites.

The metabolic profile of niacin is influenced by the rate of niacin administration. This study characterizes the effect of administration rate on the pharmacokinetics of niacin and its metabolites. Twelve healthy males were enrolled in an open-label, dose-rate escalation study and received 2000 mg niacin at 3 different dosing rates. Plasma was analyzed for niacin, nicotinuric acid, nicotinamide, and nicotinamide-N-oxide. Urine was analyzed for niacin and the metabolites nicotinuric acid, nicotinamide, nicotinamide-N-oxide, N-methylnicotinamide, and N-methyl-2-pyridone-5-carboxamide. C(max) and AUC(0-t) for niacin and nicotinuric acid increased with an increase in dosing rate. The changes observed in plasma nicotinamide and nicotinamide-N-oxide parameters, however, did not correlate to dosing rate. The total amount of niacin and metabolites excreted in urine was comparable for all 3 treatments. However, with the increase in dosing rate, urine recovery of niacin and nicotinuric acid showed a significant increase, whereas N-methyl-2-pyridone-5-carboxamide and N-methylnicotinamide showed a significant decrease.

New methylphenidate formulations for the treatment of attention-deficit/hyperactivity disorder.

dl-Methylphenidate (MPH) remains the most widely used pharmacological agent in the treatment of attention-deficit/hyperactivity disorder (ADHD). The predominantly dopaminergic mechanism of the psychostimulant actions has become more clearly defined. Neuroimaging and genetic studies are revealing the underlying neuropathology in ADHD. Novel extended-release (ER) MPH formulations now offer drug delivery options to overcome both the short-term actions of immediate-release (IR) MPH and the acute tolerance associated with the first-generation ER-MPH products. These novel MPH products apply proprietary technologies such as OROS (Alza), Diffucaps (Eurand) and SODAS (Elan) to offer both the convenience of once-a-day administration and absorption profiles resembling, to varying degrees, the standard multiple dose schedules of IR-MPH. The pharmacodynamics of the separate MPH enantiomers is in the process of further neuropharmacological characterisation. It is well established that dl-MPH undergoes marked stereoselective metabolism. Although l-MPH exhibits only minimal oral absorption, it may preferentially penetrate the brain, and interacts with ethanol to form the metabolite ethylphenidate. The newly approved resolved enantiomer product d-MPH is now available in an IR formulation, and when administered at one-half the dose to that of the racemate, is purported to produce a longer duration of clinical effect, despite essentially identical pharmacokinetics. A long-acting formulation of d-MPH, which employs the SODAS technology, is in the advanced stages of clinical development.

Registro de cáncer ginecológico Clínica San Pedro Claver 2003 / A review of patients suffering from gynaecological cancer attending the San Pedro Claver Clinic during 2003

Objetivo: revisar los casos de cáncer ginecológico atendidos durante el año 2003 en la Clínica San Pedro Claver, Bogotá, Colombia. Materiales y métodos: la captación de los casos se hizo a través de la junta de ginecología oncológica a la cual asisten todas las pacientes nuevas de este servicio. Para garantizar la inclusión de la totalidad de ellas, se realizó una búsqueda activa de casos entre las pacientes hospitalizadas, registros de programación de cirugía, reportes de patología y en consulta externa. Los datos fueron registrados en un archivo de Excel y evaluados mediante el programa EPIINFO 2002. Resultados: se encontraron 158 casos de cáncer ginecológico, siendo el cáncer de cérvix (75 mujeres) el de mayor frecuencia; para efectos del registro, se consideraron dos tipos de tumores de cérvix: los exocervicales (59 casos) y los endocervicales (16 casos). En estas dos localizaciones, la distribución por estadios mostró el mayor número de casos en estado Ib, 49 por ciento en exocérvix y 62 por ciento en los tumores de endocérvix. El tratamiento más frecuentemente indicado en las mujeres con cáncer de cérvix fue la cirugía. El carcinoma de endometrio, con 46 mujeres, mostró mayoría en estado I (50 por ciento); el tipo histológico más común fue el carcinoma endometrioide (87 por ciento). El tratamiento más usual fue el de cirugía, aplicado en el 93 por ciento de ellos. Se encontraron 34 pacientes con carcinoma de ovario, entre los que hubo una proporción igual de casos en estados tempranos I y II que en los tardíos III y IV; el tipo histológico más frecuente fue el seroso (52,3 por ciento). El tratamiento más usado fue la combinación de cirugía y quimioterapia. Conclusiones: el registro institucional de cáncer de la Clínica San Pedro Claver es una herramienta útil para conocer la distribución de los diferentes tumores ginecológicos evaluados en esta entidad. Permite establecer sus características personales, clínicas y las modalidades terapéuticas recibidas. El cáncer ginecológico registrado con mayor frecuencia en el año 2003 en esta clínica, fue el de cérvix. Este carcinoma es susceptible de prevención secundaria mediante la citología cervico-vaginal por lo que se hace imperativa la necesidad de revisar y fortalecer el programa de tamizaje para esta enfermedad.

Diagnostico de lesiones no palpables del seno / Palpable breast lesions

Resultados principales: la detección de lesiones neoplásicas en el seno cuando aún no han llegado al tamaño de hacerse palpables, representa un importante avance en el manejo y pronóstico del cáncer de seno. La mamografía es el examen que con más frecuencia permite el diagnóstico de estas lesiones. Puesto que las lesiones mamográficas, en la mayoría de las veces, representan lesiones benignas, se han acordado lineamientos de clasificación para correlacionar los hallazgos encontrados en el examen radiológico, con la posibilidad de encontrar patología maligna en la biopsia. El sistema BI-RADS ("Breast imaging reporting and data system") se usa hoy día con este propósito. Una vez definida la necesidad de establecer un diagnóstico patológico de la lesión, se desarrollan diferentes procedimientos que orientan la biopsia. El método considerado como "prueba de oro", es la marcación por arpón, pero se han desarrollado métodos basados en equipos de estereotaxia, que aunque tienen una menor precisión, poseen menos complicaciones y permiten un resultado estético óptimo. Se han propuesto otros sistemas de localización de lesiones no palpables, como el. de biopsia guiada por radiocirugía y se adelanta investigación con aplicaciones diferentes de la Resonancia Nuclear Magnética (RNM). Conclusiones: la biopsia escisional previa marcación por arpón, representa el método más preciso en el diagnóstico de lesiones no palpables de seno. Sin embargo, con equipos de estereotaxia, se pueden lograr resultados que aunque tienen menor precisión que la biopsia escisional, tienen menos complicaciones y mejor resultado estético

A new solution-based intranasal triamcinolone acetonide formulation in patients with perennial allergic rhinitis: how does the pharmacokinetic/pharmacodynamic profile for cortisol suppression compare with an aqueous suspension-based formulation?

The present study was undertaken to describe the pharmacokinetics of a new solution-based intranasal triamcinolone acetonideformulation (Tri-Nasal) in patients with perennial allergic rhinitis and to use a pharmacokinetic/pharmacodynamic (PK/PD) simulation approach to compare the potential effects on plasma cortisol with that of an aqueous suspension-based nasal triamcinolone acetonide formulation (Nasacort AQ). Data from an open-label, randomized, three-way crossover study in patients with perennial allergic rhinitis receiving three doses (100, 200, and 400 microg) of a nasal solution-based triamcinolone acetonide formulation (Tri-Nasal) over 7 days were used to describe the pharmacokinetics of this formulation. Available literature data for a suspension-based aqueous triamcinolone acetonide formulation (Nasacort AQ) were used to describe its pharmacokinetic profile after similar single doses of 110, 220, and 440 microg. A PK/PD simulation approach was used to predict the anticipated cumulative cortisol suppression (CCS) of these two formulations. These simulations suggested a cortisol suppression of 8% to 16% for the single and steady-state doses of the solution-based product. Similar CCS estimates were predicted for equivalent doses of the aqueous suspension-based triamcinolone acetonide formulation with no difference between both formulations. Post hoc power analysis suggested that the predicted cortisol suppression is not likely to be significant for either preparation, including the clinically recommended doses of 200 and 220 microg of the solution-based and suspension-based formulations, respectively. In summary, based on the results of this PK/PD simulation, the plasma levels observed afternasal administration of the solution or the aqueous suspension are unlikely to induce a clinically relevant cortisol suppression, especially for the recommended dosing regimens of 200 and 220 microg/day.