Anterior lamellar corneoscleral keratoplasty for the management of corneal thinning following treatment with mitomycin-C and interferon to treat highly suspected ocular surface squamous neoplasia: a case report

ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.

Usabilidade de um aplicativo móvel de apoio aos profissionaisde saúde para cálculos de doses de vancomicina / Usability of a mobile application supporting healthprofessionals on vancomycin dosing calculation

O aplicativo móvel CalcVAN foi desenvolvido para auxiliar os profissionais de saúde para otimizar as doses de vancomicina em pacientes hospitalizados. Porém, é imprescindível avaliar a sua usabilidade antes de disponibilizá-lo para prática clínica. Assim, o objetivo do estudo é avaliar a usabilidade do aplicativo móvel na perspectiva dos profissionais de saúde. Trata-se de um estudo descritivo, de avaliação heurística da usabilidade de um aplicativo móvel. Foram convidados profissionais da área de saúde com expertise no tema de gerenciamento de antimicrobianos e vancomicina. O instrumento validado Smartphone Usability questionnaiRE (SURE) foi utilizado para mensuração da usabilidade por meio de um questionário on-line. Vinte e um especialistas participaram do estudo, com média de idade de 32,6 anos, sendo a maioria de mulheres (n = 14, 66,7%), profissionais farmacêuticos (n = 13, 61,9%), com pós-graduação lato sensu (n = 10, 47,6%), que trabalhavam em hospitais públicos ou privados (n = 15, 71,4%) e com média de experiência em 9,7 anos. Com base na interpretação dos resultados obtidos pelo instrumento SURE, a média de usabilidade geral do CalcVAN foi de 83 pontos, com escore menor de 78 e maior de 90 pontos. O teste de usabilidade foi enquadrado nos dois últimos níveis, 70 e 80, onde os profissionais de saúde passaram a concordar fortemente e totalmente, indicando que o aplicativo móvel apresenta uma usabilidade satisfatória. O CalcVAN atingiu uma usabilidade satisfatória e atende as necessidades e exigências dos profissionais de saúde, mostrando--se eficiente para realizar as funções propostas.

The CalcVAN app was developed to assist healthcare professionals in optimizing vancomycin doses for hospitalized patients. However, the usability test before making it available for clinical practice is essential. Therefore, the study aims to evaluate the usability of the app from the perspective of health professionals. A descriptive study, a heuristic evaluation of the usability of a mobile application was conducted. Healthcare professionals with expertise in antimicrobial management and vancomycin were invited to participate. The validated Smartphone Usability questionnaiRE (SURE) was used to measure usability through an online questionnaire. Twenty-one experts participated in the study, with a mean age of 32.6 years, mostly of them women (n = 14, 66.7%), pharmacists (n = 13, 61.9%), with postgraduate education (n = 10, 47.6%), working in private or public hospitals (n = 15, 71.4%), and a mean experience of 9.7 years. Overall usability score for CalcVAN was 83 points, ranging from a minimum of 78 to a maximum of 90 points. The usability test registered within the last two levels, 70 and 80, with users expressing strongly and fully agreed, indicating that the app demonstrates satisfactory usability. CalcVAN achieved satisfactory usability, fulfilling the needs and requirements of health professionals, proving to be efficient in performing the intended functions.

Efficacy of Rituximab Versus Cyclophosphamide and Mycophenolate for the Treatment of Interstitial Lung Disease in Systemic Sclerosis: A Systematic Review.

Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc), contributing to significant morbidity and mortality in affected individuals. The optimal treatment approach for SSc-associated ILD remains uncertain, with rituximab, cyclophosphamide, and mycophenolate among potential therapeutic options. This systematic review aims to evaluate and synthesize the existing evidence on the efficacy of rituximab compared to cyclophosphamide and mycophenolate for the treatment of ILD in patients with systemic sclerosis. A comprehensive search of the following electronic databases, PubMed, Science Direct, Google Scholar, and Cochrane Library, has been conducted to identify relevant studies, including randomized controlled trials, systematic review and meta-analysis, prospective cohort studies, and retrospective cohort studies. Data on study characteristics, participant demographics, interventions, outcomes, and key findings have been extracted and synthesized. The risk of bias in the included studies has been assessed using appropriate tools such as the Cochrane Bias assessment tool for randomized controlled trials, the New Castle Ottawa tool for cohort studies, and the AMSTAR checklist for systematic reviews and meta-analysis. The research team ultimately selected 15 high-quality studies for review. Rituximab demonstrated similar efficacy to cyclophosphamide and mycophenolate in improving lung function (forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO)), with fewer severe adverse events. Cyclophosphamide, while effective, had higher toxicity, leading to more frequent adverse events such as leukopenia and infections. Mycophenolate showed comparable efficacy to cyclophosphamide but with fewer side effects, making it a well-tolerated alternative. The findings of this systematic review will provide valuable insights into the comparative efficacy of rituximab, cyclophosphamide, and mycophenolate in the management of ILD in systemic sclerosis, informing clinical decision-making and guiding future research in this area.

[Assessing the Impact of in-Hospital Formulary Policies on the Prescription Patterns of Direct Oral Anticoagulants (DOACs)].

Prescribing direct oral anticoagulants (DOACs) with off-label dosage and administration is discouraged due to concerns about their effectiveness and safety. Consequently, our hospital pharmacist established a formulary with physicians for oral anticoagulants. Our study aimed to assess the adherence to this formulary by investigating the rate of appropriate DOAC prescribing. We included patients who were newly prescribed or continued on DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) at our hospital. We calculated the percentage of patients prescribed the correct dosage and administration according to the package insert and compared this across three time periods: pre-intervention (period A; April-September 2019), post-intervention phase 1 (period B; August 2021-January 2022), and post-intervention phase 2 (period C; November 2022-April 2023). We also examined the number of inquiries and consultation requests made by hospital pharmacists regarding DOAC dosage and administration. A total of 782 patients were surveyed (191 in period A, 263 in period B, and 328 in period C). The appropriate prescribing rates for DOACs were 79.1% in period A, 84.4% in period B, and 86.6% in period C. The proportion of cases where hospital pharmacists questioned or consulted doctors about DOAC dosage and administration was 3.7% in period A, 6.1% in period B, and 10.1% in period C. These findings indicate that active intervention by hospital pharmacists using the formulary regarding oral anticoagulant formularies may promote appropriate DOAC use.

Temperature Excursion Management: A Tier-Based Approach for Commercial Oral Solid Dosage Forms.

Temperature excursions during product storage, transportation, and handling can deteriorate product quality. Following a temperature excursion event, the impact of the event on the product quality should be evaluated to determine if the product can be used or if it needs to be discarded. Pharmaceutical companies are required to have defined procedures for managing temperature excursions and performing impact assessment after an excursion occurs. In an increasingly complex supply chain, it is vital to develop processes that can expedite the review of these events. A tier-based approach is presented for analyzing the impact of temperature excursion on commercial small molecule drug products intended to be stored at room temperature. Utilization of each of the three tiers is based on whether the excursion temperature and/or excursion duration are within a predetermined, product-specific, allowable range. The stress study temperature defines the allowable temperature range, while the allowable duration is determined using a mathematical approach outlined in this article. Tier 1, specific to the product, allows products to be dispositioned for use without further assessment when temperature excursion events fall within both the product-specific allowable excursion temperature and duration ranges. Tier 2 applies when the excursion temperature is within the allowable range, but the duration exceeds it. Lot-specific release data is used for impact assessment in this tier. Finally, Tier 3 utilizes Arrhenius extrapolation to predict the final degradation and perform the impact assessment when the excursion temperature surpasses the allowable temperature range.

Esophageal transit of solid oral dosage forms - impact of different surface materials characterized in vitro and in vivo by MRI in healthy volunteers.

Acceptable swallowability and complete esophageal transit are decisive for the safe and effective administration of solid oral dosage forms. This applies in particular to the main user group of medicines, older adults, who often suffer from swallowing difficulties. It is well known that surface properties play an important role in this respect. In the past, this has led to the development of numerous coating formulations for tablets with improved swallowability. However, in vitro and especially in vivo data investigating a positive effect of different coating materials is limited. Therefore, we investigated coating materials being based on polyvinyl alcohol, hydroxypropyl methylcellulose, and a copolymer of methacrylate in respect to their influence on swallowability and esophageal transit of a tablet formulation. They were compared to uncoated tablets as well as to hard gelatin capsules. Three in vitro assays suitable for routine use in pharmaceutical development were performed: i.) Wettability test in artificial saliva; ii.) Swelling measurement in artificial saliva; iii.) Measurement of the adhesion between surface materials and a simulated mucosa surface. All three assays resulted in a differentiation of the surface materials. The coated tablets showed favorable behavior compared to uncoated tablets and hard gelatin capsules. To test the effect of the different materials in vivo, an intervention study was conducted. 36 adults were included and the likeliness of prolonged esophageal transit of (un-)coated tablets as well as a hard gelatin capsule of the same weight was objectively evaluated by means of magnetic resonance imaging. While hard gelatin capsules showed highest rates for prolonged esophageal transit, the tendency for adhesion was reduced for uncoated tablets, and least for coated tablets, i.e., prolonged esophageal transit in 22.2%, 11.1%, and ≤5.6% of the cases, respectively. Further differentiation of the coating materials was not possible. Subjective evaluations of each participant with respect to subjective swallowability and esophageal transit did not correlate well with the objective measurements by means of magnetic resonance imaging. The use of coatings in general has a positive influence on esophageal transit. However, the selection of coating type seems to be of greater importance in respect to patients' oral perception of the dosage forms compared to their influence on the probability for prolonged esophageal transit.

Aspirin in Children; are There Not Two Sides of the Same Coin?

Dose-dependent in vitro effects of aspirin on platelet inhibition and predictors of non-responsiveness have led to the recommendation of significantly higher doses of aspirin (5 mg/kg/day) in newborns and infants. The results are inconsistent with the pharmacodynamic effects of clopidogrel in newborns, where approximately 30% (0.2 mg/kg/day) of the adult dose (75 mg/day) showed equally effective antiaggregative effects. Consequently, the optimal aspirin dosage remains to be determined. The administration to newborns with congenital heart defects needs to address treatment goals, while accounting for the intricate interactions between platelets and endothelium, as well as the unique aspects of surgical and interventional procedures.

Image quality-based dose optimization in pediatric cone-beam computed tomography: A pilot methodological study.

Purpose: This study aimed to propose a methodological approach for reducing the radiation dose in pediatric conebeam computed tomography (CBCT), focusing exclusively on balancing image quality with dose optimization. Materials and Methods: The dose-area product (DAP) for exposure was reduced using copper-plate attenuation of an X-ray source. The thickness of copper (Cu) was increased from 0 to 2.2 mm, and 10 different DAP levels were used. The QUART DVT_AP phantom and pediatric radiologic dentiform were scanned under the respective DAP levels. The contrast-to-noise ratio (CNR), image homogeneity, and modulation transfer function (MTF) were analyzed using the QUART DVT_AP phantom. An expert evaluation (overall image grade, appropriateness of field of view, artifacts, noise, and resolution) was conducted using pediatric dentiform images. The critical DAP level was determined based on phantom and dentiform analysis results. Results: CNR and image homogeneity decreased as the DAP was reduced; however, there was an inflection point of image homogeneity at Cu 1.6 mm (DAP=138.00 mGy·cm2), where the value started increasing. The MTF showed constant values as the DAP decreased. The expert evaluation of overall image grades showed "no diagnostic value" for dentiform images with Cu 1.9-2.2 mm (DAP=78.00-103.33 mGy·cm2). The images with Cu 0-1.6 mm (DAP=138.00-1697.67 mGy·cm2) had a "good," "moderate," or "poor but interpretable" grade. Conclusion: Reducing DAP beyond a 1.6-mm Cu thickness degraded CBCT image quality. Image homogeneity and clinical image grades indicated crucial decision points for DAP reduction in pediatric CBCT scans.

Investigating the Effects of Formulation Variables on the Disintegration of Spray Dried Amorphous Solid Dispersion Tablets.

Amorphous solid dispersion (ASD) tablets based on hydrophilic polymer carriers may encounter disintegration challenges. In this work, the effect of different formulation composition variables on the ASD tablet disintegration performance was systematically studied. GDC-0334: copovidone (PVPVA) 60: 40 ASD prepared by spray drying was selected as the model ASD system. The effects of ASD loading, filler type and ratio, disintegrant type and level were then investigated using tablets made by direct compression process. Tablet disintegration time increased with the increase of ASD loading, especially when ASD loading exceeded 50%. At the same tablet solid fraction, when lactose was used as the soluble filler, faster tablet disintegration time was observed compared to the tablets with mannitol as the soluble filler. Among the three tested disintegrants, croscarmellose sodium performed the best in facilitating the ASD tablet disintegration, followed by sodium starch glycolate, and crospovidone was the poorest. When croscarmellose sodium was used as the disintegrant, 5% level was sufficient to enable ASD tablet disintegration at 60% ASD loading and further increase of croscarmellose sodium level to 8% did not provide additional benefit. Water uptake experiments were performed on selected tablets and the results demonstrated a positive correlation with tablet disintegration time, indicating water penetration is a major contributing step for the disintegration of our ASD tablets. Overall, this work provides a rationale for excipient selection and insights into building a platform formulation approach for developing immediate-release ASD tablets.

Application value of individualized tube voltage, contrast injection, and adaptive statistical iterative reconstruction V algorithm based on body mass index in renal computed tomography angiography for radiation and iodinated contrast dose reduction.

OBJECTIVES: To explore the application value of body mass index (BMI)-based kilovoltage peak (kVp) selection and contrast injection protocol combined with different adaptive statistical iterative reconstruction V (ASIR-V) strengths in renal computed tomography angiography (CTA) in reducing radiation and contrast medium (CM) doses. METHODS: One-hundred renal CTA patients were prospectively enrolled and were divided into individualized kVp group (group A, n = 50) and conventional 100 kVp group (group B, n = 50), both with automatic tube current modulation and CM of Iohexol at 350 mgI/mL concentration. Group A: 70 kVp, noise index (NI) of 18 and CM dose rate of 17 mgI/kg/s for 10 s for BMI <25 kg/m2 patients; 80 kVp, NI = 17, and CM dose rate of 19 mgI/kg/s for 10 s for 25 kg/m2≤BMI≤30 kg/m2 patients. Group B: 100 kVp, 50 mL of CM at the flow rate of 4.5 mL/s. The objective image quality, effective radiation dose, CM dose, injection rate, and image quality were compared between the 2 groups. RESULTS: There was no significant difference in patient characteristics between the 2 groups (P > .05). Compared to group B, group A significantly reduced effective radiation dose by 28.4%, CM dose by 27.2%, and injection rate by 22.7% (all P < .001). The 2 groups had similar SD values in erector spine (P > .05). Group A had significantly higher CT values, SNR, and CNR values of the renal arteries than group B (all P < .001). The 2 radiologists had excellent agreement (Kappa value > 0.8) in the subjective scores of renal CTA images and showed no statistically significant difference between the 2 groups (4.57 ± 0.42 vs 4.41 ± 0.49) (P > .05). CONCLUSIONS: BMI-based scan and reconstruction protocol in renal CTA significantly reduces radiation and contrast doses while maintaining diagnostic image quality. ADVANCES IN KNOWLEDGE: (i) BMI-based individualized tube voltage selection and contrast injection protocol in renal CTA reduces both radiation and contrast doses over conventional protocol. (ii) The combination of lower kVp and higher weight ASIR-V maybe used to improve image quality in terms of contrast enhancement and image noise under lower radiation and contrast dose conditions. (iii) Renal CTA of normal size (BMI ≤ 30 kg/m2) patients acquired at low radiation dosage and low iodine contrast dose through the combination of low tube voltage and ASIR-V algorithm achieves excellent diagnostic image quality with a good inter-rater agreement.

The Impact of Exposure Dosage and Host Genetics on the Shedding Kinetics of Flavobacterium psychrophilum in Rainbow Trout.

Flavobacterium psychrophilum, the causative agent of bacterial cold water disease (BCWD), is one of the leading pathogens in rainbow trout (Oncorhynchus mykiss) aquaculture. To date, there is little knowledge of the transmission kinetics of F. psychrophilum over the course of infection. In particular, how transmission is affected by host genotype and pathogen exposure dosage are not well studied. In order to fill in these knowledge gaps, we exposed two divergently selected lines of rainbow trout (ARS-Fp-R and ARS-Fp-S) to a range of dosages of F. psychrophilum (strain CSF117-10). We then measured mortality and bacterial shedding to estimate transmission risk at multiple time points since initial infection. As dosage increased, the number of fish shedding and the amount of bacteria shed increased ranging from 0% to 100% and 103 to 108 cells fish-1 h-1, respectively. In addition, we found that disease resistance (survival) was not correlated with transmission risk blocking, in that 67% of fish which shed bacteria experienced no clinical disease. In general, fish mortality began on Day 3, peaked between Days 5-7 and was higher in the ARS-Fp-R line. Results from this study could be used to develop epidemiological models and improve disease management, particularly in the context of aquaculture and selective breeding.

Therapeutic drug monitoring of linezolid in Chinese premature neonates: a population pharmacokinetic analysis and dosage optimization.

This study aimed to develop a pharmacokinetic model of linezolid in premature neonates and evaluate and optimize the administration regimen. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the blood concentration data of 54 premature neonates after intravenous administration of linezolid, and the relevant clinical data were collected. The population pharmacokinetic (PPK) model was established by nonlinear mixed effects modeling. Based on the final model parameters, the optimal administration regimen of linezolid in premature neonates with different body surface areas (BSA) was simulated and evaluated. The pharmacokinetic properties of linezolid in premature neonates are best described by a single-compartment model with primary elimination. The population typical values for apparent volume of distribution and clearance were 0.783 L and 0.154 L/h, respectively. BSA was a statistically significant covariate with clearance (CL) and volume of distribution (Vd). Monte Carlo simulations showed that the optimal administration regimen for linezolid in premature neonates was 6 mg/kg q8h for BSA 0.11 m2, 7 mg/kg q8h for BSA 0.13 m2, and 9 mg/kg q8h for BSA 0.15 m2 with minimum inhibitory concentration (MIC) ≤1 mg/L, 7 mg/kg q8h for BSA 0.11 m2, 8 mg/kg q8h for BSA 0.13 m2, and 10 mg/kg q8h for BSA 0.15 m2 with MIC = 2 mg/L. A pharmacokinetic model was developed to predict the blood concentration on linezolid in premature neonates. Based on this model, the optimal administration regimen of linezolid in premature neonates needs to be individualized according to different BSA levels.