Regulations on excipients used in 3D printing of pediatric oral forms.

A promising solution to customize oral drug formulations for the pediatric population has been found in the use of 3D printing, in particular Fused Deposition Modeling (FDM) and Semi-Solid Extrusion (SSE). Although formulation development is currently limited to research studies, the rapid advances in 3D printing warn of the need for regulation. Indeed, even if the developed formulations include pharmaceutical excipients used to produce traditional oral forms such as tablets, the quantities of excipients used must be adapted to the process. Therefore, the aim of this literature review is to provide a synthesis of the available safety data on excipients mainly used in extrusion-based 3D printing for the pediatric population. A total of 39 relevant articles were identified through two scientific databases (PubMed and Science Direct). Then, groups of the main excipients were listed including their general information (name, chemical structure and pharmaceutical use) and a synthesis of the available safety data extracted from several databases. Finally, the role of the excipients in 3D printing, the amount used in formulations and the oral dose administered per form are presented.

Preoperative progressive pneumoperitoneum and botulinum toxin type A in patients with large incisional hernia.

PURPOSE: Combination of preoperative progressive pneumoperitoneum (PPP) and botulinum toxin type A (BT) has not been previously reported in the management of large incisional hernia (LIH). METHODS: Observational study of 45 consecutive patients with LIH between June 2010 and July 2014. The diameters of the hernia sac, the volumes of the incisional hernia (VIH) and the abdominal cavity (VAC), and the VIH/VAC ratio were measured before and after PPP and BT using abdominal CT scan data. We indicated the combination of both techniques when the volume of the incisional hernia (VIH)/volume of the abdominal cavity (VAC) ratio was >20%. RESULTS: The median insufflated volume of air for PPP was 8.600 ± 3.200 cc (4.500-13.250), over a period of 14.3 ± 1.3 days (13-16). BT administration time was 40.2 ± 3.3 days (37-44). We obtained an average value of reduction of 14% of the VIH/VAC ratio after PPP and BT (p < 0.05). Complications associated with PPP were 15.5%, and with surgical technique, 26.6%. No complications occurred during the BT administration. Reconstructive technique was anterior CST and primary fascial closure was achieved in all patients. Median follow-up was 40.5 ± 19 months (12-60) and we reported 2 cases of hernia recurrence (4.4%). CONCLUSIONS: Preoperative combination of PPP and BT is feasible and a useful tool in the surgical management of LIH, although at the cost of some specific complications.

Ensayo clínico aleatorizado para la comparación de dos métodos de cura de traqueotomía en una Unidad de Cuidados Intensivos / Randomised clinical trial to compare two tracheotomy care methods in an Intensive Care Unit

Introducción: La traqueotomía es una técnica habitual en las Unidades de Cuidados Intensivos (UCI). Es sabido que los cuidados enfermeros durante y posteriores al procedimiento están directamente relacionados con el éxito del mismo, minimizando el riesgo de aparición de complicaciones como la infección del estoma y favoreciendo la adecuada evolución del paciente crítico. Objetivos: Comparar la incidencia de infección en las traqueotomías realizadas en UCI según el antiséptico empleado: cura con polihexanida (PLX) y cura con suero fisiológico + povidona yodada (PY). Material y método: Ensayo experimental, aleatorizado y abierto, realizado en una UCI polivalente de 32 camas durante 2 años. El estudio fue aprobado por el Comité Ético de Investigación del Principado de Asturias. Resultados: La tasa observada de infecciones por 100 pacientes-día de traqueotomía fue de 1,34 (IC del 95%, 0,81-2,01): 1,46 en PLX y 1,21 PY (p valor 0,685). Conclusiones: A pesar de que el tratamiento experimental (PLX) ha mostrado su eficacia en otro tipo de heridas, en nuestro estudio no se encontraron diferencias significativas entre esta técnica y la estándar. Dado que no existe un registro nacional de incidencia de infección asociada a traqueotomías, no se puede saber si la observada está dentro de los parámetros habituales

Introduction: Tracheotomy is a common technique in Intensive Care Units (ICU). It is known that nursing care during and after that procedure is directly related to its success, by reducing the possible complications to a minimum, such as the stoma infection, and contributing to a favourable outcome in critical patients. Objectives: To compare the use of polyhexanide (PLX) versus saline + povidone iodine (PY) as antiseptics and infection incidence in tracheostomies performed in Intensive Care Units. Material and method: A 2-year, experimental, randomised, open-label trial carried out in a multidiscipline ICU with 32 beds. The study was approved by the Research Ethics Committee of Principality of Asturias. Results: The overall infection rate observed for every hundred patients was 1.34 (95% CI; 0.81-2.01), with 1.46 when using PLX and 1.21 for PY (P=.685). Conclusions: In spite of the experimental treatment (PLX) was shown to be effective in other types of wounds in our study. No significant differences were found between this technique and the standard one. Since there is no national registry of tracheotomy- associated infections, it is not possible to know whether the rate observed is within the usual parameters

[Randomised clinical trial to compare two tracheotomy care methods in an Intensive Care Unit]. / Ensayo clínico aleatorizado para la comparación de dos métodos de cura de traqueotomía en una Unidad de Cuidados Intensivos.

INTRODUCTION: Tracheotomy is a common technique in Intensive Care Units (ICU). It is known that nursing care during and after that procedure is directly related to its success, by reducing the possible complications to a minimum, such as the stoma infection, and contributing to a favourable outcome in critical patients. OBJECTIVES: To compare the use of polyhexanide (PLX) versus saline+povidone iodine (PY) as antiseptics and infection incidence in tracheostomies performed in Intensive Care Units. MATERIAL AND METHOD: A 2-year, experimental, randomised, open-label trial carried out in a multidiscipline ICU with 32 beds. The study was approved by the Research Ethics Committee of Principality of Asturias. RESULTS: The overall infection rate observed for every hundred patients was 1.34 (95% CI; 0.81-2.01), with 1.46 when using PLX and 1.21 for PY (P=.685). CONCLUSIONS: In spite of the experimental treatment (PLX) was shown to be effective in other types of wounds in our study. No significant differences were found between this technique and the standard one. Since there is no national registry of tracheotomy- associated infections, it is not possible to know whether the rate observed is within the usual parameters.

Predicting 30-day Hospital Readmission with Publicly Available Administrative Database. A Conditional Logistic Regression Modeling Approach.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Big Data and Analytics in Healthcare". BACKGROUND: Hospital readmissions raise healthcare costs and cause significant distress to providers and patients. It is, therefore, of great interest to healthcare organizations to predict what patients are at risk to be readmitted to their hospitals. However, current logistic regression based risk prediction models have limited prediction power when applied to hospital administrative data. Meanwhile, although decision trees and random forests have been applied, they tend to be too complex to understand among the hospital practitioners. OBJECTIVES: Explore the use of conditional logistic regression to increase the prediction accuracy. METHODS: We analyzed an HCUP statewide inpatient discharge record dataset, which includes patient demographics, clinical and care utilization data from California. We extracted records of heart failure Medicare beneficiaries who had inpatient experience during an 11-month period. We corrected the data imbalance issue with under-sampling. In our study, we first applied standard logistic regression and decision tree to obtain influential variables and derive practically meaning decision rules. We then stratified the original data set accordingly and applied logistic regression on each data stratum. We further explored the effect of interacting variables in the logistic regression modeling. We conducted cross validation to assess the overall prediction performance of conditional logistic regression (CLR) and compared it with standard classification models. RESULTS: The developed CLR models outperformed several standard classification models (e.g., straightforward logistic regression, stepwise logistic regression, random forest, support vector machine). For example, the best CLR model improved the classification accuracy by nearly 20% over the straightforward logistic regression model. Furthermore, the developed CLR models tend to achieve better sensitivity of more than 10% over the standard classification models, which can be translated to correct labeling of additional 400 - 500 readmissions for heart failure patients in the state of California over a year. Lastly, several key predictor identified from the HCUP data include the disposition location from discharge, the number of chronic conditions, and the number of acute procedures. CONCLUSIONS: It would be beneficial to apply simple decision rules obtained from the decision tree in an ad-hoc manner to guide the cohort stratification. It could be potentially beneficial to explore the effect of pairwise interactions between influential predictors when building the logistic regression models for different data strata. Judicious use of the ad-hoc CLR models developed offers insights into future development of prediction models for hospital readmissions, which can lead to better intuition in identifying high-risk patients and developing effective post-discharge care strategies. Lastly, this paper is expected to raise the awareness of collecting data on additional markers and developing necessary database infrastructure for larger-scale exploratory studies on readmission risk prediction.

Supramolecular approaches for drug development.

Various supramolecular systems can be used as drug carriers to alter physicochemical and pharmacokinetic characteristics of drugs. Representative supramolecular systems that can be used for this purpose include surfactant/polymer micelles, (micro)emulsions, liposomes, layer-by-layer assemblies, and various molecular conjugates. Notably, liposomes are established supramolecular drug carriers, which have already been marketed in formulations including AmBisome(®) (for treatment of fungal infection), Doxil(®) (for Kaposi's sarcoma), and Visudyne(®) (for age-related macular degeneration and choroidal neovascularization). Microemulsions have been used oral drug delivery of poorly soluble drugs due to improvements in bioavailability and predictable of absorption behavior. Neoral(®), an immunosuppressant used after transplant operations, is one of the most famous microemulsion-based drugs. Polymer micelles are being increasingly investigated as novel drug carriers and some formulations have already been tested in clinical trials. Supramolecular systems can be functionalized by designing the constituent molecules to achieve efficient delivery of drugs to desired sites in the body. In this review, representative supramolecular drug delivery systems, that may improve usability of candidate drugs or add value to existing drugs, are introduced.

The detection of astrovirus in sludge biosolids using an integrated cell culture nested PCR technique.

The work presented here demonstrates the utility of the integrated cell culture-reverse transcriptase-polymerase chain reaction (ICC-RT-PCR) coupled with nested PCR to detect human astroviruses and enteroviruses in sludge biosolids. Viruses were concentrated by beef extract elution and organic flocculation prior to analysis by a plaque assay and ICC-RT-PCR. Astroviruses were detected in all but one sample and all of the samples were positive for enteroviruses. We have demonstrated the prevalence and frequency ofastrovirus in sludge and validated the ICC-RT-PCR/nested PCR technique as a useful tool to detect viruses in sludge.

Detection of astroviruses, enteroviruses, and adenovirus types 40 and 41 in surface waters collected and evaluated by the information collection rule and an integrated cell culture-nested PCR procedure.

We evaluated the use of an integrated cell culture-reverse transcription-PCR (ICC-RT-PCR) procedure coupled with nested PCR to detect human astroviruses, enteroviruses, and adenovirus types 40 and 41 in surface water samples that were collected and evaluated by using the Information Collection Rule (ICR) method. The results obtained with the ICC-RT-PCR-nested PCR method were compared to the results obtained with the total culturable virus assay-most-probable-number (TCVA-MPN) method, the method recommended by the U.S. Environmental Protection Agency for monitoring viruses in surface and finished waters. Twenty-nine ICR surface water samples were analyzed. Viruses were concentrated by using filter adsorption-beef extract elution and organic flocculation techniques, and then the preparations were evaluated for viruses by visualizing cytopathic effects in the Buffalo green monkey kidney (BGMK) cell line. In the ICC-RT-PCR-nested PCR technique we used Caco-2 cells to propagate astroviruses and enteroviruses (ICC step), and we used BGMK cells to propagate adenovirus types 40 and 41, as well as enteroviruses. Fifteen of the 29 samples (51.7%) were positive for astrovirus as determined by the ICC-RT-PCR-nested PCR method, and eight of these samples (27.5%) contained infectious astrovirus. Seventeen of the 29 samples (58.6%) were positive for enteroviruses when the BGMK cell line was used, and six (27.6%) of these samples were determined to be infectious. Fourteen of the 29 samples (48.3%) were positive for adenovirus types 40 and 41, and 11 (37.9%) of these samples were determined to be infectious. Twenty-seven of the 29 samples (93.1%) were positive for a virus, and 19 (68.9%) of the samples were positive for an infectious virus. Only 5 of the 29 samples (17.2%) were positive as determined by the TCVA-MPN method. The ICC-RT-PCR-nested PCR method provided increased sensitivity compared to the TCVA-MPN method.