The Development of an Enhanced Recovery Protocol for Kasai Portoenterostomy.

Balancing post-operative adequate pain control, respiratory depression, and return of bowel function can be particularly challenging in infants receiving the Kasai procedure (hepatoportoenterostomy). We performed a retrospective chart review of all patients who underwent the Kasai procedure from a single surgeon at Children's Healthcare of Atlanta from 1 January 2018, to 1 September 2022. 12 patients received the Kasai procedure within the study period. Average weight was 4.47 kg and average age was 7.4 weeks. Most patients received multimodal pain management including dexmedetomidine and/or ketorolac along with intravenous opioids. A balance of colloid and crystalloids were used for all patients; 57% received blood products as well. All patients were extubated in the OR and transferred to the general surgical floor without complications. Return of bowel function occurred in all patients by POD2, and enteral feeds were started by POD3. One patient had a presumed opioid overdose while admitted requiring a rapid response and brief oxygen supplementation. Simultaneously optimizing pain control, respiratory safety, and bowel function is possible in infants receiving the Kasai procedure. Based on our experience and the current pediatric literature, we propose an enhanced recovery protocol to improve patient outcomes in this fragile population. Larger, prospective studies implementing an enhanced recovery protocol in the Kasai population are required for stronger evidence and recommendations.

Ibuprofen exposure in Europe; ePiE as an alternative to costly environmental monitoring.

The EU Water Framework Directive and Priority Substance Directive provide a framework to identify substances that potentially pose a risk to surface waters and provide a legal basis whereby member states are required to monitor and comply with environmental quality standards (EQSs) set for those substances. The cost and effort to continuously measure and analyse real world concentrations in all water bodies across Europe are high. Establishing the reliability of environmental exposure models to predict concentrations of priority substances is key, both to fill data gaps left by monitoring campaigns, and to predict the outcomes of actions that might be taken to reduce exposure. In this study, we aimed to validate the ePiE model for the pharmaceutical ibuprofen by comparing predictions made using the best possible consumption data with measured river concentrations. The results demonstrate that the ePiE model makes useful, conservative exposure predictions for ibuprofen, typically within a factor of 3 of mean measured values. This exercise was performed across a number of basins within Europe, representative of varying conditions, including consumption rates, population densities and climates. Incorporating specific information pertaining to the basin or country being assessed, such as custom WWTP removal rates, was found to improve the realism and accuracy of predictions. We found that the extrapolation of consumption data between countries should be kept to a minimum when modelling the exposure of pharmaceuticals, with the per capita consumption of ibuprofen varying by nearly a factor of 10.

A simplified index to quantify the irritation/corrosion potential of chemicals - Part II: Eye.

Eye irritation is a key human health endpoint assessed by in vitro and in vivo methods. One of the commonly used scoring methods to quantify the eye irritation potential of chemicals is the Modified Maximum Average Score (MMAS). It is dependent on the eye irritation effects (e.g. corneal opacity) originally proposed by Draize and then partially adopted by the OECD TG 405. These scores are not always fully reported in regulatory dossiers and lead to several drawbacks, 1) the difficulty to translate MMAS into a classification within the existing EU CLP/UN GHS criteria, 2) the absence of corrosion (serious eye damage), and 3) the dependency on input parameters which are usually not required under the OECD TGs (e.g. eye surface area). This study determined if classification can be driven by a maximum of two observed effects thereby simplifying the scoring calculation. The Simplified Irritation Index (SIIEYE), based only on corneal opacity and conjunctival redness, was developed using validated studies representing multiple chemical groups. A correlation was observed between the MMAS and the SIIEYE allowing harmonisation of the classification for the existing data. This index proved to be useful in the development of in silico model.

A simplified index to quantify the irritation/corrosion potential of chemicals - Part I: Skin.

Skin irritation is a key human health endpoint assessed by in vitro and in vivo methods. The OECD TG 404 guideline (in vivo) is based on erythema and oedema translated semi-quantitatively into Draize scores, providing hazard statements for substance classification following EUCLP/UNGHS criteria. Draize scores require quantitation from subjective in vivo observations, to obtain a scoring index, the Primary Irritation Index (PII). However, it is not recognised under REACH due to translating difficulties, notably the cut-off limit for classification and non-inclusion of corrosive effects. The aim of this study was to determine if classification can be driven by just one of the observed effects, erythema only, to create a Simplified Irritation Index (SIISKIN). This simplifies the scoring calculation and reduces subjectivity. A quantitative approach with cut-off limits is thus proposed for classification. Substances can be classified as non-irritant, potentially irritant, irritant, or corrosive. The Simplifed Irritation Index (SIISKIN) is based on validated studies, representing multiple chemical groups. A significant correlation between SIISKIN and the harmonised classification was observed, and a proportionate relationship between the SIISKIN and the corresponding PII. The index proved to be useful in the development of an in silico model.

Local anaesthetic transperineal (LATP) prostate biopsy using a probe-mounted transperineal access system: a multicentre prospective outcome analysis.

OBJECTIVES: To assess the feasibility of local anaesthetic transperineal (LATP) technique using a single-freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability. PATIENTS AND METHODS: Observational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings: (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre-procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging-targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure-related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient-reported outcome measures (PROMs). RESULTS: Some 1218 patients underwent LATP biopsies at 10 centres: 55%, 24%, and 21% for each of the three settings, respectively. Any grade PCa was diagnosed in 816 patients (67%), of which 634 (52% of total) had clinically significant disease. Two cases of sepsis were documented (0.16%) and urinary retention was observed in 19 patients (1.6%). PROMs were distributed to 419 patients, with a 56% response rate (n = 234). In these men, pain during the biopsy was described as either 'not at all' or 'a little' painful by 64% of patients. Haematuria was the most common reported symptom (77%). When exploring attitude to re-biopsy, 48% said it would be 'not a problem' and in contrast 8.1% would consider it a 'major problem'. Most of the patients (81%) described the biopsy as a 'minor or moderate procedure tolerable under local anaesthesia', while 5.6% perceived it as a 'major procedure that requires general anaesthesia'. CONCLUSION: Our data suggest that LATP biopsy using a TP access system mounted to the ultrasound probe achieves excellent PCa detection, with a very low sepsis rate, and is safe and well tolerated. We believe a randomised controlled trial comparing LATP with transrectal ultrasound-guided biopsy (TRUS) to investigate the relative trade-offs between each biopsy technique would be helpful.

The importance of over-the-counter-sales and product format in the environmental exposure assessment of active pharmaceutical ingredients.

When assessing the environmental exposure of active pharmaceutical ingredients (APIs), the mass contributed from over the counter (OTC) sales are often not included due to difficulty obtaining this data and topical formats are overlooked completely. This study presents a comprehensive approach, investigating the significance of OTC and topical applications as sources of API releases to wastewater, in addition to temporal and subnational variations in use in the UK. The study provides methods to obtain and make use of OTC sales data which can be applied widely. The calculated releases to wastewater compared well with influent concentrations measured at several UK wastewater treatment plants (WWTPs). Consistent overestimation was observed, attributed to a number of factors, including in-sewer removal. OTC sales were found to make up a large proportion of the mass of ibuprofen (76%) and diclofenac (35%) consumed and topical formats were also found to be vital, contributing disproportionately to wastewater loadings per unit mass of ibuprofen and diclofenac used (43% and 99% of the total mass released, respectively). Releases of the APIs investigated did not vary temporally, but regional variation was significant and where possible should be considered for the most accurate exposure assessment of pharmaceuticals.

ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals.

BACKGROUND: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest. METHODS AND RESULTS: We performed an ExomeChip-wide analysis for both QT and JT intervals, including 209 449 variants, both common and rare, in 17 341 genes from the Illumina Infinium HumanExome BeadChip. We identified 10 loci that modulate QT and JT interval duration that have not been previously reported in the literature using single-variant statistical models in a meta-analysis of 95 626 individuals from 23 cohorts (comprised 83 884 European ancestry individuals, 9610 blacks, 1382 Hispanics, and 750 Asians). This brings the total number of ventricular repolarization associated loci to 45. In addition, our approach of using coding variants has highlighted the role of 17 specific genes for involvement in ventricular repolarization, 7 of which are in novel loci. CONCLUSIONS: Our analyses show a role for myocyte internal structure and interconnections in modulating QT interval duration, adding to previous known roles of potassium, sodium, and calcium ion regulation, as well as autonomic control. We anticipate that these discoveries will open new paths to the goal of making novel remedies for the prevention of lethal ventricular arrhythmias and sudden cardiac arrest.

A Review of the Environmental Degradation, Ecotoxicity, and Bioaccumulation Potential of the Low Molecular Weight Polyether Polyol Substances.

"Polyalkylene glycol" is the name given to a broad class of synthetic organic chemicals which are produced by polymerization of one or more alkylene oxide (epoxide) monomers, such as ethylene oxide (EO) and propylene oxide (PO), with various initiator substances which possess amine or alcohol groups. A generalization of this polymerization reaction is illustrated in Fig. 1.

Detection of orthopaedic implants by airport metal detectors.

OBJECTIVES: To report the effect of patient's body mass index (BMI), implant type, size, location, number, and material on detection by certified Transportation Security Administration (TSA) and Federal Aviation Administration (FAA) airport metal detectors set to today's standard sensitivity. DESIGN: Retrospective clinical study. SETTING: Level 1 university trauma center. PATIENTS: Ninety-six regularly scheduled trauma clinic patients with a wide variety of orthopaedic implants were enrolled in the study from August 2004 through December 2004. INTERVENTION: Patients walked through an airport arch metal detector and were also wanded with a handheld metal detector. MAIN OUTCOME MEASUREMENTS: Detection of implants by arch detector or wand was recorded. We also gathered information regarding BMI, location of implants, type, metal composition, and size. RESULTS: All unilateral prostheses (8/8) and bilateral prostheses (1/1) were detected. Subjects with 4 or fewer screws and no other implants were never detected by the arch metal detector (0/7). For the remaining 78 subjects, the 2 best predictors of detection by the arch were having plates of length >10 holes and having titanium nails (P < 0.001 for each predictor, Wald's test for effects in a logistic model). CONCLUSIONS: Prostheses, plates of length >10 holes, and titanium nails were the best predictors of detection by the arch. These 3 factors accounted for 42 of the 43 detections by the arch. Body mass index was not shown to affect detectability of orthopaedic implants.