Impact on healthcare resources of switch from fecal occult blood test to fecal immunochemical test within the English Bowel Cancer Screening Program: a single-center study.

BACKGROUND AND AIMS: In July 2019, the fecal immunochemistry test (FIT) replaced the fecal occult blood test (FOBT) in England as the Bowel Cancer Screening Program (BCSP) screening tool. We aimed to assess the impact of this on healthcare resources at our BCSP center. METHODS: Two 6-month periods were initially analyzed for stool sample return and positivity rates. A subsequent comparative analysis of patient screening episodes assessed utilization of specialist screening practitioner (SSP) time, endoscopy, histology, radiology, surgical, and oncology service usage. RESULTS: A total of 42,234 patients received FOBT and 42,545 patients received FIT stool kits, with FIT showing higher return (61.8% vs 58.58%, FIT vs FOBT, P < .001) and sample positivity rates (2.41% vs 1.45%, FIT vs FOBT, P < .001). Four hundred patients commenced FOBT and 616 FIT screening episodes, a 54% increase. The FIT group had of a lower mean age (67.5 vs 69.5 years, FIT vs FOBT, P = .0001) with a lower nonattendance rate (.16% vs 1.5%, FIT vs FOBT, P = .01). With higher patient numbers, the FIT group required 69% more endoscopic procedures, 58% increased SSP time, 40% more radiologic tests, and 68% higher surgical procedures. FIT also led to a 109% increase in endoscopy-derived histology samples from an increase in the proportion of patients with polyps with FIT (54.8% vs 47.2%, P = .020) and a greater number of polyps per patient in whom polyps were found (3.00 vs 2.50 polyps, P = .017). This additional service burden equated to additional financial costs of approximately $558,000 per annum. CONCLUSIONS: The implementation of FIT led to notable increases in SSP time, endoscopy procedures, radiology tests, surgical procedures, and histopathology services, resulting in considerable ongoing financial implications on the organization. Findings can be used to aid workforce and service planning in National Health Service sites delivering BCSP and countries that have already adopted or are considering FIT within their national screening programs.

Railway Point-Operating Machine Fault Detection Using Unlabeled Signaling Sensor Data.

In this study, we propose a methodology for the identification of potential fault occurrences of railway point-operating machines, using unlabeled signal sensor data. Data supplied by Network Rail, UK, is processed using a fast Fourier transform signal processing approach, coupled with the mean and max current levels to identify potential faults in point-operating machines. The method developed can dynamically adapt to the behavioral characteristics of individual point-operating machines, thereby providing bespoke condition monitoring capabilities in situ and in real time. The work described in this paper is not unique to railway point-operating machines, rather the data pre-processing and methodology is readily applicable to any motorized device fitted with current sensing capabilities. The novelty of our approach is that it does not require pre-labelled data with historical fault occurrences and therefore closely resembles problems of the real world, with application for smart city infrastructure. Lastly, we demonstrate the problems faced with handling such data and the capability of our methodology to dynamically adapt to diverse data presentations.

Prediction of diabetes prescription volumes of various geographies using regression techniques.

Background: Increasing diabetes prevalence is a major public health concern. In this study we ask whether linked open data can be used to predict prescription volumes of drugs used in the treatment of diabetes across small geographies of England. Methods: We propose and demonstrate a methodology of utilising publicly available open data to infer the geo-spatial distribution of prescribed drugs for diabetes, at the lower layer super output area level. Multiple datasets are acquired, processed, and linked together, enabling a more in-depth analysis. Combining these linked datasets with published deprivation factors of geographies across England, we build highly predictive regression models. Results: Regression models were trained and are capable of accurately predicting diabetes prescribing volumes based on deprivation indicators of various geographies across England. Models built with data covering the city of Bradford, England, produced a predicted against actual correlation value of R2 = 0.672 using multiple linear regression and 0.775 using Least Absolute Shrinkage and Selection Operator (LASSO). Median age and air quality factors proved to be significant markers for diabetes prescribing. Conclusions: The results of this study suggest our methodology is robust and accurate. Such predictive models are useful to health authorities in light of increasing costs and increasing prevalence of diabetes. While using publicly available open data negates any issues of data privacy.

Complicated Severe Acute Pancreatitis: Open and Laparoscopic Infracolic Approach.

INTRODUCTION: The heterogeneous nature of severe acute pancreatitis (SAP) renders decisions related to complications challenging. Central solid collections at the root of the mesentery are difficult to access with traditional techniques. Here we describe a case series of laparoscopic infracolic necrosectomy (ICN) and open or laparoscopic infracolic necrosectomy with Roux-en Y cystjejunostomy (ICN-RYCJ) for the management of complicated SAP. MATERIALS AND METHODS: A retrospective analysis of a prospectively maintained database identified all patients treated with infracolic necrosectomy or drainage of pancreatic collections for complicated SAP between 2012 and 2021 inclusive at a single institution. RESULTS: Forty patients were identified (median age 53 years)-ICN group 9 patients (median time to intervention-22 days) and ICN-RYCJ group 31 patients (median time to intervention-99 days). Two patients in ICN group underwent interval fistula-tract jejunostomy. Thirty-one patients had laparoscopic surgery and 9 patients underwent an open approach. Four patients required intervention post-operatively. Nineteen patients were discharged from follow-up at two years. CONCLUSION: Infracolic approach with selective Roux-en Y cystjejunostomy, as a single or staged intervention, is an effective and safe operative option to add to the armamentarium of the pancreatic surgeon when dealing with complicated SAP not amenable to drainage/debridement by traditional techniques.

Development and evaluation of ethyl cellulose-based transdermal films of furosemide for improved in vitro skin permeation.

Transdermal films of the furosemide were developed employing ethyl cellulose and hydroxypropyl methylcellulose as film formers. The effect of binary mixture of polymers and penetration enhancers on physicochemical parameters including thickness, moisture content, moisture uptake, drug content, drug-polymer interaction, and in vitro permeation was evaluated. In vitro permeation study was conducted using human cadaver skin as penetration barrier in modified Keshary-Chein diffusion cell. In vitro skin permeation study showed that binary mixture, ethyl cellulose (EC)/hydroxypropyl methylcellulose (HPMC), at 8.5:1.5 ratio provided highest flux and also penetration enhancers further enhanced the permeation of drug, while propylene glycol showing higher enhancing effect compared to dimethyl sulfoxide and isopropyl myristate. Different kinetic models, used to interpret the release kinetics and mechanism, indicated that release from all formulations followed apparent zero-order kinetics and non-Fickian diffusion transport except formulation without HPMC which followed Fickian diffusion transport. Stability studies conducted as per International Conference on Harmonization guidelines did not show any degradation of drug. Based on the above observations, it can be reasonably concluded that blend of EC-HPMC polymers and propylene glycol are better suited for the development of transdermal delivery system of furosemide.

The Safety and Tolerability of a Potential Alginate-Based Iron Chelator; Results of A Healthy Participant Study.

Evidence supporting the ferro-toxic nature of iron in the progression of inflammatory bowel disease (IBD) is becoming well established. A microbial dysbiosis is observed in IBD patients, and intra-luminal colonic-iron is able to support a more pathogenic community of bacteria; whether this is attributed to the development of IBD and how iron could be mediating these microbial changes is still unknown. Dietary fibres are commonly used in pre-biotic supplements to beneficially affect the host by improving the viability of bacterial communities within the colon. Alginates are a class of biopolymers considered as prebiotics due to their fibre-like composition and are able to bind metal cations, in particular, iron. Considering that iron excess is able to negatively alter the microbiome, the use of alginate as a food supplement could be useful in colonic-iron chelation. As such, this first-in-man study aimed to assess whether the use of alginate as a dietary iron chelator was both safe and well tolerated. In addition, the impact of alginate on the microbiome and iron levels was assessed by using an intestinal model SHIME (Simulation of the Human Intestinal Microbial Ecosystem). Alginate was supplemented into the diets (3 g/day) of healthy volunteers (n = 17) for 28 days. Results from this study suggest that daily ingestion of 3 g alginate was well tolerated with very minor side effects. There were no detrimental changes in a variety of haematological parameters or the intestinal microbiome. The bacterial communities within the SHIME model were also not influenced by iron and or alginate; it is possible that alginate may be susceptible to bacterial or enzymatic degradation within the gastro-intestinal tract.

Pharmacokinetic investigation of imatinib using accelerator mass spectrometry in patients with chronic myeloid leukemia.

PURPOSE: To investigate the potential use of accelerator mass spectrometry (AMS) in the study of the clinical pharmacology of imatinib. EXPERIMENTAL DESIGN: Six patients who were receiving imatinib (400 mg/d) as part of their ongoing treatment for chronic myeloid leukemia (CML) received a dose containing a trace quantity (13.6 kBq) of (14)C-imatinib. Blood samples were collected from patients before and at various times up to 72 h after administration of the test dose and were processed to provide samples of plasma and peripheral blood lymphocytes (PBL). Samples were analyzed by AMS, with chromatographic separation of parent compound from metabolites. In addition, plasma samples were analyzed by liquid chromatography/mass spectrometry (LCMS). RESULTS: Analysis of the AMS data indicated that imatinib was rapidly absorbed and could be detected in plasma up to 72 h after administration. Imatinib was also detectable in PBL at 24 h after administration of the (14)C-labeled dose. Comparison of plasma concentrations determined by AMS with those derived by LCMS analysis gave similar average estimates of area under plasma concentration time curve (26 +/- 3 versus 27 +/- 11 microg/mL.h), but with some variation within each individual. CONCLUSIONS: Using this technique, data were obtained in a small number of patients on the pharmacokinetics of a single dose of imatinib in the context of chronic dosing, which could shed light on possible pharmacologic causes of resistance to imatinib in CML.

Building a model for day case hiatal surgery - Lessons learnt over a 10 year period in a high volume unit: A case series.

BACKGROUND: Laparoscopic anti-reflux surgery has become the standard treatment for symptomatic gastro-oesophageal reflux disease refractory to medical therapy. Successful anti-reflux surgery involves safe, minimally invasive surgery, resulting in symptom resolution with minimal side effects. This study aims to assess the feasibility and safety of day case anti-reflux surgery focussing on peri- and post-operative outcomes as a measure of success. METHODS: Data was collected from the hospital database from 2003 to 2012. Data collection included demographics, surgeon, mode of admission, length of stay and complications. Electronic records were independently scrutinised for all patients with a length of stay of more than two nights. RESULTS: 723 patients underwent laparoscopic fundoplication ±â€¯small hiatus hernia repair (<5 cm) with a day case rate of 67.1%. The 30 day readmission rate in these patients was 2.9% (21/723 patients). Nine patients had a failure of their initial laparoscopic fundoplication (defined as recurrence of symptoms). Three patients required a re-operation within 12 months of their initial procedure (re-operation rate = 0.41% (3/723 patients)). CONCLUSION: Laparoscopic hiatal surgery can be performed safely as a day case in high volume specialist centres with good outcomes. Raising the national standard for day case fundoplication promotes good practice and should be the model for future commissioning.

Bioprinting Using Mechanically Robust Core-Shell Cell-Laden Hydrogel Strands.

The strand material in extrusion-based bioprinting determines the microenvironments of the embedded cells and the initial mechanical properties of the constructs. One unmet challenge is the combination of optimal biological and mechanical properties in bioprinted constructs. Here, a novel bioprinting method that utilizes core-shell cell-laden strands with a mechanically robust shell and an extracellular matrix-like core has been developed. Cells encapsulated in the strands demonstrate high cell viability and tissue-like functions during cultivation. This process of bioprinting using core-shell strands with optimal biochemical and biomechanical properties represents a new strategy for fabricating functional human tissues and organs.

Prediction of the effect of formulation on the toxicity of chemicals.

Two approaches for the prediction of which of two vehicles will result in lower toxicity for anticancer agents are presented. Machine-learning models are developed using decision tree, random forest and partial least squares methodologies and statistical evidence is presented to demonstrate that they represent valid models. Separately, a clustering method is presented that allows the ordering of vehicles by the toxicity they show for chemically-related compounds.

3D Microfabricated Scaffolds and Microfluidic Devices for Ocular Surface Replacement: a Review.

In recent years, there has been increased research interest in generating corneal substitutes, either for use in the clinic or as in vitro corneal models. The advancement of 3D microfabrication technologies has allowed the reconstruction of the native microarchitecture that controls epithelial cell adhesion, migration and differentiation. In addition, such technology has allowed the inclusion of a dynamic fluid flow that better mimics the physiology of the native cornea. We review the latest innovative products in development in this field, from 3D microfabricated hydrogels to microfluidic devices.

Cloacogenic polyps in an adolescent: a rare cause of rectal bleeding.

Cloacogenic polyps are rare inflammatory lesions occurring around the anal transitional zone and in the lower rectum which can mimic neoplasia. They should be given diagnostic consideration in patients presenting with symptoms of rectal bleeding, tenesmus, and altered bowel habits.