Enhancing surgical training by audio-visual simulation with hazard cognitive training and reflection tools: a design-based study in laparoscopic cholecystectomy

Abstract Background Surgical training has become more challenging in the UK with the reduction in training time and the reduced training opportunities, making every training opportunity precious. This study aims to address this curriculum challenge by enhancing surgical training and assessment in the surgical training environment. Methodology Using a design-based approach a two-step design was created. Step One involved creating an online, standalone, Cognitive Hazard Training module. It uses videos of real operations to mentally train candidates to recognise, anticipate and avoid hazards during the operation. An online example of this Module was created for laparoscopic cholecystectomy. The second design step was a Reflective Formative Assessment. The trainee and supervisor reviewed the trainee’s video-recording of a supervised-operation which involved reassessing the trainee’s performance to enhance feedback and reflection. Design feasibility was tested in the Northern Deanery training environment and the feasibility study was complemented by a theatre observation study to capture the details of the complex surgical training environment. Results The feasibility of this two-step design was tested with 2 experts, 32 trainees and 15 trainers. Trainee and trainer qualitative feedback was collected, via semi-structured interviews. Users’ feedback along with multiple additional data from the operation-recordings and video-review session were analysed and triangulated to improve the design and establish the feasibility and role of this style of video-review in the current surgical training. Observational data was also collected during live surgery in theatre to identify any factors affecting safety and training. Discussion This study has developed a novel approach to enhance surgical training, which has been tested and has received overwhelming support from both supervisors and their trainees. Cognitive Hazards Training steepened the learning curve and increased adherence to safety. The videoed operations were found to be an excellent teaching tool, which enhanced feedback and reflection. It increased trainees’ confidence and competence by tailoring the training to their individual needs. The success of this work forms the foundation for future development and testing of this new approach to surgical skills training in the UK

3D printed oral theophylline doses with innovative 'radiator-like' design: Impact of polyethylene oxide (PEO) molecular weight

Despite the abundant use of polyethylene oxides (PEOs) and their integration as an excipient in numerous pharmaceutical products, there have been no previous reports of applying this important thermoplastic polymer species alone to fused deposition modelling (FDM) 3D printing. In this work, we have investigated the manufacture of oral doses via FDM 3D printing by employing PEOs as a backbone polymer in combination with polyethylene glycol (PEG). Blends of PEO (molecular weight 100 K, 200 K, 300 K, 600 K or 900 K) with PEG 6 K (plasticiser) and a model drug (theophylline) were hot-melt extruded. The resultant filaments were used as a feed for FDM 3D printer to fabricate oral dosage forms (ODFs) with innovative designs. ODFs were designed in a radiator-like geometry with connected paralleled plates and inter-plate spacing of either 0.5, 1, 1.5 or 2 mm. X-ray diffraction patterns of the filaments revealed the presence of two distinctive peaks at 2θ = 7° and 12°, which can be correlated to the diffraction pattern of theophylline crystals. Blends of PEO and PEG yielded filaments of variable mechanically resistance (maximum load at break of 357, 608, 649, 882, 781 N for filament produced with PEO 100 K, 200 K, 300 K, 600 K or 900 K, respectively). Filaments of PEO at a molecular weight of 200-600 K were compatible with FDM 3D printing process. Further increase in PEO molecular weight resulted in elevated shear viscosity (>10  Pa.S) at the printing temperature and hindered material flow during FDM 3D printing process. A minimal spacing (1 mm) between parallel plates of the radiator-like design deemed essential to boost drug release from the structure. This is the first report of utilising this widely used biodegradable polymer species (PEOs and PEG) in FDM 3D printing. [Abstract copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

State of the water sector report 2015

The Australian Water Association and Deloitte are pleased to present the State of the Water Sector Report 2015. The Report is the only one of its kind, reporting on the trends and insights of water sector professionals about their own industry. The survey results reveal attitudes and behaviours relating to a range of topics affecting the industry. This year marks the fifth year that the survey has been run and, as such, a summary of trends across the five years has been included in this year’s report. Trends observed over the last five years operational efficiency first emerged as an issue affecting the water sector in 2013, due to growing concerns about the need to control costs and demonstrate value for money, both within the sector itself and for customers. This rose to become the primary issue and area of concern in 2014 as operational costs continued to rise and new capital investment costs were being passed on to customers. In 2015 operational efficiency remains the second biggest issue for the industry, with efficiencies still to be gained through asset management, process improvement and works management and systems improvement. Skills shortages, and talent attraction and retention were of significant concern when the survey commenced five years ago, with the issue of ageing workforces in particular seen by many as a looming threat for the industry. However, in more recent years these concerns have almost halved due to a reduction in demand for additional staff and the greater availability of skilled labour, given construction activity in the mining industry has eased. Unconventional gas came onto the industry’s radar in 2012. last year, 70% of respondents stated that they believed unconventional gas had a significant to moderate effect on the overall management of ground- or surface water. In 2015, 55% of respondents stated that produced water from unconventional gas activities can be treated to a suitable quality for irrigation and other purposes, nevertheless highlighting some concerns in relation to the oil and gas sector impact. Although climate change was identified by 86% of respondents last year as posing a significant or moderate risk to sustainable management of water, sustainability is rated as less important than in previous years, with it being ranked as one of the top issues for the sector in 2011. This may be due to broader changes in community sentiment regarding environmental issues, and more benign weather conditions. While the sector believed security of supply was being managed well, climate change, as well as population growth, is viewed as one of the greatest challenges over the next five years. from a price and regulatory perspective, satisfaction with the role of economic regulators continues to increase slowly, and an increasing proportion of respondents support regulators making deterministic decisions on prices, rather than just monitoring prices. However, a price monitoring role is still favoured by more than three times as many respondents as deterministic pricing. 2015 Key issues The price of water and water regulation Water sector professionals’ perceptions of customer beliefs Sources of water Digital technology Asset management and operational efficiency -- State based reports are also available at AWA\u27s websit

The use of solubility parameters to predict the behaviour of a co-crystalline drug dispersed in a polymeric vehicle. Approaches to the prediction of the interactions of co-crystals and their components with hypromellose acetate succinate and the characterization of that interaction using crystallographic, microscopic, thermal, and vibrational analysis.

Dispersing co-crystals in a polymeric carrier may improve their physicochemical properties such as dissolution rate and solubility. Additionally co-crystal stability may be enhanced. However, such dispersions have been little investigated to date. This study focuses on the feasibility of dispersing co-crystals in a polymeric carrier and theoretical calculations to predict their stability. Acetone/chloroform, ethanol/water, and acetonitrile were used to load and grow co-crystals in a HPMCAS film. Caffeine-malonic acid and ibuprofennicotinamide co-crystals were prepared using solvent evaporation method. The interactions between each of the co-crystals components and their mixtures with the polymer were studied. A solvent evaporation approach was used to incorporate each compound, a mixture, and co-crystals into HPMCAS films. Differential scanning calorimetry data revealed a higher affinity of the polymer to acidic compounds than their basic counterparts as noticed by the depression of the glass transition temperature (Tg). Moreover, the same drug loading produced films with different Tgs when different solvents were used. Solubility parameter values (SP) of the solvents were employed to predict that effect on the depression of polymer Tg with relative success. SP values were more successful in predicting the preferential affinity of two acidic compounds to interact with the polymer. This was confirmed using binary mixtures of naproxen, flurbiprofen, malonic acid, and ibuprofen. On the other hand, dispersing basic compounds such as caffeine or nicotinamide with malonic acid in HPMCAS film revealed the growth of co-crystals. A dissolution study showed that the average release of caffeine from films containing caffeine-malonic acid was not significantly different to that of films containing similar caffeine concentration. The stability of the caffeine-malonic acid co-crystals in HPMC-AS was prolonged to 8 weeks at 95% relative humidity and 45°C. The theory developed in this project, that an acidic drug with a SP value closer to the polymer will dominate the interaction process and prevent the majority of the other material from interacting with the polymer, may have utility in designing co-crystal systems in polymeric vehicle

Thermal and rheological approaches for the systematic enhancement of pharmaceutical polymeric coating formulations. Effects of additives on glass transition temperature, dynamic mechanical properties and coating performance in aqueous and solvent-free coating process using DSC, shear rheometry, dissolution, light profilometry and dynamic mechanical analysis.

Additives, incorporated in film coating formulations, and their process parameters are generally selected using a trial-and-error approach. However, coating problems and defects, especially those associated with aqueous coating systems, indicate the necessity of embracing a quality-by-design approach to identify the optimum coating parameters. In this study, the feasibility of using thermal and rheological measurements to help evaluate and design novel coating formulations has been investigated. Hydroxypropyl methylcellulose acetate succinate (HPMCAS), an enteric coating polymer, was used as the film forming polymer. Differential Scanning Calorimetry (DSC), Dynamic Mechanical Analysis (DMA), and Parallel Plate Shear Rheometery (PPSR) were used to evaluate the effect of different plasticisers on the performance of HPMCAS. The results illustrate that, for identical formulations, the DSC and DMA methods yielded up to 40% differences in glass transition temperature (Tg) values. Moreover, Tg measured using loss modulus signals were always 20-30 oC less than those measured using tan delta results in DMA testing. Absolute and relative Tg values can significantly vary depending on the geometry of the samples, clamp size, temperature ramping rate and the frequency of the oscillations. Complex viscosity data for different formulations demonstrated a variable shear thinning behaviour and a Tg independent ranking. It is, therefore, insufficient to rely purely on Tg values to determine the relative performance of additives. In addition, complex viscosity results, obtained using both the DMA and PPSR techniques at similar temperatures, are shown to be comparable. The results from both techniques were therefore used to produce continuous master curves for the HPMCAS formulations. Additionally, step strain tests showed that HPMCAS chains do not fully III disentangle after 105 seconds as predicted by the Maxwell model. Finally, in situ aqueous-based coating experiments proved that mixtures of triethyl acetyl citrate and acetylated monoglyceride (TEAC/AMG), even without cooling of the suspension, do not cause blocking of the spray nozzle whereas triethyl citrate (TEC) based formulae did. TEAC (alone or in a combination with AMG) exhibits superior wettability to HPMCAS than TEC/AMG formulations and can be used to enhance the efficiency and film quality of the dry coating process

Additive Manufacturing of a Point-of-Care “Polypill:” Fabrication of Concept Capsules of Complex Geometry with Bespoke Release against Cardiovascular Disease

YesPolypharmacy is often needed for the management of cardiovascular diseases and is associated with poor adherence to treatment. Hence, highly flexible and adaptable systems are in high demand to accommodate complex therapeutic regimens. A novel design approach is employed to fabricate highly modular 3D printed “polypill” capsules with bespoke release patterns for multiple drugs. Complex structures are devised using combined fused deposition modeling 3D printing aligned with hot-filling syringes. Two unibody highly modular capsule skeletons with four separate compartments are devised: i) concentric format: two external compartments for early release while two inner compartments for delayed release, or ii) parallel format: where nondissolving capsule shells with free-pass corridors and dissolution rate-limiting pores are used to achieve immediate and extended drug releases, respectively. Controlling drug release is achieved through digital manipulation of shell thickness in the concentric format or the size of the rate limiting pores in the parallel format. Target drug release profiles are achieved with variable orders and configurations, hence confirming the modular nature with capacity to accommodate therapeutics of different properties. Projection of the pharmacokinetic profile of this digital system capsules reveal how the developed approach can be applied in dose individualization and achieving multiple desired pharmacokinetic profiles

ROS-induced Oxidative Damage in Lymphocytes Ex Vivo/in Vitro From Healthy Individuals and MGUS Patients: Protection by Myricetin Bulk and Nanoforms

YesWe investigated the protective role of myricetin bulk and nanoforms, against reactive oxygen species (ROS)-induced oxidative stress caused by hydrogen peroxide and tertiary-butyl hydro peroxide in lymphocytes in vitro from healthy individuals and those from pre-cancerous patients suffering with monoclonal gammopathy of undetermined significance (MGUS). The change in intracellular reactive oxygen species was measured once cells were treated with myricetin bulk forms and nanoforms with and without either hydrogen peroxide or tertiary-butyl hydro peroxide co-supplementation. The direct and indirect antioxidant activity of myricetin was spectrofluometrically measured using the fluorescent dye 2',7'-dichlorofluorescin diacetate and using the Comet assay, respectively. Hydrogen peroxide (50 µM) and tertiary-butyl hydro peroxide (300 µM) induced a higher level of reactive oxygen species-related DNA damage and strand breaks. Addition of myricetin nanoform (20 µM) and bulk (10 µM) form could, however, significantly prevent hydrogen peroxide- and tertiary-butyl hydro peroxide-induced oxidative imbalances and the nanoform was more effective. Glutathione levels were also quantified using a non-fluorescent dye. Results suggest that myricetin treatment had no significant effect on the cellular antioxidant enzyme, glutathione. The current study also investigates the effect of myricetin on the induction of double-strand breaks by staining the gamma-H2AX foci immunocytochemically. It was observed that myricetin does not induce double-strand breaks at basal levels rather demonstrated a protective effect

Colorectal stents: Do we have enough evidence?

AbstractBackgroundThe use of colonic stents has significantly evolved over the last few years. Emergency surgery for colonic obstructions is usually associated with significant mortality, morbidity and often stoma formation. Colonic stents provide an alternative way to relieve colonic obstruction, and hence avoiding the risks associated with emergency surgery. This literature review aims to summarize the important current evidence regarding colorectal stenting and show whether further evaluation of the procedure is required.ResultsThe available large number of non-randomized studies suggests that Self-Expandable-Metal-Stents (SEMS) placement for acute colonic obstruction could be considered as safe and effective alternative to surgery in experienced hands either as a bridge to surgery or as a palliative measure. This evidence has led to SEMS being widely adopted. However, randomized evidence has begun to show the defects that are inherent in the low level evidence that has so far supported SEMS use and it may be that reports of randomized controlled trials may clarify the patient population where SEMS placement is appropriate.ConclusionWhile we are still waiting for the outcome of the multicentre randomized controlled trials in the UK and Europe, clinicians must be aware of the current evidence limitations and apply SEMS use pragmatically

From 'fixed dose combinations' to 'a dynamic dose combiner': 3D printed bi-layer antihypertensive tablets

There is an increased evidence for treating hypertension by a combination of two or more drugs. Increasing the number of daily intake of tablets has been reported to negatively affect the compliance by patients. Therefore, numerous fixed dose combinations (FDCs) have been introduced to the market. However, the inherent rigid nature of FDCs does not allow titration of the dose of each single component for individual patient needs. In this work, flexible dose combinations of two anti-hypertensive drugs in a single bilayer tablet with a range of doses were fabricated using dual fused deposition modelling (FDM) 3D printer. Enalapril maleate (EM) and hydrochlorothiazide (HCT) loaded filaments were produced via hot-melt extrusion (HME). Computer software was utilized to design sets of oval bi-layer tablet of individualised doses. Thermal analysis and x-ray diffractometer (XRD) indicated that HCT remained crystalline in the polymeric matrix whilst EM appeared to be in an amorphous form. The interaction between anionic EM and cationic methacrylate polymer may have contributed to a drop in the glass transition temperature (Tg) of the filament and obviated the need for a plasticiser. Across all tablet sets, the methacrylate polymeric matrix provided immediate drug release profiles. This dynamic dosing system maintained the advantages of FDCs while providing a superior flexibility of dosing range, hence offering an optimal clinical solution to hypertension therapy in a patient-centric healthcare service. [Abstract copyright: Copyright © 2018. Published by Elsevier B.V.

A flexible-dose dispenser for immediate and extended release 3D printed tablets

The advances in personalised medicine increased the demand for a fast, accurate and reliable production method of tablets that can be digitally controlled by healthcare staff. A flexible dose tablet system is presented in this study that proved to be suitable for immediate and extended release tablets with a realistic drug loading and an easy-to-swallow tablet design. The method bridges the affordable and digitally controlled Fused Deposition Modelling (FDM) 3D printing with a standard pharmaceutical manufacturing process, Hot Melt Extrusion (HME). The reported method was compatible with three methacrylic polymers (Eudragit RL, RS and E) as well as a cellulose-based one (hydroxypropyl cellulose, HPC SSL). The use of a HME based pharmaceutical filament preserved the linear relationship between the mass and printed volume and was utilized to digitally control the dose via an input from computer software with dose accuracy in the range of 91-95%. Higher resolution printing quality doubled the printing time, but showed a little effect on in vitro release pattern of theophylline and weight accuracy. Physical characterization studies indicated that the majority of the model drug (theophylline) in the 3D printed tablet exists in a crystal form. Owing to the small size, ease of use and the highly adjustable nature of FDM 3D printers, the method holds promise for future individualised treatment