Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers

Hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions, which biodegradable extensions are terminated on free ends with end cap monomers or oligomers capable of polymerization and cross linking are described. The hydrophilic core itself may be degradable, thus combining the core and extension functions. Macromers are polymerized using free radical initiators under the influence of long wavelength ultraviolet light, visible light excitation or thermal energy. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Preferred applications for the hydrogels include prevention of adhesion formation after surgical procedures, controlled release of drugs and other bioactive species, temporary protection or separation of tissue surfaces, adhering of sealing tissues together, and preventing the attachment of cells to tissue surfaces.Board of Regents, University of Texas Syste

Treating medical conditions by polymerizing macromers to form polymeric materials

Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, and coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules. A medical condition at a localized site is treated by applying a polymerization initiator and then applying a substantially water-soluble, degradable macromer of at least 200 mw and having at least two crosslinkable substituents, and polymerizing the macromer to form a crosslinked polymeric material at the site. The crosslinked polymeric material may adhere two surfaces together, or be a barrier that provides immunoisolation or prevents adhesion of the site to another surface such as post-surgical adhesion. A biologically active material may be present when the macromer is polymerized to provide for delivery of the biologically active material, or to provide the polymeric material with a desired property such as resistance to bacterial growth or a decrease in inflammatory response.Board of Regents, University of Texas Syste

The long-term psycho-social impact of the pandemic on people with intellectual disability and their carers

Background: People with intellectual disabilities (PWID) are at six times higher risk of death due to COVID-19. To mitigate harm, as a high-risk group, significant social changes were imposed on PWID in the UK. Alongside these changes, the uncertainty of the pandemic influence, caused PWID and their carers to encounter significant stress. The evidence of the pandemic’s psycho-social impact on PWID originates mainly from cross-sectional surveys conducted with professionals and carers. There is little research on the longitudinal psycho-social impact of the pandemic from PWID themselves. Aims: To examine the long-term psycho-social impact of the pandemic on PWID. Methods: A cross-sectional survey, following STROBE guidance, of 17 Likert scale statements (12 to PWID and 5 to their carers) to ascertain the pandemic’s psychosocial impact was conducted. Every other PWID open to a specialist Intellectual Disability service serving half a UK County (pop:500,000) was selected. The same survey was re-run with the same cohort a year later. Descriptive statistics, Mann-Whitney, Chi-square and unpaired-t tests were used to compare responses. Significance is taken at p &lt; .05. Comments were analysed using Clarke and Braun’s approach. Results: Of 250 PWID contacted, 100 (40%) responded in 2020 and 127 (51%) in 2021. 69% (2020) and 58% (2021) reported seeking medical support. Carers, (88%, 2020 and 90%, 2021) noticed emotional changes in PWID they cared for. 13% (2020) and 20% (2021) of PWID had their regular psychotropics increased. 21% (2020) and 24% (2021) had their pro re nata (PRN) medication adjusted. PWID or carers demonstrated no statistically significant variation in responses between themselves from 2020 to 2021. PWID were more likely to report being upset/distressed compared to their carers’ perceptions of them in both years ( p &lt; .001). Four themes were identified. Conclusion: This longitudinal study highlights the diverse psycho-social impact of the pandemic on PWID in the UK. The Pandemic’s psycho-social impact has been significantly underestimated. </jats:sec

Epicardial catheter ablation for ventricular tachycardia on uninterrupted warfarin: A safe approach for those with a strong indication for peri-procedural anticoagulation?

BACKGROUND: Current guidelines for epicardial catheter ablation for ventricular tachycardia (VT) advocate that epicardial access is avoided in anticoagulated patients and should be performed prior to heparinisation. Recent studies have shown that epicardial access may be safe in heparinised patients. However, no data exist for patients on oral anticoagulants. We investigated the safety of obtaining epicardial access on uninterrupted warfarin. METHODS: A prospective registry of patients undergoing epicardial VT ablation over two years was analysed. Consecutive patients in whom epicardial access was attempted were included. All patients were heparinised prior to epicardial access with a target activated clotting time (ACT) of 300-350s. Patients who had procedures performed on uninterrupted warfarin (in addition to heparin) were compared to those not taking an oral anticoagulant. RESULTS: 46 patients were included of which 13 were taking warfarin. There was no significant difference in clinical and procedural characteristics (except INR and AF) between the two groups. Epicardial access was achieved in all patients. There were no deaths and no patients required surgery. A higher proportion of patients in the warfarin group had a drop in haemoglobin of >2g/dL compared to the no-warfarin group (38.5% versus 27.3%, p=0.74) and delayed pericardial drain removal (7.8% versus 3.03%, p=0.47). There was no difference in overall procedural complication rate. No patients required warfarin reversal or blood transfusion. CONCLUSION: Epicardial access can be achieved safely and effectively in patients' anticoagulated with warfarin and heparinised with therapeutic ACT. This may be an attractive option for patients with a high stroke risk

Awareness of social care needs in people with epilepsy and intellectual disability

Background: Nearly a quarter of people with intellectual disability (ID) have epilepsy with large numbers experiencing drug-resistant epilepsy, and premature mortality. To mitigate epilepsy risks the environment and social care needs, particularly in professional care settings, need to be met. Purpose: To compare professional care groups as regards their subjective confidence and perceived responsibility when managing the need of people with ID and epilepsy. Method: A multi-agency expert panel developed a questionnaire with embedded case vignettes with quantitative and qualitative elements to understand training and confidence in the health and social determinants of people with ID and epilepsy. The cross-sectional survey was disseminated amongst health and social care professionals working with people with ID in the UK using an exponential non-discriminative snow-balling methodology. Group comparisons were undertaken using suitable statistical tests including Fisher's exact, Kruskal-Wallis, and Mann-Whitney. Bonferroni correction was applied to significant (p < 0.05) results. Content analysis was conducted and relevant categories and themes were identified. Results: Social and health professionals (n = 54) rated their confidence to manage the needs of people with ID and epilepsy equally. Health professionals showed better awareness (p < 0.001) of the findings/recommendations of the latest evidence on premature deaths and identifying and managing epilepsy-related risks, including the relevance of nocturnal monitoring. The content analysis highlighted the need for clearer roles, improved care pathways, better epilepsy-specific knowledge, increased resources, and better multi-disciplinary work. Conclusions: A gap exists between health and social care professionals in awareness of epilepsy needs for people with ID, requiring essential training and national pathways

Impact of attributed audit on procedural performance in cardiac electrophysiology catheter laboratory

PURPOSE: Audit has played a key role in monitoring and improving clinical practice. However, audit often fails to drive change as summative institutional data alone may be insufficient to do so. We hypothesised that the practice of attributed audit, wherein each individual's procedural performance is presented will have a greater impact on clinical practice. This hypothesis was tested in an observational study evaluating improvement in fluoroscopy times for AF ablation. METHODS: Retrospective analyses of fluoroscopy times in AF ablations at the Barts Heart Centre (BHC) from 2012-2017. Fluoroscopy times were compared pre- and post- the introduction of attributed audit in 2012 at St Bartholomew's Hospital (SBH). In order to test the hypothesis, this concept was introduced to a second group of experienced operators from the Heart Hospital (HH) as part of a merger of the two institutions in 2015 and change in fluoroscopy times recorded. RESULTS: A significant drop in fluoroscopy times (33.3 ± 9.14 to 8.95 ± 2.50, p < 0.0001) from 2012-2014 was noted after the introduction of attributed audit. At the time of merger, a significant difference in fluoroscopy times between operators from the two centres was seen in 2015. Each operator's procedural performance was shared openly at the audit meeting. Subsequent audits showed a steady decrease in fluoroscopy times for each operator with the fluoroscopy time (min, mean±SD) decreasing from 13.29 ± 7.3 in 2015 to 8.84 ± 4.8 (p < 0.0001) in 2017 across the entire group. CONCLUSIONS: Systematic improvement in fluoroscopy times for AF ablation procedures was noted byevaluating individual operators' performance. Attributing data to physicians in attributed audit can promptsignificant improvement and hence should be adopted in clinical practice

Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291

Precision scans of the pixel cell response of double sided 3D pixel detectors to pion and x-ray beams

hree-dimensional (3D) silicon sensors offer potential advantages over standard planar sensors for radiation hardness in future high energy physics experiments and reduced charge-sharing for X-ray applications, but may introduce inefficiencies due to the columnar electrodes. These inefficiencies are probed by studying variations in response across a unit pixel cell in a 55μm pitch double-sided 3D pixel sensor bump bonded to TimePix and Medipix2 readout ASICs. Two complementary characterisation techniques are discussed: the first uses a custom built telescope and a 120GeV pion beam from the Super Proton Synchrotron (SPS) at CERN; the second employs a novel technique to illuminate the sensor with a micro-focused synchrotron X-ray beam at the Diamond Light Source, UK. For a pion beam incident perpendicular to the sensor plane an overall pixel efficiency of 93.0±0.5% is measured. After a 10o rotation of the device the effect of the columnar region becomes negligible and the overall efficiency rises to 99.8±0.5%. The double-sided 3D sensor shows significantly reduced charge sharing to neighbouring pixels compared to the planar device. The charge sharing results obtained from the X-ray beam study of the 3D sensor are shown to agree with a simple simulation in which charge diffusion is neglected. The devices tested are found to be compatible with having a region in which no charge is collected centred on the electrode columns and of radius 7.6±0.6μm. Charge collection above and below the columnar electrodes in the double-sided 3D sensor is observed

Transseptal puncture for left atrial ablation: Risk factors for cardiac tamponade and a proposed causative classification system

AIMS: Cardiac tamponade is a high morbidity complication of transseptal puncture (TSP). We examined the associations of TSP‐related cardiac tamponade (TRCT) for all patients undergoing left atrial ablation at our center from 2016 to 2020. METHODS AND RESULTS: Patient and procedural variables were extracted retrospectively. Cases of cardiac tamponade were scrutinized to adjudicate TSP culpability. Adjusted multivariate analysis examined predictors of TRCT. A total of 3239 consecutive TSPs were performed; cardiac tamponade occurred in 51 patients (incidence: 1.6%) and was adjudicated as TSP‐related in 35 (incidence: 1.1%; 68.6% of all tamponades). Patients of above‐median age [odds ratio (OR): 2.4 (1.19–4.2), p = .006] and those undergoing re‐do procedures [OR: 1.95 (1.29–3.43, p = .042] were at higher risk of TRCT. Of the operator‐dependent variables, choice of transseptal needle (Endrys vs. Brockenbrough, p > .1) or puncture sheath (Swartz vs. Mullins vs. Agilis vs. Vizigo vs. Cryosheath, all p > .1) did not predict TRCT. Adjusting for operator, equipment and demographics, failure to cross the septum first pass increased TRCT risk [OR: 4.42 (2.45–8.2), p = .001], whilst top quartile operator experience [OR: 0.4 (0.17–0.85), p = .002], transoesophageal echocardiogram [TOE prevalence: 26%, OR: 0.51 (0.11–0.94), p = .023], and use of the SafeSept transseptal guidewire [OR: 0.22 (0.08–0.62), p = .001] reduced TRCT risk. An increase in transseptal guidewire use over time (2016: 15.6%, 2020: 60.2%) correlated with an annual reduction in TRCT (R (2) = 0.72, p < .001) and was associated with a relative risk reduction of 70%. CONCLUSIONS: During left atrial ablation, the risk of TRCT was reduced by operator experience, TOE‐guidance, and use of a transseptal guidewire, and was increased by patient age, re‐do procedures, and failure to cross the septum first pass