Showing papers by "Tim Jackson published in 2022"
TL;DR: TIGER as discussed by the authors is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial, which aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy.
Abstract: Neovascular (wet) age-related macular degeneration (AMD) can be associated with large submacular haemorrhage (SMH). The natural history of SMH is very poor, with typically marked and permanent loss of central vision in the affected eye. Practice surveys indicate varied management approaches including observation, intravitreal anti-vascular endothelial growth factor therapy, intravitreal gas to pneumatically displace SMH, intravitreal alteplase (tissue plasminogen activator, TPA) to dissolve the clot, subretinal TPA via vitrectomy, and varying combinations thereof. No large, published, randomised controlled trials have compared these management options.TIGER is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial. Eligible participants have large, fovea-involving SMH of no more than 15 days duration due to treatment-naïve or previously treated neovascular AMD, including idiopathic polypoidal choroidal vasculopathy and retinal angiomatous proliferation. A total of 210 participants are randomised in a 1:1 ratio to pars plana vitrectomy, off-label subretinal TPA up to 25 μg in 0.25 ml, intravitreal 20% sulfahexafluoride gas and intravitreal aflibercept, or intravitreal aflibercept monotherapy. Aflibercept 2 mg is administered to both groups monthly for 3 doses, then 2-monthly to month 12. The primary efficacy outcome is the proportion of participants with best-corrected visual acuity (BCVA) gain of ≥ 10 Early Treatment Diabetic Retinopathy (ETDRS) letters in the study eye at month 12. Secondary efficacy outcomes (at 6 and 12 months unless noted otherwise) are proportion of participants with a BCVA gain of ≥ 10 ETDRS letters at 6 months, mean ETDRS BCVA, Radner maximum reading speed, National Eye Institute 25-item Visual Function Questionnaire composite score, EQ-5D-5L with vision bolt-on score, Short Warwick and Edinburgh Mental Wellbeing score, scotoma size on Humphrey field analyser, and presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using independent reading centre multimodal image analysis (12 months only). Key safety outcomes are adverse events, serious adverse events, and important medical events, coded using the Medical Dictionary for Regulatory Activities Preferred Terms.The best management of SMH is unknown. TIGER aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy.ClinicalTrials.gov NCT04663750 ; EudraCT: 2020-004917-10.
8 citations
TL;DR: The goal of this statement is to offer standardization in bariatric care across Canada to provide patients with optimal access to obesity treatment and potentially improve outcomes by reducing complications, length of hospital stay and readmission rate.
Abstract: Summary
The goal of this statement is to offer standardization in bariatric care across Canada, to provide patients with optimal access to obesity treatment and potentially improve outcomes by reducing complications, length of hospital stay and readmission rate. The definition of Canadian standards also aims to promote a comprehensive, multidisciplinary approach to patients with obesity, to define the minimal qualifications for surgical and medical training and to offer credentialling for bariatric surgical and medical centres. In addition, we emphasize the importance of developing a national registry for the assessment of quality of care across the country and to evaluate outcomes of long-term treatment. These recommendations are based on expert opinion as well as the most recent clinical evidence.
5 citations
TL;DR: In this paper , the reported prevalence of retinopathy in adults with prediabetes was determined using MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, Google Scholar and the Cochrane databases from inception to August 1, 2020.
4 citations
TL;DR: Overall, in those with obeisty, allogenic FMT via colonoscopy induced favorable changes in IM, metabolites, pathway representations and networks even though other metabolic variables did not change.
Abstract: To assess the effects of faecal microbial transplant (FMT) from lean people to subjects with obesity via colonoscopy.
4 citations
TL;DR: A CMR‐compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent colocalised histology, without the need for onsite preclinical facilities.
Abstract: Cardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor cardiovascular magnetic resonance (DT‐CMR). Here, we develop a CMR‐compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states. Ten porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D‐printed chamber and perfusion circuit re‐established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT‐CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state, respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT‐CMR data using fiducial markers. Regular sustained contraction was successfully established in six out of 10 hearts, including the final five hearts. Imaging was performed in four hearts and one underwent the full protocol, including colocalised histology. The image quality was good and there was good agreement between DT‐CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2 mapping results, DT‐CMR measures and an increase in mass were consistent with development of myocardial oedema, resulting in failure to achieve a true diastolic‐like state. A contiguous stack of 313 5‐μm histological sections at and a 100‐μm thick section showing cell morphology on 3D fluorescent confocal microscopy colocalised to DT‐CMR data were obtained. A CMR‐compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent colocalised histology, without the need for onsite preclinical facilities.
2 citations
TL;DR: FRAP is a feasible and practical optical method to quantify the diffusion of macromolecules through vitreous and may provide a novel means of measuring intravitreal diffusion that could be applied to drugs and physiological macromolescules.
Abstract: Purpose Vitreous humor is a complex biofluid whose composition determines its structure and function. Vitreous viscosity will affect the delivery, distribution, and half-life of intraocular drugs, and key physiological molecules. The central pig vitreous is thought to closely match human vitreous viscosity. Diffusion is inversely related to viscosity, and diffusion is of fundamental importance for all biochemical reactions. Fluorescence Recovery After Photobleaching (FRAP) may provide a novel means of measuring intravitreal diffusion that could be applied to drugs and physiological macromolecules. It would also provide information about vitreous viscosity, which is relevant to drug elimination, and delivery. Methods Vitreous viscosity and intravitreal macromolecular diffusion of fluorescently labelled macromolecules were investigated in porcine eyes using fluorescence recovery after photobleaching (FRAP). Fluorescein isothiocyanate conjugated (FITC) dextrans and ficolls of varying molecular weights (MWs), and FITC-bovine serum albumin (BSA) were employed using FRAP bleach areas of different diameters. Results The mean (±standard deviation) viscosity of porcine vitreous using dextran, ficoll and BSA were 3.54 ± 1.40, 2.86 ± 1.13 and 4.54 ± 0.13 cP respectively, with an average of 3.65 ± 0.60 cP. Conclusions FRAP is a feasible and practical optical method to quantify the diffusion of macromolecules through vitreous.
2 citations
TL;DR: Lower comorbidity burden, earlier disease stage (among cancer cases), and early career surgeons with high case volume at a teaching hospital were consistently associated with the receipt of robotic surgery.
1 citations
1 citations
TL;DR: In this article , the authors developed and validated single and multi-output laterality, retinal presence and gradability classification deep learning (DL) models for automated curation of diabetic retinopathy screening images.
Abstract: Abstract Diabetic retinopathy (DR) screening images are heterogeneous and contain undesirable non-retinal, incorrect field and ungradable samples which require curation, a laborious task to perform manually. We developed and validated single and multi-output laterality, retinal presence, retinal field and gradability classification deep learning (DL) models for automated curation. The internal dataset comprised of 7743 images from DR screening (UK) with 1479 external test images (Portugal and Paraguay). Internal vs external multi-output laterality AUROC were right (0.994 vs 0.905), left (0.994 vs 0.911) and unidentifiable (0.996 vs 0.680). Retinal presence AUROC were (1.000 vs 1.000). Retinal field AUROC were macula (0.994 vs 0.955), nasal (0.995 vs 0.962) and other retinal field (0.997 vs 0.944). Gradability AUROC were (0.985 vs 0.918). DL effectively detects laterality, retinal presence, retinal field and gradability of DR screening images with generalisation between centres and populations. DL models could be used for automated image curation within DR screening.
1 citations
TL;DR: Evidence is found of higher rates of mortality and surgical complications within 30-days of surgery for patients in Canada as compared to the US, largely driven by higher risk of cardiac events and post-operative infections.
1 citations
TL;DR: Incidence rates of NVG appear to have increased, with a larger proportion of patients requiring surgical intervention, and delayed presentations are likely due to patient reluctance and pandemic workforce redeployment.
Abstract: PurposeThere remains a significant paucity in data on the epidemiology and management of neovascular glaucoma (NVG). We aimed to describe NVG incidence rates and establish variance in the medical and surgical management of NVG over a 6‐year period, in the context of pathway modifications implemented in response to the COVID‐19 pandemic.MethodsPatients diagnosed with and treated for NVG at our centre between January 2015 and April 2021 were identified. Data on patient demographics, co‐morbidities, aetiology and intervention were extracted. Crude incidence rates were calculated. Variation in the form of intervention and severity of disease practice was studied. Multivariate regression modelling was used to look for associations with disease potentially influencing practice.ResultsFive‐hundred seventy seven patients (M:F 327:250) were included with mean age (SD) 70.26 (12.62), baseline cup‐to‐disc ratio (CDR) 0.75 (0.23), and intraocular pressure (IOP) 28.08 mmHg (14.01). Majority of patients were diabetic (63.9% n = 368). Retinal vein occlusion was identified in 35.0% (n = 203). NVG incidence in the 5 years pre‐COVID were 2.5/100 000 (2015), 4.9/100 000 (2016), 7.8/100 000 (2017), 11.5/100 000 (2018) and 15.8/100 000 (2019) (p < 0.0001), and during COVID 11.8/100 000 (2020). Between 2018–2019 and 2020–21, there appeared to be an increasing trend towards implementing anti‐VEGF therapy and alternate forms of glaucoma surgery. Diabetes was associated with higher rates of surgical intervention (OR = 3.69, 95% CI 1.40–9.67, p = 0.008). Conversely, patients aged 50–74 were less likely to undergo surgery (OR = 0.46, 95% CI 0.21–0.99, p = 0.048).ConclusionIncidence rates of NVG appear to have increased, with a larger proportion of patients requiring surgical intervention. Discrepancies in these rates suggest a cohort of patients lost during the pandemic;these delayed presentations are likely due to patient reluctance and pandemic workforce redeployment.
TL;DR: The Bariatric Registry is a multi-center database with prospectively collected standardized data on patients undergoing bariatric surgery at ten Bariatric Centers of Excellence within the Ontario Bariatric Network in Ontario, Canada to determine weight-loss outcomes of patients undergoing LRYGB after LSG and whether outcomes differ according to indications for conversion.
TL;DR: EMB does not reduce the number of anti-vascular endothelial growth factor (VEGF) injections, either within or outside of a trial setting, and is associated with worse BCVA than anti-VEGF monotherapy.
Abstract: Background/aim To assess the long-term safety and efficacy of epimacular brachytherapy (EMB) for chronic, active, neovascular age-related macular degeneration (nAMD). Methods This pivotal, randomised, controlled surgical device trial recruited patients with chronic nAMD receiving intravitreal ranibizumab from 24 UK hospitals. Participants were randomised to either pars plana vitrectomy with 24 Gray EMB and pro re nata (PRN) ranibizumab (n=224) or PRN ranibizumab monotherapy (n=119). Although masking was not possible, masked clinicians assessed best-corrected visual acuity (BCVA) and imaging. After month 24, participants reverted to standard care, with either ranibizumab or aflibercept, returning for a month 36 study visit. Results Of 363 participants, 309 (85.1%) completed month 36. The number of injections was 12.1±8.1 in the EMB group versus 11.4±6.1 in the ranibizumab group (difference 0.7, 95% CI of difference −0.9 to 2.3, p=0.41) between months 1 and 36, and 3.6±3.3 (n=200) versus 3.9±2.7 (n=102) (difference −0.3, 95% CI of difference −1.0 to 0.4, p=0.43) between months 25 and 36 (standard care). Over 36 months, BCVA change was −19.7±18.5 letters in the EMB group and −4.8±12.5 in the ranibizumab group (difference −14.9, 95% CI of difference −18.5 to −11.2, p<0.0001). The month 36 BCVA of 20 EMB-treated participants with microvascular abnormalities (MVAs) at month 24 was similar to EMB-treated participants without MVAs (−21.8 vs −19.4 letters, p=0.65). Conclusion EMB does not reduce the number of anti-vascular endothelial growth factor (VEGF) injections, either within or outside of a trial setting, and is associated with worse BCVA than anti-VEGF monotherapy. Trial registration number NCT01006538.
TL;DR: In this article , a single-cell analysis revealed that IF significantly reduces pro-fibrotic signatures within APCs along with upregulation of the circadian pathways, suggesting that the circadian clock of APCs mediates IF-induced WAT remodeling.
Abstract: White adipose tissue (WAT) fibrosis is a hallmark of dysfunctional WAT that is directly linked to metabolic abnormalities. Recent studies have highlighted the role of dysfunctional adipose progenitor cells (APCs) in WAT fibrosis and impaired adaptive tissue plasticity, leading to systemic insulin resistance. However, therapeutic options for WAT fibrosis are limited. Intermittent fasting (IF) is an effective dietary regimen for weight control and metabolic improvement through various mechanisms, including healthy remodeling of WAT. However, whether IF is effective in improving age-associated WAT fibrosis and metabolic homeostasis is unknown. Here, we show that IF confers therapeutic benefits in aged and obese mice through reduction of WAT fibrosis. Single-cell analyses revealed that IF significantly reduces pro-fibrotic signatures within APCs along with upregulation of the circadian pathways, suggesting that the circadian clock of APCs mediates IF-induced WAT remodeling. Importantly, mice lacking core circadian gene exhibited increased fibrotic signatures in WAT and diminished beneficial response to IF, further supporting the importance of circadian rhythm in IF-mediated metabolic benefits. Lastly, insulin resistance in humans also presented with dysregulated circadian rhythm signatures in APC populations. Collectively, our findings highlight the novel role of the APC circadian rhythm in plasticity of WAT and metabolic response to IF.
TL;DR: In this paper , the abdominal hernias of the abdomen are defined as a noninguinal, non-hiatal defect in the fascia of the abdominal wall and a universal classification system is proposed.
Abstract: # 01. Operative classification of ventral abdominal hernias: new and practical classification {#article-title-2} Ventral hernias of the abdomen are defined as a noninguinal, nonhiatal defect in the fascia of the abdominal wall. Unfortunately, there is not currently a universal classification system
TL;DR: The approach resulted in a significant reduction in the number of postoperative opioids prescribed across a number of surgical specialties, indicating that evidence-based strategies derived from a regional collaborative can be leveraged to promote and sustain quality improvement activities.
Abstract: BACKGROUND
Opioid-related morbidity and mortality continue to rise in the province of Ontario. We implemented a provincial campaign to reduce the number of opioid pills prescribed at discharge after surgery in the Ontario Surgical Quality Improvement Network (ON-SQIN).
METHODS
Activities related to the provincial campaign were implemented between April 2019 and March 2020 and between October 2020 and March 2021. Self-reported data from participating hospitals were used to determine changes in postoperative opioid prescribing patterns across participating hospitals.
RESULTS
A total of 33 and 26 hospitals participated in the provincial campaign in the first and second year, respectively. During the first year of the campaign, the median morphine equivalent (MEQ) from opioid prescriptions decreased significantly in a number of surgical specialties, including General Surgery (from 105 [75-130] to 75 [55-107], p < 0.001) (median, interquartile range) and Orthopedic Surgery (from 450 [239-600] to 334 [167-435], p < 0.001). The median number of opioid pills prescribed at discharge per surgery also decreased significantly, from 25 [15-53) to 15 [11-38) for 1 mg hydromorphone (p < 0.001) and 25 [20-51] to 20 [15-30] for oxycodone (p < 0.001). The decrease in opioid prescription continued in the second year of the campaign.
CONCLUSION
Our approach resulted in a significant reduction in the number of postoperative opioids prescribed across a number of surgical specialties. Our findings indicate that evidence-based strategies derived from a regional collaborative can be leveraged to promote and sustain quality improvement activities.
TL;DR: The robotic approach is associated with fewer adverse events than an open approach but similar to a laparoscopic/thoracoscopic approach, and the benefit of the robotics approach is related to the minimally-invasive approach rather than the platform itself.
Abstract: BACKGROUND
Robotic surgery was integrated into some healthcare systems despite there being few well designed, real-world studies on safety or benefit. This study compared the safety of robotic with laparoscopic, thoracoscopic, and open approaches in common robotic procedures.
METHODS
This was a population-based, retrospective study of all adults who underwent prostatectomy, hysterectomy, pulmonary lobectomy, or partial nephrectomy in Ontario, Canada, between 2008 and 2018. The primary outcome was 90-day total adverse events using propensity score overlap weights, and secondary outcomes were minor or major morbidity/adverse events.
RESULTS
Data on 24 741 prostatectomy, 75 473 hysterectomy, 18 252 pulmonary lobectomy, and 6608 partial nephrectomy operations were included. Relative risks for total adverse events in robotic compared with open surgery were 0.80 (95 per cent c.i. 0.74 to 0.87) for radical prostatectomy, 0.44 (0.37 to 0.52) for hysterectomy, 0.53 (0.44 to 0.65) for pulmonary lobectomy, and 0.72 (0.54 to 0.97) for partial nephrectomy. Relative risks for total adverse events in robotic surgery compared with a laparoscopic/thoracoscopic approach were 0.94 (0.77 to 1.15), 1.00 (0.82 to 1.23), 1.01 (0.84 to 1.21), and 1.23 (0.82 to 1.84) respectively.
CONCLUSION
The robotic approach is associated with fewer adverse events than an open approach but similar to a laparoscopic/thoracoscopic approach. The benefit of the robotic approach is related to the minimally-invasive approach rather than the platform itself.
TL;DR: Postoperative complications after both elective and emergent general surgery procedures add substantially to hospital costs and quality improvement initiatives targeted at decreasing postoperative complications could significantly reduce costs in addition to improving patient outcomes.
Abstract: BACKGROUND
In a fiscally constrained health care environment, the need to reduce unnecessary spending is paramount. Postoperative complications contribute to hospital costs and utilization of health care resources. The purpose of this observational study was to identify the cost associated with complications of common general surgery procedures performed at a major academic hospital in Toronto, Ontario.
METHODS
The institutional National Surgical Quality Improvement Program (NSQIP) database was used to identify complications in patients who underwent general surgical procedures at our institution from April 2015 to February 2018. A mix of elective and emergent cases were included: bariatric surgery, laparoscopic appendectomy, laparoscopic cholecystectomy, thyroidectomy, right hemicolectomy, and ventral incisional hernia repair. Total cost for each visit was calculated by adding all aggregate costs of inpatient care. Median total costs and breakdown of cost components were compared in cases with and without complications.
RESULTS
A total of 2713 patients were included. Nearly 6% of patients experienced at least one complication, with an incidence ranging from 1.1% after bariatric surgery to 23.8% after right hemicolectomy. Most common type of complication varied by procedure. Median total costs were significantly higher in cases with complication, with a net increase ranging from %2989 CAD (35% increase) after bariatric surgery to %10 459 CAD (161% increase) after ventral incisional hernia repair.
CONCLUSIONS
Postoperative complications after both elective and emergent general surgery procedures add substantially to hospital costs. Quality improvement initiatives targeted at decreasing postoperative complications could significantly reduce costs in addition to improving patient outcomes.
04 Sep 2022
TL;DR: In this paper , the authors conducted 150 meetings with a range of community stakeholders including: village heads; nurses; community health workers and local government representatives, in open-aired community spaces, and built trust with local communities through these meetings with continued engagement during field work and data collection helping build rapport and create ownership of the study.
Abstract: Background: The Covid-19 pandemic has hit Western India hard, with Pune district reporting extremely high numbers of cases. During this time, the KEM Hospital Research Centre (KEMHRC), Pune undertook a study determining COVID-19 seropositivity within villages in the Pune district. Aim: To engage various stakeholders in establishing sentinel sero-surveillance to monitor the trend of SARS-CoV-2 infection transmission in the general population in rural Western India. Methods: An extensive stakeholder engagement drive was undertaken to drive successful recruitment and implementation of our study. Between February 2021 and May 2021, we conducted 150 meetings with a range of community stakeholders including: village heads; nurses; community health workers and local government representatives, in open-aired community spaces. We advised community members on the purpose and significance of the study, clarified any concerns, and gathered and incorporated their inputs regarding study implementation. Results: The team built trust with local communities through these meetings with continued engagement during field work and data collection helping build rapport and create ownership of the study. KEMHRC successfully enrolled 14,500 individuals residing in 150 villages in Pune district. Conclusion: The feedback sharing process is important in ensuring that engagement with the community is not limited to a one-time activity but continuous. Training & supplying opportunities can also generate stakeholder engagement champions. Effective communication, active engagement are key elements for effective engagement in research.
TL;DR: A 67-year-old woman with type 2 diabetes presented to the hospital with decreased left vision for 7 days as mentioned in this paper and was treated with anti-toxoplasmosis and anti-herpes therapy.
Abstract: A 67-year-old woman with type 2 diabetes presented to our hospital with decreased left vision for 7 days. On examination, right visual acuity was 20/30, and left visual acuity was 20/50. Intraocular pressures were both normal. Anterior chambers were deep and uninflamed, with bilateral nuclear sclerotic cataracts. There was mild left vitritis, but none in the right eye. Right fundoscopy was normal. Left fundoscopy showed one-disc diameter of unifocal retinitis along the superior vascular arcade (figure A). Left fluorescein angiography revealed late staining in the area of retinitis. The patient was treated presumptively with anti-toxoplasmosis and anti-herpes therapy (oral pyrimethamine [100 mg for the first day then 50 mg daily] and oral sulfadiazine [1 g three times daily] for toxoplasmosis, and intravenous aciclovir [800 mg three times daily] for herpetic retinitis), while awaiting laboratory results. PCR testing of anterior chamber taps were negative for Herpes simplex virus and toxoplasmosis. Negative Treponema pallidum hemagglutination and venereal disease research laboratory test excluded syphilis. Negative QuantiFERON-TB Gold test and tuberculin skin test were negative, and eliminated tuberculosis as a possible cause. Serum angiotensin converting enzyme and lysozyme were normal, which made sarcoidosis an unlikely explanation for the clinical findings. The patient's vision worsened to 20/200 in the left eye. Fundoscopy showed ongoing retinitis with a new retinal haemorrhage and serous macular detachment. She subsequently disclosed having episodes of malaise, headache, myalgia, skin rash (figure B), and fever (maximum 39·5°C; unresponsive to amoxicillin 500 mg three times a day), following travel to rural Algeria. Serology for Rickettsia conorii showed an elevated IgG titer of 1024 g/L, but was negative for IgM. Anterior tap PCR and cutaneous biopsy were negative for Rickettsia. Fundoscopy improved markedly after 7 days of treatment with doxycycline (200 mg daily). After 2 months, visual acuity was 20/20 and the retinitis resolved fully. This case illustrates the importance of careful history taking, and maintaining an index of suspicion for Rickettsia in patients who have travelled to an endemic area and present with fever, skin rash, and retinitis.