Specific Indications Research Articles

Disparities in Genetic Testing for Neurologic Disorders.

Genetic testing is now the standard of care for many neurologic conditions. Health care disparities are unfortunately widespread in the US health care system, but disparities in the utilization of genetic testing for neurologic conditions have not been studied. We tested the hypothesis that access to and results of genetic testing vary according to race, ethnicity, sex, socioeconomic status, and insurance status for adults with neurologic conditions. We analyzed retrospective data from patients who underwent genetic evaluation and testing through our institution's neurogenetics program. We tested for differences between demographic groups in 3 steps of a genetic evaluation pathway: (1) attending a neurogenetic evaluation, (2) completing genetic testing, and (3) receiving a diagnostic result. We compared patients on this genetic evaluation pathway with the population of all neurology outpatients at our institution, using univariate and multivariable logistic regression analyses. Between 2015 and 2022, a total of 128,440 patients were seen in our outpatient neurology clinics and 2,540 patients underwent genetic evaluation. Black patients were less than half as likely as White patients to be evaluated (odds ratio [OR] 0.49, p < 0.001), and this disparity was similar after controlling for other demographic factors in multivariable analysis. Patients from the least wealthy quartile of zip codes were also less likely to be evaluated (OR 0.67, p < 0.001). Among patients who underwent evaluation, there were no disparities in the likelihood of completing genetic testing, nor in the likelihood of a diagnostic result after adjusting for age. Analyses restricted to specific indications for genetic testing supported these findings. We observed unequal utilization of our clinical neurogenetics program for patients from marginalized and minoritized demographic groups, especially Black patients. Among patients who do undergo evaluation, all groups benefit similarly from genetic testing when it is indicated. Understanding and removing barriers to accessing genetic testing will be essential to health care equity and optimal care for all patients with neurologic disorders.

O203: HLA Matching Between Donors and Recipients Improves Clinical Liver Transplant Graft Survival

Abstract Background and Aims The importance of human leukocyte antigen (HLA) matching between liver transplant donors and recipients on graft survival remains unclear and is not a clinical consideration in liver transplantation. This study aimed to determine the relationship between HLA matching and liver graft survival using a large-scale multi-center database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication and donor status. Methods This retrospective observational analysis was performed using 22,702 liver transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs 4-6 mismatches), and then subcategorized by indication and donor status. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. Results Allograft survival and risk of acute rejection were associated with degree of HLA mismatch. This association between HLA mismatch and graft survival persisted in individuals who underwent transplant for hepatitis, metabolic, drug toxicity and congenital indications. Donor status influenced the relationship between HLA mismatch and graft survival. Graft survival in DBD recipients was longer than in DCD in the 4-6 HLA mismatch group, whereas no significant difference was found in the 0-3 HLA mismatch group. Conclusion HLA mismatch significantly reduced graft survival and increased risk of acute rejection. This association was noted only in specific indications. These findings are of potential clinical relevance to organ allocation, allograft matching algorithms, immunosuppression protocols and transplant surveillance.

(017) Comparing Complication Rates and Continence Control in Concurrent Dual Implantation of Inflatable Penile Prosthesis/Artificial Urinary Sphincter vs. Inflatable Penile Prosthesis/Male Sling: An Updated Comparative Pilot Study

Abstract Introduction Artificial urinary sphincter (AUS) and bulbourethral male sling are used frequently in the management of post prostatectomy urinary incontinence (UI) in men. Some surgeons used to combine an inflatable Penile Prosthesis (IPP) procedure at the same setting to treat concurrent erectile dysfunction (ED). Recent clinical trials have aimed to determine the comparative effectiveness between the male sling and the artificial urinary sphincter (AUS) in men with urodynamic stress urinary incontinence (SUI) after prostate surgery, focusing on non-inferiority. Objective We aim to compare continence control and complications rates in patients who underwent bulbourethral slings or AUS during IPP surgery via perineal approach. Methods A retrospective chart review was done in a large tertiary center. Post prostatectomy patients who underwent perineal dual implantation IPP and AUS or bulbourethral sling for ED and UI purposes, between 2014 and 2022 were included. Clinical data, patients’ demographics were retrieved. Post-operative outcomes with regards to IPP complication rates, revision rates for IPP/ AUS / Male sling, and continence control at 6 weeks, 6 months and 1 year were collected and included in the analysis. Continence control rates were assessed by the number of pads used per day on subsequent follow up visits for both groups. Results A total of 32 patients met the inclusion criteria. 16 Patients underwent synchronous IPP and AUS insertion, whereas another 16 patients underwent IPP with bulbourethral sling procedure. Patient demographics, median follow up &amp; complication rates are summarized below in Table 1. In both groups the procedure was done through a perineal approach. There was no significant difference in baseline data among groups. Complication rates between AUS devices and bulbourethral slings showed no statistically significant differences (12.5% vs 6.25% p= 0.22 respectively). Infection rates and need for revision also did not show any statistically significant differences. With regards to post-operative continence rates, both groups had comparable outcome with no significant differences (P = 0.81). Upon the 6 months follow up visit, the AUS group, 56% were pad free, 19% used 1 pad per day, 19% used 2 pads per day, and 6% used 3 pads or more per day, while in the sling group, 50% were pad free, 25% used 1 pad per day, 19% used 2 pads per day, and 6% used 3 pads or more per day. Patients were followed for a total of 1 year after the surgery. Conclusions The combined insertion of IPP with either AUS or sling procedures has comparable outcomes with regards to continence rate and device- related complications. Each incontinence surgery should be chosen according to surgeon experience and specific patient indications. Further prospective studies on a larger sample of patients with longer follow up period are needed to solidify these findings and will guide patient's decision and preference for incontinence surgeries along with IPP once indicated. Disclosure No.

Phytochemical, Pharmacological, and Toxicological Prospection of Morus nigra L.: A Systematic Review

Introduction: Morus nigra L. has industrial relevance due to the presence of specialized metabolites, which possess pharmaceutical potential in various parts and preparations. This review presents updated information on traditional, phytochemical, and pharmacological applications, as well as toxicity data, pertaining to different parts of Morus nigra L. Method: Phytochemical research and ethnobotanical studies were conducted using reviewed databases. Mulberry leaves have demonstrated several biological activities, attributed to the presence of phenolic acids, flavonoids, and fatty acids. Stems and roots contain additional compounds such as stilbenes and benzofurans. Morus nigra L. exhibits various biological activities, including hepatoprotective, hypolipidemic, anti-inflammatory, antioxidant, antimicrobial, neuroprotective, hypoglycemic, skin whitening, cytotoxic, antiatherosclerotic, and antiobesity effects. The choice of extraction technique and plant part is crucial to obtain a diverse range of compounds necessary for specific indications. Result: Accelerated solvent extraction (ASE) has proven to be the most advantageous method compared to supercritical fluid maceration and extraction (SFE), yielding a wide variety of compounds. Conclusion: Overall, this review aims to provide scientists and companies interested in Morus nigra L. with opportunities and challenges for innovation in this field.

Treatment and diagnostics of gout: Unsolved problems in clinical practice

The possibilities for diagnosing and treating gout have expanded significantly. However, this did not lead to solving the problem of timely diagnosis of gout, nor to improving control over it, nor to reducing mortality in patients with gout. In the article possible reasons of absence of the progress in gout control connected with the lack of usage of contemporary capabilities in diagnosis and mistakes in usage of drugs therapy is discussed. These should include the lack of conversance of medical stuff about sonography high informativity for gout diagnosis, low availability of polarizing microscopy and dual energy computer tomography; causeless ignore of prescribing prophylactic symptomatic therapy, usage of inadequate doses of drugs. Another reason may be the absence of unified concept regarding specific indications of prescribing urate-lowering drugs and choice of specific medicine.

Navigating the landscape of clinical genetic testing: insights and challenges in rare disease diagnostics

With the rapid evolution of diagnostic tools, particularly next-generation sequencing, the identification of genetic diseases, predominantly those with pediatric-onset, has significantly advanced. However, this progress presents challenges that span from selecting appropriate tests to the final interpretation of results. This review examines various genetic testing methodologies, each with specific indications and characteristics, emphasizing the importance of selecting the appropriate genetic test in clinical practice, taking into account factors like detection range, cost, turnaround time, and specificity of the clinical diagnosis. Interpretation of variants has become more challenging, often requiring further validation and significant resource allocation. Laboratories primarily classify variants based on the American College of Medical Genetics and Genomics and the Association for Clinical Genomic Science guidelines, however, this process has limitations. This review underscores the critical role of clinicians in matching patient phenotypes with reported genes/variants and considering additional factors such as variable expressivity, disease pleiotropy, and incomplete penetrance. These considerations should be aligned with specific gene-disease characteristics and segregation results based on an extended pedigree. In conclusion, this review aims to enhance understanding of the complexities of clinical genetic testing, advocating for a multidisciplinary approach to ensure accurate diagnosis and effective management of rare genetic diseases.

Technique of Colon Interposition for Oesophageal Replacement for Oesophageal Cancer

Nowadays, it is only relatively rare and in selected situations that colonic interposition is chosen rather than the stomach as a reconstructive organ for replacing the oesophagus. The colon is a reliable organ for tubular replacement of the oesophagus when the stomach is not available for reconstruction. Colon interposition is a complex and complicated operation. It requires a specific indication and thorough preoperative preparation. From a technical point of view, colon interposition places high demands on the selection and surgical dissection of the vascular supply to the reconstructed organ. The reconstruction route and elevation of the interposition graft to the proximal oesophagus and the need to create 3 or 4 gastrointestinal anastomoses also place significantly higher demands than reconstruction using a gastric tube. Overall, despite the significant surgery-related morbidity, good functional results and a good quality of life can usually be achieved. The surgical technique applied in our own practice is described in detail. An overview from literature on the results of colonic interposition is given, particularly with regard to surgical complications and quality of life after colon interposition.

Regulation for the Translation of Gene and Cell Therapy into Medical Practice in East Asian Countries

SCIENTIFIC RELEVANCE. Currently, the Russian Federation lacks a comprehensive regulatory framework for the use of gene and cell therapy (GCT) products. There is no standard for conducting clinical trials for purposes other than marketing authorisation in Russia. In contrast, international practice shows that, in addition to marketing authorisation, including approval based on incomplete data with post-approval commitments, there are regulatory mechanisms for the use of unregistered GCT products, such as hospital exemptions, expanded access, or compassionate use in the European Union and the USA. Relatively recently, this framework has been reformed in East Asian countries.AIM. This study aimed to analyse the regulatory mechanisms for translating GCT products into medical practice in East Asian countries and to assess the possibility of transferring elements of international experience to Russian practice.DISCUSSION. East Asian countries have adopted legislation on requirements for the manufacturing and medicinal use of GCT products. These requirements include having a mandatory license for production in accordance with Good Manufacturing Practice, consideration of the rationale for the use of GCT products by regulatory authorities or special committees, risk classification of investigational GCT products, approved registries of medical institutions authorised to use GCT products, and necessary monitoring and control of patients after GCT administration. Only cellbased innovative medicines, including genetically modified cells, are used within the framework of medical technologies (Japan, China, and Taiwan) or services (Republic of Korea), and in vivo gene therapy products can be used only in investigator-initiated clinical trials.CONCLUSIONS. The East Asian experience in translating GСT products into medical practice would be extremely useful for the Russian Federation, especially in terms of GСT use for specific indications based on accumulated clinical experience. The review suggests that it would be appropriate to establish legal provisions for investigator-initiated clinical research in Russian national legislation.

Articular arthrodesis with the facet wedge technique for the treatment of unstable lumbar degenerative disease and associated conditions: A retrospective study of 96 patients

BackgroundLumbar articular fusion with the facet wedge (FW) technique is gaining increasing interest among surgeons for the treatment of vertebral instability due to its limited invasiveness and ease of use. Studies on cadavers have reported biomechanical properties similar to pedicle screws. Yet, the evidence supporting their use is still limited and moreover focused only on spinal degenerative disease. Methods96 cases of lumbar articular fusion with the FW techniques performed at 3 different centers between 2014 and 2022 were retrospectively analyzed based on the specific surgical indications: 1) degenerative spondylolisthesis/unstable lumbar stenosis; 2) synovial cysts; 3) adjacent segment disease (ASD). Medical records were reviewed to identify rates of complications and measures of functional outcome (ODI, low back pain VAS and modified Macnab scale) were collected both at baseline and at the follow-up visits. Wilcoxon signed-rank test was adopted to test for significant functional improvements. ResultsSignificative clinical improvements were observed from baseline to follow-up regarding ODI and VAS scores. Overall rate of moderate and severe complications (according to Landriel–Ibañez scale) was 7.9%. Only 3.4% of patients with degenerative disease developed ASD requiring reoperations. Only one case of radicular deficit and one of device mobilization were reported. 2/4 cases of synovial cysts treated with unilateral fusions developed contralateral complications. 9 out of 16 (56.25%) patients who underwent long-term postoperative CT scans presented adequate degree of articular fusion. ConclusionFW technique is easy, safe, and effective. Its low rate of complications justifies its use for cases of mild lumbar instability.

Use of acenocoumarol in cardioembolic stroke: an evidence-based review

Stroke is the leading cause of long-term disability and the second most common cause of death worldwide. Nearly two-thirds of all strokes represent cerebral ischemia, of which about 15%-30% are of cardioembolic origin. Atrial fibrillation accounts for about 60% of all cardioembolic strokes. Current clinical evidence suggests that oral anticoagulant therapy can prevent around 70% of strokes in patients with atrial fibrillation. Oral anticoagulation therapy is preferred over antiplatelet therapy in patients with cardioembolic stroke. Vitamin K antagonists (VKAs) and nonvitamin K antagonist oral anticoagulants (NOACs) are routinely prescribed oral anticoagulants in patients at risk of stroke; however, there are specific indications where VKA use surpasses NOAC use or there are conditions where NOACs are contraindicated. A group of experts revisited the role of oral anticoagulants in the management of cardioembolic stroke in India with emphasis on VKA, specifically acenocoumarol. This article discusses various aspects of anticoagulation therapy, including the timing of initiation and patient monitoring, in patients with cardioembolic stroke with reference to current clinical evidence and expert opinion based on Indian clinical experience.

Analysis of dose-TSH response effect of levothyroxine soft-gel formulation.

Hypothyroidism is treated with daily levothyroxine (LT4). In recent years, soft gel caps of LT4 (LT4-C) have been commercialized, and their performance has been optimized. Since guidelines recommend dose LT4 according to the tablet preparation efficacy, the present study was undertaken to obtain data about the daily requirement, normalized per body weight, of LT4-C. Patients undergoing LT4-C after total thyroidectomy and radioiodine treatment for differentiated thyroid carcinoma were selected. There was no specific indication of suppression of TSH (i.e., <0.5 or <0.1 mIU/L). Patients were required to maintain a stable LT4 dose during the study period. Patients with interfering factors were excluded from this study. Thirty patients were enrolled (18 females and 12 males; median age, 50 years; median body weight, 71 kg; median LT4-C dose, 1.71 µg/kg/day). The analysis of patient age did not reveal any differences. The LT4-C dose correlated with free-T4 p = 0.03), but not with TSH (p = 0.42) and free-T3 (p = 0.13). TSH was <1.0 mIU/L in 90% of the cases. The LT4-C dose-TSH response effect was analysed by probit regression model: the probability to achieve TSH <1.0 mIU/l was 99% with a dose of 1.84 (95%CI 1.57-2.12) µg/kg/day, 75% with a dose of 1.38 µg/kg/day (95%CI 1.17-1.59), and 50% with a dose of 1.20 (95%CI 0.96-1.43). At ROC curve analysis, the most accurate cut-off of LT4-C dose to achieve TSH <1.0 mIU/l was 1.53 ug/kg/day with 70% sensitivity and 100% specificity. Athyreotic patients can be initially treated with an LT4-C dose lower than previously stated. Therefore, further prospective studies are warranted.

How many Italian cancer patients are eligible for, and may respond to, Italian Medicines Agency-approved immune checkpoint inhibitors?

This cross-sectional study was aimed at estimating the number of Italian incident cancer patients in 2020 eligible for, and respondent to, immune checkpoint inhibitors (ICI). The study is based on publicly available data: the ICI approved until August 2022 by the Italian Medicines Agency (AIFA) with their specific indications and overall observed responses, rther details can be found in the Online Supplementary Materi cancer incidence estimates at 2020 and observed cancer deaths, and published papers with estimates on the frequency of different cancer stage/histology/markers etc. corresponding to AIFA authorizations. In the analyzed period, a total of seven ICI were authorized in Italy for 20 cancer types. The estimated number of ICI-eligible patients in 2020 was 48,400, 14.3% of those tumors (including skin epitheliomas) that may fit AIFA-indications, and 10.5% of all the incident malignant tumors, including skin epitheliomas. The number of patients who may benefit from ICI therapy was 24,052, 49.7% of the ICI-eligible ones, or 5.2% of the overall estimated incident cancers in 2020. In conclusion, although the number of ICI-eligible patients is a relatively small proportion of the yearly burden of cancers, about half of them may respond to ICI-treatment.

Global trends and outcomes of nerve transfers for treatment of adult brachial plexus injuries.

The presentation, management and outcomes of brachial plexus injuries are likely to be subject to regional differences across the globe. A comprehensive literature search was performed to identify relevant articles related to spinal accessory to suprascapular, intercostal to musculocutaneous, and ulnar and/or median nerve fascicle to biceps and/or brachialis motor branch nerve transfers for treatment of brachial plexus injuries. A total of 6007 individual brachial plexus injuries were described with a mean follow-up of 38 months. The specific indication for accessory to suprascapular and intercostal to musculocutaneous transfers were considerably different among regions (e.g. upper plexus vs. pan-plexal), while uniform for fascicular transfer for elbow flexion (e.g. upper plexus +/- C7). Similarly, functional recovery was highly variable for accessory to suprascapular and intercostal to musculocutaneous transfers, while British Medical Research Council grade ≥3 strength after fascicular transfer for elbow flexion was frequently obtained. Overall, differences in outcomes seem to be inherent to the specific transfer being utilized.Level of evidence: III.

Review and update on the management of triangular fibrocartilage complex injuries in professional athletes.

Triangular fibrocartilage complex injuries are common in amateur and professional sports. These injuries are mainly caused by acute or chronic repetitive axial loads on the wrist, particularly on the ulnar side and in association with rotations or radial/ulnar deviations. In order to treat professional athletes, a detailed specific knowledge of the pathology is needed. Moreover, the clinician should fully understand the specific and unique environment and needs of the athletes, their priorities and goals, the type of sport, the time of the season, and the position played. An early diagnosis and appropriate management with the quickest possible recovery time are the uppermost goals for both the athlete and the surgeon. A compromise between conservative vs surgical indications, athletes' needs and expectations, and financial implications should be achieved. Arthroscopic procedures should be timely planned when indicated as they could allow early diagnosis and treatment at the same time. Conservative measures are often used as first line treatment when possible. Peripheral lesions are treated by arthroscopic repair, whilst central lesions are treated by arthroscopic debridement. Further procedures (such as the Wafer procedure, ulnar osteotomies, etc.) have specific indications and great implications with regard to rehabilitation.

ESPGHAN recommendations on treatment of chronic hepatitis C virus infection in adolescents and children including those living in resource-limited settings.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide, with more than three million viraemic adolescents and children. Treatment of adults with HCV infection and HCV-related liver disease has advanced considerably thanks to development and improvements in therapy. Direct-acting antiviral regimens are safe and effective. Three regimens with pangenotypic activity (glecaprevir/pibrentasvir, sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir) and three regimens with genotype-specific activity (sofosbuvir/ribavirin, sofosbuvir/ledipasvir and elbasvir/grazoprevir) have been approved with age-specific limitation for treatment of children with chronic hepatitis C by the European Medicines Agency and the United States Food and Drug Administration. The World Health Organization has set the ambitious target to eliminate hepatitis C as a major public health threat by 2030 and based its actions against HCV on the large use of direct acting antivirals. These updated European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations on treatment of hepatitis C describe the optimal therapeutic management of adolescents and children with HCV infection including specific indications for those living in resource-limited settings.

The Value of Axial Imaging to Check Reduction after Anterior Approach Open Reduction for Developmental Dysplasia of the Hip

Background: There are still many controversies regarding the diagnosis and management of developmental dysplasia of the hip (DDH). Axial imaging is routinely used after closed or open reduction to confirm reduction has occurred. In this study, we aimed to determine the rate of early re-dislocation or failure of reduction after anterior approach open reduction (AOR), to establish whether there is a true need for routinely performing post-operative axial imaging.&#x0D; Methods: We retrospectively reviewed radiographs, operation notes and post-operative CT scan images of our AOR cases from September 2018 to June 2020. The CT scan images were reviewed to check the post-operative reduction and congruency. The ‘posterior neckline’ and the ‘modified Shenton line’ were used to assess reduction. The related literature was also reviewed.&#x0D; Results: Thirty patients were included. The post-operative CT scans confirmed that all cases had reduced congruent hips. The CT scans did not change future treatment plans for any patient in this cohort and did not predict late re-dislocation.&#x0D; Conclusions: The rate of early re-dislocation or failure of reduction after AOR was negligible. Traditional routine axial imaging after this operation is therefore unjustified and has no value in predicting possible late re-dislocations. It also comes at the cost of extra radiation to the child and expense for the health system. We recommend stopping the routine use of post-operative axial imaging and using it selectively for specific indications, including teratologic and neuromuscular hips, bilateral DDH, and after revision surgery, in addition to closed reductions and medial approach open reduction.

A72 THE ENDOSCOPIC YIELD OF PRIORITIZED INDICATIONS USING A PROVINCIAL-WIDE COLONOSCOPY REFERRAL FORM

Abstract Background The widespread use of a standardized and validated province-wide colonoscopy referral form (PCRF), regrouping mutually exclusive indications into suggested priority wait time categories, has allowed for a more comprehensive assessment of routine colonoscopy practice Aims To validate the Quebec PCRF by better characterizing endoscopic finding yields according to specific clinical indications. Methods This retrospective cohort study includes consecutive adult patients with available data from the PCRF from two tertiary hospitals. The primary outcome was the diagnostic rates of colorectal cancer (CRC). Secondary outcomes assessed incidences of clinically significant lesions (CSL) on endoscopy and confirmed at pathology. These are CRC, advanced adenomas, sessile serrated polyps, polyps ≥ 5mm, colitis, colonic strictures, and miscellaneous other findings excluding hemorrhoids and diverticulosis. Descriptive and inferential statistics, and multivariable regression predictive modeling are reported. Results Overall, 14,657 patients (mean age 59.2 ± 14.0 years, 50.9% female) were included from September 2018 to August 2022. The most frequent indications for colonoscopy were polyp surveillance (IN13, 20.8%), recent change in bowel habits (IN7, 11.9%), a positive fecal immunochemical test (IN5, 8.3%), a family history of CRC or polyps (first-degree relative) (IN8, 6.4%), and suspected active inflammatory bowel disease (IBD) (IN3, 5.8%). Overall, 40.6% had CSL, including CRCs in 0.8%. CRCs were found more frequently for IN2 (19.7% vs 2.0%, pampersand:003C0.01), IN5 (29.9% vs 8.2%, pampersand:003C0.01), and an unexplained documented iron deficiency anemia (IN6) (11.8% vs 5.2%, pampersand:003C0.01). CSLs were more frequent for IN3 (1.6% vs 5.8%, p=0.04), IN7 (4.7% vs 12.0%, p=0.01), IN8 (0.8% vs 6.5%, p=0.01), IN13 (7.1% vs 20.9%, pampersand:003C0.01), IBD surveillance (IN15, 0.0% vs 4.0%, p=0.02), and surveillance for a significant family history (IN21, 0.0% vs 3.7%, p=0.02). On multivariable analysis, CRC was significantly associated with IN2 OR=31.8 (4.86; 208.7), IN5 OR=19.2 (3.86; 95.7), and IN6 OR=15.7 (2.37; 78.0) - (all are high priority PCRF referrals with a suggested shorter wait time than for most other indications). CSLs were significantly associated with age (OR=1.03 (1.02; 1.03)), IN2 (OR=2.32 (1.35; 3.99)), IN5 (OR=2.37 (1.74; 3.22)), and IN13 (OR= 1.66 (1.36; 2.02)). Conclusions This large cohort study confirms the validity of indications and corresponding prioritization of wait times of a PCRF. Funding Agencies CPAC and MSSS

A108 AN EVALUATION OF IMPLEMENTATION OF A CENTRALIZED REFERRAL AND BOOKING PROCESS ON WAIT TIMES FOR COLONOSCOPIES

Abstract Background Colonoscopies in the majority of centres in Ontario are booked by individual endoscopists via their individual offices (practices). As such, wait times for procedures will vary significant from centre to centre, or even from endoscopist to endoscopist at the same centre, depending on individual expertise, experience, procedure types, and local availability of endoscopic resources. This system could lead to significant variability in access to care for patients. Aims This study analyzed the effect of implementing a centralized referral and booking process for colonoscopy, for a specific indication, at a single centre in Ontario. Methods This was a single centre retrospective study analyzing wait times for patients that underwent a colonoscopy at Cambridge Memorial Hospital (CMH) between April 2017 to July 2022 for either positive fecal occult blood test (FOBT) or fecal immunochemistry test (FIT). The province of Ontario transitioned from FOBT to FIT as the primary tool for colon cancer screening in 2019. Prior to this transition, colonoscopy for positive FOBT performed at CMH were booked by individual endoscopists, with wait times from referral to procedure having great variability. In conjunction with Ontario’s transition to FIT for colon cancer screening, all endoscopists at CMH agreed to participate in a centralized referral and booking process specifically for colonoscopy for positive FIT indication. A chart review of all patients undergoing colonoscopy for either FOBT (non central booking) or FIT (central booking). Patients that self-delayed were excluded. Wait times (WT) was calculated as time between date of referral and date of procedure. The effect of the centralized booking system on wait times was then assessed using statistical analysis. Results In total, 344 patients were included for analysis from before March 2019 (non centralized booking process). The average WT in this group was determined to be 99.2 days (range 50-171 days), of which 147 patients had a WT of less than 56 days (42.7%). In contrast, a total 572 patients were included for analysis after March 2019 (centralized booking process), the average WT was determined to be 44.2 days (range 32-59 days), of which, 526 patients had a WT of less than 56 days (92.0%). The centralized booking process reduced average wait times by 55 days (55.4%), and improved procedure WTs meeting mandated time frame of 56 days by 49.3%. This improvement in wait times was most pronounced for endoscopists with the longest wait times in a non centralized system. Conclusions The implementation of a centralized referral and booking process (for a single indication for colonoscopy) was associated with significantly reduced WTs. These findings suggest a centralized referral and booking process (for well defined clinical needs) can potentially significantly improve patient wait times. Funding Agencies None

Strategies to Improve Cannabidiol Bioavailability and Drug Delivery.

The poor physicochemical properties of cannabidiol (CBD) hamper its clinical development. The aim of this review was to examine the literature to identify novel oral products and delivery strategies for CBD, while assessing their clinical implications and translatability. Evaluation of the published literature revealed that oral CBD strategies are primarily focused on lipid-based and emulsion solutions or encapsulations, which improve the overall pharmacokinetics (PK) of CBD. Some emulsion formulations demonstrate more rapid systemic delivery. Variability in the PK effects of different oral CBD products is apparent across species. Several novel administration routes exist for CBD delivery that may offer promise for specific indications. For example, intranasal administration and inhalation allow quick delivery of CBD to the plasma and the brain, whereas transdermal and transmucosal administration routes deliver CBD systemically more slowly. There are limited but promising data on novel delivery routes such as intramuscular and subcutaneous. Very limited data show that CBD is generally well distributed across tissues and that some CBD products enable increased delivery of CBD to different brain regions. However, evidence is limited regarding whether changes in CBD PK profiles and tissue distribution equate to superior therapeutic efficacy across indications and whether specific CBD products might be suited to particular indications.

Fecal microbiome composition and diversity of cryopreserved canine stool at different duration and storage conditions.

Fresh-frozen stool banks intended for humans with gastrointestinal and metabolic disorders have been recently established and there are ongoing efforts to establish the first veterinary fresh-frozen stool bank. Fresh frozen stored feces provide an advantage of increased availability and accessibility to high-quality optimal donor fecal material. The stability of frozen canine feces regarding fecal microbiome composition and diversity has not been reported in dogs, providing the basis for this study. We hypothesized that fecal microbial composition and diversity of healthy dogs would remain stable when stored at -20°C and -80°C for up to 12 months compared to baseline samples evaluated before freezing. Stool samples were collected from 20 apparently healthy dogs, manually homogenized, cryopreserved in 20% glycerol and aliquoted, frozen in liquid nitrogen and stored at -20°C or -80°C for 3, 6, 9, and 12 months. At baseline and after period of storage, aliquots were thawed and treated with propidium monoazide before fecal DNA extraction. Following long-read 16S-rRNA amplicon sequencing, bacterial community composition and diversity were compared among treatment groups. We demonstrated that fresh-frozen canine stools collected from 20 apparently healthy dogs could be stored for up to 12 months at -80°C with minimal change in microbial community composition and diversity and that storage at -80°C is superior to storage at -20°C. We also found that differences between dogs had the largest effect on community composition and diversity. Relative abundances of certain bacterial taxa, including those known to be short-chain fatty acid producers, varied significantly with specific storage temperatures and duration. Further work is required to ascertain whether fecal donor material that differs in bacterial community composition and diversity across storage conditions and duration could lead to differences in clinical efficacy for specific clinical indications of fecal microbiota transplantation.