Withdrawal Time Research Articles

‘If in Doubt, Sit Them Out’: How Long to Return to Elite Cycling Competition following a Sports-Related Concussion (SRC)?

A concussion or sports-related concussion (SRC) is a traumatic brain injury induced by biomechanical forces. After a SRC diagnosis is made, a concussed individual must undergo a period away from competition while they return to their baseline level of functioning. The Union Cycliste Internationale (UCI) currently recommend a minimum of 6 days restriction from competitive cycling following a SRC but there is a growing feeling amongst those involved in brain injury research that this period is too short. Therefore, how much time should cyclists be removed from competitive sporting action following a SRC? To review the time out of competition following the diagnosis of a SRC for elite cyclists within British Cycling (BC). All medical records for elite cyclists within BC were audited for diagnoses of "concussion" or "sports-related concussions" from January 2017 until September 2022. The days out of competition following the concussion until ready to compete again (that is, returned to full training) was then calculated. All diagnoses and management of SRC were undertaken by the medical team at BC and in-keeping with current international guidelines. Between January 2017 and September 2022, there were 88 concussions diagnosed, 54 being males and 8 in para-athletes. The median duration for time out of competition for all concussions was 16 days. There was no statistical difference between males (median 15.5 days) and females (median 17.5 days) for time out of competition (p-value 0.25). The median duration out of competition following a concussion for able-bodied athletes was 16 (80 athletes) compared to 51 days (8 athletes) in para-cyclists, which was not statistically different (p-value 0.39). This is the first study to report SRC concussion recovery times in elite cycling, including para-athletes. Between January 2017 and September 2022, there were 88 concussions diagnosed at BC and the median duration for time out of competition for all concussions was 16 days. There was no statistically significant difference in recovery times between male and females and para- and able-bodied athletes. This data should be used to help establish minimum withdrawal times post-SRC for elite cycling participation and we call on the UCI to review this data when establishing SRC protocols for cycling, with further research required in para-cyclists.

Assessment of anti-arthritic activity of lipid matrix encased berberine in rheumatic animal model

The purpose of this study was to evaluate the drug delivery and therapeutic potential of berberine (Br) loaded nanoformulation in rheumatoid arthritis (RA)-induced animal model. The Br-loaded NLCs (nanostructured lipid carriers) were prepared employing melt-emulsification process, and optimised through Box–Behnken design. The prepared NLCs were assessed for in-vitro and in-vivo evaluations. The optimised NLCs exhibited a mean diameter of 180.2 ± 0.31 nm with 88.32 ± 2.43% entrapment efficiency. An enhanced anti-arthritic activity with reduced arthritic scores to 0.66 ± 0.51, reduction in ankle diameter to 5.80 ± 0.27 mm, decline in paw withdrawal timing, and improvements in walking behaviour were observed in the Br-NLCs treated group. The radiographic images revealed a reduction in bone and cartilage deformation. The Br-NLCs showed promising results in the management of RA disease, can be developed as an efficient delivery system at commercial levels, and may be explored for clinical application after suitable experiments in the future.

Withdrawal time in colonoscopy, past, present, and future, a narrative review.

Colonoscopy is a time proven, safe, and gold standard screening method for colorectal cancer (CRC). In order to achieve its objectives, quality markers have been defined for colonoscopy, including withdrawal time (WT). WT is defined as the time spent from reaching the cecum or terminal ileum till the end of procedure in colonoscopies without any additional interventions. This review aims to provide evidence on WT efficacy and future directions. We conducted a comprehensive literature search of articles evaluating WT. Search was limited to English language articles from all peer-reviewed journals. The seminal study by Barclay et al., led to setting of a minimum WT of 6 minutes as the recommended amount for colonoscopy, per 2006 American College of Gastroenterology (ACG) taskforce. Since then, many observational studies have confirmed the efficacy of 6 minutes. Recently, multiple large multicenter trials suggest WT of 9 minutes as the alternative for better outcomes. Recently, novel Artificial Intelligence (AI) models have shown promise in improving WT and other outcomes and proved an exciting tool in the armamentarium of gastroenterologists. Some of these tools encourage the endoscopists to check the blind spots and clean the residual stool. This has shown to improve both WT and ADR. We recommend an improvement of these models to consider risk factors like adenoma detection in current and prior scopes to guide endoscopists spend time in each segment. In conclusion, new evidence demonstrates that WT of 9 minutes is better than 6 minutes. Future trends point toward an individualized AI-based approach combining real time and baseline data and guiding the endoscopist on how much time to spend in every segment of the colon in every colonoscopy procedure.

Safety and efficacy of a feed additive consisting of halofuginone hydrobromide (STENOROL®) for chickens for fattening and turkeys for fattening/reared for breeding (Huvepharma N.V.)

Following a request from the European Commission, EFSA was asked to deliver a new scientific opinion on the coccidiostat halofuginone hydrobromide (STENOROL®) when used as a feed additive for chickens for fattening and turkeys for fattening/reared for breeding. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concludes that the safety for turkeys for fattening established in its previous opinion can be extended to turkeys for breeding up to 12 weeks of age. Based on the new data provided on the safety for consumer, environment and efficacy, the Panel updates its previous conclusions as follows: halofuginone hydrobromide is not genotoxic. Applying an uncertainty factor of 100 to the lowest no observed adverse effect level (NOAEL) of 0.03 mg/kg body weight (bw) per day, an acceptable daily intake (ADI) of 0.3 μg halofuginone/kg bw is established. The chronic exposure of consumers to residues of halofuginone would amount to 6-19% of the ADI after 3 days of withdrawal. Therefore, the Panel considers that the additive is safe for the consumer of tissues obtained from chickens for fattening and turkeys for fattening fed the additive at a maximum level of 3 mg/kg complete feed at a 3-day withdrawal time. For control purposes, the Panel recommends the setting of the following maximum residue limits (MRLs): liver, 50 μg/kg; kidney, 40 μg/kg; muscle, 3 μg/kg; skin/fat, 10 μg/kg wet tissue. Based on an updated environmental risk assessment, no concern for groundwater is expected. Halofuginone is unlikely to bioaccumulate and the risk of secondary poisoning is not likely to occur. No safety concerns are expected for terrestrial and aquatic environments. The additive has the potential to control coccidiosis in chickens for fattening and turkeys for fattening/reared for breeding up to 12 weeks of age at a minimum level of 2 mg/kg complete feed.

Pharmacokinetics of aminocaproic acid in thoroughbred horses.

The antifibrinolytic agent aminocaproic acid (ACA) is occasionally used prior to episodes of intense training in racehorses suffering from exercise-induced pulmonary hemorrhage. Although a previous study indicated that the drug is cleared rapidly in horses, some racetrack practitioners claim that recent adverse analytical findings for ACA in postrace samples were from ACA administrations 5-7 days before the race. The purpose of this study was to re-examine the pharmacokinetics of ACA in horses to address this apparent conundrum. Eight exercise-conditioned thoroughbred horses were administered 5g of ACA IV, and blood and urine samples were collected at pre-determined time points prior to drug administration and for up to 168 h after dosing. Concentrations of ACA in the serum and urine samples were determined by LC-MS/MS. The pharmacokinetics of ACA in serum were best described by a three-compartment model with a terminal elimination half-life of 24.2 ± 2.9h. After dosing, ACA was above the lower limit of detection (1ng/mL for serum and 10ng/mL for urine) in all serum and urine samples at all time points. In a similar manner, ACA was above the lower limit of quantification (LLOQ; 10ng/mL for serum and 100 ng/mL for urine) in all serum and urine samples collected from all horses from 0.5 to 120 h post dosing. In six of the eight horses, ACA was above the LLOQ 168 h after dosing in serum and urine samples. LC-MS/MS methodology is the industry standard for testing of samples collected from racehorses with the purpose of controlling the use of medications and performance altering substances. The improved sensitivity of the analytical procedure used in the present study allowed the detection of a prolonged terminal elimination phase of ACA in horses that had not previously been described. Currently, most racing jurisdictions have not adopted a permitted concentration or threshold for ACA in postrace samples, and therefore veterinarians need to allow for an extended withdrawal time of a minimum of 11 days after the administration of ACA to racehorses to substantially reduce the risk of adverse analytical findings of ACA in postrace samples.

Elimination of Cefquinome Sulfate Residue in Cow's Milk after Intrauterine Infusion.

As set in the maximum residue limit regulations of the European Commission, this study aimed to obtain the residual parameters in milk with optimized UPLC-MS/MS conditions and to determine the conclusive drug withdrawal period to ensure food safety. In this research, an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to study cefquinome sulfate's residue elimination in milk and to calculate cefquinome's withdrawal period. Twelve healthy cows free of endometritis were selected for the experiment. Before using the drug, the vaginal orifice and perineum of each cow was disinfected. One dose of intrauterine perfusion was used for each cow, followed by an additional dose after 72 h. Before administration and 12 h, 18 h, 24 h, 36 h, 42 h, 48 h, 60 h, 66 h, 72 h, 84 h, 90 h, and 96 h after the last dose, milk (10 mL) was gathered from each cow's teat and pooled. For the measurement of cefquinome concentrations in milk, UPLC-MS/MS was performed. A calibration curve was generated using linear regression as follows: Y = 250.86X - 102.29, with a correlation coefficient of 0.9996; the limits of detection and the limits of quantitation were 0.1 μg·kg-1 and 0.2 μg·kg-1, respectively. The average recovery of cefquinome was 88.60 ± 16.33% at 0.2 μg·kg-1, 100.95 ± 2.54% at 10 μg·kg-1, and 97.29 ± 1.77% at 50 μg·kg-1. For 5 consecutive days at the three spiking levels, the intra and inter-day relative standard deviations (RSD) were 1.28%-13.73% and 1.81%-18.44%, respectively; the residual amount of cefquinome was less than the maximum residue limit of 20 μg·kg-1, 36 h after administration; and the residual amount was less than the limit of detection (0.1 μg·kg-1) 48 h after administration. The withdrawal time of cefquinome in cow's milk was 39.8 h, as calculated using WTM1.4 software. In terms of clinical practical use, the withdrawal period of milk was temporarily set at 48 h after the administration of the cefquinome sulfate uterus injection to cows, in accordance with the recommended dose and course.

Control of a sulfadoxine/trimethoprim combination in the competition horse: Elimination, metabolism and detection following an intravenous administration.

The combination of sulfadoxine (SDO) with trimethoprim (TMP) is widely used in veterinarian medicine. The aim of the present study was to compare excretion profiles and detection time windows of SDO and TMP in plasma and urine by means of a validated quantitative method. Eight horses received a single intravenous (i.v.) dose of 2.7 mg TMP and 13.4 mg SDO per kg bodyweight. Plasma and urine samples were collected up to 15 and 70 days post-administration, respectively. While urine samples underwent an enzymatic hydrolysis, plasma samples were proteolysed before further analysis. After solid-phase extraction, samples were analysed by liquid chromatography/electrospray ionisation tandem mass spectrometry in positive ionisation mode. The applied multiple reaction monitoring (MRM) method allowed the detection of SDO and TMP with a lower limit of detection of 0.03 ng/mL in plasma and 0.2 (SDO) and 0.4 ng/mL (TMP) in urine, respectively. In the present study, detection times for SDO were 15 days in plasma and 49 days in urine, respectively. TMP was detected for up to 7 days in plasma and up to 50 days in urine, respectively. The detection via the TMP metabolite 3-desmethyl-trimethoprim was possible for 70 days in urine. Detection times of the other confirmed metabolites N4 -acetylated sulfadoxine, hydroxytrimethoprim, trimethoprim-1-oxide and trimethoprim-3-oxide were significantly lower. In order to postulate reasonable screening limits (SLs) to control specific withdrawal times, a Monte Carlo simulation was performed for SDO. The proposed SL of 10 ng/mL SDO in blood and 300 ng/mL urine corresponds to a detection time of 4 days.

Trajectories of systolic blood pressure decline in kidney transplant donors prior to circulatory death and delayed graft function.

Kidneys donated after circulatory death suffer a period of functional warm ischaemia before death, which may lead to early ischaemic injury. Effects of haemodynamic trajectories during the agonal phase on delayed graft function (DGF) is unknown. We aimed to predict the risk of DGF using patterns of trajectories of systolic blood pressure (SBP) declines in Maastricht category 3 kidney donors. We conducted a cohort study of all kidney transplant recipients in Australia who received kidneys from donation after circulatory death donors, divided into a derivation cohort (transplants between 9 April 2014 and 2 January 2018 [462 donors]) and a validation cohort (transplants between 6 January 2018 and 24 December 2019 [324 donors]). Patterns of SBP decline using latent class models were evaluated against the odds of DGF using a two-stage linear mixed effects model. In the derivation cohort, 462 donors were included in the latent class analyses and 379 donors in the mixed effects model. Of the 696 eligible transplant recipients, 380 (54.6%) experienced DGF. Ten different trajectories, with distinct patterns of SBP decline were identified. Compared with recipients from donors with the slowest decline in SBP after withdrawal of cardiorespiratory support, the adjusted odds ratio (aOR) for DGF was 5.5 [95% confidence interval (CI) 1.38-28.0] for recipients from donors with a steeper decline and lowest SBP [mean 49.5mmHg (standard deviation 12.5)] at the time of withdrawal. For every 1mmHg/min reduction in the rate of decline of SBP, the respective aORs for DGF were 0.95 (95% CI 0.91-0.99) and 0.98 (95% CI 0.93-1.0) in the random forest and least absolute shrinkage and selection operator models. In the validation cohort, the respective aORs were 0.95 (95% CI 0.91-1.0) and 0.99 (95% CI 0.94-1.0). Trajectories of SBP decline and their determinants are predictive of DGF. These results support a trajectory-based assessment of haemodynamic changes in donors after circulatory death during the agonal phase for donor suitability and post-transplant outcomes.

A200 HIGH-DEFINITION CHROMOENDOSCOPY RESULTS IN MORE SIGNIFICANT DYSPLASIA DETECTION THAN WHITE LIGHT ENDOSCOPY WITH RANDOM BIOPSIES IN ULCERATIVE COLITIS PATIENTS

Abstract Background Ulcerative colitis (UC) is an inflammatory bowel disease that results in inflammation of the colonic mucosa, leading to abdominal pain, rectal bleeding, weight loss, and diarrhea. This chronic inflammation results in a 2.4-fold increased future risk of developing colorectal cancer (CRC) in UC patients compared to the general population. Thus, careful dysplasia screening modalities are required to prevent progression to CRC. Currently, both high-definition white light endoscopy with non-targeted biopsies (HD-WLR) and dye-spray chromoendoscopy (HDCE) are regularly used across Canada for dysplasia surveillance given existing research has been inconclusive regarding superiority of one particular method, and that recent guidelines do not suggest a preference. Purpose The primary objective of this study was to determine which surveillance modality yielded a higher dysplasia detection rate in UC patients, both by calculating the total number of dysplastic lesions detected, as well as calculating the number of patients with at least one dysplastic lesion detected using either technique. Method We conducted a single-centre retrospective chart review of 150 UC patients who underwent dysplasia surveillance at our site between January 2019-2021. We calculated the dysplasia detection rate of both techniques at the time of the first CRC screening colonoscopy. Result(s) Eighteen dysplastic lesions were detected in total, three by HD-WLR and fifteen by HDCE. Dysplasia was detected in 4% (3/75) and 14.5% (15/75) of UC patients by HD-WLR and HDCE respectively, with significantly fewer biopsies (4.44 + 4.3 vs 29.1 + 13.0) required. HD-WLR detected two polypoid and one non-polypoid lesion, while HDCE detected eleven polypoid and four non-polypoid lesions. No invisible dysplasia or colorectal cancer was detected. Screening was performed at 10.8 + 4.8 and 9.72 + 3.05 years following UC diagnosis for HDCE and HD-WLR respectively. Median withdrawal time was 9.0 + 2.7 min (HD-WLR) vs 9.6 + 3.9min (HDCE). Image Conclusion(s) HDCE resulted in higher dysplasia detection rates compared to HD-WLR in a UC patient population. Given the former technique is less tedious and costly, our findings suggest HDCE should be considered over HD-WLR for UC dysplasia surveillance. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Analysis of Transfer of Tiamulin to Animal Tissue after Oral Administration: An Important Factor for Ensuring Food Safety and Environmental Protection.

The administration of veterinary medicinal products containing tiamulin hydrogen fumarate (THF) leads to the appearance of the following residues in animal tissues: THF and metabolites that can be hydrolyzed to 8-α-hydroxymutilin. The marker residue for tiamulin, according to Regulation EEC 2377/90, is the sum of the metabolites that can be hydrolyzed to 8-α-hydroxymutilin. The main aim of this study was to analyze the depletion of tiamulin residues and metabolites that can be hydrolyzed to 8-α-hydroxymulinin by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in pig, rabbit and bird tissues after tiamulin administration and to determine minimum withdrawal times for products of animal origin intended for human consumption. Tiamulin was administered orally as follows: 12,000 µg/kg body weight/day for 7 days to pigs and rabbits and 20,000 µg tiamulin/kg body weight/day for 7 days to broiler chickens and turkeys. The values found for tiamulin marker residues were 3 times higher in liver than in muscle in pigs, 6 times in rabbits and 8-10 times in birds. The content of tiamulin residues in eggs from laying hens was below 1000 µg/kg at all times of analysis. The minimum withdrawal times for animal products intended for human consumption, resulting from this study, are 5 days for pigs, rabbits and turkeys, 3 days for broiler chickens and 0 days for eggs.

The transcriptional response to acute cocaine is inverted in male mice with a history of cocaine self-administration and withdrawal throughout the mesocorticolimbic system

A large body of work has demonstrated that cocaine-induced changes in transcriptional regulation play a central role in the onset and maintenance of cocaine use disorder. An underappreciated aspect of this area of research, however, is that the pharmacodynamic properties of cocaine can change depending on an organism's previous drug-exposure history. In this study, we utilized RNA sequencing to characterize how the transcriptome-wide effects of acute cocaine exposure were altered by a history of cocaine self-administration and long-term withdrawal (30 days) in the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC) in male mice. First, we found that the gene expression patterns induced by a single cocaine injection (10 mg/kg) were discordant between cocaine-naïve mice and mice in withdrawal from cocaine self-administration. Specifically, the same genes that were upregulated by acute cocaine in cocaine-naïve mice were downregulated by the same dose of cocaine in mice undergoing long-term withdrawal; the same pattern of opposite regulation was observed for the genes downregulated by initial acute cocaine exposure. When we analyzed this dataset further, we found that the gene expression patterns that were induced by long-term withdrawal from cocaine self-administration showed a high degree of overlap with the gene expression patterns of acute cocaine exposure - even though animals had not consumed cocaine in 30 days. Interestingly, cocaine re-exposure at this withdrawal time point reversed this expression pattern. Finally, we found that this pattern was similar across the VTA, PFC, NAc, and within each brain region the same genes were induced by acute cocaine, re-induced during long-term withdrawal, and reversed by cocaine re-exposure. Together, we identified a longitudinal pattern of gene regulation that is conserved across the VTA, PFC, and NAc, and characterized the genes constituting this pattern in each brain region.

An improved withdrawal interval calculation and risk assessment of doxycycline in crayfish (Procambarus clarkii) in the natural cultured environment

Doxycycline is an important medicine in aquaculture for treating fish diseases. However, its excess use causes residue exceeding to threaten human health. So, this study aimed to estimate a reliable withdrawal time (WT) of doxycycline (DC) in crayfish (Procambarus clarkii) based on statistical approaches and conduct a risk assessment for human health in the natural environment. Samples were collected at predetermined time points and determined by high-performance liquid chromatography. A novel statistical method was used to process the data of residue concentration. The homogeneity and linearity of the regressed line of data were evaluated by Bartlett’s, Cochran’s, and F tests. Outliers were excluded by establishing the standardized residual versus their cumulative frequency distribution on a normal probability scale. The calculated WT was 43 days in muscle of crayfish based on China and European stipulations. After 43 days, estimated daily intakes of DC were ranged from 0.022 to 0.052 µg/kg/d. Hazard Quotients were ranged from 0.007 to 0.014, which were far less than 1. These results indicated that established WT could avoid health risks for humans resulting from DC’s residue in crayfish.

Pharmacokinetics, withdrawal time, and dietary risk assessment of enrofloxacin and its metabolite ciprofloxacin, and sulfachloropyridazine-trimethoprim in Taihe black-boned silky fowls.

Enrofloxacin (ENR) and sulfachloropyridazine combined with trimethoprim (TMP) were commonly used in poultries to treat bacterial infections. In this study, the pharmacokinetics of these antibiotics in four tissues of Taihe black-boned silky fowls was studied. The results showed that these drugs were absorbed and distributed rapidly, with the highest concentration showing in skin. Meanwhile, ENR and its metabolite ciprofloxacin (CIP) and TMP were depleted slowly, particularly in skin with the elimination half-lives being 37.1, 36.9, and 72.7 days, respectively. It may be attributed to the abundance of melanin in skin. The dietary risk assessment suggested that the long-term dietary intakes of ENR, CIP, and TMP showed a considerable threat to human health. Based on the experiment, the withdrawal times of 284 days for ENR+CIP and 159 days for TMP were acquired, which showed that these drugs are not appropriate for the application in Taihe black-boned silky fowls.

Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool

BackgroundDomesticated animals play a role in maintaining residual transmission of Plasmodium parasites of humans, by offering alternative blood meal sources for malaria vectors to survive on. However, the blood of animals treated with veterinary formulations of the anti-helminthic drug ivermectin can have an insecticidal effect on adult malaria vector mosquitoes. This study therefore assessed the effects of treating cattle with long-acting injectable formulations of ivermectin on the survival of an important malaria vector species, to determine whether it has potential as a complementary vector control measure.MethodsEight head of a local breed of cattle were randomly assigned to either one of two treatment arms (2 × 2 cattle injected with one of two long-acting formulations of ivermectin with the BEPO® technology at the therapeutic dose of 1.2 mg/kg), or one of two control arms (2 × 2 cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3–5-day-old Anopheles coluzzii mosquitoes through direct skin-feeding assays, from 1 to 210 days after treatment. The efficacy of each formulation was evaluated and compared using Cox proportional hazards survival models, Kaplan–Meier survival estimates, and log-logistic regression on cumulative mortality.ResultsBoth formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (hazard ratio > 1). The treatments significantly reduced mosquito survival, with average median survival time of 4–5 days post-feeding. The lethal concentrations to kill 50% of the Anopheles (LC50) before they became infectious (10 days after an infectious blood meal) were maintained for 210 days post-injection for both formulations.ConclusionsThis long-lasting formulation of ivermectin injected in cattle could complement insecticide-treated nets by suppressing field populations of zoophagic mosquitoes that are responsible, at least in part, for residual malaria transmission. The impact of this approach will of course depend on the field epidemiological context. Complementary studies will be necessary to characterize ivermectin withdrawal times and potential environmental toxicity.Graphical

Increased fT4 concentrations in patients using levothyroxine without complete suppression of TSH.

In our hospital, physicians noticed high free thyroxine (fT4) concentrations without complete suppression of thyroid-stimulating hormone (TSH) in blood samples of patients at the outpatient clinic, which appeared to occur more often following the introduction of a new fT4 immunoassay. This discordance may be explained by incorrect reference intervals, analytical issues, or patient-related factors. We aimed to establish the contribution of the possible factors involved. Reference intervals of both fT4 immunoassays were re-evaluated using blood samples of healthy volunteers and the new immunoassay's performance was assessed using internal quality controls and external quality rounds. The frequency of discordant fT4 and TSH pairings obtained from laboratory requests were retrospectively analysed using a Delfia (n = 3174) and Cobas cohort (n = 3408). Last, a literature search assessed whether the time of blood draw and the time of levothyroxine (L-T4) ingestion may contribute to higher fT4 concentrations in L-T4 users. The original reference intervals of both fT4 immunoassays were confirmed and no evidence for analytical problems was found. The Delfia (n = 176, 5.5%) and Cobas cohorts (n = 295, 8.7%) showed comparable frequencies of discordance. Interestingly, 72-81% of the discordant results belonged to L-T4 users. Literature indicated the time of blood withdrawal of L-T4 users and, therefore, the time of L-T4 intake as possible explanations. High fT4 without suppressed TSH concentrations can mainly be explained by L-T4 intake. Physicians and laboratory specialists should be aware of this phenomenon to avoid questioning the assay's performance or unnecessarily adapting the L-T4 dose in patients.

The effectiveness of real-time computer-aided and quality control systems in colorectal adenoma and polyp detection during colonoscopies: a meta-analysis.

This study was conducted adhering to PRISMA guidelines. Studies were searched across PubMed, CINAHL, EMBASE, Scopus, Cochrane, and Web of Science. Keywords including the following 'Artificial Intelligence, Polyp, Adenoma, Detection, Rate, Colonoscopy, Colorectal, Colon, Rectal' were used. Odds ratio (OR) applying 95% CI for PDR and ADR were computed. SMD with 95% CI for withdrawal times were computed using RevMan 5.4.1 (Cochrane). The risk of bias was assessed using the RoB 2 tool. Of 2562 studies identified, 11 trials were included comprising 6856 participants. Of these, 57.4% participants were in the AI group and 42.6% individuals were in in the standard group. ADR was higher in the AI group compared to the standard of care group (OR=1.51, P=0.003). PDR favored the intervened group compared to the standard group (OR=1.89, P<0.0001). A medium measure of effect was found for withdrawal times (SMD=0.25, P<0.0001), therefore with limited practical applications. AI-supported colonoscopies improve PDR and ADR; however, no noticeable worsening of withdrawal times is noted. Colorectal cancers are highly preventable if diagnosed early-on. With AI-assisted tools in clinical practice, there is a strong potential to reduce the incidence rates of cancers in the near future.

P404 Persistence of subcutaneous infliximab after switching from intravenous in a French national cohort of IBD patients in remission

Abstract Background Subcutaneous infliximab (IFX-SC) was launched in France for the treatment of patients with inflammatory bowel disease (IBD) in 2021. Real-life and pharmacokinetic (PK) data after switching from intravenous infliximab (IFX-IV) to IFX-SC are needed. The PEREM study is a French multicenter prospective cohort aiming to describe the persistence of IFX-SC after switch from IFX-IV. Methods IBD patients in steroid-free clinical remission [Harvey Bradshaw Index (HBI) ≤ 4 for Crohn’s disease (CD) and partial Mayo score (PMS) ≤ 2 with each subscore ≤ 1 for UC] for at least 6 months on IFX-IV therapy were proposed to switch to IFX-SC as part of routine care. Patients were included in 40 centers between Oct 2021 and May 2022. Clinical scores (HBI, PMS), biological samples (CRP and fecal calprotectin - FC), PK and anti IFX antibodies (ATI) were evaluated 3, 6, 12 and 24 months after switch. In case of IFX-SC discontinuation, time and reason for withdrawal were documented. Safety and adverse events of interest were recorded. The primary endpoint was IFX-SC persistence at 12 months. As not all patients met this primary endpoint at the time of writing this abstract, we present here the results at 6 months (M6). Results Among the 444 patients included [44% female, median age: 37 years (Min, Max: 18-88), 72% Crohn’s], 71% were receiving IFX-IV at a dose of 5 mg/kg every 8 weeks and 84% were treated on monotherapy. Among the 417 patients analyzed, five withdrew their consent before the M6 visit and 324 were assessed at M6; 25/324 (7.7%) discontinued IFX-SC before M6 (seven for relapse, twelve for intolerance, two for pregnancy, four for unknown reasons) including one (0.3%) switch back to IFX-IV. Rate of survival without IFX-SC discontinuation at M6 was 92.6% (95% CI 89.3-95.1). Among the patients evaluated at M6, median clinical scores did not vary between inclusion and M6: HBI from 0 (IQR: 0-1) to 0 (IQR: 0-1), PMS from 0 (IQR: 0-0) to 0 (IQR: 0-0), respectively. The median CF and CRP levels were respectively 52 μg/g (IQR: 19-142) at inclusion and 37 μg/g (IQR: 14-129) at M6, and 1 mg/L (IQR: 1-4) at inclusion and 1 mg/L (IQR 0-4) at 6 months. At baseline, median infliximab levels were 6.6 μg/mL (min, max: 0-29) and 20 μg/mL (min, max: 0.3- 79.2) at M6. No major safety signals were recorded. Conclusion In a national real-life multicenter cohort, rate of persistence of IFX-SC after 6 months was 92.6% in IBD patients switched in remission, without significant clinical or biological changes. Treatment switch was associated with an increase in IFX levels. These data are confirming the good efficacy and safety of IFX-SC after switch.

OP37 Is the withdrawal of anti-tumour necrosis factor in inflammatory bowel disease patients in remission feasible without increasing the risk of relapse? Results from the randomised clinical trial of GETECCU (EXIT)

Abstract Background Background: The feasibility of anti-TNF discontinuation in inflammatory bowel disease (IBD) must be proven in clinical trials including patients in clinical, endoscopic, and radiologic remission at the time of anti-TNF withdrawal to make recommendations for clinical practice. Aims Primary: to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment vs. those who continue treatment. Secondary objectives: to know the effect of anti-TNF withdrawal on relapse-free time, mucosal healing and safety; and to identify predictive factors for relapse. Methods Prospective, quadruple-blind, multicentre, randomised, controlled trial. Patients with ulcerative colitis (UC) or Crohn’s disease (CD) in clinical remission for &amp;gt; 6 months were randomised to maintain anti-TNF treatment [maintenance arm (MA)] or to withdraw it [withdrawal arm (WA)]. Patients who were on infliximab (IFX) received IFX 5 mg/kg or an intravenous placebo every 8 weeks, while patients on adalimumab (ADA) received subcutaneous ADA 40 mg or placebo every other week. Patients were followed-up until month 12 or up to the time of clinical relapse, whichever came first. Inclusion and exclusion criteria, trial scheme and definitions are summarized in figures 1a, 1b and 1c. Results were analysed by intention-to-treat (ITT) and by per-protocol (PP). Local investigators were blinded to faecal calprotectin (FC) and IFX and ADA trough levels. On-site monitoring was performed to assess data quality. Results 159 patients were screened, from whom 140 were randomised and comprised the ITT cohort: 70 allocated to the MA and 70 to the WA. Fifteen patients dropped out before the end of follow-up (12 months or relapse), leaving 63 patients in the MA and 62 patients in the WA for the PP analysis. The characteristics of patients in the MA and WA were similar (figure 2). The proportions of patients who maintained clinical remission -59/70 (84%), 95% confidence interval (CI)=74-92% in the MA vs. 53/70 (76%), 95%CI=64-85% in the WA- and who remained without significant endoscopic lesions at the end of follow-up were similar between groups (figures 3a, 3b, 3c). Only the proportion of patients with FC &amp;gt;250 mg/g was higher in the WA at the end of follow-up (figure 3d). Maintenance of clinical remission was no different between groups (figure 4). The same percentage of patients in both groups had at least one adverse event (69%). The proportion of patients with serious adverse events was also similar between groups (4% in MA vs. 7% in WA). Conclusion Anti-TNF withdrawal in selected IBD patients in clinical, endoscopic, and radiologic remission could be feasible without an increase in the risk of clinical relapse. Long-term follow-up of these patients is warranted.

A Sustainable Approach to Delivering Programmable Peer-to-Peer Offline Payments.

Payment apps and digital wallets are powerful tools used to exchange e-money via the internet. However, with the progressive disappearance of cash, there is a need for the digital equivalent of physical banknotes to guarantee the same level of anonymity of private payments. Few efforts to solve the double-spending problem exist in P2P payments (i.e., in avoiding the possibility of a payer retaining copies of digital coins in absence of a trusted third party (TTP)), and further research efforts are needed to explore options to preserve the privacy of payments, as per the mandates of numerous central bank digital currency (CBDC) exploratory initiatives, such as the digital euro. Moreover, generic programmability requirements and energetic impacts should be considered. In this paper, we present a sustainable offline P2P payment scheme to face the double-spending problem by means of a one-time program (OTP) approach. The approach consists of wiping the business logic out of a client's app and allowing financial intermediaries to inject a certified payment code into the user's device, which will execute (asynchronously and offline) at the time of payment. To do so, we wrap each coin in a program at the time of withdrawal. Then the program exploits the trusted execution environment (TEE) of modern smartphones to transfer itself from the payer to the payee via a direct IoT link. To confirm the validity of the approach, we performed qualitative and quantitative evaluations, specifically focusing on the energetic sustainability of the proposed scheme. Results show that our payment scheme is energetically sustainable as the current absorbed for sending one coin is, at most, ~1.8 mAh on an Apple smartphone. We advance the state-of-the-art because the scheme meets the programmability, anonymity, and sustainability requirements (at the same time).

The pharmacokinetic and residue depletion study of eugenol in carp (Cyprinus carpio).

The pharmacokinetic profile and residue depletion of eugenol in carp (Cyprinus carpio) tissues and plasma were performed by a convenient and reliable high-performance liquid chromatography (HPLC) method. The eugenol in carp tissues and plasma was extracted with a mixed solution of acetonitrile and methanol. N-hexane was used to remove lipid impurities. The method was successfully applied to the pharmacokinetic and residue elimination of eugenol in carp after the carp was administered a medicated bath. The average recoveries of eugenol in tissues and plasma fortified with four concentration levels were 69.0-106.6% and 80.0-86.7%, respectively. The relative standard deviations were < 8.9%. The limit of detection (LOD) was 0.01 μg/g in tissue and 0.008 μg/ml in plasma, respectively. The pharmacokinetic parameter of Cmax for eugenol in plasma at the concentrations of 20, 35, and 75 mg/L were 10.86, 17.21, and 37.32 mg/L, respectively. The t1/2 values were 3.68, 4.22, and 9.31 h. After the investigation of the anesthetic effect, 35 mg/L of eugenol was the optimal concentration for anesthesia. The highest accumulation concentration of eugenol in carp is in the liver and the lowest is in the muscle. In addition, the eugenol in tissue was eliminated rapidly and at a lower level than the LOD at 48 h. According to the residue elimination, the withdrawal time of eugenol was suggested at 5.2 days. These results indicate that the developed method had good linearity and accuracy, and is sensitive enough for the monitoring of eugenol residue in carp. The half-life of eugenol decreased with the increase in drug concentration and the eugenol was eliminated rapidly in carp tissues. 35 mg/L eugenol was recommended as an anesthetic in carp due to its favorable anesthetic effect and no mortality. This study will contribute to the establishment of MRL regulation and setting a withdrawal period.