Withdrawal Time Research Articles

A Randomized, Controlled Trial, comparing the Total Enteroscopy Rate and Diagnostic Efficacy of Novel Motorized Spiral Enteroscopy and Single Balloon Enteroscopy in patients with Small-Bowel Disorders - THE MOTOR TRIAL (NCT 05548140).

Device-assisted enteroscopy (DAE) has revolutionized the management of Small Bowel Disorders (SBD). No study to date has compared both Novel Motorized Spiral Enteroscopy (NMSE) and Single Balloon Enteroscopy (SBE) as a randomized controlled trial. Hence, this study was planned to include patients having SBD with the primary aim to compare the Total Enteroscopy Rate (TER). This study was conducted at the Asian Institute of Gastroenterology (AIG Hospitals), Hyderabad, India from 20th September 2022 to 15th December 2022. All consecutive patients, aged more than 18 years with suspected SBD, and planned for Total Enteroscopy (TE) were screened for inclusion. The primary outcome was to compare the TER and secondary outcomes were to compare the technical success, time taken to reach the Depth of Maximal Insertion (DMI), withdrawal time, total procedure time, diagnostic yield, therapeutic success, and adverse events. Seventy-two patients out of the 110 patients screened, were randomized in either of NMSE (n=35) or SBE (n=37) group. The most common indication for the procedures was obscure GI bleed (48%), others being unexplained abdominal pain with indeterminate radiologic findings (32%) and chronic diarrhea (20%). In NMSE group the TER was 71.4%; while in the SBE group, it was 10.8%, (p<0.0001). The total procedure time (min) was much lesser with NMSE (58.17±21.5 min) versus SBE (114.2±33.5 min), (p<0.0001). The diagnostic yield of NMSE (80%) was comparatively higher than SBE (62.1%), (p = 0.096). Minor adverse events (Grade I) were observed in both the groups: NMSE (3/35, 8.5%) and SBE (2/37, 5.4%). This RCT shows that with NMSE higher TER can be achieved in shorter duration with minimal adverse events, compared to SBE.

Impact of WeChat guidance on bowel preparation for colonoscopy: a quasi-experiment study

Colonoscopy is a standard procedure for screening, monitoring, and treating colorectal lesions. To explore the impact of WeChat guidance on bowel preparation before colonoscopy. This quasi-experiment study included patients who underwent colonoscopy at Qingdao Endoscopy Center between March 2016 and September 2016. The primary outcome was bowel preparation quality (Ottawa score), the secondary outcomes were intubation time, withdrawal time, adenoma detection rate (ADR), and adverse reactions. Finally, 588 patients were included and divided into the WeChat guide (n = 295) and the non-WeChat guide (n = 293) groups, they were comparable in baseline characteristics. The Ottawa score (1.59 ± 1.07 vs. 6.62 ± 3.07, P < 0.001), intubation time (6.47 ± 1.81 vs. 11.61 ± 3.34, P < 0.001), withdrawal time (13.15 ± 3.93 vs. 14.99 ± 6.77, P < 0.001), and occurrence rate of adverse reactions (2.0% vs. 5.5%, P = 0.029) were significantly lower in the WeChat guide group than those in the non-WeChat guide group. ADR was significantly higher in the WeChat guide than that in the non-WeChat guide group (1.47 ± 2.30 vs. 0.84 ± 1.66, P < 0.001). WeChat guidance might improve the quality of bowel preparation and adenoma detection rate, shorten the time of colonoscopy, and reduce adverse reactions in bowel preparation.

Performing High-Quality, Safe, Cost-Effective, and Efficient Basic Colonoscopy in 2023: Advice From Two Experts.

Based on published evidence and our expert experience, we provide recommendations to maximize the efficacy, safety, efficiency, and cost-effectiveness of routine colonoscopy. High-quality colonoscopy begins with colon preparation using a split or same-day dose and preferably a low-volume regimen for optimal patient tolerance and compliance. Successful cecal intubation can be achieved by choosing the correct colonoscope and using techniques to facilitate navigation through challenges such as severe angulations and redundant colons. Safety is a primary goal, and complications such as perforation and splenic rupture can be prevented by avoiding pushing through fixed resistance and avoiding loops in proximal colon. Furthermore, barotrauma can be avoided by converting to water filling only (no gas insufflation) in every patient with a narrowed, angulated sigmoid. Optimal polyp detection relies primarily on compulsive attention to inspection as manifested by adequate inspection time, vigorous probing of the spaces between haustral folds, washing and removing residual debris, and achieving full distention. Achieving minimum recommended adenoma detection rate thresholds (30% in men and 20% in women) is mandatory, and colonoscopists should aspire to adenoma detection rate approaching 50% in screening patients. Distal attachments can improve mucosal exposure and increase detection while shortening withdrawal times. Complete resection of polyps complements polyp detection in preventing colorectal cancer. Cold resection is the preferred method for all polyps < 10 mm. For effective cold resection, an adequate rim of normal tissue should be captured in the snare. Finally, cost-effective high-quality colonoscopy requires the procedure not be overused, as demonstrated by following updated United States Multi Society Task Force on Colorectal Cancer postpolypectomy surveillance recommendations.

Long-Term Follow-Up of Colonoscopy Quality Monitoring.

High-quality colonoscopy is paramount for colorectal cancer prevention. Since 2009, endoscopists at our institution have received quarterly report cards summarizing individual colonoscopy quality indicators. We have previously shown that implementing this intervention was associated with short-term improvement in adenoma detection rate (ADR). However, the long-term effect of continued monitoring on colonoscopy quality is unclear. We conducted a retrospective study of prospectively administered quarterly colonoscopy quality report cards at the Roudebush Veteran's Affairs Medical Center between April 1, 2012, and August 31, 2019. The anonymized reports included individual endoscopists' ADRs, cecal intubation rates, and withdrawal times. Analyses were performed to determine slopes over time for each quality metric by physician and assess for differences based on whether ADRs were calculated quarterly or yearly. Data from the report cards of 17 endoscopists who had performed 24,361 colonoscopies were included. The mean quarterly ADR (±SD) was 51.7% (±11.7%) and mean yearly ADR was 47.2% (±13.8%). There was a small increase in overall ADR based on quarterly and yearly measurements (slope + 0.6%, P = 0.02; and slope +2.7%, P < 0.001, respectively), but no significant change in individual ADRs, cecal intubation rates, or withdrawal times. Analysis of SD of ADRs showed no significant difference between yearly and quarterly measurements ( P = 0.064). Individual endoscopists' ADR SD differences between yearly and quarterly measurements ranged from -4.7% to +6.8%. Long-term colonoscopy quality monitoring paralleled stable improvements in overall ADR. For endoscopists with baseline high ADR, frequent monitoring and reporting of colonoscopy quality metrics may not be necessary.

Modeling Government Subsidy Strategies for Railway Carriers: Environmental Impacts and Industry Competition

In this paper, we investigate the government’s optimal subsidy strategy for the China–Europe Railway Express (CERE) considering environmental impacts and industry competition. Specifically, we consider three subsidy options: no subsidies, subsidies to CERE carriers, and subsidies to shippers. A game theory framework is developed to analyze the problem of developing a sustainable supply chain consisting of the government, competitive carriers, and shippers. First of all, we find that for the government, indirect subsidies to CERE carriers and direct subsidies to shippers lead to the same total social welfare. We then examine the conditions for phasing out government subsidies. Our results indicate that the government’s optimal subsidy strategy switches at a threshold level of CERE’s environmental advantage. In particular, when the environmental advantage of CERE is high, the government should subsidize CERE by subsidizing either the carrier or shipper. In contrast, when the environmental advantage of CERE is low, the government should opt out of subsidies. At last, we find that this threshold of CERE’s environmental advantage is further impacted by CERE’s capacity and marginal operating costs. This study differs from prior research by investigating various subsidy strategies while taking into account CERE’s emission advantage and the timing of subsidy withdrawal.

Performance and Attitudes Toward Real-time Computer-aided Polyp Detection during Colonoscopy in a Large Tertiary Referral Center in the United States.

Computer aided detection (CADe) has been shown to improve polyp detection in clinical trials. Limited data exists on the impact, utilization, and attitudes toward artificial intelligence (AI)-assisted colonoscopy in daily clinical practice. We aimed to evaluate the effectiveness of the first FDA-approved CADe device in the United States and the attitudes toward its implementation. Retrospective analysis of a prospectively maintained database of patients undergoing colonoscopy at a tertiary center in the United States before and after a real-time CADe system was made available. The decision to activate the CADe system was at the discretion of the endoscopist. An anonymous survey was circulated among endoscopy physicians and staff at the beginning and at the conclusion of the study period regarding their attitudes toward AI-assisted colonoscopy. CADe was activated in 52.1% of cases. Compared with historical controls, there was no statistically significant difference in adenomas detected per colonoscopy (APC) (1.08 vs 1.04, p=0.65), even after excluding diagnostic/therapeutic indications and cases where CADe was not activated (1.27 vs 1.17, p=0.45). In addition, there was no statistically significant difference in ADR, median procedure and withdrawal times. Survey results demonstrated mixed attitudes toward AI-assisted colonoscopy, of which main concerns included high number of false positive signals (82.4%), high level of distraction (58.8%), and impression it prolonged procedure time (47.1%). CADe did not improve adenoma detection in daily practice among endoscopists with high baseline ADR. Despite its availability, AI-assisted colonoscopy was only activated in half of cases, and multiple concerns were raised by staff and endoscopists. Future studies will help elucidate the patients and endoscopists that would benefit most from AI-assisted colonoscopy.

Evaluation of the quality of colonoscopies performed by Alberta North Zone surgeons, family physicians and internists: a quality improvement initiative.

In Canada, endoscopy is primarily performed by gastroenterologists and surgeons, and some studies report that colonoscopies performed by nongastroenterologists have more complications and higher rates of future colorectal cancer. Our objective was to determine whether rural-based nongastroenterologist endoscopists are achieving quality benchmarks in colonoscopy. This quality improvement initiative prospectively evaluated 6 key performance indicators (KPIs) (cecal intubations, polyp detection [males and females; for first-time colonoscopies on patients aged ≥ 50 yr], bowel preparations, patient comfort and withdrawal times) on consecutive colonoscopies performed by participating Alberta North Zone endoscopists. The study period was June 2018 to March 2020. Overall and individual endoscopist's KPIs were compared with standard benchmarks. Additional performance indicators included mean number of polyps per colonoscopy and an exploration of study-defined sedation-related level of consciousness. Data were collected on 6212 colonoscopies performed by 16 endoscopists (9 surgeons, 5 family physicians and 2 internists) in 6 hospitals. All 6 KPI benchmarks were achieved when results were pooled over all endoscopists in the study. Overall, cecal intubation occurred in 6006 of 6209 (96.7%, 95% confidence interval 94.5%-99.0%) cases. Polyp detection was 65.9% (592/898) and 49.8% (348/699) for male and female patients, respectively, aged 50 years or older. Variability in individual endoscopist results existed, especially for the mean number of polyps per 100 colonoscopies and sedation-related level of consciousness. Overall, Alberta North Zone endoscopists are performing high-quality colonoscopies, collectively achieving all 6 KPIs. To understand endoscopic performance and encourage individual and group reflection on endoscopic practices, Canadian endoscopists are encouraged to participate in similar colonoscopy quality initiative studies.

Comparing Colonoscopy Quality Indicators between Surgeons and Gastroenterologists in A Rural Healthcare System

Background: There is a significant shortage of physicians providing colonoscopies, especially in underserved and rural areas. Surgeons are increasingly filling this role by providing endoscopy services including colonoscopy in these areas. As a result, there has been discussion regarding the quality of colonoscopies performed by different provider specialties, specifically for non-gastroenterologists. The purpose of this study was to compare colonoscopy quality measures between gastroenterologists and surgeons in a rural central New York healthcare system. Methods: All colonoscopies performed by 23 endoscopists, 14 surgeons and 9 gastroenterologists, within a rural healthcare network in 2017 were included as samples within this study, totaling 6265 colonoscopies. These included all diagnostic, screening, and surveillance colonoscopies. Quality metrics including withdrawal times and adenoma detection rates were calculated for all providers and the two groups were statistically analyzed and compared using chi-squared testing. Results: 3113 colonoscopies were performed by surgeons (average of 222 per provider) and 3159 were performed by gastroenterologists (average of 351 per provider). Adenoma detection rates for surgeons and gastroenterologists were essentially the same at 31.38% and 31.82%, respectively (p=0.6882). Withdrawal times were slightly longer for surgeons at 13.19 minutes versus 11.02 minutes for gastroenterologists, though this difference was not statistically significant (0.2985). Conclusions: Our results show that surgeons are not inferior to gastroenterologists in performing colonoscopies using the quality metrics of adenoma detection rates and withdrawal times. With the ongoing shortage of endoscopists, surgeons may be able to alleviate some of the burden without reduction in quality.

Modus Operandi on Repatriation of Afghan Refugees: A New Wave Towards Peace in Pakistan

Pakistan had a long historical background as a host country for Afghan refugees from the 1970s Soviet-Afghan to after the US withdrawal from Afghanistan. Pakistan has been a host to one of the largest refugee populations in the world, with millions of Afghan refugees living in the country for decades. With the passage of time, Pakistan is facing security threats internal as well as external. So, the presence of millions of Afghan refugees in Pakistan has been questioned by a number of Pakistanis. They are considered a huge burden on the economy, environment and infrastructure of the country. At the time of NATO withdrawal from Afghanistan, Several countries and international organizations were involved in efforts to evacuate Afghan refugees and provide them with safe haven. Pakistan has also provided them shelter. Now the government of Pakistan warned and ordered forced repatriation to Afghanistan by October 2023. It planned for 1.73 million illegal Afghan people who are living without any documents. The study finds the problem of Afghan refugees in Pakistan is a social, economic and political threat to the country. However, a great deal of repatriation is another wave towards peace after the decision.

Establishment of withdrawal time and analysis of amprolium residue in edible tissues of broiler chickens administered in drinking water

Establishment of withdrawal time and analysis of amprolium residue in edible tissues of broiler chickens administered in drinking water

003 Utility of plucked hair direct immunofluorescence as a possible replacement for conventional skin biopsy direct immunofluorescence in immunological activity monitoring and prediction of relapse in pemphigus

Abstract Pemphigus vulgaris (PV) is a potentially lethal chronically relapsing autoimmune bullous disorder with intraepithelial lesions affecting the skin and mucous membranes. The prediction of clinical relapse has been studied with conventional skin biopsy and plucked hair direct immunofluorescence (DIF; Daneshpazhooh M, Naraghi ZS, Ramezani A et al. Direct immunofluorescence of plucked hair for evaluation of immunologic remission in PV. J Am Acad Dermatol 2011; 65:173–7) which can be of use in timing treatment withdrawal and helping with better management. The aims of our study were to determine the association of plucked hair root DIF positivity status at baseline with clinical relapse within the study duration, and to determine the correlation between skin biopsy and plucked hair DIF. Seventy-eight consecutive patients diagnosed with PV in clinical remission on therapy, on minimal therapy or off therapy, were included after obtaining informed consent. Three-monthly follow-up was carried out for 12 months. Immunological monitoring with plucked hair DIF was done at baseline and repeated every 3 months for 1 year or a relapse was experienced, whichever occurred earlier. Conventional skin biopsy DIF was performed at baseline, at 3 months and at the time of relapse. In patients receiving adjuvant therapy during their present remission episode, discontinuation of therapy was done at inclusion, at 3 months and at 6 months, and occurrence of relapse in relation to the time point of discontinuation was assessed. Of 78 patients, 22 had disease relapse and 56 remained in complete remission. Clinical relapse during the study duration was significantly more frequent in patients who had higher mean Autoimmune Bullous Skin Disorder Intensity Score during the preceding active disease episode (P = 0.033), pruritus during the present clinical remission episode (P = 0.007) and early discontinuation (within 3 months of study inclusion) of concomitant adjuvant therapy (P = 0.007). Immunological parameters associated with clinical relapse were baseline IgG (P = 0.005) and C3 positivity (P = 0.047) in plucked hair, greater intensity of IgG and C3 positivity at baseline in plucked hair (IgG, P = 0.002; C3, P = 0.033) and skin biopsy specimens (IgG, P = 0.004; C3, P = 0.0.002), and positive hair DIF at the time of adjuvant therapy withdrawal (P = 0.017). Plucked hair DIF is a reliable technique to assess immunological remission in patients with PV who are in clinical remission and helps to guide treatment according to immunological remission status.

Frequency of endoscopic photodocumentation of large colorectal polyps

Colonoscopy quality affects colorectal cancer (CRC) incidence and mortality. The U.S. Multi-Society Task Force on Colorectal Cancer strongly recommends photodocumentation (PD) of lesions ≥10mm in size (ie, large polyps [LPs]) pre-resection and suggests PD postresection to enhance the quality of colonoscopy. No studies have assessed the frequency of LP PD. We evaluated the frequency of and factors associated with PD of LPs. Reports from endoscopists performing≥50 colonoscopies with LP resection between 2016 and 2021 were reviewed. The frequency of LP PD pre-resection and post-resection and factors associated with PD were collected. A composite score of 2 quality metrics (PD of completeness of examination and bowel preparation quality) was created. Endoscopists were divided into 2 tiers based on the frequency of the score on all included examinations: Tier 1,≥95% of examinations; and Tier 2,<95% of examinations. Univariate and multivariate analyses were used to assess factors associated with PD. A total of 1322 colonoscopies, 1693 LPs, and 25 endoscopists were included in this study. PD of LPs occurred in 1392 (82%) pre-resection and in 878 (52%) post-resection. Factors associated with pre-resection PD include endoscopist subspecialty (colorectal surgery vs gastroenterology: odds ratio [OR], .12; 95% confidence interval [CI], .04-.42); >1 LP on examination (2 vs 1 LP: OR, .41 [95% CI, .27-.61]; and≥3 vs 1 LP: OR, .41 [95% CI, .24-.70]), and longer withdrawal time (OR, 1.02; 95% CI, 1.01-1.04). We provide the first data on PD of LP pre-resection and post-resection, which can inform future benchmarking in this area. The implications of PD on metachronous advanced neoplasia need to be studied.

P-361 Is HIF-2α involved in pre-menstrual conditioning of the endometrium to ensure optimal repair and prevent heavy menstrual bleeding?

Abstract Study question Does HIF-2α play a key role in pre-menstrual conditioning of the non-pregnant endometrium to optimise menstrual breakdown/repair and prevent heavy menstrual bleeding (HMB)? Summary answer HIF-2 was higher in secretory endometrium of women with HMB versus controls, but manipulation of HIF-2α in the mouse model did not impact endometrial breakdown/repair. What is known already Hypoxia inducible factor (HIF) is the master regulator of the cellular response to hypoxia and has two common alpha isoforms (HIF-1α/HIF-2α) with overlapping but distinct target genes. We revealed that menstrual endometrial HIF-1α is necessary for normal menstrual endometrial repair. We detected HIF-2α in human endometrium exclusively during the secretory phase. The role of HIF-2α in the non-pregnant endometrium remains undetermined but was important for successful uterine implantation and lung vascular remodelling in mice. We hypothesised that endometrial HIF-2 is required for optimising the endometrial vasculature pre-menstrually to ensure appropriate vasoconstriction and endometrial repair during menstruation. Study design, size, duration HIF-2 was examined in human endometrial tissue and a mouse model of simulated menstruation. Hif2α +/- mice provided genetic reduction of HIF-2 during simulated menses versus wild-type littermates. HIF-2α was also pharmacologically inhibited during the secretory phase (PT2385 vs vehicle controls). To increase HIF-2, Hif1α +/- mice were treated with a HIF stabiliser (DMOG) during the secretory phase to increase HIF-2α followed by decreased HIF-1α at menses –mimicking human endometrial findings in women with HMB. Participants/materials, setting, methods Human secretory endometrium was collected (ethically approved and consented) from women with objectively measured HMB (n = 5) and controls (n = 4) and HIF-2 detected by Western blot. Mouse uterus was collected at the time of progesterone withdrawal (T0, decidualisation) and 8h (T8, endometrial breakdown) and 24h (T24, endometrial repair) after progesterone withdrawal. Histological endometrial repair and menstrual blood loss (MBL) were quantified. Decidualisation markers were examined by RT-qPCR. Endometrial vessel maturity and hypoxia were assessed using immunohistochemistry/immunofluorescence. Main results and the role of chance Human secretory endometrial HIF-2α protein levels were higher in those with HMB compared to controls (P &amp;lt; 0.05). Genetic reduction of HIF-2α in our mouse model of menses (Hif2α +/-) revealed no significant differences in endometrial breakdown (T8) or repair grade (T24) and no difference in MBL at T8 versus controls. There were no significant differences in expression of decidualisation markers (Prlr/Prl3c1) and vessel maturity at T0 (CD31/α-SMA immunofluorescence staining), or the presence of hypoxia at T8 (pimonidazole immunohistochemistry staining). Pharmacological inhibition of HIF-2 at the time of decidualisation also showed no significant difference in endometrial repair at T24 versus controls. Increasing pre-menstrual HIF-2 via pharmacological stabilisation of HIF-2α in Hif1α+/- mice similarly did not significantly affect endometrial breakdown (T8) or repair (T24) or MBL at T8 versus vehicle treated controls, in contrast to our findings in women with HMB. Limitations, reasons for caution Histological scoring of endometrial breakdown/repair in the menstruation mouse model may not be sensitive enough to detect subtle endometrial changes with increased HIF-2α. As HIF-1α delays endometrial repair, an additional timepoint 36h after progesterone withdrawal may better capture any delay in endometrial repair as a result of increased secretory HIF-2. Wider implications of the findings HIF-2α may play a greater role in implantation than pre-menstrual conditioning of the endometrium to optimise menstrual breakdown/repair and limit menstrual blood loss. Although endometrial breakdown was not significantly affected by HIF-2, the impact on repair warrants further investigation to fully delineate the role of HIF-2 in the non-pregnant endometrium. Trial registration number Not applicable

Effects of Temperature on the Pharmacokinetics, Tissue Residues, and Withdrawal Times of Doxycycline in Rainbow Trout (Oncorhynchus mykiss) following Oral Administration.

The purpose of this study was to compare the pharmacokinetics, tissue residues, and withdrawal times of doxycycline after oral administration in rainbow trout reared at 10 and 17 °C. Fish received a 20 mg/kg oral dose of doxycycline after a single or 5-day administration. Six rainbow trout were used at each sampling time point for plasma and tissue samples, including liver, kidney, and muscle and skin. The doxycycline concentration in the samples was determined using high-performance liquid chromatography with ultraviolet detector. The pharmacokinetic data were evaluated by non-compartmental kinetic analysis. The WT 1.4 software program was used to estimate the withdrawal times. The increase of temperature from 10 to 17 °C shortened the elimination half-life from 41.72 to 28.87 h, increased the area under the concentration-time curve from 173.23 to 240.96 h * μg/mL, and increased the peak plasma concentration from 3.48 to 5.50 μg/mL. At 10 and 17 °C, the doxycycline concentration was obtained in liver > kidney > plasma > muscle and skin. According to the MRL values stated for muscle and skin in Europe and China (100 μg/kg) and in Japan (50 μg/kg), the withdrawal times of doxycycline at 10 and 17 °C were 35 and 31 days, respectively, for Europe and China and 43 and 35 days, respectively, for Japan. Since temperature significantly affected pharmacokinetic behavior and withdrawal times of doxycycline in rainbow trout, temperature-dependent dosing regimens and withdrawal times of doxycycline might be necessary.

The Variation of Withdrawal of Life Sustaining Therapy in Older Adults With Traumatic Brain Injury

IntroductionThe decision to withdraw life sustaining treatment (WDLST) in older adults with traumatic brain injury is subject to wide variability leading to nonbeneficial interventions and unnecessary use of hospital resources. We hypothesized that patient and hospital factors are associated with WDLST and WDLST timing. MethodsAll traumatic brain injury patients ≥65 with Glasgow coma scores (GCS) of 4-11 from 2018 to 2019 at level I and II centers were selected from the National Trauma Data Bank. Patients with head abbreviated injury scores 5-6 or death within 24 h were excluded. Bayesian additive regression tree analysis was performed to identify the cumulative incidence function (CIF) and the relative risks (RR) over time for withdrawal of care, discharge to hospice (DH), and death. Death alone (no WDLST or DH) served as the comparator group for all analyses. A subanalysis of the composite outcome WDLST/DH (defined as end-of-life-care), with death (no WDLST or DH) as a comparator cohort was performed. ResultsWe included 2126 patients, of whom 1957 (57%) underwent WDLST, 402 (19%) died, and 469 (22%) were DH. 60% of patients were male, and the mean age was 80 y. The majority of patients were injured by fall (76%, n = 1644). Patients who were DH were more often female (51% DH versus 39% WDLST), had a past medical history of dementia (45% DH versus 18% WDLST), and had lower admission injury severity score (14 DH versus 18.6 WDLST) (P < 0.001). Compared to those who DH, those who underwent WDLST had a lower GCS (9.8 versus 8.4, P < 0.001). CIF of WDSLT and DH increased with age, stabilizing by day 3. At day 3, patients ≥90 y had an increased RR of DH compared to WDLST (RR 2.5 versus 1.4). As GCS increased, CIF and RR of WDLST decreased, while CIF and RR of DH increased (RR on day 3 for GCS 12: WDLST 0.42 versus DH 1.31).Patients at nonprofit institutions were more likely to undergo WDLST (RR 1.15) compared to DH (0.68). Compared to patients of White race, patients of Black race had a lower RR of WDLST at all timepoints. ConclusionsPatient and hospital factors influence the practice of end-of-life-care (WDLST, DH, and death), highlighting the need to better understand variability to target palliative care interventions and standardize care across populations and trauma centers.

#4760 LUPUS NEPHRITIS RELAPSE AFTER IMMUNOSUPPRESSION WITHDRAWAL: A SPANISH MULTICENTER STUDY

Abstract Background and Aims In lupus nephritis (LN), therapeutic schemas for remission induction are well known but data about duration of maintenance treatment are limited. There is no agreement between clinical practice guidelines about duration and withdrawal of therapy, and literature regarding this topic is scarce. Recently, a RCT has observed that immunosuppression discontinuation after 2‒3 years was related to LN relapse when compared with immunosuppression maintenance. However, immunosuppressive agents are related to severe adverse events and toxicity. We conducted this study with the aim to evaluate the incidence of LN relapse in a cohort of patients with discontinuation of immunosuppressive treatment after a first LN flare. We also aimed to determine factors associated to the presence of renal relapse in this population. Method Multicenter retrospective observational study including patients with biopsy proven LN who have received immunosuppressive treatment that was subsequently discontinued. Patients on prednisone at doses lower than 5 mg per day were allowed to be included. Patients were diagnosed between 1990 and 2018. The study was conducted in Spain. Relapse was defined according to Malvar et al criteria. Results 113 patients were included, mean age was 34.11 ±14.56 years-old and 85.8% were women. Serum creatinine at the time of LN diagnosis was 1.09±0.63 mg/dL, and proteinuria 3.16±2.53g/24h, ANA were positive in 85.84%, and anti-DNA Abs in 69.91%. Serum C3 and C4 levels were 72.51±44.06 and 13.04±11.27 respectively. 55.75% presented with class IV LN, 12.39% with class III or V LN, and 8.85% with class II. Mixed forms were less frequent. In a follow up period of 172.53±162.95 months, 17.7% (n = 20) presented a renal flare after immunosuppressive drugs withdrawal. Time from LN to relapse was 89.05±39.87 months, and time from immunosuppression discontinuation to relapse was 37.75±32.13 months. There were no differences in baseline characteristics between patients who relapsed and patients who did not, neither in histologic characteristics at the time of LN diagnostic biopsy except for glomerulosclerosis, that was less frequent in the relapse group (20% vs 34.41%, p = 0.0435). However, a tendency to a shorter time under immunosuppression in patients who relapsed was observed (73.55±79.06 vs 110.79±206.87 months). Data about treatment withdrawal in each group are summarized in Figure 1. Interestingly, there were no differences between both groups in steroids withdrawal (75% vs 78.49%,p = 0.7327) and hydroxychloroquine withdrawal (33.33% vs 21.74%, p = 0.3393). At the time of immunosuppression discontinuation, patients who relapsed presented lower serum C3 and C4 levels (78.79±24.89 vs 112.26±35.52, p = 0.0080 and 13.82±6.07 vs 23.09±12.56, p = 0.0333), but there were no differences in terms of renal function at this moment. At the end of follow up, patients who relapsed presented more albuminuria (227.87±259.79 vs 78.65±24.77, p = 0.0289) but creatinine levels were similar in both groups (0.84±0.30 vs 0.84±0.30, 0.5105). Only one patient died and two patients required renal replacement therapy, all in the no relapse group. Conclusion In a cohort of 113 patients with biopsy proven LN who were treated con immunosuppression and subsequently discontinued, 17.7% presented renal relapse at a mean time of 37 months after withdrawal. There was a tendency to a short time on immunosuppressive regimens in patients who relapsed. Also, lower serum C3 and C4 levels at the time of immunosuppression withdrawal were associated to renal relapse. At the end of a follow up of 14 years, patients who relapsed those who did not showed a similar maintained renal function but those who relapsed presented lower albuminuria.

MiR-9 utilizes precursor pathways in adaptation to alcohol in mouse striatal neurons.

microRNA-9 (miR-9) is one of the most abundant microRNAs in the mammalian brain, essential for its development and normal function. In neurons, it regulates the expression of several key molecules, ranging from ion channels to enzymes, to transcription factors broadly affecting the expression of many genes. The neuronal effects of alcohol, one of the most abused drugs in the world, seem to be at least partially dependent on regulating the expression of miR-9. We previously observed that molecular mechanisms of the development of alcohol tolerance are miR-9 dependent. Since a critical feature of alcohol action is temporal exposure to the drug, we decided to better understand the time dependence of alcohol regulation of miR-9 biogenesis and expression. We measured the effect of intoxicating concentration of alcohol (20 mM ethanol) on the expression of all major elements of miR-9 biogenesis: three pri-precursors (pri-mir-9-1, pri-mir-9-2, pri-mir-9-3), three pre-precursors (pre-mir-9-1, pre-mir-9-2, pre-mir-9-3), and two mature microRNAs: miR-9-5p and miR-9-3p, using digital PCR and RT-qPCR, and murine primary medium spiny neurons (MSN) cultures. We subjected the neurons to alcohol based on an exposure/withdrawal matrix of different exposure times (from 15 min to 24 h) followed by different withdrawal times (from 0 h to 24 h). We observed that a short exposure increased mature miR-9-5p expression, which was followed by a gradual decrease and subsequent increase of the expression, returning to pre-exposure levels within 24 h. Temporal changes of miR-9-3p expression were complementing miR-9-5p changes. Interestingly, an extended, continuous presence of the drug caused a similar pattern. These results suggest the presence of the adaptive mechanisms of miR-9 expression in the presence and absence of alcohol. Measurement of miR-9 pre- and pri-precursors showed further that the primary effect of alcohol on miR-9 is through the mir-9-2 precursor pathway with a smaller contribution of mir-9-1 and mir-9-3 precursors. Our results provide new insight into the adaptive mechanisms of neurons to alcohol exposure. It would be of interest to determine next which microRNA-based mechanisms are involved in a transition from the acute, intoxicating effects of alcohol to the chronic, addictive effects of the drug.

Survey to evaluate the proficiency in the use of antibacterial drugs in shrimp farming in the state of Sonora, Mexico

AbstractAntibiotic drugs (ABD) are often used in shrimp farms to treat the disease when a bacterial diagnosis is presumed. This scenario was the impetus to carry out a field survey to define how ABD are employed in the State of Sonora, the second largest producer of shrimp in Mexico. Twenty‐nine farms were surveyed through their general managers. According to interviews conducted, the most frequent bacterial diseases that were treated with antibiotics in 2020 were: Acute Hepatopancreatic Necrosis Disease (65%), vibriosis (51%), and Necrotizing hepatopancreatitis bacterium (41%). The most common ABDs were enrofloxacin, oxytetracycline and florfenicol, and drug preparations employed were often intended for non‐aquaculture species, mainly poultry, and pigs. The main criteria for selecting a given antibiotic was a direct recommendation, followed by the market price. Neither pharmacokinetics nor pharmacodynamics nor harvesting withdrawal time were taken into account. The absence of protocols to safeguard the health and integrity of workers was detected, training programs for the responsible use of ABD were not encountered, and no data on bacterial resistance to ABD is available in this region. It is concluded that at least formal studies to define the pharmacokinetics of antibiotics are needed to rationalize their use in shrimp production.

Preslaughter handling factors affecting dead on arrival, condemnations, and bruising in broiler chickens raised without an antibiotic program

In Thailand, knowledge about the factors affecting broiler losses during the preslaughter process is very limited, especially for broilers raised without an antibiotic program. The objective of this study was to determine the preslaughter factors that influence the incidence of dead on arrival (DOA), condemnations, and bruising in broilers raised without antibiotics. Data from 13,581 truckloads of broilers raised without an antibiotic program in 95 contract farms of one of Thailand's largest broiler producers in 2021 were analyzed using a generalized linear mixed model that accounted for farm as a random effect. Results showed that the following risk factors were associated with the occurrence of DOA, condemnations, and bruising: season, time of transport, sex, age at slaughter, mortality and culling rate, and weight per crate. While mean body weight affected the incidence of condemnations and bruising, transport time and lairage time affected DOA and bruising. Feed withdrawal time affected DOA and condemnations. Rearing stocking density only affected condemnation rate. Reducing or eliminating the effects of these risk factors could reduce production losses due to DOA, condemnations, and bruising, thereby improving animal welfare and producer profitability. Reducing weight per crate could reduce DOA, condemnations, and bruising. Reducing lairage time could reduce DOA and bruising, while reducing feed withdrawal time could reduce DOA and condemnations. Raising broilers at a younger age with a lower slaughter weight could prevent the occurrence of DOA, condemnations, and bruising.

Revisiting bowel preparation: The quest for the optimal low‐residue diet duration

Revisiting bowel preparation: The quest for the optimal <scp>low‐residue</scp> diet duration