Educating Nurses to Improve Awareness and Use of a Human Milk Feeding Care Pathway for Opioid-Exposed Neonates.

OBJECTIVE: To increase nurses' awareness and use of a human milk feeding (HMF) and opioid use disorder (OUD) standardized care pathway to improve rates of HMF at discharge in opioid-exposed neonates (OENs). DESIGN: Quality improvement project. SETTING/LOCAL PROBLEM: Underutilizing an HMF and OUD standardized care pathway in an academic medical center led to declining HMF rates at discharge. PARTICIPANTS: Staff nurses in the women and infants department (N = 311). INTERVENTION/MEASUREMENTS: Nurses completed an asynchronous online educational module regarding awareness and use of the HMF and OUD standardized care pathway for supporting HMF in OENs. Monthly infographics were placed in each nursing unit to reinforce content. Nurses completed pre- and posteducation surveys to evaluate their knowledge and use of the pathway. After the education, rates of OENs receiving human milk at discharge were collected from the electronic health record. RESULTS: A total of 240 (77.2%) nurses participated in the educational module; awareness of the pathway increased from 91.5% to 97.3%. HMF rate at discharge significantly increased from 29.8% to 59.4% (p = .03). CONCLUSION: Improved awareness among nurses of a standardized HMF and OUD care pathway was associated with a doubling of HMF rates at discharge in OENs.

The need for smoking cessation counselling and nicotine withdrawal therapy for hospitalised patients: A smoking point prevalence study at Groote Schuur Hospital, Cape Town, South Africa.

Background: South Africa has high tobacco-attributable mortality and a smoking prevalence of 32.5% in males and 25.6% in females. There are limited data on smoking prevalence and desire to quit in hospitalised patients, who have limited access to smoking cessation services. Objectives: To determine smoking prevalence and the extent of nicotine withdrawal symptoms, using a hospital-wide inpatient survey. Methods: A 1-day point prevalence survey was conducted at Groote Schuur Hospital, Cape Town. All wards except the haematology isolation, active labour and psychiatry lock-up wards were evaluated. Smoking status, withdrawal symptoms and desire to quit were established. Results: Smoking status was confirmed in 85.8% of inpatients (n=501/584), of whom 31.9% (n=160) were current smokers; 43.5% (n=101/232) of male and 21.9% (n=59/269) of female inpatients were smokers. Documentation and confirmation of smoking status was highest in the maternity wards (100%) and lowest in the surgical wards (79.6%) and intensive care units (70.0%). Smoking prevalence ranged from 47.6% in male surgical patients to 15.2% in maternity patients. Of the smokers, 54.5% reported being motivated to quit, with a median (interquartile range) Fagerström test for nicotine dependence score of 4 (2 - 6), and 31.4% reported moderate to severe cravings to smoke, highest in the surgical wards. Conclusion: Smoking prevalence was higher in hospitalised patients than in the local general population. Many inpatients were not interested in quitting; however, a third had significant nicotine withdrawal symptoms. All inpatients who are active smokers should be identified and given universal brief smoking cessation advice. Patients with severe withdrawal symptoms should be allowed to smoke outside, and nicotine withdrawal pharmacotherapy should be provided to those who are bedbound or express a desire to stop smoking during the current admission. Study synopsis: What the study adds. A single data point prevalence study of active smokers at Groote Schuur Hospital, Cape Town, was conducted. The prevalence of smoking was higher in the hospitalised patients than in the general community, but not all smokers were identified by the clinicians. Although symptoms of nicotine withdrawal were severe in some patients, motivation to quit smoking was not related to the degree of withdrawal being experienced. Many patients were not motivated to quit smoking.Implications of the findings. Better identification of inpatient smokers is required, and all should be given smoking cessation advice. Withdrawal symptoms can be severe in some patients, and those who are not interested in stopping smoking should allowed to smoke outside or be provided with nicotine withdrawal pharmacotherapy while in hospital. Those who are willing to quit should be supported as well as possible, including provision of nicotine replacement therapy or varenicline, and followed up after discharge as best practice.

The effect of ostracism on social withdrawal behavior: the mediating role of self-esteem and the moderating role of rejection sensitivity.

Extant studies have empirically tested the main two behavior responses following ostracism: prosocial or antisocial. Few studies have investigated the relationship between ostracism and social withdrawal. According to the temporal need-threat model and the self-verification theory, the present study aimed to examine the influence mechanism of ostracism on social withdrawal, especially the mediating role of self-esteem and the moderating role of rejection sensitivity. A total of 1,315 Chinese high school students (52.6% female) completed a written questionnaire. Results showed that ostracism was positively correlated with social withdrawal. Ostracism not only directly predicted social withdrawal, but also indirectly affected social withdrawal by threatening adolescents' self-esteem. High rejection sensitivity may help aggravate adolescents' self-esteem threaten perceive from ostracism. Adolescents with high rejection sensitivity felt a greater threat to self-esteem when ostracized. Findings suggest a new direction for understanding individuals' responses to ostracism.

Pharmacokinetics, optimal dosages and withdrawal time of amoxicillin in Nile tilapia (Oreochromis niloticus) reared at 25 and 30 °C.

Knowledge of amoxicillin (AMX) pharmacokinetics (PK) and tissue residues in fish, which is necessary for prudent drug use, remains limited. The study aimed to explore the PK characteristics of AMX in Nile tilapia (Oreochromis niloticus) reared at 25 and 30 °C as well as to determine optimal dosages and drug withdrawal time (WDT). In the PK investigation, the fish received a single dose of 40 mg/kg AMX via oral gavage, and the optimal dosage was determined by the pharmacokinetic-pharmacodynamic approach. In the tissue residue study, the fish were orally gavaged with 40 mg/kg/day AMX once daily for 5 days and the WDT was established by the linear regression analysis. The results revealed the temperature-dependent drug elimination; the clearance relative to bioavailability (CL/F) and elimination half-life at 30 °C (0.180 L/kg/h and 6.06 h, respectively) were about twice those at 25 °C (0.090 L/kg/h and 10.49 h, respectively). The optimal dosages at the minimum inhibitory concentration (MIC) of 2 µg/mL were 10.97 (25 °C) and 41.03 (30 °C) mg/kg/day, respectively. Finally, following the multiple oral administration, the muscle/skin residue of AMX on day 1 after the last dosing at 25 and 30 °C were 548 and 264 ng/g, respectively. The average tissue residues were depleted below the maximum residue limits (MRL) of 50 µg/kg on day 5 (25 °C) and 3 (30 °C), respectively, and the WDT were 6 and 4 days when rearing at 25 and 30 °C, respectively. This knowledge serves as a practical guideline for responsible use of AMX in treating bacterial diseases in Nile tilapia aquaculture.

Akinetic crisis and withdrawal syndromes: guideline "Parkinson's disease" of the German Society of Neurology.

The akinetic crisis is a well-known, rare, potentially life-threatening condition in Parkinson's disease with subacute worsening of akinesia, rigidity, fever, impaired consciousness, accompanying vegetative symptoms and transient dopa-resistance. The akinetic crisis was historically supposed to be a "withdrawal syndrome" in the sense of discontinuation of dopaminergic medication. Recently, other "withdrawal syndromes" as the specific "dopamine agonist withdrawal syndrome" or "deep brain stimulation withdrawal syndrome" have been described as emergency situations with specific subacute symptom constellations. All three conditions require immediate start of the adequate therapy to improve the prognosis. Here, the diagnostic criteria and treatment options of these three acute, severely disabling syndromes will be reported along the current guidelines of the German Parkinson Guideline Group.

How varying cue duration influences item-method directed forgetting: A novel selective retrieval interpretation.

A series of four experiments tested the assumptions of the most prominent and longstanding account of item-method directed forgetting: the selective rehearsal account. In the item-method directed forgetting paradigm, each presented item is followed by its own instructional cue during the study phase - either to-be-forgotten (F) or to-be-remembered (R). On a subsequent test, memory is poorer for F items than for R items. To clarify the mechanism underlying memory performance, we manipulated the time available for rehearsal, examining instructional cue durations of 1 s, 5 s, and 10 s. Experiments 1a and 1b, where the order of cue durations was randomized, showed no effect of cue duration on item recognition of unrelated single words, for either R or F items. Experiment 2, using unrelated word pairs, again showed no effect of randomized cue duration, this time on associative recognition. Experiments 3 and 4 blocked cue duration and showed equivalent increases in recognition of both R and F single words and word pairs with increasing cue duration. We suggest that any post-cue rehearsal is carried out only when cue duration is predictable, and that such limited rehearsal is equally likely for F items and R items. The consistently better memory for R items than for F items across cue duration depends on selective retrieval involving (1) a rapid retrieval check engaged for R items only and (2) a rapid removal process implemented for F items only.

Differences in withdrawal symptoms, microglia activity, and cognitive functioning in rats exposed to continuous low-dose heroin in-utero.

INTRODUCTION: Opioid use during pregnancy and subsequent neonatal opioid withdrawal syndrome (NOWS) have been associated with poor developmental outcomes including cognitive functioning. Less is known about the underlying molecular effects of prenatal opioid exposure and subsequent withdrawal; however, given the recent increase in NOWS cases, there is a pressing need to better understand these effects, which may partially explain cognitive deficits that have been observed in both preclinical NOWS models and patients with NOWS. This study evaluated the effects of prenatal heroin exposure and subsequent precipitated withdrawal symptoms on microglial reactivity in the nucleus accumbens (NAc), dorsal hippocampus (HC), and ventral tegmental area (VTA) in rat neonates, as well as cognitive functioning at three developmental time points using the Morris Water Maze (MWM) task. METHODS: Heroin or saline (2 mg/kg) was randomly assigned and administered to six pregnant Sprague Dawley rat dams via osmotic minipump. A total of 63 rat neonates underwent naloxone-precipitated (5 mg/kg, subcutaneous injection) withdrawal testing at postnatal day 10 (PN10). Following withdrawal testing, neonates were randomly assigned to undergo perfusion and subsequent immunohistochemistry experiments to fluoresce Iba-1 for microglia detection, or to undergo the MWM task at three separate developmental time points (PN21-23; PN37; PN60) for cognitive testing. RESULTS: Results suggest that in-utero heroin exposure led to an increase in ultrasonic vocalizations during naloxone-precipitated withdrawal; a sensitive index of withdrawal in rat neonates. Additional results suggest increased microglial reactivity in the HC and VTA, but not the NAc, as well as reduced performance during the MWM in the group exposed to heroin in-utero. DISCUSSION: Together, these data suggest that in-utero opioid exposure is associated with microglial reactivity in brain regions associated with learning and memory, and may be associated with later cognitive deficits. Further research is needed to characterize these findings, which may inform future therapeutic strategies for this vulnerable population.

The lived experience of withdrawal from Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants: A qualitative interview study.

BACKGROUND: Our knowledge of the broader impacts of antidepressant withdrawal, beyond physical side effects, is limited. Further research is needed to investigate the lived experiences of withdrawal, to aid clinicians on how to guide patients through the process. AIM: To explore antidepressant users' experiences and views on the withdrawal process and how it affected their quality of life across multiple life domains. DESIGN AND SETTING: We conducted in-depth qualitative interviews with 20 individuals from the community who had attempted to withdraw from Serotonin Reuptake Inhibitor antidepressants in the past year. METHOD: Semi-structured interviews were conducted online. A topic guide was used to ensure consistency across interviews. The interviews were audio-recorded and transcribed verbatim and analysed using inductive reflexive thematic analysis. RESULTS: Five themes were generated. The first highlighted the challenges of managing the release from emotional blunting and cognitive suppression following antidepressant discontinuation. The second related to the negative impact of withdrawal on close relationships and social interactions. The third showed that concurrent with negative physical symptoms, there was a positive impact on health (exercise was reported by some as a coping mechanism). The fourth theme focused on support from GPs and families, emphasising the importance of mental health literacy in others. The final theme underscored the importance of gradual and flexible tapering in enabling a manageable withdrawal experience, and the consideration of timing. CONCLUSION: The lived experience of withdrawal significantly impacts individuals' well-being. Participants emphasised that withdrawal is not just about physical side effects but also affects their emotional, cognitive, and social functioning. PATIENT AND PUBLIC INVOLVEMENT (PPI): Eight people attended individual online meetings to share their experiences of antidepressant withdrawal to help inform the study design and recruitment strategy. Insights from these meetings informed the development of the topic guide. Questions about GP involvement, family relationships, and mood and thinking changes were included based on this PPI work. This ensured the inclusion of topics important to antidepressant users and facilitated the researcher's questioning during the interviews.

Aetiology and management of persistent withdrawal occlusion in venous ports in oncology patients.

INTRODUCTION: Persistent withdrawal occlusion (PWO) is a specific catheter malfunction characterized by the inability to withdraw blood through the device. The most common cause of PWO in ports is the presence of a fibroblastic sleeve (FS). If malfunction occurs, medication can be applied incorrectly with the increased risk of complications. METHODS: One hundred seventy-seven cases of PWO in venous ports were managed. We focused on evaluating the cause of PWO, the frequency of occurrence of FS, and the options to address the malfunction. The patients underwent fluoroscopy with a contrast agent administration. Mechanical disruption (MD) with a syringe of saline using the flush method was used; in case of its failure, subsequent administration of a lock solution with taurolidine and urokinase, or low-dose thrombolysis with alteplase was indicated. Demographic data were compared with a control group. RESULTS: A significantly higher proportion of female patients was found in the cohort of patients with PWO (80.3% vs 66.3%, p = 0.004), dominantly patients with ovarian cancer (12.8% vs 4.8%, p = 0.022). No effect of the cannulated vein or the type of treatment on the incidence of PWO was demonstrated. The presence of FS was verified in 70% of cases. MD with a syringe was successful in 53.5% of cases. A significantly shorter time to referral (3 weeks) was demonstrated with successful management. The overall success rate of achieving desobliteration by MD alone or in combination with a thrombolytic (urokinase or alteplase) administration was 97.4%. CONCLUSION: We created a method for resolving PWO using MD +/- application of thrombolytics with 97.4% success rate. Current evidence showed that FS is not likely to be affected by thrombolytic drugs; however, we have ascertained an effect of these drugs, proposing a hypothesis of microthrombotic events at the tip of the catheter if fibroblastic sleeve is present.

Low to non-existent sperm content of pre-ejaculate in perfect-use contraceptive withdrawal, a pilot study.

OBJECTIVE: To assess pregnancy risk following perfect use of the withdrawal method by quantification of sperm in pre-ejaculate. STUDY DESIGN: We conducted a pilot study of sperm and factors linked to its presence in pre-ejaculate samples among healthy, reproductive-age, withdrawal-experienced men. Participants provided up to three paired pre-ejaculate and ejaculate specimens in 72-hour intervals. We analyzed samples for volume, consistency, sperm concentration, count, and motility. We set clinical pregnancy risk as our primary outcome, defined as sperm concentration >1million/mL. RESULTS: From 70 paired samples (N=24 participants, median age: 27 years), we identified sperm in 9 (12.9%) pre-ejaculate samples, from 6 (25.0%) participants. Only 7 samples contained sperm in concentrations of significant clinical pregnancy risk. All ejaculatory specimens contained motile sperm in concentrations of significant pregnancy risk. CONCLUSION: In this study of the pre-ejaculate of perfect-use withdrawal users, motile sperm were usually absent, or found inconsistently and in insufficient quantities to confer significant clinical pregnancy risk. IMPLICATIONS: While correct and consistent withdrawal use is likely to be highly effective, given that motile sperm in concentrations >1 million/mL are usually absent or inconsistently present in pre-ejaculate, clinical trial data is lacking.

Bottom-up PBPK modeling of phenytoin brain disposition in postpartum newborns after intrauterine dosing.

OBJECTIVES: The antiepileptic phenytoin has a narrow therapeutic window, nonlinear pharmacokinetics, and can cross the placenta causing apathy and jitteriness in postpartum newborns. Further, the sudden decay of phenytoin concentration can cause withdrawal seizures. This work aimed to assess the brain toxic exposure to phenytoin in newborns after transplacental transfer using neonatal saliva-brain correlations. METHODS: The phenytoin dose that the newborn receives transplacentally at birth was estimated using verified physiologically based pharmacokinetic (PBPK) model simulations in third-trimester pregnancy (pregnancy T3). Such doses were used as an input to the newborn PBPK model to estimate the neonatal levels of phenytoin and their correlations in brain extracellular fluid (bECF), plasma, and saliva. RESULTS: The PBPK model-estimated neonatal plasma and bECF concentrations of phenytoin were below the necessary thresholds for anticonvulsant and toxic effects. The neonatal salivary thresholds for phenytoin anticonvulsant and toxic effects were estimated to be 1.3 and 2.5 mg/L, respectively using the plasma-saliva-bECF correlations established herein. CONCLUSIONS: The salivary TDM of phenytoin can be a more convenient option for avoiding phenytoin brain toxicity in newborns of epileptic mothers. Still, the appropriateness of using the same adult values of phenytoin anticonvulsant and toxic effects for infants needs investigation.

Analyzing quality of life among people with opioid use disorder from the National Institute on Drug Abuse Data Share initiative: implications for decision making.

PURPOSE: We aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature. METHODS: Data obtained from six trials representing 1,777 individuals with OUD. We implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). We performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms. RESULTS: There were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively. CONCLUSION: We observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition.

Thus far, health-related quality of life estimates for patients with opioid use disorder in the United States are limited, and importantly, they were not generated from studies among people living with the condition. This study extracted data from six clinical trials providing data among 1,777 people with opioid use disorder, made publicly available by the National Institutes of Health, to produce estimates of health-related quality of life. Our study found higher health-related quality of life estimates as compared to previous studies, modest impact of medications for opioid use disorder and strong impact of withdrawal symptoms on this outcome. These higher values among people with opioid use disorder might reflect the very negative perception of this condition among members of the general population (among whom these estimates have been generated previously). However, these relatively high estimates could also reflect an adaptation to the condition or a lack of awareness of associated-health damage in the context of dependence. The low number of observations providing data on medications for opioid use disorder led to high uncertainty around related estimates of health-related quality of life, but our findings could also reflect real experiences by patients in the absence of the positive effects of non-medication opioids, which deserve more attention in clinical practice. Our study suggests that systematically measuring withdrawal symptoms and representing these in health economic models might provide a more accurate representation of health-related quality of life among people with opioid use disorder and therefore of the impact and cost-effectiveness of interventions.

Locomotion changes in methamphetamine and amphetamine withdrawal: a systematic review.

Despite extensive preclinical research over the years, a significant gap remains in our understanding of the specific effects of methamphetamine (METH) and amphetamine (AMPH) withdrawal. Understanding these differences could be pivotal to unveiling the unique pathophysiology underlying each stimulant. This may facilitate the development of targeted and effective treatment strategies tailored to the specific characteristics of each substance. Following PRISMA guidelines, this systematic review was conducted to examine alterations in spontaneous locomotor activity, specifically horizontal activity, in animals experiencing withdrawal from extended and repeated administration of AMPH or METH. Original articles were retrieved from four electronic databases, supplemented by a review of the references cited in the published papers. A total of thirty-one full-length articles (n = 31) were incorporated in the analysis. The results indicated that six studies documented a significant increase in horizontal activity among animals, seven studies reported decreased locomotion, and eighteen studies (8 AMPH; 10 METH) reported no significant alterations in the animals' locomotor activity. Studies reporting heightened locomotion mainly employed mice undergoing withdrawal from METH, studies reporting diminished locomotion predominantly involved rats undergoing withdrawal from AMPH, and studies reporting no significant changes in horizontal activity employed both rats and mice (12 rats; 6 mice). Drug characteristics, routes of administration, animal models, dosage regimens, duration, and assessment timing seem to influence the observed outcomes. Despite more than 50% of papers enlisted in this review indicate no significant changes in the locomotion during the stimulant withdrawal, the unique reactions of animals to withdrawal from METH and AMPH reported by some underscore the need for a more nuanced understanding of stimulant withdrawal.

Successful administration of extended-release buprenorphine in the emergency department.

INTRODUCTION: The ongoing opioid epidemic in the United States has resulted in a substantial increase in overdose deaths and related morbidity and mortality. Given that emergency departments (ED) frequently serve as the initial point of contact for individuals experiencing opioid overdose or seeking treatment for opioid use disorder (OUD), ED clinicians have a pivotal role to play in providing prompt and effective treatment for OUD. While ED clinicians routinely administer sublingual and other transmucosal formulations of buprenorphine, extended-release buprenorphine (BUP-XR) remains underutilized in the ED. CASE REPORT: We present a case involving the successful administration of BUP-XR in the ED to a patient experiencing spontaneous opioid withdrawal. The patient tolerated test dosing of sublingual buprenorphine (BUP-SL) and subsequently received BUP-XR in the ED. Following this intervention, the patient was referred to the hospital-affiliated substance use disorder outpatient clinic, where he has since demonstrated successful follow-up and retention in treatment. CONCLUSION: Our report adds to the existing limited literature on the administration of BUP-XR in the ED and highlights the need for more comprehensive clinician teaching and guidance, as well as the establishment of in-hospital protocols for BUP-XR. Despite these challenges, our case indicates that initiating BUP-XR could be a viable and effective option for ED patients with OUD.

The chain mediating role of rumination and social withdrawal in the relationship between smartphone distraction and depression among Chinese nursing students.

Smartphone distraction (SD) is closely related to depression, and the prevalence of SD among nursing students is gradually increasing. However, the potential mechanism of the effect of SD on nursing students' depression is unclear. A total of 574 nursing students were assessed using Smartphone Distraction Scale, Ruminative Response Scale, Hikikomori Questionnaire, and Patient Health Questionnaire-9. The results indicated that SD among nursing students had an impact on depression through four pathways: (1) SD was positively associated with depression (ß = 0.353, P < 0.001); (2) Rumination (ß = 0.199, 95% CI: 0.081 to 0.162) and social withdrawal (ß = 0.061, 95% CI: 0.034 to 0.091) mediated the effects of SD on depression, respectively; and (3) Rumination and social withdrawal played a chain mediating role in the effect of SD on nursing students' depression (ß = 0.027, 95% CI: 0.015 to 0.042). The negative impact of SD on nursing students' mental health should not be taken lightly. Schools and hospitals should guide nursing students to use smartphones correctly, including providing mental health education and professional psychological counselling; families could play a supervisory role and communicate regularly to understand the psychological state and learning of nursing students. These measures can help nursing students cope with stress and reduce the risk of depression.

Estimation of withdrawal interval recommendations following administration of fenbendazole medicated feed to ring-necked pheasants (Phasianus colchicus).

Introduction: Prescribing fenbendazole medicated feed for pheasants in the USA is considered extra-label drug use under CPG Sec 615.115, and a safe estimated withdrawal interval (WDI) must be applied following administration to this minor food-producing species. This study sought to determine the pharmacokinetic and residue depletion profile for fenbendazole and its major metabolites to estimate a WDI for pheasants following fenbendazole administration as an oral medicated feed. Method: Pheasants (n = 32) were administered fenbendazole as an oral medicated feed (100 ppm) for 7 days. Fenbendazole, fenbendazole sulfoxide, and fenbendazole sulfone (FBZ-SO2) in liver and muscle samples were analyzed using HPLC-UV. Tissue WDIs were estimated using FDA, European Medicines Agency (EMA), and half-life multiplication methods for US poultry tolerances, EMA maximum residue limits, and the analytical limit of detection (LOD; 0.004 ppm). Terminal tissue elimination half-lives (T1/2) were estimated by non-compartmental analysis using a naïve pooled data approach. Results: The tissue T1/2 was 14.4 h for liver, 13.2 h for thigh muscle, and 14.1 h for pectoral muscle. The maximum estimated withdrawal interval was 153 h (7 days) for FBZ-SO2 in pectoral muscle using the FDA tolerance method (95% confidence interval for the 99th percentile of the population), and the LOD as the residue limit. Discussion: The results from this study support the use of FBZ-SO2 as the marker residue in the liver of pheasants and the provision of evidence based WDIs following the extra-label administration of fenbendazole medicated feed (100 ppm) for 7 days.

Physicians' experiences and perceptions about withholding and withdrawal life-sustaining treatment in Chiang Mai University Hospital: a cross-sectional study.

BACKGROUND: Withholding or withdrawing life-sustaining treatment in end-of-life patients is a challenging ethical issue faced by physicians. Understanding physicians' experiences and factors influencing their decisions can lead to improvement in end-of-life care. OBJECTIVES: To investigate the experiences of Thai physicians when making decisions regarding the withholding or withdrawal of life-sustaining treatments in end-of-life situations. Additionally, the study aims to assess the consensus among physicians regarding the factors that influence these decisions and to explore the influence of families or surrogates on the decision-making process of physicians, utilizing case-based surveys. METHODS: A web-based survey was conducted among physicians practicing in Chiang Mai University Hospital (June - October 2022). RESULTS: Among 251 physicians (response rate 38.3%), most of the respondents (60.6%) reported that they experienced withholding or withdrawal treatment in end-of-life patients. Factors that influence their decision-making include patient's preferences (100%), prognosis (93.4%), patients' quality of life (92.8%), treatment burden (89.5%), and families' request (87.5%). For a chronic disease with comatose condition, the majority of the physicians (47%) chose to continue treatments, including cardiopulmonary resuscitation (CPR). In contrast, only 2 physicians (0.8%) would do everything, in cases when families or surrogates insisted on stopping the treatment. This increased to 78.1% if the families insisted on continuing treatment. CONCLUSION: Withholding and withdrawal of life-sustaining treatments are common in Thailand. The key factors influencing their decision-making process included patient's preferences and medical conditions and families' requests. Effective communication and early engagement in advanced care planning between physicians, patients, and families empower them to align treatment choices with personal values.

Understanding the relationship between smartphone distraction, social withdrawal, digital stress, and depression among college students: A cross-sectional study in Wuhan, China.

Background: Smartphone distraction considerably affects the depression level of college students. These two variables are highly associated with social withdrawal and digital distress. However, the underlying mechanisms of how social withdrawal and digital stress were involved in the relationship between smartphone distraction and depression remain unclear. Methods: A cross-sectional survey was conducted in seven colleges of Wuhan, Hubei Province, from September to November 2021. Participants were selected using convenience sampling. Smartphone distraction, social withdrawal, digital stress, and depression level were assessed using the Smartphone Distraction Scale (SDS), 25-item Hikikomori Questionnaire (HQ-25), Multidimensional Digital Stress Scale (DSS), and the Patient Health Questionnaire-9 (PHQ-9), respectively. All scales demonstrated good reliability in this study, the reliability of each scale was 0.920, 0.884, 0.959, and 0.942. Results: The final analysis included 1184 students (692 males and 492 females), aged between 17 and 37 years. Participants were from various academic disciplines, including medical and non-medical. The findings revealed that smartphone distraction had a significant direct effect on depression (c = 0.073, 95 % CI: 0.037 to 0.108, p < 0.001) and three significant indirect mediation effects: (1) social withdrawal (B = 0.083, 95 % CI: 0.066 to 0.101, p < 0.001), accounting for 27.76 % of the total effect; (2) digital stress (B = 0.109, 95 % CI: 0.088 to 0.132, p < 0.001), accounting for 36.45 % of the total effect; and (3) the chain mediating roles of social withdrawal and digital stress (B = 0.034, 95 % CI: 0.026 to 0.043, p < 0.001), accounting for 11.37 % of the total effect. The total mediating effect was 75.59 %. Limitations: This study is based on cross-sectional data, which limits the causality inference. Conclusions: These findings suggest that educational institutions should identify college students with excessive smartphone use early and provide timely interventions to minimize negative outcomes. It is also significant to reduce the risk of social withdrawal and digital stress to maintain the physical and mental health development of college students.

Unique Lessons From the Natural Progression of Rejection in Human Uterine Allografts.

INTRODUCTION: Uterus transplantation (UTx) is a novel treatment for absolute uterine infertility. Acute T cell-mediated rejection (TCMR) can be monitored only through serial cervical biopsies. METHODS: This study, the first of its kind in human transplantation, evaluated clinical, serological, and pathophysiological manifestations of allograft rejection from immunosuppression withdrawal (ISW) to graft hysterectomy (Hx). RESULTS: Following live birth, immunosuppression was abruptly withdrawn from six living-donor UTx recipients. ISW occurred at a median of 7.4 weeks before graft Hx. Post-ISW signs of rejection included: (1) discoloration of the cervix; (2) increased uterine size compared to day of ISW; (3) serological evidence of eosinophilia and progressive development of donor-specific antibodies (DSA) or child-specific antibodies (CSA); (4) histopathological evidence of TCMR in cervical biopsies preceding the development of antibodies in serum; and (5) C4d deposition in tissue before formation of DSA or CSA in all but two recipients. At graft Hx, endometrial glands were preferentially targeted for destruction over stroma while parametrial arteries displayed variable arteritis and fibrointimal hyperplasia. CONCLUSION: Recognition of the progression of uterine allograft rejection may be important for other human organ recipients and drive research on modulation of immunosuppression and the paradoxical relationship between adaptive cellular and humoral immunity in natural pregnancies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02656550.

Phenobarbital Dosing for the Treatment of Alcohol Withdrawal Syndrome: A Review of the Literature.

Objective: To determine the most appropriate phenobarbital dosing regimen by evaluating the safety and efficacy of the drug when specifically used in alcohol withdrawal syndrome (AWS). Data sources: A comprehensive literary search was conducted using PubMed and bibliographic mining in October 2023. Study selection and data extraction: An established monotherapy phenobarbital regimen needed to be established within the article to be included in analysis. Location of implementation was not a deterrent to evaluation, nor was the route of phenobarbital administration. Data synthesis: Six publications were evaluated in this review, and two main phenobarbital dosing regimens emerged. While fix-based dosing strategies and weight-based dosing strategies resulted, the dosing within the regimens resulted in the same or relatively similar doses employed, respectively. Each of the studies had a statistically significant decrease in their primary outcome being studied, and the use of phenobarbital as monotherapy was proven to improve AWS symptoms, significantly decrease intensive care unit and hospital length of stay, decrease the use of adjunctive medications, decrease the use of a ventilator, and prevent seizures. Conclusions: Despite benzodiazepines having been the clinical first-line therapy for AWS, research shows that the pharmacokinetic stability and clinical benefits of phenobarbital are in support creation of phenobarbital protocols, as monotherapy, in hospitals or institutions for patients with AWS.