Real-world analysis on the use of gamma-hydroxybutyric acid for alcohol withdrawal syndrome in hospitalized patients with diagnosis of cirrhosis.

The present real-world analysis aimed to evaluate and describe the use of gamma-hydroxybutyric acid (GHB) for alcohol withdrawal syndrome (AWS) in hospitalized patients with diagnosis of liver cirrhosis. An 11-year observational retrospective study on patients affected by liver cirrhosis and alcohol use disorder (AUD) was performed using data from the Medical Toxicology Unit of Careggi University Hospital in Florence (Italy). A multivariate logistic regression was performed to estimate the probability of having a CIWA-Ar Max 3-4 during hospitalization, an AWS length > 36 h, a hospitalization > 9 days, and the probability of developing drowsiness. A total of 166 AUD patients were included, of these 77 received GHB (70.13% within the first day of hospitalization) and 89 were treated without GHB. The majority were ≥ 40 years of age (87.35%) and males (80.12%). GHB patients were more likely to have a CIWA-Ar Max 3-4 during hospitalization (OR 3.76 [CI 95% 1.02-13.85]), and a longer hospitalization (OR 3.08 [95% CI 1.23-7.71]). Early GHB administration decreased the probability of CIWA-Ar Max worsening (OR 0.06 [95% CI 0.01-0.49]). GHB dose ≥ 100 mg/kg was not associated with the occurrence of drowsiness. Patients exposed to other sedative agents were more likely to experience drowsiness (OR 7.22 [95% CI 1.46-35.61]). The present real-world analysis underlines that GHB could be a valuable and safe option for the management of AWS in AUD patients affected by liver cirrhosis, also when administered early and even at higher than recommended dosages.

Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal in the Medical Intensive Care Unit (ICU): A Retrospective Cohort Study.

Background: Phenobarbital (PHB) is a safe and efficacious alternative to benzodiazepines (BZD) for treating severe alcohol withdrawal (AWS). However, the safety of utilizing PHB for patients initially treated with BZD is unknown. Objective: To evaluate the safety and efficacy of PBH compared to BZDs in severe AWS in the medical intensive care unit (ICU). Methods: This was a retrospective cohort study comparing critically ill patients admitted for AWS who received BZDs or PHB. The primary outcome was time to persistent resolution of altered mentation. Secondary outcomes included development and duration of delirium, need for mechanical ventilation, development of withdrawal seizures, and ICU and hospital length of stay. Results: Ninety-five patients were evaluated (53 in PHB group, 42 in BZD group). Before study medication, less BZD patients demonstrated abnormal mentation compared with PHB patients (RASS < -2: 2.39% vsvs. 28.12%, respectively, and RASS > +2: 9.9% vsvs. 48.76%; P <0.001 for both). No difference was seen between groups for the primary outcome (1.8 hours for BZD cohort vsvs. 13.81 hours for PHB cohort; P =0.22). More patients in the BZD cohort developed a seizure after study medication administration (5.67% vs 0%, respectively; P =0.02). No significant difference was seen in other secondary outcomes. Conclusions: This study provides support for use of PHB after BZD if patients remain in uncontrolled withdrawal. Despite significant doses of BZDs before PHB, patients in the PHB cohort demonstrated similar clinical and safety outcomes compared to BZD alone.

Is melanin-concentrating hormone in the medial preoptic area a signal for the decline of maternal care in late postpartum?

This manuscript proposes that melanin-concentrating hormone (MCH) in the medial preoptic area (MPOA) is an neurochemical signal evolved to trigger the declining process of maternal care. MCH in the MPOA appears only after parturition and is progressively increased with the progression of lactation, while maternal behavior declines progressively. Intra-MPOA injection of MCH decreases active maternal responses. MCH is also highly responsive to infant characteristics and maternal condition. Behavioral changes induced by MCH in late postpartum period are conducive to the decline of infant-directed maternal behavior. The MPOA MCH system may mediate the maternal behavior decline by suppressing the maternal approach motivation and/or increasing maternal withdrawal via its inhibitory action onto the mesolimbic dopamine D1/D2 receptors and its stimulating action on serotonin 5-HT2C receptors in the ventral tegmental area. Research into the MCH maternal effects will enhance our understanding of the neurochemical mechanisms underlying the maternal behavior decline.

Intravenous misplacement of the nephrostomy catheter following percutaneous nephrolithotomy: A case report and review of 26 cases in the literature.

Intravenous misplacement of the nephrostomy catheter following percutaneous nephrolithotomy (PCNL) is severe and extremely rare, and little information is available about this complication. Because the patient's prognosis may be poor, sufficient attention should be paid to early identification and treatment of this complication. We report a case with intravenous misplacement of nephrostomy catheter and severe bleeding from the catheter after PCNL was transferred to our hospital. The patient was successfully managed using a two-step intervention. First, the patient underwent embolization of the pseudoaneurysms in renal parenchyma, then underwent catheter withdrawal under digital subtraction angiography (DSA) and control bleeding by pushing the absorbable hemostatic material (Surgicel) into the tunneled renal drainage. There were no severe complications. Withdrawal could be performed by open surgery or under the supervision of imaging modalities. Some reports showed that minimally invasive management was safer and less invasive than open surgery.

End-of-Life Practices in an Intensive Care Unit of a Private Hospital in Mexico.

Background: Many factors, such as religion, geography, and customs, influence end-of-life practices. This variability exists even between different physicians. Objective: To observe and describe the end-of-life actions of patients in the intensive care unit (ICU) and document the variables that might influence decision-making at the end of life. Materials and Methods: This is a cross-sectional study performed in the ICU patients of a private hospital from March 2017 to March 2022. We used the Philips Tasy Electronic Medical Record database of clinical records; 298 patients were included in the study during these five years (2017-2022). The data analysis was done with the statistical package SPSS version 23 for Windows. Results: A total of 297 patients were included in this study, of which more than half were men. About 60% of our sample had private health insurance, whereas the remaining paid out of pocket. Most patients had withholding treatment, followed by failed cardiopulmonary resuscitation, withdrawal treatment, and brain death, and none of the patients had acceleration of the dying process. The main cause of admission to the ICU in our center was respiratory complications. Most of our samples were Catholics. Conclusions: Decision-making at the end of life is a complex process. Active participation of the patient, when possible, the patient's family, doctors, and nurses, can give different perspectives and a more compassionate and individualized approach to end-of-life care.

Using in silico methods to determine optimal tapering regimens for decanoate-based long-acting injectable psychosis drugs.

Background: Reducing the dose of psychosis drugs in a gradual hyperbolic manner may minimise withdrawal effects and risk of relapse. There is presently limited guidance on tapering decanoate-based long-acting injectable dopamine antagonists (LIDAs). Objectives: We aimed to apply hyperbolic principles of tapering to the decanoate-based LIDAs flupentixol, zuclopenthixol and haloperidol to develop withdrawal regimens. Design: We used in silico methodology to predict plasma drug levels and D2 occupancy for different LIDA regimens. Methods: Existing pharmacokinetic and receptor occupancy data from nuclear neuroimaging studies were used to power modelling. Abrupt discontinuation was examined as a potential strategy, and dose reduction was modelled with pre-defined constraints used in similar work of 10 (fast regimens), 5 (moderate) and 2.5 (slow) percentage points of D2 occupancy change per month. Results: Abrupt discontinuation of decanoate-based LIDAs leads to excessive change in D2 occupancy which violated our pre-defined constraints, potentially resulting in withdrawal symptoms and increased risk of relapse. Reduction of LIDA dose allowed hyperbolic reduction in plasma level consistent with imposed constraints on receptor occupancy reduction rate. For equivalent per-weekly LIDA dosing, more frequent administration allowed a more gradual reduction of D2 occupancy. However, switching to oral forms is required to continue hyperbolic tapering to full discontinuation; reduction to zero using only LIDA produces too large a reduction in D2 occupancy. Guidance for reduction and cessation of LIDAs according to slow, moderate and fast criteria is provided. Conclusion: Abrupt cessation of decanoate LIDAs is not consistent with gradual hyperbolic tapering, despite their longer half-lives compared with oral formulations. Reduction to the point of full discontinuation can only be achieved by switching to oral therapy to complete the taper. These results are limited by the in silico and theoretical nature of the study, and there is a need to confirm these findings through real-world observational and interventional studies.

Computer-based research on the best way to reduce the dose and eventually stop three depot antipsychotics What is the problem? Psychosis affects how someone experiences reality. Antipsychotics are used to treat psychosis. They work by blocking a chemical called dopamine. Stopping these too rapidly can cause psychosis to occur again. This might be because the dopamine block is removed suddenly. Sometimes antipsychotics are given by injection. Injections stay in the body for a longer time than tablets. The best way to reduce these injections is currently unknown. What did we do? We explored the best way to reduce and stop antipsychotic injections. We looked at three different types of psychosis injection. We used existing data to assess how these drugs affect the brain. We examined what would happen if an antipsychotic injection was suddenly stopped. We then evaluated the effect of reducing the dose gradually. What did we find? Stopping antipsychotic injections suddenly would lead to rapid changes at brain receptors. This might lead to symptoms of withdrawal and a high risk of psychosis recurring. Reducing the dose of injections leads to less change than stopping suddenly. Switching to a tablet allows for more control when reducing dose. Having injections more often also reduce the changes occurring between injections. We outline three different rates of dose reduction. What does this mean? Antipsychotic injections stay in the body longer than tablets. However, stopping injections suddenly may still not be safe. We recommend that people reduce the dose of their injection instead. We also recommend people switch to tablets or liquid before stopping. It should be noted that our research is computer-based. We would like to see our recommendations tested in the real world.

Possibility of maintaining remission with topical therapy alone after withdrawal of dupilumab in Japanese patients with atopic dermatitis and their characteristics in the real world.

Psossibility and appropriate timing of discontinuation of dupilumab for atopic dermatitis (AD) remain unclear. We explored the possibility of patients, who could maintain remission with topical therapy alone after withdrawing dupilumab in the real world. Furthermore, we identified their characteristics. All adult AD patients who initiated dupilumab from June 2018 to July 2022 and were treated with dupilumab for more than 3 months at our hospital were included in this study. The observation period was from June 2018 to July 2023. In 138 patients, 58 (42.0%) discontinued dupilumab at least once. Among them, 18 (13.0%) discontinued dupilumab but reinitiated dupilumab later due to exacerbation. Only seven patients (5.1%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM, VAS of pruritus, serum levels of TARC and LDH, and neutrophil counts at baseline, and those of longer duration of dupilumab until its discontinuation (24.0 ± 13.3 vs. 12.8 ± 7.3 months) and lower EASI and affected BSA at the discontinuation of dupilumab. In 118 patients treated with dupilumab for at least 1 year, 38 patients (32.2%) discontinued at least once. Only four patients (3.4%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM at baseline and lower EASI at the discontinuation of dupilumab. In conclusion, maintaining remission after withdrawing dupilumab is challenging. Discontinuation of dupilumab may be considered in patients with low baseline POEM, after more than 2 years of dupilumab treatment, with a substantial decrease in EASI.

[Factors influencing hospital readmission rates in alcohol use disorder]. / Einflussfaktoren auf die Rehospitalisierungsrate bei Alkoholabhängigkeit.

BACKGROUND: According to data from the Federal Statistical Office, the diagnosis of alcohol use disorder (AUD) (F 10) is the second most common main diagnosis for hospital treatment. Those affected by this disorder are often repeatedly hospitalized at short intervals due to relapses; however, little is known about the factors that influence readmission rates after initial treatment. AIM OF THE STUDY: The aim of this retrospective analysis is to analyze the effects of treatment type (qualified withdrawal treatment (QE) versus physical detoxification) and discharge mode on the probability of readmission in alcohol-dependent patients after inpatient treatment. MATERIAL AND METHODS: Data from 981 male and female alcohol-dependent patients who completed either qualified withdrawal treatment (QE) (68% men; mean age 47.6 years) or inpatient detoxification (74% men; mean age 48.0 years) were analyzed. Predictors of regular discharge were determined separately for both types of treatment using stepwise logistic regression. RESULTS: Patients who had completed a qualified withdrawal treatment were significantly more likely to be regularly discharged. Regular completion of the qualified withdrawal treatment (QE) led to a relative reduction in the readmission rate of 25.64% within 1 year compared to a physical detoxification. CONCLUSION: In order to prevent readmission and chronic courses of alcohol use disorder (AUD), qualified withdrawal treatment should always be recommended to affected patients instead of physical detoxification. Aktuelle Daten des Statistischen Bundesamtes für das Jahr 2022 zeigen, dass die Diagnose "Psychische und Verhaltensstörungen durch Alkohol (F 10.X)" die zweithäufigste Hauptdiagnose bei Krankenhausbehandlungen darstellt [13]. Im Gesundheitssystem entstehen durch dieses Erkrankungsbild und seine somatischen und psychischen Folgeerkrankungen jährlich ca. 10 Mrd. € direkte Kosten [13]. Dieser Sachverhalt wird dadurch kontrastiert, dass die Krankenkassen die qualifizierte Entzugsbehandlung (QE) als leitliniengerechte Goldstandardtherapie [4] wiederholt infrage stellen [10].

Identification of gene co-expression modules from zebrafish brain data: Applications in psychiatry illustrated through alcohol-related traits.

Cumulative evidence suggests that zebrafish is a useful model in psychiatric research. Weighted Gene Co-expression Network Analysis (WGCNA) enables the reduction of genome-wide expression data to modules of highly co-expressed genes, which are hypothesized to interact within molecular networks. In this study, we first applied WGCNA to zebrafish brain expression data across different experimental conditions. Then, we characterized the different co-expression modules by gene-set enrichment analysis and hub gene-phenotype association. Finally, we analyzed association of polygenic risk scores (PRSs) based on genes of some interesting co-expression modules with alcohol dependence in 524 patients and 729 controls from Galicia, using competitive tests. Our approach revealed 34 co-expression modules in the zebrafish brain, with some showing enrichment in human synaptic genes, brain tissues, or brain developmental stages. Moreover, certain co-expression modules were enriched in psychiatry-related GWAS and comprised hub genes associated with psychiatry-related traits in both human GWAS and zebrafish models. Expression patterns of some co-expression modules were associated with the tested experimental conditions, mainly with substance withdrawal and cold stress. Notably, a PRS based on genes from co-expression modules exclusively associated with substance withdrawal in zebrafish showed a stronger association with human alcohol dependence than PRSs based on randomly selected brain-expressed genes. In conclusion, our analysis led to the identification of co-expressed gene modules that may model human brain gene networks involved in psychiatry-related traits. Specifically, we detected a cluster of co-expressed genes whose expression was exclusively associated with substance withdrawal in zebrafish, which significantly contributed to alcohol dependence susceptibility in humans.

A scoping review of end-of-life discussions and palliative care: implications for neurological intensive care among Latinos in the U.S.

Goals of care (Goals-of-care) discussions and palliative care (PC) are crucial to providing comprehensive healthcare, particularly for acute neurological conditions requiring admission to a neurological intensive care unit. We identified gaps in the literature and describe insight for future research on end-of-life discussions and PC for U.S. Latinos with acute neurological conditions. We searched 10 databases including peer-reviewed abstracts and manuscripts of hospitalized U.S. Latinos with acute neurological and non-neurological conditions. We included 44 of 3231 publications and identified various themes: PC utilization, pre-established advanced directives in Goals-of-care discussions, Goals-of-care discussion outcomes, tracheostomy or percutaneous gastrostomy tube placement rates among hospitalized Latinos. Our review highlights that Latinos appear to have lower palliative care utilization compared with non-Latino Whites and may be less likely to have pre-established advanced directives, more likely to have gastrostomy or tracheostomy placement and less likely to have do-not-resuscitate status.

Exploring core symptoms of alcohol withdrawal syndrome in alcohol use disorder patients: a network analysis approach.

Background: Understanding the interplay between psychopathology of alcohol withdrawal syndrome (AWS) in alcohol use disorder (AUD) patients may improve the effectiveness of relapse interventions for AUD. Network theory of mental disorders assumes that mental disorders persist not of a common functional disorder, but from a sustained feedback loop between symptoms, thereby explaining the persistence of AWS and the high relapse rate of AUD. The current study aims to establish a network of AWS, identify its core symptoms and find the bridges between the symptoms which are intervention target to relieve the AWS and break the self-maintaining cycle of AUD. Methods: Graphical lasso network were constructed using psychological symptoms of 553 AUD patients. Global network structure, centrality indices, cluster coefficient, and bridge symptom were used to identify the core symptoms of the AWS network and the transmission pathways between different symptom clusters. Results: The results revealed that: (1) AWS constitutes a stable symptom network with a stability coefficient (CS) of 0.21-0.75. (2) Anger (Strength = 1.52) and hostility (Strength = 0.84) emerged as the core symptom in the AWS network with the highest centrality and low clustering coefficient. (3) Hostility mediates aggression and anxiety; anger mediates aggression and impulsivity in AWS network respectively. Conclusions: Anger and hostility may be considered the best intervention targets for researching and treating AWS. Hostility and anxiety, anger and impulsiveness are independent but related dimensions, suggesting that different neurobiological bases may be involved in withdrawal symptoms, which play a similar role in withdrawal syndrome.

The cell-permeant antioxidant D-thiol ester D-cysteine ethyl ester overcomes physical dependence to morphine in male Sprague Dawley rats.

The ability of morphine to decrease cysteine transport into neurons by inhibition of excitatory amino acid transporter 3 (EAA3) may be a key molecular mechanism underlying the acquisition of physical and psychological dependence to morphine. This study examined whether co-administration of the cell-penetrant antioxidant D-thiol ester, D-cysteine ethyl ester (D-CYSee), with morphine, would diminish the development of physical dependence to morphine in male Sprague Dawley rats. Systemic administration of the opioid receptor antagonist, naloxone (NLX), elicited pronounced withdrawal signs (e.g., wet-dog shakes, jumps, rears, circling) in rats that received a subcutaneous depot of morphine (150 mg/kg, SC) for 36 h and continuous intravenous infusion of vehicle (20 µL/h, IV). The NLX-precipitated withdrawal signs were reduced in rats that received an infusion of D-CYSee, but not D-cysteine, (both at 20.8 µmol/kg/h, IV) for the full 36 h. NLX elicited pronounced withdrawal signs in rats treated for 48 h with morphine (150 mg/kg, SC), plus continuous infusion of vehicle (20 µL/h, IV) that began at the 36 h timepoint of morphine treatment. The NLX-precipitated withdrawal signs were reduced in rats that received a 12 h infusion of D-CYSee, but not D-cysteine, (both at 20.8 µmol/kg/h, IV) that began at the 36 h timepoint of morphine treatment. These findings suggest that D-CYSee may attenuate the development of physical dependence to morphine and reverse established dependence to the opioid in male Sprague Dawley rats. Alternatively, D-CYSee may simply suppress the processes responsible for NLX-precipitated withdrawal. Nonetheless, D-CYSee and analogues may be novel therapeutics for the treatment of opioid use disorders.

Tranq Dope: Characterization of an ED cohort treated with a novel opioid withdrawal protocol in the era of fentanyl/xylazine.

BACKGROUND: Treating opioid use disorder has reached a new level of challenge. Synthetic opioids and xylazine have joined the non-medical opioid supply, multiplying the complexities of caring for individuals in emergency departments (ED). This combination, known as 'tranq dope,' is poorly described in literature. Inadequate withdrawal treatment results in a disproportionately high rate of patient-directed discharges (also known as against medical advice dispositions, or AMA). This study aimed to describe a cohort of individuals who received a novel order set for suspected fentanyl and xylazine withdrawal in the ED. METHODS: This is a descriptive study evaluating a cohort of ED patients who received withdrawal medications from a novel protocol and electronic health record order set. Individuals being assessed in the ED while suffering from withdrawal were eligible. Individuals under age 18, on stable outpatient MOUD or who were pregnant were excluded. Treatment strategies included micro-induction buprenorphine, short acting opioids, non-opioid analgesics, and other adjunctive medications. Data collected included: demographics including zip code, urine toxicology screening, order set utilization and disposition data. Clinical Opiate Withdrawal Scale (COWS) scores were recorded, where available, before and following exposure to the medications. RESULTS: There were 270 patient encounters that occurred between September 14, 2022, and March 9, 2023 included in the total study cohort. Of those, 66 % were male, mean age 37 with 71 % residing within Philadelphia zip codes. 100 % of urine toxicology screenings were positive for fentanyl. Of the 177 patients with both pre- and post-exposure COWS scores documented, constituting the final cohort, patients receiving medications had their COWS score decrease from a median of 12 to a median of 4 (p < 0.001). The AMA rate for this cohort was 3.9 %, whereas the baseline for the population with OUD was 10.7 %. Recorded adverse effects were few and resolved without complication. CONCLUSIONS: Fentanyl and xylazine withdrawal are challenging for patients and providers. A novel tranq dope withdrawal order set may reduce both COWS scores and rate of patient-directed discharge in this cohort of patients, though further investigation is needed to confirm findings.

Is Phenobarbital an Effective Treatment for Alcohol Withdrawal Syndrome?

BACKGROUND: Alcohol use disorder is associated with a variety of complications, including alcohol withdrawal syndrome (AWS), which may occur in those who decrease or stop alcohol consumption suddenly. AWS is associated with a range of signs and symptoms, which are most commonly treated with GABAergic medications. CLINICAL QUESTION: Is phenobarbital an effective treatment for AWS? EVIDENCE REVIEW: Studies retrieved included two prospective, randomized, double-blind studies and three systematic reviews. These studies provided estimates of the effectiveness and safety of phenobarbital for treatment of AWS. CONCLUSIONS: Based on the available literature, phenobarbital is reasonable to consider for treatment of AWS. Clinicians must consider the individual patient, clinical situation, and comorbidities when selecting a medication for treatment of AWS.

The effects of physical exercise on fitness and emotion in Chinese preschoolers.

BACKGROUND: The global prevalence of overweight and obesity in children under the age of five has emerged as a significant issue in recent years. Physical activity and fitness among children and adolescents have declined globally in the past few decades. Studies have indicated a link between levels of physical activity and cognitive performance in preschool children. METHODS: This quasi-experimental study investigated the effects of three different types of physical education programmes on the physical fitness and emotional competence of 239 preschoolers(mean age = 5.49 ± 0.60 years, 54.4% boys)in Haikou, China. The preschoolers were grouped based on which programme they were assigned to: the "Hello Sunshine" ball skills programme (HS group), ordinary physical education (OPE group), and free play (FP group). The "Hello Sunshine" ball skills programme used both a structured curriculum design and autonomous activity selection during outdoor time., which were conducive to children's physical fitness.The National Physical Fitness Measurement Standards Manual and the shortened version of the Social Competence and Behavior Evaluation Scale (SCBE-30) were used to assess physical fitness and emotional competence, respectively. These assessments were conducted both before and after the ten-week intervention period. The analysis utilised a mixed-effects model for physical fitness and a mixed-model ANOVA for the SCBE data. RESULTS: The HS group and OPE group demonstrated significantly improvement in the standing long jump, 10-m shuttle run and balance beam walking than the FP group; meanwhile, only anxious-withdrawal levels showed a significant grouping effect and group-by-time interaction effect. After the intervention, both the HS group and the FP group showed significantly lower scores for anxiety compared to the OPE group, with no significant difference observed between the HS and FP groups. CONCLUSIONS: The results suggested that structured ball skills programmes may promote physical fitness and reduce anxiety. The integration of effective physical exercise programmes into preschool curricula holds the potential for promoting holistic development.

Caffeine-Induced Psychosis: A Case Report and Review of Literature.

A 51-year-old female, with no previous history of psychosis, presented to the Emergency Department with an acute psychotic episode in the context of excess caffeine consumption. Caffeine is an adenosine antagonist. An antagonist of adenosine can lead to the release of dopamine into the synaptic cleft, which can induce psychotic symptoms in vulnerable individuals. The patient had consumed caffeine in the form of up to eight energy drinks daily. She experienced persecutory delusions alongside auditory and visual hallucinations. She did not have a history of psychotic disorder but did have a history of generalized anxiety disorder. Upon cessation of caffeine, her symptoms resolved within five days. She remained caffeine-free and symptom-free 18 months later when reviewed in the community. This case highlights the potential psychiatric consequences of excessive caffeine consumption and identifies the need to screen for excessive consumption of caffeine in individuals presenting with new psychotic symptoms or worsening of pre-existing psychotic symptoms.

Prenatal opioid exposure significantly impacts placental protein kinase C (PKC) and drug transporters, leading to drug resistance and neonatal opioid withdrawal syndrome.

Background: Neonatal Opioid Withdrawal Syndrome (NOWS) is a consequence of in-utero exposure to prenatal maternal opioids, resulting in the manifestation of symptoms like irritability, feeding problems, tremors, and withdrawal signs. Opioid use disorder (OUD) during pregnancy can profoundly impact both mother and fetus, disrupting fetal brain neurotransmission and potentially leading to long-term neurological, behavioral, and vision issues, and increased infant mortality. Drug resistance complicates OUD and NOWS treatment, with protein kinase regulation of drug transporters not fully understood. Methods: DNA methylation levels of ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, along with protein kinase C (PKC) genes, were assessed in 96 placental samples using the Illumina Infinium MethylationEPIC array (850K). Samples were collected from three distinct groups: 32 mothers with infants prenatally exposed to opioids who needed pharmacological intervention for NOWS, 32 mothers with prenatally opioid-exposed infants who did not necessitate NOWS treatment, and 32 mothers who were not exposed to opioids during pregnancy. Results: We identified 69 significantly differentially methylated SLCs, with 24 hypermethylated and 34 hypomethylated, and 11 exhibiting both types of methylation changes including SLC13A3, SLC15A2, SLC16A11, SLC16A3, SLC19A2, and SLC26A1. We identified methylation changes in 11 ABC drug transporters (ABCA1, ABCA12, ABCA2, ABCB10, ABCB5, ABCC12, ABCC2, ABCC9, ABCE1, ABCC7, ABCB3): 3 showed hypermethylation, 3 hypomethylation, and 5 exhibited both. Additionally, 7 PKC family genes (PRKCQ, PRKAA1, PRKCA, PRKCB, PRKCH, PRKCI, and PRKCZ) showed methylation changes. These genes are associated with 13 pathways involved in NOWS, including ABC transporters, bile secretion, pancreatic secretion, insulin resistance, glutamatergic synapse, and gastric acid secretion. Conclusion: We report epigenetic changes in PKC-related regulation of drug transporters, which could improve our understanding of clinical outcomes like drug resistance, pharmacokinetics, drug-drug interactions, and drug toxicity, leading to maternal relapse and severe NOWS. Novel drugs targeting PKC pathways and transporters may improve treatment outcomes for OUD in pregnancy and NOWS.

Eat, Sleep, Console model for neonatal opioid withdrawal syndrome: a meta-analysis.

Background: The rising incidence of drug abuse among pregnant women has rendered neonatal opioid withdrawal syndrome a significant global health concern. Methods: Databases including PubMed, Web of Science, the Cochrane Library, Embase, Elton B. Stephens. Company (EBSCO), China National Knowledge Infrastructure (CNKI), and Wanfang were searched for comparative studies of the Eat, Sleep, Console model vs. traditional assessment tools for neonatal opioid withdrawal syndrome. Two reviewers conducted literature searches, screened according to the inclusion criteria, extracted data, and independently verified accuracy. All meta-analyses were conducted using Review Manager Version 5.4. Results: In total, 18 studies involving 4,639 neonates were included in the meta-analysis. The Eat, Sleep, Console model demonstrated superior outcomes in assessing neonatal opioid withdrawal syndrome, significantly reducing the need for pharmacological treatment [risk ratio = 0.44, 95% confidence interval (CI) = 0.34-0.56, P < 0.001], decreasing the length of hospital stay [standard mean difference (SMD) = -2.10, 95% CI = -3.43 to -0.78, P = 0.002], and shortening the duration of opioid treatment (SMD = -1.33, 95% CI = -2.22 to -0.45, P = 0.003) compared to the Finnegan Neonatal Abstinence Scoring System. Conclusions: The Eat, Sleep, Console model is more effective than the Finnegan Neonatal Abstinence Scoring System in improving the assessment and management of neonatal opioid withdrawal syndrome.

Inpatient Growth in Infants Requiring Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome.

Aim: To assess inpatient growth parameter trajectories and to identify the type of opioid exposure and treatment characteristics influencing growth parameters of infants admitted to the newborn intensive care unit (NICU) for pharmacological treatment of neonatal opioid withdrawal syndrome (NOWS). Methods: Charts of term infants with NOWS admitted to NICU from 2012 to 2019, who received pharmacologic treatment, were reviewed. Intake (volume: mL/kg/day; calorie: kcal/kg/day) and growth parameter trajectories (weight, head circumference, and length) were analyzed based on the type of prenatal opioid exposure (short-acting opioids (SAOs), long-acting opioids (LAOs), and polysubstance), pharmacologic treatment, and sex. Growth measurement patterns over time were compared between groups using longitudinal mixed-effects models. Results: One hundred nineteen infants were included in the study with median birth weight Z-score of -0.19 at birth and decreased to a median of -0.72 at discharge. Exposure to SAO was associated with an increase in Z-scores nearing discharge across all growth parameters (Z-score for weight p = 0.03). Polysubstance exposure was associated with a decrease in Z-scores for length and head circumference throughout hospitalization. Infants with adjunct clonidine treatment had an increase in Z-score for weight trends. Male infants had a decrease in Z-scores for weight (male -0.96, female -0.59, interaction p = 0.06) and length (male -1.17, female -0.57, interaction p = 0.003) at Day 28. Despite the difference in growth trajectories, intake in terms of amount (mL/kg/day) and calorie intake (kcal/kg/day) was similar based on prenatal exposure, treatment, and sex. Conclusion: Infants with NOWS requiring pharmacologic treatment have a decrease in Z-scores for weight, length, and head circumference at birth and at hospital discharge. Infants with prenatal polysubstance exposure were at particular risk for poorer inpatient growth relative to infants exposed to SAO and LAO, indicated by lower Z-scores for length and occipital frontal circumference (OFC).

The influence of withdrawal-recharging pattern on the deformation characteristics of sand in confined aquifer.

Land subsidence caused by excessive groundwater withdrawal has become a global hazard, which demands further researches and the potential measures to control. Using the FlowTrac Ⅱ consolidation test system, six compression tests were designed to investigate the stress state and stress paths of sand within confined aquifers under conditions of withdrawal and recharging. The deformation characteristics of aquifer sand were studied under different withdrawal-recharging patterns. During pumping and recharge processes, sand deformation responses were observed to lag behind changes in applied stress. The characteristics of this hysteresis effect on deformation were summarized. The alternating phenomenon of rebound and compression of sand deformation under the recharging process is analyzed. When the recharging effect was relatively small than withdrawing effect under the stable withdrawal-recharging pattern, the compression deformation was observed in the recharging process. The research results provide a rational explanation for the continuous compression deformation of the aquifer during groundwater level recovery and offer experimental evidence for the rational design of artificial groundwater recharge in engineering construction.