Withdrawal Symptoms Research Articles

Effects of xylazine on naloxone-precipitated fentanyl withdrawal in male and female rats

PurposeThe combination of fentanyl and xylazine (i.e., “tranq-dope”) was recently declared an emerging national health threat in the United States. Given the recency of this development, very little is known regarding the behavioral pharmacology of fentanyl-xylazine combinations. The purpose of this study was to characterize the somatic and affective withdrawal symptoms of this drug combination. MethodsMale and female Long Evans rats were given twice daily (08:00 and 20:00) subcutaneous injections of fentanyl, xylazine, or combined fentanyl-xylazine for five days. On the sixth (testing) day, rats were given a final injection at 08:00. Four hours later, rats were injected intraperitoneally with either saline or a naloxone challenge before behavioral observation. Somatic withdrawal was examined using the Gellert-Holtzman scale and anxiety-like behavior was examined using the elevated plus maze. ResultsNaloxone administration did not induce somatic or affective symptoms in rats treated with fentanyl alone, a low dose of xylazine alone, or a high dose of xylazine alone. Naloxone induced somatic but not affective withdrawal symptoms in rats treated with both fentanyl and xylazine. ConclusionChronic co-exposure to fentanyl and xylazine produces an opioid-like somatic withdrawal syndrome at doses that are not apparent with either drug alone. These results corroborate clinical reports that xylazine worsens fentanyl withdrawal and suggest that novel interventions may be required to treat withdrawal from fentanyl-xylazine combinations in humans.

The effect of down-titration and discontinuation of heart failure pharmacotherapy in older people: A systematic review and meta-analysis.

The aim of this study was to investigate whether interventions to discontinue or down-titrate heart failure (HF) pharmacotherapy are feasible and associated with risks in older people. A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to 8 March 2023. Randomized controlled trials (RCTs) and observational studies included people with HF, aged ≥50 years and who discontinued or down-titrated HF pharmacotherapy. Outcomes were feasibility (whether discontinuation or down-titration of HF pharmacotherapy was sustained at follow-up) and associated risks (mortality, hospitalization, adverse drug withdrawal effects [ADWE]). Random-effects meta-analysis was performed when heterogeneity was not substantial (Higgins I2< 70%). Sub-analysis by frailty status was conducted. Six RCTs (536 participants) and 27 observational studies (810 499 participants) across six therapeutic classes were included, for 3-260 weeks follow-up. RCTs were conducted in patients presenting with stable chronic HF. Down-titrating a renin-angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% more likely than continuation (risk ratio [RR] 1.76, 95% confidence interval [CI] 1.14-2.73), with no difference in mortality (RR 0.64, 95% CI 0.30-1.64). Discontinuation of beta-blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95% CI 0.68-1.47). Participants were 25% more likely to re-initiate discontinued diuretics (RR 0.75, 95% CI 0.66-0.86). Digoxin discontinuation was associated with 5.5-fold risk of hospitalization compared to continuation. Worsening HF was the most common ADWE. One observational study measured frailty but did not report outcomes by frailty status. The appropriateness and associated risks of down-titrating or discontinuing HF pharmacotherapy in people aged ≥75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.

Index of application status transparency and availability of public information for Project Orbis agencies

The purpose of this paper is to provide a guideline for understanding and comparing the regulatory framework of Project Orbis Partners (POPs) and Project Orbis observers, with a focus on their approaches to drug approvals, rejections, and withdrawals. While each agency has its own regulatory framework and guidance, there are some similarities and differences between the language used to describe drug approvals, rejections, withdrawals, and the public availability of these decisions. Project Orbis is an international partnership of regulatory agency, led by the U.S. Food and Drug Administration (FDA), aimed at streamlining the submission and review processes to expedite the global availability of oncology medications for patients. Since its inception, Australia’s Therapeutic Goods Administration (TGA), Brazil’s National Health Surveillance Agency (ANVISA), Canada’s Health Canada (HC), Israel’s Ministry of Health (IMoH) Medical Technologies, Health Information, Innovation and Research (MTIIR) Directorate, Singapore’s Health Sciences Authority (HSA), Switzerland’s Swissmedic (SMC), and United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) have joined and become POPs. Other international agencies such as, the European Medicines Agency (EMA) and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) are currently observing Project Orbis, as of late 2023. They are not full Project Orbis partners but work closely with the FDA to facilitate oncology drug approval through international collaboration. Running Title: An Index of the FDA and international regulators involved in Project Orbis looking at the similarities and differences between approval, rejection, and withdrawal characteristics of applications and public transparency of actions.

Correlates of fentanyl preference among people who use drugs in Rhode Island

BackgroundFentanyl is increasingly pervasive in the unregulated drug supply and is a driver of drug overdose deaths in the United States. The aims of this study were to characterize and identify correlates of fentanyl preference among people who use drugs (PWUD) in Rhode Island (RI).MethodsUsing bivariate analysis, we examined associations between fentanyl preference and sociodemographic and psychosocial characteristics at baseline among participants enrolled in the RI Prescription Drug and Illicit Drug Study from August 2020-February 2023. Fentanyl preference was operationalized based on responses to a five-point Likert scale: “I prefer using fentanyl or drugs that have fentanyl in them.” Participants who responded that they “strongly disagree,” “disagree,” or were “neutral” with respect to this statement were classified as not preferring fentanyl, whereas participants who responded that they “agree” or “strongly agree” were classified as preferring fentanyl.ResultsAmong 506 PWUD eligible for inclusion in this analysis, 15% expressed a preference for fentanyl or drugs containing fentanyl as their drug of choice. In bivariate analyses, preference for fentanyl was positively associated with younger age, white race, lifetime history of overdose, history of injection drug use, past month enrollment in a substance use treatment program, past month treatment with medications for opioid use disorder, and preferences for heroin and crystal methamphetamine (all p < 0.05). Descriptive data yielded further insight into reasons for fentanyl preference, the predominant having to do with perceived effects of the drug and desire to avoid withdrawal symptoms.ConclusionsOnly a relatively small subset of study participants preferred drugs containing fentanyl. Given the increased prevalence of fentanyl contamination across substances within the unregulated drug market, the result for PWUD is increasingly less agency with respect to choice of drug; for example, people may be forced to use fentanyl due to restricted supply and the need to mitigate withdrawal symptoms, or may be using fentanyl without intending to do so. Novel and more effective interventions for PWUD, including increased access to age-appropriate harm reduction programs such as fentanyl test strips and overdose prevention centers, are needed to mitigate fentanyl-related harms.

“Withdrawal Syndrome”: The Effects of Acts of Microaggression in the Classroom on Racialized Students

“Withdrawal Syndrome”: The Effects of Acts of Microaggression in the Classroom on Racialized Students

Similarities and differences in core symptoms of problematic smartphone use among Chinese students enrolled in grades 4 to 9: A large national cross-sectional study

Children and adolescents are highly susceptible to problematic smartphone usage. We employed network analysis to explore the similarities and differences in the core symptoms of problematic smartphone use across grades 4–9, using a large nationwide sample. This study included 8552 children and adolescents (Mage = 12.98, SD=1.51) who met the critical value for problematic smartphone use. The results showed that the core symptoms of problematic smartphone use exhibit both similarities and differences between grades 4 and 9. ’Withdrawal symptoms’ and ’preoccupation symptoms’ were the stable core symptoms of problematic smartphone use across grades 4 to 9, suggesting that problematic smartphone use begin to appear from earlier grades, such as grade 4. ’Feel impatient and fretful’, ’never give up’ and ’always thinking about’ were the core symptoms in grades 4 and 5. ’Longer than I had intended’ and ’hard to concentrate’ emerged as additional core symptoms in grade 6, with the intensity indicators peaking in grades 8 and 9, suggesting that the issue of problematic smartphone use among Chinese children and adolescents has become intensified and intricate. Symptoms of problematic smartphone use vary across grades and exhibit both continuity and stage specificity. Consequently, to address this issue, the formulation of intervention measures should comprehensively consider both the grade levels and symptoms.

Treatment of spondyloarthritis with disease-modifying anti-rheumatic drugs during pregnancy and breastfeeding: comparing the recommendations and guidelines of the principal societies of rheumatology.

This paper aims to provide an overview of the use of treatments available for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) during pregnancy and breastfeeding, according to current national recommendations and international guidelines, as well as data on the impact on pregnancy outcomes of paternal exposure to treatment. We performed a narrative review of national and international recommendations and guidelines on the reproductive health of patients suffering from rheumatic diseases. The last updated recommendations and guidelines were considered source data. We reported updated information regarding the treatment of axSpA and PsA with nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs during the preconception period, pregnancy, and breastfeeding, as well as data related to paternal exposure. We highlighted any medications that should be discontinued and/or not used in the reproductive age group and also treatments that may be continued, avoiding the withdrawal of drugs that can be used in the different phases, thus preventing the risk of increasing disease activity and flares before, during, and after pregnancy in SpA patients. The best management of pregnancy in patients with SpA is based on knowledge of updated drug recommendations, a careful and wise evaluation of the risks/benefits of starting or continuing treatment from the SpA diagnosis in a woman of childbearing age through pregnancy and lactation, and sharing therapeutic choices with other healthcare providers (in particular, gynecologists/obstetricians) and the patient.

The effect of education provided with the escape room game on nursing students' learning of parenteral drug administration

AimThe present study was conducted to determine the effect of education provided to first-year nursing students with the escape room game on their learning of parenteral drug administration. BackgroundThe use of escape room games in education supports formal education in providing students with professional knowledge and skills. DesignA randomized controlled study design was used in this study. MethodThe current study was conducted with 72 first-year nursing students. Data were collected with the Descriptive Characteristics Questionnaire (DCQ), Parenteral Drug Administration Information Test (PDAIT), Parenteral Drug Administration Sub-Checklists (PDASC) and Game Evaluation Form (GEF) between May and June 2022. The initial knowledge and skills of all students participating in the study were measured after completing the parenteral drug administration theoretical course and laboratory skills course. Students were assigned to the intervention (n=36) and control (n=36) groups by the stratified block randomization method according to their initial knowledge and skill measurements. Unlike the control group, the intervention group played the escape room game once in groups of four. The control group was allowed to work freely in the laboratory during this period. The final knowledge and skills of the intervention and control groups were measured immediately after the intervention. Students' skills were measured with an objective structured clinical examination. ResultsIt was determined that the post-test knowledge level of the students in the intervention group and their post-test skill mean scores for drug withdrawal from an ampoule, subcutaneous injection administration, intradermal injection administration and intravenous push drug administration were higher than those of the students in the control group (p<0.05). Additionally, Intervention group students evaluated the escape room game positively. ConclusionThis study concluded that the escape room game supported formal education and could be used in teaching parenteral drug administration.

The Effect of a Caffeine and Nicotine Combination on Nicotine Withdrawal Syndrome in Mice.

Nicotine dependence is an important cause of excessive exposure to tobacco combustion compounds in most smokers. Nicotine replacement therapy is the main method to treat nicotine dependence, but it still has its shortcomings, such as the inability to mitigate withdrawal effects and limited applicability. It has been hypothesized that a combination of low-dose nicotine and caffeine could achieve the same psychological stimulation effect as a high dose of nicotine without causing nicotine withdrawal effects. To establish a model of nicotine dependence, male C57BL/6J mice were subcutaneously injected four times a day with nicotine (2 mg/kg) for 15 days and fed with water containing nicotine at the same time. They were randomly divided into four groups. After 24 h of withdrawal, different groups were injected with saline, nicotine (0.25 mg/kg or 0.1 mg/kg), or nicotine (0.1 mg/kg) and caffeine (20 mg/kg). Behavioral and physiological changes were evaluated by an assessment of physical signs, open field tests, elevated plus maze experiments, forced swimming tests, hot plate tests, and new-object-recognition tests. The changes in dopamine release in the prefrontal cortex (PFC) and ventral tegmental area (VTA) in the midbrain were analyzed using ELISA. The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ability and pain thresholds, reduce anxiety and depression, enhance memory and cognitive ability, and increase the level of dopamine release in the PFC and VTA. Thus, caffeine combined with nicotine has potential as a stable and effective treatment option to help humans with smoking cessation.

A protocol for enhancing the diagnostic accuracy and predictive validity of neonatal opioid withdrawal syndrome: The utility of non-invasive clinical markers.

Every 15 minutes in the US, an infant exposed to opioids is born. Approximately 50% of these newborns will develop Neonatal Opioid Withdrawal Syndrome (NOWS) within 5 days of birth. It is not known which infants will develop NOWS, therefore, the current hospital standard-of-care dictates a 96-hour observational hold. Understanding which infants will develop NOWS soon after birth could reduce hospital stays for infants who do not develop NOWS and decrease burdens on hospitals and clinicians. We propose noninvasive clinical indicators of NOWS, including newborn neurobehavior, autonomic biomarkers, prenatal substance exposures, and socioeconomic environments. The goals of this protocol are to use these indicators shortly after birth to differentiate newborns who will be diagnosed with NOWS from those who will have mild/no withdrawal, to determine if the indicators predict development at 6 and 18 months of age, and to increase NOWS diagnostic sensitivity for earlier, more accurate diagnoses.

What are the reasons for injected methadone use? A qualitative study of people who use drugs parenterally in Barcelona.

Oral methadone maintenance is a widely adopted and effective treatment for heroin and other opioid dependencies. However, injectable methadone usage may pose greater risks than heroin itself. Despite decades of oral methadone treatment in Spain, there is limited understanding of the motivations for parenteral consumption. This study aimed to examine the reasons for methadone injection, delineate its specific advantages and disadvantages compared with those of heroin use, and assess the benefits and drawbacks of supervised methadone injection within a harm reduction service from the perspective of people who inject drugs. A qualitative phenomenological study was conducted in 11 patients at a safe injection facility in Barcelona. Semistructured interviews revealed that the reasons for injecting methadone were its provision of a euphoric rush, the pleasurable sensation of needle insertion, and the avoidance of gastrointestinal discomfort associated with oral methadone use. The main attraction of methadone injection was its accessibility as a legal and fully state-funded treatment option in Spain, coupled with its effectiveness in relieving withdrawal symptoms. However, notable disadvantages included the risks inherent in injection. The benefits of supervised consumption rooms were its provision of immediate medical assistance in overdose situations, ease of access, and physical safety. Drawbacks included waiting times, limited opening hours, neighborhood stigmatization, and the distance people who inject methadone had to travel when obtaining methadone from the illicit market. Based on these findings, we make several recommendations aimed at reducing the harm associated with methadone injection and emphasize the need for comprehensive harm reduction strategies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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 > 36h, a hospitalization > 9days, 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 ≥ 40years 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 ≥ 100mg/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.

Anti-anxiety and anti-depressive effects of Thai Mucuna pruriens seed aqueous extract against ethanol withdrawal syndrome in mice

BackgroundThai Mucuna pruriens (T-MP) has been used as a traditional medicine for treating many neurological conditions due to its antioxidant and neurorestorative properties. Aim of the studyThis study was to explore the effects of T-MP seed extract on ethanol withdrawal syndrome (EWS) in mice. MethodsMice were administered either normal saline solution (NSS) or 2 g/kg of 20% ethanol intraperitoneally once daily for 10 days. Behavioral symptoms of EWS were evaluated at 12-, 24-, and 36-hours after the last dose of ethanol using the elevated plus maze (EPM), light-dark box (LDB), and tail suspension test (TST). After determining the best time interval to detect EWS, a new set of mice were induced to have EWS, at 23 h after the last ethanol dose, mice were treated with either NSS (PO), diazepam (4 mg/kg, IP), or T-MP seed extract (600 mg/kg, PO). Behavioral tests were conducted one hour after treatment. ResultsIn the ethanol withdrawal mice, anxiety- and depressive-like behavior representing EWS were seen in LDB, EPM and TST, especially at the 24-hour after the final ethanol dose. At 36-hour after the final ethanol dose, although the anxiety-like behavior could be seen in LDB and EPM, whereas no significant depressive-like in TST was observed. Treatment with DZP or T-MP could significantly reduce the anxiety- and depressive-like symptoms of EWS at 24-hour after last dose of ethanol. In addition, treatment with T-MP, but not DZP, significantly reduced the total immobility time when compared to the control ethanol withdrawal group. ConclusionAccording to this study, it was discovered that T-MP seed extract could potentially offer a beneficial effect in managing anxiety- and depression-like behaviors in EWS in mice.

The "Micro"cosm: Magnifying the Nuance of Low Dose Buprenorphine Inductions.

Now that the X-wavier is a thing of the past, patients with Opioid Use Disorder (OUD) who previously lacked access to buprenorphine may have access to lower barrier care and may be looking to make the transition from either methadone or illicit fentanyl to buprenorphine. This can be quite challenging and both fentanyl and methadone are hihghly potent drugs and can result in a difficult transtition to buprenorphine. A transition from high potency opioids to buprenorphine is challenging and can cause discomfort or withdrawal in patients. Procedures/data/observations: Patients tend to have a difficult time when undergoing a transition from significant fentanyl use (> 1 bundle/day) or high dose methadone to buprenorphine. Over the last year, we've supported this transition for our hospitalized patients and have learned some tips and tricks to ease the transitions. Through our work we've come up with a strategy to transition patients that includes utilizing full mu agonists while initiating a low dose buprenorphine induction. We have developed an informal protocol for this transition that takes advantage of the flexibility of low dose buprenorphine induction strategies and includes the use of non-opioid adjuvant medications to control symptoms of discomfort and withdrawal. A transition from the use of significant fentanyl or high dose methadone to buprenorphine is possible and can take place over a matter of a few days. Such a transition requires careful attention to patient symptoms, availability of as needed short acting opioids, and the judicious use of non-opioid adjuvants.

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.

Buprenorphine for the Treatment of Pain in Cancer Patients.

Opioids remain the cornerstone for the treatment of moderate to severe cancer pain. Due to benefits over full agonist opioids (FAO), buprenorphine has emerged as an alternative treatment. Buprenorphine is only approved for the treatment of pain that is chronic non-cancer. Cancer-related pain is often progressive with breakthrough pain. There is limited evidence for using short-acting FAO in combination with buprenorphine. There are concerns about withdrawal and the efficacy of pain control using buprenorphine. We hypothesize buprenorphine, in combination with short-acting FAOs, can adequately control cancer- related pain without causing withdrawal symptoms. Procedures/data/observations: Our prospective, single-arm, open-label study enrolls patients with cancer-related pain who are on buprenorphine in combination with an FAO at > 30 mg OME/day, either requiring long-acting pain relief or their pain is not controlled with an FAO alone. Our study is ongoing, with 15 patients enrolled and a target of 50. The patient's pain is self-assessed daily using a mobile application. Withdrawal is assessed regularly using a modified Clinical Opioid Withdrawal Scale (COWS) score. Buprenorphine appears to be effective for the treatment of cancer pain without causing withdrawal in combination with short-acting FAO >30 mg/day.

Hospital Readmissions Among Infants With Neonatal Opioid Withdrawal Syndrome

Although cases of neonatal opioid withdrawal syndrome (NOWS) increased 5-fold in recent years, no study has examined national hospital readmission rates for these infants. To examine hospital readmissions for infants with and without NOWS. This retrospective cohort study analyzed serial cross-sectional samples of US hospital discharge records from the Nationwide Readmissions Database for calendar years 2016 to 2020. Infants with NOWS were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes. The data analysis was performed between January 5, 2023, and May 6, 2024. Neonatal opioid withdrawal syndrome. Survey-weighted logistic regression was used to examine 90-day all-cause and cause-specific hospital readmissions. Multivariable models adjusted for sex, low birth weight, gestational age, multiple gestation, type of insurance, and year of birth. Of the 13 855 246 newborns identified in this weighted analysis, 89 018 (0.6%) were diagnosed with NOWS, of whom 53.8% were male and 81.1% born full-term (>36 weeks gestation). The 90-day all-cause readmission rate was 4.2% for infants with NOWS compared with 3.0% for those without NOWS (P < .001). After risk adjustment, the odds of all-cause readmission were higher among infants with NOWS (adjusted odds ratio [AOR], 1.18; 95% CI, 1.08-1.29). Infants with NOWS had significantly higher odds of readmissions for seizures (AOR, 1.58; 95% CI, 1.01-2.46), failure to thrive (AOR, 1.99; 95% CI, 1.36-2.93), traumatic brain injury (AOR, 2.95; 95% CI, 1.76-4.93), and skull fractures (AOR 3.72; 95% CI, 2.33-5.93). Infants with NOWS had higher odds of receiving a diagnosis of confirmed maltreatment (AOR, 4.26; 95% CI, 2.19-8.27), including for neglect (AOR, 14.18; 95% CI, 5.55-36.22) and physical abuse (AOR, 2.42; 95% CI, 0.93-6.29); however, the latter finding was not statistically significant. In this nationally representative cohort study, infants with NOWS were at increased risk of readmission for any cause as well as for trauma and confirmed maltreatment. These findings may in part reflect the dual stressors that mothers with opioid use disorder face in caring for a newborn with NOWS in the context of a substance use disorder and underscore the need for family-based, in-home services that focus concurrently on substance use treatment and parenting support.

Reducing 30-Day Readmissions in Patients With Alcohol Use Disorder

The 30-day hospital readmission rate for alcohol use disorder (AUD) at a Veteran’s Affairs hospital is 2% higher than the national benchmark. This quality improvement project aimed to implement a holistic approach to care of veterans with AUD through optimization of the Clinical Institute Withdrawal Assessment for Alcohol Scale-Revised protocol and development of a revised and evidence-based alcohol withdrawal syndrome order set. After implementation, there was a statistically significant decrease in 30-day readmissions and an increase in prescription of adjuvant therapies such as gabapentin and hydroxyzine. This quality improvement project improved the processes of care related to treatment of veterans with AUD admitted with alcohol withdrawal syndrome.

Food and Drug Administration (FDA) Approvals of Biological Drugs in 2023.

An increase in total drug (small molecules and biologics) approvals by the Food and Drug Administration (FDA) was seen in 2023 compared with the previous year. Cancer remained the disease most targeted by monoclonal antibodies (mAbs), followed by autoimmune conditions. Our data reveal the prevalence of approvals for biologics even during years when the total number of authorizations was low, such as in 2022. Over half the drugs that received the green light in 2023 benefited from expedited programs, as the incidence of many diseases increased. In addition, over half of the biologics approved received Orphan Drug Designation from the FDA. This narrative review delves into details of the most significant approvals in 2023, including mAbs, enzymes, and proteins, explaining their mechanisms of action, differences from previous drugs, placebo, and standards of care, and outcomes in clinical trials. Given the varying number of drugs authorized annually by the U.S. health authority, this review also examines the limits of external influences over the FDA's decisions and independence regarding drug approvals and withdrawals.

Distinct Trajectories of Prescription Opioid Exposure in Pregnancy and Risk of Adverse Birth Outcomes.

The aim of this study was to identify distinct trajectories of prescription opioid exposure in pregnancy-encompassing both medication for opioid use disorder (MOUD) and opioid analgesics-and explore their associations with birth outcomes. Trajectories were identified using latent class analysis among Wisconsin Medicaid-insured live births 2011-2019. Logistic regression estimated associations between these trajectories and neonatal opioid withdrawal syndrome (NOWS), small for gestational age, preterm birth, birth weight, and gestational age. Of 138,123 births, 27,293 (19.8%) had prenatal opioid exposure. Five trajectory classes were identified: (1) stable MOUD treatment (5.8%), (2) inconsistent MOUD treatment (3.9%), (3) chronic analgesic use (4.2%), (4) intermittent analgesic use (7.8%), and (5) low-level use of MOUD and analgesics (78.3%). NOWS incidence per 1000 infants was 667 for class 1 (adjusted odds ratio [aOR]: 21.74, 95% confidence interval [CI]: 17.89, 26.41), 570 for class 2 (aOR: 15.35, 95% CI: 12.49, 18.87), 235 for class 3 (aOR: 19.42, 95% CI: 15.93, 23.68), 67 for class 4 (aOR: 6.23, 95% CI: 4.99, 7.76), and 12 for class 5 (aOR: 1.73, 95% CI: 1.47, 2.02). Classes 1-4 had elevated risk of small for gestational age, preterm birth, lower birth weight, and shorter gestational age, with no significant differences among these classes. Among individuals with opioid use disorder, stable MOUD treatment was associated with higher birth weights and longer gestational ages compared to inconsistent treatment, despite higher odds of NOWS. Early initiation and consistent MOUD treatment may improve birth weight and gestational age. For pregnant individuals with opioid use disorder using chronic analgesics, transition to MOUD may promote birth outcomes.