Pathological polarizations from microglia to astrocyte contributes to spatial memory deficit in methamphetamine abstinence mice.

Previously, we found that dCA1 A1-like polarization of astrocytes contributes a lot to the spatial memory deficit in methamphetamine abstinence mice. However, the underlying mechanism remains unclear, resulting in a lack of promising therapeutic targets. Here, we found that methamphetamine abstinence mice exhibited an increased M1-like microglia and A1-like astrocytes, together with elevated levels of interleukin 1α and tumor necrosis factor α in dCA1. In vitro, the M1-like BV2 microglia cell medium, containing high levels of Interleukin 1α and tumor necrosis factor α, elevated A1-like polarization of astrocytes, which weakened their capacity for glutamate clearance. Locally suppressing dCA1 M1-like microglia activation with minocycline administration attenuated A1-like polarization of astrocytes, ameliorated dCA1 neurotoxicity, and, most importantly, rescued spatial memory in methamphetamine abstinence mice. The effective time window of minocycline treatment on spatial memory is the methamphetamine exposure period, rather than the long-term methamphetamine abstinence.

Increased Excitability and Synaptic Plasticity of Drd1- and Drd2-Expressing Prelimbic Neurons Projecting to Nucleus Accumbens after Heroin Abstinence Are Reversed by Cue-Induced Relapse and Protein Kinase A Inhibition.

Dysregulation of the input from the prefrontal cortex (PFC) to the nucleus accumbens (NAc) contributes to cue-induced opioid seeking but the heterogeneity in, and regulation of, prelimbic (PL)-PFC to NAc (PL->NAc) neurons that are altered has not been comprehensively explored. Recently, baseline and opiate withdrawal-induced differences in intrinsic excitability of Drd1+ (D1+) versus Drd2+ (D2+) PFC neurons have been demonstrated. Thus, here we investigated physiological adaptations of PL->NAc D1+ versus D2+ neurons after heroin abstinence and cue-induced relapse. Drd1-Cre+ and Drd2-Cre+ transgenic male Long-Evans rats with virally labeled PL->NAc neurons were trained to self-administer heroin followed by 1 week of forced abstinence. Heroin abstinence significantly increased intrinsic excitability in D1+ and D2+ PL->NAc neurons and increased postsynaptic strength selectively in D1+ neurons. These changes were normalized by cue-induced relapse to heroin seeking. Based on protein kinase A (PKA)-dependent changes in the phosphorylation of plasticity-related proteins in the PL cortex during abstinence and cue-induced relapse to cocaine seeking, we assessed whether the electrophysiological changes in D1+ and D2+ PL->NAc neurons during heroin abstinence were regulated by PKA. In heroin-abstinent PL slices, application of the PKA antagonist (R)-adenosine, cyclic 3',5'-(hydrogenphosphorothioate) triethylammonium (RP-cAMPs) reversed intrinsic excitability in both D1+ and D2+ neurons and postsynaptic strength in only D1+ neurons. Additionally, in vivo bilateral intra-PL infusion of RP-cAMPs after abstinence from heroin inhibited cue-induced relapse to heroin seeking. These data reveal that PKA activity in D1+ and D2+ PL->NAc neurons is not only required for abstinence-induced physiological adaptations but is also required for cue-induced relapse to heroin seeking.SIGNIFICANCE STATEMENT Neuronal plasticity in the medial prefrontal cortex is thought to underlie relapse to drug seeking, yet the subpopulation of neurons that express this plasticity to functionally guide relapse is unclear. Here we show cell type-specific adaptations in Drd1-expressing versus Drd2-expressing prelimbic pyramidal neurons with efferent projections to nucleus accumbens. These adaptations are bidirectionally regulated during abstinence versus relapse and involve protein kinase A (PKA) activation. Furthermore, we show that disruption of the abstinence-associated adaptations via site-specific PKA inhibition abolishes relapse. These data reveal the promising therapeutic potential of PKA inhibition for preventing relapse to heroin seeking and suggest that cell type-specific pharmacologies that target subpopulations of prefrontal neurons would be ideal for future therapeutic developments.

Alcohol Rehabilitation Within 3 Months After Alcohol Hepatitis and Survival - A National Analysis.

BACKGROUND & AIMS: There is limited understanding of the benefits of alcohol rehabilitation after alcohol hepatitis (AH). METHODS: We conducted a 2012 to 2021 national longitudinal study involving adult inpatients diagnosed with AH in France. We assessed the primary outcome of liver transplantation or death within 1 year after AH, including in its complicated form (CAH) defined as ≥2 hepatic or extrahepatic complications within 4 weeks after AH. The primary exposure was in-hospital alcohol rehabilitation within 3 months following AH. Patients who died (6.5%; n = 5282) or were censored (12.5%; n = 10,180) ≤4 weeks after AH were excluded. We measured adjusted hazard ratios (aHRs) and adjusted odds ratios (aORs) within the full cohort and propensity-matched samples. RESULTS: Among 65,737 patients (median age, 52 years; interquartile range [IQR], 44-60 years; 76% male), 12% died or underwent liver transplantation. In-hospital alcohol rehabilitation was noted for 25% of patients (15.2% among patients with CAH) and was the primary discharge diagnosis for 13.3%. The 1-year transplant-free survival rates were 94% (95% confidence interval [CI], 94%-95%) for rehabilitated patients, compared with 85% (95% CI, 85%-86%) for those without (aHR, 0.62; 95% CI, 0.57-0.69; P < .001). Among patients with CAH, transplant-free survival was 78% (95% CI, 76%-81%) with rehabilitation vs 70% (95% CI, 69%-71%) without (aHR, 0.82; 95% CI, 0.68-0.98; P = .025). In propensity-matched samples, rehabilitation was linked to an aOR of 0.54 (95% CI, 0.49-0.55; P < .001) overall, and 0.73 (95% CI, 0.60-0.89; P = .002) among matched patients with CAH. CONCLUSIONS: In-hospital alcohol rehabilitation within 3 months after AH and CAH improve transplant-free survival rate but remain underutilized.

Screening for Fibrosis Promotes Lifestyle Changes: A Prospective Cohort Study in 4796 Individuals.

BACKGROUND AND AIMS: Early detection of liver fibrosis is believed to promote lifestyle changes. We evaluated self-reported changes in alcohol intake, diet, exercise, and weight after participating in a screening study for liver fibrosis. METHODS: We conducted a prospective screening study of individuals at risk of alcohol-related liver disease (ALD) or metabolic dysfunction-associated steatotic liver disease (MASLD). We provided lifestyle advice to all participants and evaluated lifestyle changes by questionnaires after 1 week and 6 months, with re-examination of a subgroup after 2 years. RESULTS: A total of 1850 at risk of ALD and 2946 at risk of MASLD were included, of whom 383 (8%) were screening positive (transient elastography ≥8 kPa). A total of 84% replied to the 6-month questionnaire. In ALD participants, excessive drinking decreased from 46% to 32% after 6 months. Only 15% reported increased drinking, without differences between screening positive and negative individuals (P = .698). In high-risk drinkers, a positive screening test predicted abstinence or decreased alcohol use after 6 months (odds ratio, 2.45; 95% confidence interval, 1.32-4.57; P = .005). After 2 years, excessive drinking decreased from 52% to 41% in a subgroup of 752 individuals and a positive screening test predicted abstinence or decreased alcohol use after 2 years (odds ratio, 1.84; 95% confidence interval, 1.09-3.11, P = .023). MASLD participants showed similar improvements: 35% improved their diet, 22% exercised more, and 13% reported a weight loss ≥5% after 6 months. CONCLUSIONS: Screening for liver fibrosis is associated with sustained improvements in alcohol consumption, diet, weight, and exercise in at-risk ALD and MASLD. The changes are most pronounced in screening positive participants but not limited to this group.

Gut and bladder fermentation syndromes: a narrative review.

We recently reported the first clinical case of bladder fermentation syndrome (BFS) or urinary auto-brewery syndrome, which caused the patient to fail abstinence monitoring. In BFS, ethanol is generated by Crabtree-positive fermenting yeast Candida glabrata in a patient with poorly controlled diabetes. One crucial characteristic of BFS is the absence of alcoholic intoxication, as the bladder lumen contains transitional epithelium with low ethanol permeability. In contrast, patients with gut fermentation syndrome (GFS) or auto-brewery syndrome can spontaneously develop symptoms of ethanol intoxication even without any alcohol ingestion because of alcoholic fermentation in the gut lumen. In abstinence monitoring, a constellation of laboratory findings with positive urinary glucose and ethanol, negative ethanol metabolites, and the presence of yeast in urinalysis should raise suspicion for BFS, whereas endogenous ethanol production needs to be shown by a carbohydrate challenge test for GFS diagnosis. GFS patients will also likely fail abstinence monitoring because of the positive ethanol blood testing. BFS and GFS are treated by yeast eradication of fermenting microorganisms with antifungals (or antibiotics for bacterial GFS cases) and modification of underlying conditions (diabetes for BFS and gut dysbiosis for GFS). The under-recognition of these rare medical conditions has led to not only harm but also adverse legal consequences for patients, such as driving under the influence (DUI). GFS patients may be at risk of various alcohol-related diseases.

A Dyadic Framework of Care for Opioid-exposed Birthing Persons and Their Infants and Children.

OBJECTIVE: To develop a dyadic-centered framework focused on clinical care, surveillance, and research for birthing persons with opioid use disorder (OUD) and their infants and children. STUDY DESIGN: Between February and March 2023, an analysis was conducted within the US Department of Health and Human Services (HHS) of activities directed at opioid-exposed birthing persons and their infants and children (the dyad) to identify: 1) number of activities, stratified by type and 2) characteristics across health and supportive activities that serve the dyad vs birthing persons or infants and children individually. Descriptive and thematic analyses were used to assess quantity and characteristics of fiscal year 2023-2024 activities aggregated across eleven HHS agencies. RESULTS: Of 181 activities examined, 75 met inclusion criteria specific to serving birthing persons with OUD and opioid-exposed infants and children. Sixty-two percent of activities were dyad focused. Five categories of dyadic activities were identified: research (45%), education and training (28%), health and supportive services (21%), surveillance (4%), and quality improvement (2%). Eight specific characteristics were key to dyadic activities: a life course and generational approach, emphasis on relationship, dyadic outcomes, service wraparound, payment structures supporting dyadic care, data linkage, and social determinants of health. CONCLUSIONS: This analysis of HHS activities directed at birthing persons with OUD and opioid-exposed infants and children showed that most programs had a dyadic focus. Synthesizing elements identified from activities serving the dyad facilitated the development of a dyadic framework integrating clinical care, public health surveillance, and research.

Effect of ejaculatory abstinence period on fertilization and clinical outcomes in ICSI cycles: a retrospective analysis.

RESEARCH QUESTION: Does ejaculatory abstinence impact fertilization outcomes in intracytoplasmic sperm injection (ICSI) cycles in infertile couples? DESIGN: This single-centre retrospective observational study included 6919 ICSI cycles from 2013 to 2022. The primary outcome was the assessment of oocyte fertilization, measured in terms of the rate of formation of two-pronuclear (2PN), 3PN and 1PN zygotes. Secondary outcomes were blastulation, cumulative positive ß-human chorionic gonadotrophin test and clinical pregnancy rates. Relationships between ejaculatory abstinence and fertilization outcomes, and ejaculatory abstinence and clinical outcomes were evaluated with multivariable analysis, including possible confounders. RESULTS: A positive association was observed between ejaculatory abstinence and semen sample volume (P < 0.001), sperm concentration (P < 0.001) and total motile sperm count (P < 0.001). No association was found between the 1PN zygote rate and ejaculatory abstinence (P = 0.97). Conversely, for each additional day of ejaculatory abstinence, the likelihood of obtaining 2PN zygotes from all inseminated oocytes decreased by 3% [adjusted odds ratio (aOR) 0.97, 95% CI 0.94-0.99], whilst the likelihood of obtaining 3PN zygotes from all inseminated oocytes increased significantly by 14% (aOR 1.14, 95% CI 1.07-1.22). No significant associations were found between ejaculatory abstinence and blastulation, cumulative pregnancy or miscarriage rates. CONCLUSIONS: A longer ejaculatory abstinence period significantly decreases the rate of 2PN zygotes, and increases the rate of 3PN zygotes without directly affect blastulation and pregnancy rates.

Is Abstinence from Alcohol and Smoking Associated with Less Anxiety and Depressive Symptoms Among People with HIV?

Achieving abstinence from alcohol, tobacco, or both may improve mental health, but is understudied in people with HIV (PWH). The St PETER HIV randomized clinical trial compared varenicline, cytisine, and nicotine replacement therapy on alcohol and smoking behavior among 400 PWH in Russia. The primary exposure was thirty-day point prevalence abstinence (PPA) from (1) alcohol, (2) smoking, (3) both, or (4) neither and was assessed at 1, 3, 6 and 12-months as were the study outcomes of anxiety (GAD-7) and depressive (CES-D) symptoms. The primary aim was to examine the association between smoking and/or alcohol abstinence and subsequent symptoms of depression and anxiety. Primary analysis used repeated measures generalized linear modeling to relate PPA with mental health scores across time. In secondary analyses, Kruskal-Wallis tests related PPA with mental health scores at each timepoint. Primary analyses did not identify significant differences in anxiety or depressive symptoms between exposure groups over time. Secondary analyses found CES-D scores across PPA categories were similar at 1-month (11, 10, 11, 11) and 6-months (10, 10, 11, 11) but differed at 3-months (9, 11, 10, 12; p = 0.035) and 12-months (10, 6, 11, 10; p = 0.019). GAD-7 scores did not vary across PPA categories at any time point. While abstinence was associated with fewer depressive symptoms at times, findings were not consistent during follow-up, perhaps reflecting intermittent relapse. PWH with polysubstance use and mental health comorbidity are complex, and larger samples with sustained abstinence would further elucidate effects of abstinence on mental health.

Approach Bias and Tobacco Craving as Mechanisms of the Effect of Approach Bias Retraining on Smoking Cessation.

INTRODUCTION: Approach bias, the automatic tendency to advance toward, rather than move away from appetitive cues, has been associated with greater tobacco cravings, dependence, and likelihood of smoking relapse. Approach bias retraining (ABR) has emerged as one way to reduce approach bias and promote avoidance toward smoking cues. Yet, additional research is needed to identify the mechanisms that may help explain the effect of ABR on smoking cessation. METHODS: The current study uses data collected as part of a randomized controlled trial to test two unique mechanisms of action ([1] approach bias and [2] tobacco craving) for the efficacy of standard smoking cessation treatment (ST) augmented by ABR on smoking abstinence. Participants were 96 adult daily smokers (Mage=43.1, SD=10.7) motivated to quit smoking. RESULTS: Results showed that lower approach bias and lower cravings at a treatment session were significantly related to next session smoking abstinence (p's<.018). Further, deviations in approach bias partially mediated the effect of ABR on smoking abstinence (ab=-12.17, 95%CI: [-29.67, -0.53]). However, deviations in tobacco craving did not mediate this relation (ab=.40, 95%CI: [-.27, 1.34]). CONCLUSIONS: The current findings add to extant literature by identifying approach bias as a mechanism of action of the effect of ABR on smoking abstinence during smoking cessation treatment. IMPLICATIONS: The current study adds to our knowledge on the effectiveness of approach bias retraining (ABR) as a part of smoking cessation treatment. Results indicate that reductions in approach bias partially mediate the effect of ABR on smoking abstinence. These findings are consistent with previous research on alcohol-dependent adults and underline the potential of ABR to reduce approach bias and promote smoking cessation among smokers. Such findings could inform the development of future research exploring more targeted and effective smoking cessation interventions, ultimately improving outcomes for individuals attempting to quit smoking.

Women's Pornography Use Patterns and Sexuality Education in U.S. Public Schools.

This study investigated the relationship between sexuality education in U.S. public schools and women's pornography use. Utilizing quantitative methods, we examined a sample of women attending U.S. public schools who reported regular pornography use. Results revealed that, regardless of the type of sexuality education received, women exhibited similar rates of pornography use, with 60% reporting its use. A substantial portion (69%) of the women began using pornography during childhood or adolescence. Women who received abstinence only sexuality education reported higher frequencies of pornography use compared to their comprehensive sexuality education counterparts. About 79% of women using pornography perceived it as a source of sexuality learning, especially regarding sexual pleasure. However, they expressed reluctance in using pornography for sexual education and did not consider it a preferred method for learning about sexuality. The findings suggest the need for comprehensive sexuality education that addresses essential topics, such as sexual pleasure and sexual script development, to cater to women's diverse learning needs, ideally taught by parents or primary caregivers, but may be necessary for public education in the absence of parental instruction. Policymakers and educators should bridge these gaps to develop more effective sexuality education curricula. This study contributes valuable insights, highlighting the importance of an inclusive approach to sexuality education in U.S. public schools. Future research should explore the implications of different sexuality education approaches on women's sexual development and well-being, emphasizing comprehensive education to foster healthy sexual behaviors among women.

Influence of sleep quality on lapse to alcohol use during a quit attempt.

AIMS: Sleep problems are common among individuals with alcohol use disorder (AUD) and is often associated with a heightened relapse risk. The present study examines the relationship between sleep and alcohol use among individuals with current AUD during a 6-day quit attempt as part of a medication study. METHODS: The current study is a secondary analysis of a medication trial for individuals with AUD. Individuals with AUD (N = 53, 26 females) were randomized to active medication or matched placebo. Randomized participants completed a week-long medication titration (Days 1-7). Following the titration period, participants attended an in-person visit (Day 8) to begin a 6-day quit attempt. During the quit attempt, participants completed daily diary assessments to report on previous day alcohol consumption, sleep quality, and alcohol craving. In the present study, medication condition was controlled for in all models. RESULTS: Baseline global sleep quality was not a significant predictor of drinks per drinking day (P = 0.72) or percent days abstinent (P = 0.16) during the 6-day practice quit attempt. Daily diary analyses found that greater sleep quality was associated with higher next-day drinks per drinking day (b = 0.198, P = 0.029). In contrast, participants reported worse sleep quality following nights of greater alcohol intake, albeit at a trend-level (b = -0.12, P = 0.053). CONCLUSIONS: These results suggest that better sleep quality was a risk factor for drinking during the 6-day quit period, such that better sleep may be associated with increased craving for alcohol and alcohol use the next day. These findings are limited to the early abstinence period and should be considered in studies exploring longer periods of abstinence.

Effect of rifampicin on TLR4-signaling pathways in the nucleus accumbens of the rat brain during abstinence of long-term alcohol treatment.

AIMS: The treatment with the antibiotic rifampicin (Rif) led to a decrease in the frequency of neurodegenerative pathologies. There are suggestions that the mechanism of action of Rif may be mediated by its effect on toll-like receptor (TLR)4-dependent pathways. We evaluated the expression status of TLR4-dependent genes during abstinence from long-term alcohol treatments in the nucleus accumbens (NAc) of the rat brain, and also studied the effects of Rif to correct these changes. METHODS: The long-term alcohol treatment was performed by intragastric delivery of ethanol solution. At the end of alcohol treatment intraperitoneal injections of Rif (100 mg/kg) or saline were made. Extraction of the brain structures was performed on the 10th day of abstinence from alcohol. We used the SYBR Green qPCR method to quantitatively analyze the relative expression levels of the studied genes. RESULTS: The long-term alcohol treatment promotes an increase in the level of TLR4 mRNA and mRNA of its endogenous ligand high-mobility group protein B1 during abstinence drop alcohol in NAc of rats. The use of Rif in our study led to a decrease in the increased expression of high-mobility group protein B1, Tlr4, and proinflammatory cytokine genes (Il1ß, Il6) in the NAc of the rat brain during abstinence of long-term alcohol treatment. In addition, Rif administration increased the decreased mRNA levels of anti-inflammatory cytokines (Il10, Il11). CONCLUSION: The data obtained indicate the ability of Rif to correct the mechanisms of the TLR4 system genes in the NAc of the rat brain during alcohol abstinence.

Effectiveness of a self-help guide during a temporary alcohol abstinence challenge: a randomized controlled trial.

BACKGROUND: The popularity of temporary abstinence challenges (TACs) concerning alcohol consumption is increasing. Support is found to be essential for participants to help them get through a challenge. This study aimed to evaluate the additional effect of a self-help guide, based on health behaviour theories and behaviour change techniques, on (i) successful completion of a TAC and (ii) changes in drinking refusal self-efficacy (DRSE), behavioural automaticity, craving, and alcohol consumption. METHODS: A randomized controlled trial was performed (OSF registries: OSF.IO/B95VU). NoThanks participants received a questionnaire before the TAC (T0) and 8 months after the TAC (T1). Out of a subgroup of 1308 respondents who were interested in additional support, 652 were randomly assigned to receive the guide (experimental group), and 656 did not receive any additional support (control group). Logistic regressions and (generalized) linear mixed model analyses were used. RESULTS: After 8 months, all participants showed a significant decrease in behavioural automaticity, craving, and alcohol consumption, irrespective of group assignment. No significant changes were observed in the DRSE. This degree of change over time in behavioural automaticity, craving, and alcohol consumption did not differ between the experimental and control group. Sensitivity analyses with participants in the experimental group, who differed in exposure to the guide, did not show differences either. CONCLUSION: The self-help guide, and how it was designed, added no value to the TAC. Future research should focus on more bottom-up, customized support and explore what (different subgroups of) participants think they need as extra support during a TAC.

Comparison of the effect of phenobarbital & levetiracetam in the treatment of neonatal abstinence syndrome (NAS) as adjuvant treatment in neonates admitted to the neonatal intensive care unit: a randomized clinical trial.

BACKGROUND: Infants who are born from mothers with substance use disorder might suffer from neonatal abstinence syndrome (NAS) and need treatment with medicines. One of these medicines is phenobarbital, which may cause side effects in long-term consumption. Alternative drugs can be used to reduce these side effects. This study seeks the comparison of the effects of phenobarbital & levetiracetam as adjuvant therapy in neonatal abstinence syndrome. METHODS: This randomized clinical trial was performed in one year from May 2021 until May 2022. The neonates who were born from mothers with substance use disorder and had neonatal abstinence syndrome in Afzalipoor Hospital of Kerman were studied. The treatment started with morphine initially and every four hours the infants were checked. The infants who were diagnosed with uncontrolled symptoms After obtaining informed consent from the parents were randomly divided into two groups and treated with secondary drugs, either phenobarbital or levetiracetam. RESULTS: Based on the obtained results, it was clear that there was no significant difference between the hospitalization time of the two infant groups under therapy (phenobarbital: 18.59 days versus Levetiracetam 18.24 days) (P-value = 0.512). Also, there was no significant difference between both groups in terms of the frequency of re-hospitalization during the first week after discharge, the occurrence of complications, and third treatment line prescription (P-value = 0.644). CONCLUSIONS: Based on the obtained results, like hospitalization duration time (P-value = 0.512) it seems that levetiracetam can be used to substitute phenobarbital in treating neonatal abstinence syndrome. TRIAL REGISTRATION: The current study has been registered in the Iran registry of clinical trials website (fa.irct.ir) on the date 25/2/2022 with registration no. IRCT20211218053444N2.

Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

INTRODUCTION: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. MATERIAL AND METHODS: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. RESULTS: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. CONCLUSIONS: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

Neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence.

AIMS: Abuse of methamphetamine has aroused concern worldwide. Stimulant use and sexual behaviours have been linked in behavioural and epidemiological studies. Although methamphetamine-related neurofunctional differences are reported in previous studies, only few studies have examined neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence. METHODS: Neurofunctional changes were measured using a cue-reactivity task involving methamphetamine, sexual, and neutral cues in 20 methamphetamine abusers who were evaluated after a short- (1 week to 3 months) and long-term (10-15 months) abstinence. RESULTS: Five brain regions mainly involved in the occipital lobe and the parietal lobe were found with the group-by-condition interaction. Region-of-interest analyses found higher sexual-cue-related activation than other two activations in all five brain regions in the long-term methamphetamine abstinence group while no group differences were found. Negative relationships between motor impulsivity and methamphetamine- or sexual-cue-related activations in the left middle occipital gyrus, the superior parietal gyrus and the right angular gyrus were found. CONCLUSIONS: The findings suggested that methamphetamine abstinence may change the neural response of methamphetamine abusers to methamphetamine and sexual cues, and the neurofunction of the five brain regions reported in this study may partly recover with long-term methamphetamine abstinence. Given the use and relapse of methamphetamine for sexual purposes, the findings of this study may have particular clinical relevance.

Process evaluation of the Belgian one-month-without alcohol campaign 'Tournée Minérale': a mixed method approach.

BACKGROUND: The Tournée Minérale campaign [TMC] is a mass media prevention campaign challenging Belgian adults to refrain from alcohol during one month. A process evaluation may help us better understand the effect of TMC and to formulate recommendations for future editions. The current study aimed to examine reach, experiences, perceived effectiveness and maintenance of TMC. METHODS: A mixed method design was used to assess the process, using pre- and post-questionnaires (n = 49.022, 44.5 ± 13.1 years old, 37.0% men) and focus groups (n = 31, 47.3 ± 14.3 years old, 33.3% men). RESULTS: Most campaign materials were considered useful and/or motivating. Facilitators for taking part in TMC were connectedness with other participants, stimulus control (e.g. removing alcohol at home) and a supportive social environment. Most difficulties were encountered with abstaining during social occasions as participants had to change a habit or find alternative non-alcoholic beverages. Participants reported both beneficial (e.g. sleeping better) and adverse effects (e.g. drinking more soft drinks). CONCLUSIONS: Future editions of TMC should try to decrease perceived adverse effects (e.g. by providing attractive non-alcoholic beverages) and can benefit from having a forum where people can share experiences.

How a 5-Day Stay in the Tobacco-Free Environment of the Stoptober House Supports Individuals to Quit Smoking: A Mixed Methods Pilot Study.

INTRODUCTION: The Stoptober House is part of the annual national Stoptober smoking cessation campaign in the Netherlands. During the first week of October, 48 volunteers resided in the tobacco-free Stoptober House for 5 days and received smoking cessation counseling. This pilot study explored how the Stoptober House may have facilitated smoking cessation among participants. METHODS: We included 48 individuals who were selected for the Stoptober House (intervention group) and 67 individuals who were not selected (control group). Surveys were conducted at baseline, immediately after 2 and 8 weeks of post-intervention. We compared self-reported abstinence, psychosocial mediators related to smoking cessation, and perceived active elements of the Stoptober House between the intervention and control groups using t/χ2 tests and linear mixed model (LMM) analysis. Sixteen semi-structured qualitative interviews were conducted to explore participants' perspectives on the elements contributing to their success in quitting smoking. RESULTS: At 8 weeks of follow-up, a higher proportion of participants in the intervention group (24/48 [50%]) reported being abstinent compared to the control group (5/67 [7%]; p < 0.001). Among participants who reported making a quit attempt, 22/38 (57.9%) in the intervention group remained abstinent compared to 4/17 (23.5%) in the control group (p = 0.022). The intervention group also exhibited higher self-efficacy to quit smoking throughout the follow-up period and higher social support immediately after the Stoptober House. No significant differences were observed in other psychosocial factors. The interviews highlighted several perceived elements of the Stoptober House that contributed to smoking cessation success, including restricted smoking opportunities, access to smoking cessation counselors, and peer support. CONCLUSION: This pilot study suggests that the Stoptober House provides support that can help people quit smoking. Further research is needed to confirm these findings and determine the cost-effectiveness of this intervention in promoting long-term abstinence among specific groups of smokers.

Implications of Switching from Conventional to Electronic Cigarettes on Quality of Life and Smoking Behaviour: Results from the EQualLife Trial.

INTRODUCTION: Electronic cigarettes and "vaping" have become popular since their appearance in Europe and the USA in approximately 2006. They are often perceived as having fewer health risks than conventional cigarettes, which makes them of interest as a support tool in smoking cessation. However, its efficacy regarding cessation or reduction of smoking under real-life conditions remains controversial. Our objective was to clarify this question in an observational study of smoking habits after initiating vaping without targeted intervention, as compared to a validated cessation programme. METHODS: From October 2015 to April 2018, 80 subjects (60 in the e-cigarette group and 20 in the supervised smoking cessation group) were included in two trial visits, one at the start of the trial and the second after 3 months, plus 4 questionnaire surveys: at the start of the trial and after a 1, 2, and 3 month period. The questionnaire included a nicotine use inventory, a modified Fagerström test for nicotine dependence, and the WHO-QOL-BREF survey. RESULTS: E-cigarettes were effective, leading to a significant (p < 0.03) reduction (p < 0.03) in tobacco consumption and nicotine dependence, with an abstinence rate of 43% after 3 months. Compared to participants in the smoking cessation programme, their use was not associated with an improvement in quality of life during the quitting attempt, and there were no significant differences in clinical symptoms between groups. The reduction in nicotine dependence was more pronounced (p < 0.012) for the smoking cessation programme, with higher abstinence rates (p = 0.011 after 12 weeks) and lower (p < 0.003) remaining tobacco consumption compared to electronic cigarettes. DISCUSSION/CONCLUSIONS: The use of electronic cigarettes reduced nicotine dependence and tobacco consumption, but a supervised smoking cessation programme was superior in terms of achieved cessation in both regards. Electronic cigarettes did not improve the quality of life. Since e-cigarettes could be associated with long-term health risks, their usefulness in smoking cessation remains questionable, and a professionally guided and validated smoking cessation programme still appears to be superior and preferable, in terms of achieved cessation. Although this trial is limited regarding the number of participants and follow-up time, it highlights the need for additional, large clinical trials evaluating the efficacy of e-cigarettes for smoking cessation in comparison to a professionally guided smoking cessation programme.

Orbitofrontal cortex and dorsal striatum functional connectivity predicts incubation of opioid craving after voluntary abstinence.

We recently introduced a rat model of incubation of opioid craving after voluntary abstinence induced by negative consequences of drug seeking. Here, we used resting-state functional MRI to determine whether longitudinal functional connectivity changes in orbitofrontal cortex (OFC) circuits predict incubation of opioid craving after voluntary abstinence. We trained rats to self-administer for 14 d either intravenous oxycodone or palatable food. After 3 d, we introduced an electric barrier for 12 d that caused cessation of reward self-administration. We tested the rats for oxycodone or food seeking under extinction conditions immediately after self-administration training (early abstinence) and after electric barrier exposure (late abstinence). We imaged their brains before self-administration and during early and late abstinence. We analyzed changes in OFC functional connectivity induced by reward self-administration and electric barrier-induced abstinence. Oxycodone seeking was greater during late than early abstinence (incubation of oxycodone craving). Oxycodone self-administration experience increased OFC functional connectivity with dorsal striatum and related circuits that was positively correlated with incubated oxycodone seeking. In contrast, electric barrier-induced abstinence decreased OFC functional connectivity with dorsal striatum and related circuits that was negatively correlated with incubated oxycodone seeking. Food seeking was greater during early than late abstinence (abatement of food craving). Food self-administration experience and electric barrier-induced abstinence decreased or maintained functional connectivity in these circuits that were not correlated with abated food seeking. Opposing functional connectivity changes in OFC with dorsal striatum and related circuits induced by opioid self-administration versus voluntary abstinence predicted individual differences in incubation of opioid craving.