Severe Withdrawal Research Articles

Oral ethanol prescribing for alcohol withdrawal syndrome: initial findings and future directions following implementation within a United Kingdom National Health Service setting

Introduction Prescribing of ethanol may be an alternative to benzodiazepines for managing alcohol withdrawal syndrome. We present our experience of oral ethanol prescribing within an acute United Kingdom National Health Service setting. Methods A retrospective review of patients presenting with alcohol withdrawal who were managed with oral ethanol or benzodiazepines was performed from data collected across two acute care settings. Ethanol prescribing inclusion: high risk of delirium tremens, or a history of harmful alcohol consumption (typically ≥30 units/day; in which 1 unit = 8 grams of alcohol; one standard United States drink = 14 grams of alcohol) or known to have a history of severe alcohol withdrawal, alcohol-related seizures or delirium tremens. Inverse propensity score weighting was used to partially account for variance between the two patient populations. Results Fifty (82 per cent male; average age 50.9 years) and 93 (84 per cent male; average age 46.5 years) patients in receipt of benzodiazepines or ethanol, respectively, were included. The likelihood of hospital admission was significantly reduced when individuals were managed with ethanol (odds ratio 0.206 (95 per cent confidence interval; 0.066-0.641), Wald chi-square P = 0.006). In those not admitted, the treatment type had no significant impact on length of stay or the number of occasions a pharmacological agent was required. In those admitted, treatment had no significant effect on length of stay. Discussion We offer preliminary evidence to support a role of oral ethanol in the management of patients with alcohol withdrawal. We have implemented a robust and translatable guideline. Despite limitations in the data set the impact of ethanol in reducing the likelihood of admission remained significant. Conclusions In individuals at significant risk of severe alcohol withdrawal, prescribing ethanol as part of a comprehensive care plan, may reduce unplanned admissions. The preliminary findings presented here warrant further assessment through prospective studies.

Impact of an alcohol withdrawal screening and treatment protocol for hospitalized patients

IntroductionAlcohol Withdrawal Syndrome (AWS) is a potentially life-threatening complication of alcohol use disorder (AUD) that can be challenging to recognize in hospitalized patients. Our institution implemented universal AUD screening for all patients admitted to a non-critical care venue using the Prediction of Alcohol Withdrawal Severity Scale (PAWSS). At risk patients were then further assessed, utilizing the Glasgow Modified Alcohol Withdrawal Scale (GMAWS), and medicated according to a predetermined protocol. This study sought to determine whether this protocol decreased hospital length of stay, lowered the total benzodiazepine dose administered, and decreased adverse events attributable to AWS. MethodsThis retrospective cohort study was conducted over a 6-year period from 2014 to 2020. The study included patients with an ICD-10 code diagnosis of AWS and subsequently divided them into two groups: pre- and post-protocol introduction. Outcome measures were compared pre- versus post-protocol introduction. ResultsThere were 181 patient encounters pre- and 265 patient encounters post-protocol. There was no statistically significant difference in median length of stay between the two groups (2.956 days pre and 3.250 days post-protocol, p = 0.058). Post-protocol, there was a statistically significant reduction in median total benzodiazepine dose (13.5 mg and 9 mg lorazepam equivalents pre- and post-protocol, p < 0.001) and in occurrence of delirium tremens (7.7 % pre and 2.3 % post-protocol, p = 0.006). ConclusionProtocol implementation did not reduce length of stay in patients with AUD but was associated with a significant reduction in total benzodiazepine dose and, when adjusted, a non-statistically significant decrease in progression to delirium tremens in hospitalized patients, after applying Bonferroni adjustment.

A master regulator of opioid reward in the ventral prefrontal cortex.

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express μ-opioid receptors (μORs). Disrupting μOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.

Evaluation of the Use of Phenobarbital and Benzodiazepines in the Management of Alcohol Withdrawal Syndrome in Patients Requiring Neurological/Neurosurgical Critical Care: A Propensity-Matched Analysis.

Objective There is growing interest in the use of phenobarbital for alcohol withdrawal syndrome in critically ill patients, though experience in neurologically injured patients is limited. The purpose of this study was to compare the safety and effectiveness of phenobarbital-containing alcohol withdrawal regimens versus benzodiazepine monotherapy in the neurocritical care unit. Methods We conducted a retrospective cohort study of adult patients admitted to the neurocritical care unit from January 2014 through November 2021 who received pharmacologic treatment for alcohol withdrawal. Treatment groups were defined as benzodiazepine monotherapy versus phenobarbital alone or in combination with benzodiazepines. The primary outcome was the percentage of patients requiring intubation after receiving alcohol withdrawal treatment. Secondary outcomes included all-cause, in-hospital mortality, intensive care unit length of stay, discharge disposition, change in Glasgow Coma Scale (GCS) score, and the use of adjunctive agents. Results We analyzed data from 156 patients, with 77 (49%) in the benzodiazepine group and 79 (51%) in the phenobarbital combination group. The groups were well-balanced for baseline characteristics, though more males (67, 85%) were in the phenobarbital group. Only three (1.9%) patients received phenobarbital monotherapy, and the rest (153, 98.1%) received combination therapy. The percentage of patients requiring mechanical ventilation was significantly higher in the phenobarbital combination group compared to benzodiazepine monotherapy (39% (n=31) versus 13% (n=10); OR: 4.33, 95% CI: 1.94-9.66; p<0.001). The use of adjunctive propofol and dexmedetomidine was higher in the phenobarbital group (propofol 35% (n= 28) versus 9% (n=7) and dexmedetomidine 30% (n=24) versus 5% (n=4), respectively). Patients in the phenobarbital group also had lower GCS scores and higher Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) scores during their intensive care unit admission, possibly suggesting more severe alcohol withdrawal. There was no difference in intensive care unit length of stay, all-cause, in-hospital mortality, discharge disposition, or therapeutic adjuncts. Conclusions Combination therapy of phenobarbital plus benzodiazepines was associated with higher odds of requiring mechanical ventilation. Few patients received phenobarbital monotherapy. Additional studies are needed to better compare the effects of phenobarbital monotherapy versus benzodiazepines in neurocritical patients.

Rapid Metabolism of Monthly Extended-Release Buprenorphine Formulation: A Case Report

Background: Medication-assisted treatment constitutes the gold standard management for patients with opioid use disorder. Many factors can alter the response to medications, including genetic variations. In this case report, we discuss the presentation of a patient maintained on subcutaneous extended-release buprenorphine formulation who repeatedly presented objective and subjective signs of opioid withdrawal when he was switched from weekly to monthly formulation. We particularly highlight the role of metabolic pharmacogenes in this presentation. Case Presentation: Mr. Y, a 31-year-old single man, presented to our rehabilitation center seeking assistance for his polysubstance dependence, mainly opioid use disorder. As part of his multidisciplinary treatment plan, he was started on weekly extended-release buprenorphine. After maintenance for several months, he was transitioned to the monthly equivalent formulation. Since the transition, he began to develop severe withdrawal symptoms 1-2 weeks before his next due injection. This was paralleled by a noted decrease in buprenorphine level on his urine drug screening test. As soon as the patient was placed back on the weekly formulation, his symptoms resolved. Conclusion: This is a novel case highlighting the potential role of pharmacogenomics in clinical presentation and response to medications. Switching patients from weekly to monthly extendedrelease buprenorphine formulation might make rapid or ultra-rapid metabolizers at risk of earlyonset withdrawal symptoms. =In such a case, earlier provision of the injection or switching to another formulation or medication can be considered.

Endocannabinoid agonist 2-arachidonoylglycerol differentially alters diurnal activity and sleep during fentanyl withdrawal in male and female mice

Fentanyl has become the leading driver of opioid overdoses in the United States. Cessation of opioid use represents a challenge as the experience of withdrawal drives subsequent relapse. One of the most prominent withdrawal symptoms that can contribute to opioid craving and vulnerability to relapse is sleep disruption. The endocannabinoid agonist, 2-Arachidonoylglycerol (2-AG), may promote sleep and reduce withdrawal severity; however, the effects of 2-AG on sleep disruption during opioid withdrawal have yet to be assessed. Here, we investigated the effects of 2-AG administration on sleep-wake behavior and diurnal activity in mice during withdrawal from fentanyl. Sleep-wake activity measured via actigraphy was continuously recorded before and after chronic fentanyl administration in both male and female C57BL/6J mice. Immediately following cessation of fentanyl administration, 2-AG was administered intraperitoneally to investigate the impact of endocannabinoid agonism on opioid-induced sleep disruption. We found that female mice maintained higher activity levels in response to chronic fentanyl than male mice. Furthermore, fentanyl administration increased wake and decreased sleep during the light period and inversely increased sleep and decreased wake in the dark period in both sexes. 2-AG treatment increased arousal and decreased sleep in both sexes during first 24-h of withdrawal. On withdrawal day 2, only females showed increased wakefulness with no changes in males, but by withdrawal day 3 male mice displayed decreased rapid-eye movement sleep during the dark period with no changes in female mice. Overall, repeated administration of fentanyl altered sleep and diurnal activity and administration of the endocannabinoid agonist, 2-AG, had sex-specific effects on fentanyl-induced sleep and diurnal changes.

Double bad luck: pulmonary embolism and vaginal bleeding - a case report

BackgroundPulmonary embolism is a common and potentially fatal condition. Exogenous estrogens in contraceptives are associated with an increased risk of venous thrombo-embolism. However, discontinuation of a combined oral contraceptive can lead to severe withdrawal bleeding in an anticoagulated patient.Case presentationWe report a case of a 47-year-old female who presented to the emergency room with a two-day history of worsening shortness of breath and chest pain. Her chronic medication included a combined oral contraceptive pill. Transthoracic echocardiogram showed pulmonary hypertension and right ventricular dilatation. Computerized tomography scan revealed bilateral pulmonary embolism. She received thrombolysis with alteplase and was started on rivaroxaban. Five days after discharge, however, she was readmitted with severe vaginal bleeding.Discussion and conclusionWe describe a case of submassive pulmonary embolism, treated with thrombolysis and anticoagulation, who developed severe vaginal bleeding after stopping the contraceptive pill. This case highlights the importance of detailed menstrual history taking when initiating anticoagulation in women. Discontinuation of oral contraceptives, while important in reducing the risk of recurrent thrombosis, could be postponed until the end of the recommended course of anticoagulation and until a safe alternative form of contraception has been established, if required.

Predictors of cocaine use disorder treatment outcomes: a systematic review

BackgroundPsychosocial approaches are the first-line treatments for cocaine dependence, although they still present high dropout and relapse rates. Thus, there is a pressing need to understand which variables influence treatment outcomes to improve current treatments and prevent dropout and relapse rates. The aim of this study is to explore predictors of treatment retention and abstinence in CUD.MethodsThis systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched three databases—PubMed, PsychINFO and Web of Science—for randomized clinical trials (RCTs) published in English and Spanish from database inception through April 1, 2023. We selected all studies that met the inclusion criteria (adults aged ≥ 18, outpatient treatment, CUD as main addiction, and no severe mental illness) to obtain data for the narrative synthesis addressing cocaine abstinence and treatment retention as main outcome variables. After data extraction was completed, risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB-2).ResultsA total of 566 studies were screened, and, of those, 32 RCTs were included in the synthesis. Younger age, more years of cocaine use, and craving levels were significant predictors of relapse and treatment dropout. Fewer withdrawal symptoms, greater baseline abstinence, greater treatment engagement, and more self-efficacy were all predictors of longer duration of abstinence. The role of impulsivity as a predictor of CUD is unclear due to conflicting data, although the evidence generally suggests that higher impulsivity scores can predict more severe addiction and withdrawal symptoms, and earlier discontinuation of treatment.ConclusionCurrent evidence indicates which variables have a direct influence on treatment outcomes, including well-studied cocaine use-related variables. However, additional variables, such as genetic markers, appear to have a high impact on treatment outcomes and need further study.Systematic review registrationThis systematic review is registered at PROSPERO (ID: CRD42021271847). This study was funded by the Spanish Ministry of Science, Innovation and Universities, Instituto Carlos III (ISCIII) (FIS PI20/00929) and FEDER funds and Fundació Privada Hospital de la Santa Creu i Sant Pau (Pla d’acció social 2020).

Efficacy of the QuitSure App for Smoking Cessation in Adult Smokers: Cross-Sectional Web Survey.

Cigarette smoking remains one of the leading causes of preventable death worldwide. A worldwide study by the World Health Organization concluded that more than 8 million people die every year from smoking, tobacco consumption, and secondhand smoke. The most effective tobacco cessation programs require personalized human intervention combined with costly pharmaceutical supplementation, making them unaffordable or inaccessible to most tobacco users. Thus, digital interventions offer a promising alternative to these traditional methods. However, the leading smartphone apps available in the market today have either not been studied in a clinical setting or are unable to match the smoking cessation success rates of their expensive offline counterparts. We would like to understand whether QuitSure, a novel smoking cessation app built by Rapidkart Online Private Limited, is able to bridge this efficacy gap and deliver affordable and effective smoking cessation at scale. Our objective was to do an initial exploration into the engagement, efficacy, and safety of QuitSure based on the self-reported experiences of its users. Outcomes measured were program completion, the effect of program completion on smoking behavior, including self-reported cessation outcomes, and negative health events from using the app. All QuitSure registered users who created their accounts on the QuitSure app between April 1, 2021, and February 28, 2022, were sent an anonymized web-based survey. The survey results were added to their engagement data on the app to evaluate the feasibility and efficacy of the app as a smoking cessation intervention. The data were analyzed using descriptive statistics (frequencies and percentages) and the χ2 test of independence. In total, 1299 users who had completed the QuitSure program submitted the survey and satisfied the inclusion criteria of the study. Of these, 1286 participants had completed the program more than 30 days before filling out the survey, and 1040 (80.1%, 95% CI 79.1%-82.6%) of them had maintained prolonged abstinence for at least 30 days after program completion. A majority of participants (770/891, 86.4%) who were still maintaining abstinence at the time of submitting the survey did not experience any severe nicotine withdrawal symptoms, while 41.9% (373/891) experienced no mild withdrawal symptoms either. Smoking quantity prior to completing the program significantly affected quit rates (P<.001), with heavy smokers (>20 cigarettes per day) having a lower 30-day prolonged abstinence rate (relative risk=0.91; 95% CI 90.0%-96.2%) compared to lighter smokers. No additional adverse events outside of known nicotine withdrawal symptoms were reported. The nature of web-based surveys and cohort selection allows for extensive unknown biases. However, the efficacy rates of survey respondents who completed the program were high and provide a case for further investigation in the form of randomized controlled trials on the QuitSure tobacco cessation program.

Alcohol withdrawal and amphetamine co-use in an animal model for attention deficit hyperactivity disorder

ABSTRACT Background: Non-medical use of amphetamine and other stimulants prescribed for treatment of attention deficit/hyperactivity disorder (ADHD) is of special concern when combined with alcohol consumption. In a previous study, we modeled chronic ethanol-amphetamine co-use in adolescent Long-Evans (LE) rats and provided evidence that amphetamine attenuates alcohol withdrawal symptoms. Objectives: This project modeled co-use of amphetamine with alcohol in adolescents with ADHD-like symptoms by examining ethanol-amphetamine administration in adolescent Spontaneously Hypertensive Rats (SHR), an experimental model for the study of ADHD. Withdrawal symptoms were compared among SHR and two control rat strains, LE and Wistar Kyoto (WKY). Methods: At postnatal day 32, parallel groups of 12–24 male SHR, WKY and LE rats were administered a liquid diet containing ethanol (3.6%) and/or amphetamine (20 mg/L). Following administration periods up to 26 days, rats were withdrawn from their treatment and tested for overall severity of alcohol withdrawal symptoms, general locomotor activity, and anxiety-like behavior. Results: Overall withdrawal severity was lower for SHR than for LE (p < .001) or WKY (p = .027). Co-consumption of amphetamine decreased withdrawal severity for LE (p = .033) and WKY (p = .011) but not SHR (p = .600). Only WKY showed increased anxiety-like behavior during withdrawal (p = .031), but not after amphetamine co-administration (p = .832). Conclusion: Alcohol withdrawal severity may be attenuated when co-used with amphetamine. However, as a model for ADHD, SHR adolescents appeared resistant to developing significant signs of alcohol withdrawal following alcohol consumption. Whether alcohol withdrawal symptoms are attenuated or absent, potential consequences could include a decreased awareness of an emerging problem with alcohol use.

The Effect of N-acetylcysteine on Alprazolam Withdrawal Symptoms in Wistar Male Albino Rats

Introduction: Alprazolam is a benzodiazepine drug that is mainly used to treat generalized anxiety disorder and sleep disorders. Doctors' insistence on prescribing alprazolam due to its long half-life (16 hours) can lead to severe withdrawal complications. The aim of this study was to evaluate the effect of N-acetylcysteine (NAC) as an antioxidant drug on reducing the withdrawal symptoms of alprazolam in male albino rats. Material and Methods: In this experimental study, 50 albino male Wistar rats were used. 10 rats received normal saline by gavage for 26 days (sham), the rest of the rats received 1 mg / kg of alprazolam daily for 21 days and after drug dependence were randomly divided into 4 groups were divided. The negative control group received normal saline by gavage daily for up to 4 days after the dependence period. The treated groups also received 100, 200, and 400 mg / kg NAC orally for 4 days after the dependence period, after which the anti-anxiety and restless effects of N-acetylcysteine were assessed by behavioral test (Elevated plus-maze test). Results: The variables OAE (p = 0.18), CAE (p = 0.88), CAT (p = 0.53) and OAT percent (p = 0.29) did not show a significant difference between the 5 treatment groups; But OAT (p = 0.07) and OAE_percent (p = 0.001) showed a significant difference between the 5 treatment groups (p &lt;0.05). Conclusion: Due to the antioxidant properties of NAC and its ability to counteract oxidative stress in the nervous system, it can be used to control the symptoms of withdrawal syndrome in people with a history of alprazolam dependence. In the present study, a dose of 400 mg / kg NAC had the best therapeutic effects in rats. In future studies, it is recommended to obtain an appropriate dose for people who experience symptoms of alprazolam withdrawal syndrome.

Biological sex and hormonal contraceptive associations with drug cue reactivity in cannabis use disorder

Biological sex differences in Cannabis Use Disorder (CUD) progression, cannabis withdrawal severity, and pharmacotherapy response have been reported, suggesting that CUD mechanisms may differ by sex. Drug cue reactivity is an established predictor of drug use behavior, but the literature on sex differences in drug cue reactivity is mixed, including in CUD. One possible moderator of sex differences in drug cue reactivity is hormonal contraceptive (HC) use. The aim of the present study was to test whether sex differences in neural cannabis cue reactivity and craving varied by female HC use in a CUD sample. As part of a larger study, 152 adults reporting frequent cannabis use completed a drug cue reactivity task during electrocenphalogram recording. Late positive potential (LPP) amplitude modulation by cannabis cues was used to measure neural cue reactivity. Craving after the cue reactivity task was also assessed. Males (n = 74) and naturally-cycling females (n = 26), who did not differ from each other, showed significantly greater LPP enhancement to cannabis vs. neutral cues compared to HC-using females (n = 52), an effect mostly driven by neutral cues. Craving was significantly higher in naturally-cycling but not HC-using females compared to males, but only in covariate-unadjusted analyses. Exploratory analyses of HC and menstrual phase characteristics indicate a progesterone-related mechanism may underlie HC effects on cannabis cue reactivity. The present study's results suggest that mixed findings on drug cue reactivity sex differences may be due to variability in HC use, which has implications for sex-specific models of CUD progression and treatment.

Buprenorphine Enhanced Taper Tolerability Evaluation Report (BETTER): A Case Series.

Discontinuing sublingual buprenorphine (SL-BUP) has been identified by some patients as a potential outcome of success for opioid use disorder treatment. The process of tapering SL-BUP can be lengthy as unpleasant opioid withdrawal symptoms limit the pace of dose adjustments. Uncontrolled withdrawal symptoms pose a risk for return to illicit opioid use and more patient-centered options for tapering SL-BUP are needed. Previous case reports have identified using extended-release subcutaneous buprenorphine (ER-BUP) to minimize withdrawal symptoms as the dose self-decreases very gradually. Ideal dosing strategies, appropriate patient characteristics, and duration of buprenorphine release with the ER-BUP injection are not well described. We present 8 cases where a single 100 mg ER-BUP injection was administered to patients experiencing intolerable withdrawal symptoms during SL-BUP taper. Patients were taking between 2 and 6 mg SL-BUP daily prior to injection. Three patients experienced mild adverse effects the day after receiving injection, all of which were taking lower SL-BUP doses (2-3 mg). In the 12 months following injection, 3 patients experienced mild, but tolerable withdrawal symptoms at variable intervals. Two patients returned to taking SL-BUP and no patients returned to illicit opioid use. Buprenorphine urine toxicology showed elimination of buprenorphine occurred after 24 weeks. Findings from these cases support current evidence-based guidance that ER-BUP tapering is better tolerated than traditional SL-BUP tapering. These patient cases and pharmacokinetic modeling of ER-BUP suggest that a target preinjection dose of 2 to 6 mg SL-BUP will minimize the risk of more severe adverse effects or withdrawal symptoms. Patients and providers should ensure that remission is well-established before initiating SL-BUP taper. A shared decision-making approach can help support patient autonomy and understanding safety risks of discontinuing SL-BUP. Future prospective studies with larger populations could further refine dosing strategies with various SL-BUP preinjection doses and newer ER-BUP formulations.

Withdrawal during outpatient low dose buprenorphine initiation in people who use fentanyl: a retrospective cohort study

BackgroundBuprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients.MethodsWe conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics.ResultsThere were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation.ConclusionsWithdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients’ withdrawal experiences.

A Case Report on Alcohol Withdrawal Syndrome

Heavy drinkers who abruptly cut back on their alcohol intake or give it up entirely risk experiencing alcohol withdrawal. The warning signs and symptoms include agitation, anxiety, irritability, and mild to moderate tremors. Seizure, hallucinations, delirium tremens are the most severe withdrawal symptoms. These symptoms arise from abnormalities in brain chemistry brought on by alcohol, which leads to an excess of neuronal activity when the alcohol is stopped. Ayurveda is a holistic approach which not only takes body into consideration but also mental status. Madatyaya is a wide term explained in our classics, while explaining Madya, Acharaya told that it has properties opposite to that of Ojus, so these substances causing depletion to our body resources can be correlated to Madatyaya. So it’s a case report on alcohol withdrawal symptoms and its effective management using Ayurvedic treatment modalities.

Severity of premenstrual symptoms among women with musculoskeletal pain: relation to vitamin D, calcium, and psychological symptoms.

Premenstrual syndrome (PMS) has various symptoms that occur during the luteal phase of the menstrual cycle and subside after menstruation. Anxiety and depression are prevalent in women with PMS and may exacerbate the severity of PMS. Vitamin D and calcium deficiency may have a role in developing anxiety, depression, and musculoskeletal pain (MSP). The aim of this study was to evaluate selected premenstrual symptoms in relation to serum vitamin D levels, daily calcium consumption, and psychological symptoms among women with MSP. The study population consisted of 108 women with MSP and 108 healthy controls. Information about premenstrual symptoms and calcium consumption were collected. Psychological symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Vitamin D was determined by electrochemiluminescence immunoassay. Women with MSP had lower serum vitamin D levels, lower daily calcium consumption, higher HADS scores for anxiety and depression, and higher frequency of severe premenstrual symptoms including fatigue, headache, irritability, mood swings, anxiety, depression, and social withdrawal compared to controls (P < 0.01). Abnormal HADS scores for anxiety and depression were associated with increased severity of premenstrual symptoms (P < 0.05). Deficient vitamin D and calcium consumption were associated with abnormal HADS scores for anxiety and depression (P < 0.05) and with increased severity of premenstrual headache, irritability, anxiety, and depression (P < 0.05). Low calcium consumption was associated with increased severity of premenstrual irritability, anxiety, depression, and social withdrawal (P < 0.05). The results suggest that vitamin D deficiency, low calcium consumption, psychological symptoms, and MSP could be interrelated and implicated in the etiology severe premenstrual symptoms. Further studies are necessary to assess whether vitamin D and calcium supplements can relieve MSP and premenstrual symptoms.

Impact of stress coping strategy in modifying perceptions of school stress among adult learners enrolled in Home Economics and Indigenous Textiles Education in Nigerian Universities.

Studying some professions is so demanding that if not well managed it leads to severe stress, withdrawal, burnout, and other health-related problems. Hence, practical engagement and exhibition of catering, cooking, and home management are so tasking as they are time-consuming and very intensive. Many students in the specialties experience excess academic loads and internal and external demands. Given these, this study tested the impact of cognitive behavior coping strategy on school stress among adult learners enrolled in Home Economic and Indigenous Textile Education. A pretest-posttest randomized control group design was applied. Ninety-five students (43 [45.3%] males; 52 [54.7%] females) participated in the current study. Stress assessment was induced and then students were randomly allocated to the cognitive behavior coping strategy group and the waitlist conditions. Later, students on the waitlist received the cognitive behavior coping strategy contents. Data collected were analyzed using analysis of covariance. Results showed that at pretest, there was no significant difference among the participants in the 2 groups as measured by Educational Stress Scale and Perceived Stress Scale scores. However, the post-intervention test result showed a long-term impact of cognitive behavior coping strategy in improving the management of school stress among students. This study suggests that cognitive behavior coping strategy has a long-term impact on modifying the students' perception of school stress in a sample of adult learners enrolled in Home Economic and Indigenous Textile Education.

The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients.

Ibogaine is a hallucinogenic drug that may be used to treat opioid use disorder (OUD). The relationships between pharmacokinetics (PKs) of ibogaine and its metabolites and their clinical effects on side effects and opioid withdrawal severity are unknown. We aimed to study these relationships in patients with OUD undergoing detoxification supported by ibogaine. The study was performed in 14 subjects with OUD. They received a single dose of 10mg/kg ibogaine hydrochloride. Plasma PKs of ibogaine, noribogaine, and noribogaine glucuronide were obtained during 24 h. Cytochrome P450 isoenzyme 2D6 (CYP2D6) genotyping was performed. The PKs were analyzed by means of nonlinear mixed effects modeling and related with corrected QT interval (QTc) prolongation, cerebellar ataxia, and opioid withdrawal severity. The PK of ibogaine were highly variable and significantly correlated to CYP2D6 genotype (p < 0.001). The basic clearance of ibogaine (at a CYP2D6 activity score (AS) of 0) was 0.82 L/h. This increased with 30.7 L/h for every point of AS. The relation between ibogaine plasma concentrations and QTc was best described by a sigmoid Emax model. Spearman correlations were significant (p < 0.03) for ibogaine but not noribogaine with QTc (p = 0.109) and cerebellar effects (p = 0.668); neither correlated with the severity of opioid withdrawal symptoms. The clearance of ibogaine is strongly related to CYPD2D6 genotype. Ibogaine cardiac side effects (QTc time) and cerebellar effects are most likely more driven by ibogaine rather than noribogaine. Future studies should aim at exploring lower doses and/or applying individualized dosing based on CYP2D6 genotype.

Predominant affective temperaments in depressive patients with severe social withdrawal

BackgroundHikikomori (HK) is characterized by self-isolation and social refusal, being more likely also associated with affective disorders, including depression. This case–control study primarily aimed at identifying (if any) predominant affective temperaments are associated with HK in depressed versus not-depressed individuals. Secondary objectives comprise assessing which other psychopathological dimensions (e.g., boredom, anxiety) are associated with the HK specifier in depressed individuals.MethodsFrom the larger SWATCH study, 687 Italian young people were screened for depression, as measured by 9 items-Patient Health Questionnaire (PHQ-9) and HK-like social withdrawal, through the Hikikomori Questionnaire-25 (HQ-25). All subjects were administered a brief-Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-M), the 7 items-Generalized Anxiety Disorder (GAD-7) and the Multidimensional State Boredom Scale (MSBS).ResultsMales reported significantly higher scores at HQ-25 total score than females (p = 0.026). In the total sample, HK social withdrawal is positively predicted by MSBS low arousal, disengagement, depressive levels, depressive and irritable affective temperaments, while negatively by anxiety (F(6, 680) = 82.336, p < 0.001, R2 = 0.421). By selecting only depressed sample, HQ-25 is positively predicted by MSBS total score, low arousal and depressive affective temperament, while negatively by MSBS high arousal (F(4, 383) = 48.544, p < 0.001, R2 = 0.336). The logistic regression model found that the likelihood of developing depression with the HK specifier is significantly predicted by depressive and cyclothymic affective temperaments.ConclusionsThese preliminary findings could help in clinically characterizing the relationship between specific affective temperamental profiles among individuals with depression with/without HK specifier, in order to provide a more tailored and personalized therapeutic approach. Our Italian study should be extensively replicated in larger, longitudinal and multicentric pan-European studies, by specifically assessing the impact of these findings on depression clinical course, prognosis and treatment outcomes.

Alcohol Withdrawal Severity Measures for Identifying Patients Requiring High-Intensity Care.

Alcohol withdrawal syndrome (AWS) may progress to require high-intensity care. Approaches to identify hospitalized patients with AWS who received higher level of care have not been previously examined. This study aimed to examine the utility of Clinical Institute Withdrawal Assessment Alcohol Revised (CIWA-Ar) for alcohol scale scores and medication doses for alcohol withdrawal management in identifying patients who received high-intensity care. A multicenter observational cohort study of hospitalized adults with alcohol withdrawal. University of Chicago Medical Center and University of Wisconsin Hospital. Inpatient encounters between November 2008 and February 2022 with a CIWA-Ar score greater than 0 and benzodiazepine or barbiturate administered within the first 24 hours. The primary composite outcome was patients who progressed to high-intensity care (intermediate care or ICU). None. Among the 8742 patients included in the study, 37.5% (n = 3280) progressed to high-intensity care. The odds ratio for the composite outcome increased above 1.0 when the CIWA-Ar score was 24. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at this threshold were 0.12 (95% CI, 0.11-0.13), 0.95 (95% CI, 0.94-0.95), 0.58 (95% CI, 0.54-0.61), and 0.64 (95% CI, 0.63-0.65), respectively. The OR increased above 1.0 at a 24-hour lorazepam milligram equivalent dose cutoff of 15 mg. The sensitivity, specificity, PPV, and NPV at this threshold were 0.16 (95% CI, 0.14-0.17), 0.96 (95% CI, 0.95-0.96), 0.68 (95% CI, 0.65-0.72), and 0.65 (95% CI, 0.64-0.66), respectively. Neither CIWA-Ar scores nor medication dose cutoff points were effective measures for identifying patients with alcohol withdrawal who received high-intensity care. Research studies for examining outcomes in patients who deteriorate with AWS will require better methods for cohort identification.