Serotonergic neuron ribosomal proteins regulate the neuroendocrine control of Drosophila development.

The regulation of ribosome function is a conserved mechanism of growth control. While studies in single cell systems have defined how ribosomes contribute to cell growth, the mechanisms that link ribosome function to organismal growth are less clear. Here we explore this issue using Drosophila Minutes, a class of heterozygous mutants for ribosomal proteins. These animals exhibit a delay in larval development caused by decreased production of the steroid hormone ecdysone, the main regulator of larval maturation. We found that this developmental delay is not caused by decreases in either global ribosome numbers or translation rates. Instead, we show that they are due in part to loss of Rp function specifically in a subset of serotonin (5-HT) neurons that innervate the prothoracic gland to control ecdysone production. We find that these effects do not occur due to altered protein synthesis or proteostasis, but that Minute animals have reduced expression of synaptotagmin, a synaptic vesicle protein, and that the Minute developmental delay can be partially reversed by overexpression of synaptic vesicle proteins in 5-HTergic cells. These results identify a 5-HT cell-specific role for ribosomal function in the neuroendocrine control of animal growth and development.

Purifying selection drove the adaptation of mitochondrial genes along with correlation of gene rearrangements and evolutionary rates in two subfamilies of Whitefly (Insecta: Hemiptera).

Insect mitochondrial genomes (mitogenomes) are usually represented by a conserved gene order. Whiteflies exhibit gene rearrangement in their mitogenomes; however, understanding how nucleotide substitution rates shape gene rearrangement in whiteflies is unclear due to the limited number of mitogenomes. Additionally, the mechanisms by which selection pressure drives adaptations in mitochondrial genes in the two subfamilies of whiteflies are not yet known. Here, we analyzed 18 whitefly mitogenomes, including one newly generated mitogenome, to compare nucleotide substitution rates, selection pressure, and gene arrangements. The newly generated mitogenome is reported along with reannotation of Pealius mori and comparisons to other whitefly mitogenomes. Comparative studies on nucleotide composition of 18 whiteflies revealed the positive GC skewness, confirming the reversal of strand asymmetry. We found 11 rearranged gene orders within two subfamilies of whiteflies with 8-18 breakpoints of gene rearrangements. Members of the subfamily Aleyrodinae exhibit more complex pathways in the evolution of gene order as compared to the subfamily Aleurodicinae. Our findings also revealed that the increase or reduction of nucleotide substitution rates does not have an impact on any of the gene rearrangement scenarios depicting neutral correlation. Selection pressure analysis revealed that the mitogenomes from members of both the subfamilies Aleurodicinae and Aleyrodinae are characterized by intense purifying selection pressure.

Gas Sensing Properties of PLD Grown 2D SnS Film: Effect of Film Thickness, Metal Nanoparticle Decoration, and In Situ KPFM Investigation.

This study employs novel growth methodologies and surface sensitization with metal nanoparticles to enhance and manipulate gas sensing behavior of two-dimensional (2D)SnS film. Growth of SnS films is optimized by varying substrate temperature and laser pulses during pulsed laser deposition (PLD). Thereafter, palladium (Pd), gold (Au), and silver (Ag) nanoparticles are decorated on as-grown film using gas-phase synthesis techniques. X-ray diffraction (XRD), Raman spectroscopy, and Field-emission scanning electron microscopy (FESEM) elucidate the growth evolution of SnS and the effect of nanoparticle decoration. X-ray photoelectron spectroscopy (XPS) analyses the chemical state and composition. Pristine SnS, Ag, and Au decorated SnS films are sensitive and selective toward NO2 at room temperature (RT). Ag nanoparticle increases the response of pristine SnS from 48 to 138% toward 2 ppm NO2, which indicates electronic and chemical sensitization effect of Ag. Pd decoration on SnS tunes its selectivity toward H2 gas with a response of 55% toward 70 ppm H2 and limit of detection (LOD) < 1 ppm. In situ Kelvin probe force microscopy (KPFM) maps the work function changes, revealing catalytic effect of Ag toward NO2 in Ag-decorated SnS and direct charge transfer between Pd and SnS during H2 exposure in Pd-decorated SnS.

Neurocognitive Functions After 6-Month Buprenorphine (Naloxone)-Based Opioid Agonist Maintenance Treatment: A Controlled Prospective Study.

BACKGROUND: Medications for opioid use disorder (OUD) may influence neurocognitive functions. Inadequate power, confounders, and practice effects limit the validity of the existing research. We examined the change in cognitive functions in patients with OUD at 6-month buprenorphine (naloxone) posttreatment and compared the cognitive performance of the buprenorphine-treated group with control subjects. METHODS: We recruited 498 patients with OUD within a week of initiating buprenorphine. Assessments were done twice-at baseline and 6 months. Those abstinent from illicit opioids and adherent to treatment (n = 199) underwent follow-up assessments. Ninety-eight non-substance-using control subjects were recruited from the community. The neurocognitive assessments comprised the Wisconsin Card Sorting Test, Iowa Gambling Task, Trail-Making Tests A and B (TMT-A and TMT-B), and verbal and visual N-Back Test. We controlled for potential effect modifiers. RESULTS: Twenty-five of the 32 test parameters significantly improved with 6 months of buprenorphine treatment; 20 parameters withstood corrections for multiple comparisons (P < 0.001). The improved test domains spread across cognitive tests: Wisconsin Card Sorting Test (perseverative errors and response, categories completed, conceptual responses), TMTs (time to complete), verbal and visual N-Back Tests (hits, omission, and total errors). After treatment, OUD (vs control subjects) had less perseverative response and error (P < 0.001) and higher conceptual response (P = 0.004) and took lesser time to complete TMT-A (P < 0.001) and TMT-B (P = 0.005). The baseline neurocognitive functions did not differ between those who retained and those who discontinued the treatment. CONCLUSION: Cognitive functions improve in patients with OUD on buprenorphine. This improvement is unlikely to be accounted for by the practice effect, selective attrition, and potential confounders.

Characterization of Complete Mitochondrial Genome of Badri Breed of Bos indicus (Bovidae: Bovinae): Selection Pressure and Comparative Analysis.

High-altitude mammals are often subject to specific environmental obstacles, which exert selective pressure on their physiological and morphological traits, hence driving their evolutionary processes. It is anticipated that these circumstances will lead to the adaptive evolution of protein-coding genes (PCGs) in the mitochondrial genome, which play a crucial role in the oxidative phosphorylation system. In this study, we have generated the complete mitochondrial genome of the Badri breed of Bos indicus inhabiting a high-altitude environment to test the signatures of adaptive evolution on PCGs and their phylogenetic relationships. The complete mitogenome of the Badri breed is 16,339 bp and most tRNAs showed typical clover-leaf secondary structure with a few exceptions, like trnS1 and trnS2 without DHU arm and trnK without DHU loop. Comparative analysis of PCGs indicated that cox1 is the most conserved, while atp6 is the most variable gene. Moreover, the ratios of non-synonymous to synonymous substitution rates indicated the purifying selection (Ka/Ks < 1) in the protein-coding genes that shape the diversity in mitogenome of Bos indicus. Furthermore, Branch-site model (BSM) suggested that cox1, cox2, nad3, nad4L, and nad6 underwent stronger purifying selection (ω < 1) than other PCGs in 15 breeds of 4 species, including Badri. BSM also detected 10 positive sites in PCGs and one in 13 PCGs concatenated dataset. Additional analyses in Datamonkey indicated 11 positive sites and 23 purifying sites in the concatenated dataset, a relaxation of selection strength in nad3, and no evidence of episodic diversifying selection in any PCGs. Phylogeny revealed the sister relationship of the Badri with other breeds of Bos indicus as well as Bos frontalis (Gayal-2). The mitogenome of the Badri breed is an important genomic resource for conservation genetics of this species and also contributes to the understanding of the adaptive evolution of mitochondrial protein coding genes.

Effectiveness of psychosocial interventions for alcohol use disorder: a systematic review and meta-analysis update.

Background: Given the accumulating research, evolving psychosocial treatment, and equivocal findings, updating WHO's Mental Health Gap Action Programme-2015 was necessary to ensure guidelines reflect effective strategies for alcohol use disorder (AUD).Objective: To estimate the effects of psychosocial interventions on drinking and related outcomes.Methods: We included randomized controlled trials published between January 2015 and June 2022 on adults with alcohol dependence (ICD 10/DSM-IV) and moderate to severe AUD (DSM-5), and those examined psychosocial interventions against treatment-as-usual (TAU) and active controls. Eight databases and registries were searched. Relative Risk (RR) and standardized mean difference (SMD) were used for dichotomous and continuous outcomes. We used Cochrane's risk of bias assessment (RoB2).Results: Of 873 screened records, 14 and 13 studies in the narrative synthesis and meta-analysis. Of the 2,575 participants, 71.5% were men. Thirteen studies used ICD 10/DSM IV diagnosis. Compared to TAU, any psychosocial intervention increased the relative risk of abstinence by 28% [N = 7, RR = 1.28, 95% CI: 1.07 to 1.53, p = .01, NNT = 9]. There were minimal heterogeneity and no evidence of publication bias. Psychosocial interventions were not effective in reducing the drinking frequency (n = 2, Hedge's g = -0.10, 95% CI: -0.46 to 0.26, p = .57) and drinks/drinking days (N = 5, g = -0.10, 95% CI: -0.37 to 0.16, p = .43). Treatment discontinuation did not differ between intervention and control groups [RR = 1.09, 95% CI: 0.66 to 1.80].Conclusion: Psychosocial interventions are effective in improving abstinence but not in reducing drinking frequency or amount. Policymakers must consider this evidence to generate AUD treatment guidelines.Registration: PROSPERO 2022 CRD42022342608.

Characterization of complete mitochondrial genome of three Horse flies of the genus Tabanus (Diptera: Tabanidae): comparative analysis.

BACKGROUND: Tabanidae (Horse-Flies or Deer-Flies) are one of the most economically important as well as medically significant haematophagous insect family within the order Diptera. Members of this group are also responsible for the mortality of substantial number of live-stock every year. Due to their pathogen transmission potential and vector competencies makes them an important insect group to study. Till now, mitochondrial genome of 18 species of tabanids were available. METHODS AND RESULTS: The complete mitogenome of three species T. diversifrons (15,809 bp), T. rubidus (15,878 bp) and T. tenens (15,872 bp) were generated by Next generation sequencing method. They consist 37 genes, with a positive AT skew and a negative GC skew. The gene order of these three species is similar to the typical gene arrangement of infra-order Tabanomorpha. Most of the tRNAs showed typical clover-leaf secondary structure except trnS1, which lacks the DHU arm. The sliding window analysis showed that the nad4L is the most conserved while atp8, and nad6 are the most variable genes. Moreover, the ratios of non-synonymous to synonymous substitution rates indicated that all PCGs under the purifying selection. Phylogeny revealed Chrysops and Haematopota are monophyletic while species of Hybomitra are nested within the polyphyletic clade of Tabanus. T. diversifrons exhibits sister relationship with Atylotus miser. Two morphologically divergent species T. rubidus and T. tenens are found to be genetically similar and indistinguishable by mitochondrial genome. CONCLUSIONS: The hypervariable genes like atp8 and nad6 can be used as molecular markers for the identification of recently diverged lineages of family Tabanidae. Further, to address uncertainties arising from the two morphological divergent species, it is imperative to obtain data from nuclear gene markers.

Risk clustering and psychopathology from a multi-center cohort of Indian children, adolescents, and young adults.

Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics, and to examine the association of risk clusters with manifest psychopathology. Participants (n = 8300) between 6 and 23 years were recruited from seven sites in India. We administered questionnaires to elicit history of previous exposure to adverse childhood environments, family history of psychiatric disorders in first-degree relatives, and a range of antenatal and postnatal adversities. We used these variables to generate risk clusters. Mini-International Neuropsychiatric Interview-5 was administered to evaluate manifest psychopathology. Two-step cluster analysis revealed two clusters designated as high-risk cluster (HRC) and low-risk cluster (LRC), comprising 4197 (50.5%) and 4103 (49.5%) participants, respectively. HRC had higher frequencies of family history of mental illness, antenatal and neonatal risk factors, developmental delays, history of migration, and exposure to adverse childhood experiences than LRC. There were significantly higher risks of any psychiatric disorder [Relative Risk (RR) = 2.0, 95% CI 1.8-2.3], externalizing (RR = 4.8, 95% CI 3.6-6.4) and internalizing disorders (RR = 2.6, 95% CI 2.2-2.9), and suicidality (2.3, 95% CI 1.8-2.8) in HRC. Social-environmental and developmental factors could classify Indian children, adolescents and young adults into homogeneous clusters at high or low risk of psychopathology. These biopsychosocial determinants of mental health may have practice, policy and research implications for people in low- and middle-income countries.

Brief interventions for alcohol misuse among people living with HIV: a meta-analysis.

Background: One-third of people living with HIV (PLHIV) have alcohol misuse or alcohol use disorders which negatively affect course and outcome of HIV.Objectives: The meta-analysis sought to evaluate the effectiveness of brief interventions (BI) on alcohol and HIV outcomes in PLHIV with alcohol misuse.Methods: We included clinical trials published between 1990 and September 2022 on adults with harmful/hazardous alcohol use; only randomized clinical trials (RCTs) were included in the meta-analysis. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Clinical Trials.Gov, and the World Health Organization's International Clinical Trials Registry Platform databases. Cochrane's risk-of-bias assessment was used.Results: Eighteen studies were included in the narrative synthesis, and a meta-analysis could be performed on 13 studies. Among the included RCTs, seven showed a low risk and two showed a high risk of bias; others showed some concerns. There was no evidence of publication bias. Compared to the control, BI significantly reduces the drinks per drinking day (N = 5, Hedge's g= -0.45, 95%CI = -0.58, -0.32) and the number of heavy drinking days (N = 4, Hedge'sg = -0.81, 95% CI= -0.94, -0.67) between 3-6 months post-intervention. BI also reduces the odds of mortality by 42% (N = 7, OR = 0.58, 95% CI = 0.34, 0.99) in 6-12 months. BI does not change the alcohol risk scores and transition to harmful alcohol use; it does not improve adherence to Anti-Retroviral Therapy and increase viral suppression.Conclusion: Policymakers must introduce and scale up integrated screening and brief intervention services within HIV clinics and primary care.

Online Interest for Electronic Cigarettes Using Google Trends in the UK: A Correlation Analysis.

BACKGROUND: Google Trends provides an easily accessible and cost-effective method of providing real-time insight into user interest. OBJECTIVE: to address the gap in UK prevalence data for e-cigarettes by analyzing Google Trends to identify correlations with official data from Action on Smoking and Health. The study further evaluates Google Trend's sensitivity to real-time events and the ability for predictive models to forecast future data based on Google Trends. METHODS: UK Google Trends data from 2012 to 2021 was analyzed to assess (a) the most popular electronic nicotine device terminology; (b) statistically significant points in time; (c) correlations between Relative Search Volumes and official reports on electronic cigarette use and (d) whether Google Trends could predict future patterns in data. These were achieved using Locally Weighted Scatterplot Smoothing regression, Pruned Exact Linear Time Method, cross correlation, and Autoregressive Integrated Moving Average algorithms respectively. RESULTS: "Vape" was revealed to be the most popular electronic nicotine device terminology with a correlation coefficient greater than +0.9 when compared to official electronic cigarette consumption data within a one-year timescale (lag 0). Results from ARIMA modeling were varied with the algorithms forecasted trends line occasionally lying outside of a 95% prediction interval. CONCLUSION: Google Trends may correspond to population-based prevalence of electronic cigarette use. The changing trends coincide with changing policy decisions. Google Trends based prediction for online interest in electronic cigarettes requires further validation so should currently be used in conjunction with other traditional methods of data collections.

Does Prescription Length of Buprenorphine Influence Treatment Outcomes in Opioid Use Disorder? A Retrospective Cohort Study from North India.

OBJECTIVE: Buprenorphine (BUP) effectively suppresses non-prescription opioid use and increases treatment retention in opioid use disorder (OUD). However, short prescription length may interfere with treatment retention and recovery. We wanted to examine whether the outcomes of BUP treatment differ in high (HPL up to 4 wk) and low-prescription (LPL 1-2 wk) length groups. METHODS: We compared time to treatment discontinuation (TD), non-prescription opioid-positive urine screen, buprenorphine-negative urine screen, and self-reported non-prescription opioid use between two different cohorts of LPL (case record: June 2018 to August 2019; n = 105; observation endpoint: 31 October 2019) and HPL groups (case record: June 2020 to Aug 2021; n = 133; observation endpoint: 31 October 2021). We used Kaplan-Meier survival analysis and log-rank tests for between-group comparisons. We used Cox regression analysis to adjust for age, opioid potency, comorbidities, family income, and marital status. RESULTS: Subjects' age and buprenorphine dose were significantly lower, and the percentage of high-potency opioid users was significantly higher in the LPL group. In the unadjusted survival analysis, the median time to BUP discontinuation in the HPL was longer than that of the LPL [LPL= 22.4 ± 4.3 wk; HPL = 33.1 ± 8.5 wk; χ2(1)= 5.7; p=.02]. The survival distributions of other outcomes did not differ between groups. When adjusted for covariates, neither the prescription length nor other covariates independently predicted any treatment outcome. CONCLUSION: Higher prescription length might be associated with longer treatment retention. We provide preliminary evidence to support greater flexibility in BUP treatment, enhancing its scalability and attractiveness.

A Scoping Review of the Prevalence and Correlates of Sexual Dysfunction in Adults With Substance use Disorders.

BACKGROUND: Substance use may affect sexual functioning in both men and women. Comorbid sexual dysfunction adds to the clinical burden of substance use disorders (SUD). AIMS: The broad aims were to identify research conduct, types of the available evidence, and research gaps in (i) estimating the incidence, prevalence, type, and severity of sexual dysfunction in adults with SUD; (ii) exploring correlates of sexual dysfunction in SUD. METHODS: We conducted systematic searches on PubMed, Google Scholar, and Embase for studies published in the English language between August 1954 and November 2020. We included prospective and cross-sectional observational studies that had examined the prevalence or incidence of any sexual dysfunction in adults of either gender with substance use disorders. Review articles and those with an exclusive focus on tobacco use disorders were excluded. The review was registered in PROSPERO. RESULTS: Our search identified 65 relevant articles, including five prospective studies. All the prospective studies and most of the cross-sectional studies (n = 40) were done among men and subjects with alcohol (n = 20) and opioid (n = 23) use disorders in clinical populations. Substance use and sexual dysfunction were assessed by a wide range of instruments. Prospective studies reported a prevalence of sexual dysfunction at 75% and 61% for alcohol and opioid use disorders, respectively. The prevalence of any sexual dysfunction in cross-sectional studies ranged between 15 and 100 percent. Erectile dysfunction was the most commonly studied and observed sexual dysfunction. Comorbidity and socioeconomic deprivation were consistently associated with a higher occurrence of sexual dysfunctions. STRENGTHS: We did not limit our review by the type of substances and year of publication. We adhered to the standards of conducting and reporting scoping reviews; hence, our review results should be replicable, transparent, and reliable. LIMITATIONS: The wide clinical and methodological heterogeneity precluded a systematic review. CONCLUSION: Research gaps exist in women, non-clinical population, stimulants, and cannabis use disorders, and effect of treatment of SUD in sexual functioning. The quality of evidence is poor. Ghosh A, Kathiravan S, Sharma K, Mattoo SK. A Scoping Review of the Prevalence and Correlates of Sexual Dysfunction in Adults With Substance use Disorders. J Sex Med 2022;19:216-233.

White Matter Microstructure and Gray Matter Volume in Cannabis-Induced Psychosis and Schizophrenia With Cannabis Use.

OBJECTIVE: This study explored the differences in white matter (WM) microstructural integrity and gray matter (GM) volume between cannabis-induced psychosis (CIP) and schizophrenia with cannabis use (SZC). METHODS: This cross-sectional study with convenience sampling involved three groups of 20 participants each (CIP, SZC, and a control group without substance use), matched on age, handedness, and education. CIP and SZC were diagnosed with the Psychiatric Research Interview for Substance and Mental Disorders. Diffusion tensor and kurtosis imaging were done, and fractional anisotropy (FA), mean diffusivity, and mean kurtosis were estimated. GM volume was measured with voxel-based morphometry. RESULTS: Group comparisons revealed comparable age at initiation and duration and frequency of cannabis use between participants in the SZC and CIP groups. Participants with SZC had lower FA than controls in the anterior and retrolenticular internal capsule limbs, cingulate gyrus hippocampal formation, fornix, and superior fronto-occipital fasciculus (all p<0.05). Participants with CIP had lower FA than controls in the left fornix and right superior fronto-occipital fasciculus but higher FA than those with SZC in the left corticospinal tract (all p<0.05). On morphometry, participants with CIP had greater cerebellar GM volume than those with SZC and greater inferior frontal gyrus volumes than controls (all p<0.05). CONCLUSIONS: Widespread WM microstructural abnormalities were observed in participants with SZC, and fewer but significant WM disruptions were observed in those with CIP. Better WM integrity in some WM fiber tracts and greater GM volumes in crucial brain areas among those with CIP may have prevented the transition to schizophrenia.

Google Trends Data: A Potential New Tool for Monitoring the Opioid Crisis.

INTRODUCTION: There is a need to strengthen the standard surveillance of the opioid overdose crisis in the USA. The role of Google Trends (GT) was explored in this context. METHODS: In this study, a systemic GT search was done for a period from January 2004 to December 2018. "Naloxone" and "drug overdose" were chosen as search inputs. By using locally weighted scatterplot smoothing, we locally regressed and smoothed the relative search data generated by the GT search. We conducted a changepoint analysis (CPA) to detect significant statistical changes in the "naloxone" trend from 2004 to 2018. Cross-correlation function analyses were done to examine the correlation between 2 time series: year-wise relative search volume (RSV) for "naloxone" and "drug overdose" with the age-adjusted drug overdose mortality rate. Pearson's correlation was performed for the state-wise age-adjusted mortality rate due to drug overdose and RSV for "naloxone" and "drug overdose." RESULTS: Smoothed and regressed GT of "naloxone" were similar to the "opioid overdose" trend published by the National Center for Health Statistics. The CPA showed 2 statistically significant points in 2011 and 2015. CPA of year-wise RSV for "naloxone" and "drug overdose" showed significantly positive correlation with the age-adjusted drug overdose mortality at lag zero. State-wise RSV for "naloxone" and "drug overdose" too showed a strong and significant positive correlation with the state-wise mortality data. DISCUSSION/CONCLUSION: Inexpensive, publicly accessible, real-time GT data could supplement and strengthen the monitoring of opioid overdose epidemic if used in conjunction with the existing official data sources.

Predictors of Five-Year Readmission to an Inpatient Service among Patients with Alcohol Use Disorders: Report from a Low-Middle Income Country.

BACKGROUND: Alcohol use disorder (AUD) is a relapsing-remitting disease that accounted for a sizable proportion of all-cause adult inpatient stays. OBJECTIVES: To determine the predictors of any and multiple readmissions to inpatient care for AUD within 5 years of the index admission. METHODS: This retrospective, register-based cohort study assessed consecutive patients with AUD admitted to a publicly-funded inpatient service between January 2007 and December 2014. Binary logistic regression was used to determine independent predictors for readmissions based on relevant demographic, clinical, and treatment variables that showed significant differences (p < 0.05) on univariate analysis. RESULTS: Among 938 patients (age 35.9 ± 10.3 years; duration of alcohol use 159.6 ± 104.5 months; dual diagnosis 19%; comorbidity of substance use disorder 49.3%; medical disorder 34.8%, 299 (31.9%) and 115 (12.3%) had any and multiple readmissions, respectively. Comorbid "severe mental illness" (Odds ratio [OR] 1.99, 95% confidence interval [CI] 1.11-3.57) and urban residence (OR 1.58, 95% CI 1.13-2.18) increased the odds of any readmission; "Improved" status at discharge (OR 0.51, 95% CI 0.35-0.72) during index hospitalization reduced odds of readmission. Additionally, any medical or psychiatric comorbidities increased (OR 2.23, 95% CI 1.26-3.97), and comorbid substance use disorder decreased (OR 0.41, 95% CI 0.19-0.89) risk of multiple readmissions. CONCLUSIONS: Clinicians could identify patients at-risk for any and multiple readmissions during the index hospitalization. A policy aimed at reducing the risk of rehospitalization, healthcare cost, and stigma should pay attention to the predictors of readmission. Such policy should further benefit resource-limited settings.

The Effectiveness of Non-Benzodiazepine, Non-Barbiturate Medications for Alcohol Withdrawal Syndrome: A Rapid Systematic Review.

AIM: There are potential clinical, ethical and legal concerns with overdosing benzodiazepines (or barbiturates) for the treatment of moderate to severe alcohol withdrawal symptoms (AWS) through telemedicine or ambulatory outpatients. A rapid systematic review to (a) qualitatively summarize the non-benzodiazepine treatment alternatives, (b) evaluate the quality of evidence for the same to effectively manage moderate to severe AWS. METHODS: We conducted searches on PubMed (January 1990 to 31 March 2020), Cochrane Central Register of Controlled Trials, and Google Scholar. We selected the English language randomized controlled trials (RCTs) assessing the efficacy and adverse effects of non-benzodiazepine and non-barbiturate medications among adults with a diagnosis of AWS. Data extraction was done in a predefined format. Risk of bias (RoB) assessment and qualitative synthesis of evidence was done with the RoB2 tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) proGDT. RESULTS: Thirty-four RCTs were included. Gabapentin (n = 6), carbamazepine (n = 5), baclofen (n = 5), valproate (n = 3), clonidine/lofexidine (n = 3) and acamprosate (n = 2) had more than one trial with a particular comparison group. Four studies were found to have a low ROB. The GRADE evidence summary showed gabapentin had a 'moderate' level of evidence against standard benzodiazepine treatments for reducing the severity of AWS. The level of certainty was 'low' for carbamazepine, baclofen and valproate and 'very low' for acamprosate and clonidine/lofexidine. Reported adverse events between these alternative medications and benzodiazepines or placebo were generally unremarkable. CONCLUSIONS: Although benzodiazepines remain the treatment of choice for AWS, during particular circumstances, gabapentin could be an alternative although like benzodiazepines is not without risk when used in the community. Future RCTs must aim to improve upon the quality of evidence.

Disulfiram Ethanol Reaction with Alcohol-Based Hand Sanitizer: An Exploratory Study.

AIMS: We conducted a cross-sectional survey to estimate the prevalence and clinical manifestation of disulfiram ethanol reaction (DER) and isopropanol toxicity (IT) in patients with alcohol use disorders, on disulfiram. Alcohol-based hand rub contains either ethanol or isopropanol or both. COVID-19 pandemic has led to wide scale usage of sanitizers. Patients with alcohol use disorders, on disulfiram, might experience disulfiram ethanol like reactions with alcohol-based sanitizers. METHODS: We telephonically contacted 339 patients, prescribed disulfiram between January 2014 and March 2020. The assessment pertained to the last 3 months (i.e. third week of March to third week of June 2020). RESULT: The sample consisted of middle-aged men with a mean 16 years of alcohol dependence. Among the 82 (24%) patients adherent to disulfiram, 42 (12.3%) were using alcohol-based hand rubs. Out of these, a total of eight patients (19%; 95% CI 9-33) had features suggestive of DER; four of whom also had features indicative of IT. Five patients (62.5%) had mild and self-limiting symptoms. Severe systemic reactions were experienced by three (37.5%). Severe reactions were observed with exposure to sanitizers in greater amounts, on moist skin or through inhalation. CONCLUSION: Patients on disulfiram should be advised to use alternate methods of hand hygiene.

Screening and brief intervention for substance use disorders in times of COVID-19: potential opportunities, adaptations, and challenges.

The ongoing pandemic has led to a sudden disruption of routine treatment services. Consequently, the already existing treatment gap for substance use disorders is likely to widen. There is an opportunity to expand the scope of Screening and Brief Intervention (SBI) to meet this unprecedented challenge. Its brevity, flexibility, and generalizability have positioned SBI to deal with additional systemic, structural, and attitudinal barriers that pertain to the pandemic. The standard content of SBI could be modified to adapt to the current context. SBI could also be used as a vehicle to render strategies for infection risk minimization. In this Perspective, we anticipate the challenges of expanding and implementing SBI in the present circumstances and present potential solutions. SBI, with adaptations, could bridge the augmented treatment gap for substance use disorders during COVID-19.

Use and interest of electronic nicotine delivery systems (ENDS): Assessing the validity of Google Trends.

Background: Initial evidence suggests a role for Google Trends (GT) in monitoring use and interest in Electronic Nicotine Delivery Systems (ENDS).Objective: To examine the validity of GT data for assessing population behavior and interest in ENDS.Methods: GT search, done from the US and India to assess: (a) whether descriptive and statistical trends of specific search words depicting online interest in ENDS were similar to the published reports on actual use of these products in the US; (b) correlations between state-wise relative search volumes (RSV) of these words and prevalence of ENDS use; (c) the change in the online interest of ENDS after change in its regulatory policy.Results: Locally weighted scatter plot analysis showed "electronic cigarette," "vaping," and "cigarette" trends mirrored the use trend reported by the US-based National Youth Tobacco Survey (2019). Online interest in "Juul pods" followed the trends of its use. Geo-spatial RSVs of "electronic cigarette" (r=0.74, p<0.0001) and "vaping" (r=0.55, p<0.0001) correlated positively with state-wise prevalence of switch to ENDS in adults. Complete ENDS use prohibition in India was associated with a decrease in the online interest in "electronic cigarettes" (t=3.18, p=0.01) and "vaping" (t=2.3, p=0.04). Regulation of use in New Mexico (USA) was associated with a reduction in "electronic cigarettes" (t=4.09, p=0.0005) but not in "vaping."Conclusion: GT may be used to validate existing information and assess the potential effect of ENDS regulations. Its role can also be extended for monitoring interest and use of other drugs and alcohol.

Do neurocognitive functions in cannabis induced psychosis groups differ from schizophrenia with cannabis use? A controlled cross-sectional study.

OBJECTIVE: Cannabis-induced psychosis (CIP) has received little research attention. We compared neurocognitive functions in CIP, Schizophrenia with cannabis use (SZC) and healthy control group (CG). METHODS: Twenty age, education, and handedness-matched participants were recruited in each of the three groups. CIP and SZC were diagnosed with Psychiatric research interviews for substance use and mental disorders. Level of cannabis exposure, global intelligence, executive function, attention, vigilance, working, and verbal memory, and motor speed were compared by analysis of variance with post-hoc Scheffe's test. We did a post-hoc power calculation. RESULTS: Age at initiation, frequency, duration, and preparation of cannabis use did not differ significantly between CIP and SZC. CIP performed significantly better (than SZC) in tests of general cognitive ability or intelligence and attention, perceptual tracking and sequencing. SZC showed significant dysfunctions (than CG) in all parameters of the tests for executive dysfunction, sustained attention, short-term verbal memory and psychomotor functioning. CIP and CG did not differ in any cognitive domains except for non-perseverative errors in the test for executive functioning. CONCLUSIONS: CIP and SZC had different degrees of impairment compared to controls, but on direct comparisons CIP had better general intelligence and attention.KEY POINTSCannabis-induced psychosis (CIP) may have different neurocognitive impairment than Schizophrenia with cannabis use (SZC)CIP performed better in tests for general intelligence and visual attention than SZCSZC had significant impairment in executive function, attention, verbal memory, and psychomotor speed than controlsCompared to controls, CIP performed significantly worse in some domains of executive functionCIP and SZC had different degrees of cognitive impairments as compared to the controls.