Opioid use disorder and role of yoga as an adjunct in management (OUDARYAM): Study protocol for a randomized controlled trial.

Background: The proposed research aims to test the effects and mechanisms of a six-month yoga-based intervention as an add-on to standard treatment in opioid use disorder (OUD) by conducting a randomized controlled study with the following primary outcome variables: 1) clinical: abstinence (opioid negative urine test), and reductions in pain and craving, and 2) mechanisms: reward circuit activation in response to opioid visual cue craving paradigm, activation in response to a cognitive control task, and resting state functional connectivity through fMRI, and plasma beta-endorphin levels. Secondary outcome variables are perceived stress, anxiety, sleep quality, cognitive performance, pain threshold, buprenorphine dosage and side effects, withdrawal symptoms, socio-occupational functioning, vedic personality traits, heart rate variability, serum cortisol, and brain GABA levels through magnetic resonance spectroscopy (MRS). Methods: In this single-blinded, randomized, controlled, parallel-group superiority trial with 1:1 allocation ratio, 164 patients with OUD availing the outpatient/ inpatient clinical services at a tertiary mental healthcare hospital in India will be enrolled after giving informed consent. Consecutive consenting patients will be randomly allotted to one of the two groups - yoga arm (standard treatment + yoga-based intervention), or waitlist group (standard treatment alone). Allocation concealment will be followed, the clinicians, outcome assessors and data analysts will remain blind to subject-group allocation. A validated and standardized yoga program for OUD will be used as an intervention. Participants in the yoga arm will receive 10 supervised in-person sessions of yoga in the initial two weeks followed by tele-yoga sessions thrice a week for the next 22 weeks. The wait-list control group will continue the standard treatment alone for 24 weeks. Assessments will be done at baseline, two weeks, 12 weeks, and 24 weeks. Data from all randomized subjects will be analysed using intent-to-treat analysis and mixed model multivariate analysis. Dissemination: Findings will be disseminated through peer-reviewed publication, conference presentations, and social media. Trial registration number: The trial has been registered under Clinical Trials Registry-India with registration number CTRI/2023/03/050737.

Yoga as an Adjuvant with Multimodal Psychological Interventions for Excessive Use of Technology: A Randomized Controlled Trial from India.

Background: Multimodal approach of psychotherapy has been found to be effective for managing the excessive use of technology. Yoga, a holistic mind-body therapy, has been observed to be a useful adjuvant in managing substance use disorders. Yoga is also known to reduce stress and enhance overall well-being. The aim of this study was to examine whether yoga as an adjuvant treatment to psychotherapy is better than psychotherapy alone in reducing dysfunction and severity due to excessive technology use. Methods: A two-arm randomized controlled prospective study design was followed with assessor blinding and allocation concealment. Thirty consenting young adults (22 males), scoring above 36 on the Internet Addiction Test, were randomly allocated to either: Group A = psychotherapy + yoga or Group B = psychotherapy alone. Both groups received 8 sessions of psychotherapy in the 1st month. In addition, Group A received additional 10 sessions a specific yoga program (by trained professionals). After that, monthly booster sessions (supervised yoga sessions performed with direct one-on-one contact with the yoga therapist) were organized and post-assessment was conducted at 12 weeks. Each subject was assessed using the Internet Addiction Test-Short Form, Internet Gaming Disorder Scale-Short Form, Smartphone Addiction Scale-Short Version, and Kessler Psychological Distress Scale at baseline and after 12 weeks. Results: As compared to Group B, Group A had significantly reduced Internet use (F = 5.61, P = 0.02, ηp 2 = 0.17), smartphone use (F = 4.76, P = 0.03, ηp 2 = 0.15), psychological distress (F = 7.71, P = 0.01, ηp 2 = 0.22), and weekday use (Z = -2.0, P = 0.05, ηp 2 = 0.15) along with enhanced treatment adherence and retention. Conclusion: Yoga as an adjuvant therapy with multimodal psychological intervention for excessive use of technology was found to be effective. This carries clinical implications for mental health professionals.

A descriptive study of hepatitis C in people who inject drugs.

BACKGROUND OBJECTIVES: The seroprevalence of the hepatitis C virus (HCV) in general population is higher than that of human immunodeficiency virus (HIV) in India. People who inject drugs (PWIDs) constitute a high-risk group for all blood-borne infections. Multiple behavioural surveillance surveys have provided a rich typology of HIV-infected PWIDs, but this information is missing for HCV infection. We describe awareness, transmission risk factors and the treatment continuum for HCV infection among PWID. We also report spatial clustering of HCV infection in PWIDs residing in Bengaluru. METHODS: Information from clinical records was collected and telephonic interviews of retrospectively identified PWIDs who received treatment at a tertiary-level addiction treatment facility between 2016 and 2021 were conducted. RESULTS: We identified 391 PWIDs; 220 (56.26%) received an anti-HCV antibody test (4 th Generation HCV-Tridot). Individuals reporting unsafe injection practices were more often tested than those who did not ( χ2 =44.9, df=1, P <0.01). Almost half of the tested and more than a quarter of the whole sample (109/220, 49.9%; 109/391, 27.9%) were seropositive for HCV infection. The projected seropositivity in this group was between 27.9 per cent (best case scenario, all untested assumed negative) and 71.6 per cent (worst case scenario, all untested assumed positive). Only a minority of participants interviewed were aware of HCV (27/183, 14.7%). HCV infection and its associated risk behaviour (PWID) were clustered in certain localities (Diggle and Chetwynd Test; P =0.001) in Bengaluru in the southern district of Karnataka. INTERPRETATION CONCLUSIONS: Undetected HCV infection is common in PWIDs; awareness and treatment uptake is poor in this group. Spatial clustering of infections in a district shows transmission in close networks and provides opportunities for targeted interventions.

Quantification of Δ9-tetrahydrocannabinol in urine as a marker of cannabis abuse.

BACKGROUND OBJECTIVES: Cannabis use has long been associated with celebration and hospitality, although abuse must be confirmed through testing. It has always been difficult to develop an accurate and reliable confirmatory method for the quantification of tetrahydrocannabinol carboxylic acid (THC-COOH) that meets local requirements. The goal was to develop a rapid, cost-effective analytical technique that can handle large batches. METHODS: Because of the wide metabolite detection window and ease of collection, urine was preferable sample. The extraction of a pre-screened urine sample (adulteration and multidrug screening) was done on Bond Elut cartridges using a positive pressure vacuum manifold, followed by quantification using a gas chromatograph and mass spectrometer. RESULTS: The assay was linear between 15 and 300 ng/ml ( r2 of 0.99). The intra-day precision was 8.69 per cent and the inter-day precision was 10.78 per cent, respectively with a 97.5 per cent recovery rate for the lowest concentration. A total of 939 urine samples were examined, with 213 detecting cannabis. Sixty per cent of the total individuals tested positive for simply cannabinoids, 33 per cent for cannabinoids and sedatives, five per cent for cannabinoids and morphine and one for cannabis, morphine and cocaine. INTERPRETATION CONCLUSIONS: Assay characteristics included modest sample preparation, rapid chromatography, high specificity and small sample volume with a processing time of 12 h. The assay described here can be applied for diagnostic laboratories and in forensic settings as well.

Physical and chemical characterization of smokeless tobacco products in India.

The rapid proliferation of smokeless tobacco (SLT) in India has occurred without adequate information on the possible dangers and toxicity of these products. Tobacco flavors as well as nicotine (both protonated and un-protonated) are responsible for health dangers and addiction. The study aimed to offer information on the physical characteristics of commonly used smokeless tobacco products (including microscopic analysis), along with nicotine content (both total and un-protonated), pH, moisture, and flavors. The Standard Operating Procedures (SOPs) validated by the World Health Organization (WHO) recognized Tobacco Testing Laboratory TobLabNet) were applied for the analysis of various constituents of the SLTs. The microscopic analysis indicated that some of the SLT products like khaini were finely processed and available in filter pouches for users' convenience and prolonged use leading to prolonged retention and addiction potential. Nicotine absorption and availability (both protonated and un-protonated) are affected by moisture and pH. Essences provide a pleasant aroma and flavor, with an increased risk of misuse and other health problems. Few chewing tobacco and Zarda had the lowest levels of un-protonated nicotine (0.10-0.52% and 0.15-0.21%, respectively), whereas Gul, Gudhaku, and Khaini had the highest levels, ranging from 95.33 to 99.12%. Moisture and pH ranged from 4.54 to 50.19% and 5.25-10.07 respectively. Menthol (630.74-9681.42 µg/g) was the most popular flavour, followed by Eucalyptol (118.16-247.77 µg/g) and camphor (148.67 and 219.317 µg/g). SLT's health concerns and addiction dangers are exacerbated by the high proportion of bioavailable nicotine coupled with flavors. The findings of this study have important implications for the regulation and use of SLT in countries where use of SLT is prevalent.

Development of a Personalized Tobacco Cessation Intervention Package (PTCIP) for Persons with Schizophrenia in India.

Background: Among persons with schizophrenia (PwS), tobacco use is higher in comparison to the general population, contributing to greater morbidity and mortality. Pharmacological interventions combined with psychosocial interventions are effective in tobacco cessation. While the effectiveness of extant psychosocial interventions-when used in isolation-seems limited, developing better combinations of interventions could help treatment providers deliver tobacco cessation services to PwS at different stages of motivation to quit. We aimed to develop a personalized tobacco cessation intervention package (PTCIP) for PwS. Methods: The stage-based intervention package was developed through a systematic review of interventions for tobacco cessation, the authors' clinical experience, and expert validation. The components of the intervention package, developed for PwS visiting the outpatient psychiatric department, were retained, removed, or added based on the content validity ratio (CVR). Results: The final components included brief advice, principles of motivational interviewing, psychoeducation, decisional balance matrix, positive reinforcement, offering various treatment options, personalized feedback using a smoking-risk calculator, and prediction of cardiovascular risk using the WHO package of essential noncommunicable disease (PEN). The delivery of the intervention package was refined based on pilot testing in eight participants. Conclusion: The tailored package was designed to be delivered by a mental health professional as a single comprehensive 40 min to 45 min face-to-face session, integrated with routine follow-up visits, followed by two telephonic conversations in the second and third week of the initial session. The package needs to be tested in a randomized controlled trial for its effectiveness.

Effectiveness of personalized tobacco cessation intervention package among patients with schizophrenia and related psychotic disorders - A two-group experimental study.

INTRODUCTION: Persons with schizophrenia and related psychotic disorders (PwS) smoke more, and have twice the rate of mortality, with 10-25 years lower life expectancy than the general population. Evidence-based tobacco cessation interventions would help in quitting. AIM: To evaluate the effectiveness of a personalized tobacco cessation intervention package for patients attending the outpatient psychiatry department. METHODS: The study adopted a two-group experimental design in PwS, using a simple randomization method. Eligible participants were randomly allocated to either the intervention group (n = 85) receiving the intervention package or the control group (n = 85) receiving brief advice to stop tobacco. The study outcomes were measured at baseline, 1, 3, and 6 months. SPSS 23 was used for data analysis. Intention-to-treat analysis was used to manage missing data. The p-value of < 0.05 is considered statistically significant. RESULTS: At 6 months, there was a significant difference (p < 0.001) in 7 days point-prevalence abstinence (28 % vs 10.8 %), reduction of tobacco by at least 50 % (62.4 % vs 40.9 %) with an attrition rate of 15.3 % vs 30.5 % in intervention and control group respectively. Reduction in nicotine dependence and tobacco craving, an increase in motivation level, quit attempts and clinical improvement favored the intervention group. 16.5 % of participants expressed interest in pharmacotherapy for tobacco cessation, 3.5 % were referred to a specialized tobacco cessation center, two control group participants were hospitalized for drug default, and withdrawal symptoms reported were mild. CONCLUSION: Implementing a tobacco cessation intervention based on the stage of motivation aids in abstinence and reduction of tobacco use in PwS.

Relationship of anemia with COVID-19 deaths: A retrospective cross-sectional study.

Background and Aims: With the second wave of COVID-19, India lost close to three lakh people within the span of a few months. In this study, we aimed to investigate the impact of anemia on the severity of COVID-19 based on the hemoglobin (Hb) concentration of the patients noted at the time of admission to the intensive care unit (ICU), to mark Hb as a prognostic marker of disease severity for the future. Material and Methods: Retrospective data was collected from 784 patients admitted to the COVID adult ICU between March and June 2021. Patients were identified as anemic and non-anemic based on the World Health Organization (WHO) guidelines. Chi-squared test was applied to see the relationship of anemia with the patient deaths. Results: Among the 784 patients, 507 succumbed to COVID-19. Of these, 49.3% had varying degrees of anemia. Significant correlation of anemia with death due to COVID-19 was found in males and females (P = 0.002106 and P = 0.033071, respectively) and in patients without any other comorbidities except anemia (P = 0.002020). This suggests that anemia is independently an important parameter that plays a role in severity of COVID-19. Conclusion: Upon observing a significant correlation between anemia and COVID-19 severity, it can be stated that anemia should be considered as an independent prognostic risk factor for COVID-19 and that hemoglobin can be used for risk stratification in patients under home or hospital care.

Prevalence and severity of tobacco use and access to tobacco cessation among tertiary care psychiatric in-patients in India.

Background: Rates of smoking in persons with mental illness are reported to be two times higher than those without mental illness in developed countries. We aimed to examine the prevalence and severity of tobacco use, and access to tobacco cessation services among tertiary care psychiatric in-patients in India. Methods: In this cross-sectional study, 500 consecutive adult in-patients in tertiary care with ICD 10 diagnoses, F20-59, were administered a sociodemographic and clinical proforma, Clinical Global Impression-Severity scale, Fagerstrom Test for Nicotine Dependence, Tobacco Craving Questionnaire, Reasons for quitting questionnaire, and Smoke Scale-Adults. Urine cotinine levels were estimated in the last 100 patients. Details of tobacco use and cessation interventions provided were obtained. Results: Overall prevalence of current tobacco use was 34.00%; 34.3%, 32.6%, 43.6%, and 16.7% in patients of F20-29, F30-39, F40-49, and F50-59 categories, respectively. Males used tobacco products at a significantly higher rate (44.85% vs. 17.58% in females) and were highly dependent. Smokeless tobacco use was reported in 20.5% and 18% of female patients with F20-29 and F30-39 diagnoses, respectively. More than half of the tobacco users were not asked about tobacco use and 89.4% of the users were provided no prior assistance for cessation at the time of assessment. Urinary cotinine levels were significantly greater for those who use smokeless forms than smokers or dual users. Conclusions: Nearly a third of psychiatric in-patients are current users of tobacco. Moderate to severe tobacco dependence was observed across psychiatric diagnoses. The assessment and interventions provided were suboptimal.

Yoga as an Adjunct for Management of Opioid Dependence Syndrome: A Nine-Month Follow-Up Case Report.

Opioid dependence syndrome (ODS) is a chronic relapsing remitting condition associated with significant impairment and mortality risk. Opioid substitution therapy is used worldwide, but long-term retention rates are low and there is risk of misuse and diversion. Yoga practice can improve quality of life, reduce chronic pain, and enhance endogenous opioids (beta-endorphins). We describe a case of ODS where yoga was added to the conventional management and who was followed up for 9 months. Assessments were done for clinical symptoms, urine drug screening, plasma beta-endorphins, and Buprenorphine dosage. We observed an improvement in his clinical symptoms and reduction in the requirements for Buprenorphine. A slight increase in basal plasma beta-endorphin levels was also observed at the 9-month follow-up (from 2.02 pmol/L at baseline to 6.51 pmol/L).

Evidence of low levels of trace organic contaminants in terminal lakes.

Endorheic lakes (or terminal lakes, TLs) have no natural outlet other than evaporation and slow infiltration. Some TLs receive reclaimed wastewater which contains poorly removed trace organic contaminants (TrOCs). To determine if TLs accumulate TrOCs we conducted a preliminary assessment of the occurrence of ten TrOCs in three TLs receiving reclaimed wastewater and one TL which does not directly receive reclaimed wastewater. Five of ten TrOCs (carbamazepine, DEET, fluoxetine, primidone, and trimethoprim) were present in all four TLs' surface waters (~0.3-1109 ng/L), six (caffeine, carbamazepine, DEET, diphenhydramine, primidone, and trimethoprim) were present in sediment samples (0.1-77 ng/gDW) and in soil samples (0.1-137 ng/gDW). Concentrations of caffeine, carbamazepine, diphenhydramine, fluoxetine and meprobamate were significantly higher in TLs receiving wastewater from a secondary treatment plant compared to those TLs which received tertiary treated wastewater. Carbamazepine, fluoxetine, sulfamethoxazole, and trimethoprim were present at concentrations greater than is typical of other U.S. freshwater lakes, but other TrOC concentrations were present at lower concentrations than in other freshwater lakes. We conclude that some TrOCs may accumulate in TLs, but to a lesser extent than would be expected based on the accumulation of dissolved constituents alone, which indicates that there are other unidentified processes in TLs that contribute to TrOC losses. Other TLs across the globe may have similar levels of TrOCs due to anthropogenic influence and treated wastewater inputs.

Development, Validation, and Feasibility Testing of a Yoga Module for Opioid Use Disorder.

CONTEXT: Opioid use disorder (OUD) involves excessive use of opioids-such as heroin, morphine, fentanyl, codeine, oxycodone, and hydrocodone-leading to major health, social, and economic consequences. Yoga lifestyle interventions have been found to be useful as adjunct therapies in management of substance use disorders and chronic pain conditions. OBJECTIVE: The research team intended to develop, validate, and test for feasibility a yoga program for OUD patients that could reduce opiate withdrawal symptoms-such as pain, fatigue, low mood, anxiety and sleep disturbances-and cravings associated with drugs. DESIGN: The research team first performed a literature review of traditional and contemporary yoga texts, such as Hatha Yoga Pradipika and Light on Yoga, as well as modern scientific literature in the following search engines-Google Scholar, PubMed, and PsychInfo, using the keywords yoga, pranayama, hatha yoga, relaxation. meditation, substance use, addiction, impulsivity, craving, sleep quality, and fatigue. Using the information obtained, the team developed a yoga program and designed a pilot study that used the program. SETTING: The study took place in the Department of Integrative Medicine at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bangalore, India. PARTICIPANTS: Participants in the pilot study were 8 inpatients, 6 males and 2 females, who were on opioid agonist treatment (buprenorphine) for OUD. INTERVENTION: The intervention was the yoga program previously validated by the research team. In the pilot study, participants were taught a one-hour, yoga-based intervention, with sessions occurring once per day, for 10 sessions. OUTCOME MEASURES: For validation, 13 experts scored the yoga program that the research team had developed and gave suggestions for each yogic practice for use during the acute phase of withdrawal and the maintenance phase respectively. A content validity ratio (CVR) was calculated from their scoring, and the research team made changes to the program base on the scoring and suggestions. For the pilot study, assessments occurred at baseline and postintervention. The participants' yoga performance was rated by the yoga trainer on a yoga performance assessment scale (YPA). Other measurements included: (1) the Clinical Opiate Withdrawal Scale (COWS), (2) the Hamilton's anxiety rating scale (HAM-A), (3) the Hamilton's depression rating scale (HAM-D), (4) buprenorphine dosage, (5) the Clinical Global Impression Severity (CGI-S) scale, (6) a visual analog scale (VAS) for pain, (7) sleep quality (latency and duration), and (8) the module's safety. RESULTS: Four practices were removed from the program due to CVR scores below the cutoff, and one practice was found not to be feasible (Kapalabhati). Two categories of yoga modules emerged: (1) for the acute symptomatic phase (40 minutes) and (2) for the maintenance phase (one hour). Practices were added or excluded based on the phase. CONCLUSIONS: The yoga module that was developed for reducing withdrawal symptoms and cravings in OUD patients was found to be safe, feasible, and potentially useful as an adjunct therapy to conventional treatment.

Quantification of pharmaceuticals in the sealant fluids of actively used waterless urinals.

Prior measurements at bench scale revealed that waterless urinal cartridges containing oily sealant fluids are capable of partitioning pharmaceuticals from urine and therefore reducing their concentration in wastewater. We sought to measure pharmaceutical removal from in-use waterless urinals. We developed a method to quantify pharmaceuticals in the sealant phase, which resulted in 79 ± 30% and 71 ± 30% recovery of eight pharmaceuticals from two sealant fluids, respectively. The method was applied to sealant samples collected over three weeks from in-use waterless urinals on a university campus. Six of eight pharmaceuticals were present in the sealant samples from 1.4 µg/L to 241 µg/L. Loads of the six pharmaceuticals detected in the sealants were removed from the receiving wastewater from 0.02 µg/day to 3.4 µg/day across the sampling period. The concentration of the pharmaceuticals were similar over time, indicating rapid saturation and washout of the sealant. We also observed relatively rapid loss of sealant at maintenance intervals consistent with the manufacturer's instructions. These findings indicate that while waterless urinals do remove some pharmaceuticals from the wastewater stream, meaningful changes to wastewater concentrations will only result if the sealant fluid and/or the urinal cartridge are significantly modified. PRACTITIONER POINTS: We developed a quantification method for pharmaceuticals in oily waterless urinal sealants. Pharmaceuticals were present at relatively low concentrations in the sealant phase of two in-use waterless urinals. We identify engineering challenges that must be overcome to meaningfully reduce pharmaceutical loads in wastewater with waterless urinals.

Modeling the fate and human health impacts of pharmaceuticals and personal care products in reclaimed wastewater irrigation for agriculture.

Wastewater reclamation and reuse for agriculture have attracted a great deal of interest, due to water stress caused by rapid increase in human population and agricultural water demand as well as climate change. However, the application of treated wastewater for irrigation can lead to the accumulation of pharmaceuticals and personal care products (PPCPs) in the agricultural crops, grazing animals, and consequently to human dietary exposure. In this study, a model was developed to simulate the fate of five PPCPs; triclosan (TCS), carbamazepine (CBZ), naproxen (NPX), gemfibrozil (GFB), and fluoxetine (FXT) during wastewater reuse for agriculture, and potential human dietary exposure and health risk. In a reclaimed wastewater-irrigated grazing farm growing alfalfa, it took 100-535 days for PPCPs to achieve the steady-state concentrations of 1.43 × 10-6, 4.73 × 10-5, 1.17 × 10-6, 1.53 × 10-5, and 7.38 × 10-6 mg/kg for TCS, CBZ, NPX, GFB, and FXT in soils, respectively. The accumulated concentration of PPCPs in the plant (alfalfa) and grazing animals (beef) ranged 2.86 × 10-7- 4.02 × 10-3 and 4.39 × 10-15- 6.27 × 10-7 mg/kg, respectively. Human dietary exposure to these compounds through beef consumption was calculated to be 1.67 × 10-18- 1.74 × 10-10 mg/kg bodyweight/d, much lower than the acceptable daily intake (ADI). Similar results were obtained for a 'typical' reclaimed wastewater irrigated farm based on the typical setup using our model. Screening analysis showed that PPCPs with relatively high LogD value and lower ratios of degradation rate (in soils) to plant uptake have a greater potential to be transferred to humans and cause potential health risks. We established a modeling method for evaluating the fate and human health effects of PPCPs in reclaimed wastewater reuse for the agricultural system and developed an index for screening PPCPs with high potential to accumulate in agricultural products. The model and findings are valuable for managing water reuse for irrigation and mitigating the harmful effects of PPCPs.

Non-pharmacological interventions for smoking in persons with schizophrenia spectrum disorders - A systematic review.

INTRODUCTION: The rates and intensity of tobacco use are higher in persons with schizophrenia spectrum disorders (PwS) compared to the general population, contributing to increased morbidity and mortality. We aimed to systematically review randomised control trials (RCTs) that used non-pharmacological interventions to reduce or cease tobacco use in PwS. METHODS: We searched PubMed, EBSCO, ProQuest and PsycINFO for RCTs, published between January 2004 and December 2019, which included adult PwS. Studies providing self-reported or biochemically measured reduction of tobacco use and cessation after a minimum follow-up period of 6 months were included. We used the Cochrane Risk of Bias (ROB) tool for assessing the quality of selected studies. RESULTS: Of the six included trials, two compared non-pharmacological interventions alone while four compared combinations with pharmacological interventions with routine care. The non-pharmacological interventions varied widely. Continuous abstinence and seven days point-prevalence abstinence (7 PPA) were reported in 2 and 4 studies respectively, with one study assessing both. All six trials measured reduction in the number of cigarettes smoked, but only two trials reported significant reductions in intervention groups. No worsening of psychiatric symptoms was reported. CONCLUSIONS: Two trials were rated as "low risk", and 4 trials as "some concerns" on the ROB tool. Heterogeneity among trials precluded meta-analysis. Abstinence was significantly higher among groups who were given combination interventions, and intervention groups in studies showed significantly greater or a trend towards reduction in the number of cigarettes smoked than controls. No specific method of non-pharmacological management was conclusively favoured. IMPLICATIONS: Reduction in cigarettes smoked seemed to significantly favour or show non-significant trends favouring intervention groups over controls, while abstinence was significantly higher among groups in studies that used specific combination interventions. Combinations of pharmacological and non-pharmacological treatment were better than non-pharmacological interventions used in isolation, for facilitating abstinence and reduction in cigarettes smoked. Specific interventions such as home visits and contingent reinforcement merit further study. Trials included in this study were conducted in high-income and upper-middle-income countries. Thus, the application of these interventions to low and middle-income countries (LAMICs) needs to be further studied.

Changes in DNA methylation persist over time in males with severe alcohol use disorder-A longitudinal follow-up study.

Treatment strategies for alcohol use disorder (AUD) aim for abstinence or harm reduction. While deranged biochemical parameters reverse with alcohol abstinence, whether molecular changes at the epigenetic level reverse is not clearly understood. We investigated whether the reduction from high alcohol use reflects DNA methylation at the gene-specific and global level. In subjects seeking treatment for severe AUD, we assessed gene-specific (aldehyde dehydrogenase [ALDH2]/methylene tetrahydrofolate reductase [MTHFR]) and global (long interspersed elements [LINE-1]) methylation across three-time points (baseline, after detoxification and at an early remission period of 3 months), in peripheral blood leukocytes. We observed that both gene-specific and global DNA methylation did not change over time, irrespective of the drinking status at 3 months (52% abstained from alcohol). Further, we also compared DNA methylation in AUD subjects with healthy controls. At baseline, there was a significantly higher gene-specific DNA methylation (ALDH2: p < .001 and MTHFR: p = .001) and a significant lower global methylation (LINE-1: p = .014) in AUD as compared to controls. Our results suggest that epigenetic changes at the DNA methylation level associated with severe AUD persist for at least 3 months of treatment.

Trace organic contaminants in field-scale cultivated alfalfa, soil, and pore water after 10 years of irrigation with reclaimed wastewater.

Several studies have assessed the presence of trace organic contaminants (TrOCs) in reclaimed wastewater and their uptake into crops but there are limited data from field-scale studies. In this research, we studied the fate of 12 TrOCs in wastewater samples, 11 in plants and in soil pore water, and 10 in soil at an agricultural research farm, which was irrigated with reclaimed wastewater for more than 10 years. First, we examined the presence of the compounds in the primary, secondary, and treated effluent of a regional water reclamation facility which provides the irrigation water. The agricultural field produced alfalfa, and we measured the contaminants in the alfalfa, soil, and pore water. Reclaimed wastewater contained 11 of 12 TrOCs, with concentrations ranging from 26 ± 9 ng/L (DEET) to 1539 ± 1899 ng/L (trimethoprim). Atrazine was not detected. Pore water collected during non-irrigating periods contained all analyzed TrOCs, from 3 ± 0.1 ng/L (diphenhydramine) to 343 ± 360 ng/L (primidone). TrOCs measured in pore water samples indicated that they may leach to shallow groundwater even when fields are not being irrigated. Soils from 0 to 60 cm contained nine TrOCs from below the reporting limit (fluoxetine) to 329 ng/g (carbamazepine). Atrazine was not detected. TrOC concentrations decreased with increasing soil depth, except carbamazepine, which was more recalcitrant. Nine TrOCs were present in the shoots and leaves of alfalfa grown in the reclaimed wastewater irrigated plots, at concentrations ranging from <1 ng/g (diphenhydramine and fluoxetine) to 49 ng/g dry weight (carbamazepine). Atrazine and caffeine were not detected. We estimated that a maximum of 14% of DEET from the reclaimed wastewater was accumulated in alfalfa. Overall, despite some accumulation of TrOCs in the soil, alfalfa uptake was limited, which results in low exposure to foraging animals.

Do Indian patients with schizophrenia need half the recommended clozapine dose to achieve therapeutic serum level? An exploratory study.

Inter-racial differences in serum clozapine have received less scientific importance, as there are fewer studies on therapeutic drug monitoring (TDM) from Asia. We measured the serum clozapine levels in 142 patients with schizophrenia and related disorders at a tertiary care psychiatric institute in India. The clozapine concentration per milligram (mg) of oral clozapine dose (C/D ratio) was calculated, and the C/D ratio was used to estimate oral clozapine dose needed to achieve therapeutic serum clozapine level (350 ng/ml). This study examined Indian patients only and compared the results with weighted mean serum clozapine and its correlates in Caucasian population, based on published scientific literature. The median C/D ratio in our sample was 2.5 (n = 142), and the clozapine dose needed to achieve therapeutic serum clozapine level was 140 mg/d. The median C/D ratio of our subjects was nearly two and a half times higher than the weighted mean C/D ratio of Caucasians (2.5 v/s 1.07) reported elsewhere. After excluding the significant pharmacokinetic interactions and stratifying according to gender and smoking status, the estimated clozapine dose to achieve therapeutic serum level in male smokers (n = 9) and female non-smokers (n = 38) were 238 mg/d (C/D ratio; 1.47) and 120 mg/d (C/D ratio:2.93) respectively. On comparing, male smokers (600 mg/d versus 238 mg/d) and female non-smokers (300 mg/d versus 120 mg/d) in our study needed about 40% of the recommended clozapine dose for Caucasians to achieve therapeutic serum clozapine level. The pharmacogenetic correlates of lesser clozapine dose requirement in the Indian population require further research.