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.

Neurocognitive Dysfunctions in People with Concurrent Cannabis Use and Opioid Dependence: A Cross-Sectional, Controlled Study.

Cannabis and opioid co-dependence is independently associated with cognitive impairments. We examined neurocognitive dysfunctions in people with concurrent opioid dependence with cannabis dependence (OD+CD) or cannabis use (OD+CU) compared to those with only opioid dependence (OD) and healthy controls (HC). We selected adult participants, any sex, who met the diagnosis of OD (N = 268), OD+CU (N = 58), and OD + CD (N = 115). We recruited 68 education-matched HC. We administeredStandard progressive matrices (SPM), Wisconsin card sorting test (WCST), Iowa gambling task (IGT), Trail making tests A and B (TMT), and verbal and visual working memory 1-, 2-backtests. 496 (97.5%) were men, and 13 (2.5%) were women. In WCST, OD and OD+CD had significantly higher non-perseverative errors than HC. OD+CD group completed significantly lesser categories than HC. In verbal working memory 2-back, HC scored significantly fewer errors than OD and OD +CD. All patient groups, OD, OD+CU, and OD+CD, scored higher commission errors than HC in visual working memory 1-back. OD and OD+CD scored higher commission and total errors than the controls. OD+CU showed lesser error score than HC in TMT B. Cannabis and opioid co-dependence contribute to cognitive impairments, especially in working memory and executive functions.

Substance use in the correctional settings: A qualitative exploration of individual and contextual characteristics and intervention strategies using the behavior change wheel framework.

BACKGROUND AND OBJECTIVES: Planning and implementing prison-based substance use disorder (SUD) interventions are challenging. We wanted to understand why and how people in correctional settings (CS) use drugs and to explore what policies, environmental, and interpersonal factors influence substance use among incarcerated people. Using the Behavior Change Wheel (BCW) framework, we proposed a thematic map with intervention functions to reduce substance use in CS. METHODS: We used the Framework Method of qualitative analysis. We did snowball sampling for the incarcerated people with drug use (PWD) and convenience sampling for the staff. The in-depth interview sample comprised 17 adult PWD, three prison administrative, and two healthcare staff. We determined the sample size by thematic data saturation. We followed a mixed coding approach for generating categories, i.e., deductive (based on the BCW framework) and inductive. The study constructed the final theoretical framework by determining the properties of the categories and relationships among the categories. RESULTS: We identified eleven categories aligned with the BCW framework. The themes were prison routine, interpersonal dynamics of the incarcerated population, exposure to substance use, attitude of staff towards PWD, experience with prison healthcare, willingness (to reduce drug use) and coping, compassion, drug use harms, conflict between staff and residents, stigma, and family/peer support. The BCW framework aided the identification of potential intervention functions and their interactions with the organizational policies that could influence PWD's capability-opportunity-motivation (COM) and drug use behavior (B). CONCLUSION: There is a need to raise awareness of SUD prevention and intervention among decision-makers and revisit the prison policies.

Is there any association between cognitive deficits and immune markers in Acute and Transient psychotic disorders? A pilot study.

BACKGROUND: There are studies to support association between immune function and cognition in patients with schizophrenia (SZ). However, there are no such study which had tried to explore the same in patients with Acute and transient psychotic disorders (ATPDs), which is considered to similar in presentation to SZ. METHODS: This is an extended analysis of the study published in which we had recruited 19 subjects with ATPDs in acute phase of illness were age-/gender-matched with patients schizophrenia in remission. Clinical assessment and immune-marker levels (IL-6,IL-8,IL-17) were carried out along with follow -up repeat immune-marker levels assessment in the ATPD group was conducted after remission status was ensured (at least 3 months after resolution of acute phase). Cognitive assessment was done on Montreal Cognitive Assessment Scale (MoCA) in both the groups (ATPD in both phases and in SZ). RESULTS: The mean MoCA total score was 12.05 (SD-5.0) in the acute phase and 27.05 (SD-2.46) in the remission phase in the ATPD group which was statistically significant. When compared with patients with SZ in remission, patients with ATPD in remission performed better in all domains of MoCA, however only statistically significant differences in the total MoCA score and in the visuospatial domain scores of MoCA. No significant association between any of the immune marker levels (IL-6, Il-8 and IL-17) with any domains of the MoCA in patients with ATPD neither in the acute phase nor in the remission phase was found. Additionally, no significant association between the cognitive scores in the MoCA domains of the patients with schizophrenia and immune marker levels was found too. CONCLUSION: To conclude, the present study's findings suggested that there existed definite cognitive deficits in patients with ATPDs in both acute and remission phase and in patients with SZ. However, the study could not establish any relationship/association between cognitive deficits/scores in patients with ATPDs in both phases as well as in patients with SZ with immune marker levels.

Service users' perception and attitude toward telemedicine-based treatment for substance use disorders: A qualitative study from India.

Aim: We aimed to assess the service user's acceptability, feasibility, and attitude toward telemedicine practice and compare it with in-person consultation in substance use disorder (SUD). Materials and Methods: We recruited 15 adult patients with SUD who accessed both telemedicine and in-person care. We conducted in-depth interviews on awareness and access, facilitators and barriers, treatment satisfaction, and therapeutic relationship in the telemedicine context. We performed a conventional content analysis of the interview excerpts and used inductive and deductive coding. We assumed that social, personal, and logistic contexts influence patients' perceptions and experiences with telemedicine-based addiction care (TAC). Results: Most participants were middle-aged men (40.5 years, 86.7%), dependent on two or more substances (86.7%), and had a history of chronic, heavy substance use (use ~16 years, dependence ~11.5 years). Patients' perspectives on TAC could broadly be divided into three phases: pre-consultation, consultation, and post-consultation. Patients felt that TAC improved treatment access with adequate autonomy and control; however, there were technical challenges. Patients expressed privacy concerns and feared experiencing stigma during teleconsultation. They reported missing the elaborate inquiry, physical examination, and ritual of visiting their doctors in person. Additionally, personal comfort and technical difficulties determine the satisfaction level with TAC. Overall perception and suitability of TAC and the decision to continue it developed in the post-consultation phase. Conclusion: Our study provides an in-depth insight into the barriers and facilitators of telemedicine-based SUD treatment access, use, and retention; it also helps to understand better the choices and preferences for telehealth care vis-à-vis standard in-person care for SUDs.

The toll of opioid dependence: A research report on the possible role of Toll-like receptor-4 and related immune markers in opioid dependence.

Background: The opioid receptors in the central nervous system and immune system contribute to its reinforcing effect. Xenobiotics-associated molecular pattern of opioids interacts with Toll-like receptor-4 (TLR-4) on the glial cell surface and increases dopaminergic activity in the nucleus accumbens in preclinical studies. We wanted to examine whether treatment with buprenorphine-naloxone (BNX) might be associated with changes in immunological markers in individuals with opioid dependence (OD). Methods: We recruited 30 individuals with OD on buprenorphine and 30 age- and sex-matched healthy controls (HCs). We measured the neutrophil (N), lymphocyte (L), CD-4, and CD-8 T-cell count and estimated plasma TLR-4 level in the HC group once. We measured the immunological markers, craving, pain, and perceived stress in the OD group at the treatment initiation (baseline) and after 4 weeks (±2 weeks) of treatment with BNX. Results: The mean severity score on the OD questionnaire was 72.8 (SD 5.4). At baseline, OD had a higher N: L ratio and lower lymphocyte percentage than HC. Plasma TLR-4 concentration increased significantly after 1 month of treatment (t = -3.09, P = 0.004). Craving, pain, and perceived stress correlated with absolute neutrophil count, N: L ratio, and CD-8 T-cell count, although lost significance after corrections for multiple comparisons. Conclusion: The increase in TLR-4 after treatment with BNX may indicate the rescue from nonprescription opioid-induced immunosuppression or the introduction of a novel xenobiotics-associated molecular pattern of BNX.

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.

Effectiveness of buprenorphine (naloxone) for opioid dependence does not differ across opioid categories: a retrospective cohort study from India.

We aimed to examine whether treatment retention, abstinence, and adherence to buprenorphine-naloxone (BNX) differ among individuals with opioid dependence (OD) across three common categories of opioids- heroin, opium, and low-potency pharmaceutical. In a retrospective cohort study, we analyzed outpatient treatment records from March 2020 through February 2022. Opioid category was determined by lifetime and current opioid use. We defined treatment retention as weeks of uninterrupted clinic attendance. Abstinence and BNX adherence were calculated by weeks of extra-medical opioid-negative and buprenorphine-positive urine screening from treatment initiation. Four-hundred-thirteen patients were eligible; 406 (98.3%) were included in the final analysis. Two-hundred-ninety (71.4%) patients were dependent on heroin; 66 (16.3%) were natural opioid dependent, and 50 (12.3%) were dependent on low-potency pharmaceutical opioids. BNX effectiveness in treatment retention, abstinence, and adherence did not differ in patients dependent on heroin, natural, and low-potency pharmaceutical opioids. Patients on ≥8 mg daily BNX had better retention and adherence than those on <8 mg daily. Patients from lower socioeconomic status (SES) had higher odds of retention, abstinence, and adherence than those from upper/middle SES. Treatment outcomes on BNX did not differ across opioid categories. However, BNX should be dosed adequately.

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India.

Importance: Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. Objective: To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their underlying brain mechanisms. Design, Setting, and Participants: This multicenter population-based cohort study analyzed cross-sectional data of the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, recruited between November 4, 2016, and May 4, 2019. Participants aged 6 to 23 years were characterized using deep phenotyping measures of behavior, neuropsychology, psychopathology, brain neuroimaging, and exposure to developmental adversities and environmental neurotoxins. All analyses were performed between June 1, 2020, and December 31, 2021. Exposure: Arsenic levels were measured in urine as an index of exposure. Main Outcomes and Measures: Executive function measured using the cVEDA neuropsychological battery, gray matter volume (GMV) from T1-weighted magnetic resonance imaging, and functional network connectivity measures from resting state functional magnetic resonance imaging. Results: A total of 1014 participants aged 6 to 23 years (589 male [58.1%]; mean [SD] age, 14.86 [4.79] years) were included from 5 geographic locations. Sparse-partial least squares analysis was used to describe a negative association of arsenic exposure with executive function (r = -0.12 [P = 5.4 × 10-4]), brain structure (r = -0.20 [P = 1.8 × 10-8]), and functional connectivity (within network, r = -0.12 [P = 7.5 × 10-4]; between network, r = -0.23 [P = 1.8 × 10-10]). Alterations in executive function were partially mediated by GMV (b = -0.004 [95% CI, -0.007 to -0.002]) and within-network functional connectivity (b = -0.004 [95% CI, -0.008 to -0.002]). Socioeconomic status and body mass index moderated the association between arsenic and GMV, such that the association was strongest in participants with lower socioeconomic status and body mass index. Conclusions and Relevance: The findings of this cross-sectional study suggest that low-level arsenic exposure was associated with alterations in executive functioning and underlying brain correlates. These results indicate potential detrimental consequences of arsenic exposure that are below the currently recommended guidelines and may extend beyond endemic risk areas. Precision medicine approaches to study global mental health vulnerabilities highlight widespread but potentially modifiable risk factors and a mechanistic understanding of the impact of low-level arsenic exposure on brain development.

Assist-linked brief intervention to reduce risky pattern of substance use in male workers employed at a tertiary care hospital in India: A randomized controlled trial.

Background: Substance use in workplace leads to adverse effects both on the employees and on the workplace. Existing research focuses on alcohol-related harm, while workplace use of other substances has been neglected. There are no randomized controlled studies of brief interventions in Indian hospital settings. Aim: To evaluate the efficacy of World Health Organization (WHO) alcohol, smoking, and substance involvement screening test (ASSIST)-linked brief intervention (ALBI) for reducing risky patterns of substance use in male workers at a tertiary-care hospital in North India. Material and Methods: The study was conducted in two phases. In Phase-I, a random list of 400 employees was generated from the entire pool of male hospital workers, of which 360 participated. Data on the ASSIST risk categories (mild, moderate, and high) were generated from Phase I. In Phase-II, moderate- or high-risk subjects ('ASSIST screen-positive') were randomized into intervention and control groups, with 35 screen-positive subjects in each group. The intervention group was provided a 15-30-min structured session per ALBI protocol, while the control group was given a 15-30-min general talk on health-related consequences associated with substance use. The subjects were compared on ASSIST score, WHO quality-of-life brief version (WHOQOL-BREF) and readiness to change questionnaire (RCQ) at baseline and at 3-month follow up. Results: The prevalence of moderate-to-high-risk use of tobacco, alcohol, and cannabis in the total sample was 28.6%, 27.5%, and 6.9%, respectively. At 3-months postintervention follow-up of the randomized sample, recipients of ALBI had significant reduction of ASSIST scores for all substances compared to the control group (p < 0.001). More participants receiving ALBI were ready to change to RCQ action stage (p values for tobacco, alcohol, and cannabis <0.001, <0.001 and 0.007, respectively). WHOQOL-BREF scores significantly improved in ALBI group across all domains. Conclusion: ALBI was effective in reducing risky substance use, increasing readiness to change and improving the QOL of the subjects at workplace setting.

Digital screening and brief intervention for alcohol misuse in college students: A pilot, mixed-methods, cluster randomized controlled trial from a low-resourced setting.

INTRODUCTION: We examined the feasibility and acceptability of digital screening and brief intervention (d-SBI) for alcohol misuse in college students; the effectiveness of d-SBI was our secondary outcome. We also explored the barriers and facilitators of d-SBI. METHODS: The study design is a mixed-methods, pilot, and cluster randomized trial. Five colleges from a northern city in India were randomly allocated to d-SBI and control groups. One hundred and ninety-one students were screened, and 25 (male = 23 and female = 2) participants (age 19.62 ± 2.58 years) fulfilled eligibility. All participants completed follow-up assessments at 3 months. In-depth interviews were done with 11 participants. Alcohol Use Disorder Identification Test (AUDIT) based screening brief intervention was provided on a web portal- or mobile application in the d-SBI group. The control group received digital screening and brief education. Direct questions and usage statistics assessed the measurement acceptability of the intervention. We compared the change in AUDIT scores in the intervention groups over 3 months post-intervention. Thematic analyses of transcripts of interviews were done by inductive coding. RESULTS: Most participants reported that d-SBI was user-friendly (80%), advice was appropriate (80%), and perceived it to be useful (72%). Ninety-six percent of users, who logged in, completed screening. There was a significant decrease in AUDIT scores both in d-SBI (p < .001) and control groups (p < .001). Time and group significantly affected the mean AUDIT score, but time × group interaction was non-significant. Thematic analysis revealed six overarching themes. CONCLUSIONS: Digital SBI for alcohol misuse is acceptable, feasible, and possibly effective among college students from low-resource settings.

Neurocognitive Functions in Patients with Comorbid Hepatitis C and Opioid Dependence: A Comparative Study.

Background: Hepatitis C virus (HCV) infection is commonly comorbid with opioid dependence (OD). We wanted to compare the neurocognitive functions of OD subjects with or without HCV [HCV (+), HCV (-)] and healthy controls (HC). Methods: We recruited 40 adult subjects (age 18-55 years) in each group. HCV(+) group had a detectable viral load. Subjects with HIV or hepatitis B infection, head injury, epilepsy, or comorbid mental illness were excluded. We administered Standard Progressive Matrices (SPM), Wisconsin Card Sorting Test, Iowa Gambling Task (IGT), trail-making tests A and B, and verbal and visual N-back tests (NBT) one week after opioid abstinence. The group differences in cognitive performance were adjusted for age and years of education. Effect size (ES) is expressed as Cohen's D. Results: The HCV(+) and HCV(-) groups did not differ in potential effect modifiers (age and years of education) or confounders (age of opioid initiation, duration of use, dependence severity, tobacco use, and cannabis use) of neuropsychological functioning. HCV(+) showed significantly poorer performance than HCV(-) in SPM (P = 0.006; ES = 0.72). Both HCV(+) and HCV(-) performed worse than controls in IGT(P < 0.001; ES = 0.8) and visual NBT[P < 0.01 and ES > 1 for total errors]; HCV(+) had a larger ES of group difference than HCV(-). HCV(+) had higher error scores in verbal NBT than control. Conclusion: HCV(+) has poorer general intellectual ability and reasoning than HCV(-) persons and controls. Chronic HCV infection causes a higher magnitude of dysfunction in decision-making and visual working memory in opioid-dependent individuals.

Heroin use and neuropsychological impairments: comparison of intravenous and inhalational use.

BACKGROUND AND OBJECTIVES: Injection and inhalational heroin use are associated with different levels of brain exposure to heroin and its metabolites and differences in the severity of dependence, which might lead to differential impacts on neuropsychological functions. We examined the difference and the magnitude of difference in the neuropsychological functions between inhalational and injection heroin-dependent subjects and also compared them with healthy controls. METHODS: The study sample comprised three groups: 73 subjects with injection heroin dependence, 74 with inhalational heroin dependence, and 75 healthy controls (HC). We excluded patients with HIV, head injury, epilepsy, and severe mental illness. Neuropsychological assessments were done by Standard Progressive Matrices, Wisconsin Card Sorting Test (WCST), Iowa Gambling Task, Trail-Making Tests A and B (TMT), and Verbal and Visual Memory 1 and 2 Backtests (NBT). We estimated independent effects of the groups on various neuropsychological test parameters, adjusted for age and duration of dependence. RESULTS: In the WCST, the inhalational heroin-dependent group took more trials to complete the first category and had higher scores in the failure to maintain set than controls. The intravenous group had higher total errors than controls in verbal working memory tests and Visual Working Memory 2 Backtest. This group scored higher commission errors in the Verbal 2 Backtest than the controls. The two groups of heroin users differed in failure to maintain set and Verbal Working Memory 2 Backtests. The effect sizes of the group differences were modest. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Either route of heroin use is associated with cognitive impairments; inhalational and injection use involve different cognitive domains.

Digital screening and brief intervention for illicit drug misuse in college students: A mixed methods, pilot, cluster, randomized trial from India.

BACKGROUND: Adolescence and early adulthood are vulnerable periods for substance use-related disorders later in life. The use of internet-enabled interventions can be useful, especially in low-resource settings. AIMS: To examine the feasibility, acceptability, and preliminary effectiveness of single-session digital screening and brief intervention (d-SBI) for illicit drug misuse in college students and explore barriers and facilitators of d-SBI. METHODS: Design: Mixed-methods, pilot cluster randomized trial. SETTING: Four conveniently selected colleges were randomized into intervention and control groups. PARTICIPANTS: 219 students were screened, and 37 fulfilled eligibility. Twenty-four completed follow-ups. In-depth interviews were done with ten students. Intervention and Comparator: Following a digital screening, Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) based brief intervention was provided in the d-SBI group. The control group received brief education. MEASUREMENTS: Acceptability was assessed by direct questions and usage statistics. ASSIST scores of groups were assessed at baseline and 3 months. Inductive coding of the interview transcript was done. RESULTS: More than 50 % of participants found d-SBI user-friendly, appropriate, and useful. Eighty percent of users, who logged in, completed screening. Per-protocol analysis showed a reduction in cannabis-ASSIST score over 3 months. The mean ASSIST score for other drugs combined did not differ significantly between groups. The difference in risk transition (moderate to low) was not significant. Qualitative analysis revealed three overarching themes- recruitment, engagement, and behavior change. CONCLUSIONS: Digital SBI for drug misuse is feasible among college students. d-SBI might be effective in reducing cannabis use.

Federated Analysis in COINSTAC Reveals Functional Network Connectivity and Spectral Links to Smoking and Alcohol Consumption in Nearly 2,000 Adolescent Brains.

With the growth of decentralized/federated analysis approaches in neuroimaging, the opportunities to study brain disorders using data from multiple sites has grown multi-fold. One such initiative is the Neuromark, a fully automated spatially constrained independent component analysis (ICA) that is used to link brain network abnormalities among different datasets, studies, and disorders while leveraging subject-specific networks. In this study, we implement the neuromark pipeline in COINSTAC, an open-source neuroimaging framework for collaborative/decentralized analysis. Decentralized exploratory analysis of nearly 2000 resting-state functional magnetic resonance imaging datasets collected at different sites across two cohorts and co-located in different countries was performed to study the resting brain functional network connectivity changes in adolescents who smoke and consume alcohol. Results showed hypoconnectivity across the majority of networks including sensory, default mode, and subcortical domains, more for alcohol than smoking, and decreased low frequency power. These findings suggest that global reduced synchronization is associated with both tobacco and alcohol use. This proof-of-concept work demonstrates the utility and incentives associated with large-scale decentralized collaborations spanning multiple sites.

Cellulose paper sorptive extraction (CPSE): A simple and affordable microextraction method for analysis of basic drugs in blood as a proof of concept.

Aiming towards simplifying sample preparation procedure, the present work explores use of unmodified laboratory filter paper as sorbent for extraction of nine basic drugs (five antidepressants, four benzodiazepines, and ketamine) from human blood samples and their analysis by gas chromatography-mass spectrometry (GC-MS). The procedure termed as cellulose paper sorptive extraction (CPSE) is straightforward. It involves adsorption of target analytes from deproteinized diluted blood samples on the unmodified cellulose paper followed by elution into 2 mL of methanol. Multivariate optimization, consisting of Placket-Burman design (PBD) and central composite design (CCD), was used to screen and optimize significant factors for CPSE. The proposed method follows the principles of green analytical chemistry (GAC), as the unmodified filter paper used as the sorbent is inexpensive and biodegradable. The technique is easy to perform and requires only 2 mL of MeOH during the entire extraction procedure. Under the optimized conditions, the limit of detection and quantification for the target analytes were estimated to be in the range of 0.003-0.035 and 0.010-0.117 µg mL-1, respectively. In contrast, the relative standard deviations were consistently below 10 %. The calibration curves were linear in the range of 0.015-2 µg mL-1 with a coefficient of determination (R2) in the range of 0.995-0.999.Satisfactory recoveries ranging from 87 to 99 % was achieved. As proof of concept, the analysis of nine drugs in blood samples from the patients was performed to demonstrate the potential application of the proposed method.

Predictors of Five-year Readmission to an Inpatient Service among Patients with Opioid Use Disorders.

Background Opioid use disorder (OUD), a relapsing-remitting chronic medical disease, accounts for a sizable proportion of all-cause adult inpatient stays. We evaluated the incidence and predictors of any and multiple readmissions to inpatient care for OUD. Methods This retrospective, register-based cohort study assessed consecutive patients with OUD admitted to a federally-funded inpatient service of an addiction treatment center in North India between January 2007 and December 2014. Binary logistic regression was used to determine independent readmission predictors based on demographic, clinical, and treatment variables that significantly differed in bivariate analysis. Results Among 908 patients, 306 (33.7%) and 106 (11.7%) had any and multiple readmissions, respectively. Injection drug use (Odds ratio [OR] 2.92, 95% confidence interval [CI] 1.90-4.49), comorbid severe mental illness (OR 2.80, 95% CI 1.42-5.55) and common mental disorder (OR 3.4 95% CI 1.65-6.95), antagonist treatment (OR 1.6 95% CI 1.14-2.27), and urban residence (OR 1.38 95% CI 1.01-1.90) increased odds of readmission. 'Improved' discharge status (OR 0.48 95% CI 0.34-0.70) in first admissions reduced odds of any readmission. Similar risk factors also influenced multiple readmissions with higher odds ratios. Conclusions Identification and adequate treatment of risk factors may reduce the chances of readmission.