Alcohol Use Disorder

DETAILED METHODOLOGY Phase I: * Research Design: Qualitative * Research Setting: Selected public schools of Pokhara, Nepal * Population: Teachers, Parents, and Students of Pokhara, Nepal * Samples: Selected Teachers, Parents \& students * Sample Size: 38 (The sample will be collected till data Saturation) * Data collection Technique: Focus group discussion * Data collection Tool: Focus group lead questions * Data Analysis: Thematic analysis (Atlas.ti) Phase II Research design: Cluster Randomized Trial Randomization method: Cluster Randomization Research Setting: Selected public schools of Pokhara, Nepal Population: Adolescent students of Pokhara, Nepal Sample: Selected Adolescents, who are in the age group 13-15 years old and studying in 8th \& 9th grades Variables * Independent variables: School-based Substance abuse Prevention Programme (SSPP) * Dependent variables: awareness, attitudes, peer pressure, and life skills related to prevention of substance abuse. * Demographic variables: age in years, gender, religion, education/grade, family type, residence, number of siblings, education of parents, occupation of parents, sources of information, history of substance abuse in the family. Sample size: 210 The expected outcomes of the study is to enhance awareness towards prevention of substance abuse,develop a positive attitude towards the prevention of substance abuse,develop drug refusal skills among adolescents,improve life skills and helps in th reduction of drug abuse behaviour adolescents

The proposed study will be a non-pharmacological, two arm parallel, Prospective, single blind clinical trial to evaluate if there is a difference in retentive characteristics of dentition in two group of post orthodontic treatment patients with vertical growth pattern patients in one group and horizontal growth pattern patients in other group of patients. The present study will be conducted in the Department of Orthodontic and Dentofacial Orthopedics, P.G.I.D.S, Pt. B.D Sharma University of health sciences, Rohtak. The study will be carried out after the institutional approval obtained from ethical committee. Patient will be allocated to two different study group by the investigator. the data analyst will be blinded regarding the intervention group. The sample size for the proposed study was calculated by using the formula. Total sample size = N = 2σ 2 (Zβ + Zα/2) 2 / (difference of mean )2. sample size of 20 patients was calculated by using the above formula at confidence interval 95% with power 99%. GROUP 1: patient with vertical growth pattern have who had undergone, fixed orthodontic cases having FMA of 26 0 or more for hyperdivergent cases. GROUP 2 patient with horizontal growth pattern who had undergone , Fixed orthodontic cases having FMA of 24 o or less for hypodivergent cases. Changes in levels of bone turnover markers CTX-bone resorption and BALP-bone formation using ELISA. These parameters will be charted at T0, T1, T2, T3,T4 for each patient. T0 - Records will be obtained at the time of retainer delivery T1 - Records will be obtained after 1month of retainer delivery T2 - Records will be obtained after 3 month of retainer delivery T3- Records will be obtained after 6 months of retainer delivery T4- Records will be obtained after 12 months of retainer delivery Assessment of bite force will be done using bite force measuring device at T0 - Records will be obtained at the time of retainer delivery T1 - Records will be obtained after 1month of retainer delivery T2 - Records will be obtained after3month of retainer delivery T3- Records will be obtained after 6 months of retainer delivery T4- Records will be obtained after 12 months of retainer delivery

A Phase 1, Open-Label, Exploratory, Fixed-Sequence, Pharmacokinetic Single Acending Dose Study of IVL3004 Versus Vivitrol® (Naltrexone) Long-Acting Injectable(LAI) and IVL4002 in Healthy Subjects

The goal of this clinical study is to test the effectiveness of a supplemental fMRI neurofeedback and/or TMS intervention in individuals seeking treatment for Alcohol Use Disorder. After an initial visit, participants will come in once a week for four (4) weeks for an intervention session, which may or may not include TMS and MRI. Participants will be contacted for monthly follow-ups (remotely) for up to 12 months and will be asked to come in for two MRI follow-ups at 6 and 12 months.

The clinical significance of retained needle fragments remains unknown. Needle retentions can be asymptomatic, cause local symptoms, and can sometimes even lead to dangerous complications such as needle emboli to the heart or lungs. The most common injection sites are likely the peripheral veins of the arms. However, continuous IVD use leads to vein sclerosis, and patients with long-term use may therefore also use peripheral veins of their lower limbs and even the central veins of the groin or neck. Subcutaneously retained needles can pose a risk of needlestick injury to medical staff during clinical examination and treatment procedures. Unrecognized retained needles can also cause hazards during magnetic resonance imaging. The study protocol received a positive review from the Tampere University Hospital Ethics Committee (study code: R22037). The researchers subsequently received the organizational permissions necessary to conduct the study. PWIDs will be asked to give written informed consent prior to any study procedures. Participants will be asked to fill in a questionnaire about their basic information, drug use history, previous injection sites, and whether they have had any local complications due to injecting drugs. After the completion of the questionnaire, participants will undergo targeted X-ray imaging of the injection sites. As metallic objects, needle fragments can be visualized with standard X-ray imaging. Female participants of childbearing potential (\< 50 years) will undergo urine sample pregnancy testing prior to X-ray imaging. A pilot study with 20 participants will be conducted first. Experiences from the pilot will be used to refine the study protocol if needed. If modifications are made, they will be subjected to ethics review and will be provided on ClinicalTrials.gov. After the pilot study, the researchers aim to recruit an additional 80 patients (totaling up to 100 participants). Our research questions are 1) What is the prevalence of radiologically confirmed needle retention among PWIDs\*? The secondary research questions are 1. Do patient-reported symptoms and the suspicion of a retained needle fragments correspond to radiologically confirmed needle retention? 2. What are the predisposing factors to needle fragmentation? 3. Have PWIDs sought medical attention prior to the study for possible symptoms in the injection sites? 4. How frequently are verified needle fragments surgically removed within five years after their detection, and are verified needle fragments a proxy or a risk factor for mortality? \*As only patients in outpatient care will be recruited, the sample is not entirely representative of all PWIDs in the study area (e.g., people who are hospitalized or imprisoned are not recruited).

This is a single arm, open-label, dose escalation investigator initiated (IIT) study, the primary objective is to evaluate the safety and tolerability of CD19/ CD22/BCMA CAR-T therapy in patients with relapsed/refractory multiple myeloma, and determine the maximum tolerated dose (MTD). For the secondary objectives,pharmacokinetics(PK), survival of CAR-T cells in vivo,pharmacodynamics (PD) and efficacy in R/R MM will be evaluated. This study flow comprises of a screening phase( 30 to10 days prior to infusion), apheresis phase (9 to 8 days prior to infusion), lymphodepletion phase (5 to 3 days prior to infusion) , infusion of CD19/CD22/BCMA CAR-T cells on Day0, DLT assessments phase (from Day1 to Day 28) and post- treatment follow-up phase (Day 29 and up to end of the study).

This is a five year Hybrid Type 1 effectiveness-implementation study. For Aim 1, 162 female Veterans with AUD will be enrolled over 2.5 years in the study at Primary Care and Women's Comprehensive Primary Care Clinics (i.e., the Women's Health Clinic) in the VA New York Harbor Healthcare System (VA NYHHS) (n=162) for a final sample of 140 at 15 month post-baseline (i.e.,12 month post treatment) follow up. The 86% follow up rate is based on Dr. Epstein's prior Randomized Control Trial (RCT) testing FS-CBT for civilian women with AUD on which the current Veteran- Centric FS-CBT group is based. After the research baseline interview, participants will be randomly assigned to either Usual Care (UC, which is Brief Alcohol Counseling +Referral to Substance Use Disorder (SUD) Specialty Care if indicated, all called Brief Alcohol Counselling (BAC), and otherwise also known as Brief Intervention and Referral to treatment (BIRT)) or to the 12 session, rolling entry group Veteran Female Specific CBT for AUD (FS-CBT) held within the VA NYHHS Women's Health Clinic. Participants in both conditions will complete the same baseline (BL), 3-, 9- and 15-months post-BL (i.e., 0-, 6-, \& 12-months after treatment) research assessments. Primary outcome variables will be treatment access (attending least one FS- CBT group session or 1 SUD specialty care session in the FS-CBT condition, and at least 1 SUD specialty care session in the usual UC condition; treatment engagement is defined as number of treatment hours attended in each condition); drinking outcomes (percent drinking days and percent heavy drinking days during and 1 year after the treatment phase). Secondary outcomes include drug use, mental health, social support for abstinence, and health behaviors. For Aim 2, a formative evaluation will be done during the RCT using program process data to track provider interest, patient enrollment rates, reasons for refusal, and treatment adherence. Using an implementation science framework (Consolidated Framework for Implementation Research, CFIR), the investigators will evaluate implementation barriers and facilitators of FS-CBT in VA PC using qualitative interviews with 20 women Veterans in FS-CBT, 20 in UC, 15 women with AUD who were eligible but did not enroll in the RCT, and 16 providers/stakeholders. The goal of the formative evaluation is to help determine factors at the system, provider, and patient levels that affect the likelihood that FS-CBT will be successfully implemented and sustained in VA Primary Care (PC). The evaluation will allow for more rapid translational gains in terms of intervention uptake and sustainability. The evaluation will include the systematic collection of quantitative RCT process data (e.g., number and % of patient referral opt-outs by Primary Care Providers (PCPs), % of eligible women who enroll, reasons for refusal, number of group sessions completed by Veteran characteristics), and qualitative data via interviews with patient and staff stakeholders. To learn about patient-level barriers/facilitators, study personnel will conduct interviews with 20 female Veterans who were randomized to the FS-CBT condition, and 20 who were randomized to UC: (a) one-half will be drawn from those who completed the full dose (12 sessions in FS-CBT and all treatment recommendations in UC) and the other half from those who dropped out and completed less than the recommended minimal dose. Investigators will sample from participants who significantly reduced their drinking and from those who did not. Investigators will include a diverse sample of Veterans based on age, gender, race/ethnicity, era of military service, and diagnoses (e.g., PTSD). Lastly, study personnel will interview 15 women with AUD who were eligible but did not enroll in the RCT to understand their perceptions of the program and barriers to participation. The CFIR framework will be used to guide the interview approach. CFIR is a typology of 39 constructs from five main domains that identify factors associated with successful implementation and maintenance of health care innovations: (1) Intervention Characteristics; (2) Inner Setting; (3) Outer Setting; Characteristics of Individuals; (5) Process. If Aim 1 hypotheses are supported, these interviews will help guide subsequent implementation trials of FS-CBT by explaining: (a) barriers and facilitators to participation; perceptions about why FS-CBT is successful at achieving better outcomes for women Veterans with AUD; the barriers and facilitators to high fidelity implementation of FS-CBT; and the sustainability of FS-CBT in the absence of a funded research project and how to achieve this goal; and (b) how FS-CBT should be adjusted to appeal to the subgroup of Veterans. If Aim 1 hypotheses are not supported, the interviews will determine the reasons why (i.e., questions posed to staff and patients will solicit information on barriers associated with delivery of FS-CBT during the RCT, and what modifications to FS-CBT could be made to maximize effectiveness).

Investigators will develop a culturally adapted, brief, single-session PFI delivered via a mobile health application for the Android and iOS platform through an iterative approach using expert input and semi-structured interview sessions. Next, Black hazardous drinkers with clinical anxiety will assess program navigation and conduct usability testing. Finally, Black hazardous drinkers with clinical anxiety will be recruited to complete the final prototype of the mobile health application in order to evaluate the feasibility, acceptability, and initial effects. Initial screening will be conducted via Zoom; baseline and post-treatment data will be collected via Zoom and 1-week, 1-month, and 3-months follow-up data will be collected remotely.

Background and Study Purpose As is well-documented by the World Health Organization (WHO), alcohol abuse remains a major health hazard worldwide, responsible for 5.3 percent of all deaths annually. It also contributes to over 200 conditions related to disease and injury, which include an array of behavioral and mental health disorders. There is now a substantial body of literature suggesting the effectiveness of Screening and Brief Intervention (SBI) as a strategy to identify people at high risk for alcohol use disorder, and to invite them, within the context of a short motivational interview, to reflect on their drinking patterns and develop a realistic and achievable plan to reduce their consumption. The screening component of SBI typically relies on the Alcohol Use Disorders Identification Test (AUDIT), which comprises two parts. The first is a 3-item assessment (the AUDIT-C); individuals who score 8 or higher are then invited to: (1) respond to 7 additional questions about their alcohol consumption (the AUDIT-7) and (2) participate in a brief intervention that is typically conducted by their primary health care provider or a staff member. There are a variety of reasons, however, why brief interventions may fail to fulfill expectations of their positive effects. Eligible participants may be reluctant to engage fully in brief interventions because of the stigma attached to doing so; and primary health care providers may lack the time, attention, and confidence in their ability to conduct the brief intervention, or delegate responsibility for its administration to staff members who are insufficiently trained to deliver the intervention as intended, which includes establishing a sufficient rapport with the participant. Consideration has thus been given to strategies to automate the delivery of brief interventions so that they can be self-administered electronically. Prototypes of this delivery mechanism are under development, and are sufficiently far advanced that they warrant investigations of their effectiveness. The key research question to be addressed by this study is: • Are brief interventions, as electronically self-administered via an app on handheld devices, at least as effective in reducing the 30-day quantity and frequency of alcohol consumption as brief interventions administered in person by health care providers? Note that the study's purpose is not to determine whether the administration of brief interventions via a handheld device is superior to that of an in-person administration, but to investigate whether the two modes of delivery are at least of equal effectiveness. Study Setting This study will be conducted in communities in two low- and middle-income countries: Zacatecas, Mexico and Alexandra Township, South Africa. In each site approximately seven to nine hospitals and health care clinics will participate in the study. Institutional Recruitment Procedures A country-specific study contractor will recruit the hospitals and clinics where the SBI will be delivered. All participating institutions will express their willingness to permit the contractor's trained facilitators (health educators) to approach patients in waiting areas and administer the AUDIT screening tool to them via an electronic device. For those patients who score 8 or higher on the AUDIT-C, the institutions will agree to: * support the administration of the AUDIT-7; * agree to and support the assignment of all participating clinics on alternating weeks to either the traditional in-person brief intervention or the electronic brief intervention. Thus all patients qualifying for the study in any given week will be assigned to one group, and all those in the subsequent week will be assigned to the other group. Study Participant Requirements and Procedures All patients who are at least 18 years old and score 8 or above on the AUDIT will be eligible and recruited for the study as long as they have not been screened in the past six months. They will be informed of their eligibility via the consent language presented in the app after the screening and before the study survey (those who do not qualify for the study do not see the consent language or the survey but go directly from the screening to their brief intervention). Specifically, the consent form on the device will inform them that: * they are eligible to participate in a study on alcohol use patterns over time; * they will be invited to answer a few more questions about their alcohol use; * they will be asked to complete similar surveys in three months and again at six months, with various options, i.e., at the time of a follow-up clinic visit (for those with chronic health conditions), at a meeting with a clinic staff person at a convenient time and location, or via a phone interview in South Africa and via a link to the survey sent to them so they can complete it on their phone or other device at home or a phone interview in Mexico; * they will receive an incentive at the time of each survey with each successive survey incentive of increased value compared to the previous one (small cash payments in Mexico; a mobile airtime credit at baseline and grocery vouchers at the two follow-up surveys in South Africa); and * they will be asked to provide personal contact information to be used to recontact them at each of the two follow-up intervals. Study Sample All screened patients who are are aged 18 or older, who score 8 or higher on the AUDIT, and who have not been screened in the past 6 months will be eligible to participate in the study. Initial targets were to enroll 460 participants (230 in each brief intervention condition or study arm) in each country. At this point, Mexico has enrolled 563 participants (289 traditional BI; 274 electronic BI). Baseline data collection is still ongoing in South Africa. Analysis Plan In this non-inferiority trial, the null hypothesis is that the intervention (i.e., a BI delivered electronically via an app) is inferior to the comparison (i.e., an in-person brief intervention, or business as usual). This would be reflected in a statistically significant greater reduction in drinking alcohol post-intervention among those receiving an in-person BI compared to those receiving an electronic BI.

This longitudinal, observational study aims to assess whether the characteristics of a novel blood peripheral biomarker can serve as indicators for depression and schizophrenia in patients at the Royal Columbian Hospital Psychiatric Clinics. The study will evaluate whether changes in these biomarker characteristics can help distinguish between depressed patients who do or do not respond to treatment and between individuals experiencing a single psychotic episode and those at risk of progressing to schizophrenia. To achieve this, blood samples and standardized mental health assessments will be collected across three study visits from up to 500 participants, grouped into two study arms based on their diagnosis: Depression (DEP) or Psychosis/Schizophrenia (PSY).