A Molecular Docking and Pharmacokinetic Prediction of Thiazolidine-2, 4-dione Derivatives: Toward Novel Therapeutic Targets for Type-2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a leading endocrine disorder that affects millions of people worldwide. It is characterized by hyperglycemia and high insulin resistance. The commonly prescribed oral therapeutic for insulin resistance in T2DM is Thiazolidine-2, 4-diones (TZDs). TZDs are a class of oral hypoglycemic agents that act on Peroxisome proliferator activating receptor-γ (PPAR-γ) receptors and are mainly expressed in the adipose tissues. In this work, we derive novel classes of TZDs and predict the nature of structural affinity using docking studies against the PPAR-γ.

Coach-Supported Versus Self-guided Digital Training Course for a Problem-solving Psychological Intervention for Nonspecialists: Protocol for a Pre-Post Nested Randomized Controlled Trial

BACKGROUND: Psychosocial interventions delivered by nonspecialists can be effective at reducing common adolescent mental health problems in low-resource settings. However, there is a lack of evidence on resource-efficient methods for building capacity to deliver these interventions. OBJECTIVE: The objective of this study is to evaluate the effects of a digital training (DT) course, delivered in a self-guided format or with coaching, on nonspecialists' competency to deliver a problem-solving intervention intended for adolescents with common mental health problems in India. METHODS: We will conduct a pre-post study with a nested parallel, 2-arm, individually randomized controlled trial. The study aims to recruit 262 participants, randomized 1:1 to receive either a self-guided DT course or a DT course with weekly individualized coaching provided remotely by telephone. In both arms, the DT will be accessed over 4 to 6 weeks. Participants will be nonspecialists (ie, without prior practice-based training in psychological therapies) recruited from among university students and affiliates of nongovernmental organizations in Delhi and Mumbai, India. RESULTS: Outcomes will be assessed at baseline and 6 weeks post randomization using a knowledge-based competency measure that incorporates a multiple-choice quiz format. The primary hypothesis is that self-guided DT will lead to increased competency scores among novices with no prior experience of delivering psychotherapies. The secondary hypothesis is that digital training with coaching will have an incremental effect on competency scores compared with DT alone. The first participant was enrolled on April 4, 2022. CONCLUSIONS: The study will address an evidence gap on the effectiveness of training methods for nonspecialist providers of adolescent mental health interventions in low-resource settings. The findings from this study will be used to support wider efforts to scale up evidence-based mental health interventions for young people. TRIAL REGISTRATION: ClinicalTrials.gov NCT05290142; https://clinicaltrials.gov/ct2/show/NCT05290142. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41981

Feasibility and acceptability of a remote stepped care mental health programme for adolescents during the COVID-19 pandemic in India

Remote mental health services were rapidly deployed during the COVID-19 pandemic, yet there is relatively little contemporaneous evidence on their feasibility and acceptability. This study assessed the feasibility and acceptability of a stepped care mental health programme delivered remotely by lay counsellors to adolescents in New Delhi, India, during a period of ‘lockdown’. The programme consisted of a brief problem-solving intervention (“Step 1”) followed by a tailored behavioural module (“Step 2”) for non-responders. We enrolled 34 participants (M age = 16.4 years) with a self-identified need for psychological support. Feasibility and acceptability were assessed through quantitative process indicators and qualitative interviews (n = 17 adolescents; n = 5 counsellors). Thirty-one (91%) adolescents started Step 1 and 16 (52%) completed the planned Step 1 protocol. Twelve (75%) of the Step 1 completers were non-responsive. Eight (67%) non-responsive cases started Step 2, all of whom met response criteria when reassessed at 12 weeks post-enrolment. Adolescents favoured voice-only sessions over video-calls due to privacy concerns and difficulties accessing suitable devices. Counsellors noted challenges of completing remote sessions within the allotted time while recognising the importance of supervision for developing competence in new ways of working. Both adolescents and counsellors discussed the importance of working collaboratively and flexibly to fit around individual preferences and circumstances. Disentangling pandemic-specific barriers from more routine challenges to remote delivery should be a focus of future research

Development of a transdiagnostic stepped care programme for common adolescent mental health problems in Indian secondary schools: lessons from a pilot study examining acceptability and feasibility

Background The ‘PRemIum for aDolEscents’ (PRIDE) project has developed a school-based, transdiagnostic stepped care programme for common adolescent mental health problems in India. The programme comprises a brief problem-solving intervention (‘Step 1’) followed by a personalised cognitive-behavioural intervention (‘Step 2’) for participants who do not respond to the first step. Methods A mixed-method design was used to evaluate the acceptability and feasibility of the stepped care programme in five schools in New Delhi. Participants were N = 80 adolescents (mean age = 15.3 years, females = 55%) with elevated mental symptoms and associated distress/impairment. Results 61 (76%) of the enrolled sample were assessed following Step 1, from which 33 (54%) met non-remission criteria. Among these 33 non-remitted cases, 12 (36%) opted for Step 2 and five (42%) completed the full programme. The remaining non-remitted cases (n = 21, 64%) opted out of further treatment. Perceived resolution of the primary problem (n = 9, 43%) was the most common reason for opting out. The median time to complete each step was 22 and 70 days respectively, with a gap of 31 days between steps. Qualitative feedback from adolescents and counsellors indicated requirements for a shorter delivery schedule, greater continuity across steps and more collaborative decision-making. Conclusions This study provides preliminary evidence for a stepped care programme aimed at common adolescent mental health problems. Modifications are recommended to enhance the acceptability and feasibility of the programme in low-resource settings

Development of a transdiagnostic, low-intensity, psychological intervention for common adolescent mental health problems in Indian secondary schools

Background: The PRIDE programme aims to establish a suite of transdiagnostic psychological interventions organised around a stepped care system in Indian secondary schools. This paper describes the development of a low-intensity, first-line component of the PRIDE model. Method: Contextual and global evidence informed an intervention ‘blueprint’ with problem solving as the primary practice element. Successive iterations were tested and modified across two pilot cohort studies (N=45; N=39). Participants were aged 13–20 years and presenting with elevated mental health symptoms in New Delhi schools. Results: The first iteration of the intervention, based on a guided self-help modality, showed promising outcomes and user satisfaction when delivered by psychologists. However, delivery was not feasible within the intended 6-week schedule, and participants struggled to use materials outside ‘guidance’ sessions. In Pilot 2, a modified counsellor-led problem-solving intervention was implemented by less experienced counsellors over a 3–4 week schedule. Outcomes were maintained, with indications of enhanced feasibility and acceptability. High demand was observed across both pilots, leading to more stringent eligibility criteria and a modified sensitisation plan. Discussion: Findings have shaped a first-line intervention for common adolescent mental health problems in low-resource settings. A forthcoming randomised controlled trial will test its effectiveness

Effectiveness of a brief lay counsellor-delivered, problem-solving intervention for adolescent mental health problems in urban, low-income schools in India: a randomised controlled trial

Background Mental health problems are a leading cause of disability in adolescents worldwide. Problem solving is a well-tested mental health intervention in many populations. We aimed to investigate the effectiveness of a brief, transdiagnostic problem-solving intervention for common adolescent mental health problems when delivered by non-specialist school counsellors in New Delhi, India. Methods This randomised trial was done in six government-run schools (three all-boys schools, two all-girls schools, and one co-educational school) that serve low-income communities. We recruited participants from grades 9 to 12 (ages 12–20 years) by selecting students with persistently elevated mental health symptoms accompanied by distress or functional impairment. Clinical eligibility criteria were assessed by research assistants using the Hindi-language version of the Strengths and Difficulties Questionnaire (SDQ), with reference to locally validated borderline cutoff scores of 19 or greater for boys and 20 or greater for girls on the SDQ Total Difficulties scale, an abnormal score of 2 or more on the SDQ Impact scale, and persistence of more than 1 month on the SDQ Chronicity index. Participants were randomly allocated (1:1) to problem solving delivered through a brief (2–3 week) counsellor-led intervention with supporting printed materials (intervention group), or problem solving delivered via printed booklets alone (control group). Primary outcomes were adolescent-reported mental health symptoms (SDQ Total Difficulties scale) and idiographic psychosocial problems (Youth Top Problems [YTP]) at 6 weeks. Primary analyses were done on an intention-to-treat basis at the 6-week endpoint. The trial is registered with ClinicalTrials.gov, NCT03630471. Findings Participants were enrolled between Aug 20, and Dec 4, 2018. 283 eligible adolescents were referred to the trial, and 251 (89%) of these were enrolled (mean age 15·61 years; 174 [69%] boys). 125 participants were allocated to each group (after accounting for one participant in the intervention group who withdrew consent after randomisation). Primary outcome data were available for 245 (98%) participants. At 6 weeks, the mean YTP scores were 3·52 (SD 2·66) in the intervention group and 4·60 (2·75) in the control group (adjusted mean difference –1·01, 95% CI –1·63 to –0·38; adjusted effect size 0·36, 95% CI 0·11 to 0·61; p=0·0015). The mean SDQ Total Difficulties scores were 17·48 (5·45) in the intervention group and 18·33 (5·45) in the control group (–0·86, –2·14 to 0·41; 0·16, –0·09 to 0·41; p=0·18). We observed no adverse events. Interpretation A brief lay counsellor-delivered problem-solving intervention combined with printed booklets seemed to have a modest effect on psychosocial outcomes among adolescents with diverse mental health problems compared with problem-solving booklets alone. This counsellor-delivered intervention might be a suitable first-line intervention in a stepped care approach, which is being evaluated in ongoing studies

The effectiveness of a low-intensity problem-solving intervention for common adolescent mental health problems in New Delhi, India: protocol for a school-based, individually randomized controlled trial with an embedded stepped-wedge cluster randomized controlled recruitment trial

Background Conduct, anxiety and depressive disorders account for over 75% of the adolescent mental health burden globally. The current protocol will test a low-intensity problem-solving intervention for school-going adolescents with common mental health problems in India. The protocol also tests the effects of a classroom-based sensitization intervention on the demand for counselling services in an embedded recruitment trial. Methods We will conduct a two-arm individually randomized controlled trial in six Government-run secondary schools in New Delhi. The targeted sample is 240 adolescents in grades 9-12 with persistent, elevated mental health symptoms and associated impact. Participants will receive either a brief problem-solving intervention delivered over 3 weeks by lay counsellors (intervention), or enhanced usual care comprised of problem-solving booklets (control). Self-reported adolescent mental health symptoms and idiographic problems will be assessed at 6 weeks (co-primary outcomes) and again at 12 weeks post-randomization. In addition, adolescent-reported impact of mental health difficulties, perceived stress, mental wellbeing and clinical remission, as well as parent-reported adolescent mental health symptoms and impact scores, will be assessed at 6 and 12 weeks post-randomization. We will also complete a parallel process evaluation, including estimations of the costs of delivering the interventions. An embedded recruitment trial will apply a stepped-wedge, cluster (class)-randomized controlled design in 70 classes across the six schools. This will evaluate the added impact of a classroom-based sensitization intervention over school-level recruitment sensitization activities on the primary outcome of referral rate into the host trial (i.e. the proportion of adolescents referred as a function of the total sampling frame in each condition of the embedded recruitment trial). Other outcomes will be the proportion of referrals eligible to participate in the host trial, proportion of self-generated referrals, and severity and pattern of symptoms among referred adolescents in each condition. Power calculations were undertaken separately for each trial. A detailed statistical analysis plan will be developed separately for each trial prior to unblinding. Discussion Both trials were initiated on 20 August 2018. A single research protocol for both trials offers a resource-efficient methodology for testing the effectiveness of linked procedures to enhance uptake and outcomes of a school-based psychological intervention for common adolescent mental health problems