Pharmacogenomics-assisted schizophrenia management: A hybrid type 2 effectiveness-implementation study protocol to compare the clinical utility, cost-effectiveness, and barriers.

OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).

The Excited-State Lifetime of Poly(NDI2OD-T2) Is Intrinsically Short.

Conjugated polymers composed of alternating electron donor and acceptor segments have come to dominate the materials being considered for organic photoelectrodes and solar cells, in large part because of their favorable near-infrared absorption. The prototypical electron-transporting push-pull polymer poly(NDI2OD-T2) (N2200) is one such material. While reasonably efficient organic solar cells can be fabricated with N2200 as the acceptor, it generally fails to contribute as much photocurrent from its absorption bands as the donor with which it is paired. Moreover, transient absorption studies have shown N2200 to have a consistently short excited-state lifetime (∼100 ps) that is dominated by a ground-state recovery. In this paper, we investigate whether these characteristics are intrinsic to the backbone structure of this polymer or if these are extrinsic effects from ubiquitous solution-phase and thin-film aggregates. We compare the solution-phase photophysics of N2200 with those of a pair of model compounds composed of alternating bithiophene (T2) donor and naphthalene diimide (NDI) acceptor units, NDI-T2-NDI and T2-NDI-T2, in a dilute solution. We find that the model compounds have even faster ground-state recovery dynamics (τ = 45, 27 ps) than the polymer (τ = 133 ps), despite remaining molecularly isolated in solution. In these molecules, as in the case of the N2200 polymer, the lowest excited state has a T2 to NDI charge-transfer (CT) character. Electronic-structure calculations indicate that the short lifetime of this state is due to fast nonradiative decay to the ground state (GS) promoted by strong CT-GS electronic coupling and strong electron-vibrational coupling with high-frequency (quantum) normal modes.

Exploring help-seeking pathways and disparities in substance use disorder care in India: A multicenter cross-sectional study.

Background: Substance use disorders (SUDs) are among the leading causes of morbidity in the population. In low- and medium-income countries like India, there is a wide treatment gap for SUD. A multicentric study on the care pathways for SUD in India can help to understand service provision, service utilization, and challenges to improve existing SUD care in India. Aim: We aimed to map pathways to care in SUD. We compared the clinical and demographic characteristics of patients who first consulted specialized services versus other medical services. Methods: This was a cross-sectional study of consecutive, consenting adults (18-65 years) with SUD registered to each of the nine participating addiction treatment services distributed across five Indian regions. We adapted the World Health Organization's pathway encounter form. Results: Of the 998 participants, 98% were males, 49.4% were rural, and 20% were indigenous population. Addiction services dominated initial (50%) and subsequent (60%) healthcare contacts. One in five contacted private for-profit healthcare. Primary care contact was rare (5/998). Diverse approaches included traditional healers (4-6%) and self-medication (2-8%). There was a 3-year delay in first contact; younger, educated individuals with opioid dependence preferred specialized services. Conclusion: There is a need to strengthen public healthcare infrastructure and delivery systems and integrate SUD treatment into public healthcare.

Prevalence and pattern of mental disorders in the state of West Bengal: Findings from the National Mental Health Survey of India 2016.

Background: West Bengal, situated in eastern India, comprising 19 districts as of 2016 and consisting of 9.13 crore population, had been one of the participating states in the National Mental Health Survey, 2015-16. Aim: To estimate the prevalence and pattern of mental disorders in a representative population in West Bengal. Materials and Methods: Based upon a multi-stage stratified random cluster sampling with probability proportionate to each stage, 2646 eligible individuals were interviewed. Standard validated instruments in Bengali like socio-demographic profiles and Mini International Neuropsychiatric Interview (MINI) version 6 were used by trained data collectors with quality monitoring as per a standardized protocol. Results: The current prevalence of mental illness in the state of West Bengal is 13.07% (12.9-13.24 95% CI), which is more than the current national average of 10.56% (10.51-10.61 95% CI). The prevalence of severe mental illness of 2.32% and suicide risk of 1.75% (1.68-1.81 95% CI) is higher than the national average. The common mental illness prevalence is 11.29 (11.13-11.45 95% CI), which is similar to the national weighted average. In West Bengal, severe mental illness is more concentrated in the rural areas in contrast to the national trend. Also, the prevalence of alcohol use disorder is 3.04 (2.96-3.13 95% CI) and epilepsy is 0.03 (0.27-0.29 95% CI), which is less than the national average. Conclusion: The prevalence of mental disorders in the state of West Bengal is higher than the national average, and for severe mental illness, the prevalence is the highest as compared to the national average.

Management of chronic insomnia using hypnotics: a friend or a foe?

Epidemiological studies suggest that 10-15% adults meet the present criteria for the diagnosis of insomnia disorder; however, there may be geographical variations. Untreated insomnia disorders have a number of adverse health consequences in addition to economic burden caused by it. Available guidelines mention that CBT-I should be preferred over hypnotics. However, several patients of chronic insomnia are not candidate for CBT-I and for them, hypnotics are the only answer. This paper reviews the literature to answer following questions: What is the current understanding regarding place of hypnotics for in management of insomnia disorder? How many patients misuse or abuse hypnotics, especially benzodiazepines, as commonly believed? Do we have data from human studies regarding low-dose benzodiazepine dependence? What does hypnotics produce-withdrawal insomnia, rebound insomnia or end of dose phenomenon? Are adverse effects of benzodiazepines worse than other psychotropic medications? Is prescription of hypnotics more troublesome than untreated insomnia disorder? Available literature suggests that there is an unreasonable negative bias attached to the use of hypnotics. Only a sub-set of patients who are prescribed hypnotics, meet the criteria for "dependence" in long term. Other patients either discontinue it (as insomnia remits) or change to occasional use (since insomnia may be relapsing remitting disorder), or continue using it in low dose (since insomnia reappears as hypnotics are discontinued, similar to increase in blood sugar after hypoglycemics are discontinued). Meta-analysis shows that adverse effects of hypnotics are comparable to that of other psychotropic medications. Considering the consequences and risks associated with untreated insomnia disorder, even long-term use of hypnotics is justified, however with the careful watch that patients are not increasing the dose. This approach is especially important in geographical areas where trained CBT-I therapists are not available.