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.

Ultra-Narrowband Near-Infrared Responsive J-Aggregates of Fused Quinoidal Tetracyanoindacenodithiophene.

Narrowband photoresponsive molecules are highly coveted in high-resolution imaging, sensing, and monochromatic photodetection, especially those extending into the near-infrared (NIR) spectral range. Here, a new class of J-aggregating materials based on quinoidal indacenodithiophenes (IDTs) that exhibit an ultra-narrowband (full width half maxima of 22 nm) NIR absorption peak centered at 770 nm is reported. The spectral width is readily tuned by the length of the solubilizing alkyl group, with longer chains resulting in significant spectral narrowing. The J-aggregate behavior is confirmed by a combination of excited state lifetime measurements and single-crystal X-ray diffraction measurements. Their utility as electron-transporting materials is demonstrated in both transistor and phototransistor devices, with the latter demonstrating good response at NIR wavelengths (780 nm) over a range of intensities.

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.

Impact of COVID-19 lockdown on substance availability, accessibility, pricing, and quality: A multicenter study from India.

Background and Aim: Pandemic and consequent lockdowns are likely to affect the drug market by the sudden disruption of the supply chain. We explored the change in the availability, access, purity, and pricing during lockdown from respondents seeking treatment for drugs, alcohol, and tobacco dependence. Materials and Methods: A cross-sectional survey was conducted among 404 respondents from seven treatment centers across India. A structured questionnaire assessed the change in availability, access, quality, and price of substances used during the first phase (March 24-April 14) and the second phase (April 15-May 3) of lockdown. Results: A majority of the respondents in treatment used tobacco (63%) and alcohol (52%). Relatively few respondents used opioids (45%) or cannabis (5%). Heroin (44%) was the most common opioid the respondents were treated for. Seventy-five percent, 65%, and 60% of respondents treated for alcohol, tobacco, and opioid problems, respectively, reported a reduction in the availability and access during the first phase of the lockdown. In the second phase, respondents with alcohol and tobacco dependence reported greater availability than those with opioid and cannabis dependence. The reported price of all substances increased more than 50% during the first phase of lockdown and remained higher throughout the second phase. Deterioration in purity was reported by more than half of the people who used opioid. Conclusion: Lockdown could have affected both licit and illicit drug markets, albeit to a varying degree. The observed changes seemed short-lasting, as suggested by the recovering trends during the second phase of lockdown.

Does Online Newsmedia Portrayal of Substance Use and Persons with Substance Misuse Endorse Stigma? A Qualitative Study from India.

Media provides and shapes public knowledge, perceptions, and attitude towards people with substance misuse. We aimed to explore the content and specific themes of Indian online news articles on substance use or persons with substance misuse. We followed an exploratory qualitative design to analyze online news media reports published between July 1 2020 and June 30 2021. Hundred articles met the selection criteria. Our content analysis was based on a checklist. Thematic analysis was done by the coding, categorization, and theme generation after meticulous data immersion and triangulation. Sixty percent of articles had pessimistic headlines and portrayed substance use or persons with substance use negatively. Fifty-one percent articles were on alcohol. Twenty-seven percent articles focussed supply reduction, whereas only 5% positively discussed the role of treatment. We identified seven themes. Most frequent themes were legal-criminal aspects of substance use (n = 39), psychosocial and health hazards of substance use (n = 30), and propagation of public stigma (n = 25). Two other prevalent themes were the business and marketing of alcohol (n = 20) and sociocultural aspects of substance use (n = 9). The theme, treatment strategy, appeared in only five articles. There is an urgent need for media guidelines for responsible reporting of substance misuse. We suggested a set of recommendations for media reporting.

A multicentric survey among patients with substance use disorders during the COVID-19 lockdown in India.

Background: The unprecedented first wave of the COVID-19 pandemic severely impacted mental health services globally. However, the negative impact of such disruptions on people with substance use disorders (SUD) seeking treatment remains unclear. We aim to explore the behaviors adopted by these individuals to overcome the service disruptions. Materials and Methods: We explored the changes related to substance use behavior (quit attempts, withdrawal experienced, treatment-seeking, and risky behaviors), and behavioral changes in response to COVID-19 lockdown. A cross-sectional survey was conducted among 404 people with SUD seeking treatment from seven centers across India. They were assessed by a specially designed structured questionnaire during the first wave (June-September) of the pandemic. Results: An overwhelming majority experienced withdrawal symptoms, with close to half making quit attempts and seeking treatment during the lockdown. Three-fourth of the sample reported difficulty in accessing treatment services and medications. Patients with opioid use were significantly more likely to think about quitting (χ2 = 20.408, P = 0.000), make attempts (χ2 = 12.436, P = 0.000), seek treatment (χ 2 = 7.536, P = 0.006), and self-medicate for withdrawal symptoms (χ2 = 5.885, P = 0.015). In turn, those with alcohol use were more likely to use telepsychiatry services (χ2 = 35.143, P = 0.000) and experience stigma by family members (χ2 = 29.951, P = 0.000) and neighbors (χ2 = 17.725, P = 0.000). Among COVID-19 safety precautions, majority practised wearing masks and social distancing but not others. Conclusion: COVID-19 lockdown led a significant proportion of substance users, especially opioid users, to make quit attempts and seek help. However, these could not be sustained due to difficulty in accessing treatment services. Further, significant proportion failed to adhere to COVID-19 safety precautions.

Management of Chronic Insomnia Using Cognitive Behavior Therapy for Insomnia (CBT-I) During COVID-19 Pandemic: Does One Shoe Fit All?

Purpose: Insomnia is a highly prevalent disorder that is seen across all age groups causing significant morbidity to the patients. Its prevalence has further risen during COVID-19 pandemic. It is widely acknowledged that untreated insomnia can lead to significant health risks and socio-occupational dysfunction. Methods: A narrative review was conducted following focused search of databases. Results: Available guidelines mention two different approaches for the management of insomnia-pharmacological and non-pharmacological. Non-pharmacological therapies like multicomponent cognitive behavior therapy for insomnia (CBT-I) have been advocated for the management of acute as well as chronic insomnia in the literature as it has been found efficacious and useful. Multiple variants of CBT-I, e.g., digitally delivered CBT-I, brief CBT-I have been tested during pandemic owing to closure of clinics. However, there are certain issues to be considered while choosing CBT-I as therapy. For example, like other forms of psychotherapies, is there a need for assessing the candidature of patient before administering CBT-I; is CBT-I free of adverse effects as commonly thought; is CBT-I more efficacious than hypnotics; and at last, how to manage cases that are not candidate for CBT-I. Conclusion: This narrative review addresses the scientific robustness of evidence for issues related to adherence, efficacy and adverse effects of non-pharmacological therapies. Available literature suggests that data related to adherence and efficacy of CBT-I suffer from methodological shortcomings and careful selection of patient is important for the successful therapy. At the same time, attempts have been made to shed light to the areas where CBT-I can be helpful in the management of insomnia.

Doping Approaches for Organic Semiconductors.

Electronic doping in organic materials has remained an elusive concept for several decades. It drew considerable attention in the early days in the quest for organic materials with high electrical conductivity, paving the way for the pioneering work on pristine organic semiconductors (OSCs) and their eventual use in a plethora of applications. Despite this early trend, however, recent strides in the field of organic electronics have been made hand in hand with the development and use of dopants to the point that are now ubiquitous. Here, we give an overview of all important advances in the area of doping of organic semiconductors and their applications. We first review the relevant literature with particular focus on the physical processes involved, discussing established mechanisms but also newly proposed theories. We then continue with a comprehensive summary of the most widely studied dopants to date, placing particular emphasis on the chemical strategies toward the synthesis of molecules with improved functionality. The processing routes toward doped organic films and the important doping-processing-nanostructure relationships, are also discussed. We conclude the review by highlighting how doping can enhance the operating characteristics of various organic devices.

Y6 Organic Thin-Film Transistors with Electron Mobilities of 2.4 cm2 V-1 s-1 via Microstructural Tuning.

There is a growing demand to attain organic materials with high electron mobility, µe , as current reliable reported values are significantly lower than those exhibited by their hole mobility counterparts. Here, it is shown that a well-known nonfullerene-acceptor commonly used in organic solar cells, that is, BTP-4F (aka Y6), enables solution-processed organic thin-film transistors (OTFT) with a µe as high as 2.4 cm2  V-1  s-1 . This value is comparable to those of state-of-the-art n-type OTFTs, opening up a plethora of new possibilities for this class of materials in the field of organic electronics. Such efficient charge transport is linked to a readily achievable highly ordered crystalline phase, whose peculiar structural properties are thoroughly discussed. This work proves that structurally ordered nonfullerene acceptors can exhibit intrinsically high mobility and introduces a new approach in the quest of high µe organic materials, as well as new guidelines for future materials design.

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.

Adduct-based p-doping of organic semiconductors.

Electronic doping of organic semiconductors is essential for their usage in highly efficient optoelectronic devices. Although molecular and metal complex-based dopants have already enabled significant progress of devices based on organic semiconductors, there remains a need for clean, efficient and low-cost dopants if a widespread transition towards larger-area organic electronic devices is to occur. Here we report dimethyl sulfoxide adducts as p-dopants that fulfil these conditions for a range of organic semiconductors. These adduct-based dopants are compatible with both solution and vapour-phase processing. We explore the doping mechanism and use the knowledge we gain to 'decouple' the dopants from the choice of counterion. We demonstrate that asymmetric p-doping is possible using solution processing routes, and demonstrate its use in metal halide perovskite solar cells, organic thin-film transistors and organic light-emitting diodes, which showcases the versatility of this doping approach.

Can google trends search inform us about the population response and public health impact of abrupt change in alcohol policy? A case study from India during the covid-19 pandemic.

BACKGROUND: Sudden alcohol prohibition in India during the COVID-19 pandemic presented an opportunity to test whether Google Trends data could indicate population responses and the public health impact of alcohol policy. We hypothesized, following prohibition: there would be a significant change in the relative search volumes (RSV) of alcohol-related queries; that temporal analysis of the trends would reflect a public response to policy changes; and that geospatial analysis of RSV would correlate with the prevalence of alcohol use. METHODS: Three different search periods were used to test the hypotheses. The search inputs were based on potential public response to alcohol prohibition, as evidenced by the literature, newspaper articles, and consensus. We used RSV as the unit of analysis. Mean RSV of search queries, pre-post implementation of prohibition, were compared. Smoothing of scatter plots examined the temporal association of trends with policy measures. Multiple linear regression tested the relationship of state-wise RSV and alcohol use prevalence. RESULTS: Post-implementation of prohibition, a significant increase in the RSV was observed for searches related to alcohol withdrawal (p<0.001), how to extract alcohol from sanitizer (p = 0.002), alcohol home delivery online (p<0.001), alcohol home delivery (p<0.001), and sleeping pills (p = 0.006). The trends suggested a decrease in general interest in alcohol but increased demand, and a possible connection with changes in policy measures. State-level RSV and alcohol use prevalence did not reveal a significant relationship. CONCLUSION: Google trend is a potential source of rapid feedback to policymakers about population responses to an abrupt change in alcohol policies.

Changes in sleep pattern and sleep quality during COVID-19 lockdown.

INTRODUCTION: To mitigate the spread of the pandemic coronavirus infection (COVID-19), governments across the world have adopted "lockdowns" which have confined many individuals to their homes. This disrupts normal life routines, elements of which are important circadian cues. The pandemic is also associated with new stressors, altered roles, and uncertainties about health and economic security, which are also likely to affect sleep. The current study is an online survey of sleep experience, routines, physical activity, and symptoms of anxiety and depression, to study the alterations associated with the lockdown. MATERIALS AND METHODS: The survey was conducted in early May 2020 using a questionnaire circulated through social media platforms. Questions related to demographic characteristics, current and previous sleep schedules, routine, and working patterns. Insomnia (Insomnia Severity Index - 4), Stress (Perceived Stress Scale - 4), anxiety and depressive symptoms (Patient Health Questionnaire - 4) and physical activity (International Physical Activities Questionnaire) were assessed using standardized instruments. RESULTS: A total of 958 valid responses were received. Compared to the prelockdown period, there was a shift to a later bedtime and waking time, with a reduction in night-time sleep and an increase in day-time napping. These effects were visible across occupational groups, but mostly affected working individuals except health professionals. Sleep quality deteriorated across groups. Reductions in sleep duration were associated with depressive symptoms. CONCLUSIONS: The COVID-19 lockdown is associated with changes in sleep schedule and in the quantity and quality of night-time sleep. Although these changes are associated with elevated rates of emotional symptoms, it is unclear from these cross-sectional results, whether sleep deterioration produces psychological distress, or vice versa.

Long-range exciton diffusion in molecular non-fullerene acceptors.

The short exciton diffusion length associated with most classical organic semiconductors used in organic photovoltaics (5-20 nm) imposes severe limits on the maximum size of the donor and acceptor domains within the photoactive layer of the cell. Identifying materials that are able to transport excitons over longer distances can help advancing our understanding and lead to solar cells with higher efficiency. Here, we measure the exciton diffusion length in a wide range of nonfullerene acceptor molecules using two different experimental techniques based on photocurrent and ultrafast spectroscopy measurements. The acceptors exhibit balanced ambipolar charge transport and surprisingly long exciton diffusion lengths in the range of 20 to 47 nm. With the aid of quantum-chemical calculations, we are able to rationalize the exciton dynamics and draw basic chemical design rules, particularly on the importance of the end-group substituent on the crystal packing of nonfullerene acceptors.

Extended lockdown and India's alcohol policy: a qualitative analysis of newspaper articles.

OBJECTIVES: Since 25th March 2020 India went into a complete and extended lockdown. Alcohol production, sales, and purchase were barred with this overnight prohibition order. We conducted a qualitative analysis of the media reports published within the first month of the nationwide lockdown with the objectives (a) using the media reports as indications of possible public health impact and population response of a sudden alcohol prohibition in India, (b) suggesting areas for future research. METHODS: We performed thematic and content analysis of 350 articles published online in national newspapers between the 26th March, 2020 and 25th April, 2020. Initial inductive, followed by deductive coding was done in this exploratory thematic analysis. RESULTS: The thematic analysis revealed four main themes: the beneficial aspects of the policy, the harmful aspects of the policy, non-compliance and attempts to change and / or subvert the policy, popularity and level of public buy-in of the policy. We generated relevant sub-themes under main themes. Two additional themes, not directly related to the sudden prohibition, were use of stigmatizing language and ethical concerns. The content analysis showed the frequency of the appearance of the main themes and proportions of sub-themes and codes under those main themes. CONCLUSION: The harms, perceived from the media reports, should be balanced against the potential benefits. Absence of a national-level alcohol policy was made apparent by the reflexive, disconnected, and conflictual measures. Future research could systematically examine the potential ramifications of alcohol prohibition on public health, social, and economic aspects.