Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling. RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not. CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

Does the Etiology, Phenomenology and Motor Subtype of Delirium Differ When It Occurs in Patients With An Underlying Dementia?: A Multi-Site, International Study.

OBJECTIVES: To compare the etiology, phenomenology and motor subtype of delirium in patients with and without an underlying dementia. METHODS: A combined dataset (n = 992) was collated from two databases of older adults (>65 years) from liaison psychiatry and palliative care populations in Ireland and India. Phenomenology and severity of delirium were analysed using the Delirium Symptom Rating Scale Revised (DRS-R98) and contributory etiologies for the delirium groups were ascertained using the Delirium Etiology Checklist (DEC). Delirium motor subtype was documented using the abbreviated version of the Delirium Motor Subtype Scale (DMSS4). RESULTS: Delirium superimposed on dementia (DSD) showed greater impairment in short term memory, long term memory and visuospatial ability than the delirium group but showed significantly less perceptual disturbance, temporal onset and fluctuation. Systemic infection, cerebrovascular and other Central nervous system etiology were associated with DSD while metabolic disturbance, organ insufficiency and intracranial neoplasm were associated with the delirium only group. CONCLUSION: The etiology and phenomenology of delirium differs when it occurs in the patient with an underlying dementia. We discuss the implications in terms of identification and management of this complex condition.

Quality of Life Analysis in Patients with Retinitis Pigmentosa.

INTRODUCTION: Retinitis pigmentosa (RP) is a chronic progressive disease causing loss of visual acuity and ultimately blindness. This visual impairment can contribute to psychiatric comorbidity and worse overall quality of life (QOL). Our goal was to assess the relationship between the severity of disease for people with RP and QOL as it pertains to mental health, social support, disability resources, and financial factors. METHODS: This was a survey study conducted from June 2021 to February 2022 including 38 people with RP. QOL was assessed through a survey questionnaire focusing specifically on demographics, visual function, family, employment, social support, and mental health/well-being. Statistical analysis was conducted using a χ2 test for significance. RESULTS: A best corrected visual acuity (BCVA) of less than 20/200 (p = 0.0285) and living alone (p = 0.0358) were both statistically significant independent risk factors for experiencing depressive symptoms. Highest education level attained and unemployment rate were not found to be related to the development of depressive symptoms. Subjects had a higher unemployment rate (64% vs. US rate of 3.6%) and a high likelihood of reporting depressive symptoms (47.4%). CONCLUSION: People with RP are more likely to be unemployed and to develop depressive symptoms when compared to the general population. Similar to previous studies' findings, those with a BCVA of less than 20/200 were statistically more likely to experience depressive symptoms; living alone is a novel risk factor that is also associated with the presence of depressive symptoms. Contrary to prior findings, highest education level and unemployment status were found not to be related to the development of depressive symptoms. These patients may benefit from regular depression screenings and optional establishment of care with a psychiatrist or psychologist if they live alone or their BCVA is 20/200 or worse.

Author Response.

How to cite this article: Niyogi SG, Naskar C, Singh A, Kumar B, Grover S. Author Response. Indian J Crit Care Med 2024;28(2):188.

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers.

BACKGROUND: Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. OBJECTIVE: We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. METHODS: We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. RESULTS: We confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31). CONCLUSIONS: We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Clinician Reasons for Stopping Clozapine: A Retrospective Cohort Study.

BACKGROUND: Little information is available on clozapine discontinuation rates in developing country settings. AIM: The present study aimed to evaluate the incidence and reasons clinicians stopped clozapinine in patients after initiating treatment with the same. In addition, the study also aimed to assess the rechallenge rate, that is, restarting clozapine after a decision to discontinue the same by the clinicians. METHODOLOGY: The treatment records of 859 patients started on clozapine were reviewed to identify the patients for whom the clinician stopped clozapine at least once because of any reason. The reasons for stopping clozapine were reviewed. In addition, the treatment records were also examined for rechallenge with clozapine at a later date. RESULTS: Clozapine was stopped by the clinicians in 44 of the 859 patients (5.12%). The most common reason for stopping clozapine was blood dyscrasias (n = 12), followed by poor adherence making the hematological monitoring difficult (n = 9), and intolerable sedation (n = 7). In half of the patients (n = 22), clozapine was restarted by the clinicians for further management of schizophrenia. Successful rechallenge was done in 58.33% of patients with blood dyscrasias, 44.44% with poor adherence, and 71.4% with intolerable sedation. CONCLUSIONS: The present study suggests clinicians stop clozapine in only 5.14% of cases. The most common reasons for clozapine discontinuation by clinicians include blood dyscrasias, poor medication adherence making it challenging to monitor the hemogram, and sedation. However, in half of the patient's clozapine was rechallenged, and all the attempts of rechallenging were successful.

Escaping the Long Shadow Cast by Agranulocytosis: Reflections on Clozapine Pharmacovigilance Focused on the United Kingdom.

PURPOSE/BACKGROUND: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. METHODS: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. FINDINGS/RESULTS: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. IMPLICATIONS/CONCLUSIONS: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

Clozapine Use for Bipolar Disorder: An Asian Psychotropic Prescription Patterns Consortium Study.

BACKGROUND: Pharmacoepidemiological studies of clozapine use to treat bipolar disorder (BD), especially in Asia, are rare, although they can provide insights into associated clinical characteristics and support international comparisons of indications and drug dosing. METHODS: We examined the prevalence and clinical correlates of clozapine treatment for BD in 13 Asian countries and regions (China, Hong Kong SAR, India, Indonesia, Japan, Korea, Malaysia, Myanmar, Pakistan, Singapore, Sri Lanka, Taiwan, and Thailand) within an Asian Prescription Patterns Research Consortium. We compared BD patients treated with clozapine or not in initial bivariate comparisons followed by multivariable logistic regression modeling. RESULTS: Clozapine was given to 2.13% of BD patients overall, at a mean daily dose of 275 (confidence interval, 267-282) chlorpromazine-equivalent mg/day. Patients receiving clozapine were older, more likely males, hospitalized, currently manic, and given greater numbers of mood-stabilizing and antipsychotic drugs in addition to clozapine. Logistic regression revealed that older age, male sex, current mania, and greater number of other antipsychotics remained significantly associated with clozapine treatment. Clozapine use was not associated with depressed mood, remission of illness, suicidal risk, or electroconvulsive treatment within the previous 12 months. CONCLUSIONS: The identified associations of clozapine use with particular clinical features call for vigilance in personalized clinical monitoring so as to optimize clinical outcomes of BD patients and to limit risks of adverse effects of polytherapy.

Psychiatric comorbidities in patients suffering from systemic lupus erythematosus admitted to a tertiary care hospital in Northern India.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with multiorgan involvement presenting with a myriad of symptoms, including neuropsychiatric symptoms. Although many studies have evaluated screening questionnaires based psychiatric morbidity, very few studies have used contemporary diagnostic criteria. OBJECTIVE: This study aimed to evaluate the prevalence of psychiatric disorders in patients with SLE admitted to a tertiary care hospital. METHODS: A total of 79 patients diagnosed with SLE for at least for 1 year, who were not in delirium were assessed by a qualified psychiatrist for psychiatric morbidity as per the International Classification of Diseases, 10th Revision (ICD-10) criteria. Additionally, these patients were assessed on Patient Health Questionnaire-9 (PHQ-9) item version, Patient Health Questionnaire-15 (PHQ-15) item version, Generalized Anxiety Disorder-7 item scale and Montreal Cognitive Assessment (MoCA). RESULTS: 51% (n = 40) of the participants were diagnosed with a psychiatric diagnosis, with depressive disorders being the most common, seen in 36.7% (n = 29) of the participants. Additionally, 10% (n = 8) participants were diagnosed with adjustment disorder and 2.5% (n = 2) were diagnosed with anxiety (not otherwise specified). Only one patient was diagnosed with organic psychosis. On PHQ-9, 39.8% (n = 33) were diagnosed with depression. 44.3% (n = 35) expressed death wishes and/or suicidal ideations. On PHQ-15, 17.7% (n = 14) of the participants scored for severe somatic distress (score >15). On GAD-7, 55.7% (n = 44) screened positive for anxiety symptoms, but only 7.6% (n = ) had a score of 15 or more to indicate severe anxiety. Nearly half (n = 43; 52%) of the participants also had cognitive impairment as assessed on MoCA, with 13.3% (n = 11) of the participants having scores indicating severe dementia. CONCLUSIONS: Patients with SLE have a high prevalence of psychiatric comorbidities and should be routinely screened for psychiatric morbidity. They should be appropriately treated, to improve the overall treatment outcomes.

Estimating the Cost of Delivering Tobacco Cessation Intervention Package at Noncommunicable Disease Clinics in Two Districts of North India.

INTRODUCTION: Integrated care is likely to improve outcomes in strained healthcare systems while limiting costs. NCD clinics were introduced under the "National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Disease, and Stroke" (NPCDCS) in India; however, there is limited literature on the costs of delivering tobacco cessation interventions within NPCDCS. One of the study's objectives was to estimate the cost of delivering a culturally specific patient-centric behavioral intervention package in two district-level NCD clinics in Punjab, India. METHODS: Costing was undertaken using the health systems perspective. A top-down or financial costing approach and a bottom-up or activity-based approach were employed at each step of development and implementation. The opportunity cost was used to include the cost of human resources, infrastructure, and capital resources used. All infrastructure and capital costs were annualized using a 3% annual discount rate. Four additional scenarios were built up concerning three major components to reduce costs further when rolled out on a large scale. RESULTS: The cost of intervention package development, human resource training, and unit cost of implementation were estimated to be INR 6,47,827 (USD 8,874); INR 134,002 (USD 1810); and INR 272 (USD 3.67), respectively. Based on our sensitivity analysis results, the service delivery cost varied from INR 184 (USD 2.48) to INR 326 (USD 4.40) per patient. CONCLUSION: The development costs of the intervention package accounted for the majority proportion of the total cost. Of the total unit cost of implementation, the telephonic follow-up, human resources, and capital resources were the major contributory components. IMPLICATIONS: The current study aims to fill gaps by estimating the unit-level health systems cost of a culturally sensitive, disease-specific, and patient-centric tobacco cessation intervention package delivered at the outpatient settings of NCD clinics at the secondary level hospital, which represents a major link in the health care system of India. Findings from this study could be used to provide supportive evidence to policymakers and program managers for rolling out such interventions in established NCD clinics through the NPCDCS program of the Indian Government.

The factor structure of extrapyramidal symptoms evaluated using the Drug-Induced Extrapyramidal Symptoms Scale in patients with schizophrenia: Results from the 2016 REAP AP-4 study.

INTRODUCTION: Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). METHODS: The participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items, and the second for confirmatory factor analysis. RESULTS: The factor analysis identified three factors: F1 (gait and bradykinesia), F2 (muscle rigidity and tremor), and F3 (sialorrhea, akathisia, dystonia, and dyskinesia). CONCLUSION: The results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: acute parkinsonism observed during action (F1), acute parkinsonism observed at rest (F2), and central dopaminergic mechanisms with pathophysiology other than acute parkinsonism (F3).

Mental health issues in antenatal women with prior adverse pregnancy outcomes: Unmasking the mental anguish of rainbow pregnancy.

Background & objectives: Mental health issues in pregnancy have adverse implications on the quality of life, however still they go unevaluated and underreported. Women with previous history of abortions or stillbirth may have a higher risk of experiencing mental health problems. The present investigation was aimed to study the prevalence of depression, anxiety, stress and domestic violence in antenatal women with prior pregnancy losses and the need for interventions to treat the same. Methods: One hundred pregnant women with a history of prior pregnancy losses (group 1) and 100 women without obstetrical losses (group 2) were enrolled in this cross-sectional study carried out in a tertiary care hospital in India. Women were screened for depression, anxiety, stress and domestic violence using various questionnaires: EPDS (Edinburgh postnatal depression scale), PRAQ-2 (pregnancy-related anxiety questionnaire-revised 2), GAD 7 (generalized anxiety disorder-7) and PSS (perceived stress scale). Results: The prevalence of depression (EPDS scale) and pregnancy specific anxiety (PRAQ-2 scale) was significantly higher in group 1 than in group 2 (27 vs. 10%, P=0.008; and 15 vs. 6%, P=0.03). The prevalence of general anxiety (GAD 7 scale) and stress (PSS), however, was high and comparable in both the groups (33 vs. 29%, P=0.44; and 33 vs. 27%; P=0.35 respectively). Recurrent abortions was found to be an independent risk factor for depression [adjusted odds ratio=26.45; OR=28]. In group 1, 31 per cent required counselling in the psychiatry department and nine per cent required medication. Interpretation & conclusion: Mental health issues, especially depression, are prevalent in antenatal women with previous losses. Unrecognised and untreated, there is a need for counselling and developing screening protocols at India's societal and institutional levels.

Severity and determinants of psychosocial comorbidities in granulomatosis with polyangiitis and their impact on quality of life.

Depression, anxiety, sleep disturbances, and fatigue are inadequately addressed comorbidities in granulomatosis with polyangiitis (GPA). We determined the prevalence, severity, determinants, and the impact of these comorbidities on quality-of-life (QoL) in GPA. This observational study included adult GPA patients; patients with RA and lupus were included as comparators. Patient Health Questionnaire-9 for depression, Generalized Anxiety Disorder 7-item scale for anxiety, Epworth Sleepiness Scale for sleep disturbances, and Fatigue Severity Scale for fatigue were administered prospectively to estimate prevalence and severity. QoL and disability were estimated using PROMIS-HAQ, HAQ-health and HAQ-pain. Correlations among these parameters were assessed. Stepwise regression analyses were performed to identify determinants of depression, anxiety, excessive sleepiness, and fatigue. One hundred eighty-one patients-62 GPA [mean age 43 (13) years], 57 RA and 62 SLE- were included. The prevalence of depression (47%), excessive sleepiness (21%), and fatigue (39%) in GPA were comparable to RA and lupus; anxiety was less prevalent (29% versus 46% and 53%, p = 0.02). Severity was mostly mild-moderate. Younger age [OR = 0.93 (0.89-0.98)], higher BMI [OR = 1.2 (1.0-1.4)], and greater disease damage [OR = 2.0 (1.3-3.3)] independently predicted presence of depression. Higher BMI [OR = 1.3 (1.1-1.5)] and concomitant FMS [OR = 80.9 (5.1-1289.2)] were independently associated with excessive sleepiness. No association with disease activity, duration, or gender was seen. GPA patients with depression, anxiety, excessive sleepiness, and fatigue had worse PROMIS-HAQ, HAQ-pain, and HAQ-health. In conclusion, depression, anxiety, sleep disturbances, and fatigue are common in GPA. Although their severity is mostly mild-moderate, they impair QoL significantly. Potentially modifiable determinants that can form targets for future interventions have been identified.

Factors associated with lifetime suicide attempts: findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

AIM: To evaluate the risk factors associated with lifetime suicide attempts in bipolar disorder (BD) patients. METHODOLOGY: 773 BD patients with a duration of illness of at least ten years, currently in clinical remission, were evaluated for suicidal attempts in their lifetime. Those with and without lifetime suicide attempt(s) were compared for various demographic and clinical risk factors. RESULTS: 242 (31.3%) patients had a history of at least one lifetime suicide attempt. Compared to those without lifetime suicide attempts, those with suicidal attempts were less educated, were more often females, spent more time in episodes, and had a significantly more number of total episodes (in the lifetime, first five years of illness, and per year of illness), had significantly more number of total depressive episodes (in the lifetime, first five years of illness, and per year of illness), spent more time in depressive episodes, had more severe depressive episodes, more often had depression as the first episode in the lifetime, spent more time in mania/hypomania/mixed episodes, had higher residual depressive and manic symptoms, more often had rapid cycling affective disorder pattern in the lifetime, use of cannabis in dependence pattern, had poorer insight into their illness and had a higher level of disability (especially in three out of the four domains of Indian disability evaluation assessment scale). CONCLUSIONS: About one-third of the patients with BD have at least one-lifetime suicidal attempt, and those with suicide attempts usually have a poorer course of illness.

Augmentation strategies for clozapine resistance: a systematic review and meta-analysis.

BACKGROUND: Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs) have evaluated the efficacy of different strategies to augment clozapine. This systematic review and meta-analysis reviewed the available RCTs that have evaluated the clinical efficacy of various pharmacological agents, non-pharmacological strategies (occupational therapy, cognitive behaviour therapy), and somatic treatment [electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, etc.)] as augmenting agents to clozapine. METHODS: Data were extracted using standard procedures, and risk of bias was evaluated. Effect sizes were computed for the individual studies. RESULTS: Forty-five clinical trials were evaluated. The pooled effect size for various antipsychotic medications was 0.103 (95% CI: 0.288-0.493, p < 0.001); when the effect size was evaluated for specific antipsychotics for which more than one trial was available, the effect size for risperidone was -0.27 and that for aripiprazole was 0.57. The effect size for lamotrigine was 0.145, and that for topiramate was 0.392. The effect size for ECT was 0.743 (CI: 0.094-1.392). Risk of bias was low (mean Jadad score - 3.93). Largest effect sizes were seen for mirtazapine (effect size of 5.265). Most of the studies can be considered underpowered and limited by small sample sizes. CONCLUSIONS: To conclude, based on the findings of the present systematic review and meta-analysis, it can be said that compared to other treatment strategies, clozapine non-responsive patients respond maximum to mirtazapine followed by ECT.

A comparative study of retinal layer changes among patients with schizophrenia and healthy controls.

AIM: This study aimed to evaluate the retinal nerve fibre layer changes among different group of patients with schizophrenia and compare it with healthy controls by using swept-source optical coherence tomography. METHODOLOGY: Patients with first-episode schizophrenia (n = 21) in remission (n = 35) or with treatment-resistant schizophrenia (TRS) (n = 35) and 36 healthy controls were evaluated for retinal thickness. RESULTS: Patients with psychotic illnesses had significantly lower sub-foveal choroidal thickness (effect size 0.84-0.86), when compared to the healthy controls. When patients with first-episode schizophrenia were compared with patients with TRS, TRS patients had significant lower sub-foveal choroidal thickness (left eye) when the various confounders (such as age, gender, duration of treatment, smoking, current medications, body mass index, waist circumference, blood pressure, fasting glucose, HbA1c, presence or absence of metabolic syndrome) were taken into account. When the patients with TRS were compared with healthy controls, initially significant differences were observed for the macular volume (left and right) and the ganglion cell thickness (right eye) but these differences disappeared after controlling for the various covariates. CONCLUSIONS: Compared to healthy controls, patients with schizophrenia, psychotic illnesses have thinning of the retina, especially in the sub-foveal choroidal thickness.

Prevalence and Association of Digital Eye Strain with the Quality of Sleep and Feeling of Loneliness among Female College Students in Northern India.

INTRODUCTION: Because of COVID's impact on social behavior, students have become more reliant on computer-facilitated communication to continue their studies and interact with friends. While it is known that the association between screen exposure and psychological well-being is both harmful and stronger among adolescents than younger children, what is less studied are the causal factors that may mediate the relationship. OBJECTIVES: The objectives of this study were to analyze the relationship between screen exposure and two psychological outcomes, sleep quality and loneliness, using digital eye strain as a mediating factor. Eye strain is expected to have a direct and harmful influence on psychological well-being. MATERIALS AND METHODS: A structured and validated questionnaire was transcribed and administered online. A nonrepresentative sample of 497 female college students in a North Indian city participated in the study. Digital eye strain, quality of sleep, and feeling of loneliness scores were assessed using latent class analysis. RESULTS: The selected latent model suggested that Class 2 had a high percentage of students with network issues, the problem with space and noise, and various financial hardships, which had almost doubled the rate of loneliness (53.28%) and sleep-wake difficulties (75.41%) among the students affected with computer vision syndrome (89.75%). CONCLUSION: There is an urgent need to examine the implications of digital exposure across gender and age to prevent future complications. Further, awareness for improving holistic well-being in the digital era should be promoted through various platforms.

Melatonin and Melatonin Agonists for Prevention of Delirium in the Cardiac Surgical ICU: A Meta-analysis.

Aim and Background: Delirium is highly prevalent in the immediate postoperative period following cardiac surgery and adversely impacts outcomes. Melatonin has been increasingly used in pharmacological prevention of delirium. We aimed to synthesize the available evidence concerning the role of melatonin and melatonin agonists in preventing delirium in patients after cardiac surgery. Materials and methods: PubMed, Google Scholar, and Web of Science databases were searched for relevant randomized and non-randomized trials in adults undergoing cardiac surgery investigating melatonin agonists to prevent delirium. Studies incorporating transplants, preoperative organ support, prophylactic antipsychotics, or children were excluded. Risk-of-bias was assessed using Cochrane ROB 2.0 and ROBINS-I tools. A systematic review and meta-analysis were conducted, calculating pooled odds ratio (OR) for the incidence of postoperative delirium using a random effects model with the Mantel-Haenszel method with restricted maximum-likelihood estimator. Trial sequential analysis was also carried out for the primary outcome. Results: Six randomized trials and one non-randomized trial involving 1,179 patients were included. Incidence of delirium was 16.7 and 29.6% in the intervention and comparator groups respectively, indicating a pooled OR of 0.44 [95% confidence interval (CI) 0.27 - 0.71, p = 0.04] favoring melatonin. Two studies had a high risk of bias, and I2 statistics indicated significant heterogeneity. However, publication bias was insignificant, and trial sequential analysis indicated the significance of the attained effect size. Conclusion: Based on available studies, perioperative melatonin use significantly decreases postoperative incidence of delirium after adult cardiac surgery. However, the available quality of evidence is low, and larger trials with standardization of nonpharmacological delirium prevention interventions, in high-risk cohorts, and exploring various dosages and regimens should be carried out. How to cite this article: Niyogi SG, Naskar C, Singh A, Kumar B, Grover S. Melatonin and Melatonin Agonists for Prevention of Delirium in the Cardiac Surgical ICU: A Meta-analysis. Indian J Crit Care Med 2023;27(11):837-844.

Improvement of chronic HCV infection-related depression, anxiety, and neurocognitive performance in persons achieving SVR-12: A real-world cohort study.

Chronic hepatitis C virus (HCV) infection is associated with neuropsychiatric changes. Also, patients with cirrhosis may develop overt or minimal hepatic encephalopathy. Sustained virological response (SVR) with direct-acting antiviral agents (DAAs) may improve the neuropsychiatric manifestations and quality of life (QoL). Consecutive patients (with and without cirrhosis, all genders and aged 18-65 years) with hepatitis C were assessed at enrolment and at 12 weeks after therapy completion for mood (Beck's Depression Inventory [BDI]), anxiety (generalized anxiety disorder [GAD-7]), QoL (SF-36 ver.2) and computer-based tests for number connection (NCT), visual memory, Stroop test and reaction times. We recruited 385 viraemic chronic HCV patients (76.1% male, 21.0% cirrhotic, mean age 39.4 ± 14.2 years, 59.3% genotype 3, mean HCV RNA load 5.8 log). Overall SVR-12 rates were 90.6%, with cure rates 87.6% and 91.4% in patients with and without cirrhosis, respectively. Patients who achieved SVR-12 had mean percentage reduction in BDI (11.3%, p = .000), GAD (8.6%, p = .001) and Stroop test (58.4%, p = .001), with improved NCT (1.7%, p = .001), visual memory (13.7%, p = .001) and digit span (23.8%, p = .002). On multivariate logistic regression, adherence (OR, 17.5 [95% CI 2.80-110.50], p = .000), high ALT (OR 1.02 [95% CI 1.00-1.05]), and BDI score (OR 1.73 [95% CI 1.42-3.26] p = .039) predicted cure. SVR-12 was associated with improved visual memory ≥5.5 (AUC-0.708; sensitivity 62.5%, specificity 63%, p = .000) and % correct Stroop test responses >26.6% (AUC-0.918, sensitivity 94.4% specificity 80.4%, p = .000). In conclusion, given the cumulative evidence of the safety of DAAs and efficacy of improving cognitive and neuropsychological and quality-of-life outcomes irrespective of age and gender, as shown in our study, future recommendations should focus on integrated universal HCV care to enable HCV elimination.

Outcomes After Curative Metastasectomy for Patients with Malignant Melanoma: A Systematic Review and Meta-analysis.

BACKGROUND: Evidence on the role of curative metastasectomy (CM) for malignant melanoma (MM) patients is limited, especially in the current era of effective systemic therapy. A systematic review and meta-analysis were performed to ascertain the role of CM compared with incomplete or nonsurgical treatment for patients with MM. METHODS: Medline, Embase, and Scopus databases were searched for studies investigating CM for MM until 30 September 2021. The review included studies that compared CM with no-CM and reported a hazard ratio (HR) after multivariate analysis for overall survival. A random-effects model with inverse variance was used to calculate pooled HR. The Newcastle-Ottawa Scale was used to assess the risk of bias. RESULTS: For the final analysis, 40 studies including 31,282 patients (CM, 9958; no-CM, 21,324) were considered. Compared with no-CM, CM was associated with a significantly lower risk of death (HR, 0.42; 95% confidence interval [CI], 0.38-0.47; p < 0.00001). Subgroup analysis showed that the outcome was independent of the effective systemic therapy and anatomic location of metastasis. An unfavorable prognosis was associated with advancing age, elevated lactate dehydrogenase (LDH), male gender, prior stage 3 disease, multiple metastases and organ sites, and shorter disease-free interval. CONCLUSION: Curative metastasectomy for MM is associated with a lower risk of death than non-curative treatment methods. Selection bias and underlying weakness of studies reduced the strength of evidence in this review. However, CM should be a part of the multimodality treatment of MM whenever technically feasible.