Use of electroconvulsive therapy during postpartum: A retrospective chart review.

Background: There is limited data on use of electroconvulsive therapy (ECT) for management of psychiatric disorders during the postpartum period from India. Aim: We aimed to assess the demographic and clinical profile of patients receiving ECT during the postpartum period for various psychiatric disorders using a retrospective study design. Methods: ECT register of the department was reviewed for the period of January 2019 to December 2023 to identify the patients who received ECT during the postpartum period. The treatment records of these patients were evaluated to extract the demographic and clinical profile. Results: During the study period, 10 patients received ECT during the postpartum period. The mean age of the study sample was 27 (standard deviation [SD]: 2.9) years. Majority of the patients were inpatients (70%) at the time of receiving ECT. Five patients were diagnosed with first-episode depression with postpartum onset, and two patients had postpartum-onset psychotic disorder. One patient was diagnosed with recurrent depressive episode and one with bipolar disorder, current episode mania with psychotic symptom, at the time of receiving ECT. The mean number of ECTs during the ECT course was 6.7 (SD: 3.09). Nine out of the 10 patients showed good response to ECT. Conclusion: Although ECT is less frequently used for management of postpartum psychiatric disorders, its use is associated with significant clinical improvement.

Neuroprotective effect of PPAR gamma agonist in rat model of autism spectrum disorder: Role of Wnt/ß-catenin pathway.

BACKGROUND: The clinical manifestation of autism spectrum disorder (ASD) is linked to the disruption of fundamental neurodevelopmental pathways. Emerging evidences claim to have an upregulation of canonical Wnt/ß-catenin pathway while downregulation of PPARγ pathway in ASD. This study aims to investigate the therapeutic potential of pioglitazone, a PPARγ agonist, in rat model of ASD. The study further explores the possible role of PPARγ and Wnt/ß-catenin pathway and their interaction in ASD by using their modulators. MATERIAL AND METHODS: Pregnant female Wistar rats received 600 mg/kg of valproic acid (VPA) to induce autistic symptoms in pups. Pioglitazone (10 mg/kg) was used to evaluate neurobehaviors, relative mRNA expression of inflammatory (IL-1ß, IL-6, IL-10, TNF-α), apoptotic markers (Bcl-2, Bax, & Caspase-3) and histopathology (H&E, Nissl stain, Immunohistochemistry). Effect of pioglitazone was evaluated on Wnt pathway and 4 µg/kg dose of 6-BIO (Wnt modulator) was used to study the PPARγ pathway. RESULTS: ASD model was established in pups as indicated by core autistic symptoms, increased neuroinflammation, apoptosis and histopathological neurodegeneration in cerebellum, hippocampus and amygdala. Pioglitazone significantly attenuated these alterations in VPA-exposed rats. The expression study results indicated an increase in key transcription factor, ß-catenin in VPA-rats suggesting an upregulation of canonical Wnt pathway in them. Pioglitazone significantly downregulated the Wnt signaling by suppressing the expression of Wnt signaling-associated proteins. The inhibiting effect of Wnt pathway on PPARγ activity was indicated by downregulation of PPARγ-associated protein in VPA-exposed rats and those administered with 6-BIO. CONCLUSION: In the present study, upregulation of canonical Wnt/ß-catenin pathway was demonstrated in ASD rat model. Pioglitazone administration significantly ameliorated these symptoms potentially through its neuroprotective effect and its ability to downregulate the Wnt/ß-catenin pathway. The antagonism between the PPARγ and Wnt pathway offers a promising therapeutic approach for addressing ASD.

Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study.

BACKGROUND AND OBJECTIVES: The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR. METHODS: We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (ORIVW per 4.8 kg/m2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI. RESULTS: Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (ORIVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, ORIVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, ORIVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (ORIVW 0.85 [0.74-0.99], p = 0.032) than men (ORIVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant (p-interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association. DISCUSSION: Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

Effectiveness of a program to lower unwanted media screens among 2-5-year-old children: a randomized controlled trial.

Background: Limited interventions exist on reducing unwanted screen time (ST) among children from low- and middle-income countries (LMICs), so we developed and assessed the effectiveness of the program to lower unwanted media screen time (PLUMS) among children aged 2-5 years in Chandigarh, Union Territory, North India. Methods: An open-label randomized control parallel group trial per CONSORT guidelines was conducted among randomly selected 340 families with children aged 2-5 (±3 months) years in Chandigarh, India. PLUMS was implemented at the family level with a focus on modifying the home media environment and targeted individual-level interventions using parent and child modules for 2 months. A post-intervention (immediately) and a follow-up assessment after 6 months was done. During the follow-up period, the interaction was done passively via WhatsApp groups. The control group received routine healthcare services. Validated and standardized tools, including a digital screen exposure questionnaire with a physical activity component, preschool child behavior checklist, and sleep disturbance scale for children, were used to collect data at baseline, post-intervention, and follow-up periods. The primary outcome was the mean difference in ST (minutes/day) among children in the intervention group versus the control group. Generalized estimating equation (GEE) analysis was performed to adjust for clustering. Results: An equal number of families (n = 170) were randomly assigned to the intervention and control arms. In the post-intervention assessment, 161 and 166 families continued while, at the follow-up assessment, 154 and 147 were in the intervention and control arm, respectively. The mean difference in ST on a typical day [27.7 min, 95% Confidence Interval (CI) 5.1, 50.3] at the post-intervention assessment significantly (p < 0.05) decreased in the intervention (102.6 ± 98.5 min) arm as compared with the control (130.3 ± 112.8 min) arm. A significant reduction in ST (ß = -35.81 min, CI -70.6, -1.04) from baseline (ß = 123.1 min) to follow-up phase (ß = 116 min) was observed in GEE analysis. The duration of physical activity increased both at post-intervention (ß = 48.4 min, CI = +6.6, +90.3) and follow-up (ß = 73.4 min, CI = 36.2, 110.5) assessments in the intervention arm. Conclusion: The PLUMS intervention significantly reduced the children's mean ST on a typical day and increased the physical activity immediately post-intervention and during the 6-month follow-up period. These results might guide the policymakers to include strategies in the national child health programs in the Southeast Asia Region to reduce unwanted ST.Clinical trial registration: https://clinicaltrials.gov/, identifier CTRI/2017/09/009761.

Use of Clozapine in persons with a history of seizures: A retrospective study.

BACKGROUND: Seizures are considered to be one of the dreaded side effects of clozapine, and due to this, the use of clozapine is avoided in patients with treatment-resistant schizophrenia. Resultantly, there is little information about the use of clozapine among patients with seizure disorder. AIM: To assess the safety of clozapine in patients with history of seizures in their lifetime before starting clozapine and receiving clozapine for the management of psychotic disorders. RESULTS: Out of the 958 patients, 35 (3.65 %) had a history of at least one seizure episode before starting clozapine, with a mean of 5.06 (SD: 7.23; Median: 3.00) seizures before starting clozapine. The mean duration between the last seizure and the starting of clozapine was 123.75 (SD: 124.99; Median: 84) months, with nine patients having an episode of seizure in the previous 12 months and 15 patients being seizure-free for more than ten years. About one-fourth (25.7 %; nine out of 35) of the patients had recurrence of seizure while receiving clozapine for a mean duration of about five years. When the recurrence of seizure after starting clozapine was evaluated in patients receiving antiepileptics along with clozapine, the incidence of at least one seizure was 26.67 % (4 out of 15), and among those not receiving antiepileptics, the incidence of at least one seizure was 25 % (5 out of 20). The dose of clozapine at which seizure was noted ranged from 12.5 mg to 600 mg/day with a mean of 236.25 (SD: 169.04; Median: 162.5) mg/day. In none of the patients, clozapine had to be stopped due to the continuation of seizures. CONCLUSION: About one-fourth of the patients with history of an episode of seizure have recurrence of seizure while receiving clozapine. The demographic and clinical variables do not differ between those who develop and who do not develop seizures after starting clozapine, including concomitant use of antiepileptics.

An experience of using Clozapine in elderly patients with mental disorders.

BACKGROUND: There is little information on using clozapine in elderly patients with mental disorders from India. AIM: To evaluate the sociodemographic and clinical profile of elderly (age ≥ 60 years) patients started on clozapine. METHODOLOGY: The clozapine registry in the department was screened to identify elderly patients who were started on clozapine. Treatment records of these patients were reviewed to extract sociodemographic and clinical details. RESULTS: Out of the available information of 1058 patients in the registry, 42 (3.96 %) were elderly (≥ 60 years) patients. About two-thirds of the patients had treatment resistance, i.e., their psychotic illness had not responded to two adequate trials of antipsychotics, and the second most common indication for starting clozapine was tardive dystonia or tardive dyskinesia (23.8 %). The mean dose of clozapine was 135.89 (SD: 109.6; Range: 37.5-500; median: 87.5) mg/day. The mean duration of clozapine use at the time of data extraction for the study sample was 3.55 (SD: 2.15; Range 0.3-9; median: 3) years. At the last follow-up, about three-fourths of patients were experiencing at least one side effect, with constipation being the most common side effect, followed by sedation, weight gain, and hypersalivation. In only four patients, clozapine was stopped during the follow-up. In terms of effectiveness, majority of the patients were rated as much improved or very much improved on Clinical Global Impression-Improvement subscale. CONCLUSION: Clozapine can be safely used in elderly patients with mental disorders. Hence, clozapine should not be withheld in elderly patients with mental disorders whenever indicated.

Role of oral melatonin in prevention of postoperative delirium in patients undergoing elective surgery under general anesthesia: A Randomized controlled trial.

Background: Postoperative delirium is a common complication in patients undergoing elective surgery under general anesthesia. We aimed to minimize the incidence with an oral dose of 3 mg of melatonin administered the night before surgery. Methods: Hundred and sixty-two patients aged 40-80 years posted for various urological and gastrointestinal surgeries under general anesthesia with no preoperative cognitive deficits were randomly distributed equally to melatonin or control groups. In the control group, routine premedication was done with tablet alprazolam (0.25 mg) and ranitidine (150 mg), but in the melatonin group, the patients were given 3 mg melatonin orally the night before surgery along with routine premedication. The CAM scale was used for diagnosis of postoperative delirium. Results: Incidence of delirium was significantly lower in the melatonin group, 23.5%, 8.6%, and 2.5% at 6, 24, and 48 hours, respectively, and the corresponding mean (SD) values of CAM scores were 1.37 (1.30), 1.07 (1.03), and 0.69 (0.80). In contrast, the incidence of delirium was 46.9%, 30.9%, and 16% at 6, 24, and 48 hours, respectively, in the control group. There was a significant reduction in anxiety, a lower incidence of cognitive dysfunction (i.e., MoCA score <26), and improvement in sleep quality in the melatonin group at 6, 24, 48, and 72 hours after the surgical intervention. The generalized estimating equations model (GEE) model was used to study change in MoCA and CAM scores over time between the two groups, and it showed a significant interaction between time and treatment groups (P < 0.001). Conclusions: Melatonin premedication reduced incidence of postoperative delirium and cognitive dysfunction and was associated with better sleep quality and anxiolysis.

Beyond Pathology- Exploring Salutogenesis as a Novel Approach to Eye Inflammatory Disease Prevention and Management: A Perspective.

The aim of this perspective is to promote the theory of salutogenesis as a novel approach to addressing ophthalmologic inflammatory conditions, illustrating several concepts in which it is based upon and how they can be applied to medical practice. This theory can better contextualize why patients with similar demographics and exposures are not uniform in their clinical presentations. Stressors in daily life can contribute to a state of ill-health and there are various factors that help alleviate their negative impact. These alleviating factors are significantly impaired in people with poor vision, one of the most common presentations of ophthalmologic conditions. Salutogenic principles can guide the treatment of eye conditions to be more respectful of patient autonomy amidst shifting expectations of the doctor-patient relationship. Being able to take ownership of their health and feeling that their cultural beliefs were considered improves compliance and subsequently gives more optimal outcomes. Population-level policy interventions could also utilize salutogenic principles to identify previously overlooked domains that can be addressed. We identified several papers about salutogenesis in an ophthalmological context and acknowledged the relatively few studies on this topic at present and offer directions in which we can explore further in subsequent studies.

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.

SMARCA4 alterations in non-small cell lung cancer: a systematic review and meta-analysis.

AIMS: A mutation in the SMARCA4 gene which encodes BRG1, a common catalytic subunit of switch/sucrose non-fermentable chromatin-remodelling complexes, plays a vital role in carcinogenesis. SMARCA4 mutations are present in approximately 10% of non-small cell lung cancers (NSCLC), making it a crucial gene in NSCLC, but with varying prognostic associations. To explore this, we conducted a systematic review and meta-analysis on the prognostic significance of SMARCA4 mutations in NSCLC. METHODS: Electronic database search was performed from inception to December 2022. Study characteristics and prognostic data were extracted from each eligible study. Depending on heterogeneity, pooled HR and 95% CI were derived using the random-effects or fixed-effects models. RESULTS: 8 studies (11 cohorts) enrolling 8371 patients were eligible for inclusion. Data on overall survival (OS) and progression-free survival (PFS) were available from 8 (10 cohorts) and 1 (3 cohorts) studies, respectively. Comparing SMARCA4-mutated NSCLC patients with SMARCA4-wild-type NSCLC patients, the summary HRs for OS and PFS were 1.49 (95% CI 1.18 to 1.87; I2=84%) and 3.97 (95% CI 1.32 to 11.92; I2=79%), respectively. The results from the trim-and-fill method for publication bias and sensitivity analysis were inconsistent with the primary analyses. Three studies reported NSCLC prognosis for category I and II mutations separately; category I was significantly associated with OS. CONCLUSION: Our findings suggest that SMARCA4 mutation negatively affects NSCLC OS and PFS. The prognostic effects of SMARCA4-co-occurring mutations and the predictive role of SMARCA4 mutation status in immunotherapy require further exploration.

First and second-generation endometrial ablation devices: A network meta-analysis.

OBJECTIVE: First-generation and second-generation endometrial ablation (EA) techniques, along with medical treatment and invasive surgery, are considered successful lines of management for abnormal uterine bleeding (AUB). We set out to determine the efficacy of first and second-generation ablation techniques compared with medical treatment, invasive surgery and different modalities of the EA techniques themselves. DESIGN: Systematic review and network meta-analysis using a frequentist network. DATA SOURCES: We searched Medline (Ovid), PubMed, ClinicalTrials.gov, Cochrane CENTRAL, Web of Science, EBSCO and Scopus for all published studies up to 1 March 2021 using relevant keywords. ELIGIBILITY CRITERIA: We included all randomised controlled trials (RCTs) that compared premenopausal women with AUB receiving the intervention of second-generation EA techniques. DATA EXTRACTION AND SYNTHESIS: 49 high-quality RCTs with 8038 women were included. We extracted and pooled the data and then analysed to estimate the network meta-analysis models within a frequentist framework. We used the random-effects model of the netmeta package in R (V.3.6.1) and the 'Meta-Insight' website. RESULTS: Our network meta-analysis showed many varying results according to specific outcomes. The uterine balloon ablation had significantly higher amenorrhoea rates than other techniques in both short (hydrothermal ablation (risk ratio (RR)=0.51, 95% CI 0.37; 0.72), microwave ablation (RR=0.43, 95% CI 0.31; 0.59), first-generation techniques (RR=0.44, 95% CI 0.33; 0.59), endometrial laser intrauterine therapy (RR=0.18, 95% CI 0.10; 0.32) and bipolar radio frequency treatments (RR=0.22, 95% CI 0.15; 0.31)) and long-term follow-up (microwave ablation (RR=0.11, 95% CI 0.01; 0.86), bipolar radio frequency ablation (RR=0.12, 95% CI 0.02; 0.90), first generation (RR=0.12, 95% CI 0.02; 0.90) and endometrial laser intrauterine thermal therapy (RR=0.04, 95% CI 0.01; 0.36)). When calculating efficacy based only on calculated bleeding scores, the highest scores were achieved by cryoablation systems (p-score=0.98). CONCLUSION: Most second-generation EA systems were superior to first-generation systems, and statistical superiority between devices depended on which characteristic was measured (secondary amenorrhoea rate, treatment of AUB, patient satisfaction or treatment of dysmenorrhoea). Although our study was limited by a paucity of data comparing large numbers of devices, we conclude that there is no evidence at this time that any one of the examined second-generation systems is clearly superior to all others.

A randomised controlled trial to evaluate the effectiveness of a culture and disease-specific, patient-centric multi-component tobacco cessation intervention package for the patients attending non-communicable disease clinics in Punjab, India.

BACKGROUND: Developing an infrastructure to support tobacco cessation through existing systems and resources is crucial for ensuring the greatest possible access to cessation services. The present study aims to evaluate the effectiveness of a newly developed multi-component cessation among tobacco users in Non- Communicable Disease (NCD) clinics, functioning under the National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases, & Stroke (NPCDCS) of the Government of India. METHODS: The intervention package consisting of culture- and disease-specific four face-to-face counselling sessions, pamphlets, and short text messages (bilingual) with follow-ups at 3rd, 6th, and 9th months with an endline assessment at 12th months was delivered to the intervention arm of the two-arm- parallel group randomised controlled trial at two selected NCD clinics. Self-reported seven-day abstinence, frequency of use, expenditure in seven days at each follow-up, FTND score, stage of change and plasma cotinine values were assessed at baseline, follow-ups, and endline (using Liquid Chromatography -Mass Spectrometry), as applicable. RESULTS: The intervention arm reported a significantly more reduction in self-reported frequency of tobacco use at 6 months (mean: 13.6, 95% CI (7.8-19.4)), 9 months (mean: 20.3, 95% CI (12.2-28.4)) and 12 months (mean: 18.7, 95% CI (8.7-28.7)). The plasma cotinine concentration at endline in the intervention arm was statistically significantly lower than the baseline concentration. CONCLUSION: Strengthening existing health systems is crucial for offering cessation support in the resource-restraint setting of LMICs to assist in quitting sustainably.

Efficacy of melatonin in decreasing the incidence of delirium in critically ill adults: a randomized controlled trial.

OBJECTIVE: To determine whether enteral melatonin decreases the incidence of delirium in critically ill adults. METHODS: In this randomized controlled trial, adults were admitted to the intensive care unit and received either usual standard care alone (Control Group) or in combination with 3mg of enteral melatonin once a day at 9 PM (Melatonin Group). Concealment of allocation was done by serially numbered opaque sealed envelopes. The intensivist assessing delirium and the investigator performing the data analysis were blinded to the group allocation. The primary outcome was the incidence of delirium within 24 hours of the intensive care unit stay. The secondary outcomes were the incidence of delirium on Days 3 and 7, intensive care unit mortality, length of intensive care unit stay, duration of mechanical ventilation and Glasgow outcome score (at discharge). RESULTS: We included 108 patients in the final analysis, with 54 patients in each group. At 24 hours of intensive care unit stay, there was no difference in the incidence of delirium between Melatonin and Control Groups (29.6 versus 46.2%; RR = 0.6; 95%CI 0.38 - 1.05; p = 0.11). No secondary outcome showed a statistically significant difference. CONCLUSION: Enteral melatonin 3mg is not more effective at decreasing the incidence of delirium than standard care is in critically ill adults.