Sertraline with desvenlafaxine and sertraline with mirtazapine as treatment initiation in MDD patients with moderate to severe depression and effect on inflammatory markers.

BACKGROUND: This study evaluated the effect of sertraline with desvenlafaxine and sertraline with mirtazapine on HAM-D score and inflammatory markers (IL-6 and TNF-α levels) in major depressive disorder. METHODS: Patients (18-60 years) with MDD diagnosed by DSM-V criteria and HAM-D score 18 or more were included (n = 60). Group A patients (n = 30) received sertraline 50 mg/day and desvenlafaxine 50 mg/day. Group B patients (n = 30) received sertraline 50 mg/day and mirtazapine 30 mg/day. All patients were followed up for 8 weeks for the evaluation of clinical efficacy, safety, serum IL-6, and TNF-α levels. RESULTS: Our study showed a comparatively similar and statistically significant (p < 0.05) reduction in HAM-D score in both groups in the 4th and 8th week of the treatment. Both drug combinations significantly (p < 0.05) decreased serum IL-6 and TNF-α after 8 weeks of treatment. CONCLUSION: The present study suggests that the combination therapy (as treatment initiation) with sertraline and desvenlafaxine, and sertraline with mirtazapine is effective and well tolerated in MDD patients with moderate to severe depression, and their therapeutic efficacy is accompanied by decreased inflammatory markers (serum IL-6 and TNF-α).

Recent evidence indicates that combination therapy of antidepressant drugs started as treatment initiation produces superior treatment outcomes in patients of MDD with moderate to severe depression.MDD is associated with increased inflammatory markers.Combination therapy of sertraline with desvenlafaxine and sertraline with mirtazapine as treatment initiation is effective and well tolerated in MDD patients.The therapeutic efficacy of sertraline with desvenlafaxine and sertraline with mirtazapine is associated with a significant decrease in serum levels of IL-6 and TNF-α.

Satisfaction and psychological after effects of legal abortion at a tertiary care teaching hospital of North India.

Psychological assessment using the Beck Depression Inventory II (BDI) on 196 eligible Medical Termination of Pregnancy (MTP) seekers showed that the depression rate prior to MTP was 12 (6.1%) and had increased to 21 (10.7%) 1 month after MTP. Risk factors included primipara, second-trimester abortion, MTP on humanitarian grounds (rape), foetal congenital anomalies and maternal illness. Psychological morbidity due to abortion greatly interferes with the interpersonal, spousal and mother-child relationships. This demands the need of counselling centres so that each MTP seeker could be counselled prior to and after MTP. Impact statement What is already known on this subject? The association between abortion and depression has already been established. But there is a scarcity of information about the association between the psychological morbidity of abortion seekers, prior to and after legal abortions at a tertiary hospital. What do the results of this study add? Our study has not only evaluated the depression rate, but also evaluated the various individual psychological parameters of women with mild mood disorders which might go unnoticed and which certainly interferes with their interpersonal relationships. What are the implications of these findings for clinical practice and/or further research? Early diagnosis and interventions could help these women to have sound interpersonal relations.

Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-α in Patients of Major Depressive Disorder with Severe Depression.

BACKGROUND: This study evaluated the clinical efficacy of mirtazapine and its effect on serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) levels in patients of major-depressive disorder (MDD) with severe depression. METHODS: Patients (aged 18-60) with MDD diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥25 were included (n = 30). Mirtazapine was given in the doses of 30 mg/day. All patients were followed up for 12 weeks for the evaluation of clinical efficacy, safety along with serum BDNF and TNF-α levels. RESULTS: HAM-D score at the start of treatment was 30.1 ± 1.92, which significantly (p < 0.05) reduced to 13.47 ± 1.77 at 12 weeks of treatment. In responders, mean serum BDNF levels at the start of treatment were 2.32 ± 0.3 ng/ml, which significantly (p < 0.05) increased to 2.79 ± 0.33 ng/ml at 12 weeks of treatment and mean serum TNF-α levels at the start were 5.18 ± 0.67 pg/ml, which significantly decreased to 4.36 ± 0.72 pg/ml (p < 0.05) at 12 weeks of treatment. CONCLUSION: Our results suggest that mirtazapine is effective and well tolerated in severely depressed patients and treatment response is associated with an increase in serum BDNF and a decrease in serum TNF-α levels.

Comparison of effectiveness of acupuncture therapy and conventional drug therapy on psychological profile of migraine patients.

Migraine is a painful condition in which patients suffer from recurrent episodes of disabling pain, which could be very severe and can lead to grave psychological disturbances. There is no curative treatment for migraine, but there are various treatment modalities, though, with conflicting reports on their efficacy. This study was conducted to compare the effectiveness of electro acupuncture therapy and the conventional drug therapy on the psychological profile of migraneurs based on the assessment of quality of life and disability parameters. Migraneurs (n = 60) were recruited from the Psychiatry and Neurology OPD, Guru Tegh Bahadur Hospital, Delhi. Following a written consent, migraneurs were randomly allocated into 2 study groups--Group A received 10 sittings of electro acupuncture on selected acupuncture points over a period of 30 days, while for the same duration the Group D received a conventional drug therapy in the form of oral flunarizine 20 mg OD along with paracetamol 500 mg SOS. The patients were assessed twice, before and after completion of the treatment programme (30 days). The quality of life was assessed with WHOQOL BREF (WHO Quality of Life Biomedical Research and Education Foundation) questionnaire and the disability was assessed with MIDAS (Migraine Disability Assessment) questionnaire. Statistical analysis was performed using repeated measure's ANOVA with Tukey's test. Migraneurs were found to have lower quality of life and higher disability scores but following the treatment regimes, the 2 study groups showed a significant improvement in both the parameters studied. It was however observed, that the acupuncture group showed a better response and was thus found to be more effective as compared to the drug group (P = 0.005 to 0.000). We thus conclude that acupuncture is a better treatment option than the conventional drug therapy in not only relieving the pain of migraine but in also improving the psychological profile in migraneurs. Hence its use should be encouraged as an alternative/adjunct treatment for migraine.

Assessment of quality of life during treatment of pediatric oncology patients.

BACKGROUND: The objective of this study was to assess health-related quality of life (HRQOL) of pediatric cancer patients and their parents in North India. MATERIALS AND METHODS: Seventy-five cancer children were assessed for HRQOL, using Lansky play performance scale and health utility index-2 (HUI-2). Fifty-seven patients were followed-up after 4 months after therapy and reassessed. Their parents were also assessed using World Health Organisation (WHO) QOL BREF. Seventy five controls were also assessed and compared. RESULTS: Lansky and HUI-2 scores of patients, as well as WHO QOL BREF of parents were significantly poor in cancer patients when compared to controls. There was significant improvement after therapy in patients with lymphomas and miscellaneous tumors. Pain and self-care were found to be maximally affected domains on HUI-2. CONCLUSIONS: Large prospective multicenter studies may be undertaken and hence that need based interventions can be planned.

Socio-demographic features and quality of life post burn injury.

Introduction: Burn injury is a highly devastating injury accounting for the major cause of disability-adjusted life years (DALYs) lost mostly in developing countries. Physical trauma, body disfigurement, the social stigma associated with injury completely shatter an individual's life. Aim: To study the quality of life among burn injury patients. Methodology: A cross-sectional hospital-based descriptive study was done on 150 burn injury patients. During the initial recruitment from Burns and Plastic Surgery Ward, socio-demographic profile and burn incident-related data were collected, whereas the WHO QoL-BREF tool was applied after 3 months of discharge during a follow-up visit in the outpatient department of Burns and Plastic Surgery to assess the quality of life among subjects. Data were compiled in MS Excel and statistical analysis was done using SPSS 20 version. Results: The study revealed poor quality of life among four domains of QoL; it was most inferior in the psychological domain followed by the physical health domain, environment domain, and social relationship domain. Conclusion: Advancement in the medical field has improved the survival rate in victims although the patients recover from the acute painful phase of physical trauma. However, the psychological and social impacts of injury remain unaddressed leading to a poor QoL. There is a need for an integrated approach for prevention and enhancement of the quality of care for the victims in all four domains of life. More emphasis is needed on rehabilitative care for long-term improvement in the QoL of the affected person.

Correlation of mortality with Pro-BNP and precipitating factors of acute heart failure in patients presenting to a medical emergency of tertiary care hospital: an observational study from north India.

OBJECTIVE: Acute heart failure is a syndrome defined as the new onset de novo heart failure or worsening [acutely decompensated heart failure (ADHF)] leading to symptoms and signs of HF, mostly related to systemic congestion as based on the European Society of Cardiology (ESC) definition. India has a huge burden of heart failure patients. Several factors have been identified as precipitating acute HF hospitalizations. These include myocardial ischemia, no adherence to medications, arrhythmias, infection, uncontrolled hypertension (HTN), anemia, renal impairment, and diet. However, there is a dearth of studies assessing their effect on mortality in patients admitted with acute heart failure. Many previous studies have shown that BNP and NT-pro-BNP are independent predictors of mortality and other cardiac outcomes in patients with heart failure (HF) and ADHF. However, no studies have provided any clear direction with respect to the critical cut-off values that suggest high mortality. Comprehensive knowledge of the correlation of Pro-BNP and precipitating factors of heart failure with mortality can help in prognostication and clinical management of AHF patients. PATIENTS AND METHODS: This was a prospective observational cross-sectional study conducted in the Emergency Department of the Postgraduate Institute of Medical Education and Research, Chandigarh which is a teaching and research hospital located in North India. Patients were enrolled from 1st August 2021 to 28th February 2022. Patients who met inclusion criteria were enrolled; they were followed for 5 days. After 5 days outcomes were recorded. Various precipitating factors for hospitalization were identified and their clinical impact on mortality was noted. Pro-BNP values were obtained at admission and their correlation with mortality and patient outcome after 5 days was noted. Values of Pro-BNP were compared among those who survived after 5 days vs. those who had fatal outcomes. RESULTS: The most common precipitating factor for AHF was poor medical compliance which did not affect mortality. It was followed by sepsis which significantly increases mortality in patients of AHF. ACS was also an important precipitating factor for AHF, though it had no effect on mortality. The mortality in the group of patients with very high Pro-BNP levels ≥ 2000 pg/ml was significantly higher than in the group of patients who had moderately elevated Pro-BNP < 2000 pg/ml. The median value of Pro-BNP was significantly higher in patients who had fatal outcomes [3670 (IQR- 2745 to 3980)] as compared to patients who survived after 5 days of hospitalization [1340 (IQR- 987 to 1670)]. CONCLUSIONS: Poor compliance with medications and sepsis are the most common precipitating factors for acute heart failure in north Indian patients. Sepsis as a precipitating factor is a significant risk factor for in-hospital mortality in acute heart failure patients presenting to the emergency department. Pro-BNP values above 2000 pg/ml in patients with acute heart failure requiring emergency admission are associated with a poor prognosis.

Study of neurocognitive endophenotypes in drug-naïve obsessive-compulsive disorder patients, their first-degree relatives and healthy controls.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a debilitating heritable neuropsychiatric condition. Attempts to delineate genetic contributions in OCD have met with limited success, with an ongoing search for neurocognitive endophenotypes. In this study, an attempt has been made to study and compare the neurocognitive functioning of patients with OCD, their first-degree relatives (FDRs) and healthy controls. METHOD: A cross-sectional design study was carried out with thirty dyads of patients with OCD, their FDRs and thirty matched healthy controls and screened using Mini International Neuropsychiatric Interview, Verbal Adult Intelligence Scale, Yale Brown Obsessive-Compulsive Scale, Montgomery Åsberg Depression Rating Scale, International Personality Disorder Examination (Anankastic personality scale).Tests of National Institute of Mental Health and Neurosciences Neuropsychological Battery were used to assess domains of attention, verbal memory, visual memory, set-shifting, response inhibition, planning and visuoconstructive abilities. spss version 14.0 was used for descriptive and analytical data analysis. RESULTS: There were no statistically significant differences between patients with OCD and their FDRs on neurocognitive domains of delayed verbal recall, set-shifting, response inhibition and visuoconstructive abilities (P > 0.05) which were impaired compared with healthy controls. Significant differences (P < 0.05) on domains of attention, planning time and visual memory were noted between FDRs and patients. CONCLUSION: The present study supports set-shifting and inhibitory control and proposes visuoconstructive abilities and delayed verbal recall as potential endophenotypes for OCD.

Bupropion monotherapy alters neurotrophic and inflammatory markers in patients of major depressive disorder.

BACKGROUND: Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) indicate the role of neurotrophic factors and inflammation. This study assessed the association between therapeutic response of bupropion and serum brain-derived neurotrophic factor (BDNF) and tumour necrosis factor-α (TNF-α) levels in patients with MDD. METHODS: Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM-5 criteria, with Hamilton Depression Rating scale (HAM-D) score ≥ 20 were included in the study. Patients were given bupropion sustained release (SR) in the doses of 150 mg once daily. All patients were followed up for 12 weeks. RESULTS: HAM-D score at the start of the treatment was 25.57 ± 1.85 which significantly reduced to 10.8 ± 4.24 at 12 weeks of treatment. The serum BDNF level increased significantly (p < 0.05) from 2.42 ± 0.19 ng/ml to 2.97 ± 0.10 ng/ml and the levels of serum TNF-α reduced significantly (p < 0.05) from 4.45 ± 0.95 pg/ml to 2.11 ± 0.84 pg/ml at 12 weeks of treatment, in responders to treatment. CONCLUSION: The results of our study suggest that bupropion SR monotherapy is effective and well tolerated in MDD patients with moderate to severe depression, and its therapeutic efficacy is accompanied by an increase in serum BDNF levels and a decrease in serum TNF-α levels.

Potential of NO donor furoxan as SARS-CoV-2 main protease (Mpro) inhibitors: in silico analysis.

The sharp spurt in positive cases of novel coronavirus-19 (SARS-CoV-2) worldwide has created a big threat to human. In view to expedite new drug leads for COVID-19, Main Proteases (Mpro) of novel Coronavirus (SARS-CoV-2) has emerged as a crucial target for this virus. Nitric oxide (NO) inhibits the replication cycle of SARS-CoV. Inhalation of nitric oxide is used in the treatment of severe acute respiratory syndrome. Herein, we evaluated the phenyl furoxan, a well-known exogenous NO donor to identify the possible potent inhibitors through in silico studies such as molecular docking as per target analysis for candidates bound to substrate binding pocket of SARS-COV-2 Mpro. Molecular dynamics (MD) simulations of most stable docked complexes (Mpro-22 and Mpro-26) helped to confirm the notable conformational stability of these docked complexes under dynamic state. Furthermore, Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations revealed energetic contributions of key residues of Mpro in binding with potent furoxan derivatives 22, 26. In the present study to validate the molecular docking, MD simulation and MM-PBSA results, crystal structure of Mpro bound to experimentally known inhibitor X77 was used as control and the obtained results are presented herein. We envisaged that spiro-isoquinolino-piperidine-furoxan moieties can be used as effective ligand for SARS-CoV-2 Mpro inhibition due to the presence of key isoquinolino-piperidine skeleton with additional NO effect.Communicated by Ramaswamy H. Sarma.

Relationship of possible stress-related biochemical markers to oxidative/antioxidative status in obsessive-compulsive disorder.

Free radicals have been found to play an important role in obsessive-compulsive disorder (OCD). So, we measured the oxidative/antioxidative status of OCD patients, and assessed its use as a biological marker. The study was carried out on 20 healthy and 20 OCD subjects, aged between 20 and 40 years. Biochemical parameters of all subjects were assessed and compared. A significant difference in superoxide dismutase (SOD) levels was observed between the OCD and control groups (p < 0.05); malondialdehyde (MDA) levels were also significantly higher in OCD subjects (p < 0.05). Our study found an overall oxidative imbalance in OCD, leaning towards the antioxidant side in sufferers (specifically towards SOD). SOD has a protective role in overcoming oxidative stress; therefore, oxidative stress could have a pathophysiological role in OCD. Therapy specifically targeting MDA production will have a beneficial effect in overcoming the oxidative stress, anxiety and affective disorder which may be associated with OCD.

Exploring the influence of steric, electronic and lipophilic descriptors of 1,3-diarly propenones on their anti-inflammatory activity.

BACKGROUND AND THE PURPOSE OF THE STUDY: Various compounds from natural and synthetic origins containing the 1,3-diarylpropenone structure have been reported to produce a variety of biological activities like anti-microbial, anti-inflammatory, vascular muscle relaxant, etc. A systematic analysis of the structural features responsible for anti-inflammatory activity and a possible mode of their actions were proposed to be evaluated by synthesizing a set of compounds, screening them for anti-inflammatory activity and developing a QSAR model. METHODS: Two types of 1,3-diarylpropenone derivatives were synthesized employing the Claisen-Schmidt condensation. These compounds were then screened for their in vivo anti- inflammatory activity by the carrageenin induced rat paw edema method and also for in vitro cyclooxygenase-2 (COX-2) inhibition activity using a colorimetric kit for COX (ovine) inhibitor screening assay. These derivatives and their anti-inflammatory activity data were employed for QSAR analysis on Vlife MDS 3.5 software. The molecules were divided into training and test sets based on observed activity and QSAR models were generated for the training set and validated. The activity of the molecules of the test set was predicted according to the QSAR equation fit. Possible correlation between observed anti-inflammatory activity and in vitro cyclooxygenase-2 inhibition was also studied. RESULTS AND CONCLUSION: Insignificant difference between the observed and predicted biological activity revealed that the selected electronic, steric and lipophilic parameters have a significant correlation (r(2)=0.85) with anti-inflammatory activity of the selected class of compounds. On the basis of results it may be suggested that the 1,3-diaryl-2-propen-1-ones framework is an attractive template for structural optimization to achieve better potency of anti-inflammatory activity. Similarly, the relatively low correlation between anti-inflammatory activity and cyclooxygenase-2 inhibition indicates that other modes of actions may also be responsible for the anti-inflammatory activity of the tested compounds.

Prevalence of stress among resident doctors working in Medical Colleges of Delhi.

The present cross-sectional study was conducted from November 2007 to December 2008 in four medical colleges and associated hospitals of Delhi. Study subjects comprised 930 resident doctors. The overall prevalence of stress was found to be 32.8% in resident doctors from all colleges. Out of 930 resident doctors, 165 (17.7%) had mild stress, 113 (12.2%) had moderate stress, and 27 (2.9%) were severely stressed. Important reasons of stress as perceived by the study subjects included long duty hours, departmental academic activities, financial constraints, family and emotional problems in the decreasing order of preference. Important factors significantly associated with stress-included existence of children, year of residency, type of department, and presence or absence of job satisfaction, having close friends, spending time with family/friends, and place of graduation. In the multivariate model, year of residency, giving time to family and or friends, having close friends during residency, job satisfaction, and state of graduation came out as predictors of stress.

Application quantum and physico chemical molecular descriptors utilizing principal components to study mode of anticoagulant activity of pyridyl chromen-2-one derivatives.

Factors II, V, VII and Xa have materialized as a key enzymes for the intervention of blood coagulation cascade and for the development of new anti thrombotic agents. The combined density functional quantum mechanical/molecular mechanical (QM/MM) approach has been used to access inhibition of prothrombin and thrombin production. The biological activities of coumarin derivatives as clotting factor inhibitors was quantitatively analyzed in terms of physicochemical parameters utilizing the principal component analysis. Structural requirements for maximal potency were derived from the results of a quantitative structure activity relationship analysis.