Culturally adapted psychosocial interventions (CaPSI) for early psychosis in a low-resource setting: study protocol for a large multi-center RCT.

BACKGROUND: Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan. METHOD: A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety). CONCLUSIONS: A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP. TRIAL REGISTRATION: NCT05814913.

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.

Extreme creep resistance in a microstructurally stable nanocrystalline alloy.

Nanocrystalline metals, with a mean grain size of less than 100 nanometres, have greater room-temperature strength than their coarse-grained equivalents, in part owing to a large reduction in grain size. However, this high strength generally comes with substantial losses in other mechanical properties, such as creep resistance, which limits their practical utility; for example, creep rates in nanocrystalline copper are about four orders of magnitude higher than those in typical coarse-grained copper. The degradation of creep resistance in nanocrystalline materials is in part due to an increase in the volume fraction of grain boundaries, which lack long-range crystalline order and lead to processes such as diffusional creep, sliding and rotation. Here we show that nanocrystalline copper-tantalum alloys possess an unprecedented combination of properties: high strength combined with extremely high-temperature creep resistance, while maintaining mechanical and thermal stability. Precursory work on this family of immiscible alloys has previously highlighted their thermo-mechanical stability and strength, which has motivated their study under more extreme conditions, such as creep. We find a steady-state creep rate of less than 10(-6) per second-six to eight orders of magnitude lower than most nanocrystalline metals-at various temperatures between 0.5 and 0.64 times the melting temperature of the matrix (1,356 kelvin) under an applied stress ranging from 0.85 per cent to 1.2 per cent of the shear modulus. The unusual combination of properties in our nanocrystalline alloy is achieved via a processing route that creates distinct nanoclusters of atoms that pin grain boundaries within the alloy. This pinning improves the kinetic stability of the grains by increasing the energy barrier for grain-boundary sliding and rotation and by inhibiting grain coarsening, under extremely long-term creep conditions. Our processing approach should enable the development of microstructurally stable structural alloys with high strength and creep resistance for various high-temperature applications, including in the aerospace, naval, civilian infrastructure and energy sectors.

Pro-poor policies and improvements in maternal health outcomes in India.

BACKGROUND: Since 2005, India has experienced an impressive 77% reduction in maternal mortality compared to the global average of 43%. What explains this impressive performance in terms of reduction in maternal mortality and improvement in maternal health outcomes? This paper evaluates the effect of household wealth status on maternal mortality in India, and also separates out the performance of the Empowered Action Group (EAG) states and the Southern states of India. The results are discussed in the light of various pro-poor programmes and policies designed to reduce maternal mortality and the existing supply side gaps in the healthcare system of India. Using multiple sources of data, this study aims to understand the trends in maternal mortality (1997-2017) between EAG and non EAG states in India and explore various household, economic and policy factors that may explain reduction in maternal mortality and improvement in maternal health outcomes in India. METHODS: This study triangulates data from different rounds of Sample Registration Systems to assess the trend in maternal mortality in India. It further analysed the National Family Health Surveys (NFHS). NFHS-4, 2015-16 has gathered information on maternal mortality and pregnancy-related deaths from 601,509 households. Using logistic regression, we estimate the association of various socio-economic variables on maternal deaths in the various states of India. RESULTS: On an average, wealth status of the households did not have a statistically significant association with maternal mortality in India. However, our disaggregate analysis reveals, the gains in terms of maternal mortality have been unevenly distributed. Although the rich-poor gap in maternal mortality has reduced in EAG states such as Bihar, Odisha, Assam, Rajasthan, the maternal mortality has remained above the national average for many of these states. The EAG states also experience supply side shortfalls in terms of availability of PHC and PHC doctors; and availability of specialist doctors. CONCLUSIONS: The novel contribution of the present paper is that the association of household wealth status and place of residence with maternal mortality is statistically not significant implying financial barriers to access maternal health services have been minimised. This result, and India's impressive performance with respect to maternal health outcomes, can be attributed to the various pro-poor policies and cash incentive schemes successfully launched in recent years. Community-level involvement with pivotal role played by community health workers has been one of the major reasons for the success of many ongoing policies. Policy makers need to prioritise the underperforming states and socio-economic groups within the states by addressing both demand-side and supply-side measures simultaneously mediated by contextual factors.

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.

Lunate dislocation causing median nerve entrapment.

Lunate dislocation is an uncommon injury occurring in young adults due to high-energy trauma. The volar displacement of the bone may result in compression of the median nerve within the carpal tunnel and is an uncommon cause of entrapment neuropathy.

Cystathionine-gamma-lyase gene silencing with siRNA in monocytes/macrophages protects mice against acute pancreatitis.

Hydrogen sulphide (H2S) is an endogenous inflammatory mediator produced by cystathionine-γ-lyase (CSE) in monocytes/macrophages. To determine the role of H2S and macrophages in inflammation, we used small interference RNA (siRNA) to target the CSE gene and investigated its effect in a mouse model of acute pancreatitis. Acute pancreatitis is characterised by increased levels of plasma amylase, myeloperoxidase (MPO) activity and pro-inflammatory cytokines and chemokines in the pancreas and lung. SiRNA treatment attenuated inflammation in the pancreas and lungs of mice following caerulein-induced acute pancreatitis. MPO activity increased in caerulein-induced acute pancreatitis (16.21 ± 3.571 SD fold increase over control) and treatment with siRNA significantly reduced this (mean 3.555 ± 2.522 SD fold increase over control) (p < 0.0001). Similarly, lung MPO activity increased following treatment with caerulein (3.56 ± 0.941 SD fold increase over control) while siRNA treatment significantly reduced MPO activity (0.8243 ± 0.4353 SD fold increase over control) (p < 0.0001). Caerulein treatment increased plasma amylase activity (7094 ± 207 U/l) and this significantly decreased following siRNA administration (5895 ± 115 U/l) (p < 0.0001). Cytokine and chemokine levels in caerulein-induced acute pancreatitis reduced following treatment with siRNA. For example, siRNA treatment significantly decreased pancreatic and lung monocyte chemoattractant protein (MCP)-1 (169.8 ± 59.75 SD; 90.01 ± 46.97 SD pg/ml, respectively) compared to caerulein-treated mice (324.7 ± 103.9 SD; 222.8 ± 85.37 SD pg/ml, pancreas and lun,g respectively) (p < 0.0001). These findings show a crucial pro-inflammatory role for H2S synthesised by CSE in macrophages in acute pancreatitis and suggest CSE gene silencing with siRNA as a potential therapeutic approach for this condition.

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.

First metatarsophalangeal joint arthrodesis - Do joint configuration and preparation technique matter?

BACKGROUND: The purpose of this study was to investigate the influence of joint configuration and preparation on first metatarsophalangeal (MTPJ) union rates. METHODS: We performed a retrospective analysis of first MTPJ arthrodeses undertaken in our institution. Clinical notes, radiographs and postal questionnaires were used to determine outcome. RESULTS: Two hundred first MTPJ arthrodeses (172 patients) were included in the analysis (34 male: 138 female; mean age 62 yr). The overall union rate was 93.5%. Union was achieved in 109/118 MTPJs (92.4%) prepared in the flat-on-flat configuration and in 78/82 (95%) prepared in the ball-and-socket configuration (p=0.438). Higher union rates favoured low-velocity joint preparation [using rongeur only 21/21 (100%), rongeur and burr 26/27 (96.3%) and conical reamer 31/34 (91.2%)] but this did not reach statistical significance (p=0.317). There was a 95% satisfaction rate with surgery but male patients were less satisfied (p=0.031). CONCLUSION: Union rates were not influenced by joint configuration or preparation techniques.

Septo-optic dysplasia: Magnetic Resonance Imaging findings.

Septo-optic dysplasia is a rare congenital disorder involving brain and optic pathways. We present typical Magnetic Resonance Imaging (MRI) findings of a case of Septo-optic dysplasia in a 19 year old female patient.

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.

Rumour detection using deep learning and filter-wrapper feature selection in benchmark twitter dataset.

Microblogs have become a customary news media source in recent times. But as synthetic text or 'readfakes' scale up the online disinformation operation, unsubstantiated pieces of information on social media platforms can cause significant havoc by misleading people. It is essential to develop models that can detect rumours and curtail its cascading effect and virality. Undeniably, quick rumour detection during the initial propagation phase is desirable for subsequent veracity and stance assessment. Linguistic features are easily available and act as important attributes during the initial propagation phase. At the same time, the choice of features is crucial for both interpretability and performance of the classifier. Motivated by the need to build a model for automatic rumour detection, this research proffers a hybrid model for rumour classification using deep learning (Convolution neural network) and a filter-wrapper (Information gain-Ant colony) optimized Naive Bayes classifier, trained and tested on the PHEME rumour dataset. The textual features are learnt using the CNN which are combined with the optimized feature vector generated using the filter-wrapper technique, IG-ACO. The resultant optimized vector is then used to train the Naïve Bayes classifier for rumour classification at the output layer of CNN. The proposed classifier shows improved performance to the existing works.