Association of Attention Deficit Hyperactivity Disorder with the Use of Oral Propranolol in Infantile Haemangiomas: An Ambispective Comparative Study.

Previous studies have raised concerns about the effects of oral propranolol on the central nervous system in infants, the exact measure and mechanism and the long-term follow-up of which is less well studied. This was an ambispective comparative study of children with infantile haemangioma (IH) followed by a repeat visit 4-10 years after completion of propranolol therapy. Parents were asked about psychologic functioning along with an initial screening examination. All patients were evaluated by a paediatric psychiatrist. After evaluation by the Strength and Difficulties Questionnaire, and subsequently by the paediatric psychiatrist, 2 of 12 patients (16.67%) showed features of attention deficit hyperactivity disorder in comparison to 0 of 40 subjects in the control group (0.0498; α = 0.05). These results indicate an increased risk of neuropsychiatric illnesses such as attention deficit hyperactivity disorder (ADHD) in patients given propranolol for IH, as supporting evidence to previous claims.

Role of Acamprosate and Baclofen as Anti-craving Agents in Alcohol Use Disorder: A 12-Week Prospective Study.

Background Alcohol use disorder (AUD) is one of the most common substance use disorders globally. It is a chronic mental illness characterized by frequent relapses. Hence, preventing relapse is one of the most important aspects of the management of patients with AUD. Aims This study aimed to compare the role of acamprosate and baclofen as anti-craving agents in patients diagnosed with AUD. Settings and design This was a 12-week interventional follow-up study conducted in the Department of Psychiatry of S N Medical College, a tertiary care teaching hospital in Agra, Uttar Pradesh, India. Methods and materials Patients with AUD were enrolled in the study. Following medical management of alcohol withdrawal symptoms, patients were alternately assigned to receive either acamprosate or baclofen and were then followed up for 12 weeks. Measures to compare the effectiveness of the two medications were craving as measured using the Penn Alcohol Craving Scale (PACS), days to first alcohol consumption, days to relapse, number of drinks consumed at one occasion, number of patients who completed the study, and number of patients who remained abstinent throughout the duration of the study. Descriptive statistics were used to present the data while unpaired t-test and Fisher's exact test were used to compare the two groups.  Results A total of 63 patients were enrolled in the study. Following medical management of alcohol withdrawal symptoms for one week, 50 (79.37%) patients were retained in the study. Hence, these 50 patients were assigned to treatment with either acamprosate or baclofen alternately in a 1:1 ratio. Only 32 (64%) of the patients who were started on these medications completed the study and were available for analysis at the end of 12 weeks. Acamprosate-treated patients were found to have less severe cravings (p < 0.01) for alcohol at the end of the study and also had consumed less number of drinks on a single occasion (p < 0.05). For other variables being considered in the study, namely, days to first alcohol consumption, days to relapse to previous drinking pattern, number of patients who dropped from the study versus those who completed the study, and those who were abstinent versus those who relapsed, no statistically significant difference was noted. Conclusion Acamprosate-treated patients had significantly lesser cravings for alcohol and consumed a lesser number of drinks on one occasion compared to baclofen-treated patients in this 12-week study.

A Comparative Analysis of the Efficacy and Safety of Nimesulide/Paracetamol Fixed-Dose Combination With Other NSAIDs in Acute Pain Management: A Randomized, Prospective, Multicenter, Active-Controlled Study (the SAFE-2 Study).

Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac (10 mg) [Kt] alone, diclofenac (50 mg) + paracetamol (325 mg) [DP], and aceclofenac (100 mg) + paracetamol (325 mg) [AP] in patients with acute painful conditions. Methods This was a randomized, prospective, open-label, multicentre, active-controlled study involving patients aged ≥18 years, with acute painful conditions like low back pain, acute musculoskeletal disorders, and trauma such as tendinitis, tenosynovitis, bursitis, sprains and strains, migraine, dental pain, painful dental procedures, and post-surgical pain. Reduction in pain intensity and liver, renal, gastrointestinal, and cardiovascular safety were assessed on days seven and 14. Results A total of 600 patients were randomized into NP, Kt, DP, and AP groups in a 1:1:1:1 ratio. NP, DP, and AP were administered twice a day while Kt was given three times a day. The reduction of pain as measured by the numerical rating scale (NRS) scores at the end of day seven was 3.75 ± 1.58 in the NP group, 2.96 ± 1.18 in the Kt group, 3.42 ± 1.42 in the DP group, and 3.47 ± 1.30 in the AP group. The pain reduction in the NP group was significantly greater (p<0.001) as compared to the Kt group and non-inferior to the DP and AP groups on days seven and 14. Non-inferiority was concluded between the NP, DP, and AP groups as the lower limit of 95% CI of the difference in the change of pain intensity on both days seven and 14 was above the predefined margin of -1.0. All the drugs were well tolerated, but a significantly greater number of adverse events were reported in the DP group (32) as compared to the NP group (14) (p<0.05). The most common adverse events reported during the study were nausea, gastritis, and abdominal pain in all four groups. There was no significant alteration in liver and renal function tests except a rise in serum creatinine in the DP group. Conclusions The FDC of nimesulide with paracetamol is superior to ketorolac and non-inferior to the FDC of diclofenac with paracetamol and aceclofenac with paracetamol in the management of pain in patients with acute painful conditions. The tolerability profile of the FDC of nimesulide with paracetamol is similar to that of ketorolac but better than diclofenac with paracetamol and aceclofenac with paracetamol combinations.

Prevalence and clinicopathological features of driver gene mutations profile in BCR: ABL1 negative classical myeloproliferative neoplasm-A single-center study from North India.

BACKGROUND: Recurrent somatic mutations in the JAK2, CALR, and the MPL genes are noted in BCR: ABL1 negative classic myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). MATERIALS AND METHODS: Mutation profile and clinical features of MPN cases diagnosed at a tertiary care center in North India are being described. JAK2V617F mutation was screened using ARMS PCR, and CALR mutation was screened using allele-specific PCR followed by fragment analysis. MPL and JAK2 Exon 12 mutations were screened by Sanger sequencing. Some of the samples were also screened using commercial kits based on single-plex RT PCR. RESULTS: A total of 378 cases (including 124 PV, 121 ET, and 133 PMF cases) were screened over 6.5 years. JAK2V617F mutation was noted in 90.3%, 61.1%, and 69.2% of cases of PV, ET, and PMF, respectively. In PV, JAK2V617F wild-type cases were associated with a significantly lower age (44 yrs vs 54 yrs; P = 0.001), lower TLC (6.3 vs 16.9; P = 0.001), and a lower platelet count (188 × 109/L vs 435 × 109/L; P = 0.009) as compared to the JAK2V617F mutated cases. CALR and MPL mutations were noted in 17.4% and 12% and 0.8% and 5.3% of ET and PMF cases, respectively. Type 1 CALR mutations were commoner in both ET and PMF. The triple negative cases constituted 20.7% and 13.5% cases of ET and PMF, respectively. In ET, the triple negative cases were found to have a significantly lower median age of presentation (42 yrs vs 52 yrs; P = 0.001), lower median TLC (10.2 × 109/L vs 13.2 × 109/L; P = 0.024), and a higher median platelet count (1238 × 109/L vs 906 × 109/L; P = 0.001) as compared to driver genes mutated cases. In PMF, the triple negative cases were found to have a significantly lower hemoglobin level (7.9 g/dl vs 11.0 gl/dl; P = 0.001) and a significant female preponderance (P = 0.05) as compared to the mutated cases. CALR mutations were found to have a significantly lower median age (43 yrs vs 56 yrs; P = 0.001) and lower hemoglobin (9.6 g/dl vs 11.3 g/dl) as compared to the JAK2 mutations. CONCLUSION: Our data on the driver gene mutational profile of BCR: ABL1 negative MPN is one of the largest patient cohorts. The prevalence and clinicopathological features corroborate with that of other Asian studies.

Defeating the Silent Enemy: Antimicrobial Resistance Looming as the Next Global Pandemic.

Antibiotics are the magic bullets that have saved millions worldwide. Enormous and irresponsible use of antibiotics has led to resistance to antibiotics, which is a matter of global health concern. The superbugs are responsible for life-threatening infections, treatment failure, and high mortality worldwide. The urgent healthcare threat caused by antimicrobial resistance (AMR) to nonfermenting gram-negative bacteria is being increasingly acknowledged worldwide. Antibiotic resistance found in organisms in hospital settings is now increasingly found in the community. Although antimicrobial stewardship requiring a multidisciplinary approach is developing rapidly at the hospital level, it needs more attention at the community level. New therapeutics are certainly required, but the major challenge is rapidly identifying resistant infections and tailoring treatment. This review highlights the crisis that reflects the current scenario of AMR, common resistant pathogens, and the major challenges in the fight against AMR. It also discusses potential methods and strategies to address the intricacies of antibiotic resistance.

Rootstock scion interaction studies on various horticultural attributes of pomato grafts under protected structures.

Pomato is a horticultural wonder plant, as tomato and potato can be produced from a single plant. This experiment explored the influence of diverse graft combinations of tomato scions grafted onto potato rootstocks on various growth and yield-attributing traits. The investigation outcomes confirmed the significantly positive influence of scion grafted onto rootstock on various yielding attributes of tomato and potato harvested from pomato grafts. Scion "Rakshita" grafted onto the rootstock of Kufri Himalini had the maximum fruit length. In contrast, the fruits harvested from the graft combination of Avtar grafted onto Kufri Khyati had the maximum number of fruits per cluster and the number of fruits per plant. The highest average fruit weight, fruit yield per meter square, and total fruit yield quintal per hectare were recorded with control "Avtar. The longest harvest duration was noticed with the graft combination of Heemsohna grafted onto Kufri Himalini. Moreover, on, rootstock Kufri Himalini with scion Rakshita resulted in maximum tuber length, and average tuber weight, while Kufri Himalini with Avtar had maximum fruit width. The maximum number of tubers per plant was also noticed with Kufri Pukhraj with Palam Tomato hybrid -1. The potato harvested from the rootstock of Kufri Pukhraj with Avtar had the highest tuber yield per plant, total tuber yield quintal per hectare, and tuber equivalent yield. The highest survival percentage of grafted plants was noted in Heemsohna onto Kufri Jyoti. In context to the cumulative yield of tomato fruits and potato tubers obtained from the pomato graft was found to be incremented in grafts of Avtar grafted onto Kufri Pukhraj followed by Rakshita grafted onto Kufri Rakshita, which also resulted in the maximum benefit-cost ratio with highest net return and gross return. The graft combination of scion Avtar and Rakshita onto Rootstock Kufri Pukhraj resulted in a positive increment in yield attributing traits of the pomato plant than of control of un-grafted tomato and potato.

To Study the Distress, Anxiety, Depression, and Sleep Effects of the COVID-19 Pandemic on Essential Workers.

Essential care workers like police personnel, social workers, and office and administrative staff of health institutions are also at increased risk of coronavirus disease 2019 (COVID-19) exposure along with healthcare workers. The present study aims to estimate the distress, anxiety, depression, and sleep impact of COVID-19 pandemic on essential workers through an online survey. This cross-sectional study (included 369 participants) was conducted in Chandigarh through an online survey using three psychological scales: Peritraumatic Distress Inventory (PDI), Insomnia Severity Index, and Depression Anxiety Stress Scale. Three-hundred-sixty-nine frontline warriors from hospital and community settings were included in the study. The respondents include police personnel (274; 73.66%), office staff (24; 6.45%), social workers (53; 14.24%), and media staff (21; 5.65%). Maximum distress was reported by media/transport officials on duty (85.7%). The majority of them scored high (>14), and slightly less than one-fourth (23.8%) scored significantly abnormal (>23) on PDI. About 42.9% reported moderate insomnia, 52.4% exhibited severe anxiety, and 33.3% of media/transport participants reported severe depression. Psychological morbidity is high in media/transport and social workers working in the community during the COVID-19 pandemic.

Pain perception in 4-6-year-old children following intraoral dental injection with 26 and 31-gauge needles: a randomized controlled trial.

Background: Administering anesthesia in dentistry can be distressing for patients, especially those with dental fear and anxiety. Needle pain during local anesthesia is a common concern in intraoral procedures. This study aimed to compare pain perception in 4-6-year-old children following intraoral dental injections with 26- and 31-gauge needles. Methods: Fifty healthy children were divided according to age into Group I (N = 25; 4-5 years) and Group II (N = 25; 5-6 years). Each group was further subdivided according to the needle gauge as follows: Group IA (26 gauge), Group IB (31 gauge), Group IIA (26 gauge), and Group IIB (31 gauge). Using a lottery method, the gauge of the needle to be used at the first visit for local anesthesia administration was selected. Children's reactions to pain were evaluated using a Modified Behavioral Pain Scale. Immediately after administration of local anesthesia, pain perception was evaluated using the Faces pain rating scale. In the subsequent visit, another needle gauge was used to administer local anesthesia, and the previously described evaluations were performed. At the third appointment, the child was shown both syringes and asked to choose one of the syringes they preferred, and the choice was noted. Results: When local anesthesia was administered using a 31-gauge needle, pain perception was similar between the two groups. In group II, the children demonstrated significantly higher arm and leg movements (P = 0.001). However, the difference was significant in group I alone (P < 0.001). Conclusion: Irrespective of age, anesthesia with a 31-gauge needle resulted in significantly lower pain perception than anesthesia with a 26-gauge needle.

A Study of Hypertension and Related Biophysical and Health-related Lifestyle Behaviors in Patients Suffering from Schizophrenia.

Background: Schizophrenia is a life-shortening disease. The standardized mortality ratio has been higher than that of the general population, and it has doubled what it was 3-4 decades ago. This rise is mostly attributed to the increased cardiovascular risk associated with high second-generation antipsychotic (SGA) use. Evidence from the first-generation antipsychotic (FGA) era shows a lower prevalence of hypertension (HTN) but data regarding SGAs is scarce. Purpose: The purpose of the study was to assess the prevalence of HTN and related factors using standardized methodology in patients with schizophrenia on treatment with SGAs. Methods: A cross-sectional study through convenient sampling was done. Blood pressure, anthropometry, physical activity, and health-related lifestyle factors were assessed using the standard World Health Organization (WHO) methodology of cardiovascular survey methods and the Global Physical Activity Questionnaire (GPAQ) version 2. The prevalence of HTN, obesity, inadequate physical activity, and other demographic and clinical correlates like antipsychotic use, duration of illness, and family history of non-communicable diseases (NCDs) were studied. Results: The prevalence of HTN is 20.50%, and it increases with age. SGAs with the use of a single agent are the most common. In total, 45.50% of persons with schizophrenia have a positive family history of a NCD; 22.00% and 07.50% are current tobacco and alcohol users, respectively; and 70% have abdominal obesity, and 54% have generalized obesity. Waist circumference, obesity, and family history of NCDs are significant correlates of HTN. A family history of NCDs is the most significant predictor. Conclusion: The prevalence of HTN is lower than that of the general population despite the high prevalence of SGA use, obesity, and inadequate physical activity.

SADXAI: Predicting social anxiety disorder using multiple interpretable artificial intelligence techniques.

Social anxiety disorder (SAD), also known as social phobia, is a psychological condition in which a person has a persistent and overwhelming fear of being negatively judged or observed by other individuals. This fear can affect them at work, in relationships and other social activities. The intricate combination of several environmental and biological factors is the reason for the onset of this mental condition. SAD is diagnosed using a test called the "Diagnostic and Statistical Manual of Mental Health Disorders (DSM-5), which is based on several physical, emotional and demographic symptoms. Artificial Intelligence has been a boon for medicine and is regularly used to diagnose various health conditions and diseases. Hence, this study used demographic, emotional, and physical symptoms and multiple machine learning (ML) techniques to diagnose SAD. A thorough descriptive and statistical analysis has been conducted before using the classifiers. Among all the models, the AdaBoost and logistic regression obtained the highest accuracy of 88 % each. Four eXplainable artificial techniques (XAI) techniques are utilized to make the predictions interpretable, transparent and understandable. According to XAI, the "Liebowitz Social Anxiety Scale questionnaire" and "The fear of speaking in public" are the most critical attributes in the diagnosis of SAD. This clinical decision support system framework could be utilized in various suitable locations such as schools, hospitals and workplaces to identify SAD in people.

Role of miRNAs in T-cell activation and Th17/Treg-cell imbalance in acquired aplastic anemia.

BACKGROUND: Altered T-cell repertoire with an aberrant T-cell activation and imbalance of the Th17/Treg cells has been reported in acquired aplastic anemia (aAA). miRNAs are well known to orchestrate T-cell activation and differentiation, however, their role in aAA is poorly characterized. The study aimed at identifying the profile of miRNAs likely to be involved in T-cell activation and the Th17/Treg-cell imbalance in aAA, to explore newer therapeutic targets. METHODS: Five milliliters peripheral blood samples from 30 patients of aAA and 15 healthy controls were subjected to flow cytometry for evaluating Th17- and Treg-cell subsets. The differential expression of 7 selected miRNAs viz; hsa-miR-126-3p, miR-146b-5p, miR-155-5p, miR-16, miR-17, miR-326, and miR-181c was evaluated in the PB-MNCs. Expression analysis of the miRNAs was performed using qRT-PCR and fold change was calculated by 2-ΔΔCt method. The alterations in the target genes of deregulated miRNAs were assessed by qRT-PCR. The targets studied included various transcription factors, cytokines, and downstream proteins. RESULTS: The absolute CD3+ lymphocytes were significantly elevated in the PB of aAA patients when compared with healthy controls (p < 0.0035), however, the CD4:CD8 ratio was unperturbed. Th17: Treg-cell ratio was altered in aAA patients (9.1 vs. 3.7%, p value <0.05), which correlated positively with disease severity and the PNH positive aAA. Across all severities of aAA, altered expression of the 07 miRNAs was noted in comparison to controls; upregulation of miR-155 (FC-2.174, p-value-0.0001), miR-146 (FC-2.006, p-value-0.0001), and miR-17 (FC-3.1, p-value-0.0001), and downregulation of miR-126 (FC-0.329, p-value-0.0001), miR-181c (FC-0.317, p-value-0.0001), miR-16 (FC-0.348, p-value-0.0001), and miR-326 (FC-0.334, p-value-0.0001). Target study for these miRNAs revealed an increased expression of transcription factors responsible for Th1 and Th17 differentiation (T-bet, RORϒt, IL-17, IL-6, and IFN-ϒ), T-cell activation (NFκB, MYC, and PIK3R2), downregulation of FOX-P3, and other regulatory downstream molecules like SHIP-1, ETS-1, IRAK-1, TRAF-6, and PTEN. CONCLUSION: The study for the first time highlights the plausible role of different miRNAs in deregulating the Th17/Treg-cell imbalance in aAA, and comprehensively suggest the role of altered NF-kB and mTOR pathways in aAA. The axis may be actively explored for development of newer therapeutic targets in aAA.

Long-Term Use of Proton-Pump Inhibitors: Unravelling the Safety Puzzle.

Globally, over 25% of the population suffers from acid-related disorders such as dyspepsia or gastroesophageal reflux disease (GERD), and around 7.6% of Indians report having GERD symptoms on a frequent enough basis to warrant a diagnosis. Over the past three decades, proton-pump inhibitors (PPIs) have been the mainstay of medical therapy for acid-peptic diseases like GERD, etc. Additionally, they are frequently prescribed for prophylactic purposes and in conjunction with non-steroidal anti-inflammatory drugs. PPIs are generally prescribed for four to eight weeks. However, it may be prescribed for patients with comorbidities and multiple medications for a longer period of time. While this remains true in terms of effectiveness, concerns have been raised about the safety of long-term PPI use and the serious adverse effects that may result. Some of the observational and population-based cohort studies have shown an association between long-term use of PPIs and an increased risk of pneumonia, major cardiovascular events, dementia, vitamin B12 deficiency, bone fractures, gastric cancer, and kidney injury, among others. This review analyzes the clinical data supporting the long-term use of PPIs and takes a deep dive into whether these several emerging long-term concerns apply to the currently available PPIs in India. We have summarized a vast array of studies, including randomized trials, cohort studies, and meta-analyses, that report low or high incidences of major health risks linked with PPIs and have assessed their appropriateness over a given period.

Modified DeeplabV3+ with multi-level context attention mechanism for colonoscopy polyp segmentation.

The development of automated methods for analyzing medical images of colon cancer is one of the main research fields. A colonoscopy is a medical treatment that enables a doctor to look for any abnormalities like polyps, cancer, or inflammatory tissue inside the colon and rectum. It falls under the category of gastrointestinal illnesses, and it claims the lives of almost two million people worldwide. Video endoscopy is an advanced medical imaging approach to diagnose gastrointestinal disorders such as inflammatory bowel, ulcerative colitis, esophagitis, and polyps. Medical video endoscopy generates several images, which must be reviewed by specialists. The difficulty of manual diagnosis has sparked research towards computer-aided techniques that can quickly and reliably diagnose all generated images. The proposed methodology establishes a framework for diagnosing coloscopy diseases. Endoscopists can lower the risk of polyps turning into cancer during colonoscopies by using more accurate computer-assisted polyp detection and segmentation. With the aim of creating a model that can automatically distinguish polyps from images, we presented a modified DeeplabV3+ model in this study to carry out segmentation tasks successfully and efficiently. The framework's encoder uses a pre-trained dilated convolutional residual network for optimal feature map resolution. The robustness of the modified model is tested against state-of-the-art segmentation approaches. In this work, we employed two publicly available datasets, CVC-Clinic DB and Kvasir-SEG, and obtained Dice similarity coefficients of 0.97 and 0.95, respectively. The results show that the improved DeeplabV3+ model improves segmentation efficiency and effectiveness in both software and hardware with only minor changes.

Effectiveness of CBT for reducing depression and anxiety in people with epilepsy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients with epilepsy suffer from depression and anxiety that reduces quality of life. Cognitive behavioral therapy (CBT) among various non pharmacological treatment recommended for depression and anxiety. Since there are several articles reporting CBT treatment for depression in patients with epilepsy, we conduct a meta-analysis to evaluate the effectiveness of CBT for adult patients with epilepsy. METHODS: Four electronic databases PubMed, Scopus, Embase, and the Cochrane library searched for relevant studies. A detailed "RISK of bias" assessment has been done for included studies. Funnel plot was used for assessing publication Bias. R Software- RStudio 2022 was used to calculate standard mean difference (SMD). The study has been registered in PROSPERO (CRD42023447655). RESULTS: Eventually, a Total 13 studies involving 1222 patients met the eligibility criteria. There was decline in the Patient Health Questionnaire (PHQ) [SMD = -0.42, 95 % CI = -0.63 to -0.22], Neurologic Disorder Depression Inventory-Epilepsy (NDDI-E) [SMD = -0.53, 95 % CI = -0.75 to -0.31], Beck depression Inventory (BDI) [SMD = -0.69, 95 % CI = -1.08 to -0.30], Hospital Anxiety and Depression Scale-Depression (HADS-D) [SMD = -0.73 , 95 % CI = -0.94 to -0.52] and Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A) [SMD = -0.66, 95 % CI = -0.87 to -0.45] score of the CBT group than that of the control group at post-intervention. The results showed that the improvement in QOLIE-31 score of the CBT group than that of the control group [SMD = 0.67, 95 % CI = 1.33] at post-intervention. CONCLUSION: The result of our study showed that Cognitive behavioral therapy is a superior therapy for treating anxiety and depression in epilepsy patients. CBT was effective in improving Quality of life in patients with epilepsy. However, the sample size varied across the trials, additional high-quality studies are needed in the future.

Ion mobility mass spectrometry uncovers regioselectivity in the carboxylate-assisted C-H activation of palladium N-heterocyclic carbene complexes.

Carboxylate-assisted Pd-catalyzed C-H bond activation constitutes a mild and versatile synthetic tool to efficiently and selectively cleave inert C-H bonds. Herein, we demonstrate a simple method to experimentally evaluate both reactivity and selectivity in such systems using mass spectrometry (MS) methods. The N-heterocyclic carbene (NHC) cations [(NHC)PdX]+, bearing as X- ligand bases commonly used to promote the C-H activation (carboxylates and bicarbonate), are generated in the gas-phase by ESI-MS. Their C-H bond activation at the N-bound groups of the NHC is then studied using Collision Induced Dissociation (CID) experiments. Ion Mobility Spectrometry (IM)-MS is exploited to identify a number of regioisomers associated with the distinctive site selective C-H activations. It is demonstrated that such C-H activation concomitant with acetic acid release occurs from a mixture of activated [(NHC-H)Pd(CH3CO2H)]+ and non-activated [(NHC)Pd(CH3CO2)]+ complexes. The identity of the X-type ligands (X = Cl-, carboxylates and bicarbonate) has a significant impact on the regioisomer branching ratio upon CID conditions. IM-MS in conjunction with a DFT mechanistic study is presented for the acetate-assisted C-H activation of the [(NHC)Pd(CH3CO2)]+ cation featuring butyl and aryl as N-donor groups.

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.

A Randomized, Double-Blind, Parallel-Group Phase III Trial Investigating the Glycemic Efficacy and Safety Profile of Fixed-Dose Combination Dapagliflozin and Linagliptin Over Linagliptin Monotherapy in Patients with Inadequately Controlled Type 2 Diabetes with Metformin.

INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of dapagliflozin (10 mg) and linagliptin (5 mg) in comparison to linagliptin 5 mg (Trajenta) in patients with insufficiently controlled type 2 diabetes mellitus (T2DM) on metformin monotherapy. METHODS: The double-blind, randomized, multicentric, parallel-group phase III trial screened 287 adult patients with T2DM (age 18-65 years) from 16 sites across India. The recruited subjects were undergoing metformin monotherapy ≥ 1000 mg/day for at least 28 days. Patients with HbA1c of 7.5-10.5% (58-91 mmol/l) (n = 232) after 2 weeks of run-in period with linagliptin monotherapy and placebo dapagliflozin/linagliptin on metformin monotherapy were randomized (1:1) in parallel to once daily dapagliflozin/linagliptin 10/5 mg or linagliptin 5 mg for 16 weeks. Patients were stratified on the basis of HbA1c (≤ 9.0% and > 9.0%; ≤ 75 mmol/l and > 75 mmol/l)). A total of 225 subjects completed 16 weeks of treatment, 115 patients in the test group and 110 patients in the reference group. RESULTS: Dapagliflozin/linagliptin (p = 0.0003) exhibited a greater change in HbA1c from baseline than linagliptin (p < 0.0001) in 16 weeks (mean reduction, - 1.28% vs - 0.83%). Test group showed a significant decrease in fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body weight compared to the reference group. The FDC was well tolerated with adverse events being more frequent in the reference group. No serious adverse events (SAEs) were reported in the study. CONCLUSION: Dapagliflozin/linagliptin combination is a novel dipeptidyl peptidase 4 (DPP4)/sodium-glucose co-transporter 2 (SGLT2) inhibitor FDC approved in India for patients with T2DM. Potential limitations of this study are a small dose of dapagliflozin (10 mg) in the FDC, a short study duration (30 weeks) and a high minimum threshold for HbA1c (≤ 7.5%; ≤ 53 mmol/l). Results indicate the FDC to be a superior therapeutic option over linagliptin for patients with T2DM on metformin monotherapy. TRIAL REGISTRATION: CTRI/2022/08/044563; 01/08/2022.

Cognitive Function in Early Onset Type 1 Diabetes in Children.

OBJECTIVES: To assess cognitive function and factors affecting it in Indian children with early-onset type 1 diabetes (T1D) (less than 6 y). METHODS: This cross-sectional, single-centre study recruited children diagnosed with T1D before 6 y of age and having a disease duration of at least 2 y, as cases. Controls were age- and sex-matched apparently healthy children or siblings. Children with birth asphyxia, intellectual disability, syndromic children, or pre-existing psychiatric illness were excluded. Enrolled children underwent cognitive assessment using Malin's Intelligence Scale for Indian Children (MISIC), and scores in various subtests were compared between cases and controls. RESULTS: A total of 60 children were enrolled in each group. When compared to controls, cases had significantly lower scores on most subtests, verbal, performance and overall Intelligence Quotient (IQ- 100.62 ± 3.26 vs. 103.23 ± 1.22). HbA1c >9%, severe hypoglycemia and lesser duration since the last diabetic ketoacidosis (DKA) episode significantly correlated with lower neurocognitive scores. CONCLUSIONS: Children with early onset T1D showed significant deficits in various cognitive domains and IQ. Poor glycemic control, higher glycemic variability and exposure to severe hypoglycemia are risk factors for poor cognitive outcomes in these children. Further longitudinal studies could potentially aid in a finer understanding of factors affecting cognitive functioning in T1D children in developing countries.