A Descriptive Study of the Demographic and Clinicopathological Characteristics of Individuals With Gallstone-Induced Pancreatitis in a Tertiary-Level Hospital in Ranchi, Jharkhand.

BACKGROUND: Gallstones are a major cause of acute pancreatitis, which is associated with high recurrence, morbidity, and mortality. Careful consideration of demographic and clinicopathological features is required to understand the association between the cause and severity of pancreatitis in various populations, and such crucial information is lacking for Jharkhand's population. Here, we sought to describe the demographic and clinicopathological features of gallstone-induced acute pancreatitis at a tertiary hospital in Ranchi. METHODS: This hospital-based descriptive study was conducted at Rajendra Institute of Medical Sciences in Ranchi. The hospital records of patients admitted to the surgical unit with acute gallstone-induced pancreatitis from January 2023 to December 2023 were analyzed. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: Of the 72 patients admitted with acute gallstone-induced pancreatitis (mean age: 42.5 years), 46 (64%) were males and 26 (36%) were females. All 72 patients had abdominal pain and 44 (61%) were vomiting. The severe vs. non-severe pancreatitis groups differed significantly in age (≥40) and male gender (p = 0.013 and 0.031, respectively). A total of 45 (62.5%) patients had severe gallstone-induced pancreatitis, and the most common complication was acute kidney injury, followed by pleural effusion (18 (25%) and 13 (18.1%) cases, respectively). CONCLUSIONS: Our study revealed that gallstone-induced pancreatitis was more common in males and that age and gender were significantly associated with severity. However, late presentation to the hospital may have influenced our study, resulting in more severe cases being reported, with the most common complication being acute kidney injury. To our knowledge, this is the first study to describe the demographic, clinicopathological, and outcome data of acute gallstone-induced pancreatitis in Ranchi. These results can guide hospital policy development to improve patient outcomes.

Development and evaluation of a chicken embryo fibroblast cell culture based live attenuated Indian strain duck plague vaccine.

Duck plague (DP) is an acute, contagious and fatal disease, caused by duck enteritis virus (DEV), with worldwide distribution causing several outbreaks and posing severe economic losses. The present study was carried out with a goal of development of a live attenuated cell culture based DP vaccine using an Indian strain of DEV and evaluation of its safety, efficacy along with complete genome analysis. The live attenuated DP vaccine (DPvac/IVRI-19) was developed by serial propagation of a virulent isolate of DEV (DEV/India/IVRI-2016) in the chicken embryo fibroblast (CEF) primary cell culture. Adaptation of DEV in CEF cell culture was indicated by more rapid appearance of cytopathic effects (CPE) and gradual increase of virus titre, which reached up to 107.5 TCID50/mL after 41 passages. The safety, immunogenicity and efficacy of the vaccine were determined by immunization trials in ducklings. The DPvac/IVRI-19 was found to be avirulent and completely safe in the ducklings. Further, the vaccine induced both humoral and cell mediated immune responses and afforded 100% protection against the virulent DEV challenge. A comparison of the whole genome of DPvac/IVRI-19 (MZ911871) and DEV/India/IVRI-2016 (MZ824102) revealed significant number of mutations, which might be associated with viral attenuation. Phylogenetic tree of DEV/India/IVRI-2016 revealed its evolutionary relationship with other DEV isolates, but it formed a separate cluster with certain unique mutations. Thus, with the proven safety and 100% efficacy, the DPvac/IVRI-19 is suitable for large scale production with precisely pure form of vaccine and has potential utility at national and global levels.

Applications of low-valent compounds with heavy group-14 elements.

Over the last two decades, the low-valent compounds of group-14 elements have received significant attention in several fields of chemistry owing to their unique electronic properties. The low-valent group-14 species include tetrylenes, tetryliumylidene, tetrylones, dimetallenes and dimetallynes. These low-valent group-14 species have shown applications in various areas such as organic transformations (hydroboration, cyanosilylation, N-functionalisation of amines, and hydroamination), small molecule activation (e.g. P4, As4, CO2, CO, H2, alkene, and alkyne) and materials. This review presents an in-depth discussion on low-valent group-14 species-catalyzed reactions, including polymerization of rac-lactide, L-lactide, DL-lactide, and caprolactone, followed by their photophysical properties (phosphorescence and fluorescence), thin film deposition (atomic layer deposition and vapor phase deposition), and medicinal applications. This review concisely summarizes current developments of low-valent heavier group-14 compounds, covering synthetic methodologies, structural aspects, and their applications in various fields of chemistry. Finally, their opportunities and challenges are examined and emphasized.

Quantitative analysis of social influence and digital piracy contagion with differential equations on networks.

Illegal file sharing of copyrighted contents through popular file sharing networks poses an enormous threat to providers of digital contents, such as, games, softwares, music and movies. Though empirical studies of network effects on piracy is a well-studied domain, the dynamics of peer effect in the context of evolving social contagion has not been enough explored using dynamical models. In this research, we methodically study the trends of online piracy with a continuous ODE approach and differential equations on graphs to have a clear comparative view. We first formulate a compartmental model to study bifurcations and thresholds mathematically. We later move on with a network-based analysis to illustrate the proliferation of online piracy dynamics with an epidemiological approach over a social network. We figure out a solution for this online piracy problem by developing awareness among individuals and introducing media campaigns, which could be a valuable factor in eradicating and controlling online piracy. Next, using degree-block approximation, network analysis has been performed to investigate the phenomena from a heterogeneous approach and to derive the threshold condition for the persistence of piracy in the population in a steady state. Considering the dual control of positive peer influence and media-driven awareness, we examine the system through realistic parameter selection to better understand the complexity of the dynamics and suggest policy implications.

Management of Heart Failure in a Resource-Limited Setting: Expert Opinion from India.

Heart failure poses a global health challenge affecting millions of individuals, and access to guideline-directed medical therapy is often limited. This limitation is frequently attributed to factors such as drug availability, slow adoption, clinical inertia, and delayed diagnosis. Despite international recommendations promoting the use of guideline-directed medical therapy for heart failure management, personalized approaches are essential in settings with resource constraints. In India, crucial treatments like angiotensin II receptor blocker neprilysin inhibitors and sodium-glucose co-transporter 2 inhibitors are not fully utilized despite their established safety and efficacy. To address this issue, an expert consensus involving 150 specialists, including cardiologists, nephrologists, and endocrinologists, was convened. They deliberated on patient profiles, monitoring, and adverse side effects and provided tailored recommendations for guideline-directed medical therapy in heart failure management. Stressing the significance of early initiation of guideline-directed medical therapy in patients with heart failure, especially with sodium-glucose co-transporter 2 inhibitors, the consensus also explored innovative therapies like vericiguat. To improve heart failure outcomes in resource-limited settings, the experts proposed several measures, including enhanced patient education, cardiac rehabilitation, improved drug access, and reforms in healthcare policies.

Ferroelectric capacitors and field-effect transistors as in-memory computing elements for machine learning workloads.

This study discusses the feasibility of Ferroelectric Capacitors (FeCaps) and Ferroelectric Field-Effect Transistors (FeFETs) as In-Memory Computing (IMC) elements to accelerate machine learning (ML) workloads. We conducted an exploration of device fabrication and proposed system-algorithm co-design to boost performance. A novel FeCap device, incorporating an interfacial layer (IL) and Hf 0.5 Zr 0.5 O 2 (HZO), ensures a reduction in operating voltage and enhances HZO scaling while being compatible with CMOS circuits. The IL also enriches ferroelectricity and retention properties. When integrated into crossbar arrays, FeCaps and FeFETs demonstrate their effectiveness as IMC components, eliminating sneak paths and enabling selector-less operation, leading to notable improvements in energy efficiency and area utilization. However, it is worth noting that limited capacitance ratios in FeCaps introduced errors in multiply-and-accumulate (MAC) computations. The proposed co-design approach helps in mitigating these errors and achieves high accuracy in classifying the CIFAR-10 dataset, elevating it from a baseline of 10% to 81.7%. FeFETs in crossbars, with a higher on-off ratio, outperform FeCaps, and our proposed charge-based sensing scheme achieved at least an order of magnitude reduction in power consumption, compared to prevalent current-based methods.

Combination of EZH2 and ATM inhibition in BAP1-deficient mesothelioma.

BACKGROUND: More than half of mesothelioma tumours show alterations in the tumour suppressor gene BAP1. BAP1-deficient mesothelioma is shown to be sensitive to EZH2 inhibition in preclinical settings but only showed modest efficacy in clinical trial. Adding a second inhibitor could potentially elevate EZH2i treatment efficacy while preventing acquired resistance at the same time. METHODS: A focused drug synergy screen consisting of 20 drugs was performed by combining EZH2 inhibition with a panel of anti-cancer compounds in mesothelioma cell lines. The compounds used are under preclinical investigation or already used in the clinic. The synergistic potential of the combinations was assessed by using the Bliss model. To validate our findings, in vivo xenograft experiments were performed. RESULTS: Combining EZH2i with ATMi was found to have synergistic potential against BAP1-deficient mesothelioma in our drug screen, which was validated in clonogenicity assays. Tumour growth inhibition potential was significantly increased in BAP1-deficient xenografts. In addition, we observe lower ATM levels upon depletion of BAP1 and hypothesise that this might be mediated by E2F1. CONCLUSIONS: We demonstrated the efficacy of the combination of ATM and EZH2 inhibition against BAP1-deficient mesothelioma in preclinical models, indicating the potential of this combination as a novel treatment modality using BAP1 as a biomarker.

The Influence of a Microstructural Conformation of Oriented Floating Films of Semiconducting Polymers on Organic Device Performance.

Extended π-conjugation with backbone-planarity-driven π-π stacking dominates charge transport in semiconducting polymers (SCPs). The roles of SCP film morphology and macromolecular conformation concerning the substrate in influencing charge transport and its impact on device performance have been a subject of extensive debate. Face-on SCPs promote out-of-plane charge transport primarily through π-π stacking, with conjugated polymeric chains assisting transport in connecting crystalline domains, whereas edge-on SCPs promote in-plane charge transport primarily through conjugation and π-π stacking. In this work, we fabricated three different types of devices, namely, organic field effect transistors, organic Schottky diodes, and organic bistable memristors, as representatives of planar and vertical devices. We demonstrate that a planar device, i.e., an organic field effect transistor, performs well in an edge-on conformation exhibiting a field-effect mobility of 0.12 cm2V-1s-1 and on/off ratio >104, whereas vertical devices, i.e., organic Schottky diodes and organic memristors, perform well in a face-on conformation, exhibiting exceptionally high on/off ratios of ~107 and 106, respectively.

Immunometabolic Regulation of Bacterial Infection, Biofilms, and Antibiotic Susceptibility.

BACKGROUND: Upon infection, mucosal tissues activate a brisk inflammatory response to clear the pathogen, i.e., resistance to disease. Resistance to disease is orchestrated by tissue-resident macrophages, which undergo profound metabolic reprogramming after sensing the pathogen. These metabolically activated macrophages release many inflammatory factors, which promote their bactericidal function. However, in immunocompetent individuals, pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella evade this type of immunity, generating communities that thrive for the long term. SUMMARY: These organisms develop features that render them less susceptible to eradication, such as biofilms and increased tolerance to antibiotics. Furthermore, after antibiotic therapy withdrawal, "persister" cells rapidly upsurge, triggering inflammatory relapses that worsen host health. How these pathogens persisted in inflamed tissues replete with activated macrophages remains poorly understood. KEY MESSAGES: In this review, we discuss recent findings indicating that the ability of P. aeruginosa, S. aureus, and Salmonella to evolve biofilms and antibiotic tolerance is promoted by the similar metabolic routes that regulate macrophage metabolic reprogramming.

Glyceraldehyde-3-Phosphate Dehydrogenase Binds with Spike Protein and Inhibits the Entry of SARS-CoV-2 into Host Cells.

INTRODUCTION: Coronavirus disease 2019 caused by coronavirus-2 (SARS-CoV-2) has emerged as an aggressive viral pandemic. Health care providers confront a challenging task for rapid development of effective strategies to combat this and its long-term after effects. Virus entry into host cells involves interaction between receptor-binding domain (RBD) of spike (S) protein S1 subunit with angiotensin converting enzyme present on host cells. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a moonlighting enzyme involved in cellular glycolytic energy metabolism and micronutrient homeostasis. It is deployed in various cellular compartments and the extra cellular milieu. Though it is known to moonlight as a component of mammalian innate immune defense machinery, till date its role in viral restriction remains unknown. METHOD: Recombinant S protein, the RBD, and human GAPDH protein were used for solid phase binding assays and biolayer interferometry. Pseudovirus particles expressing four different strain variants of S protein all harboring ZsGreen gene as marker of infection were used for flow cytometry-based infectivity assays. RESULTS: Pseudovirus entry into target cells in culture was significantly inhibited by addition of human GAPDH into the extracellular medium. Binding assays demonstrated that human GAPDH binds to S protein and RBD of SARS-CoV-2 with nanomolar affinity. CONCLUSIONS: Our investigations suggest that this interaction of GAPDH interferes in the viral docking with hACE2 receptors, thereby affecting viral ingress into mammalian cells.

Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection.

Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), though the underlying mechanisms linking DM and TB remain ambiguous. Macrophages are a key player in the innate immune response and their phagocytic ability is enhanced in response to microbial infections. Upon infection or inflammation, they also repel invading pathogens by generating; reactive oxygen species (ROS), reactive nitrogen species (RNS), pro-inflammatory cytokines (IL-1ß and IL-6), and anti-inflammatory cytokines (IL-10). However, the robustness of these innate defensive capabilities of macrophages when exposed to hyperglycemia remains unclear. In our current work, we explored the production of these host defense molecules in response to challenge with Mycobacterium tuberculosis (Mtb) infection and lipopolysaccharide (LPS) stimulation. Utilizing peritoneal macrophages from high-fat diet + streptozotocin induced diabetic mice and hyperglycemic THP-1-derived macrophages as model systems; we found that LPS stimulation and Mtb infection were ineffective in stimulating the production of ROS, RNS, and pro-inflammatory cytokines in cells exposed to hyperglycemia. On the contrary, an increase in production of anti-inflammatory cytokines was observed. To confirm the mechanism of decreased anti-bacterial activity of the diabetic macrophage, we explored activation status of these compromised macrophages and found decreased surface expression of activation (TLR-4) and differentiation markers (CD11b and CD11c). We postulate that this could be the cause for higher susceptibility for Mtb infection among diabetic individuals.

Robust Few-Shot Learning Without Using Any Adversarial Samples.

The high cost of acquiring and annotating samples has made the "few-shot" learning problem of prime importance. Existing works mainly focus on improving performance on clean data and overlook robustness concerns on the data perturbed with adversarial noise. Recently, a few efforts have been made to combine the few-shot problem with the robustness objective using sophisticated meta-learning techniques. These methods rely on the generation of adversarial samples in every episode of training, which further adds to the computational burden. To avoid such time-consuming and complicated procedures, we propose a simple but effective alternative that does not require any adversarial samples. Inspired by the cognitive decision-making process in humans, we enforce high-level feature matching between the base class data and their corresponding low-frequency samples in the pretraining stage via self distillation. The model is then fine-tuned on the samples of novel classes where we additionally improve the discriminability of low-frequency query set features via cosine similarity. On a one-shot setting of the CIFAR-FS dataset, our method yields a massive improvement of 60.55% and 62.05% in adversarial accuracy on the projected gradient descent (PGD) and state-of-the-art auto attack, respectively, with a minor drop in clean accuracy compared to the baseline. Moreover, our method only takes 1.69× of the standard training time while being ≈ 5× faster than thestate-of-the-art adversarial meta-learning methods. The code is available at https://github.com/vcl-iisc/robust-few-shot-learning.

Methylglyoxal metabolism is altered during defence response in pigeonpea (Cajanus cajan (L.) Millsp.) against the spotted pod borer (Maruca vitrata).

Pigeonpea (Cajanus cajan ) production can be affected by the spotted pod borer (Maruca vitrata ). Here, we identified biochemical changes in plant parts of pigeonpea after M. vitrata infestation. Two pigeonpea genotypes (AL 1747, moderately resistant; and MN 1, susceptible) were compared for glyoxalase and non-glyoxalase enzyme systems responsible for methylglyoxal (MG) detoxification, γ-glutamylcysteine synthetase (γ-GCS), glutathione-S-transferase (GST) and glutathione content in leaves, flowers and pods under control and insect-infested conditions. MN 1 had major damage due to M. vitrata infestation compared to AL 1747. Lower accumulation of MG in AL 1747 was due to higher activities of enzymes of GSH-dependent (glyoxylase I, glyoxylase II), GSH-independent (glyoxalase III) pathway, and enzyme of non-glyoxalase pathway (methylglyoxal reductase, MGR), which convert MG to lactate. Decreased glyoxylase enzymes and MGR activities in MN 1 resulted in higher accumulation of MG. Higher lactate dehydrogenase (LDH) activity in AL 1747 indicates utilisation of MG detoxification pathway. Higher glutathione content in AL 1747 genotype might be responsible for efficient working of MG detoxification pathway under insect infestation. Higher activity of γ-GCS in AL 1747 maintains the glutathione pool, necessary for the functioning of glyoxylase pathway to carry out the detoxification of MG. Higher activities of GST and GPX in AL 1747 might be responsible for detoxification of toxic products that accumulates following insect infestation, and elevated activities of glyoxylase and non-glyoxylase enzyme systems in AL 1747 after infestation might be responsible for reducing reactive cabanoyl stress. Our investigation will help the future development of resistant cultivars.

Demonstration of a Gel-Polymer Electrolyte-Based Electrochromic Device Outperforming Its Solution-Type Counterpart in All Merits: Architectural Benefits of CeO2 Quantum Dot and Nanorods.

For years, solution-type electrochromic devices (ECDs) have intrigued researchers' interest and eventually rendered themselves into commercialization. Regrettably, challenges such as electrolyte leakage, high flammability, and complicated edge-encapsulation processes limit their practical utilization, hence necessitating an efficient alternate. In this quest, although the concept of solid/gel-polymer electrolyte (SPE/GPE)-based ECDs settled some issues of solution-type ECDs, an array of problems like high operating voltage, sluggish response time, and poor cycling stability have paralyzed their commercial applicability. Herein, we demonstrate a choreographed-CeO2-nanofiller-doped GPE-based ECD outperforming its solution-type counterpart in all merits. The filler-incorporated polymer electrolyte assembly was meticulously weaved through the electrospinning method, and the resultant host was employed for immobilizing electrochromic viologen species. The filler engineering benefits conceived through the tuned shape of CeO2 nanorod and quantum dots, along with the excellent redox shuttling effect of Ce3+/Ce4+, synchronously yielded an outstanding class of GPE, which upon utilization in ECDs delivered impressive electrochromic properties. A combination of features possessed by a particular device (QD-NR/PVDF-HFP/IL/BzV-Fc ECD) such as exceptionally low driving voltage (0.9 V), high transmittance change (ΔT, ∼69%), fast response time (∼1.8 s), high coloration efficiency (∼339 cm2/C), and remarkable cycling stability (∼90% ΔT-retention after 25,000 cycles) showcased a striking potential in the yet-to-realize market of GPE-based ECDs. This study unveils the untapped potential of choreographed nanofillers that can promisingly drive GPE-based ECDs to the doorstep of commercialization.

The rigidity and chelation effect of ligands on the hydrogen evolution reaction catalyzed by Ni(II) complexes.

With increasing interest in nickel-based electrocatalysts, three heteroleptic Ni(II) dithiolate complexes with the general formula [Ni(II)L(L')2] (1-3), L = 2-(methylene-1,1'-dithiolato)-5,5'-dimethylcyclohexane-1,3-dione and L' = triphenylphosphine (1), 1,1'-bis(diphenylphosphino)ferrocene (DPPF) (2), and 1,2-bis(diphenylphosphino)ethane (DPPE) (3), have been synthesized and characterized by various spectroscopic techniques (UV-vis, IR, 1H, and 31P{1H} NMR) as well as the electrochemical method. The molecular structure of complex 2 has also been determined by single-crystal X-ray crystallography. The crystal structure of complex 2 reveals a distorted square planar geometry around the nickel metal ion with a NiP2S2 core. The cyclic voltammograms reveal a small difference in the redox properties of complexes (ΔE° = 130 mV) while the difference in the catalytic half-wave potential becomes substantial (ΔEcat/2 = 670 mV) in the presence of 15 mM CF3COOH. The common S^S-dithiolate ligand provides stability, while the rigidity effect of other ligands (DPPE (3) > DPPF (2) > PPh3 (1)) regulates the formation of the transition state, resulting in the NiIII-H intermediate in the order of 1 > 2 > 3. The foot-of-the-wave analysis supports the widely accepted ECEC mechanism for Ni-based complexes with the first protonation step as a rate-determining step. The electrocatalytic proton reduction activity follows in the order of complex 1 > 2 > 3. The comparatively lower overpotential and higher turnover frequency of complex 1 are attributed to the flexibility of the PPh3 ligand, which favours the easy formation of a transition state.

Combined Inhibition of EZH2 and FGFR is Synergistic in BAP1-deficient Malignant Mesothelioma.

Malignant mesothelioma is a highly aggressive tumor with a survival of only 4-18 months after diagnosis. Treatment options for this disease are limited. Immune checkpoint blockade using ipilimumab and nivolumab has recently been approved as a frontline therapy, but this led to only a small improvement in overall patient survival. As more than half of patients with mesothelioma have alterations in the gene encoding for BAP1 this could be a potential marker for targeted therapies. In this study, we investigated the synergistic potential of combining EZH2 inhibition together with FGFR inhibition for treatment of BAP1-deficient malignancies. The efficacy of the combination was evaluated using human and murine preclinical models of mesothelioma and uveal melanoma in vitro. The efficacy of the combination was further validated in vivo by using BAP1-deficient mesothelioma xenografts and autochthonous mouse models. In vitro data showed sensitivity to the combined inhibition in BAP1-deficient mesothelioma and uveal melanoma tumor cell lines but not for BAP1-proficient subtypes. In vivo data showed susceptibility to the combination of BAP1-deficient xenografts and demonstrated an increase of survival in autochthonous models of mesothelioma. These results highlight the potential of this novel drug combination for the treatment of mesothelioma using BAP1 as a biomarker. Given these encouraging preclinical results, it will be important to clinically explore dual EZH2/FGFR inhibition in patients with BAP1-deficient malignant mesothelioma and justify further exploration in other BAP1 loss-associated tumors. SIGNIFICANCE: Despite the recent approval of immunotherapy, malignant mesothelioma has limited treatment options and poor prognosis. Here, we observe that EZH2 inhibitors dramatically enhance the efficacy of FGFR inhibition, sensitising BAP1-mutant mesothelioma and uveal melanoma cells. The striking synergy of EZH2 and FGFR inhibition supports clinical investigations for BAP1-mutant tumors.

Drug-related problems in older adults in outpatient settings: Results from a 6-year long prospective study in a tertiary hospital of north India.

AIM: Drug-related problems (DRPs) are a common cause of hospitalization in older patients. So far, these issues have been studied in hospitalized settings, and evidence on patterns and outcomes of DRPs, such as adverse drug reactions, is relatively scarce in older outpatients. The main aim of this study was to provide a comprehensive description and possible solutions for DRPs in older adults in outpatient settings. METHODS: The study was carried out from January 2015 to September 2021 in a tertiary hospital in north India. Patients aged ≥50 years with DRPs were enrolled. DRPs causing hospitalization, drug interactions and drug-disease interactions were identified, along with preventive measures. RESULTS: Of 10 400 patients registered, 1031 DRPs occurred in 666 patients (9.9%). Adverse drug reactions were the major DRPs (n = 933, 8.9%). Metabolic disorders were the commonest DRP in individuals aged ≥65 years compared with gastrointestinal disorders in the 50-64 years group. Drug interactions and drug-disease interactions contributed to 20.1% and 7.9% of patients, respectively. Nearly 15.8% of DRPs directly led to hospitalization, with drug-induced metabolic disturbances and movement disorders as the common causes. The Naranjo scale was not applicable in 35.3% of patients, and drug interactions were the commonest cause. Frequent monitoring, omission of unnecessary drugs, slow titration and proper instructions on therapy, together, could avoid one-third of DRPs. CONCLUSION: One out of 10 prescriptions of older outpatients carries a DRP. New-onset metabolic and neurological disturbances should prompt a thorough drug history. A multifaceted holistic approach can prevent significant drug-related morbidity and requires future evaluation. Geriatr Gerontol Int 2024; 24: 285-291.

Clinical and Demographic Characteristics of Patients with Coexistent Hypertension, Type 2 Diabetes Mellitus, and Dyslipidemia: A Retrospective Study from India.

BACKGROUND: Coexisting hypertension, type 2 diabetes mellitus (T2DM), and dyslipidemia (triple disease) can lead to greater risk of cardiovascular morbidity and mortality. The present study sought to comprehend the prevalence, demographic traits, clinical traits, and treatment patterns in Indian patients with these coexisting conditions. METHODS: An electronic medical record (EMR)-based, retrospective, multicenter, cross-sectional study was conducted, and data were collected for patients who were diagnosed with coexistent hypertension, T2DM, and dyslipidemia. Baseline patient variables evaluated were the percentage of patients with triple comorbidity, demographic characteristics, diagnostic laboratory parameters, and treatment pattern details. RESULTS: Data from 4793 centers (clinics) were included, with a total of 6,722,173 patients. Of these, 427,835 (6.36%) patients were found to have coexistent hypertension, T2DM, and dyslipidemia. Most of the patients belonged to the 40-64 year age group (62.10%) and were males (57.00%), while 27.40% patients had a body mass index (BMI) within normal limits, 43.30% patients were pre-obese, and 20.90% patients were class 1 obese. Further, 3402 patients (0.80%) had a recorded history of smoking. Mean glycated hemoglobin (HbA1c) for the patients included in the study was 8.35 ± 1.96 g%. Mean systolic blood pressure (SBP) was 138.81 ± 19.59 mm Hg, while mean diastolic blood pressure (DBP) was 82.17 ± 10.35 mm Hg; 27.60% cases had SBP < 130 mm Hg, while 28.37% cases had DBP < 80 mm Hg. The mean low-density lipoprotein (LDL), total cholesterol, and high-density lipoprotein (HDL) in mg/dl were 98.38 ± 40.39, 174.75 ± 46.73, and 44.5 ± 10.05, respectively. Of the enrolled cases, 55.64% had serum LDL below 100 mg/dl, 72.03% cases had serum cholesterol below 200 mg/dl, and 44.15% males and 71.77% females had serum HDL below the normal prescribed range. The most common monotherapy used for managing hypertension was angiotensin receptor blockers (ARB) (24.80%), followed by beta-blockers (24.30%). The most common combinations administered for management of hypertension were antihypertensives with diuretics (14.30%), followed by ARB plus calcium channel blockers (CCB) (13.30%). For dyslipidemia, the majority of patients (56.60%) received lipid-lowering medication in combination with drugs for other comorbidities. The most common antidiabetic agents prescribed were biguanides (74.60%). CONCLUSIONS: Coexistence of triple disease is not uncommon in the Indian population, with middle-aged patients diagnosed as pre-obese and obese being affected more commonly and receiving treatment for the same. The present study highlights that, though there are medications against the three chronic conditions, the rate of uncontrolled cases of hypertension, T2DM, and dyslipidemia remains high. Coexistence of triple disease increases the risk of cardiovascular and renal complications, which need to be closely monitored and effectively treated.

Effectiveness of Dapagliflozin as Add-On to Metformin with or without Other Oral Antidiabetic Drugs in Type 2 Diabetes Mellitus: A Multicentre, Retrospective, Real-World Database Study.

BACKGROUND: Real-world Indian studies evaluating effectiveness of dapagliflozin as an add-on to other oral antidiabetic drugs (OAD) in patients with type 2 diabetes mellitus (DM) are scarce. METHODS: An electronic medical record (EMR)-based, retrospective, multicentre study was conducted to evaluate the effectiveness of dapagliflozin as add-on therapy in adult patients with inadequately controlled DM on metformin with or without other OAD. Baseline characteristics (visit 1: metformin or metformin plus OAD treatment for at least 30 days) and treatment-related outcomes (visit 2: follow-up) considered between 60 and 140 days after adding/switching dapagliflozin [glycated haemoglobin (HbA1c), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP)] were analysed. RESULTS: A total of 3616 patients were screened from 478 centres. Most patients had received dapagliflozin (D) + metformin (M) + at least one other OAD [D + M + OAD, n = 2907 (80.4%), 408 followed-up with HbA1c reported], while 709 patients (19.6%, 138 followed-up with HbA1c reported) received dapagliflozin + metformin (D + M). Treatment with dapagliflozin as an add-on therapy resulted in significant change in HbA1c (-1.1 ± 1.44%; p < 0.05 for HbA1c subgroup ≥ 7.5%; -1.6 ± 1.41%; p < 0.05 for HbA1c subgroup ≥ 8%) at visit 2 compared with visit 1. Significant change in body weight (-1.4 ± 3.31 kg; p < 0.05 for HbA1c subgroup ≥ 7.5%; - 1.5 ± 3.22 kg; p < 0.05 for HbA1c subgroup ≥ 8%) was observed at visit 2. Similarly, a significant change in BMI was noted for the HbA1c subgroup ≥ 7.5% (-1.0 ± 8.38 kg/m2). However, the change in BMI in the HbA1c subgroup ≥ 8% was noted to be -1.4 ± 10.4 kg/m2, which was not statistically significant (p = 0.08). In the overall study population, significant change in the SBP (-4.5 ± 14.9 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; -4.5 ± 15.1 mmHg; p < 0.0001 for HbA1c subgroup ≥ 8%) was observed at visit 2 compared with visit 1. On identical lines, significant change in DBP (-1.5 ± 8.94 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; -1.4 ± 8.91 mmHg; p < 0.05 for HbA1c subgroup ≥ 8%) was noted. CONCLUSIONS: Dapagliflozin showed significant improvement in glycemic parameter, BMI and BP when added to metformin, with or without other OADs in a real-world scenario.