Migraine headache (MH) classification using machine learning methods with data augmentation.

Migraine headache, a prevalent and intricate neurovascular disease, presents significant challenges in its clinical identification. Existing techniques that use subjective pain intensity measures are insufficiently accurate to make a reliable diagnosis. Even though headaches are a common condition with poor diagnostic specificity, they have a significant negative influence on the brain, body, and general human function. In this era of deeply intertwined health and technology, machine learning (ML) has emerged as a crucial force in transforming every aspect of healthcare, utilizing advanced facilities ML has shown groundbreaking achievements related to developing classification and automatic predictors. With this, deep learning models, in particular, have proven effective in solving complex problems spanning computer vision and data analytics. Consequently, the integration of ML in healthcare has become vital, especially in developing countries where limited medical resources and lack of awareness prevail, the urgent need to forecast and categorize migraines using artificial intelligence (AI) becomes even more crucial. By training these models on a publicly available dataset, with and without data augmentation. This study focuses on leveraging state-of-the-art ML algorithms, including support vector machine (SVM), K-nearest neighbors (KNN), random forest (RF), decision tree (DST), and deep neural networks (DNN), to predict and classify various types of migraines. The proposed models with data augmentations were trained to classify seven various types of migraine. The proposed models with data augmentations were trained to classify seven various types of migraine. The revealed results show that DNN, SVM, KNN, DST, and RF achieved an accuracy of 99.66%, 94.60%, 97.10%, 88.20%, and 98.50% respectively with data augmentation highlighting the transformative potential of AI in enhancing migraine diagnosis.

Assessment and Recommendations for Website Platforms of Neuroanesthesiology Fellowship Programs.

BACKGROUND: Websites serve as recruitment and educational tools for many fellowship programs, including neuroanesthesiology. Since the COVID-19 pandemic, when interviews, conferences, and institutional visits were moved online, websites have become more important for applicants when deciding on their preferred fellowship program. This study evaluated the content of the websites of neuroanesthesiology fellowship programs. METHODS: Neuroanesthesiology fellowship program websites were identified from the websites of the International Council on Perioperative Neuroscience Training and the Society for Neuroscience in Anesthesiology and Critical Care. The content was assessed against 24 predefined criteria. RESULTS: Fifty-three fellowship programs were identified, of which 42 websites were accessible through a Google search and available for evaluation. The mean number of criteria met by the 42 fellowship websites was 12/24 (50%), with a range of 6 to 18 criteria. None of the evaluated fellowship websites met all 24 predefined criteria; 20 included more than 50% of the criteria, whereas 7 included fewer than 30% of the criteria. Having a functional website, accessibility through a single click from Google, and a detailed description of the fellowship program were the features of most websites. Information about salary and life in the area, concise program summaries, and biographical information of past and current fellows were missing from a majority of websites. CONCLUSION: Important information was missing from most of the 42 evaluated neuroanesthesiology fellowship program websites, potentially hindering applicants from making informed choices about their career plans.

Nano-residronate loaded κ-carrageenan-based injectable hydrogels for bone tissue regeneration.

Bone tissue possesses intrinsic regenerative capabilities to address deformities; however, its ability to repair defects caused by severe fractures, tumor resections, osteoporosis, joint arthroplasties, and surgical reconsiderations can be hindered. To address this limitation, bone tissue engineering has emerged as a promising approach for bone repair and regeneration, particularly for large-scale bone defects. In this study, an injectable hydrogel based on kappa-carrageenan-co-N-isopropyl acrylamide (κC-co-NIPAAM) was synthesized using free radical polymerization and the antisolvent evaporation technique. The κC-co-NIPAAM hydrogel's cross-linked structure was confirmed using Fourier transform infrared spectra (FTIR) and nuclear magnetic resonance (1H NMR). The hydrogel's thermal stability and morphological behavior were assessed using thermogravimetric analysis (TGA) and scanning electron microscopy (SEM), respectively. Swelling and in vitro drug release studies were conducted at varying pH and temperatures, with minimal swelling and release observed at low pH (1.2) and 25 °C, while maximum swelling and release occurred at pH 7.4 and 37oC. Cytocompatibility analysis revealed that the κC-co-NIPAAM hydrogels were biocompatible, and hematoxylin and eosin (H&E) staining demonstrated their potential for tissue regeneration and enhanced bone repair compared to other experimental groups. Notably, digital x-ray examination using an in vivo bone defect model showed that the κC-co-NIPAAM hydrogel significantly improved bone regeneration, making it a promising candidate for bone defects.

Inflammatory response in confirmed non-diabetic foot and ankle infections: A case series with normal inflammatory markers.

BACKGROUND: The distinction between foot and ankle wound healing complications as opposed to infection is crucial for the appropriate and efficacious allocation of antibiotic therapy. Multiple reports have focused on the diagnostic accuracy of different inflammatory markers, however, mainly in the diabetic population. AIM: To evaluate the diagnostic accuracy of white cell count (WCC) and C-reactive protein (CRP) as diagnostic tools for this distinction in the non-diabetic cohort. METHODS: Data was reviewed from a prospectively maintained Infectious Diseases Unit database of 216 patients admitted at Leicester University Hospitals-United Kingdom with musculoskeletal infections over the period between July 2014 and February 2020 (68 mo). All patients with confirmed diagnosis of diabetes were excluded while only those with confirmed microbiological or clinical diagnosis of foot or ankle infection were included in our study. For the included patients, we retrospectively retrieved the inflammatory markers (WCCs and CRP) at the time of presentation. Values of CRP 0-10 mg/L and WCC 4.0-11.0 × 109/L were considered normal. RESULTS: After exclusion of patients with confirmed diabetes, 25 patients with confirmed foot or ankle infections were included. All infections were confirmed microbiologically with positive intra-operative culture results. 7 (28%) patients with osteomyelitis (OM) of the foot, 11 (44%) with OM of the ankle, 5 (20%) with ankle septic arthritis and 2 (8%) patients with post-surgical wound infection were identified. Previous bony surgery was identified in 13 (52%) patients, either a corrective osteotomy or an open reduction and internal fixation for a foot or ankle fracture with the infection developing on top of the existing metalwork. 21 (84%) patients did have raised inflammatory markers while 4 (16%) patients failed to mount an inflammatory response even with subsequent debridement and removal of metal work. CRP sensitivity was 84%, while WCC sensitivity was only 28%. CONCLUSION: CRP has a relatively good sensitivity in the diagnosis of foot and ankle infections in non-diabetic patients, whereas WCC is a poor inflammatory marker in the detection of such cases. In presence of clinically high level of suspicion of foot or ankle infection, a normal CRP should not rule out the diagnosis of OM.

Chemical constituents of the Ajuga multiflora bunge and their protective effects on dexamethasone-induced muscle atrophy in C2C12 myotubes.

Ajuga multiflora Bunge is a perennial ornamental herb and has been used for the treatment of fever in Korean folk medicine. In the course of searching for protective agents associated with the potential of A. multiflora against dexamethsone (DEX)-induced muscle atrophy, a new phytoecdysteroid, 29-hydroxyprecyasterone (1), together with four known compounds (2-5), were isolated from A. multiflora. The structures of the compounds were determined by spectroscopic analyses, including 1D-, 2D-NMR and HR-MS interpretation. To elucidate the effects of obtained compounds on DEX-induced muscle atrophy, the myotubes diameter, myosin heavy chain (MyHC) positive area, and fusion index were evaluated by immunofluorescence staining. Overall, each compound treatment effectively prevented the atrophic myotubes through an increase of MyHC-positive myotubes and the number of nuclei. Particularly, the measurement of myotube diameter showed that compounds 1 and 5 treatment significantly alleviated the myotube thickness.

Synthesis of dihydropyrimidine stabilized silver nanoparticles with significant anti urease and catalytic applications.

We synthesized and explored biological and environmental applications of novel silver nanoparticles (AgNps) stabilized by short chain heterocyclic thiol namely Ethyl 6-methyl-4-phenyl-2-thioxo1,2,3,4-dihydropyrim-idine-5-carboxylate (DHPM). Dihydropyrimidines (DHPM), a biological active class of compounds that contain a single thiol group at the focal point which strongly stabilized the nascent AgNps. The short alkyl chain of (DHPM) effectively controlled the growth kinetics and surface morphology of AgNps. The synthesized Dihydropyrimidine stabilized silver nanoparticles (DHPM-AgNps) were investigated using Ultraviolet- visible spectroscopy (UV-Vis), Atomic force Microscopy (AFM) and Fourier-transform infrared spectroscopy (FTIR). AFM exhibited the size and shape of the DHPM-AgNps with an average diameter of 10 ± 1 nm. Our prepared DHPM-AgNps were examined for urease enzyme inhibition activity. The synthesized DHPM-AgNps showed significant level of urease inhibition activity (% of inhibition 40.3±0.28%) when compared with standard thiourea inhibition activity (% of inhibition value 79.6± 0.47%.). Moreover prepared DHPM-AgNps system successfully applied for the reduction of para-nitrophenol (p-Nip). It reduces the para-nitrophenol (p-Nip) to para-aminophenol (p-Amp) within one second in the presence of NaBH4 under ambient temperature and pressure conditions, which followed the pseudo-first-order rate kinetics. This study will provide useful guidelines for designing efficient catalysts and stabilizing agents for Silver Nanoparticles.

Identifying and addressing pill aversion in adults without physiological-related dysphagia: A narrative review.

Solid oral dosage forms (SODFs) (often called pills by patients) are the default formulation to treat medical ailments. Beneficial therapeutic outcomes rely on patients taking them as directed. Up to 40% of the population experience difficulties swallowing SODFs, resulting in reduced adherence and impaired therapeutic efficacy. Often associated with children, this also presents in adults with dysphagia, and without any organic dysphagia (non-physiological-related or functional dysphagia). This review aims to identify and appraise current interventions used to screen for and overcome pill aversion in adults with functional dysphagia. A comprehensive search of the literature was conducted. Articles reporting pill aversion in adults aged ≥18 years with no underlying cause, history of, or existing dysphagia were included. Study quality was determined using the STROBE tool for observational studies. A narrative synthesis of the findings was prepared. We identified 18 relevant cohort studies, which demonstrate that pill aversion is a global problem. Perceived ease of and/or SODF swallowability appears to be influenced by female gender, younger age, co-morbidities (e.g., depression), and physical SODF properties. Patients often modify their medicines rather than raise this issue with their healthcare team. Screening for pill aversion is haphazard but controlled postural adjustments, coating SODFs and behavioural interventions appear to be successful solutions. SODF swallowing difficulties are a barrier to effective medication use. Healthcare professionals must recognise that pill aversion is a problem requiring identification through effective screening and resolution by training interventions, appropriate formulation selection or specialist referral.

Biofunctional Hyaluronic Acid/κ-Carrageenan Injectable Hydrogels for Improved Drug Delivery and Wound Healing.

The in situ injectable hydrogel system offers a widespread range of biomedical applications in prompt chronic wound treatment and management, as it provides self-healing, maintains a moist wound microenvironment, and offers good antibacterial properties. This study aimed to develop and evaluate biopolymer-based thermoreversible injectable hydrogels for effective wound-healing applications and the controlled drug delivery of meropenem. The injectable hydrogel was developed using the solvent casting method and evaluated for structural changes using proton nuclear magnetic resonance, Fourier transforms infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. The results indicated the self-assembly of hyaluronic acid and kappa-carrageenan and the thermal stability of the fabricated injectable hydrogel with tunable gelation properties. The viscosity assessment indicated the in-situ gelling ability and injectability of the hydrogels at various temperatures. The fabricated hydrogel was loaded with meropenem, and the drug release from the hydrogel in phosphate buffer saline (PBS) with a pH of 7.4 was 96.12%, and the simulated wound fluid with a pH of 6.8 was observed to be at 94.73% at 24 h, which corresponds to the sustained delivery of meropenem. Antibacterial studies on P. aeruginosa, S. aureus, and E. coli with meropenem-laden hydrogel showed higher zones of inhibition. The in vivo studies in Sprague Dawley (SD) rats presented accelerated healing with the drug-loaded injectable hydrogel, while 90% wound closure with the unloaded injectable hydrogel, 70% in the positive control group (SC drug), and 60% in the negative control group was observed (normal saline) after fourteen days. In vivo wound closure analysis confirmed that the developed polymeric hydrogel has synergistic wound-healing potential.

Self-crosslinked chitosan/κ-carrageenan-based biomimetic membranes to combat diabetic burn wound infections.

Diabetic wound infection often leads to compromised healing with frequent chances of sepsis, amputation and even death. Traditional patient care emphasized on early debridement and fluid resuscitation followed by intravenous antibiotics therapy. However, compromised vasculature often limit the systemic effect of antibiotics. Current study focused formulation of chitosan HCl, κ- carrageenan and PVA based physical cross-linked hydrogel membrane dressings loaded with cefotaxime sodium (CTX), for potential diabetic burn wound healing by adopting solvent casting method. Results of mechanical strength shows tensile strength and % elongation of 12.63 ± 0.25 and 48 ±3.05 respectively. Water vapor transmission rate (WVTR) depicts that despite of formulation KCP3 and KCP6, all hydrogel membranes have WVTR value in range of ideal dressing i.e., 2000-2500 g/m2/day. Whereas, all hydrogel membranes have oxygen permibility values more than 8.2 mg/ml. Bacterial penetration analysis confirms the barrier property of formulated membranes. Drug loaded hydrogel membrane showed control release up to 24 hr which provide protection against bacterial proliferation. Present study aims to constructs diabetic burn rat model which demonstrate that CTX loaded hydrogel membrane shown significantly rapid wound closure higher re-epithelization and numerous granulation tissue formation as compared to positive and negative control group. Conclusively, it is confirmed that formulated hydrogel membranes are beneficial and can be considered as a promising membrane dressing to treat diabetic burn wound.

Agreement between WHO-UMC causality scale and the Naranjo algorithm for causality assessment of adverse drug reactions.

BACKGROUND: The Pharmacovigilance Program of India recommends the use of the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale, while many clinicians prefer the Naranjo algorithm for its simplicity. In the present study, we assessed agreement between the two widely used causality assessment scales, that is, the WHO-UMC criteria and the Naranjo algorithm. MATERIALS AND METHODS: In this study, 842 individual case safety reports were randomly selected from 1000 spontaneously reported forms submitted to the ADR Monitoring Center at a tertiary healthcare Institute in Central India between 2016 and 2018. Two well-trained independent groups performed the causality assessment. One group performed a causality assessment of the 842 ADRs using the WHO-UMC criteria and the other group performed the same using the Naranjo algorithm. The agreement between two ADR causality scales was assessed using the weighted kappa (κ) test. RESULTS: Cohen's kappa coefficient (κ) statistical test was applied between the two scales (WHO-UMC scale and Naranjo algorithm) to find out the agreement between these two scales. "No" agreement was found between the two scales {Kappa statistic with 95% confidence interval = 0.048 (P < 0.001)}. CONCLUSION: There was no agreement found between the WHO-UMC criteria and the Naranjo algorithm in our study.

Bioassay-Guided Isolation of Two Eudesmane Sesquiterpenes from Lindera strychnifolia Using Centrifugal Partition Chromatography.

In this study, a centrifugal partition chromatography (CPC) separation was applied to identify antioxidant-responsive element (ARE) induction molecules from the crude extract of Lindera strychnifolia roots. CPC was operated with a two-phase solvent system composed of n-hexane-methanol-water (10:8.5:1.5, v/v/v) in dual mode (descending to ascending), which provided a high recovery rate (>95.5%) with high resolution. Then, ARE induction activity of obtained CPC fractions was examined in ARE-transfected HepG2 cells according to the weight ratios of the obtained fractions. The fraction exhibiting ARE-inducing activity was further purified by preparative HPLC that led to isolation of two eudesmane type sesquiterpenes as active compounds. The chemical structures were elucidated as linderolide U (1) and a new sesquiterpene named as linderolide V (2) by spectroscopic data. Further bioactivity test demonstrated that compounds 1 and 2 enhanced ARE activity by 22.4-fold and 7.6-fold, respectively, at 100 µM concentration while 5 µM of sulforaphane induced ARE activity 24.8-fold compared to the control.

Red blood cell transfusion in critically-ill children and its association with outcome.

OBJECTIVE: To determine the indications and threshold of haemoglobin levels for packed red blood cell transfusion and its association with outcomes in a paediatric intensive care setting. METHODS: The retrospective study was conducted in the paediatric intensive care unit of the Aga Khan University Hospital, Karachi, and comprised medical records of all inpatients with age between 1 month and 16 years who received packed red blood cell transfusions between January and December 2017. Data was retrieved from the hospital database and was analyzed using SPSS 22. RESULTS: Of the 147 subjects with a mean age of 67.89±65.8 months, 76(51.7%) were males. Mean paediatric risk of mortality score was 11.72±7.86. Major admitting diagnosis included sepsis and multiorgan dysfunction 50(34%), respiratory diseases 26(17.7%) and haematology/oncology diseases 22(15%). The indications for transfusion was low haemoglobin in 90(61.2%) patients, shock 29(19.7%) and hypoxia 28(19%). Acute transfusion reaction was observed in 1(0.7%) patient; 120(82%) required mechanical ventilation; and 94(64%) required inotropic support. Of the total, 88(59.9%) patients survived. Paediatric risk of mortality score, need for inotropic support and mechanical ventilation were associated with mortality (p<0.05). CONCLUSIONS: Packed red blood cell transfusion, which is frequently prescribed in intensive care settings, was not found to be associated with favourable outcome.

Medication adherence, recall periods and factors affecting it: A community-based assessment on patients with chronic diseases in urban slums.

OBJECTIVE: To evaluate medication adherence, the effect of recall periods on self-reported adherence and factors influencing medication adherence among patients of chronic diseases, such as hypertension and diabetes, particularly in the community. METHODS: A cross-sectional cohort study was conducted among individuals with hypertension and/or diabetes coming as outpatients in community camps organised in a cluster of urban slums. Responses towards questions regarding self-reported quantitative and qualitative adherence for one week and one month along with information on pill burden, socio-demographic and other factors were recorded using a mobile application. RESULTS: Among 379 participants living in urban slum communities, who were prescribed anti-hypertensive or oral anti-diabetic medications previously, mean medication adherence over previous one week was 67.99% (standard deviation (SD) ± 38.32) and 6.87 (SD ± 3.62) on a ten-point numeric scale. The medication adherence for one month showed a strong significantly positive correlation with that of 1 week for both percentage-based (r = +0.910, 95% CI = 0.864 to 0.950, P < .0001) and Likert (ρ = +0.836, 95% CI = 0.803 to 0.863, P < .0001) scales. Age (r = 0.219, 95% CI = 0.120 to 0.313, P = .043) and pill burden (r = -0.231, 95% CI = -0.145 to -0.322, P < .0001) were found to significantly affect medication adherence. The odds of random blood sugar reduction were found to be significant (OR 1.98, 95% CI = 1.30 to 3.00, P = .001) with adequate adherence. A linear regression equation was developed to predict medication adherence percentage for a patient which was found to have 61.8% predictive power using multilayer perceptron modelling. CONCLUSION: Overall, medication adherence was sub-optimal. Adherence assessments can be reliably performed using either one week or one month recall periods. With further refinement and validation, the regression equation could prove to be a useful tool for physicians.

Reversal of hypertensive heart disease: a multiple linear regression model.

BACKGROUND: The development of left ventricular hypertrophy in primary hypertension increases cardiovascular mortality and morbidity. Reversal of left ventricular hypertrophy through therapeutic control of blood pressure reduces the risk of adverse cardiovascular incidents.   Objective:  In our study, we explored for the determinants of left ventricular hypertrophy regression.  Methods: A cohort (n=217) of patients with hypertensive left ventricular hypertrophy was identified by screening consecutive patients in medical outpatient unit. The primary inclusion criteria were (i) Blood pressure more than140/90 mm of Hg (ii) Left Ventricular Mass Index more than 115 and 95 gm/m2 for males and females respectively. Left Ventricular Mass Index was determined by echocardiography at the time of recruitment and after 24 weeks of standard pharmacotherapy. The change in Left Ventricular Mass Index was modelled using multiple linear regression with both categorical and continuous explanatory variables. The effect of drug therapy on change in Left Ventricular Mass Index was tested in the model with dummy coded variables for the treatment categories.  Results: In simple linear regression, the variables significantly correlating with change in Left Ventricular Mass Index were baseline Left Ventricular Mass Index (r=0.62, p<0.001), change in systolic blood pressure (r=0.22, p=0.001), change in mean blood pressure (r=0.16, p=0.02), baseline systolic blood pressure (r=0.15, p=0.02), age (r=0.12, p=0.09) and diabetes (r=0.12, p=0.09). The best fit model (r2=0.408) retained baseline Left Ventricular Mass Index (ß=0.59, p<0.001), change in systolic blood pressure (ß=0.14, p=0.01) and diabetes (ß=-0.104, p=0.05) as the significant predictors. Introduction of treatment effect into the model non-significantly increased the fit of the model (r2=0.414, p=0.27-0.98).   Conclusions: Pre-treatment Left Ventricular Mass Index and reduction in systolic blood pressure were the major determinants of left ventricular hypertrophy regression. We also observed that there is lesser left ventricular hypertrophy regression in diabetic patients, warranting future research to explore glycaemic control as a modifiable factor in left ventricular hypertrophy reversal.

A Novel Metric System to Quantify Antibiotic Consumption in Paediatric Population: A Hospital Based, Biphasic Pilot Study.

BACKGROUND: The Anatomical Therapeutic Chemical Classification / Defined Daily Dose (ATC/DDD) system recommended by World Health Organization is accepted worldwide as the standard method of quantification of drug consumption. However, owing to individual variation in body weight, the ATC/DDD system cannot be used for comparison across paediatric population. OBJECTIVE: This study aimed to develop a novel metric system for standard quantification of antibiotic consumption in paediatric population. METHOD: The standard unit of drug quantification in adult population is DDD/100 patient days (PD). We conceived a new unit of DDD/1000 kg-days (KD) where KD is the product of the body weight and length of hospital stay of an individual patient. We simulated the quantification and comparison of drugs in a computer model of five virtual paediatric hospitals (H1 to H5, n=100, 200, 100, 100, 100 respectively). We re-applied the metric system on two, real world, hospital-based, time cohorts (TC) (TC18, n=38 and TC19, n=47) of 2 weeks each, in two consecutive years. RESULTS: The body weights (mean±SD) in H1-H5 were 5.7±3.0, 5.7±2.8, 25.3±8.5, 20.6±11.7 and 19.8±11.4 kg, respectively. The antibiotic consumption in terms of DDD/100 PD and DDD/1000 KD in the five hospitals was 1.26, 1.20, 5.52, 4.41 and 2.00, and 2.24, 2.14, 2.22, 2.17 and 1.06 respectively. In TC18 and TC19, the mean body weight, DDD/100 PD and DDD/1000 KD were 12.24±13.17, 30.93, 20.34 and 19.51±12.28, 11.99, 6.23, respectively. CONCLUSION: DDD/1000 kg-days is a potential standard unit for drug quantification in paediatric population independent of weight distribution and size of the study sample. The universal application and comparison across diverse samples can generate useful information for resource allocation, anti-microbial stewardship, disease burden and drug use, and can help in taking policy decisions to improve healthcare delivery in the paediatric population.

Regression of the Left Ventricular Hypertrophy in Patients with Essential Hypertension on Standard Drug Therapy.

 PURPOSE: The American College of Cardiology/ American Heart Association 2017 and European Society of Cardiology/European Society of Hypertension 2018 guidelines were a paradigm shift in hypertension management in contemporary medicine. Lowering of blood pressure to less than 130 (systolic) and 80 (diastolic) mm of Hg irrespective of cardiovascular risk is recommended. While intensive blood pressure control is commonly achievable with rational pharmacotherapy, the magnitude of left ventricular hypertrophy regression is an independent factor in improvement in cardiovascular health. The regression of left ventricular hypertrophy has been adjudged as a clinically useful surrogate marker that reflects the efficacy of hypertension treatment. Though angiotensin converting enzyme inhibitors/ angiotensin receptor blockers (ACEI/ARB) are the preferred initial drug for greater regression of left ventricular mass, the choice of add-on therapy, if required, is still debatable. Therefore, in our observational study, we sought to compare the reduction in left ventricular mass index in hypertensives with left ventricular hypertrophy on standard ACEI/ARB based drug therapy.  MATERIALS AND METHODS: The cohort (n=217) comprised of patients with uncontrolled hypertension (blood pressure>140/90 mm of Hg) and left ventricular hypertrophy (left ventricular mass index>115 and 95 gram/square meter in males and females respectively). The add-on drug in ACEI/ARB therapy was either thiazide diuretics (TD) or calcium channel blockers (CCB). Four sub-cohorts were constituted: mono-therapy - group A (n=70, ACEI/ARB), dual-therapy - group B (n=48, ACEI/ARB+TD) and  group C (n=51, ACEI/ ARB+CCB), triple therapy - group D (n=48, ACEI/ ARB+TD+CCB). Left ventricular mass index was determined using echocardiography at baseline and after 24 weeks of therapy.  RESULTS: There was no significant difference in baseline clinical or demographic variables between group B and group C. Baseline blood pressure and duration of hypertension was greater in group D compared to group A (P<0.001). The reduction in left ventricular mass index (mean ±SD) in the four groups (A to D) was 16.7±18.7, 21.0±20.8, 20.5±15.5  and 29.1±21.5 g/m2  respectively (D>A, P=0.011, B versus C, P=1.00). The corresponding change in blood pressure (systolic/diastolic) was 18.5±13.6/8.9±11.2, 27.5±19.2/12.2±9.3, 23.4±16.7/ 5.4±10.1, 26.6±19.5/10.7±12.8 mm of Hg respectively (systolic, B>A, P=0.027, D>A, P=0.048) (diastolic, B>C, P=0.013).  CONCLUSION: Anti-hypertensive treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers-based therapy produced graded regression of left ventricular hypertrophy with monotherapy, dual therapy and triple therapy.  In dual therapy, add-on of either thiazide diuretics or calcium channel blockers to angiotensin converting enzyme inhibitors/angiotensin receptor blockers showed equal efficacy in regression of left ventricular hypertrophy independent of blood pressure reduction.

Development and validation of a mathematical model to quantify antibiotic consumption in paediatric population: A hospital-based pilot study.

WHAT IS KNOWN AND OBJECTIVES: A standard drug classification system and a fundamental measurement unit of drug consumption are prerequisites in a healthcare information system for generating quality data on drug use. Globally, the ATC/DDD (Anatomical Therapeutic Chemical Classification/Defined Daily Dose) system recommended by WHO is accepted as the international standard. However, owing to variability in body weight, it cannot be used directly in paediatric population. In our work, we aimed to develop a standard method of quantification of antibiotic consumption in paediatric population using a modified approach of the ATC/DDD system. METHOD: We developed a mathematical model in a simulated paediatric cohort (n = 1000) and calculated antibiotic consumption in units of days of therapy (DOT) and DDD/100 patient days (PD). We validated the model in an observational cohort (n = 38) of inpatients admitted in Paediatric Department of a tertiary care centre. RESULTS: Model simulation showed near perfect positive correlation (R = .99-1.00) between DOT and DDD/100 PD in discrete weight based sub-cohorts (weight 1-10 kg). In the validation cohort, consumption of antibiotics was 121.76 and 33.16 in terms of DOT and DDD/100 PD respectively. Strong positive correlation between the two units (R = .73) was obtained. The correlation was better in predefined age and weight categories as compared to the uncategorised consumption (R = .78-.97). The model was proved validated when weight specific (in sub-cohorts of patients weighing 4, 5, 7 kg) DDD/100 PD and DOT also showed near perfect positive correlation (R = .96-.99). WHAT IS NEW AND CONCLUSION: Weight specific DDD/100 PD can be explored further as a tool to standardise the quantification and comparison of consumption of drugs in paediatric population.

Prediction of Left Ventricular Mass Index Using Electrocardiography in Essential Hypertension - A Multiple Linear Regression Model.

BACKGROUND: Current electrocardiography (ECG) criteria indicate only the presence or absence of left ventricular hypertrophy (LVH). LVH is a continuum and a direct relationship exists between left ventricular mass (LVM) and cardiovascular event rate. We developed a mathematical model predictive of LVM index (LVMI) using ECG and non-ECG variables by correlating them with echocardiography determined LVMI. PATIENTS AND METHODS: The model was developed in a cohort of patients on treatment for essential hypertension (BP>140/90 mm of Hg) who underwent concurrent ECG and echocardiography. One hundred and forty-seven subjects were included in the study (56.38±11.84 years, 66% males). LVMI was determined by echocardiography (113.76±33.06 gm/m2). A set of ECG and non-ECG variables were correlated with LVMI for inclusion in the multiple linear regression model. The model was checked for multicollinearity, normality and homogeneity of variances. RESULTS: The final regression equation formulated with the help of unstandardized coefficients and constant was LVMI=18.494+ 1.704 (aLL) + 0.969 (RaVL+SV3) + 0.295 (MBP) + 15.406 (IHD) (aLL - sum of deflections in augmented limb leads; RaVL+SV3 - sum of deflection of (R wave in aVL + S wave in V3); MBP - mean blood pressure; IHD=1 for the presence of the disease, IHD=0 for the absence of the disease). CONCLUSION: In the model, 50.4% of the variability in LV mass is explained by the variables used. The findings warrant further studies for the development of better and validated models that can be incorporated in microprocessor-based ECG devices. The determination of LVMI with ECG only will be a cost-effective and readily accessible tool in patient care.

Bioassay-Guided Separation of Centipeda minima Using Comprehensive Linear Gradient Centrifugal Partition Chromatography.

A comprehensive linear gradient solvent system for centrifugal partition chromatography (CPC) was developed for the bioassay-guided isolation of natural compounds. The gradient solvent system consisted of three different ternary biphasic solvents types: n-hexane-acetonitrile-water (10:2:8, v/v), ethyl acetate-acetonitrile-water (10:2:8, v/v), and water-saturated n-butanol-acetonitrile-water (10:2:8, v/v). The lower phase of the n-hexane-acetonitrile-water (10:2:8, v/v) was used as the stationary phase, while its upper phase, as well as ethyl acetate-acetonitrile-water (10:2:8), and water-saturated n-butanol-acetonitrile-water (10:2:8, v/v) were pumped to generate a linear gradient elution, increasing the mobile phase polarity. We used the gradient CPC to identify antioxidant response elements (AREs), inducing compounds from Centipeda minima, using an ARE-luciferase assay in HepG2 cells, which led to the purification of the active molecules 3-methoxyquercetin and brevilin A. The developed CPC solvent systems allow the separation and isolation of compounds with a wide polarity range, allowing active molecule identification in the complex crude extract of natural products.