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Retention prediction through Artificial intelligence (AI)-based techniques has gained exponential growth due to their abilities to process complex sets of data and ease the crucial task of identification and separation of compounds in most employed chromatographic techniques. Numerous approaches were reported for retention prediction in different chromatographic techniques, and consistent results demonstrated that the accuracy and effectiveness of deep learning models outclassed the linear machine learning models, mainly in liquid and gas chromatography, as ML algorithms use fewer complex data to train and predict information. Support Vector machine-based neural networks were found to be most utilized for the prediction of retention factors of different compounds in thin-layer chromatography. Cheminformatics, chemometrics, and hybrid approaches were also employed for the modeling and were more reliable in retention prediction over conventional models. Quantitative Structure Retention Relationship (QSRR) was also a potential method for predicting retention in different chromatographic techniques and determining the separation method for analytes. These techniques demonstrated the aids of incorporating QSRR with AI-driven techniques acquiring more precise retention predictions. This review aims at recent exploration of different AI-driven approaches employed for retention prediction in different chromatographic techniques, and due to the lack of summarized literature, it also aims at providing a comprehensive literature that will be highly useful for the society of scientists exploring the field of AI in analytical chemistry. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a prevalent health condition with severe implications for cardiovascular health. Combination therapy involving Candesartan and Nifedipine has emerged as a promising approach for managing hypertension due to the synergistic effects of these medications. Methods: This study aimed to develop a Design of Experiment (DoE) based Green High-Performance Liquid Chromatography (HPLC) method for the simultaneous estimation of Candesartan and Nifedipine in a combined dosage form. Reversed-phase HPLC was utilized with UV-Vis spectrophotometry for detection. DoE principles were applied to optimize chromatographic conditions, including pH, ethanol percentage in the mobile phase, and flow rate. Results: Optimal chromatographic separation was achieved using a composite mobile phase comprising ethanol and potassium dihydrogen phosphate buffer (45:55, v/v) at pH 3.7, with a flow rate of 1 mL/min. Statistical analysis confirmed the significance of these parameters in achieving efficient separation. The developed method exhibited high precision, accuracy, and reliability across various validation parameters, including specificity, linearity, repeatability, and robustness. Conclusion: The proposed DoE-based Green HPLC method offers a sustainable and efficient approach for the simultaneous estimation of Candesartan and Nifedipine in hypertension management. By integrating green chemistry principles with systematic method development, this method provides a reliable analytical tool for routine quality control purposes in pharmaceutical formulations containing these medications. [ABSTRACT FROM AUTHOR]

Background and aim: While intensive care unit (ICU) mortality rates in India are higher when compared to countries with more resources, fewer patients with clinically futile conditions are subjected to limitation of life-sustaining treatments or given access to palliative care. Although a few surveys and audits have been conducted exploring this phenomenon, the qualitative perspectives of ICU physicians regarding end-of-life care (EOLC) and the quality of dying are yet to be explored. Methods: There are 22 eligible consultant-level ICU physicians working in multidisciplinary ICUs were purposively recruited and interviewed. The study data was analyzed using reflexive thematic analysis (RTA) with a critical realist perspective, and the study findings were interpreted using the lens of the semiotic theory that facilitated the development of themes. Results: About four themes were generated. Intensive care unit physicians perceived the quality of dying as respecting patients' and families' choices, fulfilling their needs, providing continued care beyond death, and ensuring family satisfaction. To achieve this, the EOLC process must encompass timely decision-making, communication, treatment guidelines, visitation rights, and trust-building. The contextual challenges were legal concerns, decision-making complexities, cost-related issues, and managing expectations. To improve care, ICU physicians suggested amplifying patient and family voices, building therapeutic relationships, mitigating conflicts, enhancing palliative care services, and training ICU providers in EOLC. Conclusion: Effective management of critically ill patients with life-limiting illnesses in ICUs requires a holistic approach that considers the complex interplay between the EOLC process, its desired outcome, the quality of dying, care context, and the process of meaning-making by ICU physicians. [ABSTRACT FROM AUTHOR]

Background: Intensive care unit (ICU) patients face a significant rise in mortality rates due to acute hypoxemic respiratory failure (AHRF). The diagnosis of AHRF is based on the PF ratio, but it has limitations in resource-constrained settings. Instead, the Kigali modification suggests using the oxygen saturation/fraction of inspired oxygen (SF) ratio. This study aims to correlate SF ratio and arterial oxygen pressure (PF) ratio in critically ill adults with hypoxemic respiratory failure, who required O2 therapy through different modes of oxygen supplementation. Materials and methods: In an ICU, a prospective observational study included 125 adult AHRF patients receiving oxygen therapy, with data collected on FiO2, PaO2, and SpO2. The SF ratio and PF ratio were calculated, and their correlation was assessed using statistical analysis. The receiver operator characteristics (ROC) curve analysis was conducted to assess the diagnostic precision of the SF ratio in identifying AHRF. Results: Data from a total of 250 samples were collected. The study showed a positive correlation (r = 0.622) between the SF ratio and the PF ratio. The SF threshold values of 252 and 321 were established for PF values of 200 and 300, respectively, featuring a sensitivity of 69% and specificity of 95%. Furthermore, it is worth noting that the PF ratio and SF ratio are interchangeable, regardless of the type of oxygen therapy, as the median values of both the PF ratio and SF ratio displayed statistical significance (p < 0.01) in both acidosis and alkalosis conditions. Conclusion: For patients with AHRF, the noninvasive SF ratio can effectively serve as a substitute for the invasive PF ratio across all oxygen supplementation modes. [ABSTRACT FROM AUTHOR]

Aim: To characterize the impact of adherence to quality metrics of stroke care on the clinical outcomes of ischemic stroke (IS) and intracerebral hemorrhage (ICH) admissions. Methods: Consecutive patients with acute stroke were prospectively followed up for their demographic and clinical characteristics, acute stroke management, and associated clinical outcomes at discharge. Stroke quality metrics [adopted from the American Heart Association (AHA)/American Stroke Association's Get with The Guidelines (GWTG)] with a specific interest in an association between acute reperfusion therapies and functional recovery in stroke patients are analyzed and presented. A composite measure of care was considered "0 (non-adherence) to 1 (adherence)." An all-or-none measure of care was calculated to check whether eligible patients received all the quality-of-care interventions. Multivariate Cox regression models were used to study an association between optimal adherence and clinical outcomes. Results: During the study period, of the total 256 stroke admissions, 200 (78.1%) patients had IS, and the remaining 56 (21.9%) patients had ICH. The median [interquartile range (IQR)] age of total stroke admissions was 57 (36-78) years. Male preponderance was observed (IS: 80% and ICH: 67.9%). The conformity of performance metrics in IS patients was from 69.1% [95% confidence interval (CI), 68.5-69.6] for the use of deep vein thrombosis prophylaxis (DVTp) to 97.8% (95% CI, 96.2-98.6) for the use of statins. In ICH patients, it ranged from 61.7% (95% CI, 60.4-62.5) for the use of DVTp to 89.9% (95% CI, 88.6-89.7) for stroke rehabilitation. The unadjusted odds ratio (OR) of mortality (in-hospital plus the 28th-day postdischarge) was higher in ICH patients vs IS patients (4.42, p = 0.005). Optimal adherence with intravenous recombinant tissue plasminogen activator (IV-rtPA) therapy [hazards ratio (HR) = 0.23], in-hospital acute measures [IS (HR = 0.41) and ICH (HR = 0.63)], and discharge measures [IS (HR = 0.35) and ICH (HR = 0.45)] were associated with reduced hazards of the 28th-day mortality in both cohorts. Compared to ICH, IS patients had significantly improved neurofunctional recovery [modified Rankin score (mRS) ≤ 2, p < 0.01]. Conclusion: Adherence to quality metrics and performance measures was associated with low mortality and favorable clinical outcomes. Also, DVTp as an in-hospital (acute) measure of stroke care needs attention in both cerebrovascular events. [ABSTRACT FROM AUTHOR]

The regulatory agencies all over the world have defined the pathway and the regulations for approval of simple small-molecule generics. In addition, the agencies are striving to form perspicuous regulatory frameworks for approval of biosimilar. According to this viewpoint, the approval of complex generics, also known as non-biological complex pharmaceuticals, is not subject to any clearly defined regulations (NBCDs). Although they differ from biologic products, complex medicines are constructed of huge, extremely complex, and synthetic components. The regulatory frameworks that are currently being used for complicated generics are opaque and uncertain. The market for complex generics is huge and there are fewer generic competitors in this area. In addition, the cost of bringing such generics into the market is high. Thus, there is a need for a well-defined pathway and guidance documents for the authorization of generic versions of complex drug products. The paper focus on the regulatory frameworks that the USA, EU, and Latin America have developed at this time to allow for the introduction of complicated generics to the market. In order to analyse regulatory policies in the USA, Europe, and Latin America for the marketing of NBCD copies, a case study of a product with an approved generic version is used. It also describes on the regulatory disparities existing among the three agencies in the light of complex generics. [ABSTRACT FROM AUTHOR]

Background Takotsubo syndrome (TS) is a clinical condition mimicking acute coronary syndrome characterized by reversible acute systolic dysfunction. TS is typically associated with a catecholaminergic surge resulting from physical or emotional stress while some pharmacologic agents may act as a trigger. Case summary Here, we report a case of TS secondary to rizatriptan, used for treatment of acute migraine. A 67-year-old woman with a history of dyslipidemia, type II diabetes, and migraine was admitted with chest heaviness shortly after taking rizatriptan for migraine. Deepening T wave inversion was seen in multiple territories on electrocardiogram and hs-troponin T was elevated. Cardiac imaging including echocardiogram coronary angiography and cardiac magnetic resonance imaging was consistent with a diagnosis of TS. Discussion In this case, there was no emotional trigger for TS described. Given the compelling temporal correlation between the onset of typical chest pain and medication use, a diagnosis of TS secondary to rizatriptan was made. [ABSTRACT FROM AUTHOR]

RP-HPLC technique to estimate the Telmisartan and Rosuvastatin Calcium, employing an experimental design method using response surface methodology, was developed and validated. Experimental design was used to evaluate a multivariate optimisation of experimental conditions using flow rate, buffer pH, and % of acetonitrile in the mobile phase as three independent variables. The peak symmetry and retention time of the last eluting peak were optimized employing Derringer's desirability function in which 1 ml/min flow rate, KH2PO4 buffer with pH 3.5 (altered with 1% orthophosphoric acid), and 65% v/v of acetonitrile in the mobile phase in an isocratic proportion of acetonitrile: buffer (65:35, v/v) on a C18 column. Using response surface methodology, a RP-HPLC method was developed based on DoE that resulted in a better separation of peaks with a lower retention time of less than 9 min for eluted peaks. Response of linear was reported over the range of concentration of 20-100 μg/mL for Telmisartan and 5-25 μg/mL for Rosuvastatin Calcium. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the predictive power of the Full Outline of Unresponsiveness (FOUR) score and the Glasgow Coma Scale Pupil (GCS-P) score in determining outcomes for traumatic brain injury (TBI) patients. The Glasgow Outcome Scale (GOS) was used to evaluate patients at 1 month and 6 months after the injury. Methods: We conducted a 15-month prospective observational study. It included 50 TBI patients admitted to the ICU who met our inclusion criteria. We used Pearson's correlation coefficient to relate coma scales and outcome measures. The predictive value of these scales was determined using the receiver operating characteristic (ROC) curve, calculating the area under the curve with a 99% confidence interval. All hypotheses were two-tailed, and significance was defined as P<0.01. Results: In the present study, the GCS-P and FOUR scores among all patients on admission as well as in the subset of patients who were mechanically ventilated were statistically significant and strongly correlated with patient outcomes. The correlation coefficient of the GCS score compared to GCS-P and FOUR scores was higher and statistically significant. The areas under the ROC curve for the GCS, GCS-P, and FOUR scores and the number of computed tomography abnormalities were 0.912, 0.905, 0.937, and 0.324, respectively. Conclusions: The GCS, GCS-P, and FOUR scores are all excellent predictors with a strong positive linear correlation with final outcome prediction. In particular, the GCS score has the best correlation with final outcome. [ABSTRACT FROM AUTHOR]

Background: Endotracheal intubation to protect airway patency in critically ill patients with the use of videolaryngoscopes has been emerging and their expertise to handle is crucial. Our study focuses on the performance and outcomes of King Vision video laryngoscope (KVVL) in intensive care unit (ICU) compared to Macintosh direct laryngoscope (DL). Materials and methods: This comparative study was conducted by randomizing 143 critically ill patients in ICU into two groups: KVVL and Macintosh DL (n = 73; n = 70). The intubation difficulty was assessed by Mallampati score III or IV, apnea syndrome (obstructive), cervical spine limitation, opening mouth <3 cm, coma, hypoxia, anesthesiologist nontrained (MACOCHA) score. The primary endpoint was the glottic view measured by Cormack--Lehane (CL) grading. The secondary endpoints were a first-pass success, the time required for intubation, airway morbidities, and manipulations required. Results: The KVVL group showed the primary endpoint of significantly improved glottic visualization measured in terms of CL grading compared with the Macintosh DL group (p < 0.001). In the KVVL group, the first pass success rate was higher (95.7%) compared to the Macintosh DL group (81.4%) (p < 0.05). The time required for intubation in the KVVL group (28.77 ± 2.63 seconds) was significantly less compared with Macintosh DL (38.84 ± 2.72 seconds) group (p < 0.001). The airway morbidities observed were similar in both groups (p = 0.5) and the manipulation required for endotracheal intubation was significantly less (p < 0.05) in our KVVL group (16 cases; 23%) compared to the Macintosh DL group (8 cases; 10%). Conclusion: We found that the performance and outcomes of KVVL in intubating critically ill ICU patients were promising when handled by experienced operators who are experts in anesthesiology and airway management. [ABSTRACT FROM AUTHOR]

With the revolutionary expedition of technologies being used in pharmaceutical world to collect and process data, the honesty of data is predominant factor and subject to preservation. If the data collection of the products soon to be marketed, is adulterated it would not only be a potential harm to general public but also cause of economical and reputational damage for manufacturers. To secure the value of crucial data, regulatory authorities has been producing guidance regarding the integrity of data. Data integrity guarantees that data is not tampered with be it paper or electronic. Protecting the integrity, whether electronic or handwritten, is essential for making sound business decisions. In attempt of introducing aspects of data, the FDA first developed the ALCOA principles which are still the first line defence of integrity breaches in pharmaceutical companies. With the changing times of technologies, FDA evolved the data integrity principles into requirements and specifications of current good manufacturing practice answering questions directly from manufacturers. To understand the basic yet complex terms and conditions, this article strives to outline the Data Integrity requirements of USFDA specified in its cGMP guidance for data integrity specifications. [ABSTRACT FROM AUTHOR]

Cryoglobulinemic vasculitis is a systemic inflammatory response syndrome which affects multiple systems. The distinct presentations are due to the different pathophysiological mechanisms involved in the disease process that tends to create an inflammatory response in various organs.Here, we present a rare and a challenging case of Cryoglobulinemic Vasculitis in a patient who had both cutaneous and renal involvement despite of no underlying Hepatitis-C virus (HCV) infection and responded well to the immunosuppressive agents.Cryoglobulinemic Vasculitis is a complex immunological condition which can result in a life-threatening devastating complications such as loss of limb. It is very important that an Emergency Medicine specialist is aware of this complex immunological condition called as Cryoglobulinemic Vasculitis and picks up the clues which help in its early diagnosis and management. [ABSTRACT FROM AUTHOR]

Objective: To determine whether high-flow nasal oxygen (HFNO) or noninvasive ventilator (NIV) can avoid invasive mechanical ventilation (IMV) in COVID-19-related acute respiratory distress syndrome (ADRS), and the outcome predictors of these modalities. Design: Multicenter retrospective study conducted in 12 ICUs in Pune, India. Patients: Patients with COVID-19 pneumonia who had PaO2/FiO2 ratio <150 and were treated with HFNO and/or NIV. Intervention: HFNO and/or NIV. Measurements: The primary outcome was to assess the need of IMV. Secondary outcomes were death at Day 28 and mortality rates in different treatment groups. Main results: Among 1,201 patients who met the inclusion criteria, 35.9% (431/1,201) were treated successfully with HFNO and/or NIV and did not require IMV. About 59.5% (714/1,201) patients needed IMV for the failure of HFNO and/or NIV. About 48.3, 61.6, and 63.6% of patients who were treated with HFNO, NIV, or both, respectively, needed IMV. The need of IMV was significantly lower in the HFNO group (p <0.001). The 28-day mortality was 44.9, 59.9, and 59.6% in the patients treated with HFNO, NIV, or both, respectively (p <0.001). On multivariate regression analysis, presence of any comorbidity, SpO2 <90%, and presence of nonrespiratory organ dysfunction were independent and significant determinants of mortality (p <0.05). Conclusions: During COVID-19 pandemic surge, HFNO and/or NIV could successfully avoid IMV in 35.5% individuals with PO2/FiO2 ratio <150. Those who needed IMV due to failure of HFNO or NIV had high (87.5%) mortality. [ABSTRACT FROM AUTHOR]

Bromelain, a proteolytic enzyme isolated from the stem and fruit of Ananas comosus has gained tremendous importance as anti-inflammatory, anticancer, and fibrinolytic agent in the clinical field. Recent anti-cancer and anti-thrombolytic activity of Bromelain has opened new areas of research in the field of safety and efficacy. Bromelain is widely used since time immemorial alone and in combination with other drugs in the treatment of Rheumatoid Arthritis. The review aims to evaluate various extraction and analytical techniques employed for the assay of Bromelain in complex enzymatic mixtures which involves the use of diverse derivatizing agents with variable sensitivity and accuracy. The review focuses on homogenous and heterogenous techniques used for the estimation of Bromelain in the crude extract. This review also emphasizes on separation novel techniques, such as ion-exchange chromatography for isolation and purification of Bromelain supported by Gel Chromatography. This review also aims to provide deep insight into recent reverse micellar techniques employed as an effective tool for the purification of Bromelain. An overview of hyphenated bioanalytical techniques, such as LC-MS/MS for analysis of Bromelain in Plasma is also inculcated in the study. The techniques presented in the study provide diversified tools employed for the analysis of Bromelain in crude mixtures of complex enzymes of clinical significance. [ABSTRACT FROM AUTHOR]

Gastrointestinal tract duplication cysts are rare congenital malformations which can be diagnosed as early as the prenatal period but are frequently found in infancy or incidentally in adulthood. They can be seen throughout the alimentary tract with the most common involving the distal ileum and second most common the esophagus. Many duplication cysts are asymptomatic and thus discovered as an incidental imaging finding, though they can also be symptomatic with an array of clinical presentations dependent largely on their location. The vast majority of duplication cysts are benign; however, there are rare instances of malignant transformation reported. The aim of this review is to show how multimodality imaging can help in the diagnosis of duplication cysts at various anatomical locations. Duplication cyst can become symptomatic and in rare cases undergo malignant transformation; therefore, they are typically managed with surgical excision, particularly if found prenatally or during infancy. Given the diversity of anatomic locations, multiple differential diagnoses, and the need for surgical intervention, it is valuable to comprehend the role of multimodality imaging role in diagnosing duplication cysts. [ABSTRACT FROM AUTHOR]

Introduction: Intensive care unit (ICU) admission is required for approximately 25% of patients affected with coronavirus disease-19 (COVID-19) and imposes a high economic burden on patients in resource-limited settings. Method: We conducted a retrospective direct medical care cost analysis of COVID-19 patients requiring ICU admission after obtaining the Institutional Ethics Committee approval. Data were obtained from the records of patients admitted to the COVID-19 ICU of a tertiary care trust teaching hospital from June 2020 to December 2020. Direct costs were analyzed and correlated with various demographic variables and clinical outcomes. Results: A total of 176 patients were included (males--76%). The median direct medical cost for a median stay of 13 days was INR 202248.5 ($ 2742.91). Hospital drugs and disposables accounted for 20% of the total cost followed by bed charges (19%), equipment charges (17%), biosafety protective gear (15.5%), pathological and radiological tests (15%), clinical management (7.6%), and biomedical waste management (1.6%). Government schemes accounted for 79% of medical claims followed by directly paying patients (12.5%) and private insurance (8.5%). The cost was significantly higher in patients with diabetes mellitus and sepsis and in those requiring mechanical ventilation (MV) (p <0.05). Shorter lead time to hospital admission and lesser length of hospital stay were associated with significant lower direct cost. Conclusion: Direct medical care cost is substantial for COVID-19 patients requiring ICU admission. This cost is significantly associated with increased ICU and hospital stay, longer lead time to admission, diabetes mellitus, sepsis, and those who need high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and MV. [ABSTRACT FROM AUTHOR]

Background: Very few extensive studies regarding job stressors among doctors and nurses have been conducted in India. It is important to explore the workplace to understand various stressors that adversely affect the well-being of an individual and also affect health care and needs of patients and relatives. Considering this, the present study was planned to determine stress among doctors and nurses from the critical care unit (CCU) and to find the association of stress with selected variables. Materials and methods: This observational cross-sectional study was conducted among all staff (doctors and nurses) from the CCU. Data were collected with a pilot-tested, predesigned, validated questionnaire using the Google survey tool consisting of sociodemographic details and the ICMR work stress questionnaire. Analysis of data was done with SPSS version 25. Results: Of 105 participants, 57 (54.3%) were doctors and 48 (45.7%) were nurses. A total of 48.6% (51) of participants scored 32 of 64, that is, managed stress very well, and 51.4% of participants (54) scored 65 of 95, that is, having a reasonably safe level of stress, but certain areas need improvement. Conclusion: Stress was significantly more among females and those who have sleep problems. No statistically significant difference was found between the level of stress and age, relationship with seniors, exercise, and comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: The utilization of prescription drugs as off-label is common. While this practice can be beneficial to some patients, it can raise a safety concern when scientific evidence is lacking; hence, this study was conducted to evaluate the off-label drug consumption and its adverse drug reactions (ADRs) in the medical intensive care unit (ICU). Materials and methods: In the prospective cohort study conducted for a duration of 6 months, data pertaining to ICU patients' (age ≥18 years) demography, diagnosis, treatment, and laboratory investigation were collected to assess for off-label use as well as the strength of evidence and the occurrence of ADRs by using MICROMEDEX 2017 version (Healthcare Series Thomson Reuter, Greenwood, CO). Results: Of total 3574 drugs prescribed, 1453 (41%) were off-label indications and 65 (1.81%) were off-label dose. On the evaluation of off-label indication use, 1279 (88%) were evidence-based and 174 (12%) were low/no evidence-based medications (EBMs); 59 (91%) were evidence-based and 6 (9%) were low/no EBMs for off-label dose. Most commonly prescribed evidence-based off-label drug belonged to the gastrointestinal class while low/no evidence drugs were mostly of anti-infective class. A total of 383 ADRs were identified and 139 (36.2%) were implicated due to off-label medications, of which ADRs with evidence off-label medications (87.8%) were higher than low/no evidence off-label medication (12.2%) (P < 0.001). Conclusion: Widespread presence of off-label use was observed in medical ICU. Although incidence of ADRs was similar to the FDA-approved use, ongoing monitoring of such practice is needed. [ABSTRACT FROM AUTHOR]

Background: Hormonal therapy for menopause has been found to be the most efficacious treatment, but it may be associated with adverse effects in some of the women. Rheum rhaponticum root extract ("ERr 731"), which is available worldwide, is a natural, reliable, effective, and well-tolerated remedy for women in perimenopausal women with menopausal symptoms (MSs), but there is no Indian study demonstrating its efficacy, safety, and tolerability till date. Objective: This study aimed to evaluate the efficacy and safety of ERr 731 in alleviating MSs in perimenopausal Indian women. Patients and Methods: In this open-labeled prospective study, 129 perimenopausal women were treated with tablet containing 4 mg of Rr dried root extract once daily for 12 weeks. The Menopause Rating Scale (MRS) II score, endometrial thickness (ET), blood pressure, glycemic status, lipid profile, and high-sensitivity C-reactive protein (hs-CRP) level were periodically assessed and compared. Results: A significant reduction (67% by 12th week) in the mean MRS II score was observed from baseline till the end of 12 weeks (18.1; 95% confidence interval [CI]: 17.0–19.2; P < 0.001). A monotonic reduction in the mean total MRS II score over time was found (1.51 units/week; 95% CI: 1.42–1.60 units/week; P < 0.001) noticeable. There was a reduction in the mean ET from baseline till the end of 12 weeks, although the change was not significant. There were significant reductions in the mean fasting (6.3 mg/dl; 95% CI: 1.7–11.0 mg/dl; P = 0.008) and postprandial (6.3 mg/dl; 95% CI: 1.0–11.7; P = 0.021) blood glucose levels and glycated hemoglobin level (0.30%; 95% CI: 0.085–0.520; P = 0.007) at 12 weeks. No significant changes were noted in terms of blood pressure, lipid profile, and hs-CRP level. The drug was found to be safe. Conclusion: ERr 731 was well tolerated and was found to be efficacious and safe in alleviating MSs in Indian perimenopausal women. [ABSTRACT FROM AUTHOR]

Introduction: Ventriculoatrial (VA) conduction is a critical component in many arrhythmias, has a diagnostic value in electrophysiology study (EPS), and is implicated in pacemaker-mediated arrhythmias. This study sought to characterize retrograde conduction during EPS and to utilize it as a diagnostic tool in patients without AV block.Methods and Results: Patients with intact AV conduction undergoing EPS were included in this study to systematically evaluate baseline VA conduction. If absent, parahisian pacing was used to determine the level of block (nodal or infranodal). Recovery of VA conduction with increased sympathetic activity was assessed with isoproterenol infusion. Baseline characteristics and electrophysiological data were collected and analyzed. Among the 801 patients studied, VA conduction was present in 98% (81% at baseline and 17% after isoproterenol infusion). Parahisian pacing demonstrated that the block was at the AV node level among 150 patients with VA dissociation at baseline. Among patients presenting with supraventricular tachycardia (SVT), 98.7% with atrioventricular nodal reentrant tachycardia (AVNRT) had VA conduction at baseline versus 82.7% presenting with other SVT (atrial fibrillation excluded), P < 0.001. Thus, the absence of VA conduction at baseline during an EPS for SVT carries a negative predictive value (NPV) of 96.9% for AVNRT.Conclusions: VA conduction is present in most patients (98%) with intact AV conduction. The level of VA dissociation when present at baseline is always at the level of the AV node. Patients with SVT presenting for EPS that lacked VA conduction at baseline were unlikely to have AVNRT. [ABSTRACT FROM AUTHOR]

Purpose: When patients with implantable cardioverter defibrillators (ICD) develop symptomatic atrial fibrillation (AF), external direct current cardioversion (EDCCV), as well as internal cardioversion using their ICD, are the options available. It is currently unknown which of these two methods are more effective. We compared the effectiveness of EDCCV versus internal cardioversion to terminate AF in patients with a single-coil ICD. Methods: This randomized controlled trial (clinicaltrial.gov NCT03164395) enrolled consecutive patients with a single-coil ICD that presented with symptomatic AF of less than 1-year duration. They received either the maximum energy internal shock through the ICD or an EDCCV using transcutaneous pads of 200 J. The primary endpoint was a successful conversion to sinus rhythm after one shock. Crossover was permitted if the first shock was unsuccessful. Results: Thirty-one patients were enrolled in the study, including 16 in the internal ICD cardioversion group. The study included patients with a mean age of 59.5 ± 16.0 years, 41.9% females, median AF duration 1 month (interquartile range 1–3), 45.2% non-ischemic cardiomyopathies, mean EF 28.6 ± 16.0%, and 45.2% biventricular ICD. There were no significant differences in baseline clinical characteristics between the two groups. In the internal cardioversion group, 5/16 patients (31.3%) met the primary endpoint versus 14/15 (93.3%) in the EDCCV group, p < 0.001. All patients that failed the first shock were subsequently cardioverted externally. Conclusion: Among patients with a single-coil ICD and symptomatic AF of less than 1 year, external direct current cardioversion is much more effective than internal shock through the ICD. [ABSTRACT FROM AUTHOR]

Purpose: Catheter ablation (CA) is an effective treatment for atrial fibrillation (AF). The differences in complication rates and outcomes between women and men remain poorly studied. We aimed to study the sex differences in morbidity and mortality associated with CA in AF.Methods: Using weighted sampling from the National Inpatient Sample database, women and men with a primary diagnosis of AF and a primary procedure of CA (2004-2013) were identified. We compared the following outcomes based on the sex: (1) major complications [post-procedure transfusion, cardiac drain or surgery, pulmonary embolism, cerebrovascular accident, major cardiac events, kidney failure requiring dialysis, and sepsis], (2) overall complications (minor and/or major complications), and (3) in-hospital mortality.Results: Among 85,977 patients who underwent CA for AF, 27821 (32.4%) were women. Overall complications were more frequent among women versus among men (12.4% versus 9.0%; p < 0.001), as well as major complications (4.7% versus 2.7%; p < 0.001). However, there was no difference in mortality (0.3% versus 0.2%; p = 0.22). After adjusting for other factors, women were more likely than men to have major complication (odds ratio 1.48, 95% CI 1.21-1.82; p < 0.001). Prior CABG was associated with lower risk of major complications in both sexes (odds ratio in the overall cohort 0.27, 95% CI 0.12-0.61; p = 0.002), mostly driven by the reduction in tamponade and pericardial drain.Conclusions: Among patients who underwent catheter ablation for AF, the female sex was associated with higher rate of complications compared to male but no difference in mortality. Prior CABG was associated with a significant reduction of major complications in both sexes. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous implantable cardioverter defibrillators (S‐ICDs) have gained increasing popularity because of certain advantages over transvenous ICDs. However, while conventional ICDs require a single surgical incision to implant, S‐ICDS need two or three incisions, making them less appealing. Objective: This study sought out to investigate the feasibility of using a single‐incision technique to implant S‐ICDs. Methods: Patients qualifying for S‐ICDs were considered for a single incision. A single incision is performed by making a left inframammary incision and then the subcutaneous tissue is dissected medially toward the lower sternum. Two sutures are placed in the fascia in the xiphoid area to anchor the lead and a tunneling tool is used to dissect the tissue to place the lead parallel to the sternum. Then subcutaneous tissues are dissected down the lateral chest wall over the muscle fascia to create the pulse generator pocket in the vicinity of the fifth and sixth intercostal spaces and near the mid‐axillary line. Results: Eleven patients (six males and five females) successfully underwent S‐ICD implantation with a single incision without acute complications (64% for primary prevention). The mean age is 47.4 ± 15.8 years. There were no lead dislodgements, inappropriate shocks, or any other issues during a median follow‐up of 10 months (interquartile range 5–17). One patient had a successful appropriate shock for ventricular fibrillation about one year after device implant. Conclusions: A single incision for subcutaneous ICDs is feasible and safe in our early experience. [ABSTRACT FROM AUTHOR]

Background and Purpose: Blood-brain barrier (BBB) disruption detected on magnetic resonance imaging (MRI) in acute ischemic stroke as a hyperintense acute reperfusion marker (HARM) is associated with upregulation of matrix metalloproteinase-9 (MMP-9). Although activated leukocytes, including monocytes, are the main source of MMPs, limited data exist to support relationship between leukocyte activation and BBB disruption in patients with acute ischemic stroke. The goal of this study is to investigate the relationship between neutrophils, lymphocytes, and monocytes with BBB disruption detected as HARM (+) in patients with acute ischemic stroke.Methods: We conducted a retrospective analysis of prospectively collected data in patients who did not receive any reperfusion therapy with acute (<12 hours) ischemic stroke. MRI scans were obtained at baseline, 24 hours, and 5 days. HARM was evaluated on the 24-hour follow-up scan.Results: Thirty-three patients were studied. HARM was detected in 27% of patients. Median volumes of baseline perfusion (mean transit time [MTT]) deficit (219.4 mL vs. 158.4 mL, P = .029) and DWI infarct growth at 24 hours (18.50 mL vs. .14 mL, P = .017), as well as the median absolute numbers (1 × 103 /mm3 ) of monocytes, were significantly higher in HARM (+) versus HARM (-) patients (0.9 vs. 0.6, p = 0.011).Conclusion: Increased monocyte count associated with HARM supports importance of systemic inflammation in BBB disruption in acute ischemic stroke. [ABSTRACT FROM AUTHOR]

The functioning of pharmaceutical company does not stop when a drug product is approved and its marketing starts. When a product is first approved, its manufacturing process represents the current technology standard for manufacturing and follows the cGMP standard for regulatory compliance. After approval, market demand, technological advances, GMP standards, raw material sourcing or manufacturing experience may require that the approved process or product needs to be modified. Therefore, Post Approval Change management plays an important role in maintaining the marketing status of a drug product. For the purpose of carefully assessing and successfully implementing the changes in a pharmaceutical company, the company should have an efficient and well-defined change control system in place. Complying post approval requirements enables FDA and the pharmaceutical industry to make sure that the drug product is consistent in its quality, efficacy and safety throughout its lifecycle. [ABSTRACT FROM AUTHOR]

Alcohol ethoxylates surfactants are produced via ethoxylation of fatty alcohol (FA) with ethylene oxide. The source of FA could be either palm kernel oil (PKO) or petrochemicals. The study aimed to compare the potential environmental impacts for PKO-derived FA (PKO-FA) and petrochemicals-derived FA (petro-FA). Cradle-to-gate life cycle assessment has been performed for this purpose because it enables understanding of the impacts across the life cycle and impact categories. The results show that petro-FA has overall lower average greenhouse gas (GHG) emissions (~2.97 kg COe) compared to PKO-FA (~5.27 kg COe). (1) The practices in land use change for palm plantations, (2) end-of-life treatment for palm oil mill wastewater effluent and (3) end-of-life treatment for empty fruit bunches are the three determining factors for the environmental impacts of PKO-FA. For petro-FA, n-olefin production, ethylene production and thermal energy production are the main factors. We found the judicious decisions on land use change, effluent treatment and solid waste treatment are key to making PKO-FA environmentally sustainable. The sensitivity results show the broad distribution for PKO-FA due to varying practices in palm cultivation. PKO-FA has higher impacts on average for 12 out of 18 impact categories evaluated. For the base case, when accounted for uncertainty and sensitivity analyses results, the study finds that marine eutrophication, agricultural land occupation, natural land occupation, fossil depletion, particulate matter formation, and water depletion are affected by the sourcing decision. The sourcing of FA involves trade-offs and depends on the specific practices through the PKO life cycle from an environmental impact perspective. [ABSTRACT FROM AUTHOR]

New ECG Criteria for Left-Sided AV Connections Background Accessory AV-connections capable of antegrade conduction need to be recognized because of the potential for life-threatening arrhythmias. However, the preexcited ECG pattern may be subtle, especially among left-sided AV-connections. We explored whether additional ECG criteria might help identify left-sided AV-connections. Methods We analyzed 156 patients who underwent an electrophysiology study (EPS) and ablation for paroxysmal supraventricular tachycardias (PSVT). Patients were divided into 2 groups: those with left-sided AV-connections (Group 1) and all other PSVT (Group 2). Various ECG parameters were compared before and after ablation in both groups. Results The EPS identified left-sided AV-connections among 43 patients (Group 1) and excluded it among 113 (Group 2). Baseline ECG in Group 1 demonstrated obvious preexcitation among 24/43 patients (55.8%), the remaining 19/43 missing obvious preexcitation. R/S ratio > 0.5 in V1 was noted in 38/43 (88.4%) patients in Group 1 before ablation (median 1.00; IQR 0.58-2.20), including 16/19 (84.2%) patients lacking obvious left-sided AVconnections. Conversely, only 10/113 (8.8%) patients in Group 2 had R/S ratios in V1 ≥ 0.5 (0.20; 0.10-0.31), P < 0.0001. After ablation, the R/S ratio decreased significantly in Group 1 (0.29; 0.17-0.45), P < 0.0001. Thus, a combined criterion of classic preexcitation or R/S ratio ≥ 0.5 on ECG identified 40/43 left-sided AV-connections (sensitivity 93.0%). The negative predictive value of this combined criterion was 103/106 (97.2%). Conclusions In symptomatic patients, combining the R/S ratio (≥ 0.5) in lead V1 with the classic preexcitation pattern on ECG markedly improved the sensitivity to diagnose left-sided AV-connections. This ratio may be particularly useful among patients lacking obvious preexcitation. [ABSTRACT FROM AUTHOR]

As increased angiogenesis has been related with the progression of Ovarian cancer, Metastatic colorectal cancer (mCRC), Metastatic renal cell, Glioblastoma multiforme, Non squamous non-small cell lung cancer (NSCLC), number of anti-angiogenic agents have been investigated or are currently in development, as a potential treatment options for patients with advanced disease. Bevacizumab, a recombinant monoclonal antibody having targeted action against vascular endothelial growth factor (VEGF) has gained European Medical Agency (EMA) approval for treating the cancer mentioned above in combination with chemotherapeutic agents. Globally the incidence/new cases for the cancer is about 14.1 millions, 8.2 million cancer deaths and about five year prevalence was around 32.6 million cancers individuals that were above 15 years. Globocan 2012 indicates that the number might increase to 19.3 million new cancer cases by 2025. In India there are about 1.1 million new cancer cases, 682,830 cancer deaths and five-year prevalence was around 1.8 million individuals having or diagnosed with cancer. There are very few targeted therapies that are available for treating such type of cancer and Avastin is one of innovator product are available to patients. But due to its high cost it become difficult for patients use the drug for treatment purpose. So there arises a need to bring a quality generic version of the innovator drug to benefit Indian patients. Many leading Indian companies are striving to develop or manufacture such lifesaving drugs to make it available to Indian patients. A systemic literature survey was carried out to identify data available for in such type of cancer and to foster the strategy with a vision to bring global availability of the quality product to Indian patients. [ABSTRACT FROM AUTHOR]

Blood transfusion is one of the practices that is in vogue because it expands blood volume and purportedly improves the oxygen carrying capacity. Despite this supposed physiological benefit, paradoxically, both anaemia and transfusion are independently associated with organ injury and increased morbidity. Historically, transfusion was used to maintain blood haemoglobin concentration above 10 g/dL and a haematocrit above 30%. There is now a greater emphasis on interventions to reduce the use of transfusion as it is a scarce and expensive resource with many serious adverse effects. Institutional maximum surgical blood ordering schedule algorithm developed with data analysis and consensus of surgeons, anaesthesiologists and blood banks can reduce the overuse of blood. A PubMed search was performed with search words/combination of words 'erythrocyte transfusion, adverse effects, economics, mortality, therapy, therapeutic use and utilisation'. Search yielded a total of 1541 articles that were screened for clinical relevance for the purpose of this review. [ABSTRACT FROM AUTHOR]

Aims: The association of QRS duration (QRSd) with morbidity and mortality is understudied in patients with atrial fibrillation (AF). We sought to assess any association of prolonged QRS with increased risk of death or hospitalization among patients with AF.Methods and Results: QRS duration was retrieved from the baseline electrocardiograms of patients enroled in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study and divided into three categories: <90, 90-119, ≥120 ms. Cox models were applied relating the hazards of mortality and hospitalizations to QRSd. Among 3804 patients with AF, 593 died and 2305 were hospitalized. Compared with those with QRS < 90 ms, patients with QRS ≥ 120 ms, had an increased mortality [hazard ratio (HR) 1.61, 95% confidence interval (CI): 1.29-2.03, P < 0.001] and hospitalizations (HR 1.14, 95% CI: 1.07-1.34, P = 0.043) over an average follow-up of 3.5 years. Importantly, for patients with QRS 90-119 ms, mortality and hospitalization were also increased (HR 1.31, P = 0.005 and 1.11, P = 0.026, respectively). In subgroup analysis based on heart failure (HF) status (previously documented or ejection fraction <40%), mortality was increased for QRS ≥ 120 ms patients with (HR 1.87, P < 0.001) and without HF (HR 1.63, P = 0.02). In the QRS 90-119 ms group, mortality was increased (HR 1.38, P = 0.03) for those with HF, but not significantly among those without HF (HR 1.23, P = 0.14).Conclusion: Among patients with AF, QRSd ≥ 120 ms was associated with a substantially increased risk for mortality (all-cause, cardiovascular, and arrhythmic) and hospitalization. Interestingly, an increased mortality was also observed among those with QRS 90-119 ms and concomitant HF. [ABSTRACT FROM AUTHOR]

Aims The association of QRS duration (QRSd) with morbidity and mortality is understudied in patients with atrial fibrillation (AF). We sought to assess any association of prolonged QRS with increased risk of death or hospitalization among patients with AF. Methods and results QRS duration was retrieved from the baseline electrocardiograms of patients enroled in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study and divided into three categories: <90, 90–119, ≥120 ms. Cox models were applied relating the hazards of mortality and hospitalizations to QRSd. Among 3804 patients with AF, 593 died and 2305 were hospitalized. Compared with those with QRS < 90 ms, patients with QRS ≥ 120 ms, had an increased mortality [hazard ratio (HR) 1.61, 95% confidence interval (CI): 1.29–2.03, P < 0.001] and hospitalizations (HR 1.14, 95% CI: 1.07–1.34, P = 0.043) over an average follow-up of 3.5 years. Importantly, for patients with QRS 90–119 ms, mortality and hospitalization were also increased (HR 1.31, P = 0.005 and 1.11, P = 0.026, respectively). In subgroup analysis based on heart failure (HF) status (previously documented or ejection fraction <40%), mortality was increased for QRS ≥ 120 ms patients with (HR 1.87, P < 0.001) and without HF (HR 1.63, P = 0.02). In the QRS 90–119 ms group, mortality was increased (HR 1.38, P = 0.03) for those with HF, but not significantly among those without HF (HR 1.23, P = 0.14). Conclusion Among patients with AF, QRSd ≥ 120 ms was associated with a substantially increased risk for mortality (all-cause, cardiovascular, and arrhythmic) and hospitalization. Interestingly, an increased mortality was also observed among those with QRS 90–119 ms and concomitant HF. [ABSTRACT FROM PUBLISHER]

A simple, rapid, precise and accurate high performance liquid chromatography method was developed for simultaneous estimation of enalapril and aliskiren in synthetic mixture. The separation was obtained using a mobile phase consisting of acetonitrile and water in ratio of 80:20 and adjusting pH 4.0 with ortho phosphoric acid (10%) using Phenomenex-luna C18 (250 × 4.6 mm, 5µm) column. The flow rate 1.0 mL min-1 and UV detection at 210 nm was employed. The retention time for enalapril and aliskiren was 2.63 min and 7.25 min respectively. Linearity for enalapril and aliskiren was found to be in the range of 2-10 µg/mL and 15-75 µg/mL respectively. The method was validated as per the ICH guidelines and the results were within the acceptance criteria for precision, linearity, specificity, stability of solution and robustness. [ABSTRACT FROM AUTHOR]

A simple, rapid, precise and accurate high performance liquid chromatography method was developed for simultaneous estimation of Clobetasol propionate and Fusidic acid in combined dosage form. The separation was obtained using a mobile phase consisting of acetonitrile and water in ratio of 80:20 and adjusting pH 5.0 with glacial acetic acid (10%) using Phenomenex-luna C18 (250 × 4.6 mm, 5 µm) column. The flow rate 1.0 mL min-1 and UV detection at 240 nm was employed. The retention time for Clobetasol propionate and Fusidic acid was 5.55 min and 7.48 min respectively. Linearity for Clobetasol propionate and Fusidic acid was found to be in the range of 4-12 µg/mL and 160-480 µg/mL respectively. The method was validated as per the ICH guidelines and the results were within the acceptance criteria for precision, linearity, specificity, stability of solution and robustness. [ABSTRACT FROM AUTHOR]

Serum creatinine is often not an adequate measure of renal function, especially in advanced age or in physically debilitated patients. Estimated creatinine clearance is necessary to decide on usage of drugs such as Metformin. This study included 64 nursing home residents with diabetes treated with Metformin. Creatinine clearance (CrCl) was calculated by the Cockcroft-Gault equation modified for ideal body weight. CrCl more than or equal to 60/mL min was used as a cut-off for appropriate use of Metformin. In our sample, 20.3% had renal failure when measured by serum creatinine while 56.3% had renal failure when measured by CrCl. Age >65 years and women were more likely to be classified as normal for serum creatinine but have abnormal creatinine clearance. Use of estimated creatinine clearance should be advocated instead of serum creatinine when prescribing Metformin, especially for those of older age and among women. [ABSTRACT FROM AUTHOR]

Aims Digoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our study was to determine the relationship between digoxin and mortality in patients with AF. Methods and results The association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF and/or an ejection fraction <40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard ratio (EHR) 1.41, 95% confidence interval (CI) 1.19–1.67, P < 0.001], cardiovascular mortality (EHR 1.35, 95% CI 1.06–1.71, P = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12–2.30, P = 0.009). The all-cause mortality was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05–1.79, P = 0.019 and EHR 1.41, 95% CI 1.09–1.84, P = 0.010, respectively). There was no significant digoxin–gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality. Conclusion Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF. [ABSTRACT FROM PUBLISHER]