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The study investigates the intricate influence of gender and age variability in individuals diagnosed with diabetes, aiming to gain a comprehensive understanding of the diverse impact and implications of this prevalent metabolic disorder. A real-world dataset, obtained from a renowned diabetologist and meticulously maintained by Dr. Reddys’ Lab, serves as the foundation for rigorous analysis. Leveraging the capabilities of ensemble learning, an advanced technique that combines multiple models, the predictive model’s efficiency is substantially enhanced, resulting in precise and reliable predictions of individuals’ diabetic status. Addressing the challenge of diabetes prediction, a novel ensemble learning model was proposed. The model combines the strengths of three distinct algorithms: Random Forest, Extra Trees, and Multilayer Perceptron (MLP). The model’s output comprises a ternary label categorizing individuals as “diabetic, non-diabetic, or pre-diabetic”, while the accompanying prediction score quantifies the likelihood of individuals belonging to each respective category. The findings of this research expand the existing body of knowledge on diabetes prediction, underscoring the untapped potential of ensemble learning methodologies in augmenting accuracy and predictive performance for diabetic patients.

The primary aim of this study is to characterize long-term quality of life (QOL) in patients with esophageal and gastroesophageal junction (EGEJ) cancers who underwent curative intent treatment. EGEJ survivors were recruited to participate in a one-time cross-sectional survey study using validated questionnaires assessing QOL. Chart review was conducted for patient demographics and clinical characteristics. Spearman correlation coefficients, Wilcoxon signed-rank test, and Fisher's exact test were used to assess relationships between patient characteristics and long-term outcomes. QOL was relatively high in this sample, as evidenced by high median scores on the functional scales and low median scores in the symptom domains of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, with an overall median global health score of 75.0 (range 66.7-83.3). Patients using opiates at the time of survey reported lower role functioning ( P = .004), social functioning ( P = .052), and overall global health ( P = .041). Younger patients had significantly higher rates of reflux ( P = .019), odynophagia ( P = .045), choking ( P = .005), and cough ( P = .007). Patients using opiates or of younger age had lower QOL and higher symptoms in this cohort of long-term EGEJ survivors.

Hepatitis A represents one of the major public health problems worldwide including India. Vaccination is the most effective way to prevent hepatitis A infection. Two types of hepatitis A vaccines-live attenuated (H2 strain) and inactivated (killed) are available for use in clinical practice in India with former having advantage of a single-dose compared to two-dose killed vaccine. One of the important characteristic of an ideal vaccine includes its ability to provide life-long protection. In this article we reviewed the available long-term (≥10 years follow-up) published data on live attenuated hepatitis A (H2 strain) vaccine. The data from country of origin of the vaccine (China) and India establish the long-term immunogenicity, protection, and tolerability. Based on the results of several clinical trials showing long-term protection, single dose of live attenuated hepatitis vaccine can be widely used to protect high-risk population against hepatitis A virus infection and related complications.

Background Blood stream infections (BSIs) due to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality ranging from 10 to 60%. The current anti-MRSA agents have limitations with regards to safety and tolerability profile which limits their prolonged usage. Levonadifloxacin and its oral prodrug alalevonadifloxacin, a novel benzoquinolizine antibiotic, have recently been approved for acute bacterial skin and skin structure infections including diabetic foot infections and concurrent bacteremia in India. Methods The present study assessed the potency of levonadifloxacin, a novel benzoquinolizine antibiotic, against Gram-positive blood stream clinical isolates (n = 31) collected from January to June 2019 at a tertiary care hospital in Mumbai, India. The susceptibility of isolates to antibacterial agents was defined following the Clinical and Laboratory Standard Institute interpretive criteria (M100 E29). Results High prevalence of MRSA (62.5%), quinolone-resistant Staphylococcus aureus (QRSA) (87.5%), and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) (82.35%) were observed among bacteremic isolates. Levonadifloxacin demonstrated potent activity against MRSA, QRSA, and MR-CoNS strains with significantly lower minimum inhibitory concentration MIC50/90 values of 0.5/1 mg/L as compared with levofloxacin (8/32 mg/L) and moxifloxacin (2/8 mg/L). Conclusion Potent bactericidal activity coupled with low MICs support usage of levonadifloxacin for the management of BSIs caused by multidrug resistant Gram-positive bacteria.

Background: In India, where varicella outbreaks are reported at a younger age, a two-dose vaccine schedule administered at an early age could be highly efficacious in preventing varicella infection. The aim of this study was to evaluate the immunogenicity and safety of live attenuated varicella vaccine (VR 795 Oka strain) in a two-dose, 3 months apart regimen. Methodology: Healthy children (⩾ 12 months and ⩽12 years; mean age: 4.4 years) of either sex were included. Geometric mean titers (GMT) were measured at baseline and 28 days post first- and second-dose, and seroprotection rates were measured 28 days post first and second dose. The incidence of breakthrough (BT) infections post vaccination was determined from 42 days post first and second dose of vaccine up to 12 months. Adverse events (AEs) were monitored and recorded throughout the study period. Results: Of 305 subjects enrolled, 217 were seronegative. The seroconversion rate (a change from a seronegative to a seropositive condition) was 93.3% post first-dose and 100% post two-doses. High levels (9 times) of GMT were reported since post first-dose to post second-dose in children aged 12–18 months, 18–60 months (99.43%); and in and above 60 months (99.02%). The extent of rise of anti-VZV IgG antibody titer post 28 days of first-dose at two-fold, three-fold and four-fold rise was 93.39%, 90.56% and 80.66%, respectively and 100% 4-fold rise post second-dose. A single case, a day after the first-dose of vaccination of mild BT infection, was observed after close contact with a severe case. AEs were mild and none of the serious AEs were related to the study drug. Conclusion: The two-dose schedule of varicella vaccine was safe and immunogenic when given 3 months apart. However, further comparative studies and follow up for both dosing schedules are needed to validate the advantage of early dosing.

Pidotimod, an immunostimulant, is researched for over two decades. Current evidence indicates its utility in a variety of indications in children as well as in adults. Its immunostimulant activity has been firmly established in the management of recurrent respiratory infections in children with or without asthma. Compared to standard of care alone, addition of pidotimod to standard of care significantly prevents the recurrences and reduces the severity and duration of acute episodes, ultimately resulting in reduced visits to pediatric clinics and lower absenteeism at school. In adults, pidotimod is effective in the prevention and treatment of acute infectious exacerbations of chronic bronchitis and chronic obstructive pulmonary disease (COPD). Further, it has been evaluated in indications such as pneumonia, hand–food–mouth disease, bronchiectasis, and chronic idiopathic urticaria. From a total of 32 studies conducted in child (24 studies) and adult (8 studies) population, this in-depth review discusses the current evidence of pidotimod. With further exploration, the immunostimulant activity of pidotimod might be extended to different immunological disorders.

Community-acquired bacterial pneumonia (CABP) is one of the leading causes of morbidity and mortality in India and worldwide. Evidence indicates that Gram-positive, Gram-negative, and atypical bacteria are encountered with near-equal frequency. Despite guideline recommendations and antibiotic options for the management of CABP, burden of morbidity and mortality is high, which is attributable to a variety of factors. Failure of empirical therapy, probably because of insufficient microbial coverage, increasing bacterial resistance, and adverse effects of existing treatments, underlies the unsuccessful treatment of CABP, especially in India. Multiple novel therapies that have entered clinical development phases have potential to address some of these issues. This article discusses the current treatment guidelines in CABP, management limitations, and emerging potential treatment options in the management of CABP.

Hypertension (HTN) is a complex multi-factorial disease and is considered one of the foremost modifiable risk factors for stroke, heart failure, ischemic heart disease and renal dysfunction. Over the past century, salt and its linkage to HTN and cardiovascular (CV) mortality has been the subject of intense scientific scrutiny. There is now consensus that different individuals have different susceptibilities to blood pressure (BP)-raising effects of salt and this susceptiveness is called as salt sensitivity. Several renal and extra-renal mechanisms are believed to play a role. Blunted activity of the renin–angiotensin–aldosterone system (RAAS), adrenal Rac1-MR-Sgk1-NCC/ENaC pathway, renal SNS-GR-WNK4-NCC pathway, defect of membrane ion transportation, inflammation and abnormalities of Na+/Ca2+ exchange have all been implicated as pathophysiological basis for salt sensitive HTN. While salt restriction is definitely beneficial recent observation suggests that treatment with Azilsartan may improve salt sensitivity by selectively reducing renal proximal tubule Na+/H+ exchange. This encourages the future potential benefits of recognizing and therapeutically addressing the salt sensitive phenotype in humans. Keywords: Hypertension, Salt sensitivity, Patho-physiological mechanisms, Azilsartan

Neuropathic pain (NeP) constitutes a major pain-related disorder, which is often underdiagnosed and undertreated. Adverse physical, psychological, and economic consequences associated with NeP lead to poor quality of life. Burden of NeP in developing countries like India is colossal. Various international guidelines provide effective approaches to diagnose and manage NeP. However, differences in the genetic makeup of Indian population can result in subtle differences in clinical response, considering their low body weight, drug metabolism ability, and pain perception. Similarly, treatment-related adverse effects may also vary. Practice of Indian physicians may also differ for choice of drugs based on their availability and affordability. In the absence of country-specific guidelines, this document could serve as a guiding tool for health-care providers, ensuring uniformity in the treatment of NeP. Thus, applicability of all recommendations from any of these guidelines in Indian setting demands careful evaluation. Clinical experience of Indian physicians suggests that there are lot many challenges (e.g., busy outpatient departments, nonavailability of screening questionnaires in regional languages, and availability and affordability of medications) faced by them when managing NeP. In addition, in India, there are no country-specific guidelines that would help them to address these challenges. The objective for this consensus was to develop an expert opinion guideline to harmonize the management of NeP in India. The expert panel consisted of experts from various specialties such as pain medicine, anesthesiology, diabetology, neurology, and orthopedics. The panel critically reviewed the existing literature evidence and guideline recommendations to provide India-specific consensus on the management of NeP. The final consensus document was reviewed and approved by all the experts. This expert opinion consensus will help health-care professionals as a guiding tool for effective management of NeP in India. Use of Douleur Neuropathique 4 (DN4) questionnaire for NeP screening should be routine in day-to-day clinical practice. For effective utilization of DN4 questionnaire, it should be converted to regional language. If DN4 questionnaire screening fails to identify NeP, it should not be disregarded and should not replace the sound clinical judgment from the treating physician. Diagnostic tests may be considered as a supplement to clinical judgment. Cost-effective treatment should be the initial choice. Dosing should be individualized based on efficacy and tolerability. Tricyclic antidepressants (TCAs), gabapentinoids, and serotonin-norepinephrine reuptake inhibitors (SNRIs) can be considered among initial choices. Tramadol can be considered as a second-line add-on treatment for NeP if there is partial response to the first-line agent either alone or in combination. Fixed-dose combination (FDC) of gabapentinoids such as pregabalin (75 mg) with TCA such as nortriptyline (10 mg) is synergistic and improves treatment adherence. Among other treatments, Vitamin B12 (methylcobalamin) can be used either alone or in combination for the management of NeP. Use of Vitamin D and steroids should be limited to specific NeP in individual cases. Referral to pain specialists can be considered if two drugs fail to provide relief in NeP.

Introduction: Iron administration especially intravenous iron therapy is associated with improvements in exercise capacity and quality of life in patients with chronic heart failure (CHF). Our aim was to assess effect of ferric carboxymaltose (FCM) on hospitalization and mortality outcomes in CHF. Materials and methods: A literature search across PUBMED, Google Scholar and trials database www.clinicaltrials.gov was conducted to search for randomized controlled trials (till August 2016) comparing FCM to placebo in CHF with or without anaemia. Published human studies in English language which reported data on mortality and hospitalization rates were included. Primary outcome was rates of HF hospitalizations and secondary outcomes were hospitalization due to any cardiovascular (CV) cause, death due to worsening HF and any CV death. Results: From 17 studies identified, two were included in final analysis (n = 760; 455 in FCM and 305 in placebo arms). We observed significantly lower rates of hospitalization for worsening HF in FCM arm [Risk Ratio (RR) 0.34, 95% confidence interval (CI) 0.19, 0.59, p = 0.0001] as well as for any CV hospitalizations [RR 0.49, 95% CI 0.35, 0.70; p 0.05). No significant treatment effect with FCM was noted in mortality from worsening HF (RR 0.41, 95% CI 0.02, 7.36; p = 0.55) or any CV death (RR 0.80, 95% CI 0.40, 1.57; p = 0.51). Conclusion: FCM reduces hospitalization rates in CHF but may not reduce mortality outcome. This finding needs further evaluation in a large, prospective, randomized controlled trial.

Staphylococcus aureus is the most common pathogen causing bone and joint infections (BJI). In India, prevalence of Methicillin resistant Staphylococcus aureus (MRSA) is increasing at an alarming rate and emerged as an important contributor towards the difficult to treat BJI. Currently available anti-MRSA agents have their own limitations with regards to reduced susceptibility as well as safety and tolerability. Furthermore, biofilms over the prosthesis with invariably multi-drug resistant strains leads to complex treatment processes. This necessitates the need to develop and screen new antibiotics against MRSA that can easily penetrate the deep pockets of infection and take care of the challenges discussed. This review aims to discuss on MRSA infection in bone and joint infection, current antibiotic regimen, its associated limitations, and finally, the need to develop new antibiotic therapy for effective management of patients with BJI.

Introduction: Angiotensin receptor blockers (ARBs) are emerging as an attractive first choice antihypertensive as recommended by various guidelines. However, choice among the first-line antihypertensive classes and among ARBs differs between practicing physicians. Aims: This survey aimed to understand the usage preferences of ARBs and its place in for treating hypertension (HTN) among physicians from various clinical settings in India. Methods: A cross-sectional survey was conducted with a prevalidated survey questionnaire consisting of 25 questions for HTN management. Practicing general physicians and cardiologists were approached for seeking their perception, opinions, and prescribing behavior. Results: Responses of 594 physicians and cardiologists were received. As opined by 90.1% of physicians, newly diagnosed HTN represented more than 10% of their overall patient load. As a monotherapy, 59.9% of the physicians preferred ARB as the first choice in newly diagnosed HTN patients, followed by calcium channel blocker (12.3%) and angiotensin-converting-enzyme inhibitor (8.1%). Of all ARBs, telmisartan is preferred by 73% of physicians. Most physicians prefer telmisartan among all ARBs for 24 h blood pressure (BP) control, including morning BP surge (76.4%) and for prevention of cardiovascular morbidity and mortality (78.8%) followed by olmesartan and losartan. Predominantly, majority of physicians (89.1%) agreed for the beneficial role of telmisartan in preventing onset of microalbuminuria and nephropathy. Conclusion: Indian physicians prefer ARBs as the first choice in most hypertensive patients, which shows agreement with the guideline recommendations followed globally. Telmisartan has emerged as the most preferred ARB among all, for most of the HTN patients including those with comorbidities.

Acne vulgaris is one of the most common chronic inflammatory skin disorders among adolescents and young adults. It is associated with substantial morbidity and, rarely, with mortality. The exact worldwide incidence and prevalence are currently unknown. Current challenges involve improving understanding of the underlying pathophysiology of acne vulgaris and developing a practical treatment consensus. Expert panel discussions were held in 2013 and 2014 among a group of scientists and clinicians from the Omani and United Arab Emirate Dermatology Societies to ascertain the current optimal management of acne vulgaris, identify clinically relevant end-points and construct suitable methodology for future clinical trial designs. This article reviews the discussions of these sessions and recent literature on this topic.

The emerging antimicrobial resistance leading to gram-positive infections (GPIs) is one of the major public health threats worldwide. GPIs caused by multidrug resistant bacteria can result in increased morbidity and mortality rates along with escalated treatment cost and hospitalisation stay. In India, GPIs, particularly methicillin-resistant Staphylococcus aureus (MRSA) prevalence among invasive S. aureus isolates, have been reported to increase exponentially from 29% in 2009 to 47% in 2014. Apart from MRSA, rising prevalence of vancomycin-resistant enterococci (VRE), which ranges from 1 to 9% in India, has raised concerns. Moreover, the overall mortality rate among patients with multidrug resistant GPIs in India is reported to be 10.8% and in ICU settings, the mortality rate is as high as 16%. Another challenge is the spectrum of adverse effects related to the safety and tolerability profile of the currently available drugs used against GPIs which further makes the management and treatment of these multidrug resistant organisms a complex task. Judicious prescription of antimicrobial agents, implementation of antibiotic stewardship programmes, and antibiotic policies in hospitals are essential to reduce the problem of drug-resistant infections in India. The most important step is development of newer antimicrobial agents with novel mechanisms of action and favourable pharmacokinetic profile. This review provides a synopsis about the current burden, treatment options, and the challenges faced by the clinicians in the management of GPIs such as MRSA, Quinolone-resistant Staphylococcus, VRE, and drug-resistant pneumococcus in India.

Urothelial carcinoma is a common malignancy that carries a poor prognosis when the disease includes muscle invasion. Metastatic urothelial carcinoma is almost uniformly fatal. The evidence behind treatment options in the neoadjuvant, adjuvant and metastatic settings are discussed in this manuscript, with a focused review of standard and investigational cytotoxic, targeted, and immunotherapy approaches. We have focused especially on neoadjuvant cisplatin-based therapy (supported by level one evidence) and on novel immunotherapy agents such as checkpoint inhibitors, which have shown great promise in early clinical studies.

Objective: To assess the short term safety and tolerability of a fixed dose combination (FDC) of olmesartan, amlodipine and hydrochlorothiazide (OAH) in real-world clinical setting in India. Materials and Methods: Physicians were requested to provide eight weeks observational clinical event data of the patients prescribed with FDC of Olmesartan (20/40mg), Amlodipine (5mg) and hydrochlorothiazide (12.5mg) in the prescription event monitoring (PEM) forms. Data on patients’ demographics, indication for FDC, concomitant medication and other relevant history was also collected and was analysed with descriptive statistics. Results: Two hundred thirty eight physicians provided data of 4763 patients. Mean age of the population was 55±7 years and males were 59.3%. The commonest indication for the FDC was uncontrolled hypertension (60.7%). Diabetes and dyslipidemia were present in 37.9% and 35.1% respectively. Concomitant medications included statins (42.3%), oral anti-diabetic (33.7%) and antiplatelet agents (24.7%). Pedal oedema (0.29%) was the most common adverse event (AE) reported followed by headache (0.16%), giddiness (0.15%), light headedness (0.15) and stroke (0.15%). Other less common (0.04%) reported AEs were tiredness, dizziness, gastritis, hypersomnia, hypoglycaemia, lower respiratory tract infection (LRTI), weakness, diarrhea, labyrinthitis, urinary tract infection, hyponatremia and hypotension. Occurrence of AEs was more common in patients with uncontrolled hypertension (60.74%). Conclusion: The FDC of olmesartan, amlodipine and hydrochlorothiazide prescribed most frequently for patients with uncontrolled hypertension and co-morbidities was found to be safe and well tolerated over a short period of observation.