ABSTRACT
Background: The fact that about 90 % of newly discovered API’s or new molecular entity(NME) have little or no aqueous solubility, causes a significant protest to the initialization of development and their scale up of dosage form in the Pharma Industry. Aqueous solubility of API’s has critical role in drug dissolution or availability of drug at the site of action or bioavailability, when a dosage form is administered orally.Objective: The object of this study is to formulate a modified release tablet dosage form of a poorly aqueous soluble drug, which not only have higher aqueous solubility or bioavailability but also have sustained release characteristics with high mechanical strength &their commercial viability. Numerous techniques are available for the solubility enhancement but all individual techniques have its own limitations for commercialization.Method: Aqueous solubility of drugs is improved by the known Solubility enhancement techniques like Micronization &Solid dispersions. After successful solubility enhancement, sustained release or modified release tablets of poorly aqueous soluble drug can be easily formulated into a suitable shape or size by using a known Polymer Matrix Sintering Technology with commercial feasibility. Micronization of poorly water-soluble drugs can be performed by Air Jet Mill or Ball Mill. Whereas Solid dispersion technique involves, molecular dispersion of poorly soluble drug in a suitable inert carrier, to form an amorphous and highly soluble compounds. Sintering Technology is defined as the bonding of adjacent particle surfaces in a mass of powder, or in compact, by the application of heat. Conventional sintering technique involves the heating of compact at a temperature below the melting point of the solid constituents in a controlled environment under atmospheric pressure.Results: Enhanced solubility of poorly soluble API’s by these proposed techniques is due to either conversion of crystalline compound in to amorphous form or reduction of particle size to its molecular level by the application of Micronization or solid dispersion techniques. The developed modified release tablets will show a sustained release characteristic due to Sintering aspect and provides enhanced solubility of BCS class II or IV drugs.Conclusion: Novel modified release tablets have been designed through consolidation of Solubility enhancement and Polymer Matrix Sintering technologies. Simultaneous exploitation of well-known and established approaches- Micronization (optimum particle size reduction) or solid dispersion, optional surfactant and Polymer Matrix Sintering Technique in the recent concept, produces significant enhancement of solubility of poorly water soluble API’s without compromising the content uniformity of dosage form and also provide a modified or sustained release characteristics with high mechanical strength. The release profile of drug can be easily tailored by using combination of both techniques where challenges of low solubility are prominent.
ABSTRACT
Purpose: To evaluate the outcomes of transepithelial corneal collagen crosslinking (CXL) for management of corneal ectasia after laser?assisted in situ keratomileusis (LASIK). Methods: CXL was performed on 18 eyes of 16 patients either with LASIK flap lift (n = 9; 365 nm, 30 mW/cm2, 4 minutes, pulse) or with transepithelial flap?on (n = 9 eyes; 365 nm, 3 mW/cm2, 30 minutes) technique. Postoperative change in maximum keratometry (Kmax), anterior elevation, posterior elevation, spherical equivalent (SE), logMAR uncorrected distance visual acuity (UDVA), aberrations, and central corneal thickness (CCT) were evaluated at 12 months postoperatively. Results: A total of 18 eyes of 16 patients (11 males, 5 females) were included. Overall, Kmax flattened more after flap?on CXL (P = 0.014) compared to flap?lift CXL. The endothelial cell density and posterior elevation were stable throughout the follow?up period. Index of vertical asymmetry (IVA), keratoconus index (KI), and central keratoconus index (CKI) decreased after flap?on CXL at 12 months, postoperatively (P < 0.05), whereas there were no statistically significant changes in these parameters after flap?off CXL group. The spherical aberrations and total root mean square decreased after flap?lift CXL at 12 months, postoperatively (P < 0.05). Conclusion: In our study, transepithelial collagen crosslinking was successfully used to halt disease progression in post?LASIK keratectasia. We recommend flap?on surgical technique for these cases
ABSTRACT
The goal of the current study is to develop and validate a new chromatographic method for Fosfomycin Trometamol's determination in both pure form and pharmaceutical formulation. In the present study, a pre chromatographic derivatization of Fosfomycin Trometamol was done by forming an ion-pair complex of Heterocyclic nitrogen using the acidic dye methyl orange and phthalate buffer of pH-6. The yellow ion-pair complex was extracted with chloroform and it was further extracted with aqueous solution of 0.01M HCL. The ion-pair complex of Fosfomycin Trometamol and methyl orange obeyed Beer's law in the range of 30 -70 ?g/ml with a correlation coefficient (r2) of 0.9946. A Liquid chromatography system equipped with an Agilent ACE C18 column (250 X 4.6mm, 5?m) was used as a stationary phase in this work. The developed method was validated according to ICH guidelines. For determining the medication in bulk and formulation, the devised approach was proven to be accurate, sensitive, and repeatable
ABSTRACT
Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ?-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).
ABSTRACT
Acanthamoeba keratitis (AK) is an intractable infection of the cornea. Penetrating keratoplasty is widely used for the management of severe AK but suffers from complications like graft rejection, endophthalmitis, and glaucoma. Herein, we aimed to describe the surgical technique and the results of elliptical deep anterior lamellar keratoplasty (eDALK) for the management of severe AK. In this retrospective case series, records of consecutive patients with AK poorly responsive to medical treatment who underwent eDALK from January 2012 to May 2020 were reviewed. The largest diameter of infiltration was ?8 mm and did not involve the endothelium. The recipient bed was made by an elliptical trephine, and big bubble or wet-peeling technique was performed. Postoperative best spectacle-corrected visual acuity, endothelial cell density, corneal topographic data, and complications were evaluated. Thirteen eyes of thirteen patients (eight men and five women, 45.54 ± 11.78 years old) were included in this study. The mean follow-up interval was 21.31 ± 19.59 months (range, 12–82 months). At the last follow-up, the mean best spectacle-corrected visual acuity was 0.35 ± 0.27 logarithm of the minimum angle of resolution. The mean refractive and topographic astigmatism were ? 3.21 ± 1.77 and 3.08 ± 1.14 D, respectively. Intraoperative perforation was encountered in one case and double anterior chambers occurred in two cases. One graft developed stromal rejection and one eye developed amoebic recurrence. eDALK can serve as the first-line surgical management of severe AK poorly responsive to medical treatment.
ABSTRACT
Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.
ABSTRACT
ABSTRACT Introduction: The Impella ventricular support system is a device that can be inserted percutaneously or directly across the aortic valve to unload the left ventricle. The purpose of this study is to determine the role of Impella devices in patients with acute cardiogenic shock in the perioperative period of cardiac surgery. Methods: A retrospective single-surgeon review of 11 consecutive patients who underwent placement of Impella devices in the perioperative period of cardiac surgery was performed. Patient records were evaluated for demographics, indications for placement, and postoperative outcomes. Results: Impella devices were placed for refractory cardiogenic shock preoperatively in 6 patients, intraoperatively in 4 patients, and postoperatively as a rescue in 1 patient. Seven patients received Impella CP, 1 Impella RP, 1 Impella CP and RP, and 2 Impella 5.0. Additionally, 3 patients required preoperative venovenous extracorporeal membrane oxygenation (VV-ECMO), and 1 patient required intraoperative venoarterial extracorporeal membrane oxygenation (VA-ECMO). All Impella devices were removed 1 to 28 days after implantation. Length of stay in the intensive care unit stay ranged from 2 to 53 days (average 23.9±14.6). The 30-day and 1-year mortality were 0%. Ten of 11 patients were alive at 2 years. Also, 1 patient died 18 months after surgery from complications of coronavirus disease (Covid-19). Device-related complications included varying degrees> of hemolysis in 8 patients (73%) and device malfunction in 1 patient (9%). Conclusions: The Impella ventricular support system can be combined with other mechanical support devices for additional hemodynamic support. All patients demonstrated myocardial recovery with no deaths in the perioperative period and in 1-year of follow-up. Larger studies are necessary to validate these findings.
ABSTRACT
Purpose: To evaluate the efficacy of liposomal amphotericin B (L?AMB) for the treatment of fungal keratitis. Methods: Patients with fungal keratitis confirmed by potassium hydroxide (KOH) smear and/ or confocal microscopy were administered topical L?AMB and randomized into three groups treated with three different formulations. The medication was administered two hourly till clinical improvement was achieved, followed by six hourly till complete resolution. The outcome measures were time to clinical improvement, resolution of epithelial defect, stromal infiltrate, hypopyon, extent and density of corneal opacity, neovascularization, and best corrected visual acuity (BCVA) at 3 months. Results: Mean age of the patients was 46.6 ± 14.8 years, and trauma with vegetative matter was the most common predisposing factor. Aspergillus flavus (36%) was the most common fungus cultured, followed by Fusarium (23%). Mean time to clinical improvement, time to resolution of epithelial defect, mean time to resolution of infiltrate, and time to resolution of hypopyon were 3.45 ± 1.38, 25.35 ± 8.46, 37.97 ± 9.94, and 13.33 ± 4.90 days, respectively, and they were comparable among the three groups. There was a significant difference between treatment failure and success cases in terms of days of presentation (P < 0.01), size of the epithelial defect (P?value 0.04), and infiltrate size at presentation (P?value 0.04). At 3 months follow?up, no statistically significant difference was noted in BCVA and mean scar size among groups. Conclusion: L?AMB in a gel form is an effective antifungal agent that promotes the healing of fungal ulcers with notably least vascularization and better tolerance.
ABSTRACT
Background: Although well known in clinical practice, research in lichen planus pigmentosus and related dermal pigmentary diseases is restricted due to lack of consensus on nomenclature and disease definition. Aims and Objectives: Delphi exercise to define and categorise acquired dermal pigmentary diseases. Methods: Core areas were identified including disease definition, etiopathogenesis, risk factors, clinical features, diagnostic methods, treatment modalities and outcome measures. The Delphi exercise was conducted in three rounds. Results: Sixteen researchers representing 12 different universities across India and Australia agreed to be part of this Delphi exercise. At the end of three rounds, a consensus of >80% was reached on usage of the umbrella term ‘acquired dermal macular hyperpigmentation’. It was agreed that there were minimal differences, if any, among the disorders previously defined as ashy dermatosis, erythema dyschromicum perstans, Riehl’s melanosis and pigmented contact dermatitis. It was also agreed that lichen planus pigmentosus, erythema dyschromicum perstans and ashy dermatosis did not differ significantly apart from the sites of involvement, as historically described in the literature. Exposure to hair colours, sunlight and cosmetics was associated with these disorders in a significant proportion of patients. Participants agreed that both histopathology and dermatoscopy could diagnose dermal pigmentation characteristic of acquired dermal macular hyperpigmentation but could not differentiate the individual entities of ashy dermatosis, erythema dyschromicum perstans, Riehl’s melanosis, lichen planus pigmentosus and pigmented contact dermatitis. Limitations: A wider consensus involving representatives from East Asian, European and Latin American countries is required. Conclusion: Acquired dermal macular hyperpigmentation could be an appropriate conglomerate terminology for acquired dermatoses characterised by idiopathic or multifactorial non-inflammatory macular dermal hyperpigmentation
ABSTRACT
Middle aged women presented with non-healing ulcer over foot following trivial injury. She was not having any comorbid condition. Investigations revealed APLA Syndrome with triple antibodies positive (Lupus anticoagulant, Anticardiolipin antibody and anti B2-glycoprotein antibodies). Patient responded well with anti-platelet and skin grafting at local site.
ABSTRACT
Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril–Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril–Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril–Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril–Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40–50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.
ABSTRACT
Introduction : The medical personnel especially have to deal with both the Biological and Psychological consequences originating from the influence of virus. Emergency Care Units equipped with ambulance service always should be at the fore front to face all emerging untoward incidents. Ambulance Drivers often disregard their physical health and mental stress in order to fulfil the duties entrusted on them. Methodology : Cross-sectional questionnaire based on-line survey was conducted. Ambulance drivers were North and South India were taken as study subjects. Knowledge based questions and mental stress were assessed using Perceived Stress level Scale (PSS). The questionnaires were translated toTamil, Kannada, Telugu, Malayalam and Hindi languages. Chi-square test was done to find the association between variables. Results : Among the 101 respondents, 84.2% were having good knowledge about the pandemic. Statistically significant association between number of patients transported per day and the knowledge levels of Ambulance drivers was found (p =0.048)(Chi-square value=15.65). Drivers in Government sector were having more knowledge compared to private sector (p =0.038)(Chi square value=6.53). The perceived mental stress was found to increase with a greater number of patients being transported per day, which was statistically significant (p =0.001)(Chi-square value= 30.42). Conclusion : Knowledge regarding COVID-19 virus was adequate among the Ambulance Drivers. Knowledge was found to be more among drivers who work in Government medical establishments. Mental stress was more among drivers who transported more than 5 patients per day.
ABSTRACT
An undifferentiated carcinoma (UC) of the gall bladder behaves aggressively and has a grave prognosis. Small cell type undifferentiated carcinoma of the gall bladder is a rare variant. This paper reports a case of UC of gall bladder with PAS-positive diastase-resistant eosinophilic hyaline globules present as liver mass (on imaging) in a male patient. The microscopic findings of the liver and gall bladder after a right tri-segmentectomy showed an un-differentiated malignant neoplasm composed of cells with round to oval nuclei, prominent nucleoli, and scanty neoplasm. No definite cell pattern was identified with these neoplastic cells. A section from the gall bladder revealed a tumor arising from the lining epithelium and infiltrating through the muscularis. This tumor was infiltrating the adherent liver tissue directly and forming a mass of undifferentiated malignant cells. The focal area within the tumor mass showed the presence of PAS-positive, diastase-resistant, eosinophilic hyaline globules within the neoplastic cells. The immunohistochemistry test was diffusely positive for perinuclear anti-neutrophil cytoplasmic antibodies and negative for chromogranin, vimentin, Desmin, alpha-fetoprotein, leukocyte common antigen, CD34, and bcl2. When the clinical and radiological data are inconclusive, careful analysis of the histological and immunophenotypic features is needed to make the final diagnosis of UC of the gall bladder. The biological behavior and prognosis of this tumor remain unclear because of its rarity. Further studies will be needed to understand the characteristics of this deadly tumor and to establish an effective therapy for it.
ABSTRACT
Background@#Lateral epicondylitis is an increasingly debilitating condition in working population. Evidence for conservative treatment modalities has been inconclusive. Percutaneous pie crusting of the common extensor origin at the lateral epicondyle at the time of local corticosteroid injection (CSI) has been proposed sparsely. The objective of this study was to analyze if concomitant CSI and pie-crusting of the common extensor origin provides better outcome than CSI alone in lateral epicondylitis. @*Methods@#This case-control study on 236 patients was conducted at a single center between January 1, 2020, and May 31, 2022. Patients were divided into two groups (n=118 each) based on their preference. Group A underwent CSI alone and group B underwent pie crusting along with CSI. The clinical and functional outcomes of all patients were evaluated at 2,4,6, and 12-week post-procedure using the visual analog scale (VAS) and Nirschl score. The mean time for return to daily activities was also compared. @*Results@#Both groups showed significant improvement in post-procedure outcome at successive follow-ups on intragroup longitudinal analysis (VAS: F=558.384 vs. 1,529.618, Nirschl: F=791.468 vs. 1,284.951). On intergroup analysis, VAS of group B was superior to that of group A; however, it was statistically significant (P<0.05) only from the 6-week follow-up onwards. Nirschl score of group B was significantly better throughout the period of follow-up (P<0.05). Group B returned to daily activities faster than Group A (6.2±0.44 weeks vs. 7.18±0.76 weeks). @*Conclusions@#Concomitant pie crusting with CSI is recommended for lateral epicondylitis as it provides significantly better results than CSI alone.
ABSTRACT
Methods@#The study included 60 patients graded American Society of Anesthesiologists I and II and scheduled for thoracolumbar spine surgery involving >3 vertebral levels. The patients were divided into two groups: group KD (ketodex) and group F (fentanyl). The primary objective was to compare the postoperative analgesic requirements among the groups. The secondary objectives included a comparison of the intraoperative anesthetic requirements, postoperative pain scores, hemodynamic parameters, side effects of the study drugs, and the duration of post-anesthesia care unit stay of both the groups. @*Results@#Ketodex use prolonged the mean time to first rescue analgesia (22.00±2.30 hours vs. 11.69±3.02 hours, p 0.05). The postoperative pain scores were significantly lower in the group KD than in group F at most timepoints (p 3 vertebral levels to achieve prolonged analgesia without any opioidrelated side effects.
ABSTRACT
Posterior methods for cervical myelopathy include laminoplasty and laminectomy with/without fusion. A more recent innovation in these treatments is the use of an ultrasonic bone shaver for osteotomy. In this study, we examined the perioperative results after laminectomy/laminoplasty between conventional methods (rongeur/high-speed drill) vs. piezosurgery-based instruments. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed and the search was performed on four databases (PubMed, Scopus, EMBASE, and Google Scholar). Seven comparative studies were chosen after thorough screening by the authors and a meta-analysis was performed between piezosurgery and conventional technique to ascertain intraoperative and postoperative results after laminectomy/laminoplasty. The analysis includes four retrospective cohort studies and three randomized controlled trials published between 2015 and 2022. The mean age ranged from 55.5 to 64.2 years. Blood loss was significantly reduced in the piezosurgery group, other findings were not significant. On subgroup analysis, laminoplasty dramatically reduced blood loss and the rate of iatrogenic dural rips in the piezosurgery group. The use of ultrasonic bone shaver for osteotomy in cervical spondylotic myelopathy is related to significantly decreased blood loss and no significant increase in postoperative drainage, operative time, complication rate, and functional outcomes as compared to traditional techniques. We noticed significantly reduced blood and rate of dural tears in the laminoplasty subgroup with the use of ultrasonic bone shaver, which was not mirrored in the laminectomy subgroup. Careful intraoperative handling of the instrument can help prevent iatrogenic dural tears and nerve damage.
ABSTRACT
This study was designed to systematically review and meta-analyze the functional and radiological outcomes between lateral and posterior approaches in adult degenerative scoliosis (ADS). Both lateral (lumbar, extreme, and oblique) and posterior interbody fusion (posterior lumbar and transforaminal) are used for deformity correction in patients with ADS with unclear comparison in this cohort of patients in the existing literature. A literature search using three electronic databases was performed to identify studies that reported outcomes of lateral (group L) and posterior interbody fusion (group P) in patients with ADS with curves of 10°–40°. Group P was further subdivided into minimally invasive surgery (MIS-P) and open posterior (Op-P) subgroups. Data on functional, radiological, and operative outcomes, length of hospital stay (LOHS), fusion rates, and complications were extracted and meta-analyzed using the random-effects model. A total of 18 studies (732 patients) met the inclusion criteria. No significant difference was found in functional and radiological outcomes between the two groups on data pooling. Total operative time in the MIS-P subgroup was less than that of group L (233.86 minutes vs. 401 minutes, p <0.05). The total blood loss in group L was less than that in the Op-P subgroup(477 mL vs. 1,325.6 mL, p <0.05). Group L had significantly less LOHS than the Op-P subgroup (4.15 days vs. 13.5 days, p <0.05). No significant difference was seen in fusion rates, but complications were seen except for transient sensorimotor weakness (group L: 24.3%, group P: 5.6%; p <0.05). Complications, such as postoperative thigh pain (7.7%), visceral injuries (2%), and retrograde ejaculation (3.7%), were seen only in group L while adjacent segment degeneration was seen only in group P (8.6%). Lateral approach has an advantage in blood loss and LOHS over the Op-P subgroup. The MIS-P subgroup has less operative time than group L, but with comparable blood loss and LOHS. No significant difference was found in functional, radiological, fusion rates, pseudoarthrosis, and complications, except for transient sensorimotor deficits. Few complications were approach-specific in each group.
ABSTRACT
Background: Genetic polymorphism in MMPs are associated with multiple adverse CV events. There is little evidence regarding role of MMPs and their genetic polymorphisms in young (<50 years) STsegment elevation myocardial infarction (STEMI) patients. Methods: This study included 100 young (18e50 years) STEMI patients and 100 healthy controls. Serum levels of MMP-3, MMP-9 and TIMP were estimated for both patients as well as controls. Additionally, genetic polymorphisms in the MMP-9 gene (_x0001_1562 C/T and R279Q) & MMP-3 gene (5A/6A-1612) was evaluated. All these patients were followed up for one year and major adverse cardiac events (MACE) were determined. Results: Serum levels of MMP-3 (128.16 ± 115.81 vs 102.3 ± 57.28 ng/mL; P ¼ 0.04), MMP-9 (469.63 ± 238.4 vs 188.88 ± 94.08 pg/mL; P < 0.0001) and TIMP (5.84 ± 1.93 vs 2.28 ± 1.42 ng/mL; P < 0.0001) were significantly higher in patients as compared to controls. Additionally, patients with genetic polymorphisms in the MMP genes (5A/5A, 6A/6A and the AG genotypes) had an increased risk of STEMI. Patients with MACE had significantly higher levels of MMP-9 (581.73 ± 260.93 vs 438.01 ± 223.38 pg/mL; P ¼ 0.012). A cutoff value of 375.5 pg/mL of MMP-9 was best able to discriminate patients with STEMI and MACE with sensitivity of 77.3% and specificity of 57%. Conclusion: Novel biomarkers such as MMP-3, MMP-9 and TIMP and their genetic polymorphism are associated with the susceptibility for STEMI in young individuals. Higher MMP-9 levels in STEMI patients with MACE suggests its potential role in predicting cardiac remodeling and left ventricular dysfunction