Evaluating the Efficacy, Safety, and Tolerability of Combination Therapy of Dapagliflozin and Linagliptin Over Dapagliflozin and Vildagliptin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin.

Background Type 2 diabetes mellitus (T2DM) patients commonly undergo metformin monotherapy. This study aims to compare the efficacy, safety, and tolerability of combination therapy of dapagliflozin plus linagliptin versus dapagliflozin plus vildagliptin as add-on therapy in T2DM patients inadequately controlled on metformin. Methodology This was an 18-week, multicenter, randomized, double-blind, active-controlled, parallel-group, phase III clinical study. About 236 participants were randomly assigned to receive either a fixed-dose combination of dapagliflozin 10 mg plus linagliptin 5 mg tablets or a fixed-dose combination of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets added to metformin monotherapy. The primary outcome was the mean change in hemoglobin A1c (HbA1c) from baseline to the end of week 16. The key secondary endpoints were mean change in postprandial blood glucose (PPBG), fasting blood glucose (FBG), body weight, and the proportion of participants achieving HbA1c less than 7.0%. Results The dapagliflozin/linagliptin combination therapy showed a more significant change in HbA1c from baseline to the end of 16 weeks (mean reduction: -1.59% vs. -1.25%) compared to dapagliflozin/vildagliptin (p < 0.0001). Additionally, compared to the dapagliflozin/vildagliptin group, the dapagliflozin/linagliptin group demonstrated a significant reduction in both PPBG (mean reduction: -59.99 mg/dL vs. -55.34 mg/dL) and FPG (mean reduction: -32.91 mg/dL vs. -26.78 mg/dL). A total of 18 adverse events were reported in 17 (7.20%) participants, all of which were mild and resolved completely. There were no serious adverse events. Conclusions Compared to dapagliflozin and vildagliptin combination therapy, dapagliflozin and linagliptin fixed-dose combination provided clinically significant improvements in glycemic control. Because of its effectiveness, safety, and tolerability, the fixed-dose combination of dapagliflozin and linagliptin was a better option for treating T2DM patients who had previously only received metformin monotherapy.

Study of Characteristics of COVID-19 Patients with Fatal Outcome during Wave-2 from a Tertiary Care Center in Western India.

BACKGROUND: A large surge of intensive care unit (ICU) admissions leading to mortal outcome was observed in wave-2 of coronavirus disease 2019 (COVID-19) due to the higher virulence of the Delta variant of the COVID-19 virus, which led to the scarcity of resources in hospitals. This study was done to observe the clinical characteristics of COVID-19 patients with fatal outcomeMaterials and methods: We conducted a retrospective cross-sectional study in adults with COVID-19 pneumonia having fatal outcome during wave-2 of COVID-19, and their clinical characteristics were studiedResults: Out of 136 patients included in the study, the most common risk factors leading to adverse outcome were in the male gender, age (middle and elderly), with hypertension and diabetes mellitus (DM) as predominant comorbidities, early onset dyspnea, high C-reactive protein (CRP), high neutrophil to lymphocyte ratio (NLR), high D-dimer, bilateral lower zone involvement of lungs in chest X-ray (CXR), and development of acute kidney injury (AKI)Conclusion: The characteristics of the severely ill COVID-19 patients highlighted in the study could help clinicians in the early identification and management of high-risk patients. This study would help with resource planning and preparation for further COVID-19 waves and future pandemics.

Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity.

Purpose: To evaluate the efficacy of a biosimilar ranibizumab (Razumab) on outcomes of retinopathy of prematurity (ROP) for the first time. Methods: This retrospective study included infants presenting with stage 3+ ROP either in zone 1 or zone 2 posterior or aggressive posterior ROP (APROP). All eligible infants received intravitreal razumab (0.25 mg/0.025 ml) monotherapy. Follow-up was continued monthly till complete retinal vascularization was achieved while retreatment with razumab was given when recurrent neovascularization was noted. In case of no recurrence but incomplete vascularization, laser photocoagulation was done to the residual avascular retina. Results: We included 118 eyes of 59 infants with a median gestational age of 30 weeks and median birth weight of 1250 grams. At presentation, APROP was found in 28 eyes (24%) of 14 babies while stage 3 disease was seen in zone 1 in another 28 eyes (24%) and the remaining 62 eyes (52%) had stage 3 ROP in zone 2 posterior region. Complete resolution of ROP along with complete vascularization was seen in 22 eyes (19%) at a median of 55 days (IQR = 31-56 days) and 42 eyes (35%) showed a recurrent neovascularization at a median of 51 days post razumab (IQR = 42-55 days). The cumulative incidence of recurrence of neovascularization (21%, 95% CI = 14%-29%) peaked at seven weeks and was significantly higher in eyes with APROP (43%, 95% CI = 27%-63%) compared to eyes without APROP (13.4%, 95%CI, 8%-22%) (P < 0.001). Conclusion: Razumab appears to be safe and effective in treating ROP, with about a third requiring reinjection at seven weeks after the first dose.

Hearing Impairment in Stroke Patients- Findings from a Pilot Study Conducted in India.

Auditory processing difficulties and hearing loss have been reported among stroke survivors, but is largely neglected. Post-stroke hearing impairment may affect communication between stroke survivors and healthcare professionals, thereby restricting rehabilitation and long-term patient outcome. In this prospective pilot study, we sought to determine the prevalence and pattern of hearing loss in stroke patients when compared to age and sex matched controls. 50 consecutive patients with first-ever stroke, both hemorrhagic and ischemic, and a comparison cohort of 50 age and sex matched controls were assessed. Pure Tone Audiogram was performed in all patients within 15 days of stroke onset and mean hearing loss was determined. Mean audiometric threshold was significantly higher in both ears in stroke patients (mean 44.0 ± 12.1 dB) when compared to the control subjects (36.1 ± 11.4 dB; p = 0.001). After adjusting for Diabetes mellitus and hypertension, sensorineural hearing loss was more common and severe in stroke compared to controls (p < 0.005). Most of the strokes were ischemic and involved middle cerebral artery territory. A modest correlation between hearing threshold and stroke severity in both ears was seen (mean B 0.775, R2 0.54, CI 0.122-1.427, p = 0.020). Our pilot study shows significant hearing impairment in patients with stroke, compared to age and sex matched controls with similar prevalence of cardiovascular risk factors, interestingly seen in a predominantly anterior circulation stroke population. Undetected hearing loss may impact post stroke functional recovery. Hence, current rehabilitation guidelines should include auditory screening in all patients of stroke for detection of hearing loss.

Rhino-orbital-cerebral mucormycosis: An epidemiological study from a tertiary care referral center in Western India.

Purpose: Rhino-orbital-cerebral mucormycosis (ROCM) is a rare opportunistic fungal infection with a fulminant course and an often fatal outcome. It can occur in immune-compromised patients such as those having uncontrolled diabetes, on long-term corticosteroid or immunosuppressive therapy, with COVID-19 infection, renal failure, AIDS, malignancy, or organ transplant. The aim of our study was to study the epidemiology of mucormycosis in COVID-19 patients and identify its risk factors. Methods: Ours was an epidemiological study wherein we gathered the demographic, clinical, histopathological, and radiological data of 458 patients of mucormycosis who presented to us between August 2020 and May 2021. Mucormycosis was defined through clinical and radiological findings or positive culture reports. Results: Out of all, 20.74% of patients did not have any past or concurrent history of COVID-19. The most common symptom of mucormycosis was orbital/facial pain (38.64%) and the most common sign was periocular/facial edema (50.74%). Mucormycosis involving the nose and sinuses (94.54%) was most common followed by rhino-orbital (45.41%) and brain involvement (10.04%). The most common risk factor for mucormycosis was diabetes [81.92%], followed by corticosteroid use [79.69%] and supplemental oxygen [48.90%]. Most of the patients received similar treatment with IV amphotericin B [88.64%] and local debridement [80.74%]. Conclusion: With the third wave of COVID-19 still lurking, a fatal fungal infection should be kept in mind in COVID-19 active as well as recovered patients, especially those who have co-morbid medical conditions such as uncontrolled diabetes and who are treated with large doses of corticosteroids.

Development and introduction of a communication skills module for postgraduate students of ophthalmology.

Purpose: Effective communication lies at the heart of a patient--doctor relationship. Communication skills (CS) teaching and assessment is not a part of the postgraduate (PG) curriculum. Lack of effective CS in current PG students' results in patient distrust and dissatisfaction, conflicts, and compromised healthcare. The regulatory authorities of medical education have recognized the need to inculcate soft skills among medical graduates, one of which is CS. The purpose of this study was to assess the need for teaching CS to ophthalmology PG students and develop and introduce a module for the same. Methods: In this prospective, interventional study done at the ophthalmology department of a tertiary hospital, a validated 8 day CS workshop was conducted for 60 PG students through interactive lectures, observations, video sessions, and role plays. Feedbacks were obtained through narratives, validated Google survey, reflections and verbal method and analyzed. Results: In the needs assessment done on 27 departmental faculties, 20 faculties found poor communication to be a major reason for patient complaints. All faculties agreed that CS should be taught to medical students. Statistically significant improvement in CS awareness was noted among students after the workshop. Lack of CS training, work burden, and language were identified as main barriers to effective communication. All the students were satisfied with the workshop and wanted it to be conducted regularly. Conclusion: This study establishes that CS training is essential to improve patient satisfaction and patient-doctor relationships. Barriers to effective CS could be identified, for which possible solutions could be found.

Immunogenicity and safety of the first indigenously developed Indian tetravalent influenza vaccine (split virion) in healthy adults ≥ 18 years of age: A randomized, multicenter, phase II / III clinical trial.

This phase II / III clinical trial was conducted to evaluate the immunogenicity and safety of the Tetravalent Influenza vaccine (Split virion) I.P. (TetIV) developed indigenously in the country for the first time by M/s Cadila Healthcare Limited, India containing two influenza A and two influenza B strains, one of each, Yamagata (B/Phuket) and Victoria (B/Brisbane) lineage and also compare it to that of an licensed seasonal Trivalent Influenza vaccine (TriIV) of Sanofi Pasteur India Private Limited, containing the two influenza A and only the Yamagata lineage (B/Phuket) strain. Three hundred and fifty subjects of either sex, aged more than 18 years of age, were randomized in a 1:1 ratio to receive either the TetIV or TriIV. Immunogenicity assessments (antibody against A/H1N1, A/H3N2, B/Phuket and B/Brisbane) were done by Haemagglutination Inhibition assay at baseline and 21 d after vaccination. Solicited (local and systemic) and unsolicited adverse events were recorded for up to 42 d following vaccination. The TetIV was found to fulfill the criteria set by the European and the US regulatory authorities and WHO guidance on the requirements of clinical data for licensure of seasonal inactivated influenza vaccines. The seroconversion rates with TetIV were 93.5% for A/H1N1, 90.0% for A/H3N2, 70.0% for B/Phuket and 82.9% for B/Brisbane strain. There was no significant difference in the seroconversion and seroprotection rates at day 21 for A/H1N1, A/H3N2 and B/Phuket in the two groups while the TetIV was superior to the TrivIV for the seroconversion and the seroprotection rate for the B/Brisbane strain (Victoria lineage). Both the vaccines were well tolerated by all the study participants; addition of the fourth strain in the TetIV did not compromise the safety as compared to TriIV. The most common systemic adverse event reported in both the groups was headache followed by fever.

Pullulan based oral thin film formulation of zolmitriptan: Development and optimization using factorial design.

The goal of study was to formulate and characterize pullulan based oral thin film (OTF) of zolmitriptan by solvent casting method. Based on preliminary trials, glass, PEG 400 and sucralose were selected as casting surface, water-miscible plasticizer and sweetener for OTF, respectively. A 32 factorial design was used to study the effect of amount of PEG 400 (X1) and sucralose (X2) as independent variables on tensile strength (Y1), elasticity (Y2), % in-vitro drug release in phosphate buffer of pH 6.8 at 5min (Q5min, Y3) and overall taste of OTF (Y4) as responses. OTF of batch F4 (PEG 400, 200mg; sucralose, 12mg) was identified as an optimized batch showing in-vitro, in-vivo disintegration time 20.70 and 21.58s, respectively; 95.53% Q5min; satisfactory thickness, strength, % elongation, ease of handling, smooth mouthfeel, excellent overall taste; even distribution of all ingredients in pullulan OTF (SEM study); and stable film at specified conditions concluding that pullulan, PEG 400 and sucralose are used in combination to make palatable, stable OTF of zolmitriptan.

Incidence and risk factors of retinopathy of prematurity in Western India - Report from A Regional Institute of Ophthalmology.

INTRODUCTION: Retinopathy of prematurity is an important cause of childhood blindness amongst premature babies in developing as well as developed world. OBJECTIVES: To report the incidence and risk factors of ROP from a regional institute of Ophthalmology in western India and compare it with the existing scenario. MATERIALS AND METHODS: This was prospective observational study of babies born at <34 weeks of gestational and/or <1700 grams birth weight between January 2012 and October 2013. Birth related information viz. O2 administration was recorded in consultation with a neonatologist and babies were evaluated for the presence of ROP. Multivariable logistic regression was used to identify risk factors for any-ROP and severe-ROP requiring treatment. RESULTS: Out of 280 babies screened, any-ROP was seen 54 babies(19.28%) out of which, severe-ROP was found in 28 babies(10.29%).Likelihood of developing any-ROP increased 3 fold (95%CI=1.1 - 6.5), and severe-ROP by 7 fold (95%CI=1.6 - 27.5), if oxygen therapy as administered. Older gestational age was associated with reduced likelihood of developing severe-ROP (Odds ratio=0.79, 95%CI=0.6 - 0.9) but not any-ROP. Twenty four babies (86%) with severe ROP responded well to laser or Bevacizumab therapy while 4 babies developed retinal detachment. CONCLUSION: This is the first report quoting only incidence and risk factors of ROP from western India. One in 5 babies develop any-ROP similar to that reported across rest of the country. The incidence of severe-ROP requiring treatment appears to be marginally higher, and treatment outcomes in these eyes are similar to that reported in literature.

Current knowledge on biodegradable microspheres in drug delivery.

INTRODUCTION: Biodegradable microspheres have gained popularity for delivering a wide variety of molecules via various routes. These types of products have been prepared using various natural and synthetic biodegradable polymers through suitable techniques for desired delivery of various challenging molecules. Selection of biodegradable polymers and technique play a key role in desired drug delivery. AREAS COVERED: This review describes an overview of the fundamental knowledge and status of biodegradable microspheres in effective delivery of various molecules via desired routes with consideration of outlines of various compendial and non-compendial biodegradable polymers, formulation techniques and release mechanism of microspheres, patents and commercial biodegradable microspheres. EXPERT OPINION: There are various advantages of using biodegradable polymers including promise of development with different types of molecules. Biocompatibility, low dosage and reduced side effects are some reasons why usage biodegradable microspheres have gained in popularity. Selection of biodegradable polymers and formulation techniques to create microspheres is the biggest challenge in research. In the near future, biodegradable microspheres will become the eco-friendly product for drug delivery of various genes, hormones, proteins and peptides at specific site of body for desired periods of time.

Development and optimization of modified release IPN macromolecules of oxcarbazepine using natural polymers.

The study shows development and optimization of modified release interpenetrating polymer network (IPN) macromolecules (beads) of oxcarbazepine using sodium alginate-egg albumin prepared by ionotropic gelation method and CaCl2 as a cross-linker. Independent variables were identified based on preliminary study of investigation. The effect of amount of both polymers on drug entrapment efficiency (DEE,%), bead size (µm) and cumulative drug release at 8 h (Q8h, %) were optimized using 3(2) factorial design. The DEE, average size and Q8h were found in the range of 65.08-91.02%, 976-1084 µm and 73.50-94.06% respectively. The beads were also characterized by FTIR, DSC, SEM and XRD. The experiential responses were coincided well with predicted values obtained by Design-Expert(®) 8.0.6.1 software. The swelling of beads were influenced by the pH of a release medium. The in vitro drug release from IPN beads exhibited sustained release Hixson-Crowell pattern with anomalous non-Fickian diffusion mechanism concluding that the developed sodium alginate-egg albumin IPN composite beads are suitable for sustained delivery of oxcarbazepine for desired period.

Locust bean gum in the development of sustained release mucoadhesive macromolecules of aceclofenac.

The study shows the development and optimization of locust bean gum (LBG)-alginate mucoadhesive macromolecules containing aceclofenac through ionotropic-gelation using 3(2) factorial design. The effect of amount of LBG and sodium alginate on drug entrapment efficiency (%DEE), % mucoadhesion at 8h (M8) and % in vitro drug release at 10h (%Q10h) were optimized. The percentage yield, average size and DEE of macromolecules were found within the range of 93.19 to 96.65%, 1.328 ± 0.11 to 1.428 ± 0.13 µm, and 56.37 to 68.54%, respectively. The macromolecules were also characterized by SEM, FTIR and DSC. The in vitro drug release from these macromolecules (84.95 ± 2.02 to 95.33 ± 1.56% at 10h) exhibited sustained release (first-order) pattern with super case-II transport mechanism. The swelling and mucoadhesivity of these macromolecules were affected by pH of the medium. The design established the role of derived polynomial equations and plots in predicting the values of dependent variables for the preparation and optimization.

Carrageenan: a natural seaweed polysaccharide and its applications.

Polysaccharides have been gaining interesting and valuable applications in the food and pharmaceutical fields. As they are derived from the natural source, they are easily available, non-toxic, cheap, biodegradable and biocompatible. Carrageenan is one among them, which fulfills the criteria of polysaccharide; it is a natural carbohydrate (polysaccharide) obtained from edible red seaweeds. The name Carrageenan is derived from the Chondrus crispus species of seaweed (Rhodophyceace) known as Carrageen Moss or Irish Moss, and Carraigin. A demand based on its application has been widely increasing in food and pharmaceutical sectors. Carrageenan has gained wide applications in experimental medicine, pharmaceutical formulations, cosmetics, and food industries. Through keen references of the reported literature on carrageenan, in this review, we have described about carrageenan, its properties, extraction and refining, and its food and pharmaceutical applications.

Lepidium sativum Linn.: a current addition to the family of mucilage and its applications.

Mucilage from the last decades has been found to be very attractive, interesting and useful in development of desired pharmaceutical dosage forms. Various applications of plant based mucilage have a wide potentiality in drug formulations. Lepidium sativum Linn. (family: Brassicaceae) is one of the mucilage containing fast growing, edible annual herb. Its various parts (roots, leaves and seeds) have been used to treat various human ailments. It mainly contains alkaloids, saponins, anthracene glycosides, carbohydrates, proteins, amino acids, flavanoids, and sterols as chief phytochemical constituents. Its seed extracts have been screened for various biological activities like hypotensive, anti-microbial, bronchodilator, hypoglycemic and allelopathic, whereas its seed coat mucilage has been isolated using different methods to make it effective excipient of desired functionality as a part of pharmaceutical applications. Through keen references of reported work on Lepidium sativum Linn., in this review, we have focused on its seed coat mucilage isolation methods, chemical constituents, pharmacological profile and versatile application of Lepidium sativum Linn.

Dual release paracetamol in osteoarthritis of knee: a randomized controlled clinical trial.

BACKGROUND: Paracetamol is recommended as first line agent for pain management in osteoarthritis (OA) by various guidelines. The main problem associated with management of osteoarthritis is long term patient compliance to paracetamol due to its frequent dosing. OBJECTIVE: To evaluate the efficacy and safety of Paracetamol 650 mg dual release tablet twice daily (PCM 650 dual release) compared to paracetamol 500mg immediate release tablet thrice daily (PCM 500 IR) in the treatment of Knee OA. MATERIALS AND METHODS: In this randomized, open label, parallel, active controlled clinical study, 250 patients of OA knee meeting inclusion criteria were randomized to receive either PCM 650 dual release two times daily or PCM 500 IR three times daily for 6 weeks. Patients were assessed at baseline, 2, 4 and 6 weeks. Primary efficacy measures were severity of pain (Visual Analogue Scale) and Knee injury and osteoarthritis outcome score (KOOS) subscale for pain at week 2, 4 and 6. Other KOOS subscales (symptoms other than pain, function in daily living, function in sport and recreation, quality of life) and patient's and physicians global assessment of therapy were included as secondary endpoints. RESULTS: Both treatment groups showed improvement in primary endpoints at each evaluation visit. Patients receiving PCM 650 dual release showed significant improvement of pain in both primary endpoints at each study visit compared to patients receiving PCM 500 IR (p<0.001). PCM 650 dual release was significantly superior to PCM 500 IR for improvement in all KOOS subscales at each study visit (p<0.01). Less number of patients required additional rescue analgesics in PCM 650 dual release group (16% patients vs 26%, PCM 500 IR; p>0.05). Adverse effects were significantly less in PCM 650 dual release group (6% vs. 14% in PCM 500 IR; p<0.05). Patient's and physician's global assessment of therapy favoured PCM 650 dual release than PCM 500 IR (p<0.001). CONCLUSION: Patients with symptomatic OA of the knee showed a greater improvement in pain and functional capacity with PCM 650 dual release than PCM 500 IR with better tolerability.

Development of microencapsulation delivery system for long-term preservation of probiotics as biotherapeutics agent.

The administration of probiotic bacteria for health benefit has rapidly expanded in recent years, with a global market worth $32.6 billion predicted by 2014. The oral administration of most of the probiotics results in the lack of ability to survive in a high proportion of the harsh conditions of acidity and bile concentration commonly encountered in the gastrointestinal tract of humans. Providing probiotic living cells with a physical barrier against adverse environmental conditions is therefore an approach currently receiving considerable interest. Probiotic encapsulation technology has the potential to protect microorganisms and to deliver them into the gut. However, there are still many challenges to overcome with respect to the microencapsulation process and the conditions prevailing in the gut. This review focuses mainly on the methodological approach of probiotic encapsulation including biomaterials selection and choice of appropriate technology in detailed manner.

Galactomannan: a versatile biodegradable seed polysaccharide.

Polysaccharides have been finding, in the last decades, very interesting and useful applications in the biomedical and, specifically, in the biopharmaceutical field. Galactomannans are a group of storage polysaccharides from various plant seeds that reserve energy for germination in the endosperm. There are four major sources of seed galactomannans: locust bean (Ceratonia siliqua), guar (Cyamopsis tetragonoloba), tara (Caesalpinia spinosa Kuntze), and fenugreek (Trigonella foenum-graecum L.). Through keen references of reported literature on galactomannans, in this review, we have described occurrence of various galactomannans, its physicochemical properties, characterization, applications, and overview of some major galactomannans.

Pullulan: an exopolysaccharide and its various applications.

Pullulan is a non-ionic polysaccharide obtained from fermentation of black yeast like Aureobasidium pullulans and is currently exploited in food and pharmaceutical industries due to its unique characteristics. Due to its properties like non-toxic, non-immunogenic, non-carcinogenic, non-mutagenic, pullulan is being explored for various biomedical applications viz., gene delivery, targeted drug therapy, tissue engineering, wound healing, and also being used in diagnostic applications like, perfusion, receptor, and lymph node target specific imaging and vascular compartment imaging. The unique linkage of α (1→4) and α (1→6) in pullulan endows this polymer with distinctive physical traits, including adhesive property and the ability to form fibers. This review article presents an historical outline, overview of properties, production, derivatives of pullulan, its versatile applicability and recent advances of pullulan.