Publications by authors named "Saurabh Sharma"

197 Publications

Molecular mechanisms of cognitive impairment associated with stroke.

Metab Brain Dis 2022 Jan 14. Epub 2022 Jan 14.

School of Pharmaceutical Sciences, CT University, Ludhiana, Punjab, India.

Stroke is the second leading cause of death after coronary heart disease in developed countries and is the greatest cause of disability and cognitive impairment. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, hypertension, arterial fibrillation, diabetes, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke, depressive illness duration of a stroke, location, volume, intensity, and degree of neuronal degeneration, location and size of infarction after stroke, time interval after stroke other cerebral dysfunctions. The pathophysiology of stroke associated cognitive impairment is complex and recent molecular, cellular, and animal models studies have revealed that multiple cellular changes have been implicated, including altered redox state, mitochondrial dysfunction, disruption of the blood-brain barrier, perivascular spacing, glymphatic system impairment, microglia activation and amyloid-β deposition in the parenchyma of the brain. These studies have also evidenced the involvement of various transcription factors, intracellular adhesion molecules, and endogenous growth factors in the pathogenesis of cognitive impairment associated with stroke and providing scope for developing therapeutic strategies for treatment. This review summarizes the latest research findings on molecular mechanisms involved in cognitive impairment associated with stroke.
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http://dx.doi.org/10.1007/s11011-022-00901-0DOI Listing
January 2022

COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis, and meta-regression analysis.

Indian J Pharmacol 2021 Nov-Dec;53(6):499-510

Department of Pharmacology, PGIMER, Chandigarh, India.

Background: Till now, no meta-analysis is available to address the clinical profile, risk factors, different interventions, and outcomes among COVID-19-associated rhino-orbito-cerebral mucormycosis (C-ROCM) cases.

Materials And Methods: Eight literature databases were screened using appropriate keywords from November 1, 2019, to June 30, 2021. The objectives were to analyze the clinical and microbiological profile, risk factor/comorbidity, intervention, and outcome. "R-metafor package" was used for analysis.

Results: A total of 23 studies were included. The mean age of presentation of C-ROCM was 54.6 years. The most common presentation was ptosis (72.7%), lid edema (60.6%), proptosis (60.6%), ophthalmoplegia (57.3%), loss of vision (53.7%), facial edema (34.7%), and nasal-blockage (11.8%). Evidence of intracranial spread was seen in 42.8% of cases. Rhizopus was the most common fungus (57.1%) isolated in fungal culture. Among C-ROCM patients, diabetes was the commonest comorbid condition, and the use of corticosteroids related to COVID-19 treatment was the most common risk factor (85.75%). Compared to controlled diabetics, C-ROCM was significantly higher among uncontrolled diabetics (odds ratio [OR] 0.15, 95% confidence interval [C.I.] 0.041-0.544, P = 0.0010). However, no significant association was seen between C-ROCM and COVID-19 severity (OR 0.930, 95% C.I. 0.212-4.087, P = 0.923). For treatment, amphotericin-B was the most common antifungal drug used which was followed by surgical options. However, mortality was high (prevalence 0.344, 95% C.I. 0.205-0.403) despite treatment.

Conclusion: Although local rhino-orbito symptoms were the first to appear, rapid intracranial extension was seen in a significant number of C-ROCM cases. Uncontrolled diabetes and excessive use of corticosteroid were the most common risk factors present among the C-ROCM cases. High index clinical suspicion is imperative (specifically among COVID-19 patients with diabetes), and routine screening may be helpful.
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http://dx.doi.org/10.4103/ijp.ijp_839_21DOI Listing
January 2022

Functional Gly297Ser Variant of the Physiological Dysglycemic Peptide Pancreastatin is a Novel Risk Factor for Cardiometabolic Disorders.

Diabetes 2021 Dec 3. Epub 2021 Dec 3.

Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India

Pancreastatin (PST), a chromogranin A (CHGA)-derived potent physiological dysglycemic peptide, regulates glucose/insulin homeostasis. We have identified a non-synonymous functional PST variant (p.Gly297Ser; rs9658664) that occurs in a large section of human populations. Association analysis of this single nucleotide polymorphism with cardiovascular/metabolic diseases states in Indian populations (n≈4300 subjects) displays elevated plasma glucose, glycosylated hemoglobin, diastolic blood pressure and catecholamines in Gly/Ser subjects as compared to wild-type individuals (Gly/Gly). Consistently, the 297Ser allele confers an increased risk (∼1.3-1.6-fold) for type-2 diabetes/hypertension/coronary artery disease/metabolic syndrome. In corroboration, the variant peptide (PST-297S) displays gain-of-potency in several cellular events relevant for cardiometabolic disorders (, increased expression of gluconeogenic genes, increased catecholamine secretion, greater inhibition of insulin-stimulated glucose-uptake) than the wild-type peptide (PST-WT). Computational docking analysis and molecular dynamics simulations show higher affinity binding of PST-297S peptide with glucose-regulated protein 78 (GRP78) and insulin receptor (IR) than PST-WT, providing a mechanistic basis for the enhanced activity of the variant peptide. binding assays validate these predictions of PST peptides binding to GRP78 and IR. In conclusion, the PST 297Ser allele influences cardiovascular/metabolic phenotypes and emerges as a novel risk factor for type-2 diabetes/hypertension/coronary artery disease in human populations.
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http://dx.doi.org/10.2337/db21-0289DOI Listing
December 2021

Dermatoscopy of Nail Lichen Planus: A Boon for Early Diagnosis.

J Clin Aesthet Dermatol 2021 Jul 1;14(7):34-37. Epub 2021 Jul 1.

Drs. Sharma, Kaur, and Sekhon are with the Department of Dermatology, Venereology, and Leprosy at Sri Guru Ram Das Institute of Medical Sciences and Research in Amritsar, Punjab, India.

Background: Lichen planus is an immune-mediated disorder affecting the skin, mucous membranes, scalp, and nails.

Objective: We sought to evaluate dermatoscopic nail patterns in patients with lichen planus.

Methods: This was a cross-sectional, observational study performed in the outpatient dermatology department of a tertiary care hospital. Thirty-one patients with skin biopsy-proven lichen planus with nail changes were included. An evaluation of clinical nail patterns and dermoscopic assessment of nail patterns were performed.

Results: Longitudinal ridging with splitting, longitudinal melanonychia and splinter hemorrhages were the most commonly found nail patterns in patients with lichen planus. Pterygium has been found to be most pathognomic feature of nail lichen planus.

Conclusion: Dermatoscopy has been demonstrated to be a valuable, noninvasive tool to identify subsurface nail bed changes and subclinical surface findings to facilitate early diagnosis and timely management of lichen planus to avoid long-term sequelae.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570357PMC
July 2021

Classification-Based Management of Stiff/Ankylosed Knees.

Indian J Orthop 2021 Oct 29;55(5):1158-1174. Epub 2021 Jul 29.

Asian Institute of Medical Sciences, Badkal Flyover Road, Sec 21A, Faridabad, Delhi NCR India.

Introduction: Stiff knees are defined as those with an arc of motion < 50°. They pose a considerable surgical challenge to the operating surgeon. Based on our experience to deal with these complex cases, we have developed a working classification that outlines a flowchart to manage the stiff/ankylosed knees.

Materials And Methods: It was a retrospective study conducted in our department. Out of 570 TKA performed in last 5 years, 57 had stiffness and four had bony ankyloses (total 61 knees). Patients were classified based on the fibrous or bony ankylosis and preoperative ROM.

Results: Patients were followed for an average 2.4 years (1.8-5.5 years). KSS pain scores improved from an av. 32 preop (18-64) to av. 76 postoperatively (61-90). The KSS function scores improved from a preoperative value of 36 (16-56) to an av. 78 (52-90) postoperatively. ROM improved from an average of 35.6° (0°-44°) preoperatively to an average of 95.6° (ROM 73°-118°) postoperatively. Extension lag was an av. 8° (3°-12°) and was seen in 13 patients postoperatively. Residual fixed flexion deformity was an av. 7° (3°-14°) and seen in 17 patients. The stiff knees (type 1 and type 2) fared better than ankylosed knees (type 3) in all aspects. Complication rate was high (24%) in our series.

Conclusion: Our classification of stiff/ankylosed knees guides the surgeon to decide upon which approach to take, which implants to keep handy and has a predictive and prognostic value.
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http://dx.doi.org/10.1007/s43465-021-00457-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586129PMC
October 2021

An insight into the simulation directed understanding of the mechanism in SARS CoV-2 N-CTD, dimer integrity, and RNA-binding: Identifying potential antiviral inhibitors.

J Biomol Struct Dyn 2021 Nov 9:1-13. Epub 2021 Nov 9.

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Coronavirus 2019 is a transmissible disease and has caused havoc throughout the world. The present study identifies the novel potential antiviral inhibitors against the nucleocapsid C-terminal domain that aids in RNA-binding and replication. A total of 485,629 compounds were screened, and MD was performed. The trajectory analysis (DCCM & PCA), structural integrity, and degree of compaction depicted the protein-ligand complex stability (PDB-PISA and R). Results obtained from screening shortlists 13 compounds possessing high Docking score. Further, seven compounds had a permissible RMSD limit (3 Å), with robust RMSF. Post-MD analysis of the top two compounds (204 and 502), DCCM & PCA analysis show a positive atomic displacements correlation among residues of active sites-dimer (Chain A and Chain B) & residual clustering. The ΔG of RNA-bound (-83.5 kcal/mol) and drug-bound N-CTD-204 (-40.8 kcal/mol) and 502(-39.7 kcal/mol) as compared to Apo (-35.95 kcal/mol) suggests stabilization of protein, with less RNA-binding possibility. The R values depict the loss of compactness on RNA-binding when compared to the drug-bound N-CTD complex. Further, overlapping the protein complexes (0 ns and 100 ns) display significant changes in RMSD of the protein (204-2.07 Å and 502-1.89 Å) as compared to the Apo (1.72 Å) and RNA-bound form (1.76 Å), suggesting strong interaction for compound 204 as compared to 502. ADMET profiling indicates that these compounds can be used for further experiments ( and pre-clinical). Compound 204 could be a promising candidate for targeting the N-protein-RNA assembly and viral replication.
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http://dx.doi.org/10.1080/07391102.2021.1996463DOI Listing
November 2021

Early intervention saved the life of mother and baby: Management of a parturient with snake bite with neurotoxicity.

Indian J Anaesth 2021 Sep 15;65(Suppl 3):S139-S140. Epub 2021 Sep 15.

Department of Anaesthesia, Dr RPGMC Kangra, Tanda, Himachal Pradesh, India.

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http://dx.doi.org/10.4103/ija.IJA_49_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500194PMC
September 2021

Yogic Neti-Kriya Using Povidone Iodine: Can it have a Preventive Role Against SARS-CoV-2 Infection Gateway?

Indian J Otolaryngol Head Neck Surg 2021 Oct 17:1-7. Epub 2021 Oct 17.

Department of Pharmacology, PGIMER, Chandigarh, Pin 160012 India.

During this COVID-19 pandemic, except steroid, none of the therapeutic measures have showed any evidence of efficacy. Traditionally jala-neti using lukewarm salted water remains a yogic way of maintaining upper airway hygiene. Saline irrigation decreases the concentration of inflammatory mediators (e.g. histamine, leukotriene etc.) in nasal secretions, reduces the severity and frequency of sinusitis, reduce need of antibiotic therapy and restores competency of nasal mucosa. Jala-neti is an integral part of six cleansing techniques of yogic kriyas practised in India since thousands of years. Jala-neti can clean the upper airways, prevents colonization of infectious agents, removes foreign bodies, prevents stasis of mucous and subsequently enhances the drainage of paranasal sinuses and maintain health. Regular practice of Jala neti improves nasal symptoms and overall health status of patients with sinusitis. Jala-neti sample can even be used for COVID-19 diagnosis. Povidone iodine (PVP-I) has been utilized as a time tested antimicrobial agent with broad spectrum coverage against wide range of bacteria and viruses. Anti-SARS-CoV-2 action of PVP-I was seen at a concentration as low as 0.45% PVP-I is generally well tolerated upto 5%, however nasal ciliotoxicity is reported at this concentration, however, this toxicity is not reported with lower concentrations(1.25% and 0.5%). So, theoretically, by using neti-kriya with povidone iodine (0.5-1%) as irrigation solution can combine and enhance the protection against COVID-19 and this can be an important armor in the fight against COVID-19. However, this hypothesis needs to be validated in real life clinical trial scenario before implementing.
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http://dx.doi.org/10.1007/s12070-021-02885-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520578PMC
October 2021

Effects of combined whole body vibration and resistance training on lower quadrants electromyographic activity, muscle strength and power in athletes.

Foot (Edinb) 2021 Dec 30;49:101844. Epub 2021 Jun 30.

Center for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, A Central University, New Delhi, India.

Background: Whole body vibration (WBV) with resistance training is one of the increasing ways of gaining ankle and foot complex muscle strength and power for the rehabilitative and prophylactic purpose in athletes.

Objective: The purpose of the study was to compare the effects of combined WBV and resistance training (RVE) with strength training alone (RE) on alteration of gastrocnemius lateralis and vastus medialis obliquus muscle activity and strength, and power performance in athletes.

Methods: The study was performed on 23 university-level male athletes who were randomized into two groups as RVE (n = 12; age 22.2 ± 1.94 years) and RE (n = 11; age 21.60 ± 1.78 years). The training program was scheduled three times per week for six weeks (18 sessions). Gastrocnemius lateralis (GL) and vastus medialis obliquus (VMO) were measured for muscle activity and isometric strength with surface EMG device and handheld dynamometer respectively. Counter-movement jump (CMJ) was used for measuring power. All the participants were assessed for outcome measures at baseline and then after 6 weeks. Group (RVE vs. RE) by time (pre vs. post) effects were compared through a 2-way interaction utilizing mixed model repeated measure ANOVA.

Results: After training, VMO muscle activity (group effects) increased significantly in the RVE group (p < 0.05). However, both the groups showed statistically significant time and group × time interaction effects for muscle activity of VMO, isometric strength (VMO and GL), and CMJ (p < 0.05).

Conclusion: WBV might serve as an adjunct modality for enhancement of the neuromuscular activity of the VMO muscle. However, RVE had no additive effect when compared to RE alone on muscle strength and power in athletes. The long-term impacts of combined WBV and resistance training on other foot and ankles muscle should be investigated in future studies.
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http://dx.doi.org/10.1016/j.foot.2021.101844DOI Listing
December 2021

Foramen Magnum Decompression in Hemifacial Spasm Associated with Chiari 1 Malformation.

Neurol India 2021 Jul-Aug;69(4):1063-1064

Department of Neurosurgery, Government Medical College and Hospital, Trivandrum, Kerala, India.

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http://dx.doi.org/10.4103/0028-3886.325351DOI Listing
September 2021

Folate targeted hybrid lipo-polymeric nanoplexes containing docetaxel and miRNA-34a for breast cancer treatment.

Mater Sci Eng C Mater Biol Appl 2021 Sep 10;128:112305. Epub 2021 Jul 10.

Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS Pilani), Vidya Vihar Campus, Pilani 333 031, Rajasthan, India. Electronic address:

In spite of established evidence of the synergistic combination of hydrophobic anticancer molecule and microRNA for breast cancer treatment, their in vivo delivery has not been realized owing to their instability in the biological milieu and varied physicochemical properties. The present work reports folate targeted hybrid lipo-polymeric nanoplexes for co-delivering DTX and miR-34a. These nanoplexes exhibited a mean size of 129.3 nm with complexation efficiency at an 8:1 N/P ratio. The obtained nanoplexes demonstrated higher entrapment efficiency of DTX (94.8%) with a sustained release profile up to 85% till 48 h. Further, an improved transfection efficiency in MDA-MB-231 and 4T1 breast cancer cells was observed with uptake primarily through lipid-raft and clathrin-mediated endocytosis. Further, nanoplexes showed improved cytotoxicity (~3.5-5 folds), apoptosis (~1.6-2.0 folds), and change in expression of apoptotic genes (~4-7 folds) compared to the free treatment group in breast cancer cells. In vivo systemic administration of FA-functionalized DTX and FAM-siRNA-loaded nanoplexes showed an improved area under the curve (AUC) as well as circulation half-life compared to free DTX and naked FAM-labelled siRNA. Acute toxicity studies of the cationic polymer showed no toxicity at a dose equivalent to 10 mg/kg based on the hematological, biochemical, and histopathological examination.
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http://dx.doi.org/10.1016/j.msec.2021.112305DOI Listing
September 2021

Update on geographical variation and distribution of SARS-nCoV-2: A systematic review.

Indian J Pharmacol 2021 Jul-Aug;53(4):310-316

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Knowledge of a new mutant strain of SARS-coronavirus (CoV-2) is enormously essential to identify a targeted drug and for the development of the vaccine. In this article, we systematically reviewed the different mutation strains (variant of concern [VOC] and variant of interest [VOI]) which were found in different countries such as the UK, Singapore, China, Germany, Vietnam, Western Africa, Dublin, Ireland, Brazil, Iran, Italy, France, America, and Philippines. We searched four literature databases (PubMed, EMBASE, NATURE, and Willey online library) with suitable keywords and the time filter was November 2019 to June 16, 2021. To understand the worldwide spread of variants of SARS-CoV-2, we included a total of 27 articles of case reports, clinical and observational studies in the systematic review. However, these variants mostly spread because of their ability to increase transmission, virulence, and escape immunity. So, in this paper is we found mutated strains of SARS-CoV-2 like VOCs that are found in different regions across the globe are ALPHA strain in the U.K, BETA strain in South Africa, GAMMA strain in Brazil, Gamma and Beta strains in European Countries, and some VOIs like Theta variant in the Philippines.
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http://dx.doi.org/10.4103/ijp.ijp_483_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411960PMC
September 2021

Valproic acid and Propionic acid modulated mechanical pathways associated with Autism Spectrum Disorder at prenatal and neonatal exposure.

CNS Neurol Disord Drug Targets 2021 Aug 6. Epub 2021 Aug 6.

Department of Pharmacology, Post Graduate Institute for Medical Education and Research (PGIMER), Chandigarh. India.

Autism Spectrum Disorder (ASD) is a composite disorder of brain development with uncertain etiology and pathophysiology. Genetic factors are important in ASD causation, although environmental factors are also involved in ASD pathophysiology. Environmental factors might affect the genetic processes of brain development through the modulation of molecular pathways that might be involved with ASD. Valproic acid and Propionic acid are the major environmental factors that serve as medicine and food preservative. VPA is used as an anti-epileptic medicine, but it has adverse effects on pregnant women and alters the developmental patterns of the embryo. It is a multi-targeting agent and affects through the 5-HT, GABA, etc. PPA is a secondary metabolite of gut microbiota that is commonly used as a food preservative. PPA plays a significant role in ASD causation by altering the several developmental molecular pathways like PTEN/Akt, mTOR/Gskβ, Cytokines activated pathways, etc., at the prenatal and neonatal stage. Moreover, ASD complexity might be increased by some other important factors like vitamin A deficiency and Vitamin A is important for cortical brain development and neuronal cell differentiation. Additionally, several important genes such as RELN, Lhx2, CREB, IL-6, NMDA, BDNF, etc. also altered in ASD that involved in brain development, Central Nervous System, Enteric Nervous System. These genes affect the neuronal differentiation, hyperactivity, oxidative stress, oxytocin, and GABA imbalance that lead the improper behavior in autistic individuals. These genes are also studied in VPA and PPA ASD-like animal models. In this review, we explored the mechanical pathways that might be altered with VPA and PPA exposures at the embryonic developmental stage or neonatal developmental stage.
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http://dx.doi.org/10.2174/1871527320666210806165430DOI Listing
August 2021

Functional insights into Mycobacterium tuberculosis DevR-dependent transcriptional machinery utilizing Escherichia coli.

Biochem J 2021 08;478(16):3079-3098

Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

DevR/DosR response regulator is believed to participate in virulence, dormancy adaptation and antibiotic tolerance mechanisms of Mycobacterium tuberculosis by regulating the expression of the dormancy regulon. We have previously shown that the interaction of DevR with RNA polymerase is essential for the expression of DevR-regulated genes. Here, we developed a M. tuberculosis-specific in vivo transcription system to enrich our understanding of DevR-RNA polymerase interaction. This in vivo assay involves co-transforming E. coli with two plasmids that express α, β, β' and σA subunits of M. tuberculosis RNA polymerase and a third plasmid that harbors a DevR expression cassette and a GFP reporter gene under the DevR-regulated fdxA promoter. We show that DevR-dependent transcription is sponsored exclusively by M. tuberculosis RNA polymerase and regulated by α and σA subunits of M. tuberculosis RNA polymerase. Using this E. coli triple plasmid system to express mutant variants of M. tuberculosis RNA polymerase, we identified E280 residue in C-terminal domain of α and K513 and R515 residues of σA to participate in DevR-dependent transcription. In silico modeling of a ternary complex of DevR, σA domain 4 and fdxA promoter suggest an interaction of Q505, R515 and K513 residues of σA with E178 and D172 residues of DevR and E471 of σA, respectively. These findings provide us with new insights into the interactions between DevR and RNA polymerase of M. tuberculosis which can be targeted for intercepting DevR function. Finally, we demonstrate the utility of this system for screening of anti-DevR compounds.
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http://dx.doi.org/10.1042/BCJ20210268DOI Listing
August 2021

Progressive Resistance Exercises plus Manual Therapy Is Effective in Improving Isometric Strength in Overhead Athletes with Shoulder Impingement Syndrome: A Randomized Controlled Trial.

Biomed Res Int 2021 30;2021:9945775. Epub 2021 Jun 30.

Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, New Delhi, India.

Reduction in isometric strength of the scapulohumeral muscles is a commonly seen impairment in overhead athletes afflicted with shoulder impingement syndrome (SIS). The purpose of this study was to compare the effects of two different treatment programs: progressive resistance exercises plus manual therapy (PRE plus MT) and motor control exercises (MCE), on isometric strength of upper trapezius (UT), middle trapezius (MTr), lower trapezius (LT), serratus anterior (SA), supraspinatus (Supr.), anterior deltoid (A.D), and latissimus dorsi (LD). 80 male university-level overhead athletes clinically diagnosed with SIS were randomly allocated into either of the two groups: PRE plus MT and MCE group. Athletes in the PRE plus MT group underwent graduated exercises with resistance elastic band, stretching exercises, and mobilization of the thoracic and shoulder joints. MCE group was submitted to motor control exercises in varied planar positions. Athletes in both groups underwent management 3 times a week for 8 weeks. Isometric strength of UT, MTr, LT, Supr, A.D, SA, and LD was measured at three-time points: baseline, 4th week, and 8th week. Relative to baseline, both interventions were found to be effective in increasing and optimizing the isometric strength of muscles ( < 0.05) except for supraspinatus in the MCE group ( > 0.05). However, athletes in PRE plus MT group presented a more pronounced increase in isometric strength than those in the MCE group. Between groups analysis found the largest isometric strength improvement in PRE plus MT group for A.D, followed by Supr. and UT muscles ( < 0.05; effect size: 0.39 to 0.40). The study concluded that compared to MCE, PRE plus MT provides greater improvement in the isometric strength of scapulohumeral muscles.
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http://dx.doi.org/10.1155/2021/9945775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266437PMC
September 2021

Clinicoradiological Profile and Outcome of Microsurgical Clipping of Ruptured Anterior Circulation Aneurysms: A Single-Institute Experience.

Asian J Neurosurg 2021 Apr-Jun;16(2):316-320. Epub 2021 May 28.

Department of Neurosurgery, Dayanand Medical College and Hospital, Ludhiana, Punjab, India.

Introduction: Prevalence of intracranial aneurysms is estimated to be from 1% to 5% of population, most of them are small and located in the anterior circulation. The real danger is when an aneurysm ruptures, leading to a subarachnoid hemorrhage (SAH). SAH is a catastrophic event with a mortality rate of 25% to 50%. Permanent disability occurs in nearly 50% of the survivors. Fifteen percent of patients expire before reaching the hospital and 25% die within 24 h. The purpose of our study is to report the clinicoradiological data and outcome of microsurgical clipping of ruptured anterior circulation aneurysms in our center.

Materials And Methods: This study included ruptured anterior circulation aneurysms admitted to tertiary care hospital in northern India from January 2018 to June 2020. The final outcome of patients was analyzed with Glasgow Outcome Score (GOS) at the time of discharge from the hospital.

Results: A total of 53 patients with ruptured anterior circulation aneurysm underwent microsurgical clipping comprising 25 (47.2%) males and 28 (52.8%) females. The mean neck size of all aneurysms was 3.43 ± 1.66 mm. The mean hospital stay was longer in patients having preoperative intraventricular hemorrhage (IVH) (35.96 ± 27.27 days) and postoperative complications (43.36 ± 29.76 days) compared to patients who did not have IVH (21.10 ± 15.47 days) and postoperative complications (18 ± 6.54 days). value was ≤0.05. Patients with preoperative hydrocephalus had GOS 3.44 ± 1.20 at discharge compared to nonhydrocephalus who had GOS 4.32 ± 1.07 ( = 0.009). Patients with Intracerebral Hemorrhage (ICH) and non-ICH had GOS 3.31 ± 1.38 and 4.28 ± 1.01, respectively ( = 0.009).

Conclusion: Poor outcome at the time of discharge after the surgical treatment of anterior circulation aneurysms was associated with poor world federation of neurological surgeons grade on admission, presence of IVH, hydrocephalus, intracerebral hemorrhage, and postoperative cerebral infarcts.
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http://dx.doi.org/10.4103/ajns.AJNS_483_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244689PMC
May 2021

Impact of Musculoskeletal Limitations on Cardiac Rehabilitation Participation.

Front Cardiovasc Med 2021 28;8:688483. Epub 2021 Jun 28.

Cardiovascular Rehabilitation Program, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States.

To help clarify a potential barrier to cardiac rehabilitation (CR) participation we sought to examine the association between musculoskeletal limitations (MSLs) and CR enrollment and participation. Consecutive CR eligible individuals hospitalized for a cardiac event (myocardial infarction, percutaneous coronary intervention, and/or coronary artery bypass graft) between the months of November 2007 and May 2008, were asked to complete a mailed survey within 2 weeks after hospital discharge, assessing demographic factors, Patient Health Questionnaire (PHQ-9), participation in CR and MSLs through a validated MSLs screening tool. CR enrollment rates were compared between patients with and without MSLs. Three hundred and twenty-one (37%) of patients contacted responded to our survey, including 228 males (71%), with a mean age 68 ± 10.8 years, of whom 98% were Caucasian. Eighty-two percent of responders reported a musculoskeletal disorder at the time of hospital discharge. Arthritis was the most frequent diagnosis (45%). Muscle or joint pain sufficient to limit the ability to do moderate exercise was reported in 52% of the respondents. Problems with balance affected 37%, of whom 45% reported a fall within the previous year. No significant difference in CR enrollment was observed in respondents with and without MSLs [OR = 0.98, 95% CI (0.88-1.09), = 0.750]. Similar results were found when severity and number of MSLs were taken into account. However, we found that when compared to those without MSLs, the presence of MSLs was associated with lower CR participation (OR = 0.80, 95%, CI: 0.65-0.97, = 0.0252). Despite a high prevalence of MSLs among CR-eligible patients, we found no association between MSLs and CR enrollment. However, patients with MSLs attended significantly fewer CR sessions as compared to patients without them. CR programs should consider providing additional support and interventions to patients with MSLs in order to optimize their adherence to prescribed CR sessions.
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http://dx.doi.org/10.3389/fcvm.2021.688483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273239PMC
June 2021

Effect of Preoperative Modifiable Psychological and Behavioural Factors on Early Outcome Following Total Knee Arthroplasty in an Indian Population.

Indian J Orthop 2021 Aug 19;55(4):939-947. Epub 2021 Jan 19.

Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi, India.

Background: Non-surgical factors have been found to have significant impact on outcome following Total Knee Arthroplasty (TKA). The study was conducted to know the independent effect of each of the four interacting psychological factors: anxiety, depression, pain catastrophizing and kinesiophobia on early outcome following TKA in an Indian population.

Materials And Methods: 104 consecutive patients undergoing TKA were included in the study and followed up at 6 weeks, 6 months and one year. Preoperatively, Hospital Anxiety and Depression Scale was used to diagnose and quantify anxiety and depression, pain catastrophizing and kinesiophobia were assessed using Pain Catastrophizing Scale and Tampa Scale for Kinesiophobia, respectively. Outcome was assessed on the basis of Knee Society Score and Knee Injury and Osteoarthritis Outcome Score. Regression analysis was done to know independent effect of each factor on outcome scores.

Results: Nine (8.7%) patients were found to have undiagnosed psychopathology. The patients with psychopathologies were found to have significantly worse knee outcome scores on follow-up, although the rate of improvement in knee symptoms and function was not significantly different from those without psychopathology. The degree of Anxiety correlated with worse knee pain and stiffness up to 6 months while it correlated with poor knee function for a longer duration. The degree of depression and pain catastrophizing correlated with worse knee pain, stiffness and function at all visits while kinesiophobia didn't show correlation independent other factors.

Conclusion: Psychopathology was found to be associated poor knee outcome scores with degree of preoperative depression and pain catastrophizing as significant independent predictors as poor outcome, whereas the effect of degree of anxiety on knee pain and stiffness was found to wane over time. Kinesiophobia didn't show any independent correlation.

Supplementary Information: The online version of this article (10.1007/s43465-020-00325-x) contains supplementary material, which is available to authorized users.
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http://dx.doi.org/10.1007/s43465-020-00325-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192610PMC
August 2021

Efficacy and safety of dihydroorotate dehydrogenase (DHODH) inhibitors "leflunomide" and "teriflunomide" in Covid-19: A narrative review.

Eur J Pharmacol 2021 Sep 7;906:174233. Epub 2021 Jun 7.

Department of Pharmacology, PGIMER, Chandigarh, India. Electronic address:

Dihydroorotate dehydrogenase (DHODH) is rate-limiting enzyme in biosynthesis of pyrimidone which catalyzes the oxidation of dihydro-orotate to orotate. Orotate is utilized in the biosynthesis of uridine-monophosphate. DHODH inhibitors have shown promise as antiviral agent against Cytomegalovirus, Ebola, Influenza, Epstein Barr and Picornavirus. Anti-SARS-CoV-2 action of DHODH inhibitors are also coming up. In this review, we have reviewed the safety and efficacy of approved DHODH inhibitors (leflunomide and teriflunomide) against COVID-19. In target-centered in silico studies, leflunomide showed favorable binding to active site of MPro and spike: ACE2 interface. In artificial-intelligence/machine-learning based studies, leflunomide was among the top 50 ligands targeting spike: ACE2 interaction. Leflunomide is also found to interact with differentially regulated pathways [identified by KEGG (Kyoto Encyclopedia of Genes and Genomes) and reactome pathway analysis of host transcriptome data] in cogena based drug-repurposing studies. Based on GSEA (gene set enrichment analysis), leflunomide was found to target pathways enriched in COVID-19. In vitro, both leflunomide (EC50 41.49 ± 8.8 μmol/L) and teriflunomide (EC50 26 μmol/L) showed SARS-CoV-2 inhibition. In clinical studies, leflunomide showed significant benefit in terms of decreasing the duration of viral shredding, duration of hospital stay and severity of infection. However, no advantage was seen while combining leflunomide and IFN alpha-2a among patients with prolonged post symptomatic viral shredding. Common adverse effects of leflunomide were hyperlipidemia, leucopenia, neutropenia and liver-function alteration. Leflunomide/teriflunomide may serve as an agent of importance to achieve faster virological clearance in COVID-19, however, findings needs to be validated in bigger sized placebo controlled studies.
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http://dx.doi.org/10.1016/j.ejphar.2021.174233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180448PMC
September 2021

Fractional Carbon Dioxide Laser versus Combined Fractional Carbon Dioxide Laser with Platelet-rich Plasma in the Treatment of Atrophic Post-acne Scars: A Split-face Comparative Study.

J Cutan Aesthet Surg 2021 Jan-Mar;14(1):41-46

Department of Physiology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.

Context: Though many treatment options are available for treating post-acne scars, optimized treatment still does not exist. Till date, comparative split-face studies, analyzing the efficacy of combined treatment modalities for acne scars with adequate sample size and with statistically significant results, are still lacking.

Aim: The aim of this study was to compare the effectiveness of the combined use of platelet-rich plasma (PRP) and fractional ablative CO laser (FACL) versus FACL in the management of acne scars and to study the safety of autologous PRP and FACL in the treatment of post-acne scars.

Settings And Design: This was a randomized split-face trial study.

Materials And Methods: This study was conducted in 30 patients having Goodman and Baron's grade 3 and 4 acne scars. The efficacy of PRP in combination with FACL was compared to FACL alone in the treatment of post-acne scars. Right half of the patient's face was taken as the study side where FACL was performed followed by PRP injections. The left half of the same patient's face was taken as the control side where FACL was performed followed by normal saline injections.

Statistical Analysis: Results were analyzed using Statistical Package for the Social Sciences (SPSS, Chicago).

Results: At the time of enrollment, mean Goodman and Baron Acne Qualitative Grading Scale on study and control side was 3.80 with standard deviation (SD) of 0.40 at baseline. After completion of four treatment sessions, it was reduced to 2.43 (SD = 0.76) and 2.76 (SD = 0.49) on the study and control side, respectively. Improvement on both sides was statistically significant ( = 0.000).

Conclusion: There is no single proven modality for the effective treatment of post-acne scars. Combination of FACL with newer adjuvants such as PRP has definitive role in managing post-acne scars with better safety profile than FACL alone.
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http://dx.doi.org/10.4103/JCAS.JCAS_147_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149982PMC
June 2021

Students' Perspective and Feedback on Foundation Course 2019 in a Medical College of North India.

Indian J Community Med 2021 Jan-Mar;46(1):159-160. Epub 2021 Mar 1.

Department of Community Medicine, Medical Education Unit, Subharti Medical College, Meerut, Uttar Pradesh, India.

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http://dx.doi.org/10.4103/ijcm.IJCM_126_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117921PMC
March 2021

Analyzing the Changes in Certain Infectious and Parasitic Diseases in Urban Population of India By Using Medical Certification of Cause of Death Data.

Indian J Community Med 2021 Jan-Mar;46(1):20-23. Epub 2021 Mar 1.

ICMR-National Institute of Medical Statistics, New Delhi, India.

Background: Infectious diseases are important causes of morbidity and mortality globally. At least 25% of about 60 million deaths that occur worldwide each year are estimated to be due to infectious diseases. In India, the burden of infectious diseases is enormous; although it has decreased as a result of overall socioeconomic progress and use of vaccines and antimicrobials, it is still a major health-care burden. Studying a disease trend over a certain time period is important in a country's public health system as it guides agencies to prioritize funds and other measures for its control.

Objectives: The present study tries to understand its transition in an urban population of India.

Materials And Methods: "Medical Certification of Cause of Death" data for the period from 1989 to 2015 have been used. Deaths under the head "age not stated" have been distributed in all age groups in proportion to total deaths at those age groups for all the years, and the percentage of the cause of death to total deaths has been calculated. Three years' moving average of these percentages have been calculated.

Results: The overall age group analysis showed a downward trend in both males and females. However, age-segregated analysis showed that mortality is declining among children and youth population, specifically showing a steep decline among infants and under-five population.

Conclusion: Infectious diseases are still a major public health problem in India.
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http://dx.doi.org/10.4103/ijcm.IJCM_77_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117879PMC
March 2021

Outcome and its predictors in traumatic brain injury in elderly population: Institutional study from Northern India.

J Family Med Prim Care 2021 Jan 30;10(1):289-294. Epub 2021 Jan 30.

Department of Neurosurgery, Dayanand Medical College and Hospital, Ludhiana, Punjab, India.

Introduction: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Survival and functional outcome is significantly poor in the elderly population. There is a need to develop better geriatric specific prognostic models and evidence-based geriatric traumatic brain injury management protocols for better treatment, rehabilitation, and prevention.

Aims And Objectives: To study the frequency, outcome and correlates of traumatic brain injury in elderly patients.

Material And Methods: Frequency, outcome and correlates of traumatic brain injury in patients more than 65 years of age admitted in tertiary care hospital were studied in 160 patients admitted between 1 January 2016 and 31 December 2016 (retrospective analysis) and between 1 January 2017 and 30 June 2018 (prospective analysis). Institutional ethical committee approval was taken.

Results: This study concluded that road side accident was the most common cause of traumatic brain injury in elderly in this study. Incidence of traumatic brain injury in elderly was found to be 11.45%. Both non-reacting pupils and low Glasgow coma scale on arrival were significantly associated with poor outcome in terms of mortality. Most of the patients who expired or were discharged against medical advice had associated skull bone fractures, cerebral infarct, diffuse brain edema, subarachnoid hemorrhage, midline shift, lower hemaglobin, higher random blood sugar and higher creatinine as compared to patients who were discharged. All these findings were statistically significant.

Conclusion: Low Glasgow coma scale on arrival, non reacting pupils, low hemoglobin, high random blood sugar, high creatinine and intubation on arrival are associated with increased mortality. Associated skull bone fractures, cerebral infarct, diffuse brain edema are predictors of poor outcome. Anticoagulants and associated co-morbidities do not increase the risk of mortality in traumatic brain injury in elderly.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1559_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132831PMC
January 2021

Computational basis of SARS-CoV 2 main protease inhibition: an insight from molecular dynamics simulation based findings.

J Biomol Struct Dyn 2021 May 13:1-11. Epub 2021 May 13.

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

The coronavirus disease 2019 (COVID-19) pandemic is caused by newly discovered severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). One of the striking targets amongst all the proteins in coronavirus is the main protease (M), as it plays vital biological roles in replication and maturation of the virus, and hence the potential target. The aim of this study is to repurpose the Food and Drug Administration (FDA) approved molecules via computer-aided drug designing against M (PDB ID: 6Y2F) of SARS CoV-2 due to its high x-ray resolution of 1.95Å as compared to other published Mstructures. High Through Virtual Screening (HTVS) of 2456 FDA approved drugs using structure-based docking were analyzed. Molecular Dynamics simulations were performed to check the overall structural stability (RMSD), Cα fluctuations (RMSF) and protein-ligand interactions. Further, trajectory analysis was performed to assess the binding quality by exploiting the protein-residue motion cross correlation (DCCM) and binding free energy (MM/GBSA). Tenofovir, an antiretroviral for HIV-proteases and Terlipressin, a vasoconstrictor show stable RMSD, RMSF, better MM/GBSA with good cross correlation as compared to the Apo and O6K. Moreover, the results show concurrence with Nelfinavir, Lopinavir and Ritonavir which have shown significant inhibition in studies. Therefore, we conclude that Tenofovir and Terlipresssin might also show protease inhibition but are still open to clinical validation in case of SARS-CoV 2 treatment.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1922310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127165PMC
May 2021

Indian contribution toward biomedical research and development in COVID-19: A systematic review.

Indian J Pharmacol 2021 Jan-Feb;53(1):63-72

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

COVID-19 pandemic led to an unprecedented collaborative effort among industry, academia, regulatory bodies, and governments with huge financial investments. Scientists and researchers from India also left no stone unturned to find therapeutic and preventive measures against COVID-19. Indian pharmaceutical companies are one of the leading manufacturers of vaccine in the world, are utilizing its capacity to its maximum, and are one among the forerunners in vaccine research against COVID-19 across the globe. In this systematic review, the information regarding contribution of Indian scientists toward COVID-19 research has been gathered from various news articles across Google platform apart from searching PubMed, WHO site, COVID-19 vaccine tracker, CTRI, clinicaltrials.gov, and websites of pharmaceutical companies. The article summarizes and highlights the various therapeutic and vaccine candidates, diagnostic kits, treatment agents, and technology being developed and tested by Indian researcher community against COVID-19.
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http://dx.doi.org/10.4103/ijp.ijp_168_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216129PMC
May 2021

Effects of exercise therapy plus manual therapy on muscle activity, latency timing and SPADI score in shoulder impingement syndrome.

Complement Ther Clin Pract 2021 Aug 19;44:101390. Epub 2021 Apr 19.

ENRICH PHYSIO CLINIC, Melbourne, Victoria, Australia.

Purpose: The study aimed to compare the effects of exercise therapy plus manual therapy (ET plus MT) and exercise therapy (ET) alone on muscle activity, muscle onset latency timing and shoulder pain and disability index-Hindi (SPADI-H) score in athletes with shoulder impingement syndrome (SIS).

Materials And Method: Overhead male athletes diagnosed with SIS were randomly allocated into ET plus MT group(n = 40) and ET group(n = 40). Muscle activity, muscle onset latency timings and SPADI-H score were assessed. Both the groups performed 8 weeks of intervention and were evaluated at baseline, 4th and 8th weeks.

Result: ET plus MT group was more effective in increasing muscle activity, optimising latency timings and decreasing SPADI score when compared to ET group alone(p < 0.05). After treatment muscle activity and SPADI-H improved in both groups (p < 0.05).

Conclusion: ET plus MT was superior for improving muscle activity, muscle onset latency timing and SPADI score compared to ET alone.
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http://dx.doi.org/10.1016/j.ctcp.2021.101390DOI Listing
August 2021

Assessment of knowledge and opinion regarding breastfeeding practices during COVID-19 pandemic among paediatricians and obstetricians in India: an online survey.

Sudan J Paediatr 2021 ;21(1):30-35

Department of Preventive and Social Medicine, Subharti Medical College, Meerut, India.

Coronavirus disease 19 (COVID-19) is a novel coronavirus infection that has a wide spectrum of disease severity. The virus has not been known to pass through the placenta and has not been reported in the breastmilk of affected mothers. As the cases are still on a rise, it is expected that the number of pregnant females would also rise in the coming times. Among many queries during pregnancy, to breastfeed or not is an important question that needs to be answered. We conducted this survey to assess the knowledge regarding breastfeeding practices among Indian paediatricians and obstetricians during the COVID-19 pandemic. An online survey was conducted among paediatricians and obstetricians from all over India. Only 294 (54.1%) participants have adequate knowledge regarding breastfeeding recommendations. The gap in knowledge between paediatricians and obstetricians was found statistically significant with a value of <0.01. Only 30% healthcare providers associated with perinatal care received this information through a seminar. On the other hand, 15% of participants were not aware of any guidelines on breastfeeding during the COVID-19 pandemic. More rigorous dissemination of information on breastfeeding practices in COVID-19 case management needs to be adopted.
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http://dx.doi.org/10.24911/SJP.106-1598349125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025992PMC
January 2021

Treatment of Small Keloids Using Intralesional 5-fluorouracil and Triamcinolone Acetonide versus Intralesional Bleomycin and Triamcinolone Acetonide.

J Clin Aesthet Dermatol 2021 Mar 1;14(3):17-21. Epub 2021 Mar 1.

Drs. Sharma and Vinay are with the Department of Dermatology, Venereology, and Leprosy at the Sri Guru Ram Das Institute of Medical Sciences & Research in Amritsar, Punjab, India.

The aberration of wound healing leads to scar formation in the form of hypertrophic scars and keloids. Various modalities with variable results have been used in the treatment of keloids. We sought to evaluate outcomes in the treatment of small keloids with the combination of intralesional 5-fluorouracil (5-FU) and triamcinolone acetonide versus intralesional bleomycin and triamcinolone acetonide. Sixty clinically diagnosed keloid lesions in 40 patients aged 18 to 60 years were divided equally into Groups A (n=30) and B (n=30). The combination of intralesional 5-FU and triamcinolone acetonide (TAC) was given to Group A and the combination of intralesional bleomycin and triamcinolone acetonide was given to Group B. Treatment was repeated in both groups at three-week intervals until keloid flattening was achieved or a maximum of 10 treatments were completed. Before treatment, the lesions were assessed using the Vancouver Scar Scale and their size was measured using vernier calipers. In Group A, 15 (50%) keloids showed an excellent response, 10 (33.33%) keloids showed a good response, three (10%) keloids showed a fair response, and two (6.66%) keloids showed a poor response. In Group B, 23 (76%) keloids showed an excellent response, three (10%) keloids showed a good response, two (6.66%) keloids showed a fair response, and two (6.66%) keloids showed a poor response. Patient response regarding treatment duration, flattening of lesions, improvements in the Vancouver Scar Scale score, and recurrence rates were statistically significant in Group B. A greater improvement in the signs and symptoms of keloids (with respect to cosmetic problems, restriction of movement, and tenderness) was observed in the patients treated with a combination of intralesional bleomycin and triamcinolone acetonide compared to those treated with a combination of intralesional 5-FU and triamcinolone acetonide.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021404PMC
March 2021

Emerging trends from COVID-19 research registered in the Clinical Trials Registry - India.

Indian J Med Res 2021 Jan & Feb;153(1 & 2):26-63

Clinical Trials Registry-India, ICMR-National Institute of Medical Statistics, New Delhi, India.

Since the beginning of the year, the deadly coronavirus pandemic, better known as coronavirus disease 2019 (COVID-19), brought the entire world to an unprecedented halt. In tandem with the global scenario, researchers in India are actively engaged in the conduct of clinical research to counter the pandemic. This review attempts to provide a comprehensive overview of the COVID-19 research in India including design aspects, through the clinical trials registered in the Clinical Trials Registry - India (CTRI) till June 5, 2020. One hundred and twenty two registered trials on COVID-19 were extracted from the CTRI database. These trials were categorized into modern medicine (n=42), traditional medicine (n=67) and miscellaneous (n=13). Of the 42 modern medicine trials, 28 were on repurposed drugs, used singly (n=24) or in combination (n=4). Of these 28 trials, 23 were to evaluate their therapeutic efficacy in different severities of the disease. There were nine registered trials on cell- and plasma-based therapies, two phytopharmaceutical trials and three vaccine trials. The traditional medicine trials category majorly comprised Ayurveda (n=45), followed by homeopathy (n=14) and others (n=8) from Yoga, Siddha and Unani. Among the traditional medicine category, 31 trials were prophylactic and 36 were therapeutic, mostly conducted on asymptomatic or mild-to-moderate COVID-19 patients. This review would showcase the research being conducted on COVID-19 in the country and highlight the research gaps to steer further studies.
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http://dx.doi.org/10.4103/ijmr.IJMR_2556_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184082PMC
April 2021
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