Use of computerized tests to evaluate psychomotor performance in children with specific learning disabilities in comparison to normal children.

BACKGROUND & OBJECTIVES: Children with specific learning disabilities (SpLD) have an unexplained difficulty in acquiring basic academic skills resulting in a significant discrepancy between their academic potential and achievements. This study was undertaken to compare the performance on a battery of six psychomotor tests of children with SpLD and those without any learning disabilities (controls) using computerized tests. METHODS: In this study, 25 children with SpLD and 25 controls (matched for age, socio-economic status and medium of instruction) were given three training sessions over one week. Then children were asked to perform on the six computerized psychomotor tests. RESULTS were compared between the two groups. RESULTS: Children with SpLD fared significantly worse on finger tapping test, choice reaction test, digit picture substitution test and card sorting test compared to the controls ( p <0.05). INTERPRETATION & CONCLUSIONS: Children with SpLD have impairment of psychomotor skills like attention, sensory-motor coordination and executive functioning. Further research is needed to evaluate if the remedial education plan results in improvement in psychomotor performance of children with SpLD on these selected tests.

An audit of therapeutic drug monitoring services of anticonvulsants at a tertiary care hospital in India.

BACKGROUND: Therapeutic drug monitoring (TDM) is an important adjunct to the treatment of epilepsy. However, few studies have actually correlated plasma levels of antiepileptic drugs (AEDs) with treatment response. The present audit aimed to study (i) the association between seizure control and number of AEDs, plasma AED concentration, and concomitant use of antitubercular drugs; (ii) the pattern of indications for TDM requisitions; and (iii) the association between referral for toxicity and plasma AED concentration. METHODS: This observational and retrospective study was carried out to analyze the TDM data of patients referred between January 2008 and December 2011. As per the International League Against Epilepsy Task Force 2009, patients were categorized into responders and nonresponders. Plasma AED levels were interpreted as below, within, and above the reference range. RESULTS: Of 3206 TDM requisitions, 67% were monotherapy and 33% were 2 or more AEDs. Only 8% were responders as against 92% nonresponders. Of 95 patients on concomitant antituberculosis treatment, 72 were nonresponders, with odds ratio (95% confidence interval) 3.71 [2.19 to 6.23]. Breakthrough seizure (37%) was the most common indication followed by suspected toxicity and routine monitoring in 22% each and suspected nonadherence in 11% of the total requests. In 52% of patients, plasma levels were below the reference range, and they were equally distributed amongst responders and nonresponders. Among patients referred for suspected phenytoin toxicity, only 59% (50.6 to 67.8) had plasma concentrations above the reference range. CONCLUSIONS: TDM continues to remain an important tool to support dose individualization when the patient is receiving multiple AEDs or other drugs such as antitubercular medicines, to assess compliance, and to monitor and treat toxicity.

A Multicenter Evaluation of Overall Susceptibility and Antimicrobial Resistance Among Streptococcus pneumoniae Isolates.

PURPOSE: S. pneumoniae ranks as the fourth-most lethal pathogen globally in terms of fatalities associated with or attributable to resistance. In this study, the Antimicrobial Testing Leadership and Surveillance (ATLAS) analysis from India aims to study the overall antimicrobial susceptibility (AMS) among pneumococcal isolates collected between 2018 and 2021. METHODS: Non-duplicate clinically significant S. pneumoniae isolates were collected between 2018 and 2021. In vitro activity of antibiotics was assessed against S. pneumoniae. Susceptibility was confirmed at an International Health Management Associates (IHMA) laboratory using supplied broth microdilution panels (Omron Microscan Systems, Inc., Omron Corp., Kyoto, Japan), according to the Clinical and Laboratory Standards Institute (CLSI) guidelines for all antibiotics. RESULTS: Of the total 86 non-duplicate isolates of Streptococcus pneumoniae collected from the tertiary care centers, the proportion of isolates increased from 8.14% (n=7) in 2018 to 43.02% (n=37) in 2020. Most isolates (n = 18; 48.65%) were collected from the age group of 31-60 years in the year 2020. Erythromycin revealed a decrease in susceptibility from the year 2018 (71.43%) to 2020 (16.22%). A decreased susceptibility of 90% was recorded for levofloxacin in the year 2021. Meropenem revealed a decrease in susceptibility from the year 2018 (85.71%) to 2020 (35.14%). Penicillin susceptibility decreased from 37.5% in 2019 to 27.03% in the year 2020. Clindamycin indicated a 100% susceptibility in the year 2018 which then decreased to 71.88% in 2019 and 56.76% in 2020. Linezolid and vancomycin were found to have uniform susceptibility of 100% throughout the years from 2018 to 2021. CONCLUSION: An increase in resistance to penicillin and macrolides among S. pneumoniae isolates was observed in the Indian population. Addressing the elevating rates of S. pneumoniae resistance may require pneumococcal conjugate vaccines (PCVs) with expanded serotype coverage and targeted antimicrobial stewardship efforts.

A Cardiologists' Survey on the Use of Anticoagulants and Antiplatelets in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Those Undergoing Percutaneous Coronary Intervention in India.

PURPOSE: The management of patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) requires appropriate antithrombotic regimens for stroke prevention and in-stent thrombosis. Current practice recommendations are largely based on consensus options as there is limited evidence from randomized clinical trials. Hence, by surveying a group of cardiologists across India, we sought to better understand the current practice patterns of using oral anticoagulants (vitamin K antagonist, VKA or non-vitamin K antagonist oral anticoagulant, NOAC) and antiplatelet therapy in those patients in India. METHODS: A cross-sectional questionnaire-based survey was conducted across India to better understand the clinical practices in AF management. RESULTS: A total of 151 cardiologists participated in this survey. The most commonly prescribed combination therapy in patients with AF and ACS/undergoing PCI was triple therapy (NOAC + dual antiplatelet [aspirin and P2Y12 inhibitor]) (54.30%) followed by NOAC + single antiplatelet (33.11%). Only 11.26% of cardiologists prescribed VKA + dual antiplatelet therapy. Among anticoagulants, cardiologists prescribed NOACs to 66.11% of patients and VKAs to 25.54% of patients. Among P2Y12 inhibitors, ticagrelor (50.99%) and clopidogrel (47.02%) were the most preferred medication. The physician reported patient adherence rates to NOACs were higher compared to VKAs. Around 41.06% of cardiologists reportedly changed antiplatelet therapy for patients from dual antiplatelet to single antiplatelet therapy in three months; 36.42%, in one month; and 19.21% in six months after PCI. Around 61.59% of cardiologists stopped prescribing antiplatelet therapy for patients by one year. CONCLUSION: Our survey demonstrated that the majority of cardiologists used triple therapy (NOAC + dual antiplatelet), followed by NOAC + single antiplatelet for managing patients with AF and ACS or undergoing PCI in line with the available guidelines.

'Oxidative stress'-A new target in the management of diabetes mellitus.

Diabetes mellitus (DM) is a chronic condition that poses a mammoth challenge for the healthcare system in developing as well as developed nations. Diabetes mellitus is associated with damage to the vasculature which leads to microvascular and macrovascular complications. Oxidative stress is a consequence of glucotoxicity and lipotoxicity, which are associated with diabetes. Glucotoxicity and lipotoxicity play a part in the pathogenesis of ß-cell dysfunction. The hyperglycemic state in DM leads to oxidative stress which further hampers insulin secretion. In diabetes, the biological antioxidants also get depleted along with a reduction in glutathione (GSH), an increase in the oxidized glutathione (GSSG)/GSH ratio, and a depletion of non-enzymatic antioxidants. This results in the formation of a viscous circle of hyperglycemia leading to increased oxidative stress that further hampers insulin secretion which in turn results in hyperglycemia. Antioxidants are efficacious in reducing diabetic complications. The antioxidants produced biologically fall short, hence external supplements are required. In this review, the authors have discussed the relationship between oxidative stress in DM and the advantages of antioxidant supplements in controlling blood glucose levels and also in deaccelerating the complications related to DM.

Association of CYP2C9 polymorphisms with phenytoin toxicity in Indian patients.

BACKGROUND: Genetic polymorphisms of CYP2C9 can lead to wide inter-individual variations in drug metabolism. Decreased metabolism leads to higher plasma levels, causing adverse drug reactions (ADRs). Polymorphic alleles CYP2C9 FNx01 2 and CYP2C9 FNx01 3 occur in the Indian population and this may serve as the basis for using genotyping as a tool to predict phenytoin toxicity. AIMS: To evaluate the association between the presence of polymorphic alleles CYP2C9 FNx01 2 and FNx013 and phenytoin toxicity in Indian patients with epilepsy. SETTINGS AND DESIGN: A case-control study with cases defined as those who had plasma phenytoin concentrations above 20 µg/ml. MATERIALS AND METHODS: The study population included 259 patients with epilepsy on phenytoin. Phenotyping was done using High Performance Liquid Chromatography. Those with plasma phenytoin levels above 20 µg/ml were taken as cases and the rest as controls. Genotyping was done by Polymerase Chain Reaction - Restriction Fragment Length Polymorphism. STATISTICS: Numerical data between groups was compared using unpaired-'t' test. Between-group comparison of categorical data was done using Chi square for trend with crude odds ratio (OR). Adjusted OR was calculated using binary logistic regression. RESULTS: There were 40 cases and 219 controls. Mean phenytoin dosage between groups was not statistically significant. Of the 40 cases, 25 (62.5%) cases had wild alleles versus 178 (81.3%) controls. We found a significant association between polymorphic alleles CYP2C9 FNx01 2 and FNx013 and toxic phenytoin levels. After adjusting for age, sex and dose, a significant association between polymorphic alleles and phenytoin toxicity was still found. CONCLUSIONS: This study shows significant association between polymorphic alleles and phenytoin toxicity in this study population. However, until technology for genotyping becomes cost-effective, we would recommend Therapeutic Drug Monitoring to guide dosing.

Observational designs for real-world evidence studies.

In the era of evidence-based medicine, real-world evidence (RWE) studies have opened avenues to utilize real-world data (RWD) effectively for improving clinical decision-making. However, the transformation of RWD into a meaningful RWE can only be achieved when the researcher asks the right clinical question, selects the right RWD source for variables of interest, uses the right study design, and applies the right statistical analysis. The generated RWE needs to have internal as well as external validity to be actionable. The "fit-for-purpose" observational study designs include descriptive, case-control, cross-sectional, and cohort. This article focuses on the advantages and disadvantages including the inherent bias of each study design. The RWE study decision guide has also been provided to aid the selection of appropriate study designs.

Anticoagulation for Stroke Prevention of Concomitant Atrial Fibrillation and End-Stage Renal Disease: Insights of Cardiologists and Nephrologists From India.

Introduction Patients with concomitant atrial fibrillation (AF) and end-stage renal disease (ESRD) are at increased risk of thrombosis and bleeding. Diligent anticoagulant therapy that prevents major bleeding is essential for stroke prevention. There is a dearth of evidence and guidance on anticoagulation in this patient subset. Methods A validated questionnaire was sent to 500 physicians across India. Anonymized responses from 353 consenting physicians (275 cardiologists and 78 nephrologists) were analyzed. Results Most physicians opined that the risk of progression of chronic kidney disease (CKD) stages 2-4 to ESRD was 1-5%, and that >10% of patients with ESRD had concomitant AF. Most physicians perceived that the risk of ischemic stroke, major bleeding, and mortality was 30-40%, <15%, and >40% respectively in patients with concomitant AF and ESRD. The first critical goal for the management of these patients was 'reduction of thrombotic risk', followed by 'prevention of bleeding' and finally 'prevention of ESRD progression' (72.0%, 68.0%, and 67.1% participants, respectively). Most participating physicians (93.8%) preferred non-vitamin K antagonist oral anticoagulants (NOACs) over warfarin for stroke prevention, and most of the participating physicians (94.9%) preferred an adjusted dose rather than the standard dose of the NOAC. Most of the responses were similar between cardiologists and nephrologists. Conclusion According to the survey response, patients with concomitant AF and ESRD have an increased risk of thrombosis, bleeding, and mortality. NOACs with dose adjustment are the preferred modality for stroke prevention among cardiologists and nephrologists in India, with the primary goal of preventing thrombotic events.

Safety of apixaban in Indian patients undergoing elective total knee replacement or total hip replacement surgery: A multi-center, phase-IV study.

BACKGROUND: Venous thromboembolism is a significant source of morbidity and mortality following total hip replacement and total knee replacement. Apixaban has been proven to be efficacious without increased risk of bleeding in phase-III trials in patients undergoing total knee replacement and total hip replacement. Due to paucity of data on safety of apixaban in Indian patients, this phase-IV study was conducted to evaluate safety of apixaban in patients undergoing total knee replacement and total hip replacement. METHODS: In this non-comparative phase-IV clinical trial, patients undergoing elective total knee replacement or total hip replacement surgery, or a revision of at least one component of total knee replacement or total hip replacement, were enrolled. The eligible patients were given the approved dosage of apixaban 12 to 24 h after completing the skin wound closure. The primary safety outcome was the composite of the International Society on Thrombosis and Haemostasis-defined major bleeding and clinically relevant non-major bleeding events at the end of the treatment. The secondary efficacy endpoint was the composite of venous thromboembolism/all-cause death at the end of the treatment. RESULTS: A total of 498 patients received apixaban prophylaxis therapy. Six (1.2%) bleeding adverse events were observed during the treatment period. Only one bleeding event was adjudicated as an International Society on Thrombosis and Haemostasis-defined clinically relevant non-major bleeding event (moderate severity). There were no fatal bleeding events and no deaths following the treatment. One venous thromboembolism event, that is, symptomatic distal left leg DVT, was reported in a total knee replacement patient and was adjudicated during the treatment period. CONCLUSION: Apixaban demonstrated a favorable safety profile for venous thromboembolism prevention in Indian patients undergoing total knee replacement or total hip replacement.

A study of agreement between the Naranjo algorithm and WHO-UMC criteria for causality assessment of adverse drug reactions.

OBJECTIVES: Reliability and usefulness of various adverse drug reaction (ADR) causality assessment scales have not been fully explored. There is no universally accepted method for causality grading of ADRs. In the present study we assessed agreement between the two widely used causality assessment scales, that is, the World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria and the Naranjo algorithm. MATERIALS AND METHODS: The same observer assessed all ADRs (n = 913) collected between January 2010 and December 2012 using the WHO-UMC criteria and Naranjo algorithm at a tertiary care hospital in India. We found that the most frequently assigned causality category was "possible" with both the scales. RESULTS: A disagreement in the causality assessment was found in 45 (4.9%) cases reflecting "poor" agreement between the two scales (Kappa statistic with 95% confidence interval = 0.143 [0.018, 0.268]). The mean time taken to assess causality of the ADR using the WHO-UMC criteria was shorter than that by the Naranjo algorithm. CONCLUSION: This study showed that there is a poor agreement between the WHO-UMC criteria and Naranjo algorithm with the former being less time-consuming.

Establishing institutional ethics committees: challenges and solutions - a review of the literature.

This review of the literature was conducted to identify the challenges faced while establishing institutional ethics committees (IECs) as well as to suggest some solutions. The search of the literature was carried out with the help of the PubMed search engine, using "research ethics committees" (MeSH] and "India" (MeSH]) as the key words for articles published between 2004 and 2012. We found 31 articles related to the topic, and the most common challenge mentioned was inappropriate functioning of IECs (n=17), followed by inappropriate structure (n=14). The authors identified many challenges related to the lack of oversight by regulatory bodies (n=14) as well as issues pertaining to the ethical training of IEC members and investigators (n=13). It is evident from the multitude of papers on the issue that the challenges related to the constitution and functioning of IECs must be given the attention they deserve to ensure that research participants in India are better protected.

Serum profiling of leptospirosis patients to investigate proteomic alterations.

Leptospirosis is a zoonotic infectious disease of tropical, subtropical and temperate zones, which is caused by the pathogenic spirochetes of genus Leptospira. Although this zoonosis is generally not considered as fatal, the pathogen can eventually cause severe infection with septic shock, multi-organ failure and lethal pulmonary hemorrhages leading to mortality. In this study, we have performed a proteomic analysis of serum samples from leptospirosis patients (n=6), febrile controls (falciparum malaria) (n=8) and healthy subjects (n=18) to obtain an insight about disease pathogenesis and host immune responses in leptospiral infections. 2DE and 2D-DIGE analysis in combination with MALDI-TOF/TOF MS revealed differential expression of 22 serum proteins in leptospirosis patients compared to the healthy controls. Among the identified differentially expressed proteins, 8 candidates exhibited different trends compared to the febrile controls. Functional analysis suggested the involvement of differentially expressed proteins in vital physiological pathways, including acute phase response, complement and coagulation cascades and hemostasis. This is the first report of analysis of human serum proteome alterations in leptospirosis patients, which revealed several differentially expressed proteins, including α-1-antitrypsin, vitronectin, ceruloplasmin, G-protein signaling regulator, apolipoprotein A-IV, which have not been reported in context of leptospirosis previously. This study will enhance our understanding about leptospirosis pathogenesis and provide a glimpse of host immunological responses. Additionally, a few differentially expressed proteins identified in this study may further be investigated as diagnostic or prognostic serum biomarkers for leptospirosis. This article is part of a Special Issue entitled: Integrated omics.

Proteomic investigation of falciparum and vivax malaria for identification of surrogate protein markers.

This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.

Serum proteome analysis of vivax malaria: An insight into the disease pathogenesis and host immune response.

Vivax malaria is the most widely distributed human malaria resulting in 80-300 million clinical cases every year. It causes severe infection and mortality but is generally regarded as a benign disease and has not been investigated in detail. The present study aimed to perform human serum proteome analysis in a malaria endemic area in India to identify potential serum biomarkers for vivax malaria and understand host response. The proteomic analysis was performed on 16 age and gender matched subjects (vivax patients and control) in duplicate. Protein extraction protocols were optimized for large coverage of the serum proteome and to obtain high-resolution data. Identification of 67 differentially expressed and statistically significant (Student's t-test; p<0.05) protein spots was established by MALDI-TOF/TOF mass spectrometry. Many of the identified proteins such as apolipoprotein A and E, serum amyloid A and P, haptoglobin, ceruloplasmin, and hemopexin are interesting from a diagnostic point of view and could further be studied as potential serum biomarkers. The differentially expressed serum proteins in vivax malaria identified in this study were subjected to functional pathway analysis using multiple software, including Ingenuity Pathway Analysis (IPA), Protein ANalysis THrough Evolutionary Relationships (PANTHER) and Database for Annotation, Visualization and Integrated Discovery (DAVID) functional annotation tool for better understanding of the biological context of the identified proteins, their involvement in various physiological pathways and association with disease pathogenesis. Functional pathway analysis of the differentially expressed proteins suggested the modulation of multiple vital physiological pathways, including acute phase response signaling, complement and coagulation cascades, hemostasis and vitamin D metabolism pathway due to this parasitic infection. This article is part of a Special Issue entitled: Proteomics: The clinical link.

Survey of ethics committee protocol approval letters: compliance with Schedule Y/ICMR guidelines 2006.

A study was carried out to determine the extent to which ECs comply with format requirements given in guidelines and regulations. ECs were sent a written communication requesting them to permit investigators to study their approval letter for compliance with the ICMR Guidelines and Schedule Y using a pre-designed proforma. Of the 60 ECs approached, only 20 agreed to participate. Legal experts and social scientists were not present at the approval meetings of most of the ECs. Only 7 ECs had a quorum according to Schedule Y Several ECs did not state whether documents such as the clinical trial agreement and insurance policy were reviewed. Delays in sending approval letters could be shortened with efficacious operating of ECs. There is a need to train EC members and create a better awareness of regulatory requirements. There is also a need to evolve a mechanism to monitor EC functioning.