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Fulltext Medico-legal aspects of anaesthesia practice

Krishna SR

Med J Malaysia, 1991 Dec;46(4):320-8.
PMID: 1840439

The public especially in West Malaysia are becoming more aware of their rights and litigations are on the increase. Fortunately in East Malaysia there are fewer cases. The legal aspects of anaesthesia practice are very much on the lines of British system. Here the cause for compensation or legal action depends on the proof of negligence. Currently in West Malaysia all anaesthetics are being given by medical practitioners. In East Malaysia the anaesthetics are being given mainly by Medical Assistant's who have been trained for about six months to give anaesthesia in all government hospitals. There are guidelines on minimum standard of safety for patients undergoing general anaesthesia, though this is not as elaborate as those in Western countries.
An intensive care unit in a rural area

Krishna SR

Anaesth Intensive Care, 1975 May;3(2):122-6.
PMID: 1155754

Factors that governed the setting up of a multipurpose, temporary Intensive Care Unit of six beds, in a remote area of Malaysia and the experience of operating it for more than two and a half years are outlined.
A case of rupture of a main bronchus from a closed chest injury and its management in a child

Selvarajah N, Krishna SR

Med J Malaysia, 1974 Jun;28(4):276-8.
PMID: 4278977
Fulltext Antiarthritic activity of a polyherbal formulation against Freund's complete adjuvant induced arthritis in Female Wistar rats

Petchi RR, Parasuraman S, Vijaya C, Gopala Krishna SV, Kumar MK

J Basic Clin Pharm, 2015 Jun;6(3):77-83.
PMID: 26229343 DOI: 10.4103/0976-0105.160738

OBJECTIVES:
To formulate a polyherbal formulation and evaluate its antiarthritic activity against Freund's complete adjuvant induced arthritis in Female Wistar rats.

MATERIALS AND METHODS:
Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including arthritis. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla , whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. Arthritis was induced in female Wistar rats using Freund's complete adjuvant (FCA), and the antiarthritic effect of polyherbal formulation was studied at doses of 250 and 500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, blood samples were collected for biochemical and hematological analysis. The radiological examination was carried out before terminating the study.

RESULTS:
Polyherbal formulation showed significant antiarthritic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of indomethacin. The antiarthritic activity of polyherbal formulation is supported by biochemical and hematological analysis.

CONCLUSION:
The polyherbal formulation showed signinicant antiarthritic activity against FCA-induced arthritis in female Wistar rats.

KEYWORDS:
Arthritis; Fingerprint analysis; Glycosmis pentaphylla; Mangifera indica; Tridax procumbens
Fulltext Synthesis of novel cytotoxic tetracyclic acridone derivatives and study of their molecular docking, ADMET, QSAR, bioactivity and protein binding properties

Veligeti R, Madhu RB, Anireddy J, Pasupuleti VR, Avula VKR, Ethiraj KS, et al.

Sci Rep, 2020 11 26;10(1):20720.
PMID: 33244007 DOI: 10.1038/s41598-020-77590-1

Acridone based synthetic and natural products with inherent anticancer activity advancing the research and generating a large number of structurally diversified compounds. In this sequence we have designed, synthesized a series of tetracyclic acridones with amide framework viz., 3-(alkyloyl/ aryloyl/ heteroaryloyl/ heteroaryl)-2,3-dihydropyrazino[3,2,1-de]acridin-7(1H)-ones and screened for their in vitro anti-cancer activity. The in vitro study revealed that compounds with cyclopropyl-acetyl, benzoyl, p-hydroxybenzoyl, p-(trifluoromethyl)benzoyl, p-fluorobenzoyl, m-fluorobenzoyl, picolinoyl, 6-methylpicolinoyl and 3-nicotinoyl groups are active against HT29, MDAMB231 and HEK293T cancer cell lines. The molecular docking studies performed for them against 4N5Y, HT29 and 2VWD revealed the potential ligand-protein binding interactions among the neutral aminoacid of the enzymes and carbonyl groups of the title compounds with a binding energy ranging from - 8.1394 to - 6.9915 kcal/mol. In addition, the BSA protein binding assay performed for them has confirmed their interaction with target proteins through strong binding to BSA macromolecule. The additional studies like ADMET, QSAR, bioactivity scores, drug properties and toxicity risks ascertained them as newer drug candidates. This study had added a new collection of piperazino fused acridone derivatives to the existing array of other nitrogen heterocyclic fused acridone derivatives as anticancer agents.
Fulltext Evaluation of three rapid diagnostic tests for the detection of human infections with Plasmodium knowlesi

Foster D, Cox-Singh J, Mohamad DS, Krishna S, Chin PP, Singh B

Malar J, 2014;13:60.
PMID: 24548805 DOI: 10.1186/1475-2875-13-60

Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, infects humans and can cause fatal malaria. It is difficult to diagnose by microscopy because of morphological similarity to Plasmodium malariae. Nested PCR assay is the most accurate method to distinguish P. knowlesi from other Plasmodium species but is not cost effective in resource-poor settings. Rapid diagnostic tests (RDTs) are recommended for settings where malaria is prevalent. In this study, the effectiveness of three RDTs in detecting P. knowlesi from fresh and frozen patient blood samples was evaluated.
Fulltext Repurposing Antimalarials to Tackle the COVID-19 Pandemic

Krishna S, Augustin Y, Wang J, Xu C, Staines HM, Platteeuw H, et al.

Trends Parasitol, 2021 01;37(1):8-11.
PMID: 33153922 DOI: 10.1016/j.pt.2020.10.003

Artemisinin-based combination therapies (ACTs) have demonstrated in vitro inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Artemisinins have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe coronavirus disease 2019 (COVID-19). There is now sufficient evidence for the effectiveness of ACTs, and in particular artesunate/pyronaridine, to support clinical studies for COVID-19 infections.
Drug repurposing for COVID-19: current evidence from randomized controlled adaptive platform trials and living systematic reviews

Augustin Y, Staines HM, Velavan TP, Kamarulzaman A, Kremsner PG, Krishna S

Br Med Bull, 2023 Sep 12;147(1):31-49.
PMID: 37312588 DOI: 10.1093/bmb/ldac037

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic resulted in a race to develop effective treatments largely through drug repurposing via adaptive platform trials on a global scale. Drug repurposing trials have focused on potential antiviral therapies aimed at preventing viral replication, anti-inflammatory agents, antithrombotic agents and immune modulators through a number of adaptive platform trials. Living systematic reviews have also enabled evidence synthesis and network meta-analysis as clinical trial data emerge globally.
SOURCES OF DATA: Recent published literature.
AREAS OF AGREEMENT: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community.
AREAS OF CONTROVERSY: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery.
GROWING POINTS: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine.
AREAS TIMELY FOR DEVELOPING RESEARCH: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.
Fulltext Plasmodium knowlesi genome sequences from clinical isolates reveal extensive genomic dimorphism

Pinheiro MM, Ahmed MA, Millar SB, Sanderson T, Otto TD, Lu WC, et al.

PLoS One, 2015;10(4):e0121303.
PMID: 25830531 DOI: 10.1371/journal.pone.0121303

Plasmodium knowlesi is a newly described zoonosis that causes malaria in the human population that can be severe and fatal. The study of P. knowlesi parasites from human clinical isolates is relatively new and, in order to obtain maximum information from patient sample collections, we explored the possibility of generating P. knowlesi genome sequences from archived clinical isolates. Our patient sample collection consisted of frozen whole blood samples that contained excessive human DNA contamination and, in that form, were not suitable for parasite genome sequencing. We developed a method to reduce the amount of human DNA in the thawed blood samples in preparation for high throughput parasite genome sequencing using Illumina HiSeq and MiSeq sequencing platforms. Seven of fifteen samples processed had sufficiently pure P. knowlesi DNA for whole genome sequencing. The reads were mapped to the P. knowlesi H strain reference genome and an average mapping of 90% was obtained. Genes with low coverage were removed leaving 4623 genes for subsequent analyses. Previously we identified a DNA sequence dimorphism on a small fragment of the P. knowlesi normocyte binding protein xa gene on chromosome 14. We used the genome data to assemble full-length Pknbpxa sequences and discovered that the dimorphism extended along the gene. An in-house algorithm was developed to detect SNP sites co-associating with the dimorphism. More than half of the P. knowlesi genome was dimorphic, involving genes on all chromosomes and suggesting that two distinct types of P. knowlesi infect the human population in Sarawak, Malaysian Borneo. We use P. knowlesi clinical samples to demonstrate that Plasmodium DNA from archived patient samples can produce high quality genome data. We show that analyses, of even small numbers of difficult clinical malaria isolates, can generate comprehensive genomic information that will improve our understanding of malaria parasite diversity and pathobiology.
Fulltext Susceptibility of human Plasmodium knowlesi infections to anti-malarials

Fatih FA, Staines HM, Siner A, Ahmed MA, Woon LC, Pasini EM, et al.

Malar J, 2013;12:425.
PMID: 24245918 DOI: 10.1186/1475-2875-12-425

Evidence suggests that Plasmodium knowlesi malaria in Sarawak, Malaysian Borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure. Therefore, adequate response to available anti-malarial treatments is assumed.
Fulltext Anomalous excess noise behavior in thick Al0.85Ga0.15As0.56Sb0.44 avalanche photodiodes

Lewis HIJ, Jin X, Guo B, Lee S, Jung H, Kodati SH, et al.

Sci Rep, 2023 Jun 19;13(1):9936.
PMID: 37336988 DOI: 10.1038/s41598-023-36744-7

Al0.85Ga0.15As0.56Sb0.44 has recently attracted significant research interest as a material for 1550 nm low-noise short-wave infrared (SWIR) avalanche photodiodes (APDs) due to the very wide ratio between its electron and hole ionization coefficients. This work reports new experimental excess noise data for thick Al0.85Ga0.15As0.56Sb0.44 PIN and NIP structures, measuring low noise at significantly higher multiplication values than previously reported (F = 2.2 at M = 38). These results disagree with the classical McIntyre excess noise theory, which overestimates the expected noise based on the ionization coefficients reported for this alloy. Even the addition of 'dead space' effects cannot account for these discrepancies. The only way to explain the low excess noise observed is to conclude that the spatial probability distributions for impact ionization of electrons and holes in this material follows a Weibull-Fréchet distribution function even at relatively low electric-fields. Knowledge of the ionization coefficients alone is no longer sufficient to predict the excess noise properties of this material system and consequently the electric-field dependent electron and hole ionization probability distributions are extracted for this alloy.
Fulltext Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members

Ahmed AM, Pinheiro MM, Divis PC, Siner A, Zainudin R, Wong IT, et al.

PLoS Negl Trop Dis, 2014 Aug;8(8):e3086.
PMID: 25121807 DOI: 10.1371/journal.pntd.0003086

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p = <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region.
Current Status of Training and Certification for Congenital Heart Surgery Around the World: Proceedings of the Meetings of the Global Council on Education for Congenital Heart Surgery of the World Society for Pediatric and Congenital Heart Surgery

Tchervenkov CI, Herbst C, Jacobs JP, Al-Halees Z, Edwin F, Dearani JA, et al.

World J Pediatr Congenit Heart Surg, 2021 05;12(3):394-405.
PMID: 33942697 DOI: 10.1177/21501351211003520

The optimal training of the highly specialized congenital heart surgeon is a long and complex process, which is a significant challenge in most parts of the world. The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) has established the Global Council on Education for Congenital Heart Surgery as a nonprofit organization with the goal of assessing current training and certification and ultimately establishing standardized criteria for the training, evaluation, and certification of congenital heart surgeons around the world. The Global Council and the WSPCHS have reviewed the present status of training and certification for congenital cardiac surgery around the world. There is currently lack of consensus and standardized criteria for training in congenital heart surgery, with significant disparity between continents and countries. This represents significant obstacles to international job mobility of competent congenital heart surgeons and to the efforts to improve the quality of care for patients with Congenital Heart Disease worldwide. The purpose of this article is to summarize and document the present state of training and certification in congenital heart surgery around the world.
Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery

Zheleva B, Verstappen A, Overman DM, Ahmad F, Ali SKM, Al Halees ZY, et al.

Cardiol Young, 2023 Aug;33(8):1277-1287.
PMID: 37615116 DOI: 10.1017/S1047951123002688

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
A living WHO guideline on drugs for covid-19

Agarwal A, Hunt B, Stegemann M, Rochwerg B, Lamontagne F, Siemieniuk RA, et al.

BMJ, 2020 Sep 04;370:m3379.
PMID: 32887691 DOI: 10.1136/bmj.m3379

UPDATES: This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline.
CLINICAL QUESTION: What is the role of drugs in the treatment of patients with covid-19?
CONTEXT: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics.
WHAT IS NEW?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19.
ABOUT THIS GUIDELINE: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.
FUTURE RECOMMENDATIONS: Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations.

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