Single intraoperative intravenous Co-Amoxiclav versus postoperative full oral course in prevention of postadenotonsillectomy morbidity: a randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>Adenotonsillectomy results in postoperative morbidity which otolaryngologists attempt to reduce by use of antibiotics. The regimes used as quite varied with some opting for a full oral course postoperatively while others prefer prophylactic doses. This randomised clinical trial done in Kenyatta National Hospital, Kenya had the aim of comparing the efficacy of Co-Amoxiclav given as a single intravenous dose with a full oral course in the prevention of post adenotonsillectomy morbidity.</p> <p>Methods</p> <p>126 patients below 12 years scheduled to undergo adenotonsillectomy were randomised into two groups. 63 were given a single intravenous dose of Enhancin [Co-Amoxiclav] at induction while the remaining half received a five days oral course of the same postoperatively. All received oral Pacimol [Paracetamol] in the postoperative period. Analysis was done and comparison made between the two groups with regards to pain, fever and diet tolerated in the postoperative period with a follow up period of seven days.</p> <p>Results</p> <p>There was no statistical significant difference between the two groups with regards to postoperative pain, fever and diet tolerated. All had a P-value > 0.2. Postoperative pain was highest in the first postoperative day and reduced progressively to the lowest level on the 7^thpostoperative day. As pain reduced, patients were able to tolerate a more solid diet with all but 6 tolerating their usual diet. 4 patients developed fever in the 1^stpostoperative day which did not progress to the next day. One patient had fever on the 4^thand 7^thpostoperative day and was admitted in the paediatrics' ward with a chest infection. All these patients with history of fever were in the group that was on oral postoperative Co-Amoxiclav.</p> <p>Conclusion</p> <p>A single intraoperative dose of Co-Amoxiclav given intravenously at induction was found to be just as effective as a full oral course of the same given postoperatively in the prevention of post adenotonsillectomy morbidity. The prophylactic dose is favoured over the later as it is cheaper, ensures compliance and relieves off the need for refrigeration of the oral suspension as not all have access to refrigeration in low economy countries as ours.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01267942">NCT01267942</a></p

Bacteriology of chronic suppurative otitis media (CSOM) in children in Garissa district, Kenya: A point prevalence study

Objectives To identify by type and sensitivity to drugs the bacteria found in ears of school-going children with chronic otitis media in Garissa district. Methods Study design: This was a descriptive prevalence study of CSOM bacterial flora in eligible ears conducted among a cohort of children attending public and private primary as well as Islamic religious schools, screened for chronic ear discharge in Garissa district, Kenya. Procedure and bacteriological techniques: We used sterile swab-sticks to collect a specimen of the discharge from eligible ears of consenting pupils at the induction stage of the zinc supplementation trial for treatment of chronic suppurative otitis media conducted between January and July 2010. All pupils below 18 years present on day of visit were eligible. Both aerobic and anaerobic bacterial cultures were done to identify clinically and epidemiologically important bacteria. Sensitivity tests were based on disc diffusion methods. Results are presented as frequencies and proportions. Results Of the pupils seen, 61% were still in pre- or lower primary school. Majority were aged 13 and 14 years. Of the 261 ear swab samples processed, 336 isolates – either in mixed or pure flora – were identified, being almost exclusively aerobes. Proteus spp., Enterococcus, Staphylococcus aureus and Pseudomonas spp. were isolated in 32.7%, 28.6%, 12.8% and 11.3% respectively. Proteus was susceptible to majority of the antibiotics tested for, while Enterococcus was poorly susceptible. Conclusions Aerobic bacteria were most prevalent in this study. Several of the bacteria identified are known to require iron for their growth. This may be important for CSOM treatment if biofilm formation is involved in pathogenesis. Majority of the isolates were susceptible to basic antibiotics compared to Enterococcus bacteria. This portends an important consideration for clinical management and therapeutic decision-making. Additionally, given the prevalence of Enterococcus bacteria, which is an indicator of faecal contamination of the environment, there is need to consider relevant public health components in managing childhood CSOM besides the clinical ones alone

Distribution and Molecular Diversity of Whitefly Species Colonizing Cassava in Kenya

The whitefly, Bemisia tabaci (Gennadium, Hemiptera) has been reported to transmit viruses that cause cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) in many parts of sub-Saharan Africa (SSA). Currently, there is limited information on the distribution, species and haplotype composition of the whitefly populations colonizing cassava in Kenya. A study was conducted in the major cassava growing regions of Kenya to address this gap. Analyses of mitochondrial DNA cytochrome oxidase 1 (mtCO1) sequences revealed the presence of four distinct whitefly species: Bemisia tabaci, Bemisia afer, Aleurodicus dispersus and Paraleyrodes bondari in Kenya. The B. tabaci haplotypes were further resolved into SSA1, SSA2 and Indian Ocean (IO) putative species. The SSA1 population had three haplogroups of SSA1-SG1, SSA-SG2 and SSA1-SG3. Application of KASP genotyping grouped the Bemisia tabaci into two haplogroups namely sub-Saharan Africa East and Southern Africa (SSA-ESA) and sub-Saharan Africa East and Central Africa (SSA-ECA). The study presents the first report of P. bondari (Bondar’s nesting whitefly) on cassava in Kenya. Bemisia tabaci was widely distributed in all the major cassava growing regions in Kenya. The increased detection of different whitefly species on cassava and genetically diverse B. tabaci mitotypes indicates a significant influence on the dynamics of cassava virus epidemics in the field. The study highlights the need for continuous monitoring of invasive whitefly species population on cassava for timely application of management practices to reduce the impact of cassava viral diseases and prevent potential yield losses

Real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for detection of cassava brown streak viruses

Cassava brown streak disease (CBSD) caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV) is the most economically important viral disease of cassava. As cassava is a vegetatively propagated crop, the development of rapid and sensitive diagnostics would aid in the identification of virus-free planting material and development of effective management strategies. In this study, a rapid, specific and sensitive real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay was developed for real-time detection of CBSV and UCBSV. The RT-RPA was able to detect as little as 2 pg/µl of purified RNA obtained from infected cassava leaves, a sensitivity equivalent to that obtained by quantitative real-time reverse transcription PCR (qRT-PCR), within 20 min at 37 °C. Further, the RT-RPA detected each target virus directly from crude leaf and stem extracts, avoiding the tedious and costly isolation of high-quality RNA. The developed RT-RPA assay provides a valuable diagnostic tool that can be adopted by cassava seed certification and virus resistance breeding programs to ensure distribution of virus-free cassava planting materials to farmers. This is the first report on the development and validation of crude sap-based RT-RPA assay for the detection of cassava brown streak viruses (UCBSV and CBSV) infection in cassava plants

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)