A case report: the first successful cochlear implant in Uganda.

Hearing impairment is a significant disability. According to the World Health Organization (WHO), more than 80% of the world\u2019s approximately 120 million people with hearing impairment live in developing countries. Cochlear implant is the only therapeutic intervention for those with severe-profound sensorineural hearing loss. We are reporting an interesting case of the very first cochlear implant operation carried out in Uganda. The patient was a 23 year old male whose presenting complaint was inability to hear in the left ear for three and a half years and in the right ear for one year. He had been treated for TB(Tuberculosis) mastoiditis . After the 8 months of treatment, the otorrhea persisted and he underwent a tympanomastoidectomy on the same ear. He reported no familial history of hearing loss. On examination, ENT examination revealed a small pars flaccida retration pocket of the right tympanic membrane with cholesteatoma. The left ear had an intact tympanic membrane. Pure tone audiometry revealed profound sensorineural hearing loss in both ears( see attached PTA results), CT scan of the temporal bone showed normal inner ear anatomy bilaterally and mild sclerotic changes in both mastoid bones. He then had surgery on his right ear which included cochlear implantation. The cochlear implant (CI) was activated on the first postoperative day remotely via internet with the help of the cochlear implant team at New York University Cochlear Implant Center and the patient was immediately able to appreciate some sounds. He received a pneumococcal vaccine on the first postoperative day and was discharged the following day

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise. The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included.Peer reviewe

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

A case control study of the factors associated with occurrence of aerodigestive foreign bodies in children in a regional referral hospital in South Western Uganda

Abstract Background Aerodigestive foreign bodies (ADFB) in children are a common emergency in ENT clinics globally. The aim of this study was to determine the prevalence and common types of ADFB’s presenting to a referral hospital in South Western Uganda, and to review clinical presentation and factors that influence their occurrence among children under 12 years of age. Methods We conducted a case control study comprising 40 cases and 80 unmatched controls. Consecutive and random sampling were used for the cases and controls respectively. A questionnaire was used to collect data. Clinic records were reviewed to calculate prevalence. Results Prevalence was 6.6 % of all paediatric cases seen in the ENT department that year. The most common symptoms included: history of choking [45 %], sudden cough [72.5 %], stridor [60 %] and failure to swallow [35 %]. The most common location for an airway foreign body was the right main bronchus [40 %] and the upper one third of the oesophagus [32.5 %] for digestive tract foreign bodies. Seeds and coins were most frequently removed. Children from upper level SES had a significantly lower risk of foreign body occurrence [OR = 0.29, p = 0.02] compared to those from a low SES. Also significantly, most cases were referrals from other government health centres [p = <0.01]. The male to female ratio among cases was 2:1. Children of older mothers were less likely to have an ADFB. Conclusion Prevalence of ADFB’s is relatively high. The most common symptoms are a history of choking, cough and failure to swallow. Age under 5 years, male sex, younger maternal age and low socioeconomic status increased odds of ADFBs

Seroprevalence and associated risk factors of bovine brucellosis at the wildlife-livestock-human interface in Rwanda

Bovine brucellosis is endemic in Rwanda; however, little information is available on seroprevalence and risk factors. Therefore, a cross-sectional study was conducted among cattle farmed at the wildlife-livestock-human interface (n = 1691) in five districts and one peri-urban district (n = 216). Cattle were screened using the Rose Bengal test, then the results were confirmed by indirect enzyme-linked immunesorbent assay. Potential risk factors were determined with a questionnaire and analyzed for their association with seropositivity. In all districts, the animal and herd-level seroprevalence was 7.4% (141/1907) and 28.9% (61/212), respectively, 8.3% (141/1691) and 30.9% (61/198) at the interface, and 0.0% (0/216) in peri-urban areas. Among the potential risk factors, old age (≥5 years), cattle farmed close to wildlife, herds of cattle and small ruminants, history of abortions, and replacement animals were significantly associated with brucellosis (p < 0.05). Low awareness of zoonotic brucellosis, assisting calving without biosafety protection, drinking raw milk, and manual milking were each observed in more than 21.7% of cattle keepers whose herds were seropositive. This study confirmed brucellosis endemicity in cattle farmed close to wildlife in Rwanda, suggesting the need to focus control efforts in these areas. Educated farmers with a high awareness of zoonotic brucellosis had low bovine brucellosis seropositivity, which emphasizes the importance of education.Supplementary Materials: Table S1: Univariate associations of potential risk factors with herd-level seropositivity of Brucella spp. in cattle sampled at the wildlife-livestock-human interface in Rwanda. A questionnaire used to collect herd and public health risk factors. Excel document containing all data on individual seroprevalence and potential risk factors.Institute of Tropical Medicine Antwerp, Belgiumhttp://www.mdpi.com/journal/microorganismspm2020Veterinary Tropical Disease

COVID 19: Lets act now: the urgent need for upscaling agroecology in Uganda (2020)

The COVID 19 pandemic has ravaged most parts of the world leading to multiple negative effects as restrictions in movement have ensued. Uganda as a country has not been spared with such pandemics also known to disrupt food systems. The aim of this paper is to critically reflect and argue for alternative food systems in Uganda like agroecology that are deemed more resilient in times of pandemics like COVID 19. We review and critically analyze the elements of agroecology in this respect and make strong recommendations for upscaling agroecology in Uganda