A typical presentation of COVID-19 in a patient with type 2 diabetes at an urban primary care facility in Accra, Ghana

This is a case report of a 55-year-old man with Type 2 Diabetes Mellitus who presented with progressive breathlessness, chest pain and hyperglycaemia. An initial impression of a chest infection was made. Management was initiated with antibiotics, but this was unsuccessful, and he continued to desaturate. A screen for Coronavirus Disease of 2019 (COVID-19) returned positive. There was no prodrome of fever or flu-like illness or known contact with a patient known to have COVID-19. This case is instructive as he didn’t fit the typical case definition for suspected COVID-19. There is significant community spread in Ghana, therefore COVID-19 should be a differential diagnosis in patients who present with hyperglycaemia and respiratory symptoms in the absence of a febrile illness. Primary care doctors must have a high index of suspicion in cases of significant hyperglycaemia and inability to maintain oxygen saturation.Patients known to have diabetes and those not known to have diabetes may develop hyperglycaemia subsequent to COVID-19. A high index of suspicion is crucial for early identification, notification for testing, isolation, treatment, contact tracing and possible referral or coordination of care with other specialists. Early identification will protect healthcare workers and patients alike from cross-infection

A Prospective Cohort Study of the Clinical Predictors of Bacteremia in Under-Five Children With Acute Undifferentiated Fever Attending a Secondary Health Facility in Northwestern Nigeria

Background: Children with acute febrile illness with no localizing signs often receive antibiotics empirically in most resource-poor settings. However, little is known about the burden of bacteremia in this category of patients, and an appraisal is thus warranted. This will guide clinical practice and promote rational antibiotics use. Methods: We prospectively followed up 140 under-five children who presented with acute undifferentiated fever at the emergency/outpatient pediatric unit of a secondary healthcare facility. Baseline clinical and laboratory information was obtained and documented in a structured questionnaire. We compared baseline characteristics between participants with bacteremia and those without bacteremia. We further fitted a multivariable logistic regression model to identify factors predictive of bacteremia among the cohort. Result: The prevalence of bacteremia was 17.1%, and Salmonella Typhi was the most frequently (40.9%) isolated pathogen. The majority (78.6%) of the study participants were managed as outpatients. The participants who required admission were four times more likely to have bacteremia when compared to those managed as outpatients (AOR 4.08, 95% CI 1.19 to 14.00). There is a four times likelihood of bacteremia (AOR 4.75, 95% CI 1.48 to 15.29) with a fever duration of beyond 7 days. Similarly, participants who were admitted with lethargy were six times more likely to have bacteremia (AOR 6.20, 95% CI 1.15 to 33.44). Other significant predictors were tachypnea and lymphopenia. Conclusion: Among under-five children with acute undifferentiated fever, longer duration of fever, lethargy, inpatient care, tachypnea, and lymphopenia were the significant predictors of bacteremia

A Prospective Cohort Study of the Clinical Predictors of Bacteremia in Under-Five Children With Acute Undifferentiated Fever Attending a Secondary Health Facility in Northwestern Nigeria

Background: Children with acute febrile illness with no localizing signs often receive antibiotics empirically in most resource-poor settings. However, little is known about the burden of bacteremia in this category of patients, and an appraisal is thus warranted. This will guide clinical practice and promote rational antibiotics use. Methods: We prospectively followed up 140 under-five children who presented with acute undifferentiated fever at the emergency/outpatient pediatric unit of a secondary healthcare facility. Baseline clinical and laboratory information was obtained and documented in a structured questionnaire. We compared baseline characteristics between participants with bacteremia and those without bacteremia. We further fitted a multivariable logistic regression model to identify factors predictive of bacteremia among the cohort. Result: The prevalence of bacteremia was 17.1%, and Salmonella Typhi was the most frequently (40.9%) isolated pathogen. The majority (78.6%) of the study participants were managed as outpatients. The participants who required admission were four times more likely to have bacteremia when compared to those managed as outpatients (AOR 4.08, 95% CI 1.19 to 14.00). There is a four times likelihood of bacteremia (AOR 4.75, 95% CI 1.48 to 15.29) with a fever duration of beyond 7 days. Similarly, participants who were admitted with lethargy were six times more likely to have bacteremia (AOR 6.20, 95% CI 1.15 to 33.44). Other significant predictors were tachypnea and lymphopenia. Conclusion: Among under-five children with acute undifferentiated fever, longer duration of fever, lethargy, inpatient care, tachypnea, and lymphopenia were the significant predictors of bacteremia

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Therapeutic Benefit of Radial Optic Neurotomy in a Rat Model of Glaucoma

Radial optic neurotomy (RON) has been proposed as a surgical treatment to alleviate the neurovascular compression and to improve the venous outflow in patients with central retinal vein occlusion. Glaucoma is characterized by specific visual field defects due to the loss of retinal ganglion cells and damage to the optic nerve head (ONH). One of the clinical hallmarks of glaucomatous neuropathy is the excavation of the ONH. The aim of this work was to analyze the effect of RON in an experimental model of glaucoma in rats induced by intracameral injections of chondroitin sulfate (CS). For this purpose, Wistar rats were bilaterally injected with vehicle or CS in the eye anterior chamber, once a week, for 10 weeks. At 3 or 6 weeks of a treatment with vehicle or CS, RON was performed by a single incision in the edge of the neuro-retinal ring at the nasal hemisphere of the optic disk in one eye, while the contralateral eye was submitted to a sham procedure. Electroretinograms (ERGs) were registered under scotopic conditions and visual evoked potentials (VEPs) were registered with skull-implanted electrodes. Retinal and optic nerve morphology was examined by optical microscopy. RON did not affect the ocular hypertension induced by CS. In eyes injected with CS, a significant decrease of retinal (ERG a- and b-wave amplitude) and visual pathway (VEP N2-P2 component amplitude) function was observed, whereas RON reduced these functional alterations in hypertensive eyes. Moreover, a significant loss of cells in the ganglion cell layer, and Thy-1-, NeuN- and Brn3a- positive cells was observed in eyes injected with CS, whereas RON significantly preserved these parameters. In addition, RON preserved the optic nerve structure in eyes with chronic ocular hypertension. These results indicate that RON reduces functional and histological alterations induced by experimental chronic ocular hypertension

AIDS-related mycoses: the way forward.

The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries

Transcriptomic and proteomic analysis of arbovirus-infected tick cells

Ticks are important vectors of a wide variety of pathogens including protozoa, bacteria and viruses. Many of the viruses transmitted by ticks are of medical or veterinary importance including tick-borne encephalitis virus (TBEV) and Crimean- Congo hemorrhagic fever virus causing disease in humans, and African swine fever virus and Nairobi sheep disease virus affecting livestock. Although several studies have elucidated tick antimicrobial mechanisms including cellular immune responses such as nodulation, encapsulation and phagocytosis and humoral immune responses such as the JAK/STAT pathway, complement-like proteins, antimicrobial peptides, lectin like pattern-recognition molecules and lysozymes, very little is known about the innate immune response of ticks towards viral infection. This study therefore aimed to identify molecules that might be involved in the response of ticks to viral infection. The hypothesis was that TBEV infection leads to changes in the expression of immunity-related transcripts and proteins in Ixodes spp. tick cells and that at least some of these might be antiviral. Ixodes scapularis-derived cell lines IDE8 and ISE6 were chosen since I. scapularis is currently the only tick species with a sequenced genome and an Ixodes ricinus-derived cell line, IRE/CTVM19, was used because I. ricinus is the natural vector of TBEV. Basic parameters required to study the responses of tick cells to infection were determined, including levels of virus infection, kinetics of virus replication and production, formation of replication complexes and uptake of dsRNA or siRNA. The cell lines IDE8, ISE6 and IRE/CTVM19 were infected with either of two tick-borne flaviviruses, TBEV and Langat virus (LGTV), or with the mosquito-borne alphavirus Semliki Forest virus (SFV). Infection was characterised using techniques including plaque assay, luciferase assay, immunostaining and conventional, confocal and electron microscopy. Two time points for transcriptomics and proteomics analysis of TBEVinfected IDE8 and IRE/CTVM19 cells were selected: day 2 post-infection (p.i.) when virus production was increasing and day 6 p.i. when virus production was decreasing. RNA and protein were isolated from TBEV-infected and mock-infected tick cells at days 2 and 6 p.i. and RNA-Seq and mass spectrometric technologies were used to identify changes in, respectively, transcript and protein abundance. Differential expression of transcripts was determined using the data analysis package DESeq resulting in a total of 43 statistically significantly differentially expressed transcripts in IDE8 cells and 83 in IRE/CTVM19 cells, while differential protein representation using Χ2 test statistics with Bonferroni correction in IDEG6 software resulted in 76 differentially represented proteins in IDE8 cells and 129 in IRE/CTVM19 cells. These included transcripts and proteins which could affect stages of the virus infection, including virus entry, replication, maturation and protein trafficking, and also innate immune responses such as phagocytosis, RNA interference (RNAi), the complement system, the ubiquitin-proteasome pathway, cell stress and the endoplasmic reticulum (ER) stress response. After verification of sequencing data by qRT-PCR, the ability of several of the identified transcripts or proteins to affect virus infection was determined by knockdown experiments in IDE8 and IRE/CTVM19 cells using wild type LGTV, LGTV replicons or TBEV replicons. Knockdown of genes encoding proteins including the ER chaperone gp96 and the heat-shock protein HSP90 resulted in increased virus production in both cell lines, hinting at an antiviral role. In contrast, knockdown of calreticulin, another ER chaperone, resulted in a decrease in virus production in IRE/CTVM19 cells but not in IDE8 cells, implying a requirement for virus production. This functional genomics approach has identified possible novel genes/proteins involved in the interaction between flaviviruses and tick cells and also revealed that there might be antiviral innate immune pathways present in ticks additional to the exogenous RNAi pathway

Many Labs 5:Testing pre-data collection peer review as an intervention to increase replicability

Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3?9; median total sample = 1,279.5, range = 276?3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (?r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00?.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19?.50)