Found 14781 matches for
Do you want to know more about Open Access? Find out about Act on Acceptance & ORCID from an expert? Book a place for our session on Tuesday 23rd August, 2-3pm in Room B at the WTCHG. Juliet Ralph, the Open Access Subject librarian, will be available for your toughest questions.
A Bayesian approach for estimating typhoid fever incidence from large-scale facility-based passive surveillance data
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Decisions about typhoid fever prevention and control are based on current estimates of typhoid incidence and their uncertainty, which can be difficult to measure. Limits of using facility-based estimates alone—the lack of specific clinical diagnostic criteria, poorly sensitive and specific diagnostic tests, and scarcity of accurate and complete datasets—contribute to difficulties in calculating population-level incidence of typhoid.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Using data from the Strategic Alliance across Africa & Asia (STRATAA) programme, we integrated information from demographic censuses, healthcare utilization surveys, facility-based passive surveillance, and serological surveillance from sites in Malawi, Nepal, and Bangladesh in order to adjust crude incidence estimates to account for under-detection. We developed an approach using a Bayesian framework that adjusts the count of reported blood-culture-positive cases of typhoid for each of the following phases: healthcare seeking, blood culture collection, and blood culture detection. We estimated the proportion of “true” typhoid cases occurring in the population under surveillance captured at each phase by combining information from the observed cases from the STRATAA datasets and estimates from prior published studies. We confirmed that the model was correctly formulated by comparing to simulated data.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The ratio between the observed and adjusted incidence rates was 8.2 (95% CI: 6.4-13.3) in Malawi, 13.8 (95% CI: 8.8-23.0) in Nepal, and 7.0 (95% CI: 5.5-9.1) in Bangladesh, and varied by age across the three sites. The probability of having blood drawn for culture led to the largest adjustment in Malawi, while the probability of seeking healthcare contributed the most to adjustment factors in Nepal and Bangladesh. Adjusted incidence rates were mostly within the limits of the seroincidence rate of typhoid infection determined by serological data.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Passive surveillance of blood culture-confirmed typhoid fever without adjustment for case ascertainment, sample collection and diagnostic sensitivity results in considerable underestimation of the true incidence of typhoid in the population. Our approach allows each phase of the typhoid reporting process to be synthesized to estimate the adjusted incidence of typhoid fever while correctly characterizing uncertainty in this estimate, which can inform decision-making for typhoid prevention and control.</jats:p></jats:sec>
Engagement of ethics and regulatory authorities on human infection studies: Proceedings of an engagement workshop in Zambia.
Human infection studies (HIS) have generally been used as a tool in the pathway for vaccine development in high income settings. Over the last decade, this model has been implemented in LMICs with the aim of accelerating development of next generation vaccines that would perform better in these settings. However, in most LMICs, the ethics and regulatory framework for the conduct of these studies are not in place. In Zambia, these studies are yet to be conducted and thus we conducted a stakeholder engagement workshop in October 2019. We engaged with bioethicists, regulatory authority, and scientists from within Zambia and other African countries to anticipate and address foreseeable ethical and regulatory issues when conducting HIS in Zambia for the first time. The workshop largely focused on sensitizing the stakeholders on the benefits of these studies with the following main points for consideration on the implementation of these studies in Zambia: need for in-country legal framework and guidelines; need for adequate informed consent based on comprehensive understanding of the concept of HIS and study requirements; and requirements for heightened vigilance to assure participant safety including good ethical and clinical practice with regulatory, ethical, data safety, and community oversight. Additionally, the workshop emphasized the need for rigorous health screening prior to enrolment; suitable infrastructure for containment; and personnel to provide appropriate treatment including emergency resuscitation and evacuation if indicated. Specific recommendations included compensation for burden of participation; access to care and provision for study related injury (e.g. no-fault insurance); and withdrawal and exit procedures to preserve individual and community safety. Finally, the meeting concluded that researchers should actively engage key gate keepers including civic leaders such as parliamentarians, universities, researchers, potential participants and laypersons to avoid circulation of misinformation.
Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.
Automating the Generation of Antimicrobial Resistance Surveillance Reports: Proof-of-Concept Study Involving Seven Hospitals in Seven Countries
<jats:sec> <jats:title>Background</jats:title> <jats:p>Reporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. However, analyzing data and generating a report are time consuming and often require trained personnel.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>This study aimed to develop and test an application that can support a local hospital to analyze routinely collected electronic data independently and generate AMR surveillance reports rapidly.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>An offline application to generate standardized AMR surveillance reports from routinely available microbiology and hospital data files was written in the R programming language (R Project for Statistical Computing). The application can be run by double clicking on the application file without any further user input. The data analysis procedure and report content were developed based on the recommendations of the World Health Organization Global Antimicrobial Resistance Surveillance System (WHO GLASS). The application was tested on Microsoft Windows 10 and 7 using open access example data sets. We then independently tested the application in seven hospitals in Cambodia, Lao People’s Democratic Republic, Myanmar, Nepal, Thailand, the United Kingdom, and Vietnam.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>We developed the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), which can support clinical microbiology laboratories to analyze their microbiology and hospital data files (in CSV or Excel format) onsite and promptly generate AMR surveillance reports (in PDF and CSV formats). The data files could be those exported from WHONET or other laboratory information systems. The automatically generated reports contain only summary data without patient identifiers. The AMASS application is downloadable from https://www.amass.website/. The participating hospitals tested the application and deposited their AMR surveillance reports in an open access data repository.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The AMASS is a useful tool to support the generation and sharing of AMR surveillance reports.</jats:p> </jats:sec>
Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
<jats:title>SUMMARY</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once daily by mouth or intravenously for 10 days or until discharge (or one of the other treatment arms). Patients were twice as likely to be randomised to usual care as to any of the active treatment groups. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://clinicaltrials.gov">clinicaltrials.gov</jats:ext-link> (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04381936">NCT04381936</jats:ext-link>).</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>Between 7 April and 27 November 2020, 2582 patients were randomly allocated to receive azithromycin and 5182 patients to receive usual care alone. Overall, 496 (19%) patients allocated to azithromycin and 997 (19%) patients allocated to usual care died within 28 days (rate ratio 1·00; 95% confidence interval [CI] 0·90-1·12; p=0·99). Consistent results were seen in all pre-specified subgroups of patients. There was no difference in duration of hospitalisation (median 12 days vs. 13 days) or the proportion of patients discharged from hospital alive within 28 days (60% vs. 59%; rate ratio 1·03; 95% CI 0·97-1·10; p=0·29). Among those not on invasive mechanical ventilation at baseline, there was no difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0·97; 95% CI 0·89-1·07; p=0·54).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>In patients hospitalised with COVID-19, azithromycin did not provide any clinical benefit. Azithromycin use in patients hospitalised with COVID-19 should be restricted to patients where there is a clear antimicrobial indication.</jats:p></jats:sec><jats:sec><jats:title>Funding</jats:title><jats:p>UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).</jats:p></jats:sec>
Impact of a package of diagnostic tools, clinical algorithm, and training and communication on outpatient acute fever case management in low- and middle-income countries: protocol for a randomized controlled trial.
<h4>Background</h4>The management of acute febrile illnesses places a heavy burden on clinical services in many low- and middle-income countries (LMICs). Bacterial and viral aetiologies of acute fevers are often clinically indistinguishable and, in the absence of diagnostic tests, the 'just-in-case' use of antibiotics by many health workers has become common practice, which has an impact on drug-resistant infections. Our study aims to answer the following question: in patients with undifferentiated febrile illness presenting to outpatient clinics/peripheral health centres in LMICs, can we demonstrate an improvement in clinical outcomes and reduce unnecessary antibiotic prescription over current practice by using a combination of simple, accurate diagnostic tests, clinical algorithms, and training and communication (intervention package)?<h4>Methods</h4>We designed a randomized, controlled clinical trial to evaluate the impact of our intervention package on clinical outcomes and antibiotic prescription rates in acute febrile illnesses. Available, point-of-care, pathogen-specific and non-pathogen specific (host markers), rapid diagnostic tests (RDTs) included in the intervention package were selected based on pre-defined criteria. Nine clinical study sites in six countries (Burkina Faso, Ghana, India, Myanmar, Nepal and Uganda), which represent heterogeneous outpatient care settings, were selected. We considered the expected seasonal variations in the incidence of acute febrile illnesses across all the sites by ensuring a recruitment period of 12 months. A master protocol was developed and adapted for country-specific ethical submissions. Diagnostic algorithms and choice of RDTs acknowledged current data on aetiologies of acute febrile illnesses in each country. We included a qualitative evaluation of drivers and/or deterrents of uptake of new diagnostics and antibiotic use for acute febrile illnesses. Sample size estimations were based on historical site data of antibiotic prescription practices for malarial and non-malarial acute fevers. Overall, 9 semi-independent studies will enrol a minimum of 21,876 patients and an aggregate data meta-analysis will be conducted on completion.<h4>Discussion</h4>This study is expected to generate vital evidence needed to inform policy decisions on the role of rapid diagnostic tests in the clinical management of acute febrile illnesses, with a view to controlling the rise of antimicrobial resistance in LMICs.<h4>Trial registration</h4>Clinicaltrials.gov NCT04081051 . Registered on 6 September 2019. Protocol version 1.4 dated 20 December 2019.
The invisible body of queer youth: identity and health in the margins of lesbian and trans communities.
How does complexity in gender and sexual identity construction and partnering practices generate unique vulnerabilities for queer-identified youth? We present two case studies from an ongoing ethnographic study of LGBTQ youth development: "Samantha," a queer-identified woman partnered with a transgender man, and "Reid," a queer-identified transgender man who has declined medical gender transitioning and who partners with lesbians and gay men. We consider the implications of these youths' locations on the margins of both lesbian and transgender communities and the challenges in providing health care and support services for queer-identified youth.
<jats:p>This is the first study to analyze global country level HIV-1 diversity from 1990 to 2015. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe and North America. The proportion of HIV-1 infections due to recombinants was highest in South-East Asia, China, and West and Central Africa. The highest proportions of URFs were found in Myanmar, Republic of the Congo, and Argentina. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to HIV vaccine development and diagnostic, drug resistance, and viral load assays.</jats:p>
<ns3:p>MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 <ns3:italic>Plasmodium falciparum</ns3:italic> samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.</ns3:p>
Case Report: Treating pulmonary tuberculosis with transaminitis with standard antitubercular four drugs therapy.
We report a case of pulmonary tuberculosis with transaminitis during the presentation but without any pre-existing liver disease or hepatotoxic drug use. This is a fairly common scenario seen in tuberculosis endemic areas; however, this is an under reported condition in the literature and guidelines for its management has not been established. Many clinicians including the authors have treated such cases with modified liver friendly regimens in fear of increasing the hepatotoxicity with standard drugs. However, the modified regimens may not be optimal in treating the underlying tuberculosis. In this report, we gave full dose standard antitubercular drugs, and the liver injury resolved evidenced by normalization of transaminases.
Takayasu arteritis is a rare systemic large vessel vasculitis affecting the aorta and its branches. Sarcoidosis, too, is an inflammatory disease. Both entities are granulomatous conditions with a questionable association in their etiopathogenesis. Only a few cases of their coexistence have been reported in the literature. To our knowledge, no such cases have been reported from Nepal. We report a Nepalese woman who presented with non-productive cough, progressive shortness of breath and chest tightness of 3 years duration. She had a history of recurrent bilateral granulomatous uveitis over the previous 3 years. Examination revealed clubbing of digits, absent pulses over the left radial, ulnar and brachial arteries, and a weak pulse over the right arm including the bilateral carotid arteries. Pulmonary function test showed restrictive pattern, a high-resolution computed tomography (HRCT) scan of the chest revealed findings suggestive of pulmonary sarcoidosis. A CT angiogram suggested large vessel vasculitis. Bronchoscopy with biopsy revealed granulomatous inflammation, negative for malignancy and tuberculosis. She was hence, diagnosed with co-existing Takayasu arteritis and sarcoidosis, and treated with Prednisolone 60 mg once daily with dramatic improvement over 4 days and was discharged stable on domiciliary oxygen. She is currently on azathioprine 50 mg, prednisolone 10 mg without the need for supplemental oxygen. This case report highlights the importance of a proper physical examination as a guide to the use of modern technology in making a correct diagnosis. Furthermore, in countries where tuberculosis is endemic, it should always come as the most important differential diagnosis of granulomatous inflammation.