33 research outputs found
Anti-Infective Dosing in Special Populations: Pregnancy
No full textSubstantial anatomical and physiological changes occur during pregnancy and labor, which impact on drug absorption, distribution, metabolism, and elimination. Reduced maternal concentrations may have a clinically important impact on the efficacy of anti-infectives for mother, fetus, and neonate, with potential dosing implications. However, there is a paucity of pregnancy-specific data examining this. Existing data on the pharmacokinetics of anti-infectives in pregnancy are summarized and evaluated, with emphasis on agents that are used in treatment of HIV, tuberculosis, malaria, and common bacterial infections. Limitations and challenges in achieving ideal study designs in pregnant populations are highlighted, and key quality considerations for the generation of the highest quality evidence are outlined. PubMed was searched for each chosen anti-infective. Pharmacokinetic studies which either compared pharmacokinetics from pregnant women against nonpregnant controls, or which assessed concentrations against a known minimum inhibitory concentration were included. Two independent reviewers extracted data from each study and appraised them using the 24-point ClinPK Checklist. The main finding was that there is a lack of published data for anti-infectives in pregnancy, despite their clinical importance. Of the studies identified, only those investigating cobicistat-boosted antiretroviral regimens firmly concluded that these should not be used in pregnancy. Most studies concluded either that further research was needed, or that there were significant pharmacokinetic differences between pregnant and nonpregnant participants which had uncertain clinical significance. Challenges in applying existing quality grading systems to these studies were noted, suggesting a development of a refined system for appraisal of pharmacokinetic studies in "special populations" may be warranted
Rectus sheath and retroperitoneal haematomas in patients with Coronavirus 2019 infection
No full textSARS-CoV-2 vaccine-induced humoral and cellular immunity in patients with hematologic malignancies
No full textPatients with hematologic conditions have a higher risk of severe COVID-19 and COVID-19-related death. This is related to immune deficiencies induced by hematologic conditions and/or the treatment thereof. Prospective vaccine immunogenicity studies have demonstrated that in the majority of patients, a 3-dose COVID-19 vaccination schedule leads to antibody concentrations comparable to levels obtained in healthy adults after a 2-dose schedule. In B cell depleted patients, humoral responses are poor, however vaccination did induce potent cellular immune responses. The effect of 3-dose vaccination schedules and COVID-19 booster vaccinations on the protection of patients with hematologic malignancies against severe COVID-19 and COVID-19 related death remains to be confirmed by population-based vaccine effectiveness studies
Leveraging the affordances of mobile learning for vocabulary gains
No full text© 2017. According to research findings, learners who are about to commence an undergraduate degree course with English as the medium of instruction (EMI), require a minimum English vocabulary size in order to decode and comprehend the academic texts that they have to read (Hazenberg and Hulstijn, 1996; Staehr, 2008; Laufer and Ravenhorst-Kalovski, 2010; Schmitt, 2010; Nation, 2013, Milton and Treffers-Daller, 2013). In the United Arab Emirates, several thousand Emirati students attend English foundation programmes prior to starting their EMI degrees in order to improve their academic skills, such as reading and vocabulary knowledge. However, despite the increased use of Technology-Enhanced Learning (TEL) and the introduction of mobile learning in 2012, the results of this study show that the vast majority of female Emirati still have an insufficient receptive vocabulary size for beginning an EMI undergraduate degree course. In addition, the use of a generic vocabulary learning app over a four-month period has not led to a significant increase in most students\u27 vocabulary size. The reasons for this could include the fact that the generic app does not fully utilise the affordances of mobile learning, it is not underpinned by pedagogically-sound vocabulary learning principles and that it does not focus on the particular learning needs and lexical weakness of Emirati students. Therefore, the author has worked as part of a team to develop and build a new, customised, mobile app that has attempted to address these weaknesses and help Zayed University students reach the required vocabulary learning goal
Micro-Targeting and ICT media in the Dutch Parliamentary system: Technological changes in Dutch Democracy
No full textFor the period surrounding the 2018 Dutch municipal elections, a team of researchers from the Delft University of Technology investigated the effect of the digital environment on parliamentary democracy. An interdisciplinary group of researchers combined expertise on digital ethics, political theory, big data analytics, the economics of privacy and security, epistemology, media studies and computer science. This report presents the main findings, which are grouped around two main themes: political micro-targeting and ICT media. Societal themes that came to prominence over the research period, such as the debate over ‘fake news’ and the leaks of personal information that were used for political purposes by Facebook, as well as the implementation of new EU privacy regulation helped to put the research in a larger political context. The main findings provide a qualified picture. The influence of the digital revolution on democratic politics is already revolutionary, and the weaknesses of online platforms provide ample opportunities for derailing liberal democracy. Digital platforms are too closed-off, not mindful enough of individual digital rights, and biased in their (re)presentation of political pluralism. But the Netherlands has proven to be one of the few democracies that is relatively resilient, with an open multi-party system receptive to the political fragmentation that ICT developments encourage, and relatively high trust between citizens, in shared media organizations, and between political parties. In order not to be complacent in the face of fundamental challenges, the report provides several urgent recommendations. Next to several ‘reactive’ recommendations, which seek to remedy the weaknesses and dangers the digital environment poses to democracy, it also outlines an example of how the digital environment might be proactively redesigned in order to positively enhance the quality of the Dutch parliamentary system.Ethics & Philosophy of TechnologyValues Technology and InnovationPolicy AnalysisOrganisation & Governanc
Large-sample assessment of varying spatial resolution on the streamflow estimates of the wflowsbm hydrological model
No full textDistributed hydrological modelling moves into the realm of hyper-resolution modelling. This results in a plethora of scaling-related challenges that remain unsolved. To the user, in light of model result interpretation, finer-resolution output might imply an increase in understanding of the complex interplay of heterogeneity within the hydrological system. Here we investigate spatial scaling in the form of varying spatial resolution by evaluating the streamflow estimates of the distributed wflow_sbm hydrological model based on 454 basins from the large-sample CAMELS data set. Model instances are derived at three spatial resolutions, namely 3 km, 1 km, and 200 m. The results show that a finer spatial resolution does not necessarily lead to better streamflow estimates at the basin outlet. Statistical testing of the objective function distributions (Kling–Gupta efficiency (KGE) score) of the three model instances resulted in only a statistical difference between the 3 km and 200 m streamflow estimates. However, an assessment of sampling uncertainty shows high uncertainties surrounding the KGE score throughout the domain. This makes the conclusion based on the statistical testing inconclusive. The results do indicate strong locality in the differences between model instances expressed by differences in KGE scores of on average 0.22 with values larger than 0.5. The results of this study open up research paths that can investigate the changes in flux and state partitioning due to spatial scaling. This will help to further understand the challenges that need to be resolved for hyper-resolution hydrological modelling.Water Resource
Systematic review of off-The-shelf or physician-modified fenestrated and branched endografts
No full textPurpose: To determine the safety and efficacy of off-The-shelf fenestrated/branched grafts (OSFGs) and physician-modified stent-grafts (PMSGs) for the treatment of complex abdominal aortic aneurysms. Methods: A systematic search of the MEDLINE database via PubMed from January 2001 through March 2015 retrieved 23 relevant articles evaluating the clinical outcomes following the management of patients with pararenal or thoracoabdominal aortic aneurysms. The 15 articles on PMSGs and 8 on OSFGs contained data on 308 patients (mean age 72.93±2.89 years; 213 men). The safety endpoint was major adverse events; the efficacy outcome measure was clinical treatment success (aneurysm exclusion without type I/III endoleak, permanent paralysis, long-term dialysis, or unresolved major complications). Extracted outcome data were pooled and compared between groups; data are given as the pooled proportions and 95% confidence interval (CI). Clinical data are presented as the weighted mean. Results: Of the 308 patients analyzed, almost one third were operated on an emergency basis. The mean aneurysm diameters were 75.9±17.3 mm (range 56-115) for the PMSGs and 68.1±13.7 mm (range 60-100) for the OSFGs. A total of 936 renal and visceral vessels were targeted. Major adverse events (safety) occurred in 24 (12.8%) PMSG patients (95% CI 8.6% to 18.7%) and in 9 (7.4%) OSFG patients (95% CI 3.7% to 14%). Clinical treatment success (efficacy) was observed in 171/187 (91.4%) PMSG patients (95% CI 86.2% to 94.9%) and in 115/121 (95%) OSFG patients (95% CI 89.1% to 98.0%). Corresponding cumulative 30-day target vessel and branch stent perfusion rates were 97.2% (95% CI 95.1% to 98.4%) and 97.6% (95% CI 95.5% to 98.8%) for the PMSG group and 99.6% (95% CI 98.3% to 99.9%) and 98.4% (95% CI 96.5% to 99.4%) for the OSFG group. Six (3.2%) deaths occurred in the PMSG group only; 2 (1.1%) were aneurysm related. Overall branch patency was recorded in 443/458 (96.7%) and in 468/478 (97.9%) of target vessels in the PMSG and OSFG groups, respectively. Conclusion: Off-The-shelf and physician-modified technology seems effective and safe, in both the elective and acute settings, for the treatment of complex aortic aneurysms. Future research within a randomized trial should investigate the true limitations of these devices. © The Author(s) 2015
Prevalence of Potentially Clinically Significant Drug–Drug Interactions With Antiretrovirals Against HIV Over Three Decades: A Systematic Review of the Literature
No full textContemporary first-line antiretrovirals have considerably reduced liability for clinically significant drug-drug interactions (DDI). This systematic review evaluates the prevalence of DDI among people receiving antiretrovirals across 3 decades. We searched 3 databases for studies reporting the prevalence of clinically significant DDIs in patients receiving antiretrovirals published between January 1987 and July 2022. Clinically significant DDIs were graded by severity. All data extractions were undertaken by 2 independent reviewers, adjudicated by a third. Of 21,665 records returned, 13,474 were duplicates. After screening the remaining 13,596 abstracts against inclusion criteria, 122 articles were included for full-text analysis, from which a final list of 34 articles were included for data synthesis. The proportion of patients experiencing a clinically significant DDI did not change over time (P = 0.072). The most frequently reported classes of antiretrovirals involved in DDIs were protease inhibitors and non-nucleoside reverse transcriptase inhibitors; of note, integrase use in the most recent studies was highly variable and ranged between 0% and 89%. The absolute risk of DDIs has not decreased over the period covered. This is likely related to continued use of older regimens and an ageing cohort of patients. A greater reduction in DDI prevalence can be anticipated with broader uptake of regimens containing unboosted integrase inhibitors or non-nucleoside reverse transcriptase inhibitors.</p
Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3)
No full textIntroduction Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation rates, understanding acquired immunity, and testing vaccines in a cost-effective manner. To enhance the development of effective pneumococcal vaccines against SPN3, we aim to develop a new relevant and safe SPN3 EHPC model with high attack rates which could be used to test vaccines using small sample size.Methods and analysis This is a human challenge study to establish a new SPN3 EHPC model, consisting of two parts. In the dose-ranging/safety study, cohorts of 10 healthy participants will be challenged with escalating doses of SPN3. If first challenge does not lead into colonisation, participants will receive a second challenge 2 weeks after. Experimental nasopharyngeal (NP) colonisation will be determined using nasal wash sampling. Using the dose that results in ≥50% of participants being colonised, with a high safety profile, we will complete the cohort with another 33 participants to check for reproducibility of the colonisation rate. The primary outcome of this study is to determine the optimal SPN3 dose and inoculation regime to establish the highest rates of NP colonisation in healthy adults. Secondary outcomes include determining density and duration of experimental SPN3 NP colonisation and characterising mucosal and systemic immune responses to SPN3 challenge.Ethics and dissemination This study is approved by the NHS Research and Ethics Committee (reference 22/NW/0051). Findings will be published in peer-reviewed journals and reports will be made available to participants
Practical considerations for a TB controlled human infection model (TB-CHIM); the case for TB-CHIM in Africa, a systematic review of the literature and report of 2 workshop discussions in UK and Malawi [version 1; peer review: 2 approved, 1 approved with reservations]
No full textBackground: Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns. Methods: A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome. We searched MEDLINE (1946 to current) and CINAHL (1984 to current) databases; and Google Scholar to search citations in selected manuscripts. The final search was conducted 3rd February 2022. Inclusion criteria: adults ≥18 years old; administration of live mycobacteria; and interventional trials or cohort studies with immune and/or microbiological endpoints. Exclusion criteria: animal studies; studies with no primary data; no administration of live mycobacteria; retrospective cohort studies; case-series; and case-reports. Relevant tools (Cochrane Collaboration for RCTs and Newcastle-Ottawa Scale for non-randomised studies) were used to assess risk of bias and present a narrative synthesis of our findings. Results: The search identified 1,388 titles for review; of these 90 were reviewed for inclusion; and 27 were included. Of these, 15 were randomised controlled trials and 12 were prospective cohort studies. We focussed on administration route, challenge agent and dose administered for data extraction. Overall, BCG studies including fluorescent BCG show the most immediate utility, and genetically modified Mycobacteria tuberculosis is the most tantalising prospect of discovery breakthrough. Conclusions: The TB-CHIM development group met in 2019 and 2022 to consider the results of the systematic review, to hear presentations from many of the senior authors whose work had been reviewed and to consider best ways forward. This paper reports both the systematic review and the deliberations. Registration: PROSPERO (CRD42022302785; 21 January 2022)
