18 research outputs found
Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone
The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission
Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial
Background
High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset.
Methods
We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment,
whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053.
Findings
Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups.
Interpretation
Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting.
Funding British Heart Foundation
Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial
Background
Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.
Methods
FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.
Findings
Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.
Interpretation
Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.
Funding
UK Stroke Association and NIHR Health Technology Assessment Programme
Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats
In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance
INTRODUCTION
Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic.
RATIONALE
We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs).
RESULTS
Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants.
CONCLUSION
Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
Identification of Laboratory Biomarkers for Early Detection and Clinical Management of Post-Acute Syndrome Among Survivors of the 2013-2016 West Africa Ebola Outbreak in Sierra Leone
Background: The clinical management of persistent medical conditions affecting Ebola survivors, generally described as a post-Ebola syndrome, remains a public health concern. We aimed to analyze Ebola survivors' laboratory biomarkers as compared to their non-infected household relatives to identify biomarkers that could guide the identification of survivors at increased risk of developing severe at odds with the non-severe post-Ebola syndrome. Materials and Methods: Data were extracted from medical records of the Ebola survivors clinic, and we included only Ebola survivor's parameters recorded during the first baseline follow-up visit 2 weeks interval after their second negative PCR result. Moreover, household non-infected family contacts of survivors visiting the clinic during the same period were recruited as community control. Results: The mean age of survivors was 32.65 (IQR: 15.5, 38.25) years, and Ebola IgG immunoglobulin was detected in all, thus confirming their status. The statistical significance (all p < 0.05) observed in monocyte percentage (MONO%), cluster of differentia-tion 4 percentage (CD4%), alanine aminotransferase (ALT), creatinine (CREA), and creatinine kinase (C-kinase) proved to be clinically significant as compared to the household relatives' group. Interestingly, the linear regression analysis indicated that the duration at ETU was negatively associated with lymphocyte percentage with a 5% lymphocyte decrease per day spent at ETU. Finally, there was a significant (p < 0.05) association between hematological (Hb, PCV, MCV, MCH), biochemical (ALT, CREA, C-kinase, T-cholesterol, triglycerides) parameters and the risk of developing severe complications. Conclusion: We recommend clinicians closely monitor Hb, PCV, MCV, MCH, ALT, CREA, C-kinase, T-cholesterol, triglycerides and lymphocytes as clinically relevant laboratory biomarkers to identify survivors at higher risk of developing severe post-acute syndrome upon discharge from Ebola treatment unit including headache, abdominal pain, chest pain, ocular complication, arthralgia, hearing difficulty and erectile dysfunction which can impact health-related quality of life among Ebola survivors
COVID-19 treatment in sub-Saharan Africa: If the best is not available, the available becomes the best
© 2020 Elsevier Ltd. All rights reserved.Community transmission of COVID-19 is ongoing in the majority of countries in sub-Saharan Africa (SSA), threatening, as elsewhere, the capacity of national healthcare systems (HCS) in low- and middle-income countries (LMIC). While the epidemic started slowly and late in SSA, currently - subject to often rapid changes - around 20,000 cases per day are reported, despite limited testing. Shortages of personal protective equipment (PPE), as well as sophisticated and expensive molecular diagnostic tests are of concern. However, the biggest worry is the lack of health care workers (HCW) and health care infrastructure as a few figures compellingly illustrate. SSA has only 0.2 physicians per 1000 inhabitants (Europe 3.7, North America 2.6), while 10,000 HCW across the continent were infected by the 23rd of July. In April, the WHO reported less than 2000 ventilators in 43, and only 5000 intensive care unit (ICU) beds in 41 African countries, respectively. Worst though, their distribution is highly skewed. While many countries in SSA having just a few, if any; in countries which govern such resources, like South Africa, they are mainly located in the private sector, creating corresponding access problems. Non-profit organisations help with the procurement of materials at lower prices, like the African Medical Supply Platform; yet, a single N95 mask still costs 2 USD a piece on this platform.info:eu-repo/semantics/publishedVersio
A New Methodology for Eco-friendly Construction: Utilizing Quality Function Deployment to Meet LEED Requirements
Leadership in Energy and Environmental Design and building commissioning are two eco-innovations that have contributed to the long-term efficiency and sustainability of new-building construction. The Leadership in Energy and Environmental Design system promotes green, efficient, and sustainable design and construction. Building commissioning is a quality process used to verify that the owner’s project requirements are being met by the final design, construction, and operations and maintenance. Quality function deployment has been successfully used in product development to capture the voice of the customer, translating it into engineering characteristics and then carrying the parameters into production and service to ensure the voice of the customer is met with the final product. To provide the next level of eco-innovation for commissioning and Leadership in Energy and Environmental Design, the four-phase quality function deployment model will be adapted to, and integrated with, the commissioning and Leadership in Energy and Environmental Design processes. The adapted model can effectively link the project phases to ensure the owner’s project requirements for Leadership in Energy and Environmental Design are met with the final building. The primary objective of this research is to develop an integrative and systematic methodology to adapt the four-phase quality function deployment model to the commissioning process of new-building construction, to provide practitioners the steps to take the adapted model through the commissioning process as a means to oversee the entire design and construction quality process, ensuring the owner’s Leadership in Energy and Environmental Design goals are integrated into the design and carried through construction to the operations and maintenance phase for long-term efficiency and sustainability
Thigh-length compression stockings and DVT after stroke
Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease