Impact and Cost-Effectiveness of Point-Of-Care CD4 Testing on the HIV Epidemic in South Africa.

Rapid diagnostic tools have been shown to improve linkage of patients to care. In the context of infectious diseases, assessing the impact and cost-effectiveness of such tools at the population level, accounting for both direct and indirect effects, is key to informing adoption of these tools. Point-of-care (POC) CD4 testing has been shown to be highly effective in increasing the proportion of HIV positive patients who initiate ART. We assess the impact and cost-effectiveness of introducing POC CD4 testing at the population level in South Africa in a range of care contexts, using a dynamic compartmental model of HIV transmission, calibrated to the South African HIV epidemic. We performed a meta-analysis to quantify the differences between POC and laboratory CD4 testing on the proportion linking to care following CD4 testing. Cumulative infections averted and incremental cost-effectiveness ratios (ICERs) were estimated over one and three years. We estimated that POC CD4 testing introduced in the current South African care context can prevent 1.7% (95% CI: 0.4% - 4.3%) of new HIV infections over 1 year. In that context, POC CD4 testing was cost-effective 99.8% of the time after 1 year with a median estimated ICER of US$4,468/DALY averted. In healthcare contexts with expanded HIV testing and improved retention in care, POC CD4 testing only became cost-effective after 3 years. The results were similar when, in addition, ART was offered irrespective of CD4 count, and CD4 testing was used for clinical assessment. Our findings suggest that even if ART is expanded to all HIV positive individuals and HIV testing efforts are increased in the near future, POC CD4 testing is a cost-effective tool, even within a short time horizon. Our study also illustrates the importance of evaluating the potential impact of such diagnostic technologies at the population level, so that indirect benefits and costs can be incorporated into estimations of cost-effectiveness

Short-term prospective memory deficits in chronic back pain patients

Objective: Chronic pain, particularly low back pain, is widespread. Although a great deal is known about the impact that this has on quality of life and physical activity, relatively little has been established regarding the more cognitive effects of pain. This study aims to find out whether individuals with chronic pain experience memory deficits in prospective memory (PM), the process of remembering to do things at some future point in time. Examples of PM include remembering to keep an appointment, such as a visit to a clinic, or to perform a particular task, such as paying a bill on time. Methods: The PM of 50 participants with chronic pain was compared with 50 pain-free participants. Each participant completed the Prospective Memory Questionnaire, which assesses three aspects of prospective memory (short-term habitual, long-term episodic, and internally cued), and records the use of strategies to aid remembering. Results: In comparison to those not in pain, participants with chronic pain had significantly impaired short-term prospective memory, an effect which was evident even after co-varying use of analgesics and other drugs. Conclusions: These findings provide new insights into prospective memory dysfunction in people with chronic pain. Possible mechanisms for this dysfunction are discussed and suggestions for future research given

Success Factors of European Syndromic Surveillance Systems: A Worked Example of Applying Qualitative Comparative Analysis

Introduction: Syndromic surveillance aims at augmenting traditional public health surveillance with timely information. To gain a head start, it mainly analyses existing data such as from web searches or patient records. Despite the setup of many syndromic surveillance systems, there is still much doubt about the benefit of the approach. There are diverse interactions between performance indicators such as timeliness and various system characteristics. This makes the performance assessment of syndromic surveillance systems a complex endeavour. We assessed if the comparison of several syndromic surveillance systems through Qualitative Comparative Analysis helps to evaluate performance and identify key success factors. Materials and Methods: We compiled case-based, mixed data on performance and characteristics of 19 syndromic surveillance systems in Europe from scientific and grey literature and from site visits. We identified success factors by applying crisp-set Qualitative Comparative Analysis. We focused on two main areas of syndromic surveillance application: seasonal influenza surveillance and situational awareness during different types of potentially health threatening events. Results: We found that syndromic surveillance systems might detect the onset or peak of seasonal influenza earlier if they analyse non-clinical data sources. Timely situational awareness during different types of events is supported by an automated syndromic surveillance system capable of analysing multiple syndromes. To our surprise, the analysis of multiple data sources was no key success factor for situational awareness. Conclusions: We suggest to consider these key success factors when designing or further developing syndromic surveillance systems. Qualitative Comparative Analysis helped interpreting complex, mixed data on small-N cases and resulted in concrete and practically relevant findings

Assessing Syndromic Surveillance of Cardiovascular Outcomes from Emergency Department Chief Complaint Data in New York City

Prospective syndromic surveillance of emergency department visits has been used for near-real time tracking of communicable diseases to detect outbreaks or other unexpected disease clusters. The utility of syndromic surveillance for tracking cardiovascular events, which may be influenced by environmental factors and influenza, has not been evaluated. We developed and evaluated a method for tracking cardiovascular events using emergency department free-text chief complaints.There were three phases to our analysis. First we applied text processing algorithms based on sensitivity, specificity, and positive predictive value to chief complaint data reported by 11 New York City emergency departments for which ICD-9 discharge diagnosis codes were available. Second, the same algorithms were applied to data reported by a larger sample of 50 New York City emergency departments for which discharge diagnosis was unavailable. From this more complete data, we evaluated the consistency of temporal variation of cardiovascular syndromic events and hospitalizations from 76 New York City hospitals. Finally, we examined associations between particulate matter ≤2.5 µm (PM(2.5)), syndromic events, and hospitalizations. Sensitivity and positive predictive value were low for syndromic events, while specificity was high. Utilizing the larger sample of emergency departments, a strong day of week pattern and weak seasonal trend were observed for syndromic events and hospitalizations. These time-series were highly correlated after removing the day-of-week, holiday, and seasonal trends. The estimated percent excess risks in the cold season (October to March) were 1.9% (95% confidence interval (CI): 0.6, 3.2), 2.1% (95% CI: 0.9, 3.3), and 1.8% (95%CI: 0.5, 3.0) per same-day 10 µg/m(3) increase in PM(2.5) for cardiac-only syndromic data, cardiovascular syndromic data, and hospitalizations, respectively.Near real-time emergency department chief complaint data may be useful for timely surveillance of cardiovascular morbidity related to ambient air pollution and other environmental events

Exploring spatial-frequency-sequential relationships for motor imagery classification with recurrent neural network

Abstract Background Conventional methods of motor imagery brain computer interfaces (MI-BCIs) suffer from the limited number of samples and simplified features, so as to produce poor performances with spatial-frequency features and shallow classifiers. Methods Alternatively, this paper applies a deep recurrent neural network (RNN) with a sliding window cropping strategy (SWCS) to signal classification of MI-BCIs. The spatial-frequency features are first extracted by the filter bank common spatial pattern (FB-CSP) algorithm, and such features are cropped by the SWCS into time slices. By extracting spatial-frequency-sequential relationships, the cropped time slices are then fed into RNN for classification. In order to overcome the memory distractions, the commonly used gated recurrent unit (GRU) and long-short term memory (LSTM) unit are applied to the RNN architecture, and experimental results are used to determine which unit is more suitable for processing EEG signals. Results Experimental results on common BCI benchmark datasets show that the spatial-frequency-sequential relationships outperform all other competing spatial-frequency methods. In particular, the proposed GRU-RNN architecture achieves the lowest misclassification rates on all BCI benchmark datasets. Conclusion By introducing spatial-frequency-sequential relationships with cropping time slice samples, the proposed method gives a novel way to construct and model high accuracy and robustness MI-BCIs based on limited trials of EEG signals

Evolutionary Epidemiology of Drug-Resistance in Space

The spread of drug-resistant parasites erodes the efficacy of therapeutic treatments against many infectious diseases and is a major threat of the 21st century. The evolution of drug-resistance depends, among other things, on how the treatments are administered at the population level. “Resistance management” consists of finding optimal treatment strategies that both reduce the consequence of an infection at the individual host level, and limit the spread of drug-resistance in the pathogen population. Several studies have focused on the effect of mixing different treatments, or of alternating them in time. Here, we analyze another strategy, where the use of the drug varies spatially: there are places where no one receives any treatment. We find that such a spatial heterogeneity can totally prevent the rise of drug-resistance, provided that the size of treated patches is below a critical threshold. The range of parasite dispersal, the relative costs and benefits of being drug-resistant compared to being drug-sensitive, and the duration of an infection with drug-resistant parasites are the main factors determining the value of this threshold. Our analysis thus provides some general guidance regarding the optimal spatial use of drugs to prevent or limit the evolution of drug-resistance

Using Ethnographic Methods to Articulate Community-Based Conceptions of Cultural Heritage Management

How can ethnographic methods help communities articulate and enact their own conceptions of heritage management? This and related questions are being explored through an international research project, ‘Intellectual Property Issues in Cultural Heritage’. The project includes up to twenty community- based initiatives that incorporate community-based participatory research and ethnographic methods to explore emerging intellectual property-related issues in archaeological contexts; the means by which they are being addressed or resolved; and the broader implications of these issues and concerns. We discuss three examples that use ethnography to (a) articulate local or customary laws and principles of archaeological heritage management among a First Nations group in British Columbia; (b) assemble knowledge related to land/sea use and cultural practices of the Moriori people of Rekohu (Chatham Islands) for their use in future land and heritage manage- ment policies; and (c) aid a tribal cultural centre in Michigan in crafting co-management strategies to protect spiritual traditions associated with a rock art site on state property. Such situations call for participatory methods that place control over the design, process, products, and interpretation of ‘archaeology’ in the hands of cultural descendants. We hope that these examples of community-based conceptions of archaeological heritage management, facilitated through ethnographic methods and participatory approaches, will increase awareness of the value of these and other alternative approaches and the need to share them widely

Multi-disciplinary efforts to evaluate the therapeutic potential of CDK11, a novel transcription associated cyclin dependent kinase.

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Safety and immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adults and children in Lambaréné, Gabon: A phase I randomised trial.

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine prevented Ebola virus disease when used at 2 × 107 plaque-forming units (PFU) in a trial in Guinea. This study provides further safety and immunogenicity data. METHODS AND FINDINGS: A randomised, open-label phase I trial in Lambaréné, Gabon, studied 5 single intramuscular vaccine doses of 3 × 103, 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU in 115 adults and a dose of 2 × 107 PFU in 20 adolescents and 20 children. The primary objective was safety and tolerability 28 days post-injection. Immunogenicity, viraemia, and shedding post-vaccination were evaluated as secondary objectives. In adults, mild-to-moderate adverse events were frequent, but there were no serious or severe adverse events related to vaccination. Before vaccination, Zaire Ebola virus (ZEBOV)-glycoprotein (GP)-specific and ZEBOV antibodies were detected in 11% and 27% of adults, respectively. In adults, 74%-100% of individuals who received a dose 3 × 104, 3 × 105, 3 × 106, or 2 × 107 PFU had a ≥4.0-fold increase in geometric mean titres (GMTs) of ZEBOV-GP-specific antibodies at day 28, reaching GMTs of 489 (95% CI: 264-908), 556 (95% CI: 280-1,101), 1,245 (95% CI: 899-1,724), and 1,503 (95% CI: 931-2,426), respectively. Twenty-two percent of adults had a ≥4-fold increase of ZEBOV antibodies, with GMTs at day 28 of 1,015 (647-1,591), 1,887 (1,154-3,085), 1,445 (1,013-2,062), and 3,958 (2,249-6,967) for the same doses, respectively. These antibodies persisted up to day 180 for doses ≥3 × 105 PFU. Adults with antibodies before vaccination had higher GMTs throughout. Neutralising antibodies were detected in more than 50% of participants at doses ≥3 × 105 PFU. As in adults, no serious or severe adverse events related to vaccine occurred in adolescents or children. At day 2, vaccine RNA titres were higher for adolescents and children than adults. At day 7, 78% of adolescents and 35% of children had recombinant vesicular stomatitis virus RNA detectable in saliva. The vaccine induced high GMTs of ZEBOV-GP-specific antibodies at day 28 in adolescents, 1,428 (95% CI: 1,025-1,989), and children, 1,620 (95% CI: 806-3,259), and in both groups antibody titres increased up to day 180. The absence of a control group, lack of stratification for baseline antibody status, and imbalances in male/female ratio are the main limitations of this study. CONCLUSIONS: Our data confirm the acceptable safety and immunogenicity profile of the 2 × 107 PFU dose in adults and support consideration of lower doses for paediatric populations and those who request boosting. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201411000919191