Variation in Specificity of HIV Rapid Diagnostic Tests over Place and Time: An Analysis of Discordancy Data Using a Bayesian Approach

BACKGROUND Recent trends to earlier access to anti-retroviral treatment underline the importance of accurate HIV diagnosis. The WHO HIV testing strategy recommends the use of two or three rapid diagnostic tests (RDTs) combined in an algorithm and assume a population is serologically stable over time. Yet RDTs are prone to cross reactivity which can lead to false positive or discordant results. This paper uses discordancy data from Médecins Sans Frontières (MSF) programmes to test the hypothesis that the specificity of RDTs change over place and time. METHODS Data was drawn from all MSF test centres in 2007-8 using a parallel testing algorithm. A Bayesian approach was used to derive estimates of disease prevalence, and of test sensitivity and specificity using the software WinBUGS. A comparison of models with different levels of complexity was performed to assess the evidence for changes in test characteristics by location and over time. RESULTS 106, 035 individuals were included from 51 centres in 10 countries using 7 different RDTs. Discordancy patterns were found to vary by location and time. Model fit statistics confirmed this, with improved fit to the data when test specificity and sensitivity were allowed to vary by centre and over time. Two examples show evidence of variation in specificity between different testing locations within a single country. Finally, within a single test centre, variation in specificity was seen over time with one test becoming more specific and the other less specific. CONCLUSION This analysis demonstrates the variable specificity of multiple HIV RDTs over geographic location and time. This variability suggests that cross reactivity is occurring and indicates a higher than previously appreciated risk of false positive HIV results using the current WHO testing guidelines. Given the significant consequences of false HIV diagnosis, we suggest that current testing and evaluation strategies be reviewed.The authors have no funding or support to report

Enhanced esports: Community perspectives on performance enhancers in competitive gaming

This work explores perceptions of performance enhancer usage in esports. Specifically, we explored the perception of: food and food supplements; non-medical use of prescription drugs; drugs with some social acceptance (e.g. alcohol, nicotine, cannabis); drugs with lower social acceptance (e.g., psychedelics, opioids); and non-invasive brain stimulation (e.g. transcranial direct current stimulation). A mixed-methods approach was used to triangulate findings around three data sets, including both prompted and unprompted online forum comments, as well as survey data. The studies evidence that players are willing to use or are already using enhancers to increase their in-game performance, and that players are generally concerned about the use of enhancers in professional esports contexts. Furthermore, the community perceives that a substantial number of e-athletes use enhancers. The core contribution of this work is a comprehensive investigation into perspectives of esports performance enhancement, which highlights the urgent need for further research, as well as regulation by esports leagues

Field testing of World Health Organization (WHO) 2003 recommendations for initiating anti-retroviral therapy (ART) where CD4 is not available revealed low sensitivity among stage I and II patients; a combination of Automated Total Lymphocyte Count (TLC) and Haemoglobin (Hgb) can ration the referral for CD4 testing.

2006 AIDS Conference, Toront

Microscopy Quality Control in Médecins Sans Frontières Programs in Resource-Limited Settings

Derryck Klarkowski and Daniel Orozco describe the Médecins Sans Frontières program for monitoring the quality of microscopy for malaria, pulmonary tuberculosis, and leishmaniasis

Player experience and deceptive expectations of difficulty adaptation in digital games

Increasingly, digital games are including adaptive features that adjust the level of difficulty to match the skills of individual players. The intention is to improve and prolong the player experience by allowing the player to have the feeling of challenge without it being overwhelming and leading to repeated failure and frustration. Previous work has shown that player experience is indeed improved by such adaptations but also that the player experience can be improved by simply claiming such an adaptation is present even when it is not. It is therefore possible that claims about adaptations and the actual adaptations could interact and not lead to the intended outcomes for the players or worse disappoint players. This paper reports on two studies that were conducted to experimentally investigate the interaction between game adaptations and player information about adaptations on the player experience, specifically their sense of immersion in the game. For this, two games were developed using two different kinds of adaptations to adjust difficulty based on players’ performance in the game. Participants were provided with information about game adaptations independently of whether the adaptations were present. The results suggest that players felt more immersed in the game when told that the game adapts to them, regardless of whether the adaptation was present in the game or not. This effect was observed in both games despite their different adaptations and it remained prominent even during longer gaming sessions. These findings demonstrate that players’ knowledge of adaptations influences their experience independently of adaptations. In this particular context, the knowledge reinforced the experience of the adaptations. This suggests that, at least in some circumstances, developers do not need to be concerned about negative effects of telling players about in-game adaptations

Dilution testing using rapid diagnostic tests in a HIV diagnostic algorithm: a novel alternative for confirmation testing in resource limited settings.

BACKGROUND: Current WHO testing guidelines for resource limited settings diagnose HIV on the basis of screening tests without a confirmation test due to cost constraints. This leads to a potential risk of false positive HIV diagnosis. In this paper, we evaluate the dilution test, a novel method for confirmation testing, which is simple, rapid, and low cost. The principle of the dilution test is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the sample, in order to screen out the cross reacting antibodies responsible for falsely positive RDT results. METHODS: Participants were recruited from two testing centres in Ethiopia where a tiebreaker algorithm using 3 different RDTs in series is used to diagnose HIV. All samples positive on the initial screening RDT and every 10th negative sample underwent testing with the gold standard and dilution test. Dilution testing was performed using Determine™ rapid diagnostic test at 6 different dilutions. Results were compared to the gold standard of Western Blot; where Western Blot was indeterminate, PCR testing determined the final result. RESULTS: 2895 samples were recruited to the study. 247 were positive for a prevalence of 8.5 % (247/2895). A total of 495 samples underwent dilution testing. The RDT diagnostic algorithm misclassified 18 samples as positive. Dilution at the level of 1/160 was able to correctly identify all these 18 false positives, but at a cost of a single false negative result (sensitivity 99.6 %, 95 % CI 97.8-100; specificity 100 %, 95 % CI: 98.5-100). Concordance between the gold standard and the 1/160 dilution strength was 99.8 %. CONCLUSION: This study provides proof of concept for a new, low cost method of confirming HIV diagnosis in resource-limited settings. It has potential for use as a supplementary test in a confirmatory algorithm, whereby double positive RDT results undergo dilution testing, with positive results confirming HIV infection. Negative results require nucleic acid testing to rule out false negative results due to seroconversion or misclassification by the lower sensitivity dilution test. Further research is needed to determine if these results can be replicated in other settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01716299

Don’t You Know That You’re Toxic: Normalization of Toxicity in Online Gaming

Peer ReviewedVideo game toxicity, endemic to online play, represents a pervasive and complex problem. Antisocial behaviours in online play directly harm player wellbeing, enjoyment, and retention—but research has also revealed that some players normalize toxicity as an inextricable and acceptable element of the competitive video game experience. In this work, we explore perceptions of toxicity and how they are predicted by player traits, demonstrating that participants reporting a higher tendency towards Conduct Reconstrual, Distorting Consequences, Dehumanization, and Toxic Online Disinhibition perceive online game interactions as less toxic. Through a thematic analysis on willingness to report, we also demonstrate that players abstain from reporting toxic content because they view it as acceptable, typical of games, as banter, or as not their concern. We propose that these traits and themes represent contributing factors to the cyclical normalization of toxicity. These findings further highlight the multifaceted nature of toxicity in online video games

Direct microscopy versus sputum cytology analysis and bleach sedimentation for diagnosis of tuberculosis: a prospective diagnostic study.

ABSTRACT: BACKGROUND: Diagnostic options for pulmonary tuberculosis in resource-poor settings are commonly limited to smear microscopy. We investigated whether bleach concentration by sedimentation and sputum cytology analysis (SCA) increased the positivity rate of smear microscopy for smear-positive tuberculosis. METHODS: We did a prospective diagnostic study in a Medecins Sans Frontieres-supported hospital in Mindouli, Republic of Congo. Three sputum samples were obtained from 280 consecutive pulmonary tuberculosis suspects, and were processed according to WHO guidelines for direct smear microscopy. The remainder of each sputum sample was homogenised with 2.6% bleach, sedimented overnight, smeared, and examined blinded to the direct smear result for acid-fast bacilli (AFB). All direct smears were assessed for quality by SCA. If a patient produced fewer than three good-quality sputum samples, further samples were requested. Sediment smear examination was performed independently of SCA result on the corresponding direct smear. Positivity rates were compared using McNemar's test. RESULTS: Excluding SCA, 43.2% of all patients were diagnosed as positive on direct microscopy of up to three samples. 47.9% were diagnosed on sediment microscopy, with 48.2% being diagnosed on direct microscopy, sediment microscopy, or both. The positivity rate increased from 43.2% to 47.9% with a case definition of one positive smear ([greater than or equal to]1 AFB/100 high power fields) of three, and from 42.1% to 43.9% with two positive smears. SCA resulted in 87.9% of patients producing at least two good-quality sputum samples, with 75.7% producing three or more. Using a case definition of one positive smear, the incremental yield of bleach sedimentation was 14/121, or 11.6% (95% CI 6.5-18.6, p=0.001) and in combination with SCA was 15/121, or 12.4% (95% CI 7.1-19.6, p=0.002). Incremental yields with two positive smears were 5/118, or 4.2% (95% CI 1.4-9.6, p=0.062) and 7/118, or 5.9% (95% CI 2.4-11.8, p=0.016), respectively. CONCLUSIONS: The combination of bleach sedimentation and SCA resulted in significantly increased microscopy positivity rates with a case definition of either one or two positive smears. Implementation of bleach sedimentation led to a significant increase in the diagnosis of smear-positive patients. Implementation of SCA did not result in significantly increased diagnosis of tuberculosis, but did result in improved sample quality. Requesting extra sputum samples based on SCA results, combined with bleach sedimentation, could significantly increase the detection of smear-positive patients if routinely implemented in resource-limited settings where gold standard techniques are not available. We recommend that a pilot phase is undertaken before routine implementation to determine the impact in a particular context

Greater rewards in videogames lead to more presence, enjoyment and effort

There is currently limited understanding of whether and how different amounts and diversity of virtual rewards impact on the player experience. A repeated-measures experiment was undertaken in which participants (N = 59) were compared on subjective measures (competence, presence-immersion, tension, effort and enjoyment), as well as psychophysiological measures (electrodermal activity and heart-beat rate), during the play of a videogame with three levels of video game reward (high, medium, low). Effort, enjoyment and presence-immersion significantly varied across conditions such that they were greater when all rewards were present compared to one or both of the other conditions. Heart-beat rate was found to vary across conditions consistent with the explanation that greater rewards lead to greater arousal. Our study suggest a number of advantages to greater amount and diversity of virtual rewards in the context of a casual videogame, with potential application to the design of new gamification systems

Alert, but not alarmed - a comment on "Towards more accurate HIV testing in sub-Saharan Africa: a multi-site evaluation of HIV RDTs and risk factors for false positives (Kosack et al. 2017)".

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