Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

Change Point Estimation in Monitoring Survival Time

Precise identification of the time when a change in a hospital outcome has occurred enables clinical experts to search for a potential special cause more effectively. In this paper, we develop change point estimation methods for survival time of a clinical procedure in the presence of patient mix in a Bayesian framework. We apply Bayesian hierarchical models to formulate the change point where there exists a step change in the mean survival time of patients who underwent cardiac surgery. The data are right censored since the monitoring is conducted over a limited follow-up period. We capture the effect of risk factors prior to the surgery using a Weibull accelerated failure time regression model. Markov Chain Monte Carlo is used to obtain posterior distributions of the change point parameters including location and magnitude of changes and also corresponding probabilistic intervals and inferences. The performance of the Bayesian estimator is investigated through simulations and the result shows that precise estimates can be obtained when they are used in conjunction with the risk-adjusted survival time CUSUM control charts for different magnitude scenarios. The proposed estimator shows a better performance where a longer follow-up period, censoring time, is applied. In comparison with the alternative built-in CUSUM estimator, more accurate and precise estimates are obtained by the Bayesian estimator. These superiorities are enhanced when probability quantification, flexibility and generalizability of the Bayesian change point detection model are also considered

Foraging Fidelity as a Recipe for a Long Life: Foraging Strategy and Longevity in Male Southern Elephant Seals

Identifying individual factors affecting life-span has long been of interest for biologists and demographers: how do some individuals manage to dodge the forces of mortality when the vast majority does not? Answering this question is not straightforward, partly because of the arduous task of accurately estimating longevity in wild animals, and of the statistical difficulties in correlating time-varying ecological covariables with a single number (time-to-event). Here we investigated the relationship between foraging strategy and life-span in an elusive and large marine predator: the Southern Elephant Seal (Mirounga leonina). Using teeth recovered from dead males on îles Kerguelen, Southern Ocean, we first aged specimens. Then we used stable isotopic measurements of carbon () in dentin to study the effect of foraging location on individual life-span. Using a joint change-point/survival modelling approach which enabled us to describe the ontogenetic trajectory of foraging, we unveiled how a stable foraging strategy developed early in life positively covaried with longevity in male Southern Elephant Seals. Coupled with an appropriate statistical analysis, stable isotopes have the potential to tackle ecological questions of long standing interest but whose answer has been hampered by logistic constraints

Identifying stroke therapeutics from preclinical models: A protocol for a novel application of network meta-analysis

Introduction: Globally, stroke is the second leading cause of death. Despite the burden of illness and death, few acute interventions are available to patients with ischemic stroke. Over 1,000 potential neuroprotective therapeutics have been evaluated in preclinical models. It is important to use robust evidence synthesis methods to appropriately assess which therapies should be translated to the clinical setting for evaluation in human studies. This protocol details planned methods to conduct a systematic review to identify and appraise eligible studies and to use a network meta-analysis to synthesize available evidence to answer the following questions: in preclinical in vivo models of focal ischemic stroke, what are the relative benefits of competing therapies tested in combination with the gold standard treatment alteplase in (i) reducing cerebral infarction size, and (ii) improving neurobehavioural outcomes? Methods: We will search Ovid Medline and Embase for articles on the effects of combination therapies with alteplase. Controlled comparison studies of preclinical in vivo models of experimentally induced focal ischemia testing the efficacy of therapies with alteplase versus alteplase alone will be identified. Outcomes to be extracted include infarct size (primary outcome) and neurobehavioural measures. Risk of bias and construct validity will be assessed using tools appropriate for preclinical studies. Here we describe steps undertaken to perform preclinical network meta-analysis to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. This will be a novel use of this evidence synthesis approach in stroke medicine to assess pre-clinical therapeutics. Combining all evidence to simultaneously compare mutliple therapuetics tested preclinically may provide a rationale for the clinical translation of therapeutics for patients with ischemic stroke.  Dissemination: Review findings will be submitted to a peer-reviewed journal and presented at relevant scientific meetings to promote knowledge transfer. Registration: PROSPERO number to be submitted following peer review

Correction of Severe Ptosis with a Silicone Implant Suspensor: 22 Years of Experience

Background: Patients with severe ptosis caused by poor or absent function of the levator muscle but with good frontalis muscle excursion usually benefit from a frontalis sling procedure. This is currently carried out using organic or inorganic material to connect the upper eyelid to the frontalis muscle. Methods: The aim of this study was to evaluate retrospectively 112 patients who underwent frontalis sling procedures between 1989 and 2011 using a preformed silicone implant suspensor to correct severe ptosis. Results: The results obtained using this technique were good or fair in 95.54 percent of the cases and poor in 4.46 percent of the cases. The authors discuss the results of the study and the cases in which the procedure should be indicated and highlight the advantages of the method. Conclusion: The availability of this low-cost sterile device, together with the fact that it is ready to use, requires less invasive surgery, saves time, and is sufficiently versatile to allow adjustments to be made at any time, makes the silicone eyelid sling an attractive choice for correcting ptosis. (Plast. Reconstr. Surg. 129: 453e, 2012.