Rapid development and deployment of diagnostic testing for COVID-19 have been a key component of the public health response to the pandemic. Out of necessity, academic and other clinical laboratories developed laboratory testing innovations for COVID-19 to meet clinical testing demands. In addition to constraints on local testing supplies and equipment, a rapidly changing regulatory framework created challenges for translational scientists. Illustrative examples of approaches used to develop laboratory tests during the early stages of the COVID-19 pandemic demonstrate effective team science approaches to this challenging clinical care and public health emergency. These experiences and the associated lessons learned are relevant to the development of public health response plans for future pandemics.

In 2003/2004 a field trial was conducted in Northern Ireland to assess the diagnostic accuracy of six serological tests for bovine brucellosis caused by Brucella abortus. Whereas between-test comparisons have been used to calculate test performances so far, the present study used a latent class approach to estimate diagnostic test accuracy parameters in the absence of a gold standard for these six tests simultaneously and to estimate the true prevalence, while accounting for clustering in the study population and risk factors for true prevalence. Results obtained in this study with regard to prevalence, sensitivity and specificity were largely in accordance with previous findings. Screening tests (SAT and EDTA) appeared to be the most sensitive; however, at low prevalences the EDTA and CFT showed the highest positive predictive values of all investigated tests. The specificities and negative predictive values of all diagnostic tests were found to be very high. Differences of prevalence between three groups of the study population with different risk of exposure could be attributed to the mode of sampling indicating that a more risk-based sampling will result in a higher prevalence than a cross-sectional sampling mode. Age, dairy status and history of abortion were shown to influence the prediction of the latent true infection status.

Heart transplantation offers excellent survival benefit to children with end-stage heart failure. With its success, the number of potential recipients continues to exceed the number of available donors. Developing strategies to safely increase donor utilisation is crucial to decreasing wait-list mortality. A new paediatric heart allocation policy is set to be implemented with the goal of prioritising the most urgent listed candidates. Owing to excellent outcomes of ABO-incompatible heart transplantation, the sickest infants will soon receive priority for heart offers irrespective of blood group. Allosensitisation poses unique challenges within the paediatric population; ongoing multi-centre studies are poised to refine our understanding of key risk factors and optimal treatment strategies. Biomarkers for acute cellular rejection, such as donor-specific cell-free DNA, and cardiac allograft vasculopathy, such as VEGF-A, may lead to a decreased need for invasive screening. Ultimately, well-designed and executed randomised control trials of post-transplant immunosuppression are required to improve long-term outcomes after paediatric heart transplantation.

Objective: The aim of this study was to present a clear process of synthesizing test accuracy data when conducting economic evaluations of diagnostic tests for health technology assessment (HTA) assessors and health economists.

Methods: We appraised the methods advocated for using diagnostic test accuracy data in economic evaluations. We used a case study of fetal anemia in which data from a screening test are used in combination with a confirmatory test.

Results: We developed a step-by-step guide and consider two scenarios: when data on test accuracy from several studies are based on (i) the same test threshold for positivity and (ii) different test thresholds.

Conclusions: We conclude that each approach has its strengths and limitations. We show that the optimal operating point of the test should be identified to determine the true cost-effectiveness of the test. We advocate that these issues require a multidisciplinary team of health economists, decision modelers and statisticians.

Objectives: The aim of this study was to assess the test performance and clinical effectiveness of photodynamic diagnosis (PDD) compared with white light cystoscopy (WLC) in people suspected of new or recurrent bladder cancer.

Methods: A systematic review was conducted of randomized controlled trials (RCTs), nonrandomized comparative studies, or diagnostic cross-sectional studies comparing PDD with WLC. Fifteen electronic databases and Web sites were searched (last searches April 2008). For clinical effectiveness, only RCTs were considered.

Results: Twenty-seven studies (2,949 participants) assessed test performance. PDD had higher sensitivity than WLC (92 percent, 95 percent confidence interval [CI], 80–100 percent versus 71 percent, 95 percent CI, 49–93 percent) but lower specificity (57 percent, 95 percent CI, 36–79 percent versus 72 percent, 95 percent CI, 47–96 percent). For detecting higher risk tumors, median range sensitivity of PDD (89 percent [6–100 percent]) was higher than WLC (56 percent [0–100 percent]) whereas for lower risk tumors it was broadly similar (92 percent [20–95 percent] versus 95 percent [8–100 percent]). Four RCTs (709 participants) using 5-aminolaevulinic acid (5-ALA) as the photosensitising agent reported clinical effectiveness. Using PDD at transurethral resection of bladder tumor (TURBT) resulted in fewer residual tumors at check cystoscopy (relative risk [RR], 0.37, 95 percent CI, 0.20–0.69) and longer recurrence-free survival (RR, 1.37, 95 percent CI, 1.18–1.59), compared with WLC.

Conclusions: PDD detects more bladder tumors than WLC, including more high-risk tumors. Based on four RCTs reporting clinical effectiveness, 5-aminolaevulinic acid–mediated PDD at TURBT facilitates a more complete resection and prolongs recurrence-free survival.

The risk of foreign animal disease introduction continues to exist despite Canada's strict regulations concerning the importation of animals and animal products. Given the rapidity with which these diseases can spread, especially in areas with dense livestock populations, eradication efforts which rely solely on quarantine and stamping-out measures can present a formidable undertaking. This, combined with growing economic and ethical considerations, has led to renewed interest in the use of vaccination as a tool in controlling foreign animal disease outbreaks. Vaccination has effects at the individual and population levels. Efficacious vaccines reduce or prevent clinical signs without necessarily preventing virus replication. They may also increase the dose of virus needed to establish an infection and/or reduce the level and duration of virus shedding following infection. Vaccine effectiveness within a population is a function of its ability to reduce virus transmission. Transmission is best described by the reproductive ratio, R, which is defined as the average number of new infections caused by one infectious individual. By helping to reduce the R-value below 1, vaccination can be an effective adjunct in abbreviating an outbreak. Nevertheless, vaccination can also complicate serological surveillance activities that follow eradication, if the antibody response induced by vaccination is indistinguishable from that which follows infection. This disadvantage can be overcome by the use of DIVA vaccines and their companion diagnostic tests. The term DIVA (differentiating infected from vaccinated individuals) was coined in 1999 by J. T. van Oirschot of the Central Veterinary Institute, in the Netherlands. It is now generally used as an acronym for ‘differentiating infected from vaccinated animals’. The term was originally applied to the use of marker vaccines, which are based on deletion mutants of wild-type microbes, in conjunction with a differentiating diagnostic test. The DIVA strategy has been extended to include subunit and killed whole-virus vaccines. This system makes possible the mass vaccination of a susceptible animal population without compromising the serological identification of convalescent individuals. The DIVA approach has been applied successfully to pseudorabies and avian influenza eradication, and has been proposed for use in foot-and-mouth disease and classical swine fever eradication campaigns. This paper will survey current vaccine technology, the host immune response, and companion diagnostic tests that are available for pseudorabies, foot-and-mouth disease, classical swine fever and avian influenza.

Objectives: Pre-admission clinics are traditionally run jointly by nurses and doctors. Within an adult ENT pre-admission clinic, we wished to assess what doctors added tonurses’ pre-clerking, to determine whether doctors were actually needed in the clinic.

Methods: Prospective study,looking at how often doctors, seeing patients after ward-based nurses, changed or added to clerking or tests as organized by nurses.

Results: Out of 184 patients, doctors changed or added to nurses’ clerking or planned investigations in 47 patients (26 per cent), making 64 different changes. The commonest reasonsfor changes were ordering blood tests (22 changes), chest X-rays (eight), cancelling due to hypertension (seven), altering drug history (five) and requesting electrocardiograms (five changes).

Conclusion: Most changes made by doctors could be eliminated by designing a pre-admission clinic protocol that could easily be used by nurses. We recommend that all ENT departments consider implementing nurse-led pre-admission clinics.

Objectives: To collect and summarize information published by INAHTA agencies on the indications, habitual attitudes and practices, and economic and legal implications of preoperative evaluation in elective surgeries.

Method: The authors appraised the information contained in six papers published between 1989 and 1999 in Sweden, France, Basque Country, the Netherlands, United Kingdom, and Catalonia. The section on indications in preoperative evaluation does not present global conclusions. The sections addressing habitual attitudes and practices among physicians and those addressing economic and legal considerations cover only the similarities among the reports and the main ideas relating to these issues.

Results: The conclusions found in the reports about indications in preoperative evaluation are similar or differ slightly, e.g., as regards age limits in patients for whom the tests are recommended. However, more important differences are shown in other areas, especially in reports where consensus methods were used. In some instances, the opinions, attitudes, and customary practices of professionals during the preoperative stage do not concur with the recommendations extracted from the assessment reports and the customary practice of doctors. In relation to economic considerations, a substantial quantity of resources could be liberated if the recommended general clinical practices were followed. From the point of view of civil law, the evidence-based recommendations could be considered as a kind of coded lex artis.

A prospective multicentre pilot study was undertaken in 20 Italian hospitals to assess the influence of a routine pre-operative chest radiograph on anaesthetic management and to characterise which patients might benefit from it. A total of 6111 patients undergoing elective surgery and submitted for routine pre-operative chest radiograph were enrolled. Abnormal pre-operative chest radiographs were reported in 1116 patients (18.3%). Pre-operative chest radiograph altered the anaesthetic management (i.e. useful pre-operative chest radiograph) in 313 patients (5.1%). Male sex, age >60 years, ASA classes ≥3, respiratory diseases, and the presence of two or more co-existing diseases were significantly related to the probability of a useful pre-operative chest radiograph using multivariate analysis (P<0.01). The classification of the surgical intervention and, of the co-existing diseases, the presence of cardiac disease had a very low influence when determining the probability that a pre-operative chest radiograph would be useful. A simple equation includes the effects of all the variables studied and allows calculation of the probability of a useful pre-operative chest radiograph. This study indicates that in healthy, female, ≤60-year-old patients, submitted for standard surgery, the probability of a useful pre-operative chest radiograph ranges from 0.2% to 3.5% according to the hospital. The probability increases in male or elderly subjects, or in the presence of co-existing respiratory diseases, or in ASA classes ≥3, but there is a wide variation between hospitals.

As children with autism have pervasive executive difficulties it is necessary to determine whether these contribute to their often-reported failure on the false belief task. Failure on this task is frequently taken to diagnose the lack of a “theory of mind”. We report two studies using two tasks that make similar executive demands to the false belief task. The first experiment showed that children with autism are significantly challenged by a “conflicting desire” task, which suggests that their difficulty with the false belief task is not rooted in difficulty with grasping the representational nature of belief. In the second study children with autism were also found to be impaired on a novel version of the “false photograph task”. A parsimonious reading of these data is that their difficulty with all three tasks is due to commonalities in the tasks' executive structure.

Estimation of haemoglobin is still undertaken routinely before ENT surgery in many centres despite evidence that it is unnecessary, traumatic and expensive. The haemoglobin was estimated of all 372 children about to undergo ENT surgery in a busy district general hospital over a one year period. No child was noted to be clinically anacmic, and no child had a haemoglobin of less than 9 g/dl. Of 18 children with a haemoglobin level of 10.5 or less, 10 had their operations postponed and eight did not. There were no complications in the latter group. We can find no published evidence that operating on children with mild anaemia is unsafe. Ceasing routine pre-operative haemoglobin estimation would safely save an estimated £9000 per year in our unit.