An evaluation of computational methods for aggregate data meta-analyses of diagnostic test accuracy studies.

BACKGROUND: A Generalized Linear Mixed Model (GLMM) is recommended to meta-analyze diagnostic test accuracy studies (DTAs) based on aggregate or individual participant data. Since a GLMM does not have a closed-form likelihood function or parameter solutions, computational methods are conventionally used to approximate the likelihoods and obtain parameter estimates. The most commonly used computational methods are the Iteratively Reweighted Least Squares (IRLS), the Laplace approximation (LA), and the Adaptive Gauss-Hermite quadrature (AGHQ). Despite being widely used, it has not been clear how these computational methods compare and perform in the context of an aggregate data meta-analysis (ADMA) of DTAs. METHODS: We compared and evaluated the performance of three commonly used computational methods for GLMM - the IRLS, the LA, and the AGHQ, via a comprehensive simulation study and real-life data examples, in the context of an ADMA of DTAs. By varying several parameters in our simulations, we assessed the performance of the three methods in terms of bias, root mean squared error, confidence interval (CI) width, coverage of the 95% CI, convergence rate, and computational speed. RESULTS: For most of the scenarios, especially when the meta-analytic data were not sparse (i.e., there were no or negligible studies with perfect diagnosis), the three computational methods were comparable for the estimation of sensitivity and specificity. However, the LA had the largest bias and root mean squared error for pooled sensitivity and specificity when the meta-analytic data were sparse. Moreover, the AGHQ took a longer computational time to converge relative to the other two methods, although it had the best convergence rate. CONCLUSIONS: We recommend practitioners and researchers carefully choose an appropriate computational algorithm when fitting a GLMM to an ADMA of DTAs. We do not recommend the LA for sparse meta-analytic data sets. However, either the AGHQ or the IRLS can be used regardless of the characteristics of the meta-analytic data.

Fidelity of implementation of national guidelines on malaria diagnosis for children under-five years in Rivers State, Nigeria.

BACKGROUND: Malaria is still a disease of global public health importance and children under-five years of age are the most vulnerable to the disease. Nigeria adopted the "test and treat" strategy in the national malaria guidelines as one of the ways to control malaria transmission. The level of adherence to the guidelines is an important indicator for the success or failure of the country's roadmap to malaria elimination by 2030. This study aimed to assess the fidelity of implementation of the national guidelines on malaria diagnosis for children under-five years and examine its associated moderating factors in health care facilities in Rivers State, Nigeria. METHODS: This was a descriptive, cross-sectional study conducted in Port Harcourt metropolis. Data were collected from 147 public, formal private and informal private health care facilities. The study used a questionnaire developed based on Carroll's Conceptual Framework for Implementation Fidelity. Frequency, mean and median scores for implementation fidelity and its associated factors were calculated. Associations between fidelity and the measured predictors were examined using Mann Whitney U test, Kruskal Wallis test, and multiple linear regression modelling using robust estimation of errors. Regression results are presented in adjusted coefficient (ß) and 95% confidence intervals. RESULTS: The median (IQR) score fidelity score for all participants was 65% (43.3, 85). Informal private facilities (proprietary patent medicine vendors) had the lowest fidelity scores (47%) compared to formal private (69%) and public health facilities (79%). Intervention complexity had a statistically significant inverse relationship to implementation fidelity (ß = - 1.89 [- 3.42, - 0.34]). Increase in participant responsiveness (ß = 8.57 [4.83, 12.32]) and the type of malaria test offered at the facility (e.g., RDT vs. no test, ß = 16.90 [6.78, 27.03]; microscopy vs. no test, ß = 21.88 [13.60, 30.16]) were positively associated with fidelity score. CONCLUSIONS: This study showed that core elements of the "test and treat" strategy, such as testing all suspected cases with approved diagnostic methods before treatment, are still not fully implemented by health facilities. There is a need for strategies to increase fidelity, especially in the informal private health sector, for malaria elimination programme outcomes to be achieved.

The deimplementation of laboratory testing in low-risk patients as recommended by the American society of anesthesiologists: An ACS-NSQIP longitudinal analysis.

BACKGROUND: In 2012, the American Society of Anesthesiologists (ASA) published guidelines recommending against routine preoperative laboratory testing for low-risk patients to reduce unnecessary medical expenditures. The aim of this study was to assess the change in routine preoperative laboratory testing in low-risk versus higher-risk patients before and after release of these guidelines. METHODS: The ACS-NSQIP database, 2005-2018, was separated into low-risk versus higher-risk patients based upon a previously published stratification. The guideline implementation date was defined as January 2013. Changes in preoperative laboratory testing over time were compared between low- and higher-risk patients. A difference-in-differences model was applied. The primary outcome included any laboratory test obtained ≤90 days prior to surgery. RESULTS: Of 7,507,991 patients, 972,431 (13.0%) were defined as low-risk and 6,535,560 (87.0%) higher-risk. Use of any preoperative laboratory test declined in low-risk patients from 66.5% before to 59.6% after guidelines, a 6.9 percentage point reduction, versus 93.0%-91.9% in higher-risk patients, a 1.1 percentage point reduction (p < 0.0001, comparing percentage point reductions). After risk-adjustment, the adjusted odds ratio for having any preoperative laboratory test after versus before the guidelines was 0.77 (95% CI 0.76-0.78) in low-risk versus 0.93 (0.92-0.94) in higher-risk patients. In low-risk patients, lack of any preoperative testing was not associated with worse outcomes. CONCLUSIONS: While a majority of low-risk patients continue to receive preoperative laboratory testing not recommended by the ASA, there has been a decline after implementation of guidelines. Continued effort should be directed at the deimplementation of routine preoperative laboratory testing for low-risk patients.

Systematic review and meta-analysis: assessing the accuracy of rapid immunochromatographic tests in dengue diagnosis.

The objective of this systematic review is to analyze the diagnostic accuracy of rapid dengue diagnostic tests. The search was conducted in the following databases: LILACS, Medline (Pubmed), CRD, The Cochrane Library, Trip Medical Database and Google Scholar. ELISA and PCR assays were adopted as reference methods. Thirty-four articles were included in this systematic review. Receiver operating characteristic (ROC) and Forest Plot were performed to evaluate sensitivity and specificity for each parameter analyzed (NS1, IgM and IgG). The results revealed that the combined analysis of the IgM antibody with the NS1 antigen resulted in greater sensitivity than the isolated analysis of IgM. The three analytes together showed the best performance, with a combined sensitivity of 90 % (95 % CI: 89-92 %) using ELISA as a comparator. Thus, the present review provides relevant knowledge for decision-making between the available rapid diagnostic tests.

Auditory Processing Disorder: Protocols and Controversy.

PURPOSE: This study examined current auditory processing disorder (APD) protocols and audiologists' perspectives on the active debate seen in the literature regarding the status of APD as a unique disorder. METHOD: This study used a cross-sectional, nonexperimental survey design. The participants were 134 U.S. audiologists, representing diversity across experience level and work setting. RESULTS: Popular APD tests from prior surveys remain popular, and a few new tests have emerged. Most audiologists use diverse strategies to identify potential comorbid disorders as part of their APD protocol, including multidisciplinary assessment and referral to other specialists. Most participants disagreed with the assertion that APD is not a unique disorder; however, many also pointed out that patients' struggles with listening need to be the primary focus of APD assessment and management, regardless of the label of the disorder. Qualitative analysis of participant comments on the controversy yielded six themes: Clinical Experience, Comorbidity, Listening Skills, Literature Support, Overdiagnosis, and More Information Needed. CONCLUSION: Most participants consider APD to be a unique disorder, citing clinical experience and the literature for support; however, many also indicated APD is complicated by comorbidity and APD may be overdiagnosed.

Utility of Borrelia-specific IgM and IgG antibody titer determinations during a 12-year period - results from a clinical laboratory in Northern Sweden.

Interpretation of serological findings in suspected Lyme borreliosis (LB) is challenging and IgM reactivities may have low predictive value. Therefore, if used indiscriminately, there is a risk for incorrect diagnosis of LB. To evaluate the usefulness of IgM titer determination, we performed a study of the prevalence of Borrelia-specific antibodies in serological samples from patients with suspected LB analyzed during the period 2010 - 2021 at the University Hospital of Umeå in Sweden. In total, 19,335 samples had been analyzed for the presence of IgG and IgM antibodies. Overall, there were higher percentages of IgM positive or borderline titers, 1,847 (9.6%) and 905 (4.7%), respectively, than IgG positive or borderline titers, 959 (5.0%) and 406 (2.1%), respectively. Peak number of samples were recorded 2012 - 2013, exceeding 1,800, whereas there were around 1,200 during 2020 - 2021. The peak number of positive IgG and/or positive IgM samples were observed during the period 2015 - 2017 with close to, or above 400, and concomitantly, the proportion of IgG positive samples increased markedly. For IgG positive samples, the increase followed a positive linear time trend (P< 0.001). Peak monthly numbers were observed during August, September, and October. This seasonal increase was significant for the IgG positive group (P< 0.05), but not for the IgM positive/IgG negative group. Repeated samples were obtained from 3,188 individuals and of the initial samples 2,817 were (88%) IgG negative and 2,315 (72%) were IgM negative and of these, 130 (4%) showed IgG seroconversion and 300 (9%) IgM seroconversion. Collectively, the data demonstrate that IgG and/or IgM positive samples represented a minority of all samples, even when repeated sampling had occurred, and IgM positive samples were much more common than IgG positive samples. Thus, the accuracy of the clinical suspicion was low and this will lead to a low predictive value of the analysis, in particular of IgM. These findings question the use of IgM titer determination as a routine analysis.

Refining Timely Diagnosis of Early Syphilis by Using Treponema pallidum PCR or IgM Immunoblotting Next to Conventional Serology for Syphilis.

Treponema pallidum subsp. pallidum is a fastidious spirochete and the etiologic agent of syphilis, a sexually transmitted infection (STI). Syphilis diagnoses and disease staging are based on clinical findings and serologic testing. Moreover, according to most international guidelines, PCR analysis of swab samples from genital ulcers is included in the screening algorithm where possible. It has been suggested that PCR might be omitted from the screening algorithm due to low added value. As an alternative to PCR, IgM serology might be used. In this study, we wanted to establish the added value of PCR and IgM serology for diagnosing primary syphilis. Added value was defined as finding more cases of syphilis, preventing overtreatment, or limiting the extent of partner notification to more recent partners. We found that both PCR and IgM immunoblotting could aid the timely diagnosis of early syphilis in ~24% to 27% of patients. PCR has the greatest sensitivity and can be applied to cases with an ulcer with suspected reinfection or primary infection. In the absence of lesions, the IgM immunoblot could be used. However, the IgM immunoblot has better performance in cases with suspected primary infection than in reinfections. The target population, testing algorithm, time pressures, and costs should determine whether either test provides sufficient value to be implemented in clinical practice.

Ultrasonographic monitoring of feline epaxial muscle height as part of an annual wellness examination to assess for the development of sarcopenia.

OBJECTIVES: The aim of this study was to determine if epaxial muscle height (EMH) could be reliably incorporated into annual routine wellness screenings, and also determine its relationship to age, body condition score (BCS), subjective muscle assessment (SMA), breed and sex in mature cats. METHODS: EMH was determined independently by three observers from ultrasonographic examinations - collected by an additional trained individual - of cats enrolled at the Feline Healthy Ageing Clinic, University of Liverpool, UK. Age, body weight, BCS and SMA data were also collected. RESULTS: A total of 92 cats were included, 35 of which had repeat ultrasonographic examinations 12 months apart. Enrolled cats were a median age of 8 years and 9 months at the time of the first measurement. Variation in the quality of ultrasonographic images collected did not affect muscle depth measurements (P = 0.974). Further, there was good intra- and inter-observer repeatability for all observations (intraclass correlation range 0.97-0.99). There was a moderate positive association between EMH and body weight (r = 0.49, P <0.001) but no association with age (r = -0.05, P = 0.680). There were also positive associations in EMH among cats with different BCSs (P = 0.001) and SMAs (thoracic spine, P = 0.021; lumbar spine, P = 0.014), but breed (P = 0.429) and sex (P = 0.187) had no effect. Finally, there was no change in EMH measurements in the paired samples (P = 0.145) or correlation between percentage weight and EMH change over 12 months. CONCLUSIONS AND RELEVANCE: The accuracy of EMH measurement using ultrasonographic imaging is good, irrespective of observer experience and provided that the ultrasonographer has some training. This suggests that ultrasonographic measurement of EMH could have a major practical impact as a non-invasive determination of muscle mass in pet cat populations. Further research is required to assess longitudinal changes in muscle mass over time in senior pet cats.

Choosing which in-hospital laboratory tests to target for intervention: a scoping review.

INTRODUCTION: Some laboratory testing practices may be of low value, leading to wasted resources and potential patient harm. Our scoping review investigated factors and processes that developers report using to inform decisions about what tests to target for practice improvement. METHODS: We searched Medline on May 30th, 2019 and June 28th, 2021 and included guidelines, recommendation statements, or empirical studies related to test ordering practices. Studies were included if they were conducted in a tertiary care setting, reported making a choice about a specific test requiring intervention, and reported at least one factor informing that choice. We extracted descriptive details, tests chosen, processes used to make the choice, and factors guiding test choice. RESULTS: From 114 eligible studies, we identified 30 factors related to test choice including clinical value, cost, prevalence of test, quality of test, and actionability of test results. We identified nine different processes used to inform decisions regarding where to spend intervention resources. CONCLUSIONS: Intervention developers face difficult choices when deciding where to put scarce resources intended to improve test utilization. Factors and processes identified here can be used to inform a framework to help intervention developers make choices relevant to improving testing practices.

Serum versus synovial fluid interleukin-6 for periprosthetic joint infection diagnosis: a systematic review and meta-analysis of 30 diagnostic test accuracy studies.

BACKGROUND: Early and accurate detection of periprosthetic joint infection (PJI) after hip and/or knee arthroplasty remains challenging. This systematic review and meta-analysis of diagnostic test accuracy studies aimed to evaluate the diagnostic accuracy of serum and synovial fluid interleukin (IL)-6 in detecting PJI. METHODS: We searched 3 databases for studies through December 31, 2021, using medical sub-headings terms and keywords. Studies reported sensitivity and specificity of serum and synovial fluid IL-6 in detecting PJI were considered. We calculated the pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic curve (AUC) to evaluate the diagnostic accuracy of serum and synovial fluid IL-6. RESULTS: Thirty studies were included. The pooled sensitivity, specificity, positive and negative likelihood ratio, DOR, and AUC of serum IL-6 in detecting PJI were 0.76 (0.69-0.81), 0.88 (0.82-0.92), 6.2 (4.3-9.0), 0.28 (0.22-0.35), 22 (14-36), and 0.88 (0.85-0.91), respectively. However, synovial fluid IL-6 achieved a pooled sensitivity of 0.87 (0.75-0.93), specificity of 0.90 (0.85-0.93), positive and negative likelihood ratio of 8.5 (5.3-13.6) and 0.15 (0.08-0.29), DOR of 57 (21-156), and AUC of 0.94 (0.92-0.96), which were higher than serum IL-6. CONCLUSIONS: Synovial fluid IL-6 test may be a promising test for PJI after hip and/or knee arthroplasty. However, considering the limited volume of synovial fluid and invasive acquisition of synovial fluid IL-6, serum IL-6 test may be also considered.

Blood routine reference value range should be adjusted according to regional and ethnic characteristics.

Objective: To further understand the influence of regional and ethnic factors on blood routine indicators. Methods: The routine blood test (RBT) results of 617 healthy men aged 18-45 years old of the Li, Tibet, and Han nationalities living in the city of Sanya, Hainan Province (200 m), the city of Xining, Qinghai Province (2,300 m), and Maduo County of Qinghai Province (4,300 m) for a long time were studied. Eight indexes, such as the red blood cell (RBC), hemoglobin (Hb), and platelet (PLT) counts, were compared and analyzed. Results: With an increase in altitude, the RBT index values and change trends of the different ethnic groups were different. When the altitude increased by 2,000 m, the RBC and Hb increased by 6.6 and 8.1%, respectively, and the PLT decreased by 16.8%. However, the RBC, Hb, and PLT of the Tibetan subjects decreased by 7.4, 5.1, and 3.0%, respectively. In the same region, there were also significant differences in the RBT index values among the ethnic groups. The RBC increased, Hb decreased, and PLT did not change in the Li nationality in Sanya compared with the Han nationality. The RBC, Hb, and PLT of Tibetans in the Xining area were significantly higher than those of the Han population. Referring to the current RBT reference value range in China, the abnormal rates of the various RBT index values of the enrolled population were high. By utilizing Hb as an example, 27.7% of the Li nationality in Sanya was low, 67.0% of the Tibetan nationality in Xining was high, and 89.4% of the Maduo Han nationality was high. The PLT was lower in the Sanya Li nationality (13.8%) and the Maduo Han nationality (88.3%). Conclusion: Regional and ethnic factors have a significant impact on the RBT, and the current range of normal values of the RBT in China needs to be revised and adjusted.

Diagnostic performance of mycological tests for invasive pulmonary aspergillosis in non-haematological patients: protocol for a systematic review and meta-analysis.

INTRODUCTION: Increasing numbers of patients with non-haematological diseases are infected with invasive pulmonary aspergillosis (IPA), with a high mortality reported which is mainly due to delayed diagnosis. The diagnostic capability of mycological tests for IPA including galactomannan test, (1,3)-ß-D-glucan test, lateral flow assay, lateral flow device and PCR for the non-haematological patients remains unknown. This protocol aims to conduct a systematic review and meta-analysis of the diagnostic performance of mycological tests to facilitate the early diagnosis and treatments of IPA in non-haematological diseases. METHODS AND ANALYSIS: Database including PubMed, CENTRAL and EMBASE will be searched from 2002 until the publication of results. Cohort or cross-sectional studies that assessing the diagnostic capability of mycological tests for IPA in patients with non-haematological diseases will be included. The true-positive, false-positive, true-negative and false-negative of each test will be extracted and pooled in bivariate random-effects model, by which the sensitivity and specificity will be calculated with 95% CI. The second outcomes will include positive (negative) likelihood ratio, area under the receiver operating characteristic curve and diagnostic OR will also be computed in the bivariate model. When applicable, subgroup analysis will be performed with several prespecified covariates to explore potential sources of heterogeneity. Factors that may impact the diagnostic effects of mycological tests will be examined by sensitivity analysis. The risk of bias will be appraised by the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2). ETHICS AND DISSEMINATION: This protocol is not involved with ethics approval, and the results will be peer-reviewed and disseminated on a recognised journal. PROSPERO REGISTRATION NUMBER: CRD42021241820.

Rethinking the routine: Preoperative laboratory testing among American Society of Anesthesiologists class 1 and 2 patients before low-risk ambulatory surgery in the 2017 National Surgical Quality Improvement Program cohort.

BACKGROUND: Routine preoperative laboratory testing is not recommended for American Society of Anesthesiologists classification 1 or 2 patients before low-risk ambulatory surgery. METHODS: The 2017 National Surgical Quality Improvement Program data set was retrospectively queried for American Society of Anesthesiologists class 1 and 2 patients who underwent low-risk, elective outpatient anorectal, breast, endocrine, gynecologic, hernia, otolaryngology, oral-maxillofacial, orthopedic, plastic/reconstructive, urologic, and vascular operations. Preoperative laboratory testing was defined as any chemistry, hematology, coagulation, or liver function studies obtained ≤30 days preoperatively. Demographics, comorbidities, and outcomes were compared between those with and without testing. The numbers needed to test to prevent serious morbidity or any complication were calculated. Laboratory testing costs were estimated using Centers for Medicare and Medicaid Services data. RESULTS: Of 111,589 patients studied, 57,590 (51.6%) received preoperative laboratory testing; 26,709 (46.4%) had at least 1 abnormal result. Factors associated with receiving preoperative laboratory testing included increasing age, female sex, non-White race/ethnicity, American Society of Anesthesiologists class 2, diabetes, dyspnea, hypertension, obesity, and steroid use. Mortality did not differ between patients with and without testing. The complication rate was 2.5% among tested patients and 1.7% among patients without tests (P < .01). The numbers needed to test was 599 for serious morbidity and 133 for any complication. An estimated $373 million annually is spent on preoperative laboratory testing in this population. CONCLUSION: Despite American Society of Anesthesiologists guidelines, a majority of American Society of Anesthesiologists class 1 and 2 patients undergo preoperative laboratory testing before elective low-risk outpatient surgery. The differences in the rates of complications between patients with and without testing is low. Preoperative testing should be used more judiciously in this population, which may lead to cost savings.

Diagnostic accuracy of Truenat Tuberculosis and Rifampicin-Resistance assays in Addis Ababa, Ethiopia.

BACKGROUND: Rapid and sensitive Tuberculosis (TB) diagnosis closer to patients is a key global TB control priority. Truenat assays (MTB, MTB Plus, and MTB-RIF Dx) are new TB molecular diagnostic tools for the detection of TB and Rifampicin (RIF)-resistance from sputum samples. The diagnostic accuracy of the assays is needed prior to implementation in clinical use in Ethiopia. This study aimed to determine the sensitivity and specificity of Truenat assays; and aimed to compare the assays to the Xpert MTB/RIF assay. METHODS: A prospective evaluation study was conducted among 200 presumptive TB patients in microscopy centers in Addis Ababa, Ethiopia from May 2019 to December 2020. Culture (Solid and Liquid methods) and phenotypic (liquid method) drug susceptibility testing (DST) were used as a reference standard. RESULTS: Of 200 adult participants, culture confirmed TB cases were 25 (12.5%), and only one isolate was resistant to RIF by phenotypic DST. The sensitivity of Truenat MTB was 88.0% [95% CI 70.1, 95.8], while 91.7 [95% CI 74.2, 97.7] for Truenat MTB Plus at the microscopy centers. The specificity of Truenat MTB was 97.2% [95% CI 93.1, 98.9], while for Truenat MTB Plus was 97.2% [95% CI 93.0, 99.0]. The sensitivity of Truenat MTB was 90.5% while for MTB Plus, 100% compared to the Xpert MTB/RIF assay. CONCLUSION: Truenat assays were found to have high diagnostic accuracy. The assays have the potential to be used as a point of care (POC) TB diagnostic tests.

Assessment of Rapid Diagnostic Tests for Typhoid Diagnosis and Assessment of Febrile Illness Outbreaks in Fiji.

Typhoid is an endemic in Fiji with increases observed since the early 2000s and frequent outbreaks reported. We assessed the diagnostic accuracy of currently available typhoid rapid diagnostic tests (RDTs) (TUBEX, Typhidot Rapid, and Test-It assay) to establish their performance against blood culture in Fiji and to examine their suitability for rapid typhoid outbreak identification. The performance of RDTs was assessed in the public health reference laboratory in Suva, Fiji, according to the manufacturers' instructions. A simulation was used to examine the potential use of RDTs for attribution of a febrile illness outbreak to typhoid. For the diagnostic evaluation, 179 patients were included; 49 had blood culture-confirmed typhoid, 76 had fever as a result of non-typhoid etiologies, and 54 were age-matched community controls. The median (interquartile range) age was 29 (20-46) years. Of the participants, 92 (51.4%) were male and 131 (73.2%) were indigenous Fijians. The sensitivities of the tests were 77.6% for TUBEX, 75.5% for Typhidot Rapid, and 57.1% for Test-It assay. The Test-It assay had the highest specificity of 93.4%, followed by Typhidot Rapid 85.5% and TUBEX 60.5%. Typhidot Rapid had the best performance in the simulation for attribution of a febrile illness outbreak to typhoid. Typhoid RDTs performed suboptimally for individual patient diagnosis due to low sensitivity and variable specificity. We demonstrate that RDTs could be useful in the field for rapid attribution of febrile illness outbreaks to typhoid. Typhidot Rapid had the best combination of sensitivity, specificity, positive and negative predictive values, cost, and ease of use for this purpose.

Diagnostics to support elimination of lymphatic filariasis-Development of two target product profiles.

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools.

Ten Years of Universal Testing: How the Rapid Diagnostic Test Became a Game Changer for Malaria Case Management and Improved Disease Reporting.

In 2010, the World Health Organization changed its guidance on malaria case management, recommending parasitological confirmation of all suspected cases before treatment with an antimalarial. This recommendation was in large part as a result of the availability of quality assured malaria rapid diagnostic tests (RDTs) that made it possible for malaria diagnosis to be performed by laboratory staff in all health facilities irrespective of the facility's place in the tiered health system. Community health workers and other non-laboratory health workers who traditionally did not perform malaria testing due to the technical and logistic demands of smear microscopy were now able to test for malaria. The use of RDTs has led to substantial increases in testing rates, improved quality of case management, as well as more accurate reporting of malaria cases. Although current RDTs have limitations, they remain one of the most important tools in contemporary malaria control. Further improvements to existing products, such as increased sensitivity for non-falciparum tests, diversification of Plasmodium falciparum antigen targets, along with strengthened health system support for current RDTs will further enhance their utility in malaria control and prevention.

Evaluating the diagnostic test accuracy of molecular xenomonitoring methods for characterising the community burden of Onchocerciasis.

BACKGROUND: Molecular xenomonitoring (MX), the detection of parasite nucleic acid in the vector population, is recommended for onchocerciasis surveillance in elimination settings. However, the sensitivity of MX for detecting onchocerciasis-positive communities has not previously been evaluated. MX may have additional applications for control programmes but its utility is restricted by a limited understanding of the relationship between MX results and human prevalence. METHODS: We conducted a systematic review of studies reporting the prevalence of Onchocerca volvulus DNA in wild-caught Simulium spp. flies (MX rate) and corresponding prevalence of microfilaria (mf) in humans. We evaluated the sensitivity of MX for detecting onchocerciasis-positive communities and describe the characteristics of studies with reduced sensitivity. We conducted a linear regression to evaluate the relationship between mf prevalence and MX rate. RESULTS: We identified 15 relevant studies, with 13 studies comprising 34 study communities included in the quantitative analyses. Most communities were at advanced stages towards elimination and had no or extremely low human prevalence. MX detected positive flies in every study area with >1% mf prevalence, with the exception of one study conducted in the Venezuelan Amazonian focus. We identified a significant relationship between the two measurements, with mf prevalence accounting for half of the variation in MX rate (R2 0.50, p<0.001). CONCLUSION: MX is sensitive to communities with ongoing onchocerciasis transmission. It has potential to predict human mf prevalence, but further data is required to understand this relationship, particularly from MX surveys conducted earlier in control programmes before transmission has been interrupted.

Validation of grading of non-invasive urothelial carcinoma by digital pathology for routine diagnosis.

BACKGROUND: Pathological grading of non-invasive urothelial carcinoma has a direct impact upon management. This study evaluates the reproducibility of grading these tumours on glass slides and digital pathology. METHODS: Forty eight non-invasive urothelial bladder carcinomas were graded by three uropathologists on glass and on a digital platform using the 1973 WHO and 2004 ISUP/WHO systems. RESULTS: Consensus grades for glass and digital grading gave Cohen's kappa scores of 0.78 (2004) and 0.82 (1973). Of 142 decisions made on the key therapeutic borderline of low grade versus high grade urothelial carcinoma (2004) by the three pathologists, 85% were in agreement. For the 1973 grading system, agreement overall was 90%. CONCLUSIONS: Agreement on grading on glass slide and digital screen assessment is similar or in some cases improved, suggesting at least non-inferiority of DP for grading of non-invasive urothelial carcinoma.

Clinical utility of Abbott Alinity hq extended red blood cell parameters in differentiating ß-thalassemia trait and iron deficiency anemia.

INTRODUCTION: The objective of the study was to evaluate the performance of the Abbott Alinity hq advanced multi angle polarized scatter separation (MAPSSTM )-based optical RBC technology, for the differentiation between iron deficiency anemia (IDA) and ß-thalassemia carrier status. METHODS: Four hundred and sixty-four samples were analyzed. 228 were healthy controls, 30 were ß-thalassemia carriers, and 40 were IDA. Receiver operating characteristics analysis evaluated the performance of red cell parameters and mathematical formulas. RESULTS: RBC concentration was the most efficient discriminant (area under the curve; AUC of 0.963, Youden Index of 0.88) followed by red blood cell distribution width in size distribution (AUC of 0.960 and YI of 0.86), and red blood cell distribution width coefficient of variation (AUC of 0.924, and YI of 0.74). The absolute reticulocyte concentration showed good diagnostic efficiency, with AUC of 0.808. Hemoglobin distribution width, the %CV of directly measured cellular hemoglobin concentration, and CHCr, the average hemoglobin concentration of reticulocytes have emerged as novel discriminating parameters, with AUC of 0.749 and 0.785, respectively. The England and Fraser index was the best discriminating mathematical formula based on Youden Index of 0.91. The Ricerca, red blood cell distribution width index, Green and King, and Mentzner Index formulas also showed strong discriminative power. The Shine and Lal index, together with the recent mathematical formula M/H, (ratio of percent microcytic and hypochromic red blood cells) demonstrated moderate performance with AUC of 0.796 and 0.740, respectively. CONCLUSION: Extended red cell analysis delivered by the advanced optical technology on the Alinity hq hematology analyzer has efficient diagnostic utility in the initial discrimination of the two most common microcytic anemias: IDA and ß-thalassemia trait.