Contextual factors and G6PD diagnostic testing: a scoping review and evidence and gap map.

BACKGROUND: Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is an important consideration regarding treatment for malaria. G6PD deficiency may lead to haemolytic anaemia during malaria treatment and, therefore, determining G6PD deficiency in malaria treatment strategies is extremely important. METHODS: This report presents the results of a scoping review and evidence and gap map for consideration by the Guideline Development Group for G6PD near patient tests to support radical cure of Plasmodium vivax. This scoping review has investigated common diagnostic tests for G6PD deficiency and important contextual and additional factors for decision-making. These factors include six of the considerations recommended by the World Health Organization (WHO) handbook for guideline development as important to determining the direction and strength of a recommendation, and included 'acceptability', 'feasibility,' 'equity,' 'valuation of outcomes,' 'gender' and 'human rights'. The aim of this scoping review is to inform the direction of future systematic reviews and evidence syntheses, which can then better inform the development of WHO recommendations regarding the use of G6PD deficiency testing as part of malaria treatment strategies. RESULTS: A comprehensive search was performed, including published, peer-reviewed literature for any article, of any study design and methodology that investigated G6PD diagnostic tests and the factors of 'acceptability', 'feasibility,' 'equity,' 'valuation of outcomes,' 'gender' and 'human rights'. There were 1152 studies identified from the search, of which 14 were determined to be eligible for inclusion into this review. The studies contained data from over 21 unique countries that had considered G6PD diagnostic testing as part of a malaria treatment strategy. The relationship between contextual and additional factors, diagnostic tests for G6PD deficiency and study methodology is presented in an overall evidence and gap, which showed that majority of the evidence was for the contextual factors for diagnostic tests, and the 'Standard G6PD (SD Biosensor)' test. CONCLUSIONS: This scoping review has produced a dynamic evidence and gap map that is reactive to emerging evidence within the field of G6PD diagnostic testing. The evidence and gap map has provided a comprehensive depiction of all the available literature that address the contextual and additional factors important for decision-making, regarding specific G6PD diagnostic tests. The majority of data available investigating the contextual factors of interest relates to quantitative G6PD diagnostic tests. While a formal qualitative synthesis of this data as part of a systematic review is possible, the data may be too heterogenous for this to be appropriate. These results can now be used to inform future direction of WHO Guideline Development Groups for G6PD near patient tests to support radical cure of P. vivax malaria.

Malaria community case management usage and quality of malaria care in a moderate Plasmodium falciparum burden region of Chadiza District, Zambia.

BACKGROUND: Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. METHODS: Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. RESULTS: Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5-14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p < 0.001). Reported malaria treatment was similar by provider, and 85.9% of those with a reported positive malaria test reported getting malaria treatment; 66.9% of the subset with prior fever and a positive survey RDT reported malaria treatment. Age under 5 years, monthly or more frequent CHW home visits, and greater wealth were associated with increased odds of receiving healthcare. CONCLUSIONS: Chadiza District had high CHW coverage among individuals who sought care for fever. Further interventions are needed to increase the proportion of febrile individuals who receive healthcare. Strategies to decrease barriers to healthcare, such as CHW home visits, particularly targeting those of all ages in lower wealth strata, could maximize the benefits of CHW programmes.

Visualizing and diagnosing spillover within randomized concurrent controlled trials through the application of diagnostic test assessment methods.

BACKGROUND: Spillover of effect, whether positive or negative, from intervention to control group patients invalidates the Stable Unit Treatment Variable Assumption (SUTVA). SUTVA is critical to valid causal inference from randomized concurrent controlled trials (RCCT). Spillover of infection prevention is an important population level effect mediating herd immunity. This herd effect, being additional to any individual level effect, is subsumed within the overall effect size (ES) estimate derived by contrast-based techniques from RCCT's. This herd effect would manifest only as increased dispersion among the control group infection incidence rates above background. METHODS AND RESULTS: The objective here is to explore aspects of spillover and how this might be visualized and diagnosed. I use, for illustration, data from 190 RCCT's abstracted in 13 Cochrane reviews of various antimicrobial versus non-antimicrobial based interventions to prevent pneumonia in ICU patients. Spillover has long been postulated in this context. Arm-based techniques enable three approaches to identify increased dispersion, not available from contrast-based techniques, which enable the diagnosis of spillover within antimicrobial versus non-antimicrobial based infection prevention RCCT's. These three approaches are benchmarking the pneumonia incidence rates versus a clinically relevant range, comparing the dispersion in pneumonia incidence among the control versus the intervention groups and thirdly, visualizing the incidence dispersion within summary receiver operator characteristic (SROC) plots. By these criteria there is harmful spillover effects to concurrent control group patients. CONCLUSIONS: Arm-based versus contrast-based techniques lead to contrary inferences from the aggregated RCCT's of antimicrobial based interventions despite similar summary ES estimates. Moreover, the inferred relationship between underlying control group risk and ES is 'flipped'.

Reducing Erythrocyte Sedimentation Rate Ordering: De-implementation and Diagnostic Stewardship.

OBJECTIVES: The Choosing Wisely campaign recommends against the routine use of erythrocyte sedimentation rate (ESR) for the assessment of acute undiagnosed inflammation or infection. We examined ESR and C-reactive protein (CRP) ordering practices at a large, freestanding children's hospital. We found that 80% of ESR orders were placed concurrently with a CRP order. We aimed to reduce the ESR testing rate by 20% within 6 months in both inpatient and emergency department (ED) settings. METHODS: Applying Lean process improvement principles, we interviewed stakeholders from multiple subspecialties and engaged the institutional laboratory stewardship committee to identify the root causes of ESR ordering and design interventions. We conducted provider education (November 2020) and employed clinical decision support through an order panel in the electronic health record (April 2021). The outcome measures were monthly ESR testing rate per 1000 patient days (inpatient) and per 1000 ED visits, analyzed using statistical process control charts. CRP testing rate was a balancing measure. RESULTS: After intervention implementation, the ESR testing rate decreased from 11.4 to 8.9 tests per 1000 inpatient patient days (22% decrease) and from 49.4 to 29.5 tests per 1000 ED visits (40% decrease). This change has been sustained for >1 year postintervention. Interventions were effective even during the coronavirus disease 2019 pandemic when there was a rise in baseline ED ESR ordering rate. CRP testing rates did not increase after the interventions. CONCLUSIONS: Education and clinical decision support were effective in reducing the ESR ordering rate in both inpatient and ED settings.

Examining the Association Between the COVID-19 Pandemic and the Rate of Diagnostic Tests for Breast, Cervical, and Colorectal Cancer in Manitoba, Canada.

Background: Strategies to minimize the impact of the COVID-19 pandemic led to a reduction in diagnostic testing. It is important to assess the magnitude and duration of this impact to plan ongoing care and avoid long-lasting impacts of the pandemic. Objective: We examined the association between the COVID-19 pandemic and the rate of diagnostic tests for breast, cervical, and colorectal cancer in Manitoba, Canada. Design and Participants: A population-based, cross-sectional study design with an interrupted time series analysis was used that included diagnostic tests from January 1, 2015 until August 31, 2022. Setting: Manitoba, Canada. Main Outcomes: Outcomes included mammogram, breast ultrasound, colposcopy, and colonoscopy rates per 100,000. Cumulative and percent cumulative differences between the fitted and counterfactual number of tests were estimated. Mean, median, and 90th percentile number of days from referral to colonoscopy date by referral type (elective, semiurgent, urgent) were determined. Results: In April 2020, following the declaration of the COVID-19 public health emergency, bilateral mammograms decreased by 77%, unilateral mammograms by 70%, breast ultrasounds by 53%, colposcopies by 63%, and colonoscopies by 75%. In Winnipeg (the largest urban center in the province), elective and semiurgent colonoscopies decreased by 76% and 39%, respectively. There was no decrease in urgent colonoscopies. As of August 2022, there were an estimated 7270 (10.7%) fewer bilateral mammograms, 2722 (14.8%) fewer breast ultrasounds, 836 (3.3%) fewer colposcopies, and 11 600 (13.8%) fewer colonoscopies than expected in the absence of COVID-19. As of December 2022, in Winnipeg, there were an estimated 6030 (23.9%) fewer elective colonoscopies, 313 (2.6%) fewer semiurgent colonoscopies, and 438 (27.3%) more urgent colonoscopies. Conclusions: In Manitoba, the COVID-19 pandemic was associated with sizable decreases in diagnostic tests for breast, colorectal, and cervical cancer. Two and a half years later, there remained large cumulative deficits in bilateral mammograms, breast ultrasounds, and colonoscopies.

Proactive home-based malaria management in rural communities of Bassar Health District in northern Togo from 2014 to 2017: PECADOM + , a pilot experiment.

BACKGROUND: Togo's National Malaria Control Programme has initiated an active home-based malaria management model for all age groups in rural areas of Bassar Health District. This report describes the model, reports its main results, and determines the factors associated with positive rapid diagnostic test results. METHODS: From 2014 to 2017, in three peripheral care units of Bassar Health District (Binaparba, Nangbani, and Baghan), community health workers visited residents' homes weekly to identify patients with malaria symptoms, perform rapid diagnostic tests in symptomatic patients, and give medication to positive cases. Univariate and multivariate logistic regression models were used to determine the factors associated with positive tests. RESULTS: The study covered 11,337 people (817 in 2014, 1804 in 2015, 2638 in 2016, and 6078 in 2017). The overall mean age was 18 years (95% CI 5-29; min-max: 0-112 years). The median age was 10 years (SD: 16.9). The proportions of people tested positive were 75.3% in Binaparba, 77.4% in Nangbani, and 56.6% in Baghan. The 5-10 age group was the most affected category (24.2% positive tests). Positive tests were more frequent during the rainy than during the dry season (62 vs. 38%) and the probability of positive test was 1.76 times higher during the rainy than during the dry season (adjusted OR = 1.74; 95% CI 1.60-1.90). A fever (37.5 °C or higher) increased significantly the probability of positive test (adjusted OR = 2.19; 95% CI 1.89-2.54). The risk of positive test was 1.89 times higher in passive than in active malaria detection (adjusted OR = 1.89; 95% CI 1.73-2.0). CONCLUSIONS: This novel experimental community and home-based malaria management in Togo suggested that active detection of malaria cases is feasible within 24 h, which allows rapid treatments before progression to often-fatal complications. This PECADOM + program will help Togo's National Malaria Control Programme reduce malaria morbidity and mortality in remote and hard-to-reach communities.

Screening for hepatitis C virus at the time of mammography using rapid diagnostic tests in women aged between 50 and 74 years (Mamm'OC NCT05067374).

Chronic hepatitis C Virus (HCV) infection presents a global health challenge, with significant morbidity and mortality worldwide. Despite remarkable progress in treatment options, achieving elimination targets by 2030, as set by the World Health Organization, remains elusive. Our study aimed to address this gap by integrating HCV screening into a national breast cancer screening program. Between March 2022 and March 2023, a prospective cross-sectional multicenter study was conducted in four radiology centers in Montpellier, France. We proposed HCV screening to consecutive women undergoing mammography, targeting 1,500 participants aged 50-74 years. A rapid diagnostic test (RDT) for HCV antibodies (HCV Ab) was performed on capillary whole blood, with positive cases undergoing serological and RNA confirmation. Participants also completed a questionnaire on demographic data and risk factors. Acceptance rates, HCV prevalence, and linkage to care were assessed. The acceptance rate for this integrated screening approach was 82.4%. Notably, the seroprevalence of HCV was found to be 0.65%. Linkage to care was prompt, and the cascade of care demonstrated successful treatment outcomes. Importantly, the majority of detected infections were successfully resolved. These findings underscore the feasibility and acceptability of integrating HCV screening with breast cancer screening programs providing updated prevalence data and valuable insights for refining future screening strategies.

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.

Establishing the Reportable Interval for Routine Clinical Laboratory Tests: A Data-Driven Strategy Leveraging Retrospective Electronic Medical Record Data.

BACKGROUND: This paper presents a data-driven strategy for establishing the reportable interval in clinical laboratory testing. The reportable interval defines the range of laboratory result values beyond which reporting should be withheld. The lack of clear guidelines and methodology for determining the reportable interval has led to potential errors in reporting and patient risk. METHODS: To address this gap, the study developed an integrated strategy that combines statistical analysis, expert review, and hypothetical outlier calculations. A large data set from an accredited clinical laboratory was utilized, analyzing over 124 million laboratory test records from 916 distinct tests. The Dixon test was applied to identify outliers and establish the highest and lowest non-outlier result values for each test, which were validated by clinical pathology experts. The methodology also included matching the reportable intervals with relevant Logical Observation Identifiers Names and Codes (LOINC) and Unified Code for Units of Measure (UCUM)-valid units for broader applicability. RESULTS: Upon establishing the reportable interval for 135 routine laboratory tests (493 LOINC codes), we applied these to a primary care laboratory data set of 23 million records, demonstrating their efficacy with over 1% of result records identified as implausible. CONCLUSIONS: We developed and tested a data-driven strategy for establishing reportable intervals utilizing large electronic medical record (EMR) data sets. Implementing the established interval in clinical laboratory settings can improve autoverification systems, enhance data reliability, and reduce errors in patient care. Ongoing refinement and reporting of cases exceeding the reportable limits will contribute to continuous improvement in laboratory result management and patient safety.

Changing patterns of routine laboratory testing over time at children's hospitals.

BACKGROUND: Research into low-value routine testing at children's hospitals has not consistently evaluated changing patterns of testing over time. OBJECTIVES: To identify changes in routine laboratory testing rates at children's hospitals over ten years and the association with patient outcomes. DESIGN, SETTINGS, AND PARTICIPANTS: We performed a multi-center, retrospective cohort study of children aged 0-18 hospitalized with common, lower-severity diagnoses at 28 children's hospitals in the Pediatric Health Information Systems database. MAIN OUTCOMES AND MEASURES: We calculated average annual testing rates for complete blood counts, electrolytes, and inflammatory markers between 2010 and 2019 for each hospital. A >2% average testing rate change per year was defined as clinically meaningful and used to separate hospitals into groups: increasing, decreasing, and unchanged testing rates. Groups were compared for differences in length of stay, cost, and 30-day readmission or ED revisit, adjusted for demographics and case mix index. RESULTS: Our study included 576,572 encounters for common, low-severity diagnoses. Individual hospital testing rates in each year of the study varied from 0.3 to 1.4 tests per patient day. The average yearly change in hospital-specific testing rates ranged from -6% to +7%. Four hospitals remained in the lowest quartile of testing and two in the highest quartile throughout all 10 years of the study. We grouped hospitals with increasing (8), decreasing (n = 5), and unchanged (n = 15) testing rates. No difference was found across subgroups in costs, length of stay, 30-day ED revisit, or readmission rates. Comparing resource utilization trends over time provides important insights into achievable rates of testing reduction.

A qualitative study on determinants of the use of malaria rapid diagnostic test and anti-malarial drug prescription practices by primary healthcare workers in Ebonyi state, Nigeria.

BACKGROUND: The increased availability and use of malaria rapid diagnostic test (RDT) by primary healthcare (PHC) workers has made universal diagnostic testing before malaria treatment more feasible. However, to meaningfully resolve the problem of over-treatment with artemisinin-based combination therapy and the heightened risk of selection pressure and drug resistance, there should be appropriate response (non-prescription of anti-malarial drugs) following a negative RDT result by PHC workers. This study explored the determinants of the use of RDT and anti-malarial drug prescription practices by PHC workers in Ebonyi state, Nigeria. METHODS: Between March 2 and 10, 2020, three focus group discussions were conducted in English with 23 purposively-selected consenting PHC workers involved in the diagnosis and treatment of malaria. Data was analysed thematically as informed by the method by Braun and Clarke. RESULTS: The determinants of the use of RDT for malaria diagnosis were systemic (RDT availability and patient load), provider related (confidence in RDT and the desire to make correct diagnosis, PHC worker's knowledge and training, and fear to prick a patient), client related (fear of needle prick and refusal to receive RDT, and self-diagnosis of malaria, based on symptoms, and insistence on not receiving RDT), and RDT-related (the ease of conducting and interpreting RDT). The determinants of anti-malarial drug prescription practices were systemic (drug availability and cost) and drug related (effectiveness and side-effects of the drugs). The determinants of the prescription of anti-malarial drugs following negative RDT were provider related (the desire to make more money and limited confidence in RDT) and clients' demand while unnecessary co-prescription of antibiotics with anti-malarial drugs following positive RDT was determined by the desire to make more money. CONCLUSIONS: This evidence highlights many systemic, provider, client, and RDT/drug related determinants of PHC workers' use of RDT and anti-malarial drug prescription practices that should provide tailored guidance for relevant health policy actions in Ebonyi state, Nigeria, and similar settings.

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.

Diagnostic test accuracy in longitudinal study settings: theoretical approaches with use cases from clinical practice.

OBJECTIVES: In this study, we evaluate how to estimate diagnostic test accuracy (DTA) correctly in the presence of longitudinal patient data (ie, repeated test applications per patient). STUDY DESIGN AND SETTING: We used a nonparametric approach to estimate the sensitivity and specificity of three tests for different target conditions with varying characteristics (ie, episode length and disease-free intervals between episodes): 1) systemic inflammatory response syndrome (n = 36), 2) depression (n = 33), and 3) epilepsy (n = 30). DTA was estimated on the levels 'time', 'block', and 'patient-time' for each diagnosis, representing different research questions. The estimation was conducted for the time units per minute, per hour, and per day. RESULTS: A comparison of DTA per and across use cases showed variations in the estimates, which resulted from the used level, the time unit, the resulting number of observations per patient, and the diagnosis-specific characteristics. Intra- and inter-use-case comparisons showed that the time-level had the highest DTA, particularly the larger the time unit, and that the patient-time-level approximated 50% sensitivity and specificity. CONCLUSION: Researchers need to predefine their choices (ie, estimation levels and time units) based on their individual research aims, estimands, and diagnosis-specific characteristics of the target outcomes to make sure that unbiased and clinically relevant measures are communicated. In cases of uncertainty, researchers could report the DTA of the test using more than one estimation level and/or time unit.

Interval estimation in three-class receiver operating characteristic analysis: A fairly general approach based on the empirical likelihood.

The empirical likelihood is a powerful nonparametric tool, that emulates its parametric counterpart-the parametric likelihood-preserving many of its large-sample properties. This article tackles the problem of assessing the discriminatory power of three-class diagnostic tests from an empirical likelihood perspective. In particular, we concentrate on interval estimation in a three-class receiver operating characteristic analysis, where a variety of inferential tasks could be of interest. We present novel theoretical results and tailored techniques studied to efficiently solve some of such tasks. Extensive simulation experiments are provided in a supporting role, with our novel proposals compared to existing competitors, when possible. It emerges that our new proposals are extremely flexible, being able to compete with contestants and appearing suited to accommodating several distributions, such, for example, mixtures, for target populations. We illustrate the application of the novel proposals with a real data example. The article ends with a discussion and a presentation of some directions for future research.

Heterogeneity in Systematic Reviews of Medical Imaging Diagnostic Test Accuracy Studies: A Systematic Review.

Importance: Systematic reviews of medical imaging diagnostic test accuracy (DTA) studies are affected by between-study heterogeneity due to a range of factors. Failure to appropriately assess the extent and causes of heterogeneity compromises the interpretability of systematic review findings. Objective: To assess how heterogeneity has been examined in medical imaging DTA studies. Evidence Review: The PubMed database was searched for systematic reviews of medical imaging DTA studies that performed a meta-analysis. The search was limited to the 40 journals with highest impact factor in the radiology, nuclear medicine, and medical imaging category in the InCites Journal Citation Reports of 2021 to reach a sample size of 200 to 300 included studies. Descriptive analysis was performed to characterize the imaging modality, target condition, type of meta-analysis model used, strategies for evaluating heterogeneity, and sources of heterogeneity identified. Multivariable logistic regression was performed to assess whether any factors were associated with at least 1 source of heterogeneity being identified in the included meta-analyses. Methodological quality evaluation was not performed. Data analysis occurred from October to December 2022. Findings: A total of 242 meta-analyses involving a median (range) of 987 (119-441 510) patients across a diverse range of disease categories and imaging modalities were included. The extent of heterogeneity was adequately described (ie, whether it was absent, low, moderate, or high) in 220 studies (91%) and was most commonly assessed using the I2 statistic (185 studies [76%]) and forest plots (181 studies [75%]). Heterogeneity was rated as moderate to high in 191 studies (79%). Of all included meta-analyses, 122 (50%) performed subgroup analysis and 87 (36%) performed meta-regression. Of the 242 studies assessed, 189 (78%) included 10 or more primary studies. Of these 189 studies, 60 (32%) did not perform meta-regression or subgroup analysis. Reasons for being unable to investigate sources of heterogeneity included inadequate reporting of primary study characteristics and a low number of included primary studies. Use of meta-regression was associated with identification of at least 1 source of variability (odds ratio, 1.90; 95% CI, 1.11-3.23; P = .02). Conclusions and Relevance: In this systematic review of assessment of heterogeneity in medical imaging DTA meta-analyses, most meta-analyses were impacted by a moderate to high level of heterogeneity, presenting interpretive challenges. These findings suggest that, despite the development and availability of more rigorous statistical models, heterogeneity appeared to be incomplete, inconsistently evaluated, or methodologically questionable in many cases, which lessened the interpretability of the analyses performed; comprehensive heterogeneity assessment should be addressed at the author level by improving personal familiarity with appropriate statistical methodology for assessing heterogeneity and involving biostatisticians and epidemiologists in study design, as well as at the editorial level, by mandating adherence to methodologic standards in primary DTA studies and DTA meta-analyses.

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.

Reducing unnecessary routine laboratory testing for noncritically ill patients with COVID-19.

BACKGROUND: Reducing unnecessary routine laboratory testing is a Choosing Wisely® recommendation, and new areas of overuse were noted during the COVID-19 pandemic. OBJECTIVE: To reduce unnecessary repetitive routine laboratory testing for patients with COVID-19 during the pandemic across a large safety net health system. DESIGNS, SETTINGS AND PARTICIPANTS: This quality improvement initiative was initiated by the System High-Value Care Council at New York City Health + Hospitals (H + H), the largest public healthcare system in the United States consisting of 11 acute care hospitals. INTERVENTION: four overused laboratory tests in noncritically ill hospitalized patients with COVID-19 were identified: C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and procalcitonin. A two-pronged electronic health record intervention was implemented consisting of (1) nonintrusive, informational nudge statements placed on selected order sets, and (2) a forcing function of one consecutive day limit on ordering. MAIN OUTCOME AND MEASURES: The average of excess tests per encounter days (ETPED) for each of four target laboratory testing only in patients with COVID-19. OBJECTIVE: Interdisciplinary System High-Value Care Council identified four overused laboratory tests (inflammatory markers) in noncritically ill hospitalized patients with COVID-19: C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and procalcitonin. Within an 11-hospital safety net health system, a two-pronged electronic health record intervention was implemented consisting of (1) nonintrusive, informational nudge statements placed on selected order sets, and (2) a forcing function of one consecutive day limit on ordering. The preintervention period (March 16, 2020 to January 24, 2021) was compared to the postintervention period (January 25, 2021 to March 22, 2022). RESULTS: Time series linear regression showed decreases in CRP (-17.9%, p < .05), ferritin (-37.6%, p < .001), and LDH (-30.1%, p < .001). Slope differences were significant (CRP, ferritin, and LDH p < 0.001; procalcitonin p < 0.05). Decreases were observed across weekly averages: CRP (-19%, p < .01), ferritin (-37.9%, p < .001), LDH (-28.7%, p < .001), and procalcitonin (-18.4%, p < .05). CONCLUSION: This intervention was associated with reduced routine inflammatory marker testing in non-intensive care unit COVID-19 hospitalized patients across 11 hospitals. Variation was high among individual hospitals.

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.

Evaluating performance of multiplex real time PCR for the diagnosis of malaria at elimination targeted low transmission settings of Ethiopia.

BACKGROUND: Malaria incidence has declined in Ethiopia in the past 10 years. Current malaria diagnostic tests, including light microscopy and rapid antigen-detecting diagnostic tests (RDTs) cannot reliably detect low-density infections. Studies have shown that nucleic acid amplification tests are highly sensitive and specific in detecting malaria infection. This study took place with the aim of evaluating the performance of multiplex real time PCR for the diagnosis of malaria using patient samples collected from health facilities located at malaria elimination targeted low transmission settings in Ethiopia. METHODS: A health facility-based, cross-sectional survey was conducted in selected malaria sentinel sites. Malaria-suspected febrile outpatients referred to laboratory for malaria testing between December 2019 and March 2020 was enrolled into this study. Sociodemographic information and capillary blood samples were collected from the study participants and tested at spot with RDTs. Additionally, five circles of dry blood spot (DBS) samples on Whatman filter paper and thick and thin smear were prepared for molecular testing and microscopic examination, respectively. Multiplex real time PCR assay was performed at Ethiopian Public Health Institute (EPHI) malaria laboratory. The performance of multiplex real time PCR assay, microscopy and RDT for the diagnosis of malaria was compared and evaluated against each other. RESULTS: Out of 271 blood samples, multiplex real time PCR identified 69 malaria cases as Plasmodium falciparum infection, 16 as Plasmodium vivax and 3 as mixed infections. Of the total samples, light microscopy detected 33 as P. falciparum, 18 as P. vivax, and RDT detected 43 as P. falciparum, 17 as P. vivax, and one mixed infection. Using light microscopy as reference test, the sensitivity and specificity of multiplex real time PCR were 100% (95% CI (93-100)) and 83.2% (95% CI (77.6-87.9)), respectively. Using multiplex real time PCR as a reference, light microscopy and RDT had sensitivity of 58% (95% CI 46.9-68.4) and 67% (95% CI 56.2-76.7); and 100% (95% CI 98-100) and 98.9% (95% CI 96-99.9), respectively. Substantial level of agreement was reported between microscopy and multiplex real time PCR results with kappa value of 0.65. CONCLUSIONS: Multiplex real-time PCR had an advanced performance in parasite detection and species identification on febrile patients' samples than did microscopy and RDT in low malaria transmission settings. It is highly sensitive malaria diagnostic method that can be used in malaria elimination programme, particularly for community based epidemiological samples. Although microscopy and RDT had reduced performance when compared to multiplex real time PCR, still had an acceptable performance in diagnosis of malaria cases on patient samples at clinical facilities.

Price, quality, and market dynamics of malaria rapid diagnostic tests: analysis of Global Fund 2009-2018 data.

BACKGROUND: Rapid diagnostic tests (RDTs) for malaria are a vital part of global malaria control. Over the past decade, RDT prices have declined, and quality has improved. However, the relationship between price and product quality and their larger implications on the market have yet to be characterized. This analysis used purchase data from the Global Fund together with product quality data from the World Health Organization (WHO) and Foundation for Innovative New Diagnostics (FIND) Malaria RDT Product Testing Programme to understand three unanswered questions: (1) Has the market share by quality of RDTs in the Global Fund's procurement orders changed over time? (2) What is the relationship between unit price and RDT quality? (3) Has the market for RDTs financed by the Global Fund become more concentrated over time? METHODS: Data from 10,075 procurement transactions in the Global Fund's database, which includes year, product, volume, and price, was merged with product quality data from all eight rounds of the WHO-FIND programme, which evaluated 227 unique RDT products. To describe trends in market share by quality level of RDT, descriptive statistics were used to analyse trends in market share from 2009 to 2018. A generalized linear regression model was then applied to characterize the relationship between price and panel detection score (PDS), adjusting for order volume, year purchased, product type, and manufacturer. Third, a Herfindahl-Hirschman Index (HHI) score was calculated to characterize the degree of market concentration. RESULTS: Lower-quality RDTs have lost market share between 2009 and 2018, as have the highest-quality RDTs. No statistically significant relationship between price per test and PDS was found when adjusting for order volume, product type, and year of purchase. The HHI was 3,570, indicating a highly concentrated market. CONCLUSIONS: Advancements in RDT affordability, quality, and access over the past decade risk stagnation if health of the RDT market as a whole is neglected. These results suggest that from 2009 to 2018, this market was highly concentrated and that quality was not a distinguishing feature between RDTs. This information adds to previous reports noting concerns about the long-term sustainability of this market. Further research is needed to understand the causes and implications of these trends.