US Laboratory Research Articles

Protozoan intestinal invasions in military personnel of the Northern region of Ukraine

Objective — to study the prevalence and spectrum of intestinal parasitic infestations (IPI) agents in groups of military personnel of the Northern region of Ukraine, which differed according to the criteria of having symptoms of gastrointestinal disorders and passing the serving in a combat zone. Materials and methods. From February to November 2023, the study covered 302 servicemen during inpatient medical care at the Military Medical Clinical Center of the Northern Region of Ukraine. Detection and identification of intestinal parasites in samples of feces (SF) was carried out by classical methods of microscopy using the enrichment procedure (formalin‑ethyl acetate sedimentation) and the preparation (from each enriched sediment) of four smears: two thick wet with 50% aqueous solution of glycerol and D’ Anthony iodine solution; two thin, fixed, permanently stained with Whitley’s modified trichrome (mWT) or Heidenhain’s iron hematoxylin (HIH) and the modified Ziehl‑Neelsen acid method (mZN). Smear microscopy results were evaluated according to the criteria of the US Clinical and Laboratory Standards Institute. Results. It was established that the level of prevalence of IPI among the examined servicemen reached 10.6% with variation in the value of this indicator in different groups of soldiers from 2.2% to 12.6%. A specific share of protozoan monoinvasions in soldiers reached 65.6%, and mixed invasions (with two parasites at the same time) — 34.4%. Soldiers with symptoms of gastrointestinal diseases had significantly higher rates of IPI than did asymptomatic. In addition, the infestation rates among soldiers were higher in the cold season (October‑February) with a seasonality index of 1.9. All cases of IPI in servicemen (n=32) were caused by protozoan parasites (n=39), in the etiological spectrum of which the vast majority (84.6%) were pathogenic species (Blastocystis sp., Dientamoeba fragilis, Giardia lamblia), and a smaller proportion (15.4%) were commensal species (Chilomastix mesnili, Iodamoeba butschliі). Among pathogenic protozoa (n=33), Blastocystis sp. (51.5%) and D. fragilis had the highest proportion (42.4%), G. lamblia (6.1%) had significantly less one. Conclusions. Optimizing the management tactics of military medicine to reduce the negative impact of IPI on the health and combat capacity of servicemen requires knowledge about the prevalence and spectrum of pathogens of invasions among specific groups of soldiers. A necessary condition for increasing the efficiency of microscopic detection/identification of protozoan parasites (primarily D. fragilis) in the SF is the production of permanently stained (mWT or HIH) smears. Microscopic examination of such smears at high resolution (100ґ objective, oil immersion) provides an increased incidence of detection/identification of Blastocystis sp. by 47.1% and D. fragilis by 100%.

Machine learning progressive CKD risk prediction model is associated with CKD-mineral bone disorder

BackgroundRecently, we developed the machine learning (ML)-based Progressive CKD Risk Classifier (PCRC), which accurately predicts CKD progression within 5 years. While its performance is robust, it is unknown whether PCRC categorization is associated with CKD-mineral bone disorder (CKD-MBD), a critical, yet under-recognized, downstream consequence. Therefore, we aimed to 1) survey real-world testing utilization data for CKD-MBD and 2) evaluate ML-based PCRC categorization with CKD-MBD. MethodsThe cohort study utilized deidentified data from a US laboratory outpatient network, composed of 330,238 outpatients, over 5 years. The main outcomes were: 1) Laboratory testing utilization of eGFR, urine albumin creatinine ratio (UACR), parathyroid hormone (PTH), calcium, phosphate; and 2) PCRC categorization and biochemical abnormalities associated with CKD-MBD over 5 years. ResultsWe identified significant under-utilization of laboratory testing for UACR, phosphate and PTH, which ranged from −40 % to −100 % against the minimum standard-of-care. At five years, the CKD progression group, as predicted by the PCRC, was associated with 15.5 % increase in phosphate (P value <<0.01) and 94.9 % increase in PTH (P value <<0.01), consistent with CKD-MBD. ConclusionsWe identified significant under-utilization of laboratory testing for CKD-MBD. Moreover, we demonstrated that CKD progression, as predicted by the PCRC, is associated with CKD-MBD, several years in advance of disease. To our knowledge, this investigation is the first to examine the role of predictive analytics for CKD progression on mineral bone disorder. While further studies are required, these findings have the potential to advance AI/ML-based risk stratification and treatment of CKD and CKD-MBD.

B-096 Are we truly Choosing Wisely? An Assessment of non-specific testing, time to diagnosis and costs related to the diagnosis of Rheumatoid Arthritis

Abstract Background Treatment of Rheumatoid Arthritis (RA) early in the disease course can significantly impact patient quality of life by preventing the development of joint erosion and slowing down disease progression. Timely diagnosis is a critical aspect of early treatment. Most patients initially present within a primary care (PC) setting where a variety of non-specific tests/test algorithms are used. We reviewed 8 years’ worth of RA real-world laboratory data to assess time to diagnosis (TTD) between different tests/test combinations. Methods Data extraction spanning 2014–2021 was pulled from a US laboratory, using Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide (CCP) positivity as the primary inclusion criteria. Additionally, sex, age, ordering physician specialty, ICD-10 codes, test order date and test codes (ESR, CRP, ANA screen, RF isotypes) were pulled longitudinally. Results This data set includes 3024 patients with RA (RA ICD code). Of these, 45% were first suspected and evaluated within PC. TTD between patients initially tested with only CRP or ESR had a median TTD of 920 days and those tested with ANA only had a median TTD of 685 days. Those tested with RF + CCP or RF + CCP + ANA had a median TTD of 367 days and 290 days, respectively. Conclusion Our data set highlights the impact of test methods on TTD of patients with RA, with tests combinations more specific for RA significantly decreasing TTD. Further analysis will be conducted to determine the downstream implications resulting between these diagnostic delays. Standardizing and implementing initial testing algorithms could potentially decrease RA TTD, and directly impact burden of care.

Burkholderia pseudomallei Laboratory Exposure, Arizona, USA

We describe an incidental Burkholderia pseudomallei laboratory exposure in Arizona, USA. Because melioidosis cases are increasing in the United States and B. pseudomallei reservoirs have been discovered in the Gulf Coast Region, US laboratory staff could be at increased risk for B. pseudomallei exposure.

The 2019 medical genetics workforce: A focus on laboratory geneticists

PurposeThe aim of this report is to inform the genetics and genomics field about the results of a 2019 workforce survey of US laboratory geneticists. MethodsThe American Board of Medical Genetics and Genomics distributed an electronic survey to board-certified/eligible diplomates in 2019. Analysis of the responses was performed by the American College of Medical Genetics and Genomics. ResultsA total of 422 individuals identified as laboratory geneticists. The respondents represent the range of possible certifications. Nearly one-third were Clinical Cytogenetics and Genomics diplomates, another third were Molecular Genetics and Genomics diplomates, and the others were Clinical Biochemical Genetics diplomates or held a combination of certificates. The majority of laboratory geneticists are PhDs. The others were physicians or other degree combinations. Most laboratory geneticists work in academic medical centers or commercial laboratories. Most respondents identified as females and White. The median age was 53 years. A third of the respondents have been in the profession for 21+ years and plan to reduce hours or retire in the next 5 years. ConclusionThe genetics field needs to foster the next generation of laboratory geneticists to meet the increasing complexity and demand for genetic testing.

1132: MAKING PRISM EASY: DEVELOPMENT OF A STATA COMMAND FOR RISK-OF-MORTALITY CALCULATION

Introduction: PRISM scores have been used in pediatric research to estimate mortality risk and control for illness severity. A major barrier to the usage of this score is the complexity of the calculation and the lack of publicly available implementations. The single publicly available calculator is inconsistently accurate depending on units used and supports data entry for only one patient at a time. Usage of the score over large datasets requires developing custom code to assign scores to physiological variables and calculate the probability of mortality, a resource-intensive and error-prone process. Custom implementations duplicate efforts and are not guaranteed to be accurate. Here we describe the development of a STATA command that calculates PRISM III and PRISM IV scores. Methods: A STATA command that performs PRISM III and PRISM IV score calculations was developed on STATA/MP 17.0. The command implemented the scoring described in the original papers while adding robust error-proofing, data validation, the ability to use both SI and US laboratory value units, and a graphical user interface. Command validation was accomplished by performing unit tests and calculating scores based on deidentified data. Spot checks were performed to ensure the accuracy of the calculations. The command was additionally tested by generating datasets of 10,000,000 simulated patient records containing random realistic data with predetermined PRISM scores and comparing the command output with the predetermined score. To test the run-time of the command, the command was run over 5 distinct datasets using STATA/MP 17.0 2-cores. Results: The STATA command achieved 100% accuracy on both the spot checks and the generated data. The median run-time for PRISM III calculations over 10,000,000 simulated patient records is 50.48 seconds (IQR 46.74 - 50.83). The median run-time for PRISM IV calculations over 10,000,000 simulated patient records is 51.52 seconds (IQR 50.46 - 53.44). Conclusions: The prismscore STATA command performs PRISM III and PRISM IV calculations accurately and efficiently over datasets of all sizes. The tool improves the reproducibility of research involving the scores, streamlines data analysis for pediatric critical care datasets, and offers significant time and resource savings to the research community.

The efficient design of Nested Group Testing algorithms for disease identification in clustered data

Group testing study designs have been used since the 1940s to reduce screening costs for uncommon diseases; for rare diseases, all cases are identifiable with substantially fewer tests than the population size. Substantial research has identified efficient designs under this paradigm. However, little work has focused on the important problem of disease screening among clustered data, such as geographic heterogeneity in HIV prevalence. We evaluated designs where we first estimate disease prevalence and then apply efficient group testing algorithms using these estimates. Specifically, we evaluate prevalence using individual testing on a fixed-size subset of each cluster and use these prevalence estimates to choose group sizes that minimize the corresponding estimated average number of tests per subject. We compare designs where we estimate cluster-specific prevalences as well as a common prevalence across clusters, use different group testing algorithms, construct groups from individuals within and in different clusters, and consider misclassification. For diseases with low prevalence, our results suggest that accounting for clustering is unnecessary. However, for diseases with higher prevalence and sizeable between-cluster heterogeneity, accounting for clustering in study design and implementation improves efficiency. We consider the practical aspects of our design recommendations with two examples with strong clustering effects: (1) Identification of HIV carriers in the US population and (2) Laboratory screening of anti-cancer compounds using cell lines.

A retrospective analysis of the tuberculin skin test reactions of a single source population of Mauritian Macaca fascicularis held in quarantine during 2017.

A published range of reactions to the tuberculin skin test (TST) using mammalian (human) old tuberculin (MOT) in a population of Mauritius origin Macaca fascicularis in US laboratory animal medicine does not exist. The objectives of this report are to quantify the reactions among juvenile, adolescent, and male adult cynomolgus macaques and to provide the laboratory animal medicine practitioner with a reference range of reactions to MOT in Mauritian juvenile macaques. Monkeys in a US foreign animal quarantine must be tested negative for mycobacterial infection including Mycobacterium tuberculosis (Mtb) using MOT as required by the CDC Division of Global Migration and Quarantine. The TST relies on visual observation post injection of an individual animal’s reaction or nonreaction. During 2017, 933 Mauritius origin macaques from one supplier were quarantined in nine separate cohorts in our facility. 848 or > 90% of the animals were juveniles between 1.5 to 3 years of age, comprised of 425 males and 423 females. The population also included 46 adolescents (21 males, 25 females) and 39 adult males. A total of 33 TST sets were performed on the nine cohorts, resulting in 3418 individual TSTs being administered. 1595 (46.6%) injections were made in juvenile males and 1529 (44.7%) in juvenile females. A total of 172 reactions to the TST were recorded at the final assessment completed at the 72-hour post injection time point from all animal ages and sexes. 162 reactions (94.2% of all reactions) occurred in juvenile animals, consisting of 96 bruises (59.3% of all juvenile reactions) in males and 58 bruises (35.8% of all juvenile reactions) in females. Bruising was the most common reaction in juvenile animals and in all animals regardless of age or sex. Bruising occurred within all 33 TST sets ranging from a low of 0% to a high of 30% in male juveniles and a low of 0% to a high of 17% in female juveniles. Bruising was the only finding in the adolescents and adult males. Erythema was observed only in juvenile animals, two males and three females. Generalized eyelid edema was observed only in juvenile animals, one male and one female. These animals had concurrent erythema in the affected eyelid. Animals with generalized eyelid edema and erythema are considered suspect for active tuberculosis and warrant further diagnostics. In this report, the most observed reaction among all age groups and sexes was bruising. Erythema and edema were rarely observed. Only juvenile animals were observed with either erythema, edema or both.

Clinical and Epidemiological Characteristics of Stenotrophomonas maltophilia Associated Lower Respiratory Tract Infections in Qatar: A Retrospective Study.

BackgroundStenotrophomonas maltophilia is a rapidly emerging nosocomial pathogen with intrinsic or acquired resistance mechanisms to several antibiotic classes. It can cause life-threatening opportunistic pneumonia, particularly among hospitalized patients. Incidence of infections by S. maltophilia has been reported as 0.07-0.4% of hospital discharges, but its mortality is 20 -60%. This is the first study from Qatar indexing the clinical and epidemiological characteristics and antibiotic susceptibility of S. maltophilia.Materials and methodsThis retrospective descriptive epidemiological study was conducted in 6 tertiary care hospitals under Hamad Medical Corporation in Doha, Qatar, analyzing inpatient respiratory isolates of S. maltophilia during 2016-17. Out-patients, children below 14 years, and non-respiratory samples except blood cultures in patients with pneumonia were excluded. Clinical records were reviewed to identify possible risk factors. Infection and colonization were identified using the Centers for Disease Control and Prevention (CDC) algorithm for clinically defined pneumonia and statistically analyzed using the chi-square test and Pearson's correlation.ResultsS. maltophilia was isolated from 2.07% (317/15312) of all respiratory samples received in the microbiology lab during our study period. Three hundred seventeen patients studied had a mean age of 60 ± 20 years, and 68% were men. Most of the isolates were from sputum (179), followed by tracheal aspirate (82) and bronchoscopy (42). Fourteen blood culture samples from patients diagnosed with pneumonia were also included. 67% were hospitalized for more than two weeks, 39.1% were on mechanical ventilators, and 88% had received a broad-spectrum antibiotic before the event. 29.1% were deemed to have an infection and 70.9% colonization. Incidence of infection in those with Charlson’s Co-morbidity Index (CCI) ≥ 3 was 36.5% compared to 24.2% in those with CCI < 3 (Relative Risk (RR)=1.52; 95% CI: 1.04,2.18; p=0.01). Patients with recent chemotherapy, immunosuppressant, or steroid use had a significantly higher infection risk than those without (69.2% v/s 23.3% RR=2.96; 95% CI:2.2,3.9; p<0.005). The most common symptoms in patients with infection were fever (96%) and expectoration (61.9%). The most common radiological finding was lobar consolidation (71.6%). Mean CRP and procalcitonin were 106.5±15.5 mg/l and 12.3 ± 14 ng/ml. Overall mortality was 16.3%. Patients on mechanical ventilator with IBMP-10 score ≥ 2 had 22.8% mortality compared to 5.7% in those with score < 2 (RR=3.9;95%CI:0.9,16.6; p<0.015). As per The US Clinical and Laboratory Standards Institute (CSLI) breakpoint values, Trimethoprim-Sulfamethoxazole (TMP-SMX) showed the highest sensitivity (97.8%), followed by levofloxacin (71.6%). 0.3% of samples were pan-drug resistant.ConclusionsS. maltophilia is a frequent nosocomial colonizer, but it can cause nosocomial pneumonia in almost one-third of cases, specifically in immunocompromised and patients with CCI ≥ 3 with a high risk of mortality due to ventilator-associated pneumonia (VAP) in those with IBMP-10 ≥ 2. Prolonged hospital stay is a risk factor for colonization by S. maltophilia, while recent chemotherapy, immunosuppressant, or steroid use are risk factors for hospital-acquired pneumonia due to S. maltophilia. TMP-SMX and levofloxacin are the only reliable agents for monotherapy of respiratory infections due to S. maltophilia in Qatar.

Perceptions and use of phenylbutyrate metabolite testing in urea cycle disorders: Results of a clinician survey and analysis of a centralized testing database

The nitrogen scavengers sodium and glycerol phenylbutyrate (PB), approved for chronic treatment of urea cycle disorders (UCDs), undergo hepatic conversion to phenylacetate (PAA), which conjugates glutamine to form phenylacetylglutamine for urinary nitrogen excretion. Elevated PAA has been associated with reversible neurological toxicity, with symptoms similar to hyperammonemia. Plasma PB metabolite analysis can assess for toxicity and therapeutic drug levels. An online survey was undertaken to assess US clinician perceptions and use of the test in addition to an analysis of centralized US laboratory records. Survey responses from 52 clinicians were analyzed, including 58% who reported using plasma PB metabolite testing. Test users reported managing more UCD patients than nonusers. Users rated the test as “often helpful” for ruling out PAA toxicity (44%), informing PB dosing decisions (42%), and assessing adherence (28%). Test results were reported as most often unremarkable (61%) or suggestive of poor adherence (13%); 46% of users had never encountered results indicative of PAA toxicity. Analyses of laboratory records for 1668 plasma metabolite tests determined that only 5% of samples had plasma PAA-to-phenylacetylglutamine ratios associated with increased risk of PAA toxicity. Nearly half of surveyed clinicians were unsure of metabolite targets; those conducting ad hoc (versus regular) testing were significantly more likely to be unsure of targets. One-fifth of test users identified uncertainties, including questions about test validation, timing, and interpretation. Increased awareness of published PB metabolite data and further clinician education on test interpretation may help to inform the use of metabolite testing to optimize UCD care.

Awareness and Epidemiology of Chronic Hepatitis C Virus Infections in Florida.

IntroductionProgress towards achieving hepatitis C virus (HCV) elimination in Florida has been hampered by barriers to screening, linkage to care, and treatment. This study aims to describe the HCV care cascade and patient characteristics in Florida.MethodsThis analysis combined HCV-related laboratory data and patient characteristics from two, large US laboratory datasets that included individuals tested for HCV antibody (Ab) and HCV ribonucleic acid (RNA) viral load between January 2015 and December 2019. A decline in sequential HCV RNA viral loads was used to impute HCV treatment. Machine-learning algorithms were used to identify cured patients. The actual number of individuals with HCV Ab screening, and the number and percentage of persons who were HCV RNA-positive and treated, were calculated.ResultsThe number of persons in Florida diagnosed as HCV RNA-positive was 31,659 in 2019. The number of individuals HCV Ab screened in 2019 was 1,024,379, an increase of 82.5% from 2015. The percentage of HCV Ab-positive individuals was 4.1%, demonstrating a 16.2% decrease from 2015. The percentage of HCV RNA-positive patients who were treated was 27.0%, a 10.5% decrease from 2015 to 2019.ConclusionAn Ab positivity rate > 4-times higher than national estimates with increased screening among baby boomers, but decreased screening among younger individuals, suggests risk-based screening is still common practice in Florida, despite universal screening recommendations. Public health efforts to decrease barriers to screening, linkage to care, and treatment are needed to reduce the burden of HCV in Florida and to ensure progress toward virus elimination.

Epidemiology and Clinical Characteristics of Individuals with Hepatitis C Virus Infection in the United States, 2017-2019.

IntroductionHepatitis C virus (HCV) is the most common bloodborne chronic infection in the US. Following approval of highly effective, direct-acting antivirals in 2014, the diagnostic and treatment rates for HCV infection in the US have evolved. This study assessed the number of individuals with HCV screening or diagnostic testing and the clinical characteristics and treatment of HCV-infected individuals between 2017 and 2019.MethodsIndividuals screened for HCV antibody and/or tested for HCV ribonucleic acid (RNA) from 2017 to 2019 by two large US laboratory companies were included in this analysis. Clinical characteristics, such as HCV genotype, fibrosis stage, HIV coinfection and demographics, were assessed in HCV RNA-positive individuals. HCV treatment and subsequent achievement of sustained virologic response were imputed using data-driven algorithms based on successive viral load decline and negativity.ResultsFrom 2017 to 2019, the number of individuals tested for HCV antibody increased by 5.7%, from 7,580,303 in 2017 to 8,009,081 in 2019. The percentage of individuals tested who were HCV antibody positive was stable, ranging from 5.0% in 2017 to 4.9% in 2018 and 2019. The number of HCV RNA-positive individuals decreased by 5.0% from 382,500 in 2017 to 363,532 in 2019. Of HCV RNA-positive individuals, the proportions with genotype (GT) 3 and minimal fibrosis increased over time; proportions of individuals aged < 40 years increased, while the proportion aged 50 to 59 years decreased. Treatment rates increased from 23.4% in 2017 to 26.8% in 2019.ConclusionsThe percentage of HCV antibody-positive individuals remained stable from 2017 to 2019. The number of individuals tested HCV RNA positive decreased over the years. Demographics shifted toward a younger population with less fibrosis and higher rates of GT3. More than 70% of diagnosed individuals were not treated during this interval, highlighting a need for unfettered access to treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01928-y.

Three-dimensional ultrasound is a reliable alternative in endovascular aortic repair surveillance

ObjectiveThree-dimensional ultrasound (3D-US) has already demonstrated improved reproducibility with a high degree of agreement (intermodality variability), reproducibility (interoperator variability), and repeatability (intraoperator variability) compared with conventional two-dimensional ultrasound (2D-US) when estimating the maximum diameter of native abdominal aortic aneurysms (AAAs). The aim of the present study was, in a clinical, multicenter setting, to evaluate the accuracy of 3D-US with aneurysm model quantification software (3D-US abdominal aortic aneurysm [AAA] model) for endovascular aortic aneurysm repair (EVAR) sac diameter assessment vs that of computed tomography angiography (CTA) and 2D-US. MethodsA total of 182 patients who had undergone EVAR from April 2016 to December 2017 and were compliant with a standardized EVAR surveillance program were enrolled from five different vascular centers (Rigshospitalet, Copenhagen, Denmark; Catharina Ziekenhuis, Eindhoven, Netherlands; L'hospital de la Timone, Paris, France; Cleveland Clinic, Cleveland, Ohio; and The Christ Hospital, Cincinnati, Ohio) in four countries. All image acquisitions were performed at the local sites (ie, 2D-US, 3D-US, CTA). Only the 2D-US and CTA readings were performed both locally and centrally. All images were read centrally by the US and CTA core laboratory. Anonymized image data were read in a randomized and blinded manner. ResultsThe sample used to estimate the accuracy of the 3D-US AAA model and 2D-US included 164 patients and 177 patients, respectively. The Bland-Altman analysis revealed that the mean difference between CTA and 3D-US was −2.43 mm (95% confidence interval [CI], −5.20 to 0.14; P = .07) with a lower and upper limit of agreement of −8.9 mm (95% CI, −9.3 to −8.4) and 2.7 mm (95% CI, 2.3-3.2), respectively. For 2D-US and CTA, the mean difference was −3.62 mm (95% CI, −6.14 to −1.10; P = .002), with a lower and upper limit of agreement of −10.3 mm (95% CI, −10.8 to −9.8) and 2.5 mm (95% CI, 2-2.9), respectively. ConclusionsThe 3D-US AAA model showed no significant difference compared with CTA for measuring the anteroposterior diameter, indicating less bias for 3D-US compared with 2D-US. Thus, 3D-US with AAA model software is a viable modality for anteroposterior diameter assessment for surveillance after EVAR.

Clinical risk assessment of biotin interference with a high-sensitivity cardiac troponin T assay.

Objectives Biotin >20.0ng/mL (81.8nmol/L) can reduce Elecsys® Troponin T Gen 5 (TnT Gen 5; Roche Diagnostics) assay recovery, potentially leading to false-negative results in patients with suspected acute myocardial infarction (AMI). We aimed to determine the prevalence of elevated biotin and AMI misclassification risk from biotin interference with the TnT Gen 5 assay. Methods Biotin was measured using an Elecsys assay in two cohorts: (i) 797 0-h and 646 3-h samples from 850 US emergency department patients with suspected acute coronary syndrome (ACS); (ii) 2023 random samples from a US laboratory network, in which biotin distributions were extrapolated for higher values using pharmacokinetic modeling. Biotin >20.0ng/mL (81.8nmol/L) prevalence and biotin 99th percentile values were calculated. AMI misclassification risk due to biotin interference with the TnT Gen 5 assay was modeled using different assay cutoffs and test timepoints. Results ACS cohort: 1/797 (0.13%) 0-h and 1/646 (0.15%) 3-h samples had biotin >20.0ng/mL (81.8nmol/L); 99th percentile biotin was 2.62ng/mL (10.7nmol/L; 0-h) and 2.38ng/mL (9.74nmol/L; 3-h). Using conservative assumptions, the likelihood of false-negative AMI prediction due to biotin interference was 0.026% (0-h result; 19ng/L TnT Gen 5 assay cutoff). US laboratory cohort: 15/2023 (0.74%) samples had biotin >20.0ng/mL (81.8nmol/L); 99th percentile biotin was 16.6ng/mL (68.0nmol/L). Misclassification risk due to biotin interference (19ng/L TnT Gen 5 assay cutoff) was 0.025% (0-h), 0.0064% (1-h), 0.00048% (3-h), and <0.00001% (6-h). Conclusions Biotin interference has minimal impact on the TnT Gen 5 assay's clinical utility, and the likelihood of false-negative AMI prediction is extremely low.

Factors influencing susceptibility testing of antifungal drugs: a critical review of document M27-A4 from the Clinical and Laboratory Standards Institute (CLSI).

Due to the increasing numbers of fungal infections and the emergence of drug-resistant fungi, optimization and standardization of diagnostic methods for the measurement of antifungal susceptibility are ongoing. The M27-A4 document by the US Clinical and Laboratory Standards Institute (CLSI) is presently used for the interpretation of minimum inhibitory concentrations of major opportunistic yeast species as measured by broth microdilution testing in many countries. Although microdilution is considered a benchmark for reproducible and accurate results, increased testing capacity, and limited human bias, the method is often inaccessible to routine clinical laboratories and researchers, especially in low-income countries. Furthermore, several studies suggest that there are still a considerable number of factors that make the estimation of in vitro activity of antifungal agents challenging. This review article summarizes the limitations of the M27-A4 standard which, despite the advances and improvements obtained by the standardization of antimicrobial resistance testing methods by CLSI, still persist.

The Clinical and Molecular Epidemiology of Noncarbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae: A Case-Case-Control Matched Analysis.

BackgroundRisk factors and outcomes associated with carbapenem-resistant Enterobacteriaceae (CRE) acquisitions are derived primarily from cohorts consisting of carbapenemase-producing (CP) strains. Worldwide epidemiology of non-CP-CRE is evolving, but controlled epidemiological analyses are lacking.MethodsA matched case-case-control investigation was conducted at Shamir (Assaf Harofeh) Medical Center, Israel, on November 2014–December 2016. Noncarbapenemase-producing CRE (as defined by the US Clinical and Laboratory Standards Institute Standards) carriers were matched to patients with non-CRE Enterobacterales and to uninfected controls (1:1:1 ratio). Matched and nonmatched multivariable regression models were constructed to analyze predictors for acquisition and the independent impact of carriage on multiple outcomes, respectively. Representative isolates were whole genome sequenced and analyzed for resistome and phylogeny.ResultsNoncarbapenemase-producing CRE carriers (n = 109) were matched to the 2 comparative groups (overall n = 327). Recent exposure to antibiotics (but not specifically to carbapenems), prior intensive care unit admission, and chronic skin ulcers were all independent predictors for non-CP-CRE acquisition. Acquisitions were almost exclusively associated with asymptomatic carriage (n = 104), and despite strong associations per univariable analyses, none were independently associated with worse outcomes. Genomic analyses of 13 representative isolates revealed polyclonality, confirmed the absence of carbapenemases, but confirmed the coexistence of multiple other genes contributing to carbapenem-resistance phenotype (multiple beta-lactamases and efflux pumps).ConclusionsNoncarbapenemase-producing CRE acquisitions are primarily associated with asymptomatic carriage, specifically among prone populations with extensive recent exposures to antibiotics. The prevalent mode of acquisition is “emergence of resistance” (not “patient-to-patient transmission”), and therefore the role of stewardship interventions in reducing the spread of these therapeutically challenging pathogens should be further explored.

A laboratory-based algorithm to predict future kidney function decline in older adults with reduced estimated glomerular filtration rate

Reduced estimated glomerular filtration rate (eGFR) in older adults is common and may reflect normal aging or significant kidney disease. Our objective was to develop a predictive model to better triage these individuals using routine laboratory data. Using a large US laboratory data set, we calculated individual eGFR regression slopes for 43,523 individuals aged 60-75 years with baseline eGFRs between 30 and 59 mL/min/1.73m2. We developed general linear models to predict the eGFR regression slope using urine protein measurements and other routinely available laboratory data as dependent variables. We validated these models on a similar data set comprised of 11,979 individuals. In a model utilizing log10 urine albumin/creatinine (UACR), the variables that significantly predicted the eGFR regression slope were log10 UACR, initial eGFR, serum albumin, chloride, glucose, and aspartate aminotransferase (AST). In an otherwise identical model substituting log10 urine protein/creatinine (UPCR) for UACR, results were similar except that serum calcium was significant and AST was not. We analyzed the correspondence between actual eGFR regression slopes and those predicted by our models using receiver operator characteristic (ROC) statistics to calculate areas under the curves (AUC) for four eGFR slope cut points: -2, -3, -4, and -5mL/min/year. AUCs using the UACR and UPCR models ranged from 0.716to0.900 and 0.751to0.868, respectively, for the training data set. Results were nearly identical for the validation data set. Use of a laboratory-based predictive model of eGFR decline for older adults with eGFR 30-59 mL/min/1.73m2 may help distinguish between individuals with and without risk for further decline in kidney function.

What makes a cookstove usable? Trials of a usability testing protocol in Uganda, Guatemala, and the United States

Improved cookstoves, which are designed to address the health and environmental damage caused by inefficient biomass cooking and heating, are generally engineered to prioritize technical emissions and efficiency improvements over practical user cooking needs. As a result, improved stoves are often only used alongside traditional technologies, or are rejected by cooks entirely, and may fall short in efforts to address health and environmental problems even if they are technically capable of doing so. A testing protocol for cookstove usability was developed by the authors to help stove designers and implementers evaluate user needs for a given stove technology and cooking culture, and balance them with technical design criteria more effectively. The protocol is based on established usability practices and includes ethnographic testing methods to increase validity in cross-cultural testing applications. This paper discusses evaluative trials of the protocol in 10 rural and urban households and 2 institutional kitchens near Lira, Uganda, 4 rural households in Antigua, Guatemala, and 11 stove designs in a US laboratory, as well as preliminary results from a usability study on 20 rural households near Gulu, Uganda by an international NGO. These trials, along with feedback from test administrators in Uganda and Guatemala, demonstrated that the protocol is a viable tool for increasing the understanding of cookstove usability, though more work is needed to improve its validity and connect the results to effective stove design and selection decisions, as well as health and environmental impact. As a result of this research, various improvements were made to the protocol, and opportunities for further validation, expansion, and improvement were identified. In addition, methods used by the protocol elicited related data from participants regarding their attitudes towards improved cookstoves and the relative importance of reducing air pollution and fuel use in the larger context of their lives. Finally, this research highlights the value of an interdisciplinary approach, in this case based in anthropology and engineering, to increase the accessibility of user input in international development more broadly.

Host-derived markers of Lyme disease: their discovery and diagnostic potential

Lyme disease (LD) is a multisystem infection caused by tick-borne spirochaetes of the Borrelia burgdorferii sensu lato group. UK and US laboratory diagnosis of LD involves the two-tier serological approach. The negative predictive value of the test has been challenged, particularly in early stage LD. There is considerable interest, therefore, in the development of improved diagnostic tests. The main aim of the project is to identify new markers that could form the basis for improved tests. A mass spectrometry biomarker discovery study was undertaken on LD positive and negative residual diagnostic samples from UK LD testing by Public Health England and a cohort of patient samples from collaboration with a research group in the Czech Republic. A ‘related-disease control group’ including serum samples from syphilis, leptospirosis and chronic fatigue syndrome was also included. Several proteins were found at a significantly higher or lower in abundance in the ld-positive patients compared with ld-negative. Of particular interest was Lipocalin-2 (LCN2), a protein involved in immunity. LCN2 has previously been found in increased abundance in mice exposed to B. burgdorferi. Further analysis of LD samples using Illumina RNA sequencing revealed further markers of interest. Transcriptomic analysis including Ingenuity Pathway Analysis (IPA) gave insights into the host response to LD infection. Proteins of interest from proteomic and transcriptomic analysis were taken forward for further analysis by WB or ELISA in a larger sample set.

Method of determining the rational composition of arable unit

Using the technical characteristics of the PBS-10P trailed single-furrow plow and the results of tractor tests made by the Nebraska Tractor Test US laboratory, the value of towing tension of Case Magnum 340 (239 kW), New Holland Т9020 (213 kW), Challenger MT 835 (271 kW), John Deer 9120 (182 kW), Versatile 375 (226 kW), Versatile 400 (247 kW), New Holland Т9030 (310 kW) tractors and traction resistance of the PBS-10P plow at appropriate speeds were determined. The analytical dependencies of the traction force of the tractors and the traction resistance of the plow on the speed of movement are determined. The method of determining the rational composition of the arable unit is described, including: experimental determination of the plow traction at different tillage depth and speed; determination of the tractor force at the maximum traction power of the tractor; approximation of the obtained results in the form of empirical formulas; building graphical dependencies by empirical formulas and determining the optimal speed of the arable unit, which is used to calculate the productivity of the arable unit.