Cut-off Concentration Research Articles

Evaluation of Fungitell (1,3)-β-D-glucan assay in tear samples for rapid diagnosis of fungal keratitis.

Fungal keratitis (FK) is a serious suppurative and ulcerative corneal infection leading to blindness and vision loss. Rapid diagnosis of FK can contribute to prompt clinical management with early recovery. The study aimed to standardize the detection of (1,3)-β-D-glucan (BDG) and establish the diagnostic cut-off concentration in tears of suspected FK patients along with non-infected controls. This prospective multicentric study was conducted between the period of August 2022 and April 2024. Samples were collected from three tertiary eye-care facilities across India. All suspected FK patients were enrolled in the study. Prior to tear collection, the eye and eyelid were gently cleansed using sterile normal saline (NS) and lint-free tissue paper. Subsequently, 50 µL of sterile NS was instilled into the eye, followed by tear sample collection after 60 s using sterile fine microtips. Tear samples were collected from the contralateral eyes of the FK patients, and those from healthy volunteers served as controls. The concentration of BDG in tears in varying dilutions was quantitatively measured using the Fungitell Assay Kit (Associates of Cape Cod, East Falmouth, Massachusetts). A total of 53 tear samples were analyzed at 1:10 and 1:20 dilutions. The receiver operating curve revealed an area under the curve (AUC) of 0.919 for the 1:10 dilution, with a cut-off value of 123 pg/mL, yielding a sensitivity of 100% and specificity of 84.85%. The corresponding Youden Index was 0.798. At the 1:20 dilution, the AUC was 0.898 with a cut-off of 84 pg/mL, achieving a sensitivity of 70% and specificity of 96.88% with a Youden Index of 0.670. Given the higher specificity at the 1:20 dilution, it was further validated in 145 tear samples. The validation cohort demonstrated a sensitivity of 95.56%, specificity of 83%, positive predictive value (PPV) of 71.67%, negative predictive value (NPV) of 97.65%, and diagnostic odds ratio of 112.4. Notably, a significantly higher BDG concentration (P < 0.0001) was observed in infected tear samples compared to controls (270.6 ± 128.5 vs 37.31 ± 31.32). Detection of BDG in tear samples is a new, non-invasive, and rapid technique showing excellent performance and can be effectively implemented for diagnosing FK in laboratories.

Unveiling the Interplay: Antioxidant Enzyme Polymorphisms and Oxidative Stress in Preterm Neonatal Renal and Hepatic Functions.

To explore the relationship between oxidative stress biomarkers and the occurrence of acute kidney injury (AKI) alongside notable liver function disturbances in preterm neonates. Given the immaturity of kidneys and incomplete liver development in preterm neonates, oxidative stress poses a considerable threat to their renal and hepatic health. To find out the association between various oxidative stress biomarkers and polymorphisms of antioxidant enzymes with renal and live functions. In this cross-sectional study, we gathered umbilical cord blood and peripheral blood samples for assessing oxidative stress biomarkers and identifying single nucleotide polymorphisms (SNPs) in antioxidant enzymes. Utilizing enzyme-linked immunosorbent assay kits, we quantified these oxidative stress biomarkers. Receiver-operating characteristics curve analysis was employed to ascertain the predictive capacity of these biomarkers, denoted by the area-under-the-curve (AUC). Our findings revealed that umbilical cord heat-shock proteins emerged as robust predictors of neonatal AKI (AUC: 0.92; 95% CI: 0.8-1) with a defined cut-off concentration of 1.8 ng/mL. Likewise, umbilical cord 8-hydroxy-2-deoxy guanosine demonstrated significant predictability for liver function alterations (AUC: 0.7; 95% CI: 0.6-0.9) at a cut-off concentration of 2487.6 pg/mL. We observed significant associations between SNPs in endothelial nitric oxide synthase and catalase with both AKI and impaired liver functions. Prospective studies are warranted to validate these findings, with a particular focus on exploring potential antioxidant interventions aimed at mitigating AKI and liver function abnormalities.

B-289 Assessing the Shift in Positivity Rates of Cocaine and Its Metabolites in a Community Based Population: A Transition from utilization of Cutoff Concentrations to Qualitative Structure Identification

Abstract Background Semi-quantitative cutoff concentrations have traditionally been employed for urine drug detection. Research suggests that these cutoffs may be set too high, leading to the risk of overlooking positive cases. The advent of liquid chromatography-high-resolution mass spectrometry (LC-HR/MS) technology allows for the detection of drugs at lower concentrations. This study aims to assess the impact of transitioning from cutoff concentrations to qualitative structure identification on the positivity rates of cocaine and its metabolites in a community-based population. Methods Data analysis was conducted on results obtained from a community laboratory from April 2021 to October 2023. Screening of drugs was carried out using the Sciex X500R QTOF MS System. Cutoff concentrations were applied from April 2021 to September 2022 for screening cocaine and its metabolites (benzoylecgonine, norcocaine, and cocaethylene) in 62,816 samples. From October 2022 to October 2023, a qualitative structure identification approach was adopted for screening 47,676 samples. Results The previous screening for cocaine, benzoylecgonine, norcocaine, and cocaethylene was performed with a cutoff concentration of 50 ng/mL. Employing a qualitative structure identification approach, cocaine, benzoylecgonine, and cocaethylene were detectable at 5 ng/mL, while norcocaine could be identified at 10 ng/mL. Consequently, when qualitative identification was applied, the positivity rates for cocaine and its metabolites showed an increase. The prevalence of cocaine and its metabolites in the positive samples also demonstrated a corresponding shift. Conclusions Moving from using cutoff concentrations to employing qualitative structure identification with LC-HR/MS markedly enhances the detection of positive cases for cocaine and its metabolites. Although the detection sensitivity of drugs is improved, the presence of drugs at low concentrations can pose challenges with interpretation of results.

B-299 Comparison of a Recently FDA-Cleared Urine Benzodiazepine Screening Assay with β-Glucuronidase Hydrolysis to Liquid Chromatography-Mass Spectrometry

Abstract Background Benzodiazepines are a class of prescribed psychoactive drugs that act as a depressant on the central nervous system. Over the last decade, the fast-acting sedative effects of these drugs have led to misuse, therefore making detection important for monitoring proper drug compliance. Immunoassays on urine samples are commonly used as a screening method and the results are confirmed using high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS). The metabolites of benzodiazepine in urine are predominantly excreted as glucuronides which may lead to false negative results when utilizing immunoassay-based methods. The purpose of this study was to compare a new generation of benzodiazepine reagent, that includes a β-glucuronidase enzyme to increase sensitivity, to LC-MS/MS. Secondly, the positivity rate was compared before and after the increased sensitivity screening assay was implemented. Methods Validation of benzodiazepine II assay was performed on an automated chemistry analyzer (Roche Diagnostics, cobas c502), utilizing a kinetic interaction of microparticles in a solution (KIMS) method. A total of thirty urine samples that screened positive on the benzodiazepine II assay and thirty samples that screened negative, were compared with LC-MS/MS. The LC-MS/MS panel included α- hydroxytriazolam, 7- aminoclonazepam, nordiazepam, temazepam, oxazepam, lorazepam, and α-hydroxyalprazolam. The lower limit of quantitation was 40 ng/mL for all compounds except α-hydroxyalprazolam which was 60 ng/mL. The cutoff concentration for the benzodiazepine II assay was 200 ng/mL. Three months of data was also collected before and after converting to the new generation of benzodiazepine assay. Results Conclusions The addition of β-glucuronidase to the benzodiazepine II assay allowed for high sensitivity when detecting urine benzodiazepine metabolites. With the increased sensitivity, almost a doubling of positivity rate was observed. The overall high diagnostic accuracy of the test makes it a reliable screening method for urine benzodiazepine detection.

B-295 Sensitive and Rapid Homogeneous Immunoassay for the Detection of Zolpidem and its Major Metabolite in Urine

Abstract Background Zolpidem, a schedule IV controlled substance under the Controlled Substances Act, is commonly known as Ambien and Ambien CR, a prescription only treatment for insomnia. Zolpidem is one of the most common prescribed sleep aids in the U.S. due to its rapid sedative effects. The recommended duration of treatment is between two days and four weeks, as long-term use of zolpidem increases the risk of habit formation. Addiction to zolpidem can cause severe side effects, including memory loss, delusion, and in extreme cases, fatal overdose. From 2005-2010, Zolpidem-related emergency room visits doubled, underscoring the need for accurate testing as zolpidem testing plays an important role in cases of misuse, diversion, and forensics. The sole commercially available homogeneous immunoassay for the detection of zolpidem in urine has a relatively high cutoff at 20 ng/mL and poor cross-reactivity (0.02%) to major metabolite zolpidem 4-carboxylic acid. ARK Diagnostics has developed the ARK™ Zolpidem Assay to detect zolpidem at a cutoff concentration of 10 ng/mL with high cross-reactivity to its metabolite, Zolpidem phenyl 4-carboxylic acid and no cross-reactivity to zaleplon and zopiclone at concentrations below 100,000 ng/mL. Methods The ARK™ Zolpidem Assay is a liquid stable homogeneous enzyme immunoassay, consisting of two reagents, with a cutoff concentration of 10 ng/mL and semi-quantitative range up to 40 ng/mL. Preliminary performance characterization for this assay was evaluated on the Beckman Coulter AU680 Automated Clinical Chemistry Analyzer. Precision, analytical recovery, specificity, Histogram Overlap Analysis of ±50% controls and the cutoff, and method comparison with LC-MS/MS were evaluated. Results In semi-quantitative mode, total precision ranged from 2.6 to 3.1% CV. Spiked recovery of zolpidem ranged from 88.6% (2.5 ng/mL) to 96.8% (10 ng/mL). The major metabolite, zolpidem phenyl-4-carboxylic acid, showed an approximate equivalence to the 10 ng/mL zolpidem cutoff at 30 ng/mL (33.3% cross-reactivity). Histogram overlap analysis showed no overlap between cutoff and control levels. Method correlation with LC-MS/MS using authentic urine samples showed an excellent agreement with a specificity of 100% and sensitivity of 100% (15 positives and 100 negatives). Conclusions The ARK™ Zolpidem Assay measures zolpidem and its major metabolite zolpidem phenyl-4-carboxylic acid in human urine with acceptable performance. The assay is sensitive, rapid, and applicable to a wide range of clinical chemistry analyzers.

B-275 Trends of urine drug testing findings in a pediatric hospital from 2019 to 2023

Abstract Background Semi-quantitative immunoassays (IA) are commonly used as the initial urine drug screen (UDS), with positive results confirmed by additional testing. However, substantial false negative (FN) rates have been reported in the classes of opioids and amphetamines. In our pediatric hospital, a semi-quantitative comprehensive urine drug testing by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF) MS (referred as QTOF) is offered as either a direct order or a reflexive order following positive IA UDS. The lab also reflexes to run an IA UDS with every direct QTOF order. This study presents paired urine drug IA and QTOF results in the classes of opiate, synthetic opioid, and amphetamine/methamphetamine between 2019 and 2023 to understand trends and to evaluate assay accuracy. Methods Paired results from IA (Siemens Atellica) and QTOF (Sciex 4600) were analyzed with reporting cutoff concentrations from representative drugs in each class listed in Figure 1. The opiate class reported on QTOF includes 6-monoacetylmorphine, morphine, hydrocodone, codeine and metabolites. The synthetic opioid class includes buprenorphine, fentanyl, levorphanol, methadone, naloxone, oxycodone, tramadol and metabolites. Simultaneous findings of opiate and synthetic opioid were counted as the opiate class. FN rate of IA was calculated using QTOF as the reference. Results As shown in Figure 1, QTOF testing nearly doubled from 2019 to 2023, with an expected high FN rate in the synthetic opioid class and alarmingly rising FN rates in opiate and amphetamine classes. Within the synthetic opioid class, percentage of positive fentanyl results increased from 37.6% to 59.0% in 5 years, and ∼10% are only positive for norfentanyl, which is detected in very few commercial fentanyl IAs. Conclusions Our study clearly demonstrates the gap in pediatric toxicology investigation, reporting high FN rates in common drug classes by urine IA, calling for more comprehensive and sensitive UDS to be broadly adopted.

B-271 High Sensitivity Homogeneous Enzyme Immunoassay for Benzodiazepines and Metabolites

Abstract Background Benzodiazepines are widely prescribed for treating various conditions such as anxiety, insomnia, and seizures due to their sedative and anxiolytic properties. Despite their therapeutic benefits, concerns persist regarding their potential for misuse, dependence, and addiction. Urine drug screening immunoassays serve as an important tool in monitoring benzodiazepine usage, ensuring adherence to prescribed regimens, identifying misuse or abuse, and facilitating necessary medical interventions. However, limitations of benzodiazepine immunoassays are well-documented in literature, with issues surrounding their lack of sensitivity to glucuronidated and 7-amino metabolites, inability to detect newer benzodiazepines, and poor cross-reactivity with different benzodiazepines. ARK Diagnostics has developed a highly sensitive homogeneous enzyme immunoassay capable of detecting both classic and designer benzodiazepines, in addition to their glucuronide and 7-amino metabolites in human urine at a cutoff concentration 200 ng/mL, without the need for glucuronidase or sample pretreatment. Methods The ARKTM Benzodiazepine Plus Assay is a liquid-stable homogenous enzyme immunoassay consisting of two reagents. The assay uses temazepam as the 200 ng/mL cutoff calibrator. The performance characteristics of this assay, including precision, spiked recovery, specificity, and method comparison to LC-MS/MS, were evaluated on the Beckman Coulter AU680 automated clinical analyzer. Results The ARKTM Benzodiazepine Plus demonstrated acceptable precision, with no overlap between cutoff (200 ng/mL) and ±25% control levels (150 ng/mL and 250 ng/mL) in a histogram overlap analysis, and ≤3.6% CV in semi-quantitative mode. Spiked temazepam samples spanning the semi-quantitative assay range of 1000 ng/mL were recovered between 95.0% and 103.7% of the spiked levels. Thirty-eight benzodiazepines produced cross-reactivities &amp;gt;80%, including the following benzodiazepines and metabolites: lorazepam, clonazepam, diazepam, alprazolam, temazepam, oxazepam glucuronide, lorazepam glucuronide, temazepam glucuronide, 7-aminoclonazepam, and 7-aminoflunitrazepam. In method comparison studies, a total of 103 urine samples containing benzodiazepines with LC-MS/MS values ranging from 1.3 ng/mL to 3257.6 ng/mL were tested with the ARKTM Benzodiazepine Plus Assay. Eighty samples tested positive with values ≥200 ng/mL and 23 samples tested negative with values &amp;lt;200 ng/mL by the ARKTM Benzodiazepine Plus assay. Of the 23 samples that tested negative, 21 had LC-MS/MS values &amp;lt;200 ng/mL and 2 samples were identified as midazolam samples with metabolite a-OH-midazolam levels &amp;gt;200 ng/mL. Conclusions The ARKTM Benzodiazepine Plus Assay enables the sensitive, rapid, and reliable measurement of benzodiazepines and their metabolites in human urine, without the need for hydrolysis or pretreatment. The assay addresses the present constraints of currently available benzodiazepine immunoassays, including their insufficient sensitivity, limited cross-reactivity to metabolites, and the requirement for glucuronidase pretreatment. The ARKTM Benzodiazepine Plus Assay is applicable to a wide range of clinical chemistry analyzers.

Total bilirubin modified the association between diabetes and stroke: a cross-sectional study from NHANES 2011–2016

BackgroundTotal bilirubin (TBIL) has antioxidant and anti-inflammatory properties. This study aimed to determine whether elevated TBIL could modify the association between diabetes and stroke.MethodData were obtained from the National Health...

Subcutaneous infliximab cut-off points in patients with inflammatory bowel disease. Data from the ENEIDA registry.

Switching from the intravenous to the subcutaneous biosimilar infliximab (SC-IFX) has been shown to safely maintain clinical remission and increase drug levels in patients with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate long-term outcomes after switching from intravenous IFX (IV-IFX) to SC-IFX, the drug concentration thresholds for maintaining remission and other predictors for loss of response after the switch. Multicenter observational study involving CD and UC patients who were in clinical remission for at least 24 weeks and scheduled to switch from IV-IFX to SC-IFX. Two hundred and twenty patients were included [74 UC (34%) and 146 (66%) CD]. IV-IFX was administered for 52.5 months [range 25-89]. Pre-switch, 106 (49%) patients were receiving intensified IV-IFX. While SC-IFX levels significantly increased following the switch from IV to SC-IFX, clinical parameters, C-reactive protein and faecal calprotectin remained unchanged during follow-up. SC-IFX levels were significantly higher between patients receiving the standard IV-IFX dose than those with the intensified dose. Immunomodulator therapy at baseline and perianal disease had no effect on IFX trough levels, whereas higher body mass index was associated with increased levels. The suggested optimal SC-IFX cut-off concentration for clinical and biochemical remission based on ROC analysis was 12.2 μg/mL (AUC: 0.62) at week 12 and 13.2 μg/mL (AUC: 0.57) at week 52. Drug persistence was 92% at week 52, with a good safety profile. Switching from IV-IFX to SC-IFX safely maintains long-term remission in patients with CD and UC. In maintenance, the optimal cut-off point associated with remission was 12-13 μg/mL.

The Effect of Progesterone Elevation on the Day of Trigger Administration: A Review of the Literature.

Since the advent of assisted reproductive technology, different variables have been shown to affect pregnancy outcomes. One of the most prevalent studied events is the premature rise in serum progesterone concentrations on the day of trigger administration during cycles of ovarian stimulation. This phenomenon, classically known as premature luteinization, has been observed significantly for decades and has been linked to adverse pregnancy outcomes and lower live birth rates. Ultimately, a quest to find a precise serum progesterone concentration cut-off value that can be effectively used to predict pregnancy outcomes prior to trigger administration is still underway. The purpose of the current research was to study the available literature on the relationship between serum progesterone on the day of trigger administration in controlled ovarian stimulation cycles used for IVF in an attempt to identify a cut-off serum progesterone concentration that can be used to effectively predict future pregnancy outcomes in fresh transfers. This study is a review of the literature and is based on information and data gathered from 36 published articles. The majority of the literature shows that a serum progesterone concentration cut-off of 1.5 ng/ml (4.77 nmol/L) can be used prior to trigger administration to effectively predict pregnancy outcomes. Premature progesterone elevation on the day or prior to the trigger administration is associated with adverse pregnancy outcomes in IVF cycles. Other factors such as follicle number, serum concentration of other hormones, and ovarian response to ovarian stimulation should also be considered to predict the success of IVF protocols.

Association of Serum Programmed Cell Death Protein 1 (PD-1) and Gene Polymorphism with Some Valid Predictors for Systemic Lupus Erythematosus (SLE) Patients in Basra Province, Iraq

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a systematic autoimmune disorder characterized by the production of autoantibodies against nuclear antigens and inflammation initiation. We aimed to examine the correlation between IL-18, IL-37, and PD-1, and the potential link between polymorphisms in the PD-1 gene located in intron-4 and the susceptibility to SLE. MATERIALS AND METHODS: This cross-sectional study included 43 SLE and 53 healthy individuals. Blood samples were obtained and underwent biochemical examination. The polymorphisms were screened by amplifying the intron-4 of the PD-1 gene using particular primers and then verified through sequencing. RESULTS: Our findings demonstrated statistically significant positive correlations between IL-18, IL-37, and PD-1, while the AUC of the ROC curve is 0.985, 0.968, and 0.940, and cut-off concentration is ≥132.87, ≥62.98, and ≥169.02, respectively. Moreover, two separate SNPs (rs6705653 and rs41386349) were discovered within intron-4 of the PD-1 gene. The genotype AA of the +7499 (G/A) SNP was significantly related with an increased risk of SLE (OR=3.11, 95%CI=1.52–5.94, p-value=0.031). Additionally, the A allele was identified as a risk allele (OR=1.59, 95%CI=1.09–2.31, p-value=0.043). Nevertheless, our study didn’t find any noteworthy connection between the allele and genotype of the +7209 (C/T) polymorphism region of the PD-1 gene frequencies and the susceptibility to SLE. CONCLUSION: IL-18, IL-37, and PD-1 may play significant roles in SLE immune responses and processes. Furthermore, the sequencing examination of intron-4 within the PD-1 gene demonstrated a noteworthy correlation between the A allele and the AA genotypes of PD-1 +7499 (G/A) SNP presence with the increased SLE susceptibility.

Thermodynamic theorical and parametric analysis of a photovoltaic-photo/thermochemistry synergistic conversion system with full spectrum cascading utilization

Solar spectral splitting and cascade utilization is an efficient way to improve solar energy conversion efficiency. This study analyzes the photovoltaic-photo/thermochemistry synergistic conversion system from a thermodynamic perspective. The photo/thermochemistry conversion combined with photochemistry and thermochemistry can effectively utilize the residual spectrum that photovoltaic cannot efficiently use. Through the established thermodynamic model, the thermodynamic limitation of the photovoltaic-photo/thermochemistry synergistic conversion system is calculated. The analysis examines the effects of parameters such as cutoff wavelengths, concentration ratios, and internal irreversibility on system performance, including photovoltaic output voltage, available energy per absorbed photon of photocatalysis, conversion temperature, and selective absorption cutoff wavelength. The results indicate a high thermodynamic limitation of 47.1% at one sun and 68.56% at full concentrations. Energy and exergy flow analysis identifies the proportion of system energy and exergy loss. Compared with other spectral splitting systems, the proposed system demonstrates a significant advantage in solar cascading utilization. This study provides a thermodynamic foundation for the development and design of photovoltaic-photo/thermochemistry synergistic conversion systems.

Biphasic Medium Using Nicotinamide for Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis.

Reliable drug susceptibility testing of pyrazinamide (PZA) is technically difficult, since PZA activity is pH sensitive. The aim of this study was to evaluate a biphasic medium assay (BMA) for the reliable detection of PZA resistance in Mycobacterium tuberculosis (MTB) using nicotinamide (NIC) as a surrogate for PZA and identifying the appropriate cut-off value for the assay. The PZA susceptibility of 122 multidrug-resistant tuberculosis (MDR-TB) isolates and 39 drug-susceptible tuberculosis (DS-TB) isolates was examined using the BMA with NIC at four different concentrations (250, 500, 1000, and 2000 mg/L) and comparing the results with results from the BACTEC MGIT 960 reference method. Out of 122 MDR-TB isolates, 40 were identified as resistant by the BACTEC MGIT 960 system, of which 92.5% contained mutations within their pncA gene plus promoter region. A minimum inhibitory concentration of NIC ≥ 1000 mg/L was used as the cut-off concentration to define resistance in correlation with the MGIT 960 outcomes. NIC-BMA had a sensitivity of 90.91%, a specificity of 100%, and an accuracy of 97.52% compared with the MGIT 960 method. NIC-BMA is a promising assay to screen PZA resistance in microbiological laboratories without automation or advanced molecular instruments.

Prospective Validation of Glial Fibrillary Acidic Protein, d ‐Dimer, and Clinical Scales for Acute Large‐Vessel Occlusion Ischemic Stroke Detection

Background Large‐vessel occlusion (LVO) ischemic stroke is responsible for significant morbidity and mortality. We have previously described a novel tool for acute LVO detection that combines blood‐based biomarkers (glial fibrillary acidic protein and d ‐dimer) with stroke severity scales to achieve high accuracy. Accordingly, the present study sought to prospectively validate cutoff values that we had previously established for biomarkers and scales. Methods The TIME (Testing for Identification Markers of Stroke) trial was designed as a prospective observational diagnostic accuracy study. All ambulance‐identified stroke code activations &lt;18 hours from symptom onset were recruited at Brandon Regional Hospital (Brandon, FL) between May 2021 and August 2022. Previously determined cutoff concentrations of plasma glial fibrillary acidic protein (213 pg/mL) and d ‐dimer (600 ng/mL) were used in combination with prehospital stroke scales to detect LVO. We compared rates of LVO detection against a reference standard using computed tomography/magnetic resonance angiography. Results A total of 382 patients with suspected stroke were recruited. The final cohort was composed of 323 patients with suspected stroke with the following distribution: LVO ischemic stroke (n = 29, 9%), non‐LVO ischemic stroke (n = 48, 15%), hemorrhagic stroke (n = 13, 4%), transient ischemic attack (n = 12, 3.9%), and stroke mimics (n = 220, 68.1%). Combining blood‐based biomarkers (glial fibrillary acidic protein and d ‐dimer) with the scale field assessment stroke triage for emergency destination yielded the best performance for LVO detection, with specificity of 94% and sensitivity of 71%. Performance was found to be higher in a subanalysis focusing on patients presenting &lt;6 hours from symptom onset, with 93% specificity and 81% sensitivity. Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage. Conclusion The present work prospectively validated the potential utility of previously defined glial fibrillary acidic protein and d ‐dimer cutoff levels (ie, 213 pg/mL and 600 ng/mL, respectively), demonstrating their value for discrimination of LVO stroke from differential diagnoses during code stroke workups. (ClinicalTrials.gov number, NCT04292600.)

Association of urinary bisphenol A levels with heart failure risk in U.S. adults from the NHANES (2003-2016).

Although heart failure (HF) has been linked to bisphenol A (BPA), few studies have investigated the cut-off values for the effects of urinary BPA levels on heart failure risk. The association between urinary BPA levels and HF prognosis has not been investigated. This study included 11,849 adults over 20 years old using information from the National Health and Nutrition Examination Survey (NHANES), which was conducted from 2003 to 2016. The relationship between urinary BPA levels and the risk of HF was determined via a multivariable logistic regression model, and restricted cubic spline (RCS) methods were used to determine the cut-off for the effect of BPA levels on HF risk. Based on the available NT-proBNP concentration data from the NHANES (2003-2004), multivariable linear regression was applied to determine the linear association between the NT-proBNP concentration and urinary BPA concentration. The results revealed a positive correlation between a urinary BPA concentration in the fourth quartile and the occurrence of heart failure [OR 1.49, 95% CI (1.09, 2.04), p = 0.012]. A one-unit increase (1 ng/mg creatinine) in the ln-transformed BPA concentration was linked to a 15% increase in the incidence of HF [OR 1.15, 95% CI (1.03, 1.29), p = 0.014]. The cut-off urinary BPA concentration for HF risk was 1.51 ng/mg creatinine. There was a positive correlation between urinary BPA and NT-proBNP concentrations [β = 0.093, 95% CI (0.014, 0.171), p = 0.02] in males, but there was no linear association [β = 0.040, 95% CI (-0.033, 0.113), p = 0.283] in females. Increased urinary BPA levels are linked to an increased risk of heart failure and poor prognosis. There is a significant increase in the risk of heart failure if the urinary concentration of BPA exceeds 1.51 ng/mg creatinine.

Novel Tools for Single Comparative and Unified Evaluation of Qualitative and Quantitative Bioassays: SS/PV-ROC and SS-J/PV-PSI Index-ROC Curves with Integrated Concentration Distributions, and SS-J/PV-PSI Index Cut-Off Diagrams.

Background: This investigation is both a study of potential non-invasive diagnostic approaches for the bladder cancer biomarker UBC® Rapid test and a study including novel comparative methods for bioassay evaluation and comparison that uses bladder cancer as a useful example. The objective of the paper is not to investigate specific data. It is used only for demonstration, partially to compare ROC methodologies and also to show how both sensitivity/specificity and predictive values can be used in clinical diagnostics and decision making. This study includes ROC curves with integrated cut-off distribution curves for a comparison of sensitivity/specificity (SS) and positive/negative predictive values (PPV/NPV or PV), as well as SS-J index/PV-PSI index-ROC curves and SS-J/PV-PSI index cut-off diagrams (J = Youden, PSI = Predictive Summary Index) for the unified direct comparison of SS-J/PV results achieved via quantitative and/or qualitative bioassays and an identification of optimal separate or unified index cut-off points. Patients and Methods: According to the routine diagnostics, there were 91 patients with confirmed bladder cancer and 1152 patients with no evidence of bladder cancer, leading to a prevalence value of 0.073. This study performed a quantitative investigation of used-up test cassettes from the visual UBC® Rapid qualitative point-of-care assay, which had already been applied in routine diagnostics. Using a photometric reader, quantitative data could also be obtained from the test line of the used cassettes. Interrelations between SS and PV values were evaluated using cumulative distribution analysis (CAD), SS/PV-ROC curves, SS-J/PV-PSI index-ROC curves, and the SS-J/PV-PSI index cut-off diagram. The maximum unified SS-J/PV-PSI index value and its corresponding cut-off value were determined and calculated with the SS-J/PV-PSI index cut-off diagram. Results: The use of SS/PV-ROC curves with integrated cut-off concentration distribution curves provides improved diagnostic information compared to "traditional" ROC curves. The threshold distributions integrated as curves into SS/PV-ROC curves and SS-J/PV-PSI index-ROC curves run in opposite directions. In contrast to the SS-ROC curves, the PV-ROC and the novel PV-PSI index-ROC curves had neither an area under the curve (AUC) nor a range from 0% to 100%. The cut-off level of the qualitative assay was 7.5 µg/L, with a sensitivity of 65.9% and a specificity of 63.3%, and the PPV was 12.4% and the NPV was 95.9%, at a threshold value of 12.5 µg/L. Based on these set concentrations, the reader-based evaluation revealed a graphically estimated 5% increase in sensitivity and a 13% increase in specificity, as compared to the visual qualitative POC test. In the case of predictive values, there was a gain of 8% for PPV and 10% for NPV. The index values and cut-offs were as follows: visual SS-J index, 0.328 and 35 µg/L; visual PV-PSI index, 0.083 and 5.4 µg/L; maximal reader Youden index, 0.0558 and 250 µg/L; and maximal PV-PSI index, 0.459 and 250 µg/L, respectively. The maximum unified SS-J/PV-PSI index value was 0.32, and the cut-off was 43 µg/L. The reciprocal SS-J index correctly detected one out of three patients, while the reciprocal PV-PSI index gave one out of twelve patients a correct diagnosis. Conclusions: ROC curves including cut-off distribution curves supplement the information lost in "traditionally plotted" ROC curves. The novel sets of ROC and index-ROC curves and the new SS/PV index cut-off diagrams enable the simultaneous comparison of sensitivity/specificity and predictive value profiles of diagnostic tools and the identification of optimal cut-off values at maximal index values, even in a unifying SS/PV approach. Because the curves within an SS-J/PV-PSI index cut-off diagram are distributed over the complete cut-off range of a quantitative assay, this field is open for special clinical considerations, with the need to vary the mentioned clinical diagnostic parameters. Complete or partial areas over the x-axis (AOX) can be calculated for summarized quantitative or qualitative effectivity evaluations with respect to single and/or unified SS-J and PV-PSI indices and with respect to single, several, or several unified assays. The SS-J/PV-PSI index-AOX approach is a new tool providing additional joint clinical information, and the reciprocal SS-J indices can predict the number of patients with a correct diagnosis and the number of persons who need to be examined in order to correctly predict a diagnosis of the disease. These methods could be used in applications like medical or plant epidemiology, machine learning algorithms, and neural networks.

Reliability of roadside oral fluid testing devices for ∆9 -tetrahydrocannabinol (∆9 -THC) detection.

Driving under the influence of cannabis (DUIC) is increasing worldwide, and cannabis is the most prevalent drug after alcohol in impaired driving cases, emphasizing the need for a reliable traffic enforcement strategy. ∆9 -tetrahydrocannabinol (THC) detection in oral fluid has great potential for identifying recent cannabis use; however, additional data are needed on the sensitivities, specificities, and efficiencies of different oral fluid devices for detecting cannabinoids at the roadside by police during routine traffic safety enforcement efforts. At the roadside, 8945 oral fluid THC screening tests were performed with four devices: AquilaScan®, Dräger DrugTest®, WipeAlyser Reader®, and Druglizer®. A total of 530 samples screened positive for THC (5.9%) and were analyzed by liquid chromatography-tandem mass spectrometry at multiple cutoff concentrations (2ng/mL, 10ng/mL, and manufacturers' recommended device cutoffs) to investigate device performance. Results varied substantially, with sensitivities of 0%-96.8%, specificities of 89.8%-98.5%, and efficiencies of 84.3%-97.8%. The Dräger DrugTest® outperformed the other devices with a 96.8% sensitivity, 97.1% specificity, and 97.0% efficiency at a 5-ng/mL LC-MS/MS confirmation cutoff. The WipeAlyser Reader® had good performance with a 91.4% sensitivity, 97.2% specificity, and 96.4% efficiency. AquilaScan® and Druglizer® had unacceptable performance for cannabinoid detection, highlighted by sensitivity <13%. The choice of roadside oral fluid testing device must offer good analytical performance for cannabinoids because of its high prevalence of use and impact on road safety.

Prevalence of Penicillin Resistance Among Streptococcus pneumoniae Isolates in a General Hospital in Southwest Saudi Arabia: A Five-Year Retrospective Study.

Background The rise in infections caused by penicillin-resistant strains of Streptococcus pneumoniae has become a global concern. However, the magnitude of this problem in Southwest Saudi Arabia has never been investigated. Therefore, this study aims to determine the prevalence of this bacteria in the region using in vitro data. Materials and methods This study retrospectively studied pneumococcal isolates collected by the Microbiology Laboratory of a general hospital in Al Baha, Saudi Arabia, from January 2013 to December 2017. A minimum inhibitory concentration (MIC) ≥ 8 mg/L was used as a cutoff concentration to detect the resistant isolates. Results A total of 201 S. pneumoniae isolates were identified using the VITEK® 2 system (bioMérieux SA, Marcy-l'Étoile, France). Most of these isolates (61%) were obtained from respiratory specimens, including sputum, tracheal aspirates, and bronchoalveolar lavage. Eye swabs accounted for 15% of the isolates, blood samples contributed 12%, ear swabs accounted for 7%, and cerebrospinal fluid (CSF) 3.4%. The resistance of S. pneumoniae during the five years varied from 61% to 76%, with an overall resistance of 70% (141/201). The resistance rate per year was 71% (43/60) in 2013, 76% (35/46) in 2014, 61% (22/36) in 2015, 68% (20/29) in 2016, and 66% (21/30) in 2017. Conclusion The data confirm the presence of penicillin-resistant S. pneumoniae in Southwest Saudi Arabia. Furthermore, the high resistance suggests a potential concern, emphasizing the need for penicillin control, surveillance, and vaccination to address this growing problem.

Evaluation of the Canadian approved drug screening equipment cut-off levels for tetrahydrocannabinol (THC).

In 2018, Canada introduced roadside oral fluid (OF) screening devices, called Approved Drug Screening Equipment (ADSE), as an investigative tool in impaired driving investigations to detect tetrahydrocannabinol (THC), cocaine and/or methamphetamine in drivers. In this work, we compare the detection and concentration of THC in blood samples collected from suspected impaired drivers that tested positive at the roadside for THC on an ADSE. The two ADSEs that were utilized were the Dräger DrugTest® 5000 (DDT) and the Abbott SoToxa™ (SoToxa), both configured with a THC OF concentration cut-off concentration of 25 ng/mL. Blood samples were screened for cannabinoids using immunoassay and positive results were followed up by confirmation/quantitation of THC by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS-MS). A total of 230 cases were available where a blood sample was collected from a suspected impaired driver subsequent to a positive THC screen result on an ADSE. The blood samples were taken an average of 1.4 hours (range = 9 minutes to 3.2 hours) after the ADSE test. THC was confirmed in 98% of blood samples with concentrations across all samples ranging from not detected (cut = off 0.5 ng/mL) to greater than 20 ng/mL. Further, 90% of the blood samples had a THC concentration of 2.0 ng/mL (the lower per se limit in Canada) or greater. A positive ADSE test of a suspected impaired driver may predict that the driver has a detectable level of THC in their blood, and there is a high likelihood that the THC blood concentration is 2.0 ng/mL or higher. Hence, ADSE may be a useful tool for law enforcement and aid in the development of grounds to believe that a driver is operating a conveyance with a THC concentration exceeding Canadian per se limits.

Statistical Study of Membrane Performance for Different Pharmaceutical Compounds Removal

One of the most important emerging pollutants is pharmaceutical active compounds, which may be responsible, for example, for ecotoxicological changes and microbiological resistance. Wastewater treatment plants are not adequately equipped to remove all of the emerging pollutants contained in the wastewater. The ultrafiltration process has been proven to be effective in traditional wastewater treatment, so it is important to assess the performance of such a technique in the partial elimination of pharmaceutical compounds to avoid contamination. In this work, an assessment of ultrafiltration process operating conditions for eliminating six pharmaceutical compounds: Ibuprofen, Acetaminophen, Naproxen, Diclofenac, Caffeine, and trimethoprim, present in different types of water is performed. Experimental design is a systematic and structured approach to conducting experiments, and its application can significantly improve the study of membrane technology, reducing the number of assays necessary to obtain meaningful results. The statistical principles application ensures that the results obtained are reliable and representative of the true effects of the variables being studied. Its application helps to obtain valid conclusions from the data and provides a solid basis for making decisions or recommendations regarding the tests and variables to take into account. Membrane processes can involve complex interactions between several factors. Experimental design helps to identify and understand these interactions, allowing researchers to discern the combined effects of different variables. This is crucial to accurately predict and optimize membrane performance. In this work, ANOVA analysis has been carried out in order to determine the influence of membrane cut-off, solution pH, and feed concentration, as well as their interactions, in permeate flux and the rejection index. The results obtained show similar behavior for Ibuprofen, Naproxen, Diclofenac, and Trimethoprim, being the pH the most important factor. However, no significant factors were found for the acetaminophen and the Caffeine.