Acceptable Sensitivity Research Articles

Magnetic RuCo aerogels with enhanced peroxidase-like activity by regulation of boron and oxygen vacancies for colorimetric biosensing applications.

Metallic aerogels (MAs) are self-supported porous nanomaterials with excellent catalytic activity, which could be a promising candidate for high-performance nanozymes. The interface regulation by heteroatom and vacancies is an effective strategy for boosting the enzyme-mimicking activity. Herein, magnetic RuCo aerogels with doping of boron and oxygen vacancies were prepared by a one-pot spontaneous NaBH4 gelation method under a low temperature. The three-dimensional network structure with high specific surface area and interlinked pores of RuCo aerogels afford abundant active sites to facilitate the interaction with substrates. Moreover, the monolithic structure avoided conventional aggregation, thus enhancing stability during catalysis. Introducing elemtalboron and oxygen vacancies adjusted the electronic structure of RuCo aerogels to achieve enhanced enzyme-like performances. It is found that the RuCo aerogel nanozyme can mimic nature peroxidase, demonstrating their viable applications in the bioassay of H2O2 and glucose. The constructed glucose sensor possesses acceptable sensitivity and stability with a linear range of 0.002 ~ 5mM and a low detection limit (1.66μM). This work provides insights into the rational design of advanced nanozymes and paves the avenue for the applications of metallic aerogels in the bioassay field. A boron-doped RuCo bimetallic aerogel with rich oxygen vacancies was prepared by a facile self-assembly method under an ice bath. The unique physical and electronic structure of RuCo aerogel results in the improvement of the intrinsic peroxidaselike activity, and thus, a sensitive and robust colorimetric glucose sensor could be developed.

Development and validation of a LC-MS/MS method for analysis of vortioxetine in postmortem specimens. First data from an authentic case.

Vortioxetine is an antidepressant recently licensed in USA and EU for the treatment of major depressive disorder. Neither fatal case due to overdose nor data about postmortem concentrations on blood or other specimens have been reported. The aims of this study were the development and validation of a method for vortioxetine analysis by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) in postmortem samples and its application in an authentic case. The method was validated and applied on blood, vitreous humor, bile, brain, liver, kidney, and gastric content. After protein precipitation, the supernatant was directly injected into LC-MS/MS. Analysis was carried out by Multiple Reaction Monitoring (MRM) mode. The authentic case concerned a 38 years-old woman, affected by depression, who was found hanged at home. The method determined an acceptable sensitivity, selectivity, linearity, precision, and accuracy for all matrices. No interference was shown for all matrices. The matrices do not significantly reduce the peak intensity of vortioxetine. No carryover was shown. Toxicological analysis of the authentic case showed vortioxetine in blood (234 ng/ml), vitreous humor (10.5ng/ml), brain (490 ng/g), lung (479 ng/g), liver (3751 ng/g), kidney (798 ng/g), bile (2267 ng/ml) and gastric content (253 ng/ml). Our case suggests that even at blood concentrations of vortioxetine equal to 234 ng/ml, the subject was able to stage and carry out the hanging. Vortioxetine concentrations found in the other cadaveric samples (biological fluids, organs, and gastric content) may be helpful to evaluate further similar comparable cases.

Udayana COVID-19 Scoring System: a simple diagnosing aid for early detection of COVID-19

Coronavirus Disease-19 (COVID-19) is a highly transmittable disease. While the most common symptoms of COVID-19 include fever, cough, and fatigue, severe symptoms could feature acute respiratory distress syndrome and severe pneumonia. Reverse-transcription polymerase chain reaction (RT-PCR) remains the gold standard for diagnosing COVID-19. Unfortunately, it has high cost, extensive waiting time, and low availability in remote areas. Therefore, we developed the Udayana COVID-19 Scoring System (UCSS) for quick detection of COVID-19. This study aims to determine the cutoff score and measure the sensitivity and specificity of the UCSS. We conducted an observational cross-sectional study from June 2020 to July 2020. A questionnaire consisting of 3 objective and subjective scores assesses COVID-19 symptoms and risk factors. Participants were patients suspected of COVID-19 awaiting RT-PCR test results. The UCSS total score then compared with the RT-PCR test result and analyzed to determine the cutoff score, sensitivity, and specificity. 150 participants were included in this study (74 male, 49.3%; mean age 42 ± 15.7). The UCSS total score was significantly correlated with RT-PCR test result (p-value = 0.000). The receiving operator characteristic analysis showed an optimal cutoff score of 7, with a sensitivity of 72% and specificity of 71%. Therefore, the UCSS’ accuracy is at a moderate level. The UCSS showed acceptable sensitivity and specificity, and has the potential to be used as a diagnostic aid for COVID-19 early detection. Further study in diverse areas and larger sample size are needed.

A prospective evaluation of breast thermography enhanced by a novel machine learning technique for screening breast abnormalities in a general population of women presenting to a secondary care hospital.

Artificial intelligence-enhanced breast thermography is being evaluated as an ancillary modality in the evaluation of breast disease. The objective of this study was to evaluate the clinical performance of Thermalytix, a CE-marked, AI-based thermal imaging test, with respect to conventional mammography. A prospective, comparative study performed between 15 December 2018 and 06 January 2020 evaluated the performance of Thermalytix in 459 women with both dense and nondense breast tissue. Both symptomatic and asymptomatic women, aged 30-80 years, presenting to the hospital underwent Thermalytix followed by 2-D mammography and appropriate confirmatory investigations to confirm malignancy. The radiologist interpreting the mammograms and the technician using the Thermalytix tool were blinded to the others' findings. The statistical analysis was performed by a third party. A total of 687 women were recruited, of whom 459 fulfilled the inclusion criteria. Twenty-one malignancies were detected (21/459, 4.6%). The overall sensitivity of Thermalytix was 95.24% (95% CI, 76.18-99.88), and the specificity was 88.58% (95% CI, 85.23-91.41). In women with dense breasts (n = 168, 36.6%), the sensitivity was 100% (95% CI, 69.15-100), and the specificity was 81.65% (95% CI, 74.72-87.35). Among these 168 women, 37 women (22%) were reported as BI-RADS 0 on mammography; in this subset, the sensitivity of Thermalytix was 100% (95% CI, 69.15-100), and the specificity was 77.22% (95% CI, 69.88-83.50). Thermalytix showed acceptable sensitivity and specificity with respect to mammography in the overall patient population. Thermalytix outperformed mammography in women with dense breasts and those reported as BI-RADS 0.

Smartphone-based on-site detection of hydrogen peroxide in milk by using a portable ratiometric fluorescent probe

The on-site detection of hydrogen peroxide (H2O2) is important for maintaining food safety as the ingestion of H2O2 can lead to serious pathological conditions. However, most reported fluorescent probes require a fluorometer to ensure readable signal output and reliable detection result. Consequently, the fluorescent detection of H2O2 can be realized only within a standard laboratory setting. Herein, we report a novel supramolecular strategy that can successfully convert the typical off-on response to H2O2 into a ratiometric response, which allows the on-site detection of H2O2 when used in conjunction with a smartphone-based 3D-printed miniaturized testing system. This method has acceptable sensitivity, good anti-interference ability, and desirable accuracy compared to a standard detection method. More importantly, this portable ratiometric method can be used to detect H2O2 residue in commercial milk samples with the simple testing apparatuses.

Association of Renal Impairment with Interleukin-6 Levels on Clinical Outcomes among COVID-19 Patients in a Tertiary Government COVID-19 Referral Hospital.

The objective of the study is to determine the association of renal impairment (AKI or CKD) with IL-6 levels on mortality, intubation, and length of hospitalization among COVID-19 positive patients. This is a retrospective cohort study involving chart review of COVID-19 patients with IL-6 levels and admitted from May 2020 to April 2021. The KDIGO criteria was used for determining renal impairment. The subsequent data processing and analysis was carried out using the statistical software, Stata 13. A total of 1,120 charts were included with patients classified as having AKI (33%), CKD (14%), and no renal impairment (58%). Overall mortality and need for intubation were 27% and 30%, respectively, with average length of stay at 12 days. The IL-6 values were divided into low (0 to less than 51 pg/mL), intermediate (51 to 251 pg/mL), and high (greater than 251 pg/mL) tertiles, which showed acceptable sensitivity and specificity for mortality and need for intubation. The presence of renal impairment (CKD or AKI) with increasing IL-6 levels had an effect of increasing risk of adverse outcomes; however, within tertile groups, the presence of renal impairment did not significantly change the risk of adverse outcomes. The tertile groups have acceptable sensitivity and specificity for clinical use.

Polynitro-functionalized 4-phenyl-1H-pyrazoles as heat-resistant explosives.

A new class of heat-resistant explosives was synthesized by coupling N-methyl-3,5-dinitropyrazole with polynitrobenzene moieties through carbon-carbon bonds. Simple Pd(0)-based Suzuki cross-coupling reactions between N-methyl-4-bromo-3,5-dinitropyrazole and 4-chloro/3-hydroxy-phenylboronic acid followed by nitration, amination and oxidation lead to the formation of C-C connected penta-nitro energetic derivatives 6 and 10. Various other energetic derivatives, such as amino (5), azido (7), nitramino (8) and energetic salts (11-14), were also explored to fine-tune their properties. All the compounds were thoroughly characterized using IR, NMR [1H, 13C{1H}], differential scanning calorimetry (DSC), elemental analysis, and HRMS studies. Compounds 5, 10 and 13 were further characterized through 15N NMR, and the crystal structures of 6 and 14 were confirmed through single-crystal X-ray diffraction studies. The physicochemical and energetic properties of all the energetic compounds were explored. Most of the synthesized compounds demonstrated high thermal stability (decomposition temperature Tdec > 250 °C), among which compounds 5 and 6 showed excellent thermal stability, having decomposition temperatures above 300 °C. The excellent thermal stability, acceptable sensitivity and good energetic properties of compounds 5, 6, 10 and 13 make them promising heat-resistant explosives. Furthermore, these compounds were found to be more thermally stable than the known N-methyl-3,5-dinitropyrazole-based and C-N coupled 3,4,5-trinitrobenzene-azole-based energetic compounds.

The possible relation between temporal muscle mass and glioblastoma multiforme prognosis via sarcopenia perspective.

The optimal sarcopenia measurement method in patients with a diagnosis of glioblastoma multiforme (GBM) is unknown. It has been found that temporal muscle thickness (TMT) may reflect sarcopenia and be associated with survival, but the relationship between temporal muscle area (TMA) and GBM prognosis has never been evaluated before. The primary outcome of the study was to evaluate the relationship between TMA/TMT and overall survival (OS) time in newly diagnosed GBM patients. The data of patients who presented at the university hospital between January 2009 and January 2019 with a confirmed diagnosis of glioblastoma multiforme at the time of diagnosis were analyzed retrospectively. Temporal muscle thickness and TMA were measured retrospectively from preoperative MRIs of patients diagnosed with GBM. Due to the small number of patients and the failure to determine a cut-off value with acceptable sensitivity and specificity using ROC analysis, the median values were chosen as the cut-off value. The patients were basically divided into two according to their median TMT (6.6 mm) or TMA (452 mm2 ) values, and survival analysis was performed with the Kaplan-Meier analysis. The median TMT value was 6.6 mm, and the median TMA value was 452 mm2 . The median overall survival (OS) was calculated as 25.8 months in patients with TMT < 6.6 mm, and 15.8 months in patients with TMT ≥ 6.6 mm (p = 0.29). The median overall survival (OS) of patients with TMA < 452mm2 was 26.3 months, and the group with TMA ≥ 452mm2 was 14.6 months (p = 0.06). The median disease-free survival was 18.3 months (%95 CI: 13.2-23.4) in patients with TMT < 6.6mm, while mDFS was 10.9 (%95 CI: 8.0-13.8) months in patients with TMT ≥ 6.6mm (p = 0.21). The median disease-free survival was found to be 21.0 months (%95 CI: 15.8-26.1) in patients with TMA < 452 mm2 and 10.5 months (%95 CI: 7.8-13.2) in patients with TMA ≥ 452 mm2 (p = 0.018). No association could be demonstrated between TMT or TMA and OS of GBM patients. In addition, the median DFS was found to be longer in patients with low TMA. There is an unmet need to determine the optimal method of sarcopenia in GBM patients.

Transcriptomics secondary analysis of severe human infection with SARS-CoV-2 identifies gene expression changes and predicts three transcriptional biomarkers in leukocytes

SARS-CoV-2 is the causative agent of COVID-19, which has greatly affected human health since it first emerged. Defining the human factors and biomarkers that differentiate severe SARS-CoV-2 infection from mild infection has become of increasing interest to clinicians. To help address this need, we retrieved 269 public RNA-seq human transcriptome samples from GEO that had qualitative disease severity metadata. We then subjected these samples to a robust RNA-seq data processing workflow to calculate gene expression in PBMCs, whole blood, and leukocytes, as well as to predict transcriptional biomarkers in PBMCs and leukocytes. This process involved using Salmon for read mapping, edgeR to calculate significant differential expression levels, and gene ontology enrichment using Camera. We then performed a random forest machine learning analysis on the read counts data to identify genes that best classified samples based on the COVID-19 severity phenotype. This approach produced a ranked list of leukocyte genes based on their Gini values that includes TGFBI, TTYH2, and CD4, which are associated with both the immune response and inflammation. Our results show that these three genes can potentially classify samples with severe COVID-19 with accuracy of ∼88% and an area under the receiver operating characteristic curve of 92.6--indicating acceptable specificity and sensitivity. We expect that our findings can help contribute to the development of improved diagnostics that may aid in identifying severe COVID-19 cases, guide clinical treatment, and improve mortality rates.

Comparison of laboratory methods for identifying members of the family Mycobacteriaceae.

The introduction of a method based on matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-ToF mass spectrometry) into the practice of laboratories significantly increased the identification of acid-resistant bacteria (ARB). Seventy-four nontuberculous mycobacteria (NTM) cultures identified by deoxyribonucleic acid (DNA) hybridization, polymerase chain reaction, Sanger sequencing, and MALDI-ToF mass spectrometry. Analysis of the identification results obtained by the methods of DNA hybridization and Sanger sequencing showed a complete match only for 67.6% of samples of the total number of cultures included in the study. The partial match of the identification results was 68.9%. When comparing the results of the identification of 74 samples obtained by MALDI-ToF mass spectrometry to the results obtained by sequencing, full match of identification of Mycobacterium chimaera/Mycobacterium intracelullare, Mycobacterium porcinum/Mycobacterium peregrinum and Mycobacterium tuberculosis complex was found for 90.5% of the samples; the partial match of the results - for 4.1%.. DNA hybridization as a method for identifying NTM showed acceptable sensitivity and specificity; however, for mass spectrometry, a significantly higher sensitivity with comparable specificity was determined. Mass spectrometry is an important element in the modern system of species identification of microorganisms. The optimization of sample preparation protocols and assessment of the impact on the identification of new techniques of cultivation of microorganisms can significantly improve the quality of identification of microorganisms from the ARB group. In this case, accurate species identification and the development of algorithms for its application will improve the diagnosis of diseases caused by ARB.

HEART versus GRACE Score in Predicting the Outcomes of Patients with Acute Coronary Syndrome; a Systematic Review and Meta-Analysis.

Several scoring systems have been proposed to predict the outcomes of patients with ischemic heart disease. Global Registry of Acute Coronary Events (GRACE) and History, ECG, Age, Risk Factors, and Troponin (HEART) scores are two of the more widely used risk prediction tools in patients with acute coronary syndrome (ACS). The present systematic review and meta-analysis aimed to compare the value of GRACE and HEART scores in the outcome prediction of ACS patient. The online databases of Medline, Embase, Web of Science, and Scopus were search until September 2022 for articles directly comparing GRACE and HEART scores value in prediction of outcome in patients with ACS. GRACE score cut-offs were categorized into two groups of less than and equal to 100 and more than 100, and HEART score cut-offs were categorized into three groups of less than 4, equal to 4, and more than 4. Investigated outcomes were major adverse cardiovascular events (MACE), acute myocardial infraction (AMI) and all-cause mortality. 25 articles were included. The sensitivity and specificity of the GRACE score for prediction of MACE were 0.96 and 0.26 for cut-offs of ≤ 100, and 0.58 and 0.69 for cut-offs of >100, respectively. The sensitivity and specificity of the HEART score for prediction of MACE were 0.99 and 0.16 for cut-offs less than 4, 0.93 and 0.47 for equal to 4, and 0.77 and 0.78 for cut-offs greater than 4. GRACE score was shown to be predictive of AMI with sensitivity and specificity of 0.95 and 0.29, respectively. The analysis for the value of HEART score in the prediction of AMI a sensitivity and specificity of 0.94 and 0.48, respectively. The risk scores were not found to be suitable predictors of all-cause mortality. The results demonstrated the low specificity of GRACE and HEART scores in predicting the MACE, AMI and all-cause mortality, irrespective of the utilized cut-off. Considering the acceptable sensitivity of two scores in predicting the MACE and AMI, these scores were more suitable to be used as a rule-out tool for identification of ACS patients with low risk of developing adverse outcomes.

Correlation analysis of serum levels of H19 and CRP levels and ulcerative colitis.

To elucidate clinical applications of detecting serum levels of H19 and CRP in predicting the severity of ulcerative colitis (UC). Two hundred UC patients were recruited, and classified to mild/moderate group and severe group according to the Truelove-Witts grading system. Serum levels of H19 and CRP in UC patients were detected by turbidimetric inhibition immuno assay and qRT-PCR. Differences in serum levels of H19 and CRP between mild/moderate group and severe group were analyzed. By plotting ROC curves, the diagnostic potentials of H19 and CRP in UC were evaluated. Kappa conformance test was conducted to validate the conformance of detecting serum levels of H19 and CRP to clinical diagnosis of UC. Serum levels of H19 and CRP were higher in UC patients of severe group than those of mild/moderate group. Their levels were both positively correlated to the severity of UC. High sensitivity (83.3%) and specificity (80.0%), as well as the maximum Youden index (0.633) were obtained at the cut-off value for H19 level of 2.755, and AUC was 0.8835. Meanwhile, Kappa coefficient (k) was 0.760 at the cut-off value for H19 level of 2.755, showing a high conformance to clinical diagnosis of UC. In addition, acceptable sensitivity (68.49%) and high specificity (85.83%), as well as the maximum Youden index (0.543) were obtained at the cut-off value for CRP level of 6.390 mg/L, and AUC was 0.8018. k was 0.435, showing an acceptable conformance to clinical diagnosis of UC based on serum level of CRP. Serum levels of H19 and CRP increase with the deterioration of UC. Detecting their serum levels has a consistent result to clinical diagnosis of UC, with a superior performance of H19 than that of CRP.

Synthesis and characterization of pyrochlore-type lanthanum cerate nanoparticles: Electrochemical determination of antibiotic drug sulfadiazine in biological and environmental samples

In recent eras, antibiotic drugs are essential for humans and the veterinary health system. However, the improper discarding of their residues are simply contaminating the food products and environmental samples. Here, pyrochlore-type lanthanum cerate nanoparticles (LaCe NPs) were prepared through a simple co-precipitation route and used as effective electrocatalyst for the detection of antibiotic drug sulfadiazine (SDZ). The structural investigations of prepared material were carried out using XRD, FT-IR, XPS, SEM, HR-TEM, and EDX along with Elemental mapping analysis, which confirm the good formation of pyrochlore type LaCe in the form of particle-like morphology with well-crystalline nature. A nanosized LaCe revealed superior electrochemical activity towards SDZ owing to the large surface area, facilitating mass and ionic transport and chemical stability phenomena. The as-prepared LaCe NPs demonstrated an excellent electrochemical performance towards SDZ determination with a low LOD (50 nM), a wide dynamic range of 0.04–1525 μM, and an acceptable sensitivity of 1.92 μA μM−1 cm−2. Furthermore, the LaCe NPs/GCE revealed excellent reproducibility, storage stability, and selectivity parameters. Additionally, the proposed sensor achieves a good SDZ recovery in milk and human urine samples. The results strongly suggest that the rare earth metal oxide of lanthanum cerate is an efficient catalyst for portable detection of SDZ.

Relationship between raltegravir trough plasma concentration and virologic response and the impact of therapeutic drug monitoring during pregnancy.

Limited data is available on raltegravir (RAL) pharmacokinetics during pregnancy and the value of therapeutic drug monitoring (TDM) in pregnancy is unknown. This study aims to describe RAL trough plasma concentrations (Ctrough) during pregnancy and review the impact of RAL TDM on outcomes. Women from the prospective mother-infant HIV cohort of Mother and Children's Infectious Diseases Center who received RAL during their pregnancy between 2011-2020 were included. TDM reports were reviewed and Ctrough values estimated when possible, using historical RAL half-lives. We included 76 pregnant women of which 47 underwent TDM. We observed a significant association between virological response and Ctrough (p-value .034) with an increase of 0.1mg/L corresponding to a 2.96 reduction in the risk of having a detectable viral load. The results indicated that in pregnant women a RAL Ctrough threshold of 0.04mg/L has a higher specificity (75%) as compared to our current Ctrough target value of 0.02mg/L (25%) and an acceptable sensitivity (77%). No significant differences were observed between Ctrough at each trimester. When comparing pregnancies with and without TDM, no statistically significant differences were observed in the virologic response during pregnancy and at delivery, or with the need for triple antiretroviral prophylaxis in newborns. An association between RAL Ctrough and viral load was observed and achieving a RAL Ctrough of 0.04mg/L or greater is a predictor of virologic response in pregnant women. The impact of TDM in pregnancy, however, could not be demonstrated.

Simultaneous screening and classification of diabetic retinopathy and age-related macular degeneration based on fundus photos-a prospective analysis of the RetCAD system.

To assess the accuracy of an artificial intelligence (AI) based software (RetCAD, Thirona, The Netherlands) to identify and grade age-related macular degeneration (AMD) and diabetic retinopathy (DR) simultaneously based on fundus photos. This prospective study included 1245 eyes of 630 patients attending an ophthalmology day-care clinic. Fundus photos were acquired and parallel graded by the RetCAD AI software and by an expert reference examiner for image quality, and staging of AMD and DR. Adjudication was provided by a second expert examiner in case of disagreement between the AI software and the reference examiner. Statistical analysis was performed on eye-level and on patient-level, by summarizing the individual image level-gradings into and eye-level or patient-level score, respectively. The performance of the RetCAD system was measured using receiver operating characteristics (ROC) analysis and sensitivity and specificity for both AMD and DR were reported. The RetCAD achieved an area under the ROC (Az) of 0.926 with a sensitivity of 84.6% at a specificity of 84.0% for image quality. On image level, the RetCAD software achieved Az values of 0.964 and 0.961 with sensitivity/specificity pairs of 98.2%/79.1% and 83.9%/93.3% for AMD and DR, respectively. On patient level, the RetCAD software achieved Az values of 0.960 and 0.948 with sensitivity/specificity pairs of 97.3%/73.3% and 80.0%/90.1% for AMD and DR, respectively. After adjudication by the second expert examiner sensitivity/specificity increases on patient-level to 98.6%/78.3% and 100.0%/92.3% for AMD and DR, respectively. The RetCAD offers very good sensitivity and specificity compared to manual grading by experts and is in line with that obtained by similar automated grading systems. The RetCAD AI software enables simultaneous grading of both AMD and DR based on the same fundus photos. Its sensitivity may be adjusted according to the desired acceptable sensitivity and specificity. Its simplicity cloud base integration allows cost-effective screening where routine expert evaluation may be limited.

1165. Ascertainment of anthropometric thresholds to identify glucose intolerance in HIV-endemic African populations: results from a population-based survey in rural KwaZulu-Natal, South Africa

Abstract Background Improved screening and diagnostic algorithms are needed to achieve 2030 targets proposed by the Global Diabetes Compact. We sought to explore anthropometric thresholds to optimally screen and refer individuals for glucose intolerance testing in an HIV-endemic rural South African population. Methods We analyzed data from the cross-sectional Vukuzazi study that enrolled adults living in rural KwaZulu-Natal, South Africa. We assessed screening thresholds for waist circumference (WC), body mass index (BMI), and waist hip ratio (WHR) to detect glucose intolerance (hemoglobin A1c &amp;gt;6.5%) using weighted, non-parametric ROC regression analyses. We then assessed the diagnostic validity of traditional obesity thresholds, explored optimal thresholds for the South African population, and fit models stratified by sex, age, and HIV. Results In the total cohort (n=17,868), the prevalence of glucose intolerance was 7.8% (95% CI 7.4–8.2) and HIV prevalence was 33.8% (95% CI 33.1-34.5). WC outperformed BMI and WHR in detecting glucose intolerance (males p&amp;lt; 0.001; females p&amp;lt; 0.001). Whereas guideline WC thresholds for females performed well for glucose intolerance (Sensitivity 91% [95% CI 89.5-92.5], positive predictive value [PPV] 14.9%), substantially lower thresholds were needed to achieve acceptable sensitivity and positive predictive values among men. We found significant sub-groups effects by sex and age, but HIV status did not affect WC thresholds for identifying glucose intolerance. Conclusion Waist circumference improves anthropometric screening for glucose intolerance in South Africa. Guideline-based WC thresholds are appropriate for females, but male-derived WC cutoffs were optimized at lower thresholds. HIV did not affect the performance of WC thresholds in either sex. In rural African populations, thresholds that maximize specificity and PPV for efficient resource allocation may be preferred. Disclosures All Authors: No reported disclosures.

A Platform analytical method for intact polysorbates in protein-containing biopharmaceutical products via HPLC-CAD

Polysorbate (also known as “Tween”) 80 (PS80) is the most common surfactant in biopharmaceuticals. Here, we report a sensitive, and specific platform analytical method using reversed-phase high performance liquid chromatography employing a charged aerosol detector (HPLC-CAD), that offers the ability to quantitate intact PS80 and can distinguish between low recovery of PS80 and degraded PS80 by also monitoring several PS80 degradants which offers multiple improvements over various previously reported polysorbate analytical methods. The method employs protein/monoclonal antibody precipitation and is designed to be a quality control (QC) lab-friendly method. The method is distinguishable from other published methods because the quantification of the PS80 mono-esters is free from interference from known PS80 degradants. The method has demonstrated acceptable accuracy, precision, specificity, and sensitivity through qualification studies. The specificity afforded by the method allows for employment in forced degradation studies to discern kinetic information. Lastly, the method also has promising applications with other polysorbates (PS60, PS40, and all-laurate PS20) and shows acceptable performance with several types of biopharmaceutical proteins.

Colon capsule endoscopy following incomplete colonoscopy in routine clinical settings.

Colon capsule endoscopy (CCE) was introduced in our department on two indications; following incomplete colonoscopy as an alternative to CT colonography, and in patients with a history of incomplete colonoscopy as an alternative to anesthesia-assisted (AA) colonoscopy. We aimed to compare the quality of CCE, defined by completion rate and polyp detection rate (PDR), with that of CT colonography and AA colonoscopy, respectively. Patients referred for CCE from May 2020 until November 2021 were consecutively included in this prospective cohort study. Demographics, indication and CCE outcomes were registered from the electronic patient record. Completion rate and PDR in CCE as an alternative to CT colonography were compared with those of a historical cohort undergoing CT colonography following incomplete colonoscopy. Completion rate and PDR in CCE as an alternative to AA colonoscopy were compared with those of a time true parallel cohort undergoing AA colonoscopy. In 65 patients undergoing CCE, 36 (57%) were referred as an alternative to CT colonography. The completion rate in this group was 44% compared to 96% in CT colonography (p < 0.001). The PDR in complete CCE in this group was 75% in CCE compared to 20% in CT colonography (p < 0.001). The remaining 27 (43%) of the sample were referred for CCE as an alternative to AA colonoscopy. The completion rate in this group was 33% compared to 100% in AA colonoscopy (p < 0.001). The PDR in complete CCE in this group was 78% in CCE compared to 35% in AA colonoscopy (p = 0.013). The completion rate of CCE following incomplete colonoscopy is inferior to that of CT colonography and AA colonoscopy. The PDR of CCE was high, indicating an acceptable sensitivity in complete investigations, but in our settings the completion rate of CCE on this indication is unacceptably low. NCT04307901 (ClinicalTrials.gov, March 13, 2020).

Determining the amyloid PET and CSF inclusion criteria for the SKYLINE secondary prevention study with gantenerumab

AbstractBackgroundSKYLINE is a secondary prevention study in Alzheimer's disease (AD) enrolling amyloid‐positive, cognitively normal (CN) individuals at risk for clinical AD between 60–80 years and treating them with gantenerumab or placebo for 4 years. There is no gold standard for determining amyloid positivity for this purpose. Thresholds for amyloid positivity used in trials in symptomatic AD may be suboptimal in a secondary prevention setting, where amyloid positivity prevalence is lower. We compared various amyloid‐positive definitions in a CN elderly population based on how well they enrich for clinical progression over 4 years and operational feasibility.MethodFour cohorts (ADNI, BioFINDER‐1, AIBL, and HABS) were used to explore the relationship between amyloid PET visual read, centiloid values and CSF pTau/Abeta42 values in a CN population. For amyloid PET, we compared visual read with centiloid thresholds by evaluating the amyloid positivity prevalence, magnitude and variability of endpoint progression, and positive and negative predictive value (PPV and NPV). Operational advantages of CSF motivated a comparison of elevated CSF pTau/Abeta42 thresholds with amyloid PET. We interrogated which CSF thresholds were robust to preanalytical differences, had a high PPV and NPV compared with amyloid PET, and resulted in an acceptable degree of cognitive decline and variability.ResultHigher centiloid thresholds (≥40 CL) showed good agreement with visual read, but visual read resulted in a lower coefficient of variation (CV) for change from baseline in PACC5, the primary endpoint in SKYLINE (CV=118–210 vs. CV=150–336). An elevated CSF pTau/Abeta42 threshold resulted in a similar amyloid positivity prevalence to amyloid PET (14–17% vs. 10–20%), had acceptable NPV (95–97%), PPV (69–87%), sensitivity (71–82%), and specificity (95–98%) for visual read, and resulted in a similar CV for change from baseline in PACC5.ConclusionThere is no gold standard for determining the optimal amyloid positivity threshold in a secondary prevention trial. Determining patients to be amyloid‐positive if they are amyloid PET visual read‐positive or have elevated CSF pTau/Abeta42 offers not only operational advantages but also likely results in a trial population that has an acceptable level of endpoint progression and variability over the trial duration.

Psychometric Properties of the Enfranchisement Scale of the Community Participation Indicators

<h3>Research Objectives</h3> The content of most community participation measures is limited to participation in community activities, and lacks the personal and contextual elements that are critical to the construct of participation. The Enfranchisement scale of the Community Participation Indicators measures the sense of belonging and inclusion that is missing from other measures. However, the psychometric properties necessary for use in clinical trials have not been established. Our objective was to examine the construct validity, sensitivity to change, and cut points of this measure. <h3>Design</h3> We examined construct validity using cross-sectional data from a sample of adults with mixed disabilities. We examined cut points and sensitivity to change using longitudinal data in a sample of adults with traumatic brain injury (data were collected at two time points, 3 months apart). To examine construct validity, we examined correlations between the Enfranchisement scale and measures of participation, activity, and impairment. To examine cut points, we used the prospective dataset and used the software SAS PROC Logistic and the macro %ROCPlot. To examine sensitivity to change, we calculated minimum detectable change (MDC) and minimal clinically important difference (MCID). <h3>Setting</h3> Assessments were administered in community settings. <h3>Participants</h3> The cross-sectional cohort included 604 adults with disabilities; the longitudinal cohort included 44 adults with brain injury. <h3>Interventions</h3> N/A. <h3>Main Outcome Measures</h3> The Enfranchisement Scale has a Control subscale and an Importance subscale. <h3>Results</h3> Both subscales were strongly associated with participation (Control: r=.56; Importance: r=.52) and weakly associated with cognition (Control: r=.03; Importance: r=.03). We found a cut point of 44 on the Control subscale (AUC=.75) and a cut point of 39 on the Importance subscale (AUC=.81). On both subscales, we found a MDC of 8 and a MCID of 5. <h3>Conclusions</h3> We found evidence of convergent and discriminant validity to support the use of the scale. Cut points resulted in good classification accuracy, providing support for their reliability. We found acceptable sensitivity to change. <h3>Author(s) Disclosures</h3> The authors have no conflicts of interest to declare.