Lower Cut-off Levels Research Articles

Utilization of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for noninvasive assessment of chronic kidney disease in type 2 diabetes

BackgroundsAccumulating data demonstrated that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) of diffusion-weighted magnetic resonance imaging (DWI) was a better correlation with kidney fibrosis, tubular atrophy progression, and a predictor of kidney function evolution in chronic kidney disease (CKD). ObjectivesWe aimed to assess the value of ΔADC in evaluating disease severity, differential diagnosis, and the prognostic risk stratification for patients with type 2 diabetes (T2D) and CKD. MethodsTotal 119 patients with T2D and CKD who underwent renal MRI were prospectively enrolled. Of them, 89 patients had performed kidney biopsy for pathological examination, including 38 patients with biopsy-proven diabetic kidney disease (DKD) and 51 patients with biopsy-proven non-diabetic kidney disease (NDKD) and Mix (DKD + NDKD). Clinicopathological characteristics were compared according to different ΔADC levels. Moreover, univariate and multivariate-linear regression analyses were performed to explore whether ΔADC was independently associated with estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR). The diagnostic performance of ΔADC for discriminating DKD from NDKD + Mix was evaluated by receiver operating characteristic (ROC) analysis. In addition, an individual's 2- or 5-year risk probability of progressing to end-stage kidney disease (ESKD) was calculated by the kidney failure risk equation (KFRE). The effect of ΔADC on prognostic risk stratification was assessed. Additionally, net reclassification improvement (NRI) was used to evaluate the model performance. ResultsAll enrolled patients had a median ΔADC level of 86 (IQR 28, 155) × 10−6 mm2/s. ΔADC significantly decreased across the increasing staging of CKD (P < 0.001). Moreover, those with pathological-confirmed DKD has a significantly lower level of ΔADC than those with NDKD and Mix (P < 0.001). It showed that ΔADC was independently associated with eGFR (β = 1.058, 95% CI = [1.002,1.118], P = 0.042) and UACR (β = −3.862, 95% CI = [-7.360, -0.365], P = 0.031) at multivariate linear regression analyses. Besides, ΔADC achieved an AUC of 0.707 (71% sensitivity and 75% specificity) and AUC of 0.823 (94% sensitivity and 67% specificity) for discriminating DKD from NDKD + Mix and higher ESKD risk categories (≥50% at 5 years; ≥10% at 2 years) from lower risk categories (<50% at 5 years; <10% at 2 years). Accordingly, the optimal cutoff value of ΔADC for higher ESKD risk categories was 66 × 10−6 mm2/s, and the group with the low-cutoff level of ΔADC group was associated with 1.232 -fold (95% CI 1.086, 1.398) likelihood of higher ESKD risk categories as compared to the high-cutoff level of ΔADC group in the fully-adjusted model. Reclassification analyses confirmed that the final adjusted model improved NRI. ConclusionsΔADC was strongly associated with eGFR and UACR in patients with T2D and CKD. More importantly, baseline ΔADC was predictive of higher ESKD risk, independently of significant clinical confounding. Specifically, ΔADC <78 × 10−6 mm2/s and <66 × 10−6 mm2/s would help to identify T2D patients with the diagnosis of DKD and higher ESKD risk categories, respectively.

Abstract 15710: Sex-Specific High-Sensitivity Cardiac Troponin Thresholds for Rule-Out of Non-ST-Elevation Myocardial Infarction

Introduction: The use of sex-specific cut-offs is recommended when high-sensitivity cardiac troponins (hs-cTn) are used for diagnosing acute myocardial infarction (MI). In this prospective, multi-centre study we evaluated the prognostic performance of sex-specific cut-offs for predicting low risk of MI in the Emergency Department (ED). Methods: 1895 patients (45% female) from two Norwegian centres where evaluated for potential non-ST-elevation myocardial infarction (NSTEMI). Cardiac troponins were tested with hs-cTnT (Roche) and hs-cTnI (Abbott and Siemens). Sex-specific differences in performance for a single-sample NSTEMI rule-out were investigated. Results: NSTEMI was diagnosed in 98 women (11.5%), 135 men (12.9%). Baseline hs-cTn concentrations were consistently lower in women compared to men, though not significantly so in the NSTEMI subgroup (Table 1). ROC curves showed consistent, though non-significantly, smaller AUCs for women compared to men with all three assays (Figure 1). Cut-offs for single sample rule-out aiming at &gt;97% or &gt;99% sensitivity for NSTEMI were evaluated. Women had consistently lower cut-off levels compared with men, with significantly lower (p &lt; 0.001) Youden index for all three assays at &gt;99% sensitivity and for the hs-cTnI assays at &gt;97% sensitivity (Table 2). Conclusions: Sex-specific cut-offs for single sample rule-out should be considered in accelerated diagnostic protocols for evaluation of NSTEMI.

Net reclassification index in comparison of prognostic value of disseminated intravascular coagulation diagnostic criteria by Japanese Society on Thrombosis and Hemostasis and International Society on Thrombosis and Haemostasis: a multicenter prospective cohort study

BackgroundWe compared the prognostic value of the Japanese Society on Thrombosis and Hemostasis (JSTH) disseminated intravascular coagulation (DIC) diagnostic criteria with that of the International Society on Thrombosis and Haemostasis (ISTH) DIC diagnostic criteria for 28-day in-hospital mortality.MethodsWe conducted a multicenter prospective cohort study involving two hematology departments, four emergency departments, and one general medicine department in Japan between August 2017 and July 2021. We assessed three ISTH DIC diagnostic criteria categories using low cutoff levels of D-dimer (low D-dimer), high cutoff levels of D-dimer (high D-dimer), and fibrinogen/fibrin degradation products (FDP) as fibrin-related markers. The main outcome was diagnosis-based category additive net reclassification index (NRI).ResultsA total of 222 patients were included: 82 with hematopoietic disorders, 86 with infections, and 54 with other diseases. The 28-day in-hospital mortality rate was 14% (n = 31). The DIC rates diagnosed by the JSTH, ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were 52.7%, 47.3%, 42.8%, and 27.0%, respectively. The overall category additive NRI by JSTH DIC diagnosis vs. ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were − 10 (95% confidence interval [CI]: −28 to 8, p = 0.282), − 7.8 (95% CI: −26 to 10, p = 0.401), and − 11 (95% CI: −26 to 3, p = 0.131), respectively.ConclusionsJSTH criterion showed the highest sensitivity for DIC diagnosis that did not improve but reflected the same prognostic value for mortality evaluated using ISTH DIC diagnosis criteria. This finding may help clinicians to use JSTH DIC criterion as an early intervention strategy in patients with coagulopathy.

Effects of Ambient Air Pollutants on Hospital Admissions among Children Due to Asthma and Wheezing-Associated Lower Respiratory Infections in Mysore, India: A Time Series Study.

Air pollutants are known to trigger asthma and wheezing-associated lower respiratory infections in children, but evidence regarding their effect on hospital admissions in India is limited. We conducted a time-series study over a period of five years to assess the role of ambient air pollutants in daily asthma-related hospital admissions in children in Mysore, India. Daily asthma and wheeze (associated with lower respiratory infections) admissions were modelled using a generalised additive model (GAM) to examine the non-linear effects and generalised linear models (GLM) for linear effects, if any. Models were adjusted by day of the week and lag days, with smooth terms for time, maximum temperature, and relative humidity, and they were stratified by sex and age group. Of the 362 children admitted, more than 50% were boys, and the mean age was 5.34 years (±4.66). The GAMs showed non-linear associations between NO2, PM2.5, and NH3. For example, a 10 µgm-3 (or 10%) increase in NO2 increased admissions by 2.42. These non-linear effects were more pronounced in boys. A linear effect was detected for PM10 with a relative risk (95% CI) of 1.028, 1.013, and 1.043 with admission. Further research is needed to explore whether these findings can be replicated in different cities in India. Air pollution needs to be controlled, and policies that focus on lower cut-off levels for vulnerable populations are necessary.

A multi-class drug and metabolite screen of 231 analytes by LC-MS/MS

The use of pain management drugs has been steadily increasing. As a result, labs are seeing an increase in patient samples that must be screened for a wide variety of drugs to prevent drug abuse and to ensure patient safety and adherence to their medication regiment. Therapeutic drug monitoring can be challenging due to the low cut-off levels, potential matrix interferences and isobaric drug compounds. To address these challenges, many drug testing facilities are turning to liquid chromatography coupled with mass spectrometry (LC-MS/MS) for its increased speed, sensitivity, and specificity. In this example, a method was developed for a multi-class drug and metabolite screen containing 231 compounds. There are many challenges one must consider when developing a large screening assay. Experiments performed included mobile phase considerations, sample diluent, isomer resolution, drug interferences, and instrumentation capabilities. Analytes were diluted in water and injected into a Shimadzu Nexera UHPLC equipped with an AB SCIEX API 4500™ MS/MS. Detection was performed using electrospray ionization in positive and negative ion modes using scheduled multiple reaction monitoring (MRM). During mobile phase investigations, it was found that methanol provided the best retention of early eluting analytes, such as morphine, oxymorphone, nicotine and norcotinine. Sample diluent was optimized to improve the peak shape of the early eluting compounds. Scan rates and retention time windows were optimized to ensure enough data points per peak were collected. 231 compounds with a final optimized separation gradient run time of 10 minutes, with a total cycle time of 12 minutes.

Subclinical cardiovascular disease and frailty risk: the atherosclerosis risk in communities study

BackgroundCardiovascular disease (CVD) is associated with a greater frailty risk, but it remains unknown if pathways that contribute to CVD are associated with the frailty risk. Thus, we aimed to investigate whether elevations in high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for those without known CVD at baseline are associated with a higher frailty risk.MethodsThis study used data from the Atherosclerosis Risk in Communities study. Cardiac biomarkers were measured from stored plasma samples collected at Visit 2 (1991–1993). Frailty was recorded at Visit 5 (2011–2013). Cox regression models were used to determine the association of cardiac biomarkers with frailty risk.ResultsOverall, 360/5199 (6.9%) participants aged 55.1 ± 5.1 years developed frailty during a median follow-up of 21.7 years. The incidence of frailty was significantly higher in participants with hs-cTnT ≥14 ng/L (vs. < 14 ng/L: 17.9% vs. 6.7%) or NT-proBNP ≥300 pg/ml (vs. < 300 pg/ml: 19.7% vs. 6.8%) (all P < 0.001). Comparing higher vs. lower cut-off levels of either hs-cTnT (14 ng/l) or NT-proBNP (300 pg/ml) demonstrated a greater than two-fold higher frailty risk, with hazard ratios (HRs) of 2.13 (95% confidence interval (CI): 1.130–4.01, P = 0.020) and 2.61 (95% CI: 1.28–5.33, P = 0.008), respectively. Individuals with both elevated hs-cTnT and NT-proBNP had a higher frailty risk than those without it (HR: 4.15; 95% CI: 1.50–11.48, P = 0.006).ConclusionsHigh hs-cTnT and NT-proBNP levels are strongly associated with incident frailty in the community-dwelling population without known CVD. Subclinical cardiac damage (hs-cTnT) and/or wall strain (NT-proBNP) may be the key pathway of CVD patients developing frailty. Detection of hs-cTnT and NT-proBNP may help for early screening of high-risk frailty and providing individualised intervention.Trial registrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT00005131.

Relationship Between Pituitary Siderosis and Endocrinological Disorders in Pediatric Patients with Beta-Thalassemia.

IntroductionExcess iron accumulation occurs mainly in organs such as reticuloendothelial cells, the pituitary gland, and the pancreas in beta-thalassemia because of blood transfusions. In the present study, it was aimed to investigate the relationship between T2* values on magnetic resonance imaging (MRI) and clinically diagnosed pituitary endocrinological disorders in children with thalassemia major.MethodsThis study enrolled patients diagnosed with beta-thalassemia at pediatric hematology outpatient clinics. In the study, in addition to the medical history of the patients, routinely performed tests, including hemoglobin electrophoresis, routine biochemical tests, and tests for pubertal development (follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, etc.), as well as iron deposition measured by hepatic MRI T2* (STAR) sequence, were retrospectively assessed. A total of 29 patients were enrolled.ResultsHypothyroidism was detected in 34.6% (9/26) of patients, short stature in 37% (10/27), and pubertal retardation in 50% (14/28) of the patients. There was no significant correlation between hypothyroidism and pituitary MRI T2* values. No significant correlation was found between laboratory parameters and pituitary MRI examination. Although the sensitivity of T2* levels could rise above 80%, their specificity remained low. This is one of the major limitations of the pituitary MR T2* study for the prediction of short stature. The best lower cut-off level of MR T2* to predict short stature was found 14.6 ms.ConclusionThe diagnostic specificity pituitary MR examination levels for short stature were detected as low. Thus, the clinical standardization and validation of pituitary MR T2* values examination are needed before clinical follow-up and multifaceted studies are needed.

Estimates of Non-Alcoholic Food-Derived Ethanol and Methanol Exposure in Human.

Food-derived alcohol is almost not in question due to its low concentration. Nevertheless, could it pose a problem for some risk groups and forensic cases? To answer this, we aimed to simultaneously evaluate ethanol and methanol ingredients of a variety of non-alcoholic foods in two different countries and estimate their possible health and forensic consequences. Alcohols in foods were analysed by headspace gas chromatography (HS-GC). Human average acute daily food consumptions and food-derived blood alcohol concentrations (BAC) were determined by using the data of the EFSA Nutrition Survey. Methanol and ethanol ingredients of similar foods varied between the two cities. Most foods produce higher methanol concentrations than the Maximum Allowable Dose Level (23 mg). Especially fruit juices lead to the critical level of ethanol for children (6.0 mg/kg bw). Based on the results, adult daily intake of selected food groups does not bear ethanol that exceeds the legal limit of BAC or the limit not allowed by the religious and does not lead to acute alcohol toxicity. But these low levels of ethanol and methanol consumed via non-alcoholic foods for life can raise the vulnerability to chronic health problems (cancer, liver cirrhosis, Alzheimer's disease, autism, ocular toxicity, alterations in fetal development), and may lead to positive ethanol metabolite results (e. g. Ethyl glucuronide) when a low cut-off level is used. Therefore, studies on the alcohol contents of various natural and processed non-alcoholic foods along with their effects on humans, and new regulations on labeling the food products and conscious food consumption are in particular importance. It would also be important to consider unintentional alcohol consumption via non-alcoholic foods in the evaluation of clinical and forensic cases.

30-Minute Delta Cortisol Post-ACTH Stimulation Test and Proposed Cut-Off Levels for Adrenal Insufficiency Diagnosis.

The ACTH stimulation test is used to diagnose adrenal insufficiency (AI). This study evaluated the diagnostic performance of serum delta cortisol from ACTH stimulation tests and determined appropriate cut-off levels of serum 30-minute delta cortisol for the diagnosis of AI, allowing a reduction in the number of 60-minute cortisol tests. A 6-year retrospective study in 471 patients was conducted. The performance of the serum delta cortisol in diagnosing AI was assessd using a multivariable logistic regression model and the area under ROC curves (AuROC). Both serum 30-minute and 60-minute delta cortisol demonstrated equally high diagnostic accuracy for AI (AuROC for LDT : 0.91 vs 0.90 ; HDT : 0.91 vs 0.92, respectively). The 30-minute delta cortisol test was chosen to develop proposed diagnostic cut-off levels due to its simplicity. The proposed lower cut-off level for 30-minute delta cortisol was Δ < 1.8 µg/dL for both LDT and HDT. The upper cut-off levels were Δ > 11.8 µg/dL for LDT and Δ > 10.5 µg/dL for HDT. These cut-off levels yielded high sensitivity and specificity > 90%. The 30-minute serum delta cortisol using the proposed cut-off levels provides diagnostic performance for AI equal to that of the 60-minute test and is more convenient, requires less time, less invasive and is cost-saving. 67 : 95-101, February, 2020.

Wexner score and quality of life in women with obstetric anal sphincter injury.

Obstetric anal sphincter injury causes anal incontinence in half of the women affected. However, most symptoms are mild. The objective of this study was to evaluate the prevalence of anal incontinence and quality of life in women at long term after delivery with obstetric anal sphincter injury. We also wanted to identify a relevant cutoff level of the Wexner score (also known as the Cleveland Clinic Incontinence Score) to indicate affected quality of life in these women. We performed a population-based questionnaire cohort study with prospective follow-up, including all women in Denmark with obstetric anal sphincter injury and one subsequent delivery between 1997 and 2005. We performed uni- and multivariate analyses and calculated the area under the ROC curve. In Denmark, 3885 women had an obstetric anal sphincter injury in their first delivery and a second delivery between 1997 and 2005 and no subsequent deliveries until 2010-2011. Questionnaires were sent to 3259 eligible women, and the response rate was 74.6%. In total, 2004 women could be included in the final analyses. Of these, 29.2% (n = 584) reported affected quality of life due to anal incontinence at long-term follow-up. We found that all symptoms of anal incontinence were associated with affected quality of life. The median age at follow-up was 40.3years. The area under the ROC curve was 0.96 (95% CI 0.95-0.97) with a sensitivity of 0.94 (95% CI 0.92-0.96) and a specificity of 0.85 (95% CI 0.84-0.87) corresponding to an optimal cutoff level of the Wexner score of ≥ 2 to identify women with affected quality of life due to anal incontinence. In women with obstetric anal sphincter injury, 29% reported affected quality of life due to anal incontinence at long-term follow-up, and we found a low Wexner score cutoff level of ≥ 2 to identify women with affected quality of life.

Replacing Iodine Staining with Size of Lesion: The Performance of Modified Reid Colposcopic Index.

Aim:This study of diagnostic accuracy aimed to assess the performance of authors’ proposing colposcopic index for detecting histological diagnosis of cervical intraepithelial neoplasia grade 2 or worse (CIN2 or worse). Methods:Retrospective analysis of data was carried out on medical records of women who underwent colposcopy in Rajavithi hospital from January 2007 to December 2014. The authors’ proposed score included the first 3 criteria of RCI (margin, color, vascular pattern) and replacing the last RCI criterion (iodine staining) with the detail of size and location of a lesion which was retrospectively retrieved from medical records. Total score for detecting any lesion was ranged from 0-8, similar to the RCI. Performance of the score was assessed for sensitivity, specificity, and positive and negative predictive values at every cut-off level. Results:Among 207 eligible women, 87 (42%) had CIN2 or worse. Cut-off level of score ≥ 6 had a sensitivity, specificity, and positive and negative predictive values of 54.0%,97.5%,94.0%,74.5%, respectively while cut-off value ≥ 2 had sensitivity , specificity, positive and negative predictive values of 94.2% ,55.8% ,60.7%, and 93.0%, respectively, for histological diagnosis of CIN 2 or worse. The area under ROC curve was 0.88. In women with type 3 T-zone, the area under ROC curve was 0.94 which was excellent. Conclusion:The performance of the colposcopic score that replaces iodine staining with the size and location of the lesion is good and practical. High cut-off level can be used in see and treat approach for high-grade squamous intraepithelial lesions. Low cut-off level may be used for omitting biopsy in case of low grade impression. This scoring system seems to have greater performance in womens with type 3 T- zone.

Screening with an ADHD-specific rating scale in preschoolers: A cross-cultural comparison of the Early Childhood Inventory-4.

The Early Childhood Inventory-4 (ECI-4) Hyperactivity-Impulsivity (HI) and Inattention (IA) subscales are screeners for attention-deficit/hyperactivity disorder (ADHD). There have been few studies of the screening properties of these subscales, particularly outside the United States. We investigated the classification accuracy of the parent and teacher versions of the HI and IA subscales and the cross-cultural validity of the cutoff values based on norms from a United States sample. The present study was part of the Norwegian Mother and Child Cohort Study. Parents and teachers rated boys (n = 332) and girls (n = 319) with the ECI-4 (mean Age 3.5 years). Interviewers who were blind to the ratings used the Preschool Age Psychiatric Assessment Interview to assign ADHD diagnoses. The ECI-4 HI and IA subscales showed acceptable accuracy in identifying ADHD in boys and girls (areas under the curve ranged from .67 to .85). In a multivariate regression analysis, the parent and teacher HI subscale scores significantly contributed to ADHD identification, but not the IA subscale scores. To achieve the necessary sensitivity to detect children with ADHD, lower cutoff levels than those specified by the United States ECI-4 norms were needed. For screening purposes, the parent and teacher ECI-4 showed acceptable accuracy in identifying preschoolers at risk for ADHD, and it may be sufficient to use the HI subscale scores. The suggested cutoff values provided by the United States ECI-4 norms had limited cross-cultural validity. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Multiple rounds of one sample versus two sample faecal immunochemical test-based colorectal cancer screening: a population-based study

Faecal immunochemical test (FIT)-based colorectal cancer screening requires successive rounds for maximum preventive effect. Advanced neoplasia can bleed intermittently and thus might be missed by single faecal sampling. Few studies have been done on two sample FIT (2-FIT) screening over multiple rounds. Therefore, we compared multiple rounds of one sample FIT (1-FIT) with 2-FIT screening with respect to participation, positive predictive value (PPV), diagnostic yield, and interval colorectal cancer. In this population-based study, a random selection of asymptomatic individuals aged 50-74 years in the Rotterdam-Rijnmond region, Netherlands, were invited by post for four rounds (every 2 years) of 1-FIT or 2-FIT screening. Key exclusion criteria were a history or colorectal cancer or inflammatory bowel disease, colon imaging in the previous 2 years, and life expectancy of less than 5 years. Per round, invitees received one or two FITs to sample either one or two consecutive bowel movements. OC-Sensor Micro (Eiken Chemical Co., Ltd, Japan) FITs were used by all participants, except the fourth round of screening for the 1-FIT cohort, for which participants used either an OC-Sensor or a FOB-Gold (Sentinel Diagnostics, Milan, Italy). A faecal haemoglobin cutoff concentration of 10 μg/g of faeces in at least one test was used for referral for colonoscopy. Between 2006 and 2015, of 10 008 invited individuals for the 1-FIT cohort, 9787 were eligible for inclusion, of whom 7310 participated at least once in four successive rounds. Of 3197 invited individuals for the 2-FIT cohort, 3131 were eligible for inclusion, and 2269 participated at least once in four successive rounds. In the 1-FIT screening cohort, 74·7% (7310 of 9787) of invitees participated at least once versus 72·5% (2269 of 3131) of invitees in the 2-FIT cohort (p=0·013). Among participants who participated at least once, the cumulative positivity rate over four rounds was 19·2% (1407 of 7310) for the 1-FIT cohort versus 28·5% (647 of 2269) for the 2-FIT cohort (p<0·0001). The cumulative PPV for advanced neoplasia was 33·0% (432 of 1308 colonoscopies) for the 1-FIT cohort versus 24·2% (147 of 607 colonoscopies) for the 2-FIT cohort (p<0·0001). The cumulative diagnostic yield of advanced neoplasia among invited individuals was 4·4% (432 of 9787) for 1-FIT versus 4·7% (147 of 3131) for 2-FIT screening (p=0·46)). FIT interval colorectal cancers were detected in eight (0·1%) of 7310 participants in the 1-FIT cohort and two (0·1%) of 2269 with 2-FIT screening (p=1·00). Four rounds of 2-FIT screening with a low faecal haemoglobin cutoff level did not result in a significant increase in diagnostic yield or a decrease in interval colorectal cancers compared with 1-FIT, despite higher colonoscopy demand. Therefore, 1-FIT colorectal cancer screening programmes should be preferred. None.

Predictive Values of Serum Uric Acid and Alanine-aminotransferase for Fatty Liver Index in Montenegrin Population.

SummaryBackgroundAlanine-aminotransferase (ALT) and uric acid cut-off levels used in non-alcoholic fatty liver disease (NAFLD) diagnosis are advised to be lowered. Due to contradictory results on the utility of both these biomarkers for NAFLD screening, we aimed to determine their cut-off levels that can be applied to Montenegrin population with the fatty liver disease.MethodsA total of 771 volunteers were enrolled. A fatty liver index (FLI) score ≥60 was used as proxy of NAFLD. The receiver operating characteristic curve analysis with the area under the curve (AUC) was used to determine the cut-off values of ALT and uric acid associated with FLI ≥60.ResultsALT was independent predictor of FLI in both men and women, whereas serum uric acid was its independent predictor only in women. Lower cut-off levels of ALT are associated with the increased prevalence of NAFLD [i.e., ALT was 19 IU/L (AUC=0.746, sensitivity 63%, specificity 72%, P<0.001) in women and 22 IU/L (AUC=0.804, sensitivity 61%, specificity 95%, P<0.001) in men]. The cut-off value for uric acid was 274 μmol/L (AUC=0.821, sensitivity 68%, specificity 82%, P<0.001) in women.ConclusionsLower cut-off levels of ALT in both genders, and serum uric acid in females, can be reliable predictors of the FLI.

Commentary on "The point-of-care Bilistick method has very short turn-around-time and high accuracy at lower cut-off levels to predict laboratory-measured TSB."

Commentary on "The point-of-care Bilistick method has very short turn-around-time and high accuracy at lower cut-off levels to predict laboratory-measured TSB."

Temporal Dynamics of Cerebral Blood Flow During the Acute Course of Severe Subarachnoid Hemorrhage Studied by Bedside Xenon-Enhanced CT

BackgroundCompromised cerebral blood flow (CBF) is a crucial factor in delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Repeated measurement of CBF may improve our understanding of the temporal dynamics following SAH. The aim of this study was to assess CBF at different phases of the acute course in poor-grade SAH patients, hypothesizing more pronounced disturbances at day 4–7, and that the initial level of CBF determines the following course of CBF.MethodsMechanically ventilated SAH patients were scheduled for bedside measurement of regional and global cortical CBF at day 0–3, 4–7, and 8–12, using xenon-enhanced computed tomography in a mobile setup. Patients were dichotomized depending on high or low initial global cortical CBF and cutoff level 30 ml/100 g/min.ResultsEighty-one patients were included, and 51 had measurements at day 0–3 and 4–7. In patients with high initial CBF, the level was unchanged at day 4–7; 37.7 (IQR 32.6–46.7) ml/100 g/min versus 36.8 (IQR 29.5–44.8). The low-CBF group showed a slight increase from 23.6 (IQR 21.0–28.1) ml/100 g/min to 28.4 (IQR 22.7–38.3) (P = 0.025), still markedly lower than the high-CBF group (P = 0.016). In the low-CBF group, CBF increased in patients who received hypertension, hypervolemia, and hemodilution (HHH therapy) but remained low in standard treated patients. For the subset of 27 patients examined also at day 8–12, the differences depending on initial CBF level were no longer statistically significant. Among patients with still low CBF at day 4–7, the proportion who had poor short-term outcome was 55% compared to 35% (n.s.) for patients with high CBF.ConclusionsCBF studied in poor-grade SAH patients at large did not show any statistically significant changes over time. Stratifying patients by high or low initial CBF and whether HHH therapy was given revealed an association between low initial CBF and persistent low CBF at day 4–7. These findings may be of clinical relevance in managing SAH patients with low early CBF.

The point-of-care Bilistick method has very short turn-around-time and high accuracy at lower cutoff levels to predict laboratory-measured TSB.

This study aimed to determine the accuracy of a point-of-care Bilistick method for measuring total serum bilirubin (TSB) and its turn-around-time (TAT) against hospital laboratory methods. This prospective study was carried out on 561 term-gestation jaundiced neonates in two Malaysian hospitals. Venous blood sample was collected from each neonate for contemporary measurement of TSB by hospital laboratories and Bilistick. TAT was the time interval between specimen collection and TSB result reported by each method. The mean laboratory-measured TSB was 194.85 (±2.844) µmol/L and Bilistick TSB was 169.37 (±2.706) µmol/L. Pearson's correlation coefficient was: r = 0.901 (p < 0.001). The mean difference of [laboratory TSB- Bilistick TBS] was 26.48 (±29.41) µmol/L. The Bland-Altman plots show that the 95% limits of agreement (-31.1577, 84.11772) contain 94.7% (=531/561) of the difference in TSB readings. Bilistick has a 99% accuracy and 100% sensitivity to predict laboratory TSB levels of ≥80 µmol/L and ≥360 µmol/L at lower Bilistick TSB levels of ≥55 and ≥315 µmol/L, respectively. TAT of Bilistick TSB (2.0 min) was significantly shorter than TAT (105 min) of laboratory TSB (p < 0.001). Bilistick has shorter TAT. The accuracy and sensitivity of Bilistick TSB for predicting laboratory TSB is high at lower cutoff levels.

Microfluidic electrochemical immunosensor for the trace analysis of cocaine in water and body fluids.

Quick but accurate testing and on-the-spot monitoring of cocaine in oral fluids and urine continues to be an important toxicological issue. In terms of drug testing, a number of devices have been introduced into the market in recent decades, notably for workplace inspection or roadside testing. However, these systems do not always fulfill the requirements in terms of reliability, especially when low cut-off levels are required. With respect to surface water, the presence of anthropogenic small organic molecules such as prescription and over-the-counter pharmaceuticals as well as illicit drugs like cannabinoids, heroin, or cocaine, has become a challenge for scientists to develop new analytical tools for screening and on-site analysis because many of them serve as markers for anthropogenic input and consumer behavior. Here, a modular approach for the detection of cocaine is presented, integrating an electrochemical enzyme-linked immunosorbent assay (ELISA) performed on antibody-grafted magnetic beads in a hybrid microfluidic sensor utilizing flexible tubing, static chip and screen-printed electrode (SPE) elements for incubation, recognition, and cyclic voltammetry measurements. A linear response of the sensor vs. the logarithm of cocaine concentration was obtained with a limit of detection of 0.15ng/L. Within an overall assay time of 25minutes, concentrations down to 1ng/L could be reliably determined in water, oral fluids, and urine, the system possessing a dynamic working range up to 1mg/L.

Impact of results-based financing on effective obstetric care coverage: evidence from a quasi-experimental study in Malawi

BackgroundResults-based financing (RBF) describes health system approaches addressing both service quality and use. Effective coverage is a metric measuring progress towards universal health coverage (UHC). Although considered a means towards achieving UHC in settings with weak health financing modalities, the impact of RBF on effective coverage has not been explicitly studied.MethodsMalawi introduced the Results-Based Financing For Maternal and Neonatal Health (RBF4MNH) Initiative in 2013 to improve quality of maternal and newborn health services at emergency obstetric care facilities. Using a quasi-experimental design, we examined the impact of the RBF4MNH on both crude and effective coverage of pregnant women across four districts during the two years following implementation.ResultsThere was no effect on crude coverage. With a larger proportion of women in intervention areas receiving more effective care over time, the overall net increase in effective coverage was 7.1%-points (p = 0.07). The strongest impact on effective coverage (31.0%-point increase, p = 0.02) occurred only at lower cut-off level (60% of maximum score) of obstetric care effectiveness. Design-specific and wider health system factors likely limited the program’s potential to produce stronger effects.ConclusionThe RBF4MNH improved effective coverage of pregnant women and seems to be a promising reform approach towards reaching UHC. Given the short study period, the full potential of the current RBF scheme has likely not yet been reached.

Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease.

Iron deficiency anemia (IDA) is a major problem in chronic kidney disease (CKD), causing increased mortality. Ferritin stores iron, representing iron status. Hepcidin binds to ferroportin, thereby inhibiting iron absorption/efflux. Inflammation in CKD increases ferritin and hepcidin independent of iron status, which reduce iron availability. While intravenous iron therapy (IIT) is superior to oral iron therapy (OIT) in CKD patients with inflammation, OIT is as effective as IIT in those without. Inflammation reduces predictive values of ferritin and hepcidin for iron status and responsiveness to iron therapy. Upper limit of ferritin to predict iron overload is higher in CKD patients with inflammation than in those without. However, magnetic resonance imaging studies show lower cutoff levels of serum ferritin to predict iron overload in dialysis patients with apparent inflammation than upper limit of ferritin proposed by international guidelines. Compared to CKD patients with inflammation, optimal ferritin levels for IDA are lower in those without, requiring reduced iron dose and leading to decreased mortality. The management of IDA should differ between CKD patients with and without inflammation and include minimization of inflammation. Further studies are needed to determine the impact of inflammation on ferritin, hepcidin and therapeutic strategy for IDA in CKD.