Serum vancomycin levels predict the short-term adverse outcomes of peritoneal dialysis–associated peritonitis

Background: The role of monitoring serum vancomycin levels during treatment of peritoneal dialysis (PD)–associated peritonitis is controversial. Substantial inter-individual variability may result in suboptimal serum levels despite similar dosing of vancomycin. The published predictors of suboptimal serum vancomycin levels remain limited. Methods: Data were retrospectively collected from 541 patients on continuous ambulatory peritoneal dialysis between 1 January 2018 and 31 December 312019. For gram-positive cocci and culture-negative peritonitis, we adopted a vancomycin administration and monitoring protocol. Short-term adverse outcomes of PD-associated peritonitis, including transfer to haemodialysis, death, persistent infection beyond planned therapy duration and relapse, were observed. The association between trough serum vancomycin levels and short-term adverse outcomes was evaluated. Results: Intraperitoneal vancomycin was used in 61 gram-positive cocci or culture-negative peritonitis episodes in 56 patients. Fourteen episodes of short-term adverse outcomes occurred in 12 patients, whose average trough serum vancomycin levels on day 5 of treatment were significantly lower than those who didn’t experience any adverse outcomes (8.4 ± 1.7 vs 12.5 ± 4.3 mg/L, p = 0.003). In gram-positive cocci or culture-negative peritonitis patients, those with higher day 5 trough serum vancomycin levels had a lower risk of short-term adverse outcomes (odds ratio: 0.6, 95% confidence interval: 0.4 to 0.9, p = 0.011). Receiver operating charecteristic curve (ROC) analyses showed that the day 5 trough serum vancomycin levels diagnostic threshold value for short-term adverse outcomes was 10.1 mg/L. After adjustments for gender, exchange volume and residual kidney function (RKF), baseline higher peritoneal transport was associated with a suboptimal (<10.1 mg/L) day 5 serum vancomycin level. Conclusions: Serum vancomycin levels are correlated with short-term adverse outcomes of PD-associated peritonitis, and higher peritoneal solute transport status is associated with suboptimal trough serum vancomycin levels on day 5.

Evaluation of the Efficacy and Threshold of Serum Anti-mullerian Hormone (AMH) Levels for Diagnosis and Prediction of Polycystic Ovary Syndrome (PCOS) Among Indian Women.

Purpose: PCOS women exhibit higher levels of AMH and has been proposed to add value to diagnosis of PCOS incase ambiguity. However, variable cutoffs of AHM for PCOS prediction have been reported. This study was designed to determine diagnostic threshold of serum AMH levels and its correlation with clinical, hormonal and ultrasonographic parameters among women with PCOS.Materials: In this prospective study, 113 women with PCOS as per Rotterdam criteria 2003 and 75 normo-ovulatory women were included. Clinical, biochemical, hormonal and sonographic assessment in addition to serum AMH levels were determined using standard methodology.Results: Mean age was comparable (23.43±3.42vs.24.21±3.18 years) between cases and controls. The mean number of menstrual cycles per year were lower while as mean BMI, FG score, and serum testosterone were higher in cases than controls (p<0.05). The mean serum AMH level was significantly higher in PCOS group (7.84±3.67vs. 3.23 ±1.56 ng/mL) than controls. The serum AMH levels showed a positive correlation(p<0.05) with LH/FSH ratio (r = 0.206, p = 0.029), number of ovarian follicles(r=0.461) and volume,(r=0.521), but no correlation significant with age and BMI. As per receiver operating characteristic (ROC) curve, cut-off was worked out to be 3.76 ng/mL with 86.7% sensitivity and 62.7% specificity. Conclusion: Serum AMH levels correlate positively with PCOM among PCOS women and may be a potent diagnostic marker of ovarian dysfunction either alone or in conjunction with other tools to ensure timely diagnosis and early treatment of the disorder.

Latent subtypes of manic and/or irritable episode symptoms in two population-based cohorts

Background Mood disorders are characterised by pronounced symptom heterogeneity, which presents a substantial challenge both to clinical practice and research. Identification of subgroups of individuals with homogeneous symptom profiles that cut across current diagnostic categories could provide insights in to the transdiagnostic relevance of individual symptoms, which current categorical diagnostic systems cannot impart. Aims To identify groups of people with homogeneous clinical characteristics, using symptoms of manic and/or irritable mood, and explore differences between groups in diagnoses, functional outcomes and genetic liability. Method We used latent class analysis on eight binary self-reported symptoms of manic and irritable mood in the UK Biobank and PROTECT studies, to investigate how individuals formed latent subgroups. We tested associations between the latent classes and diagnoses of psychiatric disorders, sociodemographic characteristics and polygenic risk scores. Results Five latent classes were derived in UK Biobank (N = 42 183) and were replicated in the independent PROTECT cohort (N = 4445), including ‘minimally affected’, ‘inactive restless’, active restless’, ‘focused creative’ and ‘extensively affected’ individuals. These classes differed in disorder risk, polygenic risk score and functional outcomes. One class that experienced disruptive episodes of mostly irritable mood largely comprised cases of depression/anxiety, and a class of individuals with increased confidence/creativity reported comparatively lower disruptiveness and functional impairment. Conclusions Findings suggest that data-driven investigations of psychopathological symptoms that include sub-diagnostic threshold conditions can complement research of clinical diagnoses. Improved classification systems of psychopathology could investigate a weighted approach to symptoms, toward a more dimensional classification of mood disorders.

Fractals disruption as the footprint of subthreshold depressive symptoms on the heart rate

Psychopathology, and in particular depression, is a cardiovascular risk factor independent from co-occurring pathology. This link is traced back to the mind-heart-body connection, whose underlying mechanisms are, to date, not completely known. It is clear, however, that the autonomic nervous system plays a leading role in the mediation between the parts of that connection. Therefore, to study psychopathology in relation to the heart, it is necessary to observe the autonomic nervous system, whose gold standard of evaluation is the study of heart rate variability (HRV). Two short-term HRV recordings (5 min - supine and sitting) were analysed in 77 healthy subjects. Here we adopted a three-fold approach to evaluate HRV: a set of scores belonging to the time domain (SDNN, pNN50, RMSSD); the frequency analyses that gauges three main components (high, low, and very low frequencies) and a new set of complexity nonlinear parameters. The PHQ-9 scale was used to detect depressive symptoms. Depressive symptoms were associated only with a parameter from the non-linear approach and specifically the long-term fluctuations of fractal dimensions (DFA-α2). This association remained significant even after controlling for age, gender, BMI, arterial hypertension, anti-hypertensive drugs, dyslipidaemia, and smoking habit. Moreover, the DFA-α2 was not affected by the baroreflex (postural change), unlike other autonomic markers. In conclusion, fractal analysis of HRV (DFA-α2) allows to predict depressive symptoms below diagnostic threshold in healthy subjects regardless of their health status. DFA-α2 may be then considered as an imprint of subclinical depression on the heart rhythm.

Homoarginine test for evaluation of metabolic renal dysfunction

Low plasma L-homoarginine (hArg) concentration is an independent predictor of adverse cardiovascular outcomes and overall mortality, as well as the progression of chronic kidney disease (CKD). The enzyme L-arginine:glycinamidinotransferase (AGAT, EC 2.1.4.1) acts in the mitochondrial membrane of the renal tubular epithelium, forming the precursor of creatine, guanidinoacetic acid, and additionnaly by-product hArg. As it was shown recently, there is a decreased level of hArg in the late stages of CKD, however, the the level of hArg in the early stages of CKD remained unexplored. The aim of this study was to determine the diagnostic threshold levels of hArg in the blood of patients with stages 1 and 2 of CKD. In patients with the initial stages of CKD (n = 44) at the age of 58 (45-67) years, compared with the group of donors of 55 (42-58) years (n = 30), a significant decrease of hArg level was found. In the subgroup with stage CKD 2, the cut-off point of 1.59 μM threshold was characterized by greater sensitivity and specificity than in the subgroup with stage CKD 1 with 1.66 μM threshold level of hArg. For the full group, the hArg cut-off threshold was 1.60 μM, which is about to 0.2 μM lower than the lower limit of the reference interval for healthy individuals. It can be assumed that even before the formation of symptoms of proteinuria and albuminuria, a significant part of individuals from population cohort develops a state of decreased AGAT activity, since the expression of this enzyme is associated with a certain regulatory feedback inhibition at the body level. As a result of the study, it can be noted that in patients with early stages of CKD in the age group 45-67 years, there is a disturbance of the kidneys metabolic function. These metabolic changes can be detected by testing the level of hArg.

Psychometric Evaluation of the NORC Diagnostic Screen for Gambling Problems (NODS) for the Assessment of DSM-5 Gambling Disorder

The National Opinion Research Center (NORC) Diagnostic Screen for Gambling Problems (NODS) is one of the most used outcome measures in gambling intervention trials. However, a screen based on DSM-5 gambling disorder criteria has yet to be developed or validated since the DSM-5 release in 2013. This omission is possibly because the criteria for gambling disorder only underwent minor changes from DSM-IV to DSM-5: the diagnostic threshold was reduced from 5 to 4 criteria, and the illegal activity criterion was removed. Validation of a measure that captures these changes is still warranted. The current study examined the psychometric properties of an online self-report past-year adaptation of the NODS based on DSM-5 diagnostic criteria for gambling disorder. Additionally, the new NODS was evaluated for how well it identifies ICD-10 pathological gambling. A diverse sample of participants (N = 959) was crowdsourced via Amazon’s TurkPrime. Internal consistency and one-week test-retest reliability were good. High correlations (r = .74–.77) with other measures of gambling problem severity were observed in addition to moderate correlations (r = .21–.36) with related but distinct constructs (e.g., gambling expenditures, time spent gambling, other addictive behaviours). All nine of the DSM-5 criteria loaded positively on one principal component, which accounted for 40% of the variance. Classification accuracy (i.e., sensitivity, specificity, predictive power) was generally very good with respect to the PGSI and ICD-10 diagnostic criteria. Future validation studies are encouraged to establish a gold standard measurement of gambling problem severity.

Evaluating Diagnostic Accuracy and Determining Optimal Diagnostic Thresholds of Three Different Approaches to [68Ga]-DOTATATE PET/MRI Analysis in Patients with Meningioma

PURPOSEMultiple approaches with [Ga68]-DOTATATE, a somatostatin analog PET radiotracer, have demonstrated clinical utility in evaluation of meningioma but have not been compared directly. Our purpose was to compare diagnostic performance of three approaches to quantitative brain [68Ga]-DOTATATE PET/MRI analysis in patients with suspected meningioma recurrence and to establish the optimal diagnostic threshold for each method.METHODSPatients with suspected meningioma were imaged prospectively with [68Ga]-DOTATATE brain PET/MRI. Lesions were classified as meningiomas and post-treatment change (PTC), based on pathology findings and follow up MRI appearance. Lesions were reclassified using the following methods: absolute SUV threshold (SUV), SUV ratio (SUVR) to superior sagittal sinus (SSS) (SUVRsss), and SUVR to the pituitary gland (SUVRpit). Diagnostic performance of the three methods was compared using contingency tables and McNemar’s test. Previously published pre-determined thresholds were assessed where applicable. The optimal thresholds for each method were identified using Youden’s J statistics.RESULTS166 meningiomas and 41 PTC lesions were identified across 62 patients. SUV, SUVRsss, and SUVRpit of meningioma were significantly higher than those of PTC (P<0.0001). The optimal thresholds for SUV, SUVRsss, and SUVRpit were 4.65, 3.23, and 0.260, respectively. At the optimal thresholds, SUV had the highest specificity (97.6%) and SUVRsss had the highest sensitivity (86.1%). An ROC analysis of SUV, SUVRsss, and SUVRpit revealed AUC of 0.932, 0.910, and 0.915, respectively (P<0.0001).CONCLUSIONWe found that the SUVRsss method may have the most robust combination of sensitivity and specificity in the diagnosis of meningioma in the post-treatment setting, with the optimal threshold of 3.23. Future studies validating our findings in different patient populations are needed to continue optimizing the diagnostic performance of [68Ga]-DOTATATE PET/MRI in meningioma patients. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04081701. Registered 9 September 2019. https://clinicaltrials.gov/ct2/show/NCT04081701

A Factor Structure within Misophonia: The Sussex Misophonia Scale for researchers and clinicians

Misophonia is an unusually strong aversion to a specific class of sounds -- most often human bodily sounds such as chewing, crunching, or breathing. A number of questionnaires exist to diagnose misophonia, but few have been validated, and fewer still show any factor structure within the symptoms of the condition. Here we present a novel tool, the Sussex Misophonia Scale, which represents all key theme from previous questionnaires within a single easy-to-use measure. We validated our questionnaire in a sample of 501 adults, including people with and without misophonia. Our exploratory factor analyses revealed five factors tied to misophonia (Feelings/ Isolation; Life consequences; Intersocial reactivity; Avoidance/ Repulsion; Pain). Receiver Operator Characteristic showed our questionnaire to be an excellent measure for identifying people with misophonia, and we present it here with its diagnostic threshold for researchers and clinicians.

Parameters of Glucose Homeostasis in the Recognition of the Metabolic Syndrome in Young Adults with Prader–Willi Syndrome

To verify the accuracy of different indices of glucose homeostasis in recognizing the metabolic syndrome in a group of adult patients with Prader–Willi syndrome (PWS), 102 PWS patients (53 females/49 males), age ±SD 26.9 ± 7.6 yrs, Body Mass Index (BMI) 35.7 ± 10.7, were studied. The following indices were assessed in each subject during an oral glucose tolerance test (OGTT): 1 h (>155 mg/dL) and 2 h (140–199 mg/dL) glucose levels, the oral disposition index (ODI), the insulinogenic index (IGI), the insulin resistance (HOMA-IR) were evaluated at baseline, 1 h and 2 h. Although minor differences among indices were found, according to the ROC analysis, no index performed better in recognizing MetS. Furthermore, the diagnostic threshold levels changed over the years and therefore the age-related thresholds were calculated. The easily calculated HOMA-IR at baseline may be used to accurately diagnose MetS, thus avoiding more complicated procedures.

Meta-Analysis of D-Dimer, hsCRP and Cytokines in COVID-19 Severe/Critical Patients in China

Objective: To analyze the relationship between D-dimer, inflammatory markers, cytokines and disease severity, and the possibility of early identification of COVID-19 critical type patients. Methods: PubMed, EMBASE and CNKI databases were searched by computer, and references of related reviews and systematic reviews were manually searched as supplements. The retrieval deadline is February 9, 2021. According to the inclusion and exclusion criteria, the literatures were screened and the quality was evaluated, and then the data were extracted for meta-analysis. The fixed/random effects model was used to calculate the weighted mean difference (WMD) and 95% CI to evaluate whether the levels of D-dimer, hsCRP, IL-6, IL-8, IL-10 and TNF-α in critical type patients were statistically different from those in severe type patients. If there were statistical differences, logistic regression analysis was used, and establish the receiver operating characteristic curve (ROC) and area under the curve (AUC) of each index for the diagnosis of critical type patients. The best diagnostic value of COVID-19 critical type patients was calculated by Youden index. Results: A total of 3519 literatures entered the screening process. According to the inclusion and exclusion criteria, 40 articles were finally included in this study, and all of them were high-quality studies after evaluation. The results of meta-analysis showed that the levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in critical type group were significantly higher than those in severe type group (P&lt;0.05). Based on ROC curve, the AUC of D-dimer was 0.785 (95% CI: 0.671-0.899), AUC of hsCRP was 0.884 (95% CI: 0.632-1.000), AUC of IL-6 was 0.819 (95% CI: 0.700-0.939), which had diagnostic significance for critical type patients (P&lt;0.05). The optimal diagnostic threshold of D-dimer was ≥2.00 mg/L (sensitivity 89.3%, specificity 64.0%); the optimal diagnostic threshold of hsCRP was ≥64.22 mg/L (sensitivity 75.0%, specificity 100%); the optimal diagnostic threshold of IL-6 was ≥33.01 ng/L (sensitivity 68.0%, specificity 92.0%). Conclusion: The levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in COVID-19 critical type patients were significantly higher than those in severe type patients. Our results might be helpful in identify and risk reduction of mortality in critical types patients infected with COVID-19. Disclosures No relevant conflicts of interest to declare.