Age-specific testosterone thresholds: reconsidering diagnostic criteria for hypogonadism across generations of Vietnamese men.

The definition and diagnosis of functional hypogonadism (FH) remains challenging due to the nonspecific nature of symptoms and the inconsistency in normal testosterone thresholds. We conducted this single-center cross-sectional study on medical records of men aged 18 and above undergoing annual health check-ups to evaluate the correlation of age and metabolic components with testosterone. A total of 5,374 healthy men were included in the analysis. Total testosterone levels peaked at 18 years and gradually declined to age 40, followed by a mild increase. Based on the American Urology Association guideline, age-specific cutoffs for low testosterone were 14.61 nmol/l, 12.74 nmol/l, 12.70 nmol/l, and 13.98 nmol/l for those under 30, 30-40, 40-50, and over 50 years old respectively. Triglyceride - Glucose index showed a consistent negative correlation with testosterone across all age groups. In conclusion, testosterone levels demonstrated an age-related decline in early adulthood but a potential increase thereafter among healthy Vietnamese men. Metabolic components, rather than aging, had a consistent negative correlation with testosterone. Age-specific cutoffs for low testosterone may improve the detection of functional hypogonadism.

High-Sensitive Cardiospecific Troponins: The Role of Gender-Specific Concentration in the Diagnosis of Acute Coronary Syndrome (Descriptive Review).

Cardiospecific troponins are specifically localized in the troponin-tropomyosin complex and in the cytoplasm of cardiac myocytes. Cardiospecific troponin molecules are released from cardiac myocytes upon their death (irreversible damage in acute coronary syndrome) or reversible damage to cardiac myocytes, for example, during physical exertion or the influence of stress factors. Modern high-sensitive immunochemical methods for detecting cardiospecific troponins T and I are extremely sensitive to minimal reversible damage to cardiac myocytes. This makes it possible to detect damage to cardiac myocytes in the early stages of the pathogenesis of many extra-cardiac and cardiovascular diseases, including acute coronary syndrome. So, in 2021, the European Society of Cardiology approved diagnostic algorithms of acute coronary syndrome, which allow the diagnosis of acute coronary syndrome in the first 1-2 hours from the moment of admission of the patient to the emergency department. However, high-sensitive immunochemical methods for detecting cardiospecific troponins T and I may also be sensitive to physiological and biological factors, which are important to consider in order to establish a diagnostic threshold (99 percentile). One of the important biological factors that affects the 99 percentile levels of cardiospecific troponins T and I are gender characteristics. This article examines the role of gender-specific concentration of cardiospecific troponins in the diagnosis of acute coronary syndrome and the mechanisms of formation of gender-specific serum levels of cardiospecific troponins T and I.

Upper Reference Limits for High-Sensitivity Cardiac Troponin T and N-Terminal Fragment of the Prohormone Brain Natriuretic Peptide in Patients With CKD.

RATIONALE & OBJECTIVE: The utility of conventional upper reference limits (URL) for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease. EXPOSURE: Estimated glomerular filtration rate (eGFR). OUTCOME: NT-proBNP and hsTnT at baseline. ANALYTICAL APPROACH: We described the proportion of participants above the conventional URL for NT-proBNP (125pg/mL) and hsTnT (14ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99th percentile, we modeled the association of eGFR with NT-proBNP and hsTnT. RESULTS: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above the conventional URL, respectively. In those with eGFR <30mL/min/1.73m2, 71% and 68% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, respectively. Among all CKD participants, the 99th percentile for NT-proBNP was 3,592 (95% CI, 2,470-4,849) pg/mL and for hsTnT it was 126 (95% CI, 100-144) ng/L. Each 15mL/min/1.73m2 decrement in eGFR was associated with a ~40% higher threshold for the 99th percentile of NT-proBNP (1.43 [95% CI, 1.21-1.69]) and hsTnT (1.45 [95% CI, 1.31-1.60]). LIMITATIONS: Study included ambulatory patients, and we could not test the accuracy of the URL of NT-proBNP and hsTnT in the acute care setting. CONCLUSIONS: In this ambulatory CKD population with no self-reported history of cardiovascular disease, a range of 40%-88% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, depending on eGFR strata. Developing eGFR-specific thresholds for these commonly used cardiac biomarkers in the setting of CKD may improve their utility for evaluation of suspected heart failure and myocardial infarction.

Evaluation of sensitivity and specificity of diagnostic criteria for Behçet's disease in the absence of a gold standard.

OBJECTIVE: The performance of existing diagnostic criteria for Behçet's disease (BD) is usually evaluated by comparison with expert opinions, which may be limited by misclassification and disagreement among experts. We aim to evaluate these criteria in the absence of a gold standard. METHODS: We obtained two datasets involving possible BD and other mimickers from a uveitis registry using case-cohort and nested case-control analyses, respectively. With a Bayesian inference approach, the sensitivity and specificity of International Study Group (ISG) and International Criteria for Behçet's Disease (ICBD) criteria were simultaneously estimated when true BD state was unknown. RESULTS: A total of 2440 and 2224 participants were included in case-cohort and nested case-control analyses, respectively. In case-cohort analysis, with scores of ≥4 for BD diagnosis, ICBD criteria showed higher sensitivity (median 97.6%; 95% credible interval 96.9, 98.2) than ISG criteria (median 90.0%; 95% credible interval 88.8, 91.2) but had lower specificity (median 90.8%; 95% credible interval 89.4, 92.1) than ISG criteria (median 98.8%; 95% credible interval 98.3, 99.3). With scores of ≥5 for diagnosis, ICBD criteria demonstrated higher sensitivity (median 97.5%; 95% credible interval 96.8, 98.1) and specificity (median 99.6%; 95% credible interval 99.3, 99.8) than the sensitivity (median 92.3%; 95% credible interval 91.2, 93.3) and specificity (median 98.8%; 95% credible interval 98.2, 99.2) for ISG criteria. The highest diagnostic consistency was observed between ISG criteria and ICBD criteria with scores of ≥5 for diagnosis (Kappa = 0.999; P < 0.001). Nested case-control analysis showed similar results. CONCLUSION: ICBD criteria showed optimum discriminatory properties in sensitivity and specificity with scores of ≥5 for BD diagnosis in uveitis. The diagnostic threshold of ICBD criteria could be considered adjustable according to medical specialty, disease prevalence and local practice characteristics.

Determination of diagnostic threshold in harmonization and comparison of clinical utility for five major antiphospholipid antibody assays used in Japan.

BACKGROUND: Anticardiolipin antibodies (aCL) and anti-ß2 -glycoprotein I antibodies (aß2 GPI) are essential in diagnosing antiphospholipid syndrome (APS) according to the international APS guideline. Five commercial assays for aCL and aß2 GPI are available in Japan, but their test results are quite discordant. For harmonization of diagnosing APS, upper reference limit (URL) and diagnostic accuracy of each assay were evaluated and compared by testing common sets of specimens across all assays. METHODS: We evaluated two manual and three automated assays for aCL and aß2 GPI of IgG- and IgM classes. 99%URL (the upper limit of reference interval: as per guideline) together with 97.5%URL were determined by testing sera from 198 to 400 well-defined healthy subjects. Both URLs were compared with the cutoff values, which were determined based on ROC analysis by testing 50 each of plasma specimens from patients with/without APS. Diagnostic accuracy was evaluated as area under curve (AUC) of the ROC curve. RESULTS: A variable degree of discrepancy between URLs and the cutoff values was observed, which was partly attributable to between-year assay variability. 97.5%URLs were set lower and closer to the cutoff values than 99%URLs. For all assays, diagnostic accuracies of both aß2 GPI-IgG and aCL-IgG were generally high (AUC: 0.84-0.93); whereas those for IgM-class assays were low (AUC: 0.57-0.67), implicating its utility is limited to rare IgG negative APS cases. CONCLUSION: To ensure harmonized APS diagnosis, the diagnostic thresholds of the five assays were evaluated by common procedures. Contrary to the guideline, 97.5%URL is rather recommended for diagnosing APS, which showed a closer match to the cutoff value.

Lower versus higher diagnostic criteria for the detection of gestational diabetes for reducing maternal and perinatal morbidity: study protocol for the GEMS randomised trial.

BACKGROUND: Gestational diabetes mellitus (GDM) has lifelong implications for the woman and her infant. Treatment reduces adverse maternal and perinatal outcomes although uncertainty remains about the optimal diagnostic criteria. The GEMS Trial aims to assess whether detection and treatment of women with GDM using the lower International Association of Diabetes in Pregnancy Study Groups diagnostic criteria compared with the higher criteria recommended in New Zealand reduces infant morbidity without increasing maternal morbidity. METHODS: GEMS is a multicentre, randomised trial. Women with a singleton pregnancy at 24 to 34 weeks' gestation are eligible who give written informed consent. Women are randomly allocated to the Lower Criteria Group or the Higher Criteria Group. Women with a normal OGTT by their allocated criteria receive routine care (Higher criteria: fasting plasma glucose < 5.5 mmol/L, AND 2 hour < 9.0 mmol/L; Lower criteria: fasting plasma glucose < 5.1 mmol/L, AND 1 hour < 10.0 mmol/L, AND 2 hour < 8.5 mmol/l). Women with GDM on OGTT by their allocated criteria receive standard care for GDM (Higher criteria: fasting plasma glucose ≥ 5.5 mmol/L, OR 2 hour ≥ 9.0 mmol/L; Lower criteria: fasting plasma glucose ≥ 5.1 mmol/L, OR 1 hour ≥ 10.0 mmol/L, OR 2 hour ≥ 8.5 mmol/L). The primary outcome is large for gestational age (birth weight > 90th centile). Secondary outcomes for the infant include a composite of serious outcomes, gestational age, anthropometry, Apgar score < 4 at 5 minutes, lung disease, use of respiratory support, hypoglycaemia, hyperbilirubinaemia, infection, and encephalopathy; and for the woman, a composite of serious outcomes, preeclampsia, induction of labour, mode of birth, weight gain, postpartum haemorrhage and infectious morbidity. A study with 4,158 women will detect an absolute difference of 2.9% in the proportion of large for gestational age infants from 10.0% using the lower criteria to 12.9% with the higher criteria. DISCUSSION: The GEMS Trial will provide high-level evidence relevant for clinical practice. If use of the lower diagnostic criteria results in significantly fewer large for gestational age infants and/or improves maternal and perinatal outcomes these criteria should be recommended for diagnosis of gestational diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry registration number ACTRN12615000290594 . Date registered: 27th March 2015.

Defining the Optimal Threshold Scores for Adult Autism Subthreshold Spectrum (AdAS Spectrum) in Clinical and General Population.

BACKGROUND: The Adult Autism Subthreshold Spectrum (AdAS Spectrum) is a recently developed instrument tailored to assess the broad range of full-threshold as well as sub-threshold manifestations related to the autism spectrum. Although it has proved to be a valuable instrument for quantitative assessment of autistic symptoms, the AdAS Spectrum still lacks validated diagnostic thresholds. OBJECTIVE: The aim of this study was to define the best cut-off scores of the AdAS Spectrum for determining the presence of subthreshold autistic traits as well as a clinically significant autism spectrum disorder (ASD). METHODS: Our sample was composed of 39 patients with full-blown ASD, 73 subjects with autistic traits, and 150 healthy controls. Subjects were evaluated by trained psychiatrists, who performed a clinical diagnosis according to DSM-5 and then assessed with the AdAS Spectrum and the Autism Spectrum Quotient. RESULTS: Our results showed that the most discriminant cut-off scores were 70 for identifying subjects with full-blown ASD, and 43 for determining the presence of significant autistic traits. CONCLUSION: The threshold values proposed here showed satisfying levels of specificity and sensibility, as well as a good agreement with the diagnosis according to DSM-5 criteria, confirming the validity of the AdAS Spectrum as a psychometric tool for measuring ASD-related conditions in the clinical and general population.

Is caries equally distributed in adults? A population-based cross-sectional study in Norway - the TOHNN-study.

OBJECTIVES: The aim of the study was to examine the prevalence and distribution of dental caries in an adult population and identify factors associated with being caries free. MATERIAL AND METHODS: Data were collected from a randomized population sample in Northern Norway (N = 1932; 988 women; mean age 47.0 years, SD 15.3). The study included a structured questionnaire and a clinical examination. The sum of enamel and dentine caries, DS1-5, formed the main outcome measures for caries prevalence. RESULTS: Mean DMFT was 15.1 (95% CI 14.8, 15.4), mean DFT was 12.0 (CI 11.7, 12.2), and mean DT was 1.1 (CI 1.0, 1.2). The mean value for dentine caries (DS3-5) was 0.8 (CI 0.7, 0.9), and mean DS1-5 was 3.8 (CI 3.6, 4.1). Mean DS1-5 was highest in the youngest age group (mean 6.9, 95% CI 6.3, 7.6) and in rural areas (mean 5.0, CI 4.4, 5.6). The most caries-prone 20% in the youngest age group had 52% of the total number of carious lesions compared with 80% in the two oldest age groups. Tooth brushing twice daily (p = .005), drinking sugar containing soft drink (p =.029), and attending dental services every year (p < .001), were associated with being caries free. CONCLUSION: Dental caries is still a common condition, particularly in the youngest age group. Living in a rural area, low socioeconomic status, less frequent tooth cleaning and sugar containing soft drinks were associated with a higher prevalence of dental caries. The different caries distribution among adults calls for different preventive strategies at both population and individual levels.

CT perfusion diagnoses delayed cerebral ischemia in the early stage of the time-window after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: It has been acknowledged that delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) can be diagnosed by CT perfusion (CTP) in the DCI time-window. We evaluated the diagnostic accuracy of CTP for DCI during the early stage of the time-window. MATERIALS AND METHODS: We prospectively enrolled patients with aneurysmal SAH. DCI was defined as both new cerebral infarction and clinical deterioration after SAH. CTP was performed by using a standardized protocol with predefined regions of interest in 4 to 6 days after SAH. We quantitatively evaluated the diagnostic accuracy of eight CTP parameters (4 for absolute parameters and 4 for relative parameters). The receiver operator characteristic (ROC) curves of all parameters were generated and the optimal threshold values were derived for the calculation of sensitivities and specificities. RESULTS: Fifty-three patients were enrolled and 20 patients were diagnosed with DCI. In the analysis of absolute CTP parameters, CBF and MTT had areas under the curve (AUC) >0.75 and the optimal threshold value was 40.4mL/100g/min and 3.78seconds, respectively. Through the evaluation of relative CTP parameters, all 4 parameters had AUC >0.75 and the optimal threshold value was 0.9 for CBV ratio, 0.85 for CBF ratio, 0.32seconds for MTT difference and 1.31seconds for TTP difference. CONCLUSIONS: Besides two absolute CTP parameters (CBV and TTP), all six CTP parameters can be used as good diagnostic tests for DCI in the early stage of the time-window.

Evaluating the scripts and thresholds of general practitioners for diagnosing heart failure in elderly people.

BACKGROUND: Multiple diagnostic algorithms for heart failure exist. However, it is unclear whether these algorithms are incorporated in the 'scripts' clinicians use in every day practice. Scripts are networks of organised knowledge that are acquired and accumulated during clinical training and are refined with each clinical encounter. This study was conducted to evaluate the scripts and thresholds that GPs use to diagnose heart failure in patients aged 75 years and older. METHODS: The scripts and thresholds of 130 Belgian GPs in training and 63 experienced trainers were compared using an online questionnaire based on the same principles as the script concordance test. Two major cases with an open question and 19 minor cases with closed questions were presented. For the minor cases, all of the respondents were asked to assign a diagnostic power to individual cues. Based on these powers, a diagnostic threshold was calculated for each respondent for the two major cases. RESULTS: The trainers and trainees used the same scripts to diagnose heart failure in the two major cases. Only ~50 % of the participants used natriuretic peptides in their scripts, although they judged it as the most powerful marker to demonstrate or exclude heart failure. The power that respondents gave to several cues differed significantly according to the context in which these cues were presented. In general, the average exclusive power of different cues was lower than the demonstrative power of the cues. There was no difference in diagnostic threshold between the trainers and trainees. CONCLUSION: Young, inexperienced GPs used the same scripts as older, more experienced GPs. In general, technical investigations were less frequently queried, compared to elements of the medical history and the clinical examination. The clinical context had a strong impact on the diagnostic power that was assigned to different factors.

Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug-induced liver injury in rats.

Traditional biomarkers such as alanine and aspartate aminotransferase (ALT, AST) and total bilirubin (TBIL) have been widely used for detecting drug-induced liver injury (DILI). Although the Food and Drug Administration (FDA) proposed standardized thresholds for human as Hy's law, those for animals have not been determined, and predictability of these biomarkers for future onset of hepatic lesions remains unclear. In this study, we investigated these diagnostic and predictive performance of 10 traditional biomarkers for liver injury by receiver-operating characteristic (ROC) curve, using a free-access database where 142 hepatotoxic or non-hepatotoxic compounds were administrated to male rats (n=5253). Standardization of each biomarker value was achieved by calculating the ratio to control mean value, and the thresholds were determined under the condition of permitting 5% false positive. Of these 10 biomarkers, AST showed the best diagnostic performance. Furthermore, ALT and TBIL also showed high performance under the situation of hepatocellular necrosis and bile duct injury, respectively. Additionally, the availability of the diagnostic thresholds in difference testing facility was confirmed by the application of these thresholds to in-house prepared dataset. Meanwhile, incorrect diagnosis by the thresholds was also observed. Regarding prediction, all 10 biomarkers showed insufficient performance for future onset of hepatic lesions. In conclusion, the standardized diagnostic thresholds enable consistent evaluation of traditional biomarkers among different facilities, whereas it was suggested that novel biomarker is required for more accurate diagnosis and prediction of DILI.

Cognitive Profiles are Better Predictors of Literacy Attainment Than Diagnostic Outcomes in Children with High ADHD Symptoms.

We examined whether cognitive profiles or diagnostic outcomes are better predictors of literacy performance for children being considered for an ADHD diagnosis. Fifty-five drug naïve children (Mage = 103.13 months, SD = 18.65; 29.09% girls) were recruited from an ADHD clinical referral waiting list. Children underwent assessment of IQ, Executive Functions (EF) and literacy attainment. Hierarchical cluster analysis was used to generate subgroups of children using EF scores. Data were then grouped based on presence of a clinical ADHD diagnosis and the results compared. Grouping participants by profiles of cognitive test scores led to groups which also differed on literacy scores. However, categorising by whether children had received an ADHD diagnosis or not did not differentiate either cognitive tests scores or literacy scores. Cognitive performance, rather than children's diagnostic outcomes, is more informative for identifying groups who differ in their literacy attainment which has important implications for remedial support.

Risk factors for ICU-acquired weakness in sepsis patients: A retrospective study of 264 patients.

Background: Sepsis is a common critical illness in intensive care unit (ICU) and an important risk factor for intensive care unit-acquired weakness (ICU-AW). The objective of the study is to analyze the risk factors of ICU-AW in septic patients. Methods: A total of 264 septic patients admitted to the General Hospital of the Western Theater Command from January 2018 to April 2022 were included in this study. The cohort was divided into 2 groups according to the presence or absence of ICU-AW. Clinical characteristics included age, sex, body mass index, length of ICU stay, multiple organ dysfunction syndrome, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), mechanical ventilation time, intubation, tracheotomy, protective constraint, lactic acid, fasting blood glucose, etc. The clinical characteristics of sepsis were evaluated using logistic regression analysis. Results: A total of 114 septic patients suffered ICU-AW during their ICU stay. Multivariate binary logistic regression analysis showed that APACHE Ⅱ score, mechanical ventilation time, protective constraint, and lactic acid were independent risk factors for ICU-AW in septic patients. The areas under the receiver operating characteristic curve (AUCs) were 0.791, 0.740 and 0.812, all P < 0.05, and the optimal cut-off values were 24 points, 5 days and 2.12 mmol/L, respectively. Conclusions: A high APACHE Ⅱ score, long mechanical ventilation time, protective constraint and high lactate concentration are independent risk factors for ICU-AW in septic patients. An APACHE Ⅱ score greater than 24 points, mechanical ventilation time longer than 5 days and lactate concentration higher than 2.12 mmol/L are likely to cause ICU-AW.

Differences between DSM-5-TR and ICD-11 revisions of attention deficit/hyperactivity disorder: A commentary on implications and opportunities.

Current ICD-11 descriptions for attention deficit hyperactivity disorder (ADHD) were recently published online, in the same year as the DSM-5-TR (text revised edition) was released. In this commentary, we compare and contrast the DSM-5/DSM-5-TR and ICD-11 diagnostic criteria, summarize important differences, and underscore their clinical and research implications. Overall, three major differences emerge: (1) The number of diagnostic criteria for inattention (IA), hyperactivity (HY) and impulsivity (IM) symptoms (i.e., DSM-5-TR has nine IA and nine HY/IM symptoms, whereas ICD-11 has 11 IA and 11 HY/IM sym-ptoms); (2) the clarity and standardization of diagnostic thresholds (i.e., the diagnostic thresholds for symptom count in IA and HY/IM domains are explicitly specified in DSM-5-TR, whereas in ICD-11 they are not); and (3) the partitioning of HY and IM symptoms into sub-dimensions (i.e., difference in partitioning HY and IM symptom domains relates to the differences between the current and previous editions of DSM and ICD, and this has important research implications). Currently, no ICD-11 based ADHD rating scales exist and while this absence represents an obstacle for respective research and clinical practice, it also presents opportunities for research development. This article highlights these challenges, possible remedies and novel research opportunities.

High-sensitive cardiospecific troponins: the role of sex-specific concentration in the diagnosis of acute coronary syndrome (mini-review).

Cardiospecific troponins are specifically localized in the troponin-tropomyosin complex and the cytoplasm of cardiac myocytes. Cardiospecific troponin molecules are released from cardiac myocytes upon their death (irreversible damage in acute coronary syndrome) or reversible damage to cardiac myocytes, for example, during physical exertion or the influence of stress factors. Modern high-sensitive immunochemical methods for detecting cardiospecific troponins T and I are extremely sensitive to minimal reversible damage to cardiac myocytes. This makes it possible to detect damage to cardiac myocytes in the early stages of the pathogenesis of many extra-cardiac and cardiovascular diseases, including acute coronary syndrome. So, in 2021, the European Society of Cardiology approved diagnostic algorithms for the acute coronary syndrome, which allow the diagnosis of acute coronary syndrome in the first 1-2 hours from the moment of admission of the patient to the emergency department. However, high-sensitive immunochemical methods for detecting cardiospecific troponins T and I may also be sensitive to physiological and biological factors, which are important to consider in order to establish a diagnostic threshold (99 percentile). One of the important biological factors that affect the 99 percentile levels of cardiospecific troponins T and I are sex characteristics. This article examines the mechanisms underlying the development of sex-specific serum levels of cardiospecific troponins T and I and the importance of sex-specific cardiospecific troponin concentrations in diagnosing acute coronary syndrome.

Diagnostic Policies Optimization for Chronic Diseases Based on POMDP Model.

During the process of disease diagnosis, overdiagnosis can lead to potential health loss and unnecessary anxiety for patients as well as increased medical costs, while underdiagnosis can result in patients not being treated on time. To deal with these problems, we construct a partially observable Markov decision process (POMDP) model of chronic diseases to study optimal diagnostic policies, which takes into account individual characteristics of patients. The objective of our model is to maximize a patient's total expected quality-adjusted life years (QALYs). We also derive some structural properties, including the existence of the diagnostic threshold and the optimal diagnosis age for chronic diseases. The resulting optimization is applied to the management of coronary heart disease (CHD). Based on clinical data, we validate our model, demonstrate how the quantitative tool can provide actionable insights for physicians and decision makers in health-related fields, and compare optimal policies with actual clinical decisions. The results indicate that the diagnostic threshold first decreases and then increases as the patient's age increases, which contradicts the intuitive non-decreasing thresholds. Moreover, diagnostic thresholds were higher for women than for men, especially at younger ages.

Clinical and Prognostic Features of Essential Thrombocythemia: Comparison of 2001 WHO Versus 2008/2016 WHO Criteria in a Large Single-center Cohort.

BACKGROUND: According to 2008/2016 classification of the World Health Organization (WHO), a platelet (PLT) count ≥ 450 × 109/L, reduced from the previously published WHO 2001 indicated level ≥ 600 × 109/L, was considered the new PLT threshold for the diagnosis of essential thrombocythemia (ET). PATIENTS AND METHODS: To validate this important diagnostic change in a setting of current clinical practice, we retrospectively analyzed clinical and hematologic features at diagnosis and during follow-up of 162 patients with ET, diagnosed in our center from January 2008 to December 2017. We subdivided patients according to PLT value at baseline into Group A (PLT ≥ 600 × 109/L) (124 patients; 76.5%) and Group B (PLT ≥ 450 × 109/L < 600 × 109/L) (38 patients; 23.5%). RESULTS: Among clinical features, only the median value of leukocytes (P < .001) was significantly higher in Group A. Cytostatic treatment was administered in 103 patients, with a significantly higher rate in patients of group A (P < .001). After a median follow-up of 42.4 months (interquartile range, 22.1-70.6 months), 8 thrombotic events were recorded in the entire cohort, without differences between the 2 groups (P = .336). The 5-year overall survival (OS) of the entire cohort was 96.9% (95% confidence interval, 92.6%-100%), without differences between the 2 groups (P = .255). CONCLUSIONS: Our data indicate a substantial homogeneity among patients with ET regardless of the PLT count at diagnosis, thus confirming the usefulness of the 2008/2016 WHO diagnostic criteria.

Performance of early pregnancy HbA1c for predicting gestational diabetes mellitus and adverse pregnancy outcomes in obese European women.

AIMS: To investigate the performance of early pregnancy HbA1c for predicting gestational diabetes mellitus (GDM) and adverse pregnancy outcomes in obese women. METHODS: Post hoc analysis using data from the Vitamin D And Lifestyle Intervention for GDM prevention trials conducted across 9 European countries (2012-2014). Pregnant women (BMI ≥ 29 kg/m2) underwent a baseline HbA1c and oral glucose tolerance tests at < 20 weeks, 24-28 weeks, and 35-37 weeks. Women with GDM were referred for treatment. RESULTS: Among the 869 women tested, the prevalence of GDM was 25.9% before 20 weeks, with a further 8.6% at 24-28 weeks. The areas under the curves for HbA1c at the two time points were 0.55 (0.50-0.59) and 0.54 (0.47-0.61), respectively. An early HbA1c ≥ 5.7% (39 mmol/mol) (N = 111) showed low sensitivity (18.2%) with 89.1% specificity for GDM before 20 weeks, at 24-28 weeks (sensitivity of 8.0% and specificity of 88.6% after excluding early GDM), and throughout gestation (sensitivity of 15.9% and specificity of 89.4%). The ≥ 5.7% (39 mmol/mol) threshold was significantly associated with concurrent GDM before 20 weeks (adjusted OR (aOR) 2.77(1.39-5.51)) and throughout gestation (aOR 1.72 (1.02-2.89)), but not adverse pregnancy outcomes. CONCLUSIONS: Early pregnancy HbA1c is of limited use for predicting either GDM or adverse outcomes in overweight/obese European women.

Unlike ROC analysis, a new IRT method identified clinical thresholds unbiased by disease prevalence.

OBJECTIVE: This study introduces a new method to establish clinical thresholds for multi-item tests, based on item response theory (IRT), as an alternative to receiver operating characteristic (ROC) analysis. The performance of IRT method was examined and compared with the ROC method across multiple simulated data sets and in a real data set. STUDY DESIGN AND SETTING: Simulated data sets (sample size: 1,000) varied in means and variability of the test scores and the prevalence of disease. The true clinical threshold was defined as a predetermined location on the latent trait underlying the questionnaire, with its corresponding expected test score. The real data set (sample size: 295) comprised Hospital Anxiety Depression Scale (HADS) depression scores and Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition major depressive disorder (MDD) diagnoses. RESULTS: The IRT method recovered the clinical thresholds without bias, whereas the ROC method identified thresholds that were biased by the prevalence of disease. Mild MDD was clinically diagnosed in 23%, moderate MDD in 12%, and severe MDD in 14% of the participants. The IRT method identified the following HADS depression score thresholds for mild, moderate, and severe MDD: 10.7, 13.2, and 15.1, respectively. CONCLUSION: The new IRT method identifies clinical thresholds that are unbiased by disease prevalence.

Evaluation of Diagnostic Thresholds for Criterion A in the Alternative DSM-5 Model for Personality Disorders.

The Level of Personality Functioning Scale (LPFS) of the Alternative DSM-5 Model for Personality Disorders (AMPD) was formulated to assess the presence and severity of personality disorders (PDs). Moderate impairment (Level 2) in personality functioning, as measured by the LPFS, was incorporated into the AMPD as a diagnostic threshold for PD in Criterion A of the general criteria, as well as for the "any two areas present" rule for assigning a specific PD diagnosis. This study represents the first evaluation of the diagnostic decision rules for Criterion A, in a clinical sample (N = 282). The results indicate that an overall diagnostic threshold for PDs should be used with caution because it may not identify all DSM-IV PDs. The "any two areas present" rule proved to be a reasonable alternative, although this finding should be interpreted with caution because the LPFS does not measure the disorder-specific A criteria.