Routine Clinical Measurements Research Articles

985-P: Prediction Models Combining Clinical Measures Identify Participants with Youth-Onset Diabetes Who Maintain Insulin Secretion

With the high prevalence of pediatric obesity, it is challenging to accurately classify diabetes (DM) type, especially in a diverse population of youth. Maintained fasting C-peptide ≥ 0.75ng/ml (250pmol/L) , a level associated with type 2 diabetes and successful insulin withdrawal in adult cohorts, may have implications for treatment and risks of acute complications. We developed clinical prediction models to identify individuals with youth onset DM who will retain endogenous insulin secretion. We studied 2991 youth in the SEARCH study (DM diagnosed ≤ age years) to develop logistic regression based prediction models using clinical measures (race/ethnicity, BMI Z-score, age at diagnosis, triglycerides and HDL-C) with or without islet autoantibodies (Aab) (GADA, IA-2A, ZnT8A) , to identify those with fasting C-peptide ≥ 0.75ng/ml at 3-yr (median 75 months) DM duration. Model covariates (measured median 9 months duration) were chosen based on previous literature and availability. A prediction model using clinical measures was highly accurate in identifying participants with C-peptide ≥75 ng/ml (17% of participants, 3% and 59% of those with and without positive Aab) : area under receiver operator curve (AUC ROC) 0.950 (95%CI 0.938-0.962) , model pseudo-R2 0.69. Adding Aab improved discrimination to AUC ROC 0.976 (0.968,0.983) , pseudo-R2 0.81. In internal validation, optimism was very low, with excellent calibration (slope 0.995-0.999) . Performance remained high in difficult to classify groups: AUC ROC was 0.947 (0.927, 0.966) in those with negative Aab and 0.923 (0.960, 0.984) (model with Aab) in youth with high BMI (Z-score >2) . Discrimination was lower in non-Hispanic white participants (AUC ROC 0.94) compared to participants of other race and ethnic groups (AUC ROC 0.97-0.99) (model with Aab) . In conclusion, prediction models combining routine clinical measures can accurately identify youth with DM who maintain endogenous insulin secretion. Disclosure A.Jones: None. A.H.Williams: None. S.M.Marcovina: None. C.Pihoker: None. J.Divers: None. M.J.Redondo: Advisory Panel; Provention Bio, Inc. B.Shields: None. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. D.Dabelea: None. W.Hagopian: Research Support; Janssen Research & Development, LLC. E.Lustigova: None. A.S.Shah: None. A.K.Mottl: Advisory Panel; Bayer AG, Board Member; Bayer AG, Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. Funding Centers for Disease Control and Prevention (PA numbers 00097, DP-05-069, and DP-10-001) and the National Institute of Diabetes and Digestive and Kidney Diseases. This work is also supported by NIH RO1 awards DK124395 and DK121843-01.

M099 Comparison of four matrixes for diluting insulin in routine clinical measurements

M099 Comparison of four matrixes for diluting insulin in routine clinical measurements

Two-year administration data of an oral testosterone undecanoate (TU) formulation in hypogonadal men

ABSTRACT Introduction An oral testosterone (T) replacement therapy (TRT) would be the preferred administration route for many hypogonadal men. Until recently, the only oral TRT approved in the US was methyl-T which has been associated with hepatotoxicity. The safety of a novel oral T undecanoate (TU) formulation was evaluated in hypogonadal men with two-year follow up. Methods Two open-label, multicenter, dose-titration trials were conducted in hypogonadal men (serum T ≤ 300 ng/dL) age 18-75 years. Trial I was a randomized, active-controlled, 2-arm, 12-month study. Trial 2 was a long-term extension of those who completed Trial 1. Statistical analyses were only conducted with the subjects who completed Trial 1 and continued treatment in Trial 2, thus providing up to 2 full years of data. Safety was assessed by physical exam, AE reporting, and routine clinical laboratory measurements. Results Overall, 86 subjects participated in both studies. T concentration increased from 193.75 ± 9.44 ng/dL (Mean ± SEM) at baseline (BL) to 475.5 ± 49.7 ng/dL after 24 Mo of therapy with oral TU, and 84% of men achieved T in eugonadal range (300-1000 ng/dL) after 90 days of therapy. Mean T concentrations remained in the eugonadal range throughout Trial 2. There were no clinically significant changes in liver function tests – ALP (64.05 ± 1.95 to 53.74 U/L ± 1.86 U/L), ALT (27.8 ± 1.40 to 26.7 ± 1.6 U/L), AST (21.6 ± 0.76 to 22.0 ± 1.0 U/L), and bilirubin (0.58 ± 0.03 to 0.52 ± 0.03 mg/dL) throughout the two studies. At d270, one subject had an ALT level of 227 U/L, which was > 4x the ULN (ULN for ALT = 45 U/L). Despite continued use of oral TU, ALT was measured again on d290, and the level dropped to 87 U/L, < 2x ULN. This was the only instance of an LFT elevation. There was a modest initial increase in prostate-related growth endpoints (i.e. PSA and prostate volume) that stabilized over time. Although there was a slight increase in prostate-growth related endpoints, there were no significant changes in IPSS total score (-0.06 ± 3.9 vs BL). There were significant, yet modest, increases in mean HCT (44.3 ± 0.3 to 46.6 ± 0.5%, p < 0.001) and cuff systolic BP (127.1 ± 1.2 to 131.8 ± 1.67 mmHg vs BL, p = 0.006). The change in CV endpoints, including HDL-C, hematocrit, and BP, changed initially and stabilized throughout the 2 trials. For example, systolic BP varied 3 – 6 mm Hg from BL throughout the study. Conclusion This oral TU formulation is an option for hypogonadal men and has a safety profile consistent with other approved T products, such as a rise in hematocrit and a decrease in HDL-C. Notably, no evidence of liver toxicity was observed over 2 years. The long-term efficacy and safety profile of oral TU may provide a treatment option that avoids issues associated with other TRTs, such as injection site pain or transference to partners and children. Disclosure Work supported by industry: yes, by Clarus Therapeutics. A consultant, employee (part time or full time) or shareholder is among the authors (Clarus Therapeutics).

Assessment of repeated reference measurements to inform the validity of optical breast spectroscopy.

Mammographic breast density is a strong breast cancer risk factor, and its routine clinical measurement could potentially be used to identify women at higher risk of breast cancer and/or monitor primary prevention strategies. Previous reports of optical breast spectroscopy (OBS), a novel approach to measuring breast density, demonstrated that it is safe (no ionizing radiation), portable, low-cost, and does not require image interpretation but have been limited to small, single-center studies. Reference measurements taken on a phantom breast prior to and after each woman's OBS assessment are required for the calibration of the system transfer function as a part of processing participant data. To inform the validity of participant data, a detailed description of the reference measurements and a repeatability analysis of these measurements taken before and after participant assessment is presented. Reference measurements for OBS from 539 women aged 18-40 years were obtained as a part of a high-throughput epidemiological pilot study. Of these, measurements from 20 women with no useable data due to device failure (3.7%) were excluded and from another 12 women due to user error. The intra-class correlation (ICC) within complete pairs of reference data (taken before and after assessment) was high (all ICC > 0.84). The analysis presented here confirms the OBS participant data as valid for use in ongoing epidemiological research, providing further supporting evidence of OBS as a measure of breast density. A novel method of measuring breast density is needed to bridge large gaps in the knowledge of breast density in younger women and its relation to later-life breast cancer risk.

Two-Year Administration Data of an Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men

ABSTRACT Introduction An oral testosterone (T) replacement therapy (TRT) would be the preferred administration route for many hypogonadal men. Until recently, the only oral TRT approved in the US was methyl-T which has been associated with hepatotoxicity. Objective The safety of a novel oral T undecanoate (TU) formulation was evaluated in hypogonadal men with two-year follow up. Methods Two open-label, multicenter, dose-titration trials were conducted in hypogonadal men (serum T ≤ 300 ng/dL) age 18-75 years. Trial I was a randomized, active-controlled, 2-arm, 12-month study. Trial 2 was a long-term extension of those who completed Trial 1. Statistical analyses were only conducted with the subjects who completed Trial 1 and continued treatment in Trial 2, thus providing up to 2 full years of data. Safety was assessed by physical exam, AE reporting, and routine clinical laboratory measurements. Results Overall, 86 subjects participated in both studies. T concentration increased from 193.75 ± 9.44 ng/dL (Mean ± SEM) at baseline (BL) to 475.5 ± 49.7 ng/dL after 24 Mo of therapy with oral TU, and 84% of men achieved T in eugonadal range (300-1000 ng/dL) after 90 days of therapy. Mean T concentrations remained in the eugonadal range throughout Trial 2. There were no clinically significant changes in liver function tests – ALP (64.05 ± 1.95 to 53.74 U/L ± 1.86 U/L), ALT (27.8 ± 1.40 to 26.7 ± 1.6 U/L), AST (21.6 ± 0.76 to 22.0 ± 1.0 U/L), and bilirubin (0.58 ± 0.03 to 0.52 ± 0.03 mg/dL) throughout the two studies. At d270, one subject had an ALT level of 227 U/L, which was > 4x the ULN (ULN for ALT = 45 U/L). Despite continued use of oral TU, ALT was measured again on d290, and the level dropped to 87 U/L, < 2x ULN. This was the only instance of an LFT elevation. There was a modest initial increase in prostate-related growth endpoints (i.e. PSA and prostate volume) that stabilized over time. Although there was a slight increase in prostate-growth related endpoints, there were no significant changes in IPSS total score (-0.06 ± 3.9 vs BL). There were significant, yet modest, increases in mean HCT (44.3 ± 0.3 to 46.6 ± 0.5%, p < 0.001) and cuff systolic BP (127.1 ± 1.2 to 131.8 ± 1.67 mmHg vs BL, p = 0.006). The change in CV endpoints, including HDL-C, hematocrit, and BP, changed initially and stabilized throughout the 2 trials. For example, systolic BP varied 3 – 6 mm Hg from BL throughout the study. Conclusions This oral TU formulation is an option for hypogonadal men and has a safety profile consistent with other approved T products, such as a rise in hematocrit and a decrease in HDL-C. Notably, no evidence of liver toxicity was observed over 2 years. The long-term efficacy and safety profile of oral TU may provide a treatment option that avoids issues associated with other TRTs, such as injection site pain or transference to partners and children. Disclosure Yes, this is sponsored by industry/sponsor: Clarus Therapeutics Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Clarus Therapeutics

Symptom and performance validity in samples of adults at clinical evaluation of ADHD: a replication study using machine learning algorithms

ABSTRACT Introduction Research has shown non-trivial base rates of noncredible symptom report and performance in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. The goal of this study is to estimate and replicate base rates of symptom and performance validity test failure in the clinical evaluation of adult ADHD and derive prediction models based on routine clinical measures. Methods This study reuses data of a previous publication of 196 adults seeking ADHD assessment and replicates the findings on an independent sample of 700 adults recruited in the same referral context. Measures of symptom and performance validity (one SVT, two PVTs) were applied to estimate base rates. Prediction models were developed using machine learning. Results Both samples showed substantial rates of noncredible symptom report (one SVT failure: 35.7% – 36.6%), noncredible test performance (one PVT failure: 32.1% – 49.3%; two PVT failures: 18.9% – 27.3%), or both (each one SVT and PVT failure: 13.3% – 22.4%; one SVT and two PVT failures: 9.7% – 13.7%). Machine learning algorithms resulted in generally moderate to weak prediction models, with advantages of the reused sample compared to the independent replication sample. Associations between measures of symptom and performance validity were negligible to small. Conclusions This study highlights the necessity to include measures of symptom and performance validity in the clinical evaluation of adult ADHD. Further, this study demonstrates the difficulty to characterize the group failing symptom or performance validity assessment.

Feasibility of Dialysate Bolus-Based Absolute Blood Volume Estimation in Maintenance Hemodialysis Patients.

BackgroundAbsolute blood volume (ABV) is a critical component of fluid status, which may inform target weight prescriptions and hemodynamic vulnerability of dialysis patients. Here, we utilized the changes in relative blood volume (RBV), monitored by ultrasound (BVM) upon intradialytic 240 mL dialysate fluid bolus-infusion 1 h after hemodialysis start, to calculate the session-specific ABV. With the main goal of assessing clinical feasibility, our sub-aims were to (i) standardize the BVM-data read-out; (ii) determine optimal time-points for ABV-calculation, “before-” and “after-bolus”; (iii) assess ABV-variation.MethodsWe used high-level programming language and basic descriptive statistics in a retrospective study of routinely measured BVM-data from 274 hemodialysis sessions in 98 patients.ResultsRegarding (i) and (ii), we automatized the processing of RBV-data, and determined an algorithm to select the adequate RBV-data points for ABV-calculations. Regarding (iii), we found in 144 BVM-curves from 75 patients, that the average ABV ± standard deviation was 5.2 ± 1.5 L and that among those 51 patients who still had ≥2 valid estimates, the average intra-patient standard deviation in ABV was 0.8 L. Twenty-seven of these patients had an average intra-patient standard deviation in ABV <0.5 L.ConclusionsWe demonstrate feasibility of ABV-calculation by an automated algorithm after dialysate bolus-administration, based on the BVM-curve. Based on our results from this simple “abridged” calculation approach with routine clinical measurements, we encourage the use of multi-compartment modeling and comparison with reference methods of ABV-determination. Hopes are high that clinicians will be able to use ABV to inform target weight prescription, improving hemodynamic stability.

Development of an Automated Chemiluminescent Enzyme Immunoassay for Measuring Thrombopoietin in Human Plasma.

Plasma thrombopoietin (TPO) measurements help distinguish between different types of thrombocytopenia but are not feasible in routine clinical practice. We developed a fully automated quantitative chemiluminescent enzyme immunoassay (CLEIA) for measuring TPO (TPO-CLEIA), which is a one-step sandwich-type assay. This assay utilizes a mouse monoclonal capture antibody, which has the neutralizing epitope of the interaction between TPO and the TPO receptor, and a newly generated rabbit monoclonal detector antibody. In analytical performance studies, this assay showed good linearity over the measuring range and high sensitivity. The limit of quantification (LoQ) of this assay was 3.4 pg/mL; low TPO concentration values of almost all healthy individuals exceeded the LoQ value. In clinical validation studies, TPO levels obtained from patients with aplastic anemia (AA) significantly increased, whereas those of patients with immune thrombocytopenia (ITP) were normal or slightly increased. The cutoff value for TPO-CLEIA corresponding to the previously reported values was useful for distinguishing between ITP and AA. These results suggest that TPO-CLEIA can quantify human plasma TPO levels with high accuracy and sensitivity and has the potential to facilitate routine clinical measurement of TPO in patients with various types of thrombocytopenia.

Can single‐cell RNA sequencing reshape the clinical biochemistry of haematology? New clusters of circulating blood cells

AbstractscRNA‐seq is on track for use as a routine measurement of clinical biochemistry and to assist in clinical decision‐making and guide the performance of molecular medicine, but there are still a large number of challenges to be overcome. In conclusion, scRNA‐seq‐based clusters and differentiations of circulating blood cells have been examined and informative in patients with various diseases, although the information generated from scRNA‐seq varies between different conditions, technologies and diseases. Most of the clinical studies published have focused on the landscape of circulating immune cells, disease‐specific patterns of new clusters, understanding of potential mechanisms, and potential correlation between cell clusters, differentiations, cell interactions and circulating and migrated cells. It is clear that the information from scRNA‐seq advances the understanding of the disease, identifies disease‐specific target panels and suggests new therapeutic strategies. The adaptation of scRNA‐seq as a routine clinical measurement will require standardisation and normalisation of scRNA‐seq‐based comprehensive information and validation in a large population of healthy and diseased patients. The integration of public databases on human circulating cell clusters and differentiations with application of artificial intelligent and computational science will accelerate the application of scRNA‐seq for clinical practice. Thus, we call special attention from scientists and clinicians to the clinical and translational discovery, validation and medicine opportunities of scRNA‐seq development.

Evaluation of the Value of Waist Circumference and Metabolomics in the Estimation of Visceral Adipose Tissue.

Visceral adipose tissue (VAT) is a strong prognostic factor for cardiovascular disease and a potential target for cardiovascular risk stratification. Because VAT is difficult to measure in clinical practice, we estimated prediction models with predictors routinely measured in general practice and VAT as outcome using ridge regression in 2,501 middle-aged participants from the Netherlands Epidemiology of Obesity study, 2008–2012. Adding waist circumference and other anthropometric measurements on top of the routinely measured variables improved the optimism-adjusted R2 from 0.50 to 0.58 with a decrease in the root-mean-square error (RMSE) from 45.6 to 41.5 cm2 and with overall good calibration. Further addition of predominantly lipoprotein-related metabolites from the Nightingale platform did not improve the optimism-corrected R2 and RMSE. The models were externally validated in 370 participants from the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS, 2006–2009) and 1,901 participants from the Multi-Ethnic Study of Atherosclerosis (MESA, 2000–2007). Performance was comparable to the development setting in PIVUS (R2 = 0.63, RMSE = 42.4 cm2, calibration slope = 0.94) but lower in MESA (R2 = 0.44, RMSE = 60.7 cm2, calibration slope = 0.75). Our findings indicate that the estimation of VAT with routine clinical measurements can be substantially improved by incorporating waist circumference but not by metabolite measurements.

Estimated glomerular filtration rate as a measurement of kidney function.

Estimated glomerular filtration rate is an established, routine clinical measurement for kidney function, but the estimate has limitations and cannot be used in all clinical situations. Estimated glomerular filtration rate has a high coefficient of variation, and deviations in the patient's height, weight or muscle mass may result in an imprecise estimate. If an accurate measurement of kidney function is essential, glomerular filtration rate can be measured using an exogenous substance.

Age-Associated Decline in Blood Parameters in Individuals with Sickle Cell Disease

IntroductionIndividuals with sickle cell disease (SCD) in resource-rich countries are now living longer due to the implementation of newborn screening, use of prophylactic penicillin, and introduction of hydroxyurea. The impact of SCD on the bone marrow and peripheral blood counts as individuals with SCD age is not well described in the hydroxyurea era. As a result of increased red blood cell (RBC) turnover due to hemolysis in SCD, potential ineffective erythropoiesis, and well-described systemic inflammatory processes, the increased stress in the bone marrow may manifest as decreased peripheral blood cell counts over time in a during an aging process unique to those with SCD.ObjectiveThe objective was to model routine clinical blood measurements (n=5,328) with a longitudinal cohort of 447 patients, resulting in models of circulating blood counts as a potential marker of bone marrow function across the lifespan in adults with SCD. Our working hypothesis was that increasing age would be associated with decreases in certain blood counts, with trends modified by SCD genotype severity.MethodsIn this large, single institution retrospective cohort study, we analyzed blood count measurements from adults with SCD. We used an accelerated longitudinal cohort design to examine changes in white blood cell count (WBC), hemoglobin (HGB), absolute reticulocyte count (ARC), and platelet count over time. Genotypes were grouped as severe (HbSS or HbSβ 0-thalassemia; n=301), non-severe (HbSC or HbSβ +-thalassemia; n=136), or other (n=10). For HGB and ARC, we adjusted for estimated glomerular filtration rate (eGFR) and serum creatinine.ResultsPatients ranged in age at enrollment from 18 to 84 (M = 31.9, SD=12.9), with median follow-up time of 3.6 years and a median of 6 measurements per patient. Overall, HGB and ARC decreased across the lifespan; however, trends were moderated by genotype. Compared to individuals with non-severe genotypes, those with the severe genotypes had consistently lower HGB levels that did not differ by age. For ARC, the severe genotypes had higher levels in young adulthood, which slowly decreased with age. WBC also decreased with age for this group. In contrast, individuals with the non-severe genotype showed an increase in WBC by age. Platelet counts decreased with increasing age for those with the severe genotype while those with non-severe genotypes showed an increase with age.ConclusionSevere SCD genotypes are associated with decreases in HGB, ARC, WBC, and platelet count by age. For HGB and ARC, these declines are significantly attenuated by renal function, suggesting that such declines are largely related to worsening renal function with age. However, an intrinsic bone marrow contribution to this aging process should also be explored in future studies. Decreases in WBC and platelet count with time, observed in the severe genotypes, support the presence of pathological processes of bone marrow dysfunction that may worsen with age. A possible etiology of the increasing bone marrow dysfunction in SCD may be a result of bone marrow exhaustion or cellular senescence. Prospective studies to explore contributors to reduced blood counts during the aging process in individuals with SCD are needed. We are actively exploring potential biomarkers associated with this process. [Display omitted] DisclosuresCarden: Forma Therapeutics: Current Employment. Derebail: Novartis: Consultancy; UpToDate: Patents & Royalties; Travere Therapeutics: Consultancy; Bayer: Consultancy. Ataga: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Sit-to-Stand Weight-Bearing Symmetry Performance in Total Knee Arthroplasty: Recovery Curves, Correlates, and Predictive Validity With Gait Speed.

After total knee arthroplasty, the ability to weight bear symmetrically during the sit-to-stand task provides important information regarding altered movement patterns. Despite this, comprehensive recovery curves and validity data for sit-to-stand weight-bearing symmetry are lacking in the total knee arthroplasty population. Our study aimed to (1) develop recovery curves with reference ranges, (2) identify the correlates of standard and constrained sit-to-stand weight-bearing symmetry, and (3) evaluate their predictive validity with gait speed. We performed a retrospective longitudinal study of 706 patients with primary unilateral total knee arthroplasty. Monthly, for 4 mos after surgery, sit-to-stand weight-bearing symmetry, knee pain, knee range of motion, quadriceps strength, and gait speed were quantified. Standard and constrained sit-to-stand weight-bearing symmetry measures improved nonlinearly over time. Standard sit-to-stand weight-bearing symmetry was most strongly associated with bilateral quadriceps strength, whereas constrained sit-to-stand weight-bearing symmetry was most strongly associated with ipsilateral quadriceps strength. Knee range of motion and contralateral knee pain were additional correlates. Both standard sit-to-stand and constrained sit-to-stand weight-bearing symmetry were independently and nonlinearly associated with gait speed in multivariable models. Our study provided recovery curves and validity data to support routine clinical measurement of sit-to-stand weight-bearing symmetry in total knee arthroplasty. Our results also indicate that constrained sit-to-stand may promote greater use of the operated limb than standard sit-to-stand.

Clinical Characteristics and the Long-Term Post-recovery Manifestations of the COVID-19 Patients-A Prospective Multicenter Cross-Sectional Study.

Objective: Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global issue. In addition to managing acute cases, post-COVID-19 persisting symptoms/complaints and different hematological values are of great concern. These have an impact on the patient's well-being and are yet to be evaluated. Therefore, clinical and primary diagnosis based on routine laboratory findings bears high importance during the initial period of COVID-19, especially in regions with fewer diagnostic facilities.Methods: Clinical information and associated complaints of the COVID-19 illness confirmed by reverse transcription-polymerase chain reaction (RT-PCR) were collected directly from the patients. Regular follow-ups were obtained on the phone every 2 weeks following recovery for 20 weeks. Initial hematological and radiology findings of the hospitalized patients except for intensive care unit (ICU) and high dependency units (HDUs) and a follow-up evaluation after 4 weeks following recovery were analyzed.Results: The post-COVID-19 persisting symptoms/complaints were found among 21.4% of symptomatic patients, which persisted for ≥20 weeks and had a significant relationship with the duration of COVID-19 illness and the existing comorbidity (p < 0.05). Post-COVID-19 primary type 2 diabetes mellitus (DM, 0.64%) and hypertension (HTN, 1.28%) and unstable DM (54.55%) and HTN (34.78%) to the pre-existing diabetic and hypertensive patients were observed. Post-recovery remarkable changes in the laboratory values included leukocytosis (16.1%), lymphocytosis (14.5%), and an increased prothrombin time (PT, 25.8%). Abnormalities in the D-dimer, serum ferritin, hemoglobin, and erythrocyte sedimentation rate (ESR) levels were present to an extent. Laboratory findings like chest X-ray, ESR, white blood cell (WBC) count, lymphocyte count, C-reactive protein (CRP), serum glutamic pyruvic transaminase (SGPT), serum ferritin, PT, D-dimer, and serum creatinine are important markers for the diagnosis and prognosis of COVID-19 illness (p < 0.05).Conclusion: Post-COVID-19 persisting symptoms and the changes in the laboratory values need to be considered with importance and as a routine clinical measure. Post-COVID-19 periodic follow-up for evaluating the patient's physical condition and the biochemical values should be scheduled with care and managed accordingly to prevent future comorbidity in patients with the post-COVID-19 syndrome.

The measurement of ocular axial length in normal human eyes based on an improved Twyman-Green interferometer.

In order to meet the demands of myopia prevention, as well as the increasing needs of measurement for refractive and cataract operations in China, a new axial length (AL) measurement system combining an improved Twyman-Green interferometer with digital signal processing has been established. The ALs of 33 eyes of different optical refractive subjects (-8.50 ~ 0.50 D) were measured with the New AL and intraocular lens (IOL) master. The repeatability of measurements with the New AL was assessed using coefficient of variation (CoV) and intra-group correlation coefficient (ICC). Comparison, correlation, linear regression and agreement of AL between devices were analyzed. There was good repeatability (CoV=0.0617%, ICC=0.9999) with the New AL and great agreement has been obtained with both devices. These show that the New AL is capable of providing precise AL values over the normal AL range compared to the IOL master, and indicate that the New AL developed can be used for routine clinical AL measurements.

Creative Music Therapy and Neurodevelopmental Outcomes in Pre-term Infants at 2 Years: A Randomized Controlled Pilot Trial.

Impaired neurodevelopment is increasingly recognized as a major health issue in children born prematurely. Creative music therapy (CMT) intends to prevent and or reduce neurobehavioral deficits in pre-term infants using musical stimulation and socio-emotional co-regulation. We conducted a randomized, clinical pilot CMT trial to test feasibility and to examine long-term neurodevelopmental outcomes in pre-term infants (NCT02434224: https://clinicaltrials.gov/ct2/show/NCT02434224). Eighty-two pre-term infants were randomized either to CMT or standard care. A specially trained music therapist provided family-integrating CMT via infant-directed singing during hospitalization. Fifty-six infants underwent follow-up at 2 years of corrected age. No significant beneficial nor adverse effects of CMT were identified in routine clinical neurodevelopmental measures (Bayley-III Scales of Infant and Toddler Development and the standardized neurological examination). Longer term follow-up (5 years) and larger future studies are recommended to elucidate possible long-term effects of music in relation to more sensitive outcomes including executive function, detailed language processing and social-emotional development.

187-OR: Advanced Glycation End Products Predict Loss of Renal Function and High-Risk Chronic Kidney Disease in Type 2 Diabetes in the ACCORD Trial

Individual advanced glycation end products (AGEs) have been implicated in the development of chronic kidney disease (CKD). We evaluated the prognostic utility of a comprehensive multicomponent AGE panel in predicting long-term renal function loss and CKD when added to routine clinical measures in persons with type 2 diabetes (T2D) followed for 12.5 years (including risk factor intervention and observation phases). The five key AGEs (carboxymethyl and carboxyethyl lysine, and methylglyoxal, 3-deoxyglucosone and glyoxal hydroimidazolone) were measured via LC-MS/MS in baseline serum from 1,151 the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. A composite AGE score was calculated as the mean of individual AGE z-scores. Outcomes were (1) renal function loss (≥40% decline in estimated glomerular filtration rate [eGFR]), (2) macroalbuminuria (MAU), and (3) high-risk CKD (hrCKD, KDIGO classification). Higher AGE score predicted greater risks of renal function loss (n=260 events, hazard ratio 1.49 [95%CI 1.24-1.79], p&amp;lt;0.0001), MAU (n=96, 1.45 [1.06-1.98], p=0.005) and hrCKD (n=128, 1.95 [1.47-2.57], p&amp;lt;0.0001), independent of baseline eGFR, urine albumin:creatinine, randomization arms, other standard risk factors and hemoglobin A1c. Higher AGE score predicted renal function loss even in those with normal renal function (1.40 [1.06-1.84], p=0.02). When added to routine risk factors, AGE score improved net-reclassification and integrated discrimination for renal function loss (by 19% and 17%, p=0.002) and hrCKD (by 34% and 4.9%; p=0.02), but not MAU (0.8% and 1.3%, p=0.6). There is a strong independent association between AGE burden and progression of CKD in T2D. Adding AGE measures to standard clinical parameters improves the prediction of multiple kidney outcomes, indicating its potential as prognostic biomarker of diabetes nephropathy. Disclosure J. Koska: None. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. P. J. Beisswenger: Stock/Shareholder; Self; PreventAGE Healthcare LLC. P. Reaven: Research Support; Self; AstraZeneca, Dexcom, Inc. Funding National Institutes of Health (R21HL150268)

MO615SUPPORT FOR CHRONIC KIDNEY DISEASE PATIENTS DURING COVID-19: PERSPECTIVES FROM PATIENTS, FAMILY AND HEALTHCARE PROFESSIONALS

Background and AimsPatients with non-dialysis chronic kidney disease (CKD patients) require specialised management, including routine clinical visits, laboratory measures, and medication adjustments. Inevitably, the COVID-19 pandemic has resulted in changes to delivery of care in a bid to prevent virus transmission in this clinically vulnerable group. The extent of the impact of any changes in support provision for patients is largely unknown. The study aimed to capture the views of CKD patients, family or other significant person in their lives (SO), and nephrology healthcare professionals (HCPs) on how patients’ healthcare needs were and could be supported during this time.MethodCKD patients, their SO (e.g., family member, friend) and HCPs from 10 secondary care sites across England were invited to take part in a bespoke online survey, as part of the DIMENSION-KD portfolio adopted study. Participants responded to yes/no and free-text questions about their satisfaction with available healthcare support (CKD, SO) and patients’ need for additional support (CKD, SO, HCP). Thematic analysis was applied to the free-text responses.Results230 CKD patients (mean age 63.8, SD 13.8 years), 67 SO (74% spouses), and 59 HCP of various specialties completed the survey between August and December 2020. 84% of CKD participants felt they could get the support they needed. The most frequent explanation (25%) was that direct contact with a member of their renal team was available when needed. Other explanations included 1. being monitored by the renal team, 2. continuation of regular appointments and having additional treatment when necessary, 3. an accessible local General Practice (GP), and 4. a particularly “helpful” nephrologist or “good relationships” with their doctors. All SO felt the patient could get the help they required. Their explanations were in line with those of CKD patients, i.e., readily available contact and access to the renal team (25%), followed by good relationship or highly positive experience with member(s) of the renal team, regularity of contact/ appointments, and GP accessibility. When asked about additional healthcare information and support they would like, “none” was the most common response by CKD patients (28%), followed by the need for reliable information around COVID-19 and renal conditions, access to local GP, and a reliable point of contact when kidney condition deteriorates. Similarly, for many SO there was no need for additional support, whilst the most often suggested type of support was provision of reliable information on COVID-19 and renal health. For HCP, accessible service and guidance (36%) and psychosocial support for patients (25%) were most frequently cited types of additional support that would benefit patients.ConclusionAn accessible point of contact for renal care and continuation of regular monitoring of some form emerged as key factors in CKD patient support across the three stakeholder groups. Some needs raised, such as limited access to GP, are relevant to local primary or secondary healthcare services, while practices adopted by some renal teams, such as a number for patients to ring when needed, seemed to offer reassurance and satisfaction among patients and their SO.

Safety Analysis of an Oral Testosterone Undecanoate (TU) Formulation Following 2 Years of Administration in Hypogonadal Men

Introduction: An oral testosterone (T) replacement therapy (TRT) would be the preferred choice for many hypogonadal men. Until recently, the only oral TRT approved in the US was methyl-T which has been associated with hepatotoxicity. The safety of a novel oral T undecanoate (TU) formulation was evaluated in hypogonadal men for up to 2 years. Subjects and Methods: Two open-label, multicenter, dose-titration trials were conducted in hypogonadal men (serum T ≤ 300 ng/dL) age 18-75 years. Trial I was a randomized, active-controlled, 2-arm, 12-month study. Trial 2 was a long-term extension of those who completed Trial 1. Statistical analyses were only conducted with the subjects who completed Trial 1 and continued treatment in Trial 2, thus providing up to 2 full years of data. Safety was assessed by physical exam, AE reporting, and routine clinical laboratory measurements. Results: Overall, up to 81 subjects were available for evaluation. T concentration increased from 208.3 ± 102.4 ng/dL (Mean ± SD) at baseline (BL) to 470.1 ± 396.5 ng/dL after 24 Mo of therapy with oral TU, and 84% of men achieved T in eugonadal range (300-1000 ng/dL) after 90 days of therapy. Mean T concentrations remained in the eugonadal range throughout Trial 2. There were no clinically significant changes in liver function tests - ALT (28.0 ± 12.3 to 26.6 ± 12.8 U/L), AST (21.8 ± 6.8 to 22.0 ± 8.2 U/L), and bilirubin (0.58 ± 0.22 to 0.52 ± 0.19 mg/dL) throughout the two studies. At Day 270, one subject had an ALT level of 227 U/L, which was > 4x the ULN (ULN for ALT = 45 U/L). Despite continued use of oral TU, ALT was measured again on Day 290, and the level dropped to 87 U/L, < 2x ULN. This was the only instance of an LFT elevation. There was a modest initial increase in prostate-related growth endpoints (i.e. PSA and prostate volume) that stabilized over time. There were not any significant changes in IPSS total score (-0.06 ± 3.9 vs BL). There were significant, yet modest, increases in mean HCT (+2.52 ± 3.7% vs BL, p < 0.001) and cuff systolic BP (+5.6 ± 15.0 mmHg vs BL, p = 0.006). The change in prostate-related growth variables and CV endpoints changed initially and stabilized throughout the 2 trials. For example, systolic BP consistently showed a mean increase from BL between 3 - 6 mmHg. Conclusion: This oral TU formulation is an effective long-term therapy for hypogonadal men and has a safety profile consistent with other approved T products. Notably, no evidence of liver toxicity was observed. The long-term efficacy and safety profile of oral TU may provide a treatment option that avoids issues associated with other TRTs, such as injection site pain or transference to partners and children.

Development and Internal Validation of a Prognostic Model for 4-Year Risk of Metabolic Syndrome in Adults: A Retrospective Cohort Study.

PurposeA prognostic prediction model for metabolic syndrome can help nurses or physicians evaluate the future individual absolute risk of MetS in order to develop personalized care strategies. We aimed to derive and internally validate a prognostic prediction model for 4-year risk of metabolic syndrome in adults.Patients and MethodsThis was a retrospective cohort study conducted in a tertiary care setting, and the dataset was obtained from the Healthcare Information and Management Systems of a tertiary hospital. The cohort included Chinese adults attending health examination from 1 January 2011 to 31 December 2014. A total of 6793 participants without metabolic syndrome were included in the cohort and were followed up for 4 years. Available candidate predictors in the dataset were weight, MCV, MCH, AST, ALT, BMI, NGC, TC, serum uric acid, gender, smoking, WBC, LC, Hb, HCT, and age. A logistic regression model was adopted to build the risk equation, and bootstrapping was used when considering internal validation. Calibration, discrimination, and the clinical utility were calculated for the model’s performance.ResultsOf the 6793 participants, 1750 participants were diagnosed with metabolic syndrome within 4 years. The developed prediction model contained 5 predictors (body mass index, age, total cholesterol, alanine transaminase, and serum uric acid). After internal validation, the C-statistic was 0.783 (95% CI, 0.772–0.795). Additionally, the current model had good calibration. Calibration slope was 0.995 (95% CI, 0.934–1.058), and calibration intercept was −0.008 (95% CI, −0.088–0.073). The Brier score was 0.156. The decision-curve analysis indicated that the prediction model provided greater net benefit than the default strategies of providing treatment or not providing treatment for all patients.ConclusionA prognostic risk prediction model for determining 4-year risk of metabolic syndrome onset in adults was developed and internally validated. This model was based on routine clinical measurements that quantified individual future risk of metabolic syndrome.