Routine Clinical Measurements Research Articles

ABIDE: An Accurate Predictive Model of Liver Decompensation in Patients With Nonalcoholic Fatty Liver-Related Cirrhosis.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly important cause of liver cirrhosis and subsequent complications. We retrospectively developed and validated a model to predict hepatic decompensation in patients with NAFLD and cirrhosis and compared this with currently available models. Baseline variables from an international cohort of 299 patients with biopsy-proven NAFLD with compensated cirrhosis were examined to construct a model using competing risk multivariate regression and Akaike/Bayesian information criteria. Validation was performed in 244 patients with biopsy-proven NAFLD cirrhosis from the United States. Prognostic accuracy was compared with the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4), Model for End-Stage Liver Disease (MELD), Child-Turcotte-Pugh (CTP), and albumin-bilirubin (ALBI)-FIB-4 score using time-dependent area under the curve (tAUC) analysis. During a median follow-up of 5.6years (range 2.4-14.1) and 5.4years (range 1.5-13.8), hepatic decompensation occurred in 81 and 132 patients in the derivation and validation cohorts, respectively. In the derivation cohort, independent predictors of hepatic decompensation (Aspartate aminotransferase/alanine aminotransferase ratio, Bilirubin, International normalized ratio, type 2 Diabetes, andEsophageal varices) were combined into the ABIDE model. Patients with a score ≥4.1 compared with those with a score <4.1 had a higher risk of decompensation (subhazard ratio, 6.7; 95% confidence interval [CI], 4.0-11.2; P<0.001), a greater 5-year cumulative incidence (37% vs. 6%, P<0.001), and shorter mean duration to decompensation (3.8 vs 6.7years, P<0.001). The accuracy of the ABIDE model at 5years was good in the derivation (tAUC, 0.80; 95% CI, 0.73-0.84) and validation cohorts (0.78; 95% CI, 0.74-0.81) and was significantly more accurate than the NFS (0.72), FIB-4 (0.74), MELD (0.69), CTP (0.72), and ALBI-FIB-4 (0.73) (all P<0.001). In patients with NAFLD and compensated cirrhosis, ABIDE, a predictive model of routine clinical measures, predicts future hepatic decompensation.

The Alzheimer's Association international guidelines for handling of cerebrospinal fluid for routine clinical measurements of amyloid β and tau

AbstractThe core cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers amyloid beta (Aβ42 and Aβ40), total tau, and phosphorylated tau, have been extensively clinically validated, with very high diagnostic performance for AD, including the early phases of the disease. However, between‐center differences in pre‐analytical procedures may contribute to variability in measurements across laboratories. To resolve this issue, a workgroup was led by the Alzheimer's Association with experts from both academia and industry. The aim of the group was to develop a simplified and standardized pre‐analytical protocol for CSF collection and handling before analysis for routine clinical use, and ultimately to ensure high diagnostic performance and minimize patient misclassification rates. Widespread application of the protocol would help minimize variability in measurements, which would facilitate the implementation of unified cut‐off levels across laboratories, and foster the use of CSF biomarkers in AD diagnostics for the benefit of the patients.

An MRI approach to assess placental function in healthy humans and sheep.

Human placental function is evaluated using non-invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption ( ) is only possible during Caesarean delivery. This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental by MRI was ∼4mlmin-1 kg-1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques. Our MRI approach can quantify uteroplacental , which involves the quantification of maternal- and fetal-placental blood flows, fetal oxygen delivery and , and the oxygen gradient between uterine- and umbilical-venous blood, providing a comprehensive assessment of placental function with clinical potential. It has not been feasible to perform routine clinical measurement of human placental oxygen consumption ( ) and in vitro studies do not reflect true metabolism in utero. Here we propose an MRI method to non-invasively quantify in utero placental and fetal oxygen delivery ( ) and in healthy humans and sheep. Women (n=20) and Merino sheep (n=10; 23sets of measurements) with singleton pregnancies underwent an MRI in late gestation (36±2weeks and 128±9days, respectively; mean±SD). Blood flow (phase-contrast) and oxygen content (T1 and T2 relaxometry) were measured in the major uterine- and umbilical-placental vessels, allowing calculation of uteroplacental and fetal and . Maternal (mlmin-1 kg-1 fetus) to the gravid uterus was similar in humans and sheep (human=54±15, sheep=53±21, P=0.854), while fetal (human=25±4, sheep=22 ± 5, P=0.049) was slightly lower in sheep. Uteroplacental and fetal (mlmin-1 kg-1 fetus; uteroplacental: human=4.1±1.5, sheep=3.5±1.9, P=0.281; fetus: human=6.8±1.3, sheep=7.2±1.7, P=0.426) were similar between species. Late gestational uteroplacental:fetal ratio did not change with age (human, P=0.256; sheep, P=0.121). Human umbilical blood flow (mlmin-1 kg-1 fetus) decreased with advancing age (P=0.008), while fetal was preserved through an increase in oxygen extraction (P=0.046). By contrast, sheep fetal was preserved through stable umbilical flow (mlmin-1 kg-1 ; P=0.443) and oxygen extraction (P=0.582). MRI derived measurements of uteroplacental and fetal between humans and sheep were similar and in keeping with prior data obtained using invasive techniques. Taken together, these data confirm the reliability of our approach, which offers a novel clinical 'placental function test'.

A simple and reliable measurement procedure for determination of glycocholic acid in human serum by isotope-dilution liquid chromatography-tandem mass spectrometry

Glycocholic acid (GCA) is an important identified biomarker for various hepatobiliary diseases. However, results obtained from routine clinical measurement significantly varied due to the interference from the extremely similar structure analogues, which cause confusion to clinical diagnosis. In this study, a bracketing calibration-based isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method was developed. The established method exhibited good performance criteria through the adoption of isotope dilution, calibrator bracketing, and gravimetric measurements. The satisfactory precision (0.16%–2.01%) and good recoveries were achieved at five spiked levels (98.0–100.9%). The limit of detection (LOD) and limit of quantification (LOQ) were 0.01 ng/mL and 0.05 ng/mL, respectively. No interference, matrix effect, and carryover were observed. The sample preparation process was easier to operate, without further solvent evaporation and time-saving. The optimized method was successfully applied to quantify GCA with a wide range of concentrations in clinical human serum samples and also compared with clinical routine systems.

Recommendations for Standardizing Thorax PET-CT in Non-Human Primates by Recent Experience from Macaque Studies.

Simple SummaryWith computed tomography (CT) only anatomical information is obtained, but there is no information about function. Positron emission tomography (PET) only gives functional information about a target organ/tissue by the distribution of a specific contrast agent, a radiotracer. Combining the two imaging techniques provides synergy and they can amplify each other. In clinical practice, this combined PET–CT technique is already broadly used. For monkeys, it is increasingly used, with procedures and protocols mainly based on clinical practice. In this publication, we make recommendations about key steps towards standardization and optimization of non-human primate PET–CT (from study preparation to image interpretation).Despite the possibilities of routine clinical measures and assays on readily accessible bio-samples, it is not always essential in animals to investigate the dynamics of disease longitudinally. In this regard, minimally invasive imaging methods provide powerful tools in preclinical research. They can contribute to the ethical principle of gathering as much relevant information per animal as possible. Besides, with an obvious parallel to clinical diagnostic practice, such imaging platforms are potent and valuable instruments leading to a more refined use of animals from a welfare perspective. Non-human primates comprise highly relevant species for preclinical research to enhance our understanding of disease mechanisms and/or the development of improved prophylactic or therapeutic regimen for various human diseases. In this paper, we describe parameters that critically affect the quality of integrated positron emission tomography and computed tomography (PET–CT) in non-human primates. Lessons learned are exemplified by results from imaging experimental infectious respiratory disease in macaques; specifically tuberculosis, influenza, and SARS-CoV-2 infection. We focus on the thorax and use of 18F-fluorodeoxyglucose as a PET tracer. Recommendations are provided to guide various stages of PET–CT-supported research in non-human primates, from animal selection, scan preparation, and operation, to processing and analysis of imaging data.

Prevalence and risk characteristics of COVID-19 in outpatients: A cross-sectional study of New York-area clinics.

Outpatients can be at heightened risk of COVID-19 due to interaction between existing non-communicable diseases in outpatients and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study measured the magnitude of COVID-19 prevalence and explored related risk characteristics among adult outpatients visiting medicine clinics within a New York state-based tertiary hospital system. Data were compiled from 63,476 adult patients visiting outpatient medicine clinics within a New York-area hospital system between March 1, 2020, and August 28, 2020. The outcome was a clinical diagnosis of COVID-19. Crude and adjusted prevalence ratios (PR) of a COVID-19 were analyzed using univariable and multivariable Poisson regression with robust standard errors. The prevalence of COVID-19 was higher among these outpatients (3.0%) than in the total population in New York State (2.2%) as of August 28, 2020. Multivariable analysis revealed adjusted prevalence ratios significantly greater than one for male sex (PR=1.10), age 40 to 64 compared to <40 (PR=1.19), and racial/ethnic minorities in comparison to White patients (Hispanic: PR=2.76; Black: PR=1.89; and Asian/others: PR=1.56). Nonetheless, factors including the advanced age of ≥65 compared to <40 (PR=0.69) and current smoking compared to non-smoking (PR=0.60) were related to significantly lower prevalence. Therefore, the prevalence of COVID-19 in outpatients was higher than that of the general population. The findings also enabled hypothesis generation that routine clinical measures comprising sex, age, race/ethnicity, and smoking were candidate risk characteristics of COVID-19 in outpatients to be further verified by designs capable of assessing temporal association.

ED to EPI: protocol for a pragmatic randomised controlled trial of an SMS (text) messaging intervention to improve the transition from the emergency department to early psychosis intervention for young people with psychosis

IntroductionWhile nearly half of all new psychotic disorders are diagnosed in the emergency department (ED), most young people who present to the ED with psychosis do not receive timely follow-up...

Urinary Soluble CD163 and Disease Activity in Biopsy-Proven ANCA-Associated Glomerulonephritis.

ANCA-associated GN is a common cause of rapidly progressive GN, with high relapse rates. The early recognition of an ANCA-associated GN relapse is of importance to prevent loss of kidney function. Urinary soluble CD163 has been identified as a promising marker of active ANCA-associated GN. Previous studies, however, are limited by the lack of histologic data. We analyzed urinary soluble CD163 in 95 patients with ANCA-associated vasculitis who underwent a kidney biopsy. In total, 125 kidney tissue sections (first kidney biopsy, n=67; repeated biopsy, n=58) with concurrent 24-hour urine samples were studied. Correlation analyses comparing urinary soluble CD163 levels and morphologic features of ANCA-associated GN were performed using Spearman rank correlation analysis. The diagnostic performance of biomarkers to detect relapsing ANCA-associated GN was evaluated using receiver operating characteristics curve analysis. High levels of urinary soluble CD163 were found in 96 (87%) of 110 biopsies with active ANCA-associated GN compared with one (7%) of 15 biopsies without active ANCA-associated GN and one (6%) of 17 healthy controls. Urinary soluble CD163 correlated with fibrinoid necrosis (Rho=0.48, P<0.001) and cellular crescents (Rho=0.70, P<0.001) on kidney biopsy. In repeated biopsies, urinary soluble CD163's sensitivity of 0.94 and specificity of 0.91 for the recognition of relapsing ANCA-associated GN appeared better than routine clinical measures. The presence of CD163+ cells in affected glomeruli confirmed urinary soluble CD163's origin. Urinary soluble CD163 is associated with active ANCA-associated GN and correlates with histologic features as seen in ANCA-associated GN. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_11_17_CJN07210520_final.mp3.

Feasibility of Using Strength Measures, Including Peak Inspiratory Flow, for Routine Monitoring in Case Management Patients Aged 65 and over

Peak inspiratory flow (PIF) is a portable, relatively new method for measuring respiratory function and indirect muscle strength; the feasibility of its routine clinical measurement is unknown. To investigate the acceptability, reliability and short-term stability of PIF, alongside the established measures of peak expiratory flow (PEF) and grip strength in community dwelling case management patients. Patients were tested in a sitting position, initially on two occasions, one week apart; seven patients having repeated measures taken on a further four occasions over a seven-week period. The best of three attempts for all measures were recorded. Reliability was tested using intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimal detectable change (MDC) and Bland–Altman analysis. Eight patients aged 69–91 years (mean age 81.5 ± 7.7 years; 5 males) participated. For between-day reliability using the first two time points, one week apart the ICCs (3,1) were 0.97, 0.98 and 0.99 for PIF, PEF and grip strength respectively; using all five time points resulted in ICCs of 0.92, 0.99 and 0.99 respectively. Bland–Altman plots also illustrated a good level of agreement across days. Feedback on the acceptability of the measures was gathered from patients. PIF, PEF and grip strength showed excellent reliability and acceptability. Whilst excellent reliability was observed over the seven-week period, the occurrence of clinically significant symptoms and adverse events in the presence of unchanging PIF, PEF and grip strength, suggests that the measures may not be suitable to identify patients with multiple health conditions entering a period of acute decline.

Apolipoprotein B Level and the Apolipoprotein B/Apolipoprotein A-I Ratio as a Harbinger of Ischemic Stroke: A Prospective Observation in Taiwan

Aim: Prospective studies indicate that apolipoprotein (apo) measurements predict coronary heart disease risk. However, few population-based follow-up studies have addressed the predictive value of apo measurements in stroke risk. The aims of the present study were to analyze the predictive ability of apo measurements in the risk of ischemic stroke. Methods: Serum apo A-I and apo B levels and calculated apo B/apo A-I ratio were measured at baseline in 2002 in a cohort of 4,204 participants who were followed for a mean of 4.61 years for a stroke event. Results: After adjustment for potential confounders, a significantly stepwise increase in the incidence rate of stroke across quartiles of both apo B and the apo B/apo A-I ratio was evident in both genders and across age-groups. The predictive ability of apo B to detect ischemic stroke was comparable with that of the apo B/apo A-I ratio. Furthermore, both apo B and the apo B/apo A-I ratio were better predictors of the risk of ischemic stroke than total cholesterol (TC), low-density lipoprotein cholesterol, and the TC/high-density lipoprotein cholesterol ratio. Conclusions: This cohort study demonstrates that apo B and the apo B/apo A-I ratio were a significant risk predictor of stroke. Furthermore, the predictive ability of apo B and the apo B/apo A-I ratio in stroke risk was better than routine clinical lipid measurements. Thus, measurements of apolipoproteins have superior clinical utility over traditional lipid measurements in identifying subjects at risk for ischemic stroke.

Phase I trial of drug resistant immunotherapy: A first-in-class combination of MGMT-modified γδ t cells and temozolomide chemotherapy in newly diagnosed glioblastoma multiforme.

TPS3150 Background: Temozolomide (TMZ) transiently upregulates GBM-specific stress-induced NKG2D ligands that are targeted by innate immune effector cells. Leveraging this effect is problematic, however, due to the lymphodepleting effects of TMZ.Genetic modification of ex vivo expanded and activated with an MGMT-expressing lentivector allows simultaneous chemotherapy and γδ T cell therapy that targets the tumor when NKG2DL are maximally expressed. We have termed this Drug Resistant Immunotherapy (DRI). Patient-derived xenograft mouse models of both primary and recurrent GBM treated with DRI have shown a significant survival advantage that were otherwise impervious to either cell therapy or TMZ. These preclinical findings and associated safety data provide the rationale to initiate a Phase I trial of DRI in primary GBM. Methods: This first in human study will evaluate the safety and optimal dosing frequency of the DRI with TMZ (NCT04165941).Eligibility criteria include the following: GBM eligible for resection, ≥18y, adequate organ and marrow function, and KPS≥70. Six to 12patients with newly diagnosed GBM are being enrolled in a 3 + 3 design into 1 of 2 fixed dose levels (DL) of DRI. Following tumor resection and immediately prior to induction chemo/radiotherapy, an apheresis product is collected and γδ T cells expanded in Zoledronic Acid (Novartis) and rhIL-12 (Miltenyi) and transduced with a P140K-MGMT lentivector (Miltenyi Lentigen, Gaithersburg, MD), harvested, and cryopreserved. At initiation of maintenance phase TMZ therapy, patients receive 150mg/m2 intravenous TMZ concurrently with intracranial injection of 1 x 107 γδ T cells (DL1) delivered through a Rickham reservoir previously inserted into the tumor cavity at resection. The patient then receives 4 daily doses of oral TMZ followed by 24d rest. Treatment cycles escalate from 1 to 3 (DL2) DRI doses following a safety observation period and absence of dose limiting toxicity. Maintenance TMZ treatment will continue for 6 cycles. Safety evaluations consist of routine laboratory analyses, clinical measurements (physical exams, vital signs), neurological function and evidence DRI γδ T cell related toxicity. Peripheral blood will be obtained for comprehensive immuno-phenotyping and T cell function analysis. Clinical benefit of DRI will be characterized by evaluating responses (CR, PR, SD and PD) and determining progression-free, median, and overall survival. As of February 2020, enrollment into DL 1 is ongoing. Clinical trial information: NCT04165941 .

The Role of the Clinically Obtained Acoustic Reflex as a Research Tool for Subclinical Hearing Pathologies.

The acoustic reflex (AR) shows promise as an objective test for the presence of cochlear synaptopathy in rodents. The AR has also been shown to be reduced in humans with tinnitus compared to those without. The aim of the present study was twofold: (a) to determine if AR strength (quantified as both threshold and growth) varied with lifetime noise exposure, and thus provided an estimate of the degree of synaptopathy and (b) to identify which factors should be considered when using the AR as a quantitative measure rather than just present/absent responses. AR thresholds and growth functions were measured using ipsilateral and contralateral, broadband and tonal elicitors in adults with normal hearing and varying levels of lifetime noise exposure. Only the clinical standard 226 Hz probe tone was used. AR threshold and growth were not related to lifetime noise exposure, suggesting that routine clinical AR measures are not a sensitive measure when investigating the effects of noise exposure in audiometrically normal listeners. Our secondary, exploratory analyses revealed that AR threshold and growth were significantly related to middle-ear compliance. Listeners with higher middle-ear compliance (though still in the clinically normal range) showed lower AR thresholds and steeper AR growth functions. Furthermore, there was a difference in middle-ear compliance between the sexes, with males showing higher middle-ear compliance values than females. Therefore, it may be necessary to factor middle-ear compliance values into any analysis that uses the AR as an estimate of auditory function.

Estimates of blood plasma water content using portable NMR relaxometry

Although blood plasma water content (PWC) is a relevant metric for many medical diagnostic procedures, the routine clinical measurement of PWC has remained elusive. Portable nuclear magnetic resonance (NMR) offers one way to nondestructively and quickly measure PWC. Contrived pseudoplasma samples that mimic blood plasma while also allowing rigorous control over water content are used to demonstrate the role of NMR in this work. Calibration curves relating measured NMR relaxation time constants (T2 and T1) to gravimetric PWC values for a set of human lyophilized plasma samples are used to predict the PWC in porcine and model human blood plasma from respective NMR T2 and T1 values. It is shown that the T2 and T1 decay constants measured with low field NMR relaxometry correlate with the PWC values for pseudoplasma and human lyophilized plasma samples. Statistical testing of the NMR-PWC correlation model demonstrated a prediction accuracy exceeding 98%. The PWC obtained in this way was used to correct sodium cation concentrations reported from direct ion-selective electrode tests. The accuracy of PWC determination with NMR is comparable to that of the gravimetric method that requires sample lyophilization. The rapid turnaround time, non-destructive nature, and portable footprint of the NMR-PWC measurement makes rapid, point-of-care clinical electrolyte estimates possible.

DETERMINANTS OF QUALITY OF LIFE IN COMMUNITY-DWELLING OLD ADULTS

Background: Quality of life (QoL) has been regarded as a critical predictor of successful aging in gerontological research. Aim: The aim of this study was to examine the associations between physical activity, muscle strength, body composition, physical-/cognitive function and disease with quality of life community-dwelling older adults. Methods: Participants (N=225, 73.7±5.7yrs, 58.2% female) from the Reykjavik capital area in Iceland took part in this cross-sectional study. Socioeconomics, QoL, body composition, muscular strength, timed up and go test (TUG), six minute walk for distance (6MWD) and disease related information were measured. Fasting blood samples were analyzed for routine clinical measures. Results: In our subjects, only 19.1% had QoL below the age and gender corrected norm score of 50. A simple comparison between subjects with QoL below 50 vs subjects with a score above 50 indicated that participants with higher QoL had higher physical and cognitive function, higher muscular strength, lower blood glucose, exercised more and used a lower number of medicines. Differences in education, smoking, alcohol consumption, dietary intake and gender distribution were not significant. According to age and gender corrected linear models, TUG (B=-0.54,P=0.022), number of drugs (B=-0.67,P=0.018) and fasting glucose (B=-0.96,P=0.025) were the strongest independent correlates of QoL. In the models insulin/glucose and TUG/6MWD were interchangeable. Conclusion: Physical function, number of drugs and glucose metabolism are independently related to QoL and represent therefore potentially modifyable targets for future interventions in order to improve QoL in community dwelling old adults.

Derivation and external validation of a risk prediction algorithm to estimate future risk of cardiovascular death among patients with type 2 diabetes and incident diabetic nephropathy: prospective cohort study

ObjectiveTo derive, and externally validate, a risk score for cardiovascular death among patients with type 2 diabetes and newly diagnosed diabetic nephropathy (DN).Research design and methodsTwo independent prospective cohorts with...

PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes.

Type 1 diabetes mellitus (T1DM) has traditionally been characterized by a complete destruction of β-cell mass (BCM); however, there is growing evidence of possible residual BCM present in T1DM. Given the absence of in vivo tools to measure BCM, routine clinical measures of β-cell function (e.g., C-peptide release) may not reflect BCM. We previously demonstrated the potential utility of PET imaging with the dopamine D2 and D3 receptor agonist 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (11C-(+)-PHNO) to differentiate between healthy control (HC) and T1DM individuals. Methods: Sixteen individuals participated (10 men, 6 women; 9 HCs, 7 T1DMs). The average duration of diabetes was 18 ± 6 y (range, 14-30 y). Individuals underwent PET/CT scanning with a 120-min dynamic PET scan centered on the pancreas. One- and 2-tissue-compartment models were used to estimate pancreas and spleen distribution volume. Reference region approaches (spleen as reference) were also investigated. Quantitative PET measures were correlated with clinical outcome measures. Immunohistochemistry was performed to examine colocalization of dopamine receptors with endocrine hormones in HC and T1DM pancreatic tissue. Results: C-peptide release was not detectable in any T1DM individuals, whereas proinsulin was detectable in 3 of 5 T1DM individuals. Pancreas SUV ratio minus 1 (SUVR-1) (20-30 min; spleen as reference region) demonstrated a statistically significant reduction (-36.2%) in radioligand binding (HCs, 5.6; T1DMs, 3.6; P = 0.03). Age at diagnosis correlated significantly with pancreas SUVR-1 (20-30 min) (R2 = 0.67, P = 0.025). Duration of diabetes did not significantly correlate with pancreas SUVR-1 (20-30 min) (R2 = 0.36, P = 0.16). Mean acute C-peptide response to arginine at maximal glycemic potentiation did not significantly correlate with SUVR-1 (20-30 min) (R2 = 0.57, P = 0.05), nor did mean baseline proinsulin (R2 = 0.45, P = 0.10). Immunohistochemistry demonstrated colocalization of dopamine D3 receptor and dopamine D2 receptor in HCs. No colocalization of the dopamine D3 receptor or dopamine D2 receptor was seen with somatostatin, glucagon, or polypeptide Y. In a separate T1DM individual, no immunostaining was seen with dopamine D3 receptor, dopamine D2 receptor, or insulin antibodies, suggesting that loss of endocrine dopamine D3 receptor and dopamine D2 receptor expression accompanies loss of β-cell functional insulin secretory capacity. Conclusion: Thirty-minute scan durations and SUVR-1 provide quantitative outcome measures for 11C-(+)-PHNO, a dopamine D3 receptor-preferring agonist PET radioligand, to differentiate BCM in T1DM and HCs.

Counseling With Guided Use of a Mobile Well-Being App for Students Experiencing Anxiety or Depression: Clinical Outcomes of a Feasibility Trial Embedded in a Student Counseling Service.

BackgroundAnxiety and depression continue to be prominent experiences of students approaching their university counseling service. These services face unique challenges to ensure that they continue to offer quality support with fewer resources to a growing student population. The convenience and availability of mobile phone apps offer innovative solutions to address therapeutic challenges and expand the reach of traditional support.ObjectiveThe primary aim of this study was to establish the feasibility of a trial in which guided use of a mobile phone well-being app was introduced into a student counseling service and offered as an adjunct to face-to-face counseling.MethodsThe feasibility trial used a two-arm, parallel nonrandomized design comparing counseling alone (treatment as usual, or TAU) versus counseling supplemented with guided use of a mobile phone well-being app (intervention) for 38 university students experiencing moderate anxiety or depression. Students in both conditions received up to 6 sessions of face-to-face counseling within a 3-month period. Students who approached the counseling service and were accepted for counseling were invited to join the trial. Feasibility factors evaluated include recruitment duration, treatment preference, randomization acceptability, and intervention fidelity. Clinical outcomes and clinical change were assessed with routine clinical outcome measures administered every counseling session and follow-up phases at 3 and 6 months after recruitment.ResultsBoth groups demonstrated reduced clinical severity by the end of counseling. This was particularly noticeable for depression, social anxiety, and hostility, whereby clients moved from elevated clinical to low clinical or from low clinical to nonclinical by the end of the intervention. By the 6-month follow-up, TAU clients’ (n=18) anxiety had increased whereas intervention clients’ (n=20) anxiety continued to decrease, and this group difference was significant (Generalized Anxiety Disorder–7: t22=3.46, P=.002). This group difference was not replicated for levels of depression: students in both groups continued to decrease their levels of depression by a similar amount at the 6-month follow-up (Physical Health Questionnaire–9: t22=1.30, P=.21).ConclusionSupplementing face-to-face counseling with guided use of a well-being app is a feasible and acceptable treatment option for university students experiencing moderate anxiety or depression. The feasibility trial was successfully embedded into a university counseling service without denying access to treatment and with minimal disruption to the service. This study provides preliminary evidence for using a well-being app to maintain clinical improvements for anxiety following the completion of counseling. The design of the feasibility trial provides the groundwork for the development of future pilot trials and definitive trials embedded in a student counseling service.Trial registrationISRCTN registry ISRCTN55102899; http://www.isrctn.com/ISRCTN55102899

Estimating Waist and Hip Circumference from Routine Clinical DXA

Introduction: Waist circumference and waist:hip ratio have body mass index-independent detrimental effects on health and mortality. Dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine and hip can provide site-specific measures of soft-tissue thickness, and we hypothesized that this could be used to opportunistically estimate body circumference in patients undergoing DXA for osteoporosis assessment. Methodology: We assessed the correlation and explained variance (as coefficient of determination, R2) between directly measured body circumference (waist circumference, hip circumference, and waist:hip circumference ratio) with DXA-derived measures of soft tissue thickness (spine DXA tissue thickness, hip DXA tissue thickness, and spine:hip tissue thickness ratio) in 214 women and 96 men (mean age 66.1 and 63.7 yr, respectively) undergoing DXA screening for osteoporosis. Results: DXA-derived spine tissue thickness explained most of the variance in measured waist circumference (female R2 0.90, male R2 0.88). Explained variance was slightly lower for measured hip circumference (female R2 0.87, male R2 0.76) and waist:hip ratio (female R2 0.68, male R2 0.72). Final models predicted waist circumference with an adjusted R2 0.91, hip circumference with R2 0.86, and waist:hip ratio with R2 0.70. Conclusion: Routine clinical DXA measurements of the spine and hip can be used to estimate body circumference measurements.

A multimodal approach to cardiovascular risk stratification in patients with type 2 diabetes incorporating retinal, genomic and clinical features

Cardiovascular diseases are a public health concern; they remain the leading cause of morbidity and mortality in patients with type 2 diabetes. Phenotypic information available from retinal fundus images and clinical measurements, in addition to genomic data, can identify relevant biomarkers of cardiovascular health. In this study, we assessed whether such biomarkers stratified risks of major adverse cardiac events (MACE). A retrospective analysis was carried out on an extract from the Tayside GoDARTS bioresource of participants with type 2 diabetes (n = 3,891). A total of 519 features were incorporated, summarising morphometric properties of the retinal vasculature, various single nucleotide polymorphisms (SNPs), as well as routine clinical measurements. After imputing missing features, a predictive model was developed on a randomly sampled set (n = 2,918) using L1-regularised logistic regression (lasso). The model was evaluated on an independent set (n = 973) and its performance associated with overall hazard rate after censoring (log-rank p < 0.0001), suggesting that multimodal features were able to capture important knowledge for MACE risk assessment. We further showed through a bootstrap analysis that all three sources of information (retinal, genetic, routine clinical) offer robust signal. Particularly robust features included: tortuousity, width gradient, and branching point retinal groupings; SNPs known to be associated with blood pressure and cardiovascular phenotypic traits; age at imaging; clinical measurements such as blood pressure and high density lipoprotein. This novel approach could be used for fast and sensitive determination of future risks associated with MACE.

Exploiting Routine Clinical Measures to Inform Strategies for Better Hearing Performance in Cochlear Implant Users.

Neuroprostheses designed to interface with the nervous system to replace injured or missing senses can significantly improve a patient’s quality of life. The challenge remains to provide implants that operate optimally over several decades. Changes in the implant-tissue interface may precede performance problems. Tools to identify and characterize such changes using existing clinical measures would be highly valuable. Modern cochlear implant (CI) systems allow easy and regular measurements of electrode impedance (EI). This measure is routinely performed as a hardware integrity test, but it also allows a level of insight into the immune-mediated response to the implant, which is associated with performance outcomes. This study is a 5-year retrospective investigation of MED-EL CI users at the University of Southampton Auditory Implant Service including 176 adult ears (18–91) and 74 pediatric ears (1–17). The trend in EI in adults showed a decrease at apical electrodes. An increase was seen at the basal electrodes which are closest to the surgery site. The trend in the pediatric cohort was increasing EI over time for nearly all electrode positions, although this group showed greater variability and had a smaller sample size. We applied an outlier-labeling rule to statistically identify individuals that exhibit raised impedance. This highlighted 14 adult ears (8%) and 3 pediatric ears (5%) with impedance levels that deviated from the group distribution. The slow development of EI suggests intra-cochlear fibrosis and/or osteogenesis as the underlying mechanism. The usual clinical intervention for extreme impedance readings is to deactivate the relevant electrode. Our findings highlight some interesting clinical contradictions: some cases with raised (but not extreme) impedance had not prompted an electrode deactivation; and many cases of electrode deactivation had been informed by subjective patient reports. This emphasizes the need for improved objective evidence to inform electrode deactivations in borderline cases, for which our outlier-labeling approach is a promising candidate. A data extraction and analysis protocol that allows ongoing and automated statistical analysis of routinely collected data could benefit both the CI and wider neuroprosthetics communities. Our approach provides new tools to inform practice and to improve the function and longevity of neuroprosthetic devices.