General Clinical Settings Research Articles

Dependence of the AUC of NTCP models on the observational dose-range highlights cautions in comparison of discriminative performance

BackgroundNormal tissue complication probability (NTCP) models are probabilistic models that describe the risk of radio-induced toxicity in tissues or organs. In the field of radiotherapy, the area under the ROC curve (AUC) is widely used to estimate the performance in risk prediction of NTCP models. MethodsIn this work, we derived an analytical expression of the AUC for the logistic NTCP model in the case of both symmetrical and asymmetrical dose (to the normal tissue) windows around D50. Using numerical simulations, we studied the behavior of the AUC in general clinical settings, enforcing non-logistic NTCP models (Lyman-Kutcher-Burman and LogEUD) and including risk factors beyond the dose. We validated our findings using real-world radiotherapy data sets of prostate cancer patients. ResultsOur analytical expression of the AUC made explicit the dependence on both the steepness of the logistic curve (β) and the dose window width (w), showing that an increase of w pushes AUC towards higher values. Increasing values of the AUC with increasing values of w were consistently observed across simulated data sets with diverse clinical settings from published studies and real clinical data sets. ConclusionOur results reveal that the AUC of NTCP models inherits intrinsic characteristics from the clinical setting of the data set on which the models are developed, and warn against the use of the AUC to compare the performance of models constructed upon data from trials in which substantially different dose ranges were administered or accounting for different risk factors beyond the dose.

#5650 METABOLIC BLOOD BIOMARKER PROFILING FOR CHRONIC KIDNEY DISEASE PREDICTION – EVIDENCE FROM 275,000 INDIVIDUALS IN THE UK BIOBANK

Abstract Background and Aims Early identification of individuals at high risk of developing chronic kidney disease and other chronic conditions is essential for targeted prevention. Here, we assess the utility of metabolic blood biomarkers in predicting the onset of chronic kidney disease in over 250,000 individuals from UK Biobank, beyond established risk factors and polygenic risk scores. Method Circulating blood biomarkers, including lipids, fatty acids, amino acids, glycolysis metabolites and inflammation markers were measured by a low-cost nuclear magnetic resonance (NMR) metabolomics assay in around 275,000 plasma samples from the UK Biobank. During a prospective 10-year follow-up, over 6000 incident chronic kidney disease events were obtained from national health registries. Using multivariable regression modelling, we derived a 10-year risk score for chronic kidney disease onset. We assessed the predictive performance of the biomarker risk score in comparison to standard risk factors (age, sex, prevalent diabetes, body mass index, systolic and diastolic blood pressure, smoking status and use of cholesterol lowering medication), clinical chemistry measurements (HbA1c, LDL and HDL cholesterol, total cholesterol and eGFR) and polygenic risk scores. We evaluated the performance of the risk score in two practical scenarios: in a general population screening setting and in a clinical use case of stratifying kidney disease risk among prevalent type 2 diabetics. We further illustrate applications of the biomarker risk scores in predicting the risk of other chronic diseases, such as cardiovascular outcomes, in general population settings. Results In the general population screening setting, adding the metabolic biomarkers to a simple model of standard risk factors substantially improved the predictive performance, with area under the receiver operating characteristic curve (AUC) increasing from 0.74 to 0.82. When compared to more comprehensive model including also clinical chemistry measurements and polygenic risk scores, the improvements were also significant, albeit more modest, with the AUC increasing from 0.81 to 0.83. Even more substantial gains were observed in a clinical use case scenario of stratifying risk of chronic kidney disease onset among prevalent type 2 diabetics. Among diabetics with mildly to moderately decreased kidney function at the time of blood sampling (eGFR 60-90), adding the metabolic biomarkers in a comprehensive model including standard risk factors, clinical chemistry measurements and polygenic risk scores increased the AUC from 0.60 to 0.70. Conclusion Circulating metabolic biomarkers enhanced the prediction of chronic kidney disease onset beyond standard risk factors and polygenic risk scores. From a translational perspective, this may complement the identification of high-risk individuals in both general population and clinical settings beyond current risk factor assessment, while simultaneously informing on the risk of other chronic diseases.

Adapting and Implementing Apps for Mental Healthcare.

Purpose of ReviewTo describe examples of adapting apps for use in mental healthcare and to formulate recommendations for successful adaptation in mental healthcare settings.Recent FindingsInternational examples are given to explore implementation procedures to address this multitude of challenges.SummaryThere are only few published examples of adapting apps for use in mental healthcare. From these examples and from results of studies in implementation science in general clinical settings, it can be concluded that the process of adapting apps for mental healthcare needs to address clinician training and information needs, user needs which include cultural adaptation and go beyond mere translation, and organizational needs for blending app use into everyday clinical mental healthcare workflows.

Accessibility to Medication for Opioid Use Disorder After Interventions to Improve Prescribing Among Nonaddiction Clinics in the US Veterans Health Care System

With increasing rates of opioid use disorder (OUD) and overdose deaths in the US, increased access to medications for OUD (MOUD) is paramount. Rigorous effectiveness evaluations of large-scale implementation initiatives using quasi-experimental designs are needed to inform expansion efforts. To evaluate a US Department of Veterans Affairs (VA) initiative to increase MOUD use in nonaddiction clinics. This quality improvement initiative used interrupted time series design to compare trends in MOUD receipt. Primary care, pain, and mental health clinics in the VA health care system (n = 35) located at 18 intervention facilities and nonintervention comparison clinics (n = 35) were matched on preimplementation MOUD prescribing trends, clinic size, and facility complexity. The cohort of patients with OUD who received care in intervention or comparison clinics in the year after September 1, 2018, were evaluated. The preimplementation period extended from September 1, 2017, through August 31, 2018, and the postimplementation period from September 1, 2018, through August 31, 2019. The multifaceted implementation intervention included education, external facilitation, and quarterly reports. The main outcomes were the proportion of patients receiving MOUD and the number of patients per clinician prescribing MOUD. Segmented logistic regression evaluated monthly proportions of MOUD receipt 1 year before and after initiative launch, adjusting for demographic and clinical covariates. Poisson regression models examined yearly changes in clinician prescribing over the same time frame. Overall, 7488 patients were seen in intervention clinics (mean [SD] age, 53.3 [14.2] years; 6858 [91.6%] male; 1476 [19.7%] Black, 417 [5.6%] Hispanic; 5162 [68.9%] White; 239 [3.2%] other race [including American Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, and multiple races]; and 194 [2.6%] unknown) and 7558 in comparison clinics (mean [SD] age, 53.4 [14.0] years; 6943 [91.9%] male; 1463 [19.4%] Black; 405 [5.4%] Hispanic; 5196 [68.9%] White; 244 [3.2%] other race; 250 [3.3%] unknown). During the preimplementation year, the proportion of patients receiving MOUD in intervention clinics increased monthly by 5.0% (adjusted odds ratio [AOR], 1.05; 95% CI, 1.03-1.07). Accounting for this preimplementation trend, the proportion of patients receiving MOUD increased monthly by an additional 2.3% (AOR, 1.02; 95% CI, 1.00-1.04) during the implementation year. Comparison clinics increased by 2.6% monthly before implementation (AOR, 1.03; 95% CI, 1.01-1.04), with no changes detected after implementation. Although preimplementation-year trends in monthly MOUD receipt were similar in intervention and comparison clinics, greater increases were seen in intervention clinics after implementation (AOR, 1.04; 95% CI, 1.01-1.08). Patients treated with MOUD per clinician in intervention clinics saw greater increases from before to after implementation compared with comparison clinics (incidence rate ratio, 1.50; 95% CI, 1.28-1.77). A multifaceted implementation initiative in nonaddiction clinics was associated with increased MOUD prescribing. Findings suggest that engagement of clinicians in general clinical settings may increase MOUD access.

Adherence to Oral Nutritional Supplements in Patients With Gastrointestinal Cancer: A Mixed-Method Study.

Oral nutritional supplements (ONS) is a cost-effective nutritional therapy in patients with gastrointestinal cancer. However, information is lacking about adherence to ONS in general clinical settings. Figuring out adherence to ONS and related factors will provide evidence for the improvement of ONS usage practice. The aim of this study was to survey adherence to ONS in gastrointestinal cancer patients with an ONS prescription and the factors associated with it. A mixed-method prospective study was conducted. Multivariate analysis and semistructured interviews were performed to identify factors that affected patient adherence to ONS. Of 111 gastrointestinal cancer patients provided with an ONS prescription, the median of adherence to ONS was 50.00% (interquartile range, 28.57%-91.67%). Multivariate analysis indicated that participants with low weight showed higher adherence to ONS than those with normal weight (β = -2.61, P = .011) or overweight (β = -3.25, P = .002). Semistructured interviews on 14 participants suggested that factors related to adherence to ONS were needs perception and benefits, clarity of the target daily ONS intake, tolerance to ONS, the impact of disease or treatment, personal preference, and professional support. This study reveals poor adherence to ONS in patients with gastrointestinal cancer and factors related to it in current clinical settings. Our findings could provide evidence for the development of strategies to improve ONS usage practice. It suggests that the practice in ONS should be improved from aspects of nutritional assessment, education, tolerance, and symptom management, as well as follow-up and monitoring of patients.

Eating Disorders: Identification and Management in General Medical and Psychiatric Settings.

Eating disorders (EDs) are serious, complex illnesses with both behavioral and physical health features. EDs have high rates of medical and psychiatric morbidity, and a 6% mortality rate, the highest of any mental illness. Early detection of EDs offers the best opportunity for recovery; yet, estimates are that as few as one in 10 individuals with an ED receive treatment. The purpose of this article is to provide an ED identification and management overview for inpatient nurse clinicians in general psychiatric and medical settings, helping to facilitate timely recognition and care. An overview of ED diagnostic criteria and two evidence-based ED tools are introduced for consideration. Opportunities to identify and help manage an ED are numerous. Most individuals with an ED make several health care visits in either medical or psychiatric settings without ever being screened for an ED. General ED screening and assessment tool familiarization can facilitate a treatment trajectory for these patients, improve overall quality of life, and may potentially result in a life-saving intervention for this often-deadly cluster of medical and psychiatric disorders. Screening and assessment in general clinical settings, identifying patients with undiagnosed EDs, beginning basic treatment plans, and referrals for appropriate follow-up care, have the potential to reduce ED recidivism and related health care costs. Simultaneously, and most important, long-term outcomes for patients with EDs may improve.

A host-based two-gene model for the identification of bacterial infection in general clinical settings

ObjectivesIn this study, we aimed to develop a simple gene model to identify bacterial infection, which can be implemented in general clinical settings. MethodsWe used a clinically availablereal-time quantitative polymerase chain reaction platform to conduct focused gene expression assays on clinical blood samples. Samples were collected from 2 tertiary hospitals. ResultsWe found that the 8 candidate genes for bacterial infection were significantly dysregulated in bacterial infection and displayed good performance in group classification, whereas the 2 genes for viral infection displayed poor performance. A two-gene model (S100A12 and CD177) displayed 93.0% sensitivity and 93.7% specificity in the modeling stage. In the independent validation stage, 87.8% sensitivity and 96.6% specificity were achieved in one set of case-control groups, and 93.6% sensitivity and 97.1% specificity in another set. ConclusionsWe have validated the signature genes for bacterial infection and developed a two-gene model to identify bacterial infection in general clinical settings.

Full wave 3D inverse scattering transmission ultrasound tomography in the presence of high contrast

We present here a quantitative ultrasound tomographic method yielding a sub-mm resolution, quantitative 3D representation of tissue characteristics in the presence of high contrast media. This result is a generalization of previous work where high impedance contrast was not present and may provide a clinically and laboratory relevant, relatively inexpensive, high resolution imaging method for imaging in the presence of bone. This allows tumor, muscle, tendon, ligament or cartilage disease monitoring for therapy and general laboratory or clinical settings. The method has proven useful in breast imaging and is generalized here to high-resolution quantitative imaging in the presence of bone. The laboratory data are acquired in ~ 12 min and the reconstruction in ~ 24 min—approximately 200 times faster than previously reported simulations in the literature. Such fast reconstructions with real data require careful calibration, adequate data redundancy from a 2D array of 2048 elements and a paraxial approximation. The imaging results show that tissue surrounding the high impedance region is artifact free and has correct speed of sound at sub-mm resolution.

Portable Pen-Like Device With Miniaturized Tactile Sensor for Quantitative Tissue Palpation in Oral Cancer Screening

Oral cancer has consistently been ranked among the top ten cancers in terms of mortality with five year survival rates being among the lowest for all major cancers. Consequently, great efforts are being made to develop new diagnostic tools that can enable early detection in a clinical setting. In this study, we report on the design and development of a novel pen-like handheld device, with a miniaturized tactile sensor mounted on the front-end and integrated with a portable back-end readout module. The device can be used for tissue palpation in the oral cavity and obtain quantitative information regarding the elasticity of oral lesions and abnormalities, thus eliminating the need for manual palpation by the clinician. The sensing mechanism of the proposed tactile sensor is based on the two-spring model and employs two components with varying stiffness values, namely a hard copper ball embedded in a soft elastomeric packaging. The differential voltage output of the piezoelectric sensing film corresponding to the two components can provide information regarding the elasticity of the tissue under contact. To simulate feasibility of the tactile sensor in differentiating tissue elasticity, we have contacted the sensor with different elastomeric silicone materials under the same applied force. The experiments confirmed that the sensor response could be used to differentiate five silicones with varying Young’s moduli ranging from 0.2 to 3.1 MPa and a corresponding Shore hardness of 2 to 56 Shore A. A two-stage linear trend was observed with a sensitivity of 0.356/MPa for softer silicones (2 ~ 9 Shore A) and 0.059/MPa for harder silicones (24 ~ 56 Shore A). Furthermore, the portable readout module that we have developed can analyze the data from the tactile sensor and transmit it wirelessly via Bluetooth for cloud computing. The proposed device is easy-to-use in general clinical settings and could enable early detection and improved prognosis of oral cancer.

COVID-19 insights from transfusion medicine.

The emergence of CoVID‐19 infection in the first months of 2020 resulted in a massive surge in admissions to hospitals and intensive care units due to the nature of the respiratory pathophysiology. In some countries, health care systems were rapidly overwhelmed, while in others their hospitals coped with the first wave and all patients received the level of care needed, depending upon both the containment measured and the level of development of the heath care systems.

M121. CLINICAL PREDICTION MODELS FOR TRANSITION TO PSYCHOSIS: AN EXTERNAL VALIDATION STUDY IN THE PRONIA SAMPLE

BackgroundA multitude of clinical models to predict transition to psychosis in individuals at clinical high risk (CHR) have been proposed. However, only limited efforts have been made to systematically compare these models and to validate their performance in independent samples.Therefore, in this study we identified psychosis risk models based on information readily obtainable in general clinical settings, such as clinical and neuropsychological data, and compared their performance in the PRONIA study (Personalised Prognostic Tools for Early Psychosis Management, www.pronia.eu) as an independent sample.MethodsOf the 278 CHR participants in the PRONIA sample, 150 had available data until month 18 and were included in the validation of eleven psychosis prediction models identified through systematic literature search. Discrimination performance was assessed with the area under the receiver operating characteristic curve (AUC), and compared to the performance of the prognosis of clinical raters. Psychosocial functioning was explored as an alternative outcome.ResultsDiscrimination performance varied considerably across models (AUC ranging from 0.42 to 0.79). High model performance was associated with the inclusion of neurocognitive variables as predictors. Low model performance was associated with predictors based on dichotomized variables. Clinical raters performed comparable to the best data-driven models (AUC = 0.75). Combining raters’ prognosis and model-based predictions improved discrimination performance (AUC = 0.84), particularly for less experienced raters. One of the tested models predicted transition to psychosis and psychosocial outcomes comparably well.DiscussionThe present external validation study highlights the benefit of enriching clinical information with neuropsychological data in predicting transition to psychosis satisfactorily and with good generalizability across samples. Integration of data-driven risk models and clinical expertise may improve clinical decision-making in CHR for psychosis, particularly for less experienced raters. This external validation study provides an important step toward early intervention and the personalized treatment of psychotic disorders.

Examining the utility of the Personality Assessment Screener in three criminal justice samples.

Many individuals in forensic/correctional settings experience significant mental health problems, yet effective screening tools to identify such difficulties are in relatively short supply. This study investigates the clinical utility of the Personality Assessment Screener (PAS; Morey, 1997), a 22-item self-report measure of risk for emotional and behavioral dysfunction, across three archival criminal justice samples (incarcerated sex offenders, prison inmates housed in general population and psychiatric units, and jail detainees). The PAS is derived from the Personality Assessment Inventory (PAI; Morey, 1991, 2007), a more comprehensive measure of emotional and behavioral disturbances that is widely used in forensic/correctional settings. The PAS total score effectively identified those with clinically significant elevations on the PAI and also significantly correlated with various criterion measures tapping psychological dysfunction. Existing interpretive ranges and labels used to describe PAS scores in general clinical settings were problematic, however, and may require revision for use in these contexts. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Caring for people with mental health conditions in general clinical settings.

Nurses often care for people with mental health conditions in general clinical settings. In these situations, they have a responsibility to ensure that the individual's physical, social and psychological needs are assessed and met. Nurses practising in general clinical settings should be familiar with the skills and knowledge required to meet the needs of people with mental health conditions. This article aims to provide nurses practising in general clinical settings with an understanding of such conditions and the associated effects on an individual's physical health. It also details the signs and symptoms of various mental health conditions, and outlines the communication skills that nurses can use when caring for people with these conditions in general clinical settings.

Cardiovascular disease risk screening by pharmacists: a behavior change wheel guided qualitative analysis.

In common with many developed countries, Saudi Arabia is currently experiencing an increasing cardiovascular disease (CVD) burden. However, systematic screening programs for early identification and minimization of CVD risk within community or general clinical settings are limited. Globally, research suggests that pharmacists can play an effective role in identifying, assessing, managing and referring people at risk of CVD in the community as well as in the hospital setting. This role is not yet developed in Saudi Arabia. This study aimed to explore the perspectives of hospital and community pharmacists in Saudi Arabia about potential roles in CVD risk screening. The purpose of the study was to propose potential interventions to facilitate the development of pharmacist delivered models for CVD risk prevention and management services in Saudi Arabia. A qualitative study was conducted using semi-structured in-depth interviews and focus group discussions with a purposive convenience sample of hospital and community pharmacists in Saudi Arabia. Data collection continued until saturation was achieved. All interviews were audio recorded, transcribed verbatim and thematically analyzed. A total of 50 pharmacists (26 hospital and 24 community pharmacists) participated in this study. Twenty hospital and eight community pharmacists were interviewed individually, while the remaining participants contributed to three focus groups discussions. Currently, it appears that CVD risk prevention services are rarely provided, and when offered involved provision of discrete elements only such as blood pressure measurement, rather than a consolidated evidence based approach to risk assessment. Participating pharmacists did not appear to have a clear understanding of how to assess CVD risk. Four key themes were identified: pharmacists' perception about their current roles in CVD, proposed future clinical and service roles, impeding factors and enabling factors. Subthemes were mainly related to determinants likely to influence future CVD services. These subthemes included public perception of pharmacists' roles, pharmacist-physician collaboration, legislative restrictions, systemic issues, sociocultural barriers, organizational pharmacy issues, lack of professional motivation, government and organizational support and professional pharmacy support frameworks. These influencing factors need to be addressed at micro, meso and macro systems level in order to facilitate development of new pharmacist delivered cognitive services in Saudi Arabia. Pharmacists in Saudi Arabia are willing to expand their role and offer pharmacy-based services, but influencing determinants have to be addressed at the individual, professional and health system levels. Further work is needed to clarify and develop practical and appropriate protocols for pharmacist CVD prevention and management services within the Saudi public and health care system. Such work should be guided by implementation science frameworks rather than embarking on conventional research trial pipelines where public benefit of generated evidence is delayed or limited.

Delusion, excitement, violence, and suicide history are risk factors for aggressive behavior in general inpatients with serious mental illnesses: A multicenter study in China

Little is known about the risk factors for aggression in general clinical settings in China. The aim of this study is to explore potential risk factors for inpatients with serious mental illness. The study was conducted from 15 March to 14 April 2013 and involved 16 general psychiatric institutions in China. A standardized data collection form was used to collect demographic and clinical characteristics data, including information on current hallucinations, delusions, depression, excitement, aboulia, apathy, and adherence to treatment. Information on lifetime history of violence and suicidality was also collected. The Modified Overt Aggression Scale (MOAS) was also administered to indicate recent (past week) aggression. A total of 511 inpatients were enrolled. On the basis of a score of five or greater on the MOAS, 245 inpatients were assigned to aggressive group and 266 were assigned to non-aggressive group. A lifetime history of violent behaviour (OR = 3.1, 95% CI = 1.95–5.11), suicide (OR = 3.0, 95% CI = 1.49–6.10), as well as current delusions (OR = 1.92, 95% CI = 1.24–2.97), and excitement (OR = 2.63, 95% CI = 1.57–4.39) were associated with aggression. The study suggested violent history, suicide history, current delusions, and excitement are the risk factors for aggression among general psychiatric inpatients with serious mental illnesses.

Hope Springs Eternal: An Exploration of Hope at a Local Jail

Prevention and intervention research has indicated the malleability of hope in a variety of populations and the positive impact on treatment outcomes in general clinical settings and substance use treatment. However, despite its prospective role in improving well-being, research on hope is not often situated behind bars. Thus, the current project intended to explore the nature of theory-driven hope discussions for women involved in justice systems. The aim was to maintain and enhance hope, activate positivity, and thereby enhance the quality of life.Four weekly focus group sessions were conducted with women detained at a local jail (n = 23), with discussion prompts based on Snyder’s theory of hope (goal setting, agency thinking, and pathway thinking). Using interactional delivery methods, we emphasized hope among jailed women by: (1) facilitating the development and maintenance of hopeful thinking; (2) developing concrete goals towards rehabilitation and a positive life; (3) enhancing the capacity for developing enduring, cross-sectional strategies for goal attainment; and (4) facilitating self-analysis on their overall ability to produce workable plans required to reach the goals. Weekly journaling was also included to complement the process.Results from the qualitative analysis suggest hope for these jailed women was constructed as belief in a better future and was also often embedded within a religious worldview. Further, jailed women’s perceptions of meeting goals were heavily dependent upon outside sources that would provide structure and discipline. Implications include providing strength-based reentry programs, offering mentorship, emphasizing goal-setting strategies, and reviewing visitation policies.

Testicular Cancer in New Zealand (TCNZ) study: protocol for a national case–control study

Testicular cancer (TC) is by far the most common cancer to affect young men; however, the exposures that cause this disease are still poorly understood. Our own research has shown...

Timing of the Diagnoses of Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder in Taiwan.

ADHD comorbidity has been associated with delayed diagnosis of ASD, but no study has investigated this association in an Asian country. Children with ASD were included and divided into three groups: ADHD before ASD, ADHD same/after ASD, and ASD only. Timing of ASD and ADHD diagnoses were assessed. The logistic regression model was performed to investigate the likelihood of being diagnosed with ASD after 6years of age between three groups. ADHD before ASD (OR 10.93) group was more likely to being diagnosed with ASD after 6years of age compared with ADHD same/after ASD (OR: 1.37) and ASD only groups. ADHD comorbidity would delay the diagnosis of ASD in the general clinical settings in Taiwan.

Symptom overlap on the srs-2 adult self-report between adults with asd and adults with high anxiety.

Many people diagnosed with autism spectrum disorder (ASD) also experience significant symptoms of anxiety, while many people with anxiety disorders likewise experience social difficulties. These concerns can be difficult to tease apart in general clinical settings. The Social Responsiveness Scale (SRS) is one of the most frequently used measures of dimensional ASD symptoms. In order to investigate the overlap of autism and anxiety on the SRS, we compared three groups of adults (an ASD group, n = 40; a high anxious group, n = 56; and a typical comparison group, n = 29) using the new Adult Self Report version of the SRS-2nd Edition (SRS-2-ASR) alongside a battery of anxiety questionnaires. Based on previous research with children from the parent-report SRS (first edition), we hypothesized that the SRS-2-ASR would have difficulty discriminating between the ASD and high anxious groups. Results showed that both these clinical groups scored significantly higher on the SRS than a typical control group. Discriminant validity was poor, including sensitivity of 0.65 when including all participants and 0.48 when only the two clinical groups were included. In particular, the Social Motivation subscale of the SRS-ASR failed to distinguish between ASD and anxiety groups. As recommended in the SRS-2 manual, we highlight the need for caution when using the SRS-2-ASR to support diagnostic decision making, especially in clinical settings involving anxiety, ADHD, or other concerns that can affect reciprocal social communication and/or behavioral flexibility. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1215-1220. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Insulin sensitivity index (ISI 0-120) from oral glucose tolerance test in healthy young adults

Background: Insulin sensitivity (IS) is the body’s systemic responsiveness to glucose and it is the measure of the ability of endogenous insulin to reduce the glucose in extracellular fluids by inhibition of gluconeogenesis and increase peripheral glucose uptake. IS reflects on the efficiency of insulin in response to glucose intake in the body. In diabetics, IS subjects are interpreted to require smaller amounts of insulin to lower blood glucose levels than someone who has low sensitivity. There is a need to detect insulin resistance (IR) in the pre-disease state, i.e., before the onset of impaired glucose tolerance (IGT). Early detection of IR or decreased IS in healthy subjects before the onset of IGT is of importance as it facilitates implementation of preventive measures in subject with such high risk. Aims and Objectives: The objective of the study is detect early occurrence of low Insulin Sensitivity in healthy young adults, using Insulin Sensitivity Index derived from OGTT. Materials and Methods: A total of 80 healthy volunteers in the age group of 18-25 years were recruited for the study, 40 subjects were siblings of diabetics and 40 subjects were siblings of non-diabetics (SND) a standard (75 g) OGTT was performed for the study. Blood samples for determination of plasma glucose and insulin levels drawn at 0 (fasting), 30, 120 min after glucose solution ingestion. Assays of fasting (basal), 30, 120 min venous plasma glucose during OGTT was performed with glucose oxidase method on site using glucose auto analyzer. The serum plasma was stored at −20°C until assayed. Corresponding specific insulin concentration was determined using radioimmunoassay (RIA) with human specific antibody RIA kit IS was calculated using physiological OGTT based mathematical models. QUICKI was derived for fasting insulin and fasting glucose values. ISI 0-120: Uses OGTT values, using only 0 and 120 min post-glucose challenge insulin and glucose concentrations. The reference values for various IR and IS indexes for our urban population with normal OGTT (n = 79) are QUICKI = 0.31 (0.20-0.52) sibling of diabetics (SD) - 0.07, ISI 0-120 = 63.62 (27.37-134.79) SD - 22.71. We observed that SD had significantly lower IS indices ISI 0-120 (56.27, P < 0.002) and a trend toward significance for QUICKI (0.29578, P < 0.056). Results: We observed that the mathematical models ISI 0-120 to be a fairly reliable tool for assessment of IS in normoglycemic young adults, compared to QUICKI. ISI 0-120 take into consideration the all the parameters of the 2 h OGTT glucose and also includes insulin into consideration for evaluation. Simple OGTT based mathematical models can be used as a reasonable alternative to measure IS or IR instead of the cumbersome glucose clamp or other expensive techniques in epidemiological or general clinical settings. Conclusion: Detection of IR in pre-disease condition in healthy individuals, allows the physician to initiate preventive measures, such as lifestyle modification, diet and exercise, thereby preventing the high-risk subjects from progressing to disease state.