Perceived glucose levels matter more than CGM-based data in predicting diabetes distress in type 1 or type 2 diabetes: a precision mental health approach using n-of-1 analyses.

AIMS/HYPOTHESIS: Diabetes distress is one of the most frequent mental health issues identified in people with type 1 and type 2 diabetes. Little is known about the role of glucose control as a potential contributor to diabetes distress and whether the subjective perception of glucose control or the objective glycaemic parameters are more important for the experience. With the emergence of continuous glucose monitoring (CGM), this is a relevant question as glucose values are now visible in real-time. We employed a precision monitoring approach to analyse the independent associations of perceived and measured glucose control with diabetes distress on a daily basis. By using n-of-1 analyses, we aimed to identify individual contributors to diabetes distress per person and analyse the associations of these individual contributors with mental health at a 3 month follow-up. METHODS: In this prospective, observational study, perceived (hypoglycaemia/hyperglycaemia/glucose variability burden) and measured glucose control (time in hypoglycaemia and hyperglycaemia, CV) were assessed daily for 17 days using an ecological momentary assessment (EMA) approach with a special EMA app and CGM, respectively. Mixed-effect regression analysis was performed, with daily diabetes distress as the dependent variable and daily perceived and CGM-measured metrics of glucose control as random factors. Individual regression coefficients of daily distress with perceived and CGM-measured metrics were correlated with levels of psychosocial well-being at a 3 month follow-up. RESULTS: Data from 379 participants were analysed (50.9% type 1 diabetes; 49.6% female). Perceived glucose variability (t=14.360; p<0.0001) and perceived hyperglycaemia (t=13.637; p<0.0001) were the strongest predictors of daily diabetes distress, while CGM-based glucose variability was not significantly associated (t=1.070; p=0.285). There was great heterogeneity between individuals in the associations of perceived and measured glucose parameters with diabetes distress. Individuals with a stronger association between perceived glucose control and daily distress had more depressive symptoms (ß=0.32), diabetes distress (ß=0.39) and hypoglycaemia fear (ß=0.34) at follow-up (all p<0.001). Individuals with a stronger association between CGM-measured glucose control and daily distress had higher levels of psychosocial well-being at follow-up (depressive symptoms: ß=-0.31; diabetes distress: ß=-0.33; hypoglycaemia fear: ß=-0.27; all p<0.001) but also higher HbA1c (ß=0.12; p<0.05). CONCLUSIONS/INTERPRETATION: Overall, subjective perceptions of glucose seem to be more influential on diabetes distress than objective CGM parameters of glycaemic control. N-of-1 analyses showed that CGM-measured and perceived glucose control had differential associations with diabetes distress and psychosocial well-being 3 months later. The results highlight the need to understand the individual drivers of diabetes distress to develop personalised interventions within a precision mental health approach.

Technical note: Validation of a system for monitoring individual behavior of Holstein cows.

The objectives of the 2 studies reported herein were to validate the accuracy of an automated monitoring device (AMD) to detect side lying, resting, activity, rumination, eating, walking, and panting in nonlactating and lactating dairy cows. Additionally, we aimed to determine whether the total time per cow-state recorded by the AMD within a 30-min interval corresponds to the total time per cow-state recorded simultaneously by visual observation. Study personnel (n = 2) observed pregnant nonlactating Holstein cows (n = 10) for 30 min in the morning and 30 min in the afternoon for 6 consecutive days and recorded continuously each cow-state. In study 2, study personnel (n = 2) observed lactating Holstein cows (n = 10) for 30 min in the morning and 30 min in the afternoon for 6 consecutive days. In both studies, cow-state was recorded every second, and within 1 min, the most prevalent cow-state was considered to be the behavior presented by the cow during that interval. Using the observer as the gold standard, test characteristics were calculated for the minute-by-minute interval analyses. For the 30-min interval analyses, the concordance correlation coefficient (pc) and the coefficient of determination (R2) between the total minutes for each cow-state recorded by the observer and the AMD were calculated. In study 1, for the minute-by-minute interval analyses, test characteristics were high for rumination (≥90.1%) and eating (≥73.8%), moderate for resting (≥62.9%), but negligible for medium activity (≥17%). For the 30-min interval analyses, the correlations between the total time of visual observations compared with the total time recorded by AMD for rumination (R2 = 0.97, pc = 0.98) and eating (R2 = 0.91, pc = 0.94) were very high, for resting (R2 = 0.77, pc = 0.79) was high, and for medium activity (R2 = 0.41, pc = 0.41) was low. In study 2, for the minute-by-minute interval analyses, test characteristics were high for rumination (≥79.4%), eating (≥74.2%), and resting (≥73.0%), but they were low for panting (≥31.3%) and negligible for medium activity (≥22.2%). For the 30-min interval analyses, the correlations were similar to study 1 (rumination: R2 = 0.85, pc = 0.91; eating: R2 = 0.95, pc = 0.97; resting: R2 = 0.84, pc = 0.90; medium activity: R2 = 0.44, pc = 0.57; and panting: R2 = 0.21, pc = 0.42). In summary, the AMD used in this study provided accurate data regarding resting, rumination, and eating of pregnant nonlactating and lactating Holstein cows.

Precision medicine in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an incurable disease characterized by remission-relapse cycles throughout its course. Both Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of IBD, exhibit tendency to develop complications and substantial heterogeneity in terms of frequency and severity of relapse, thus posing great challenges to the clinical management for IBD. Current treatment strategies are effective in different ways in induction and maintenance therapies for IBD. Recent advances in studies of genetics, pharmacogenetics, proteomics and microbiome provide a strong driving force for identifying molecular markers of prognosis and treatment response, which should help clinicians manage IBD patients more effectively, and then, improve clinical outcomes and reduce treatment costs of patients. In this review, we summarize and discuss precision medicine in IBD, focusing on predictive markers of disease course and treatment response, and monitoring indices during therapeutic drug monitoring.

Precision Medicine in Type 1 Diabetes.

Type 1 diabetes is a complex, chronic disease in which the insulin-producing beta cells in the pancreas are sufficiently altered or impaired to result in requirement of exogenous insulin for survival. The development of type 1 diabetes is thought to be an autoimmune process, in which an environmental (unknown) trigger initiates a T cell-mediated immune response in genetically susceptible individuals. The presence of islet autoantibodies in the blood are signs of type 1 diabetes development, and risk of progressing to clinical type 1 diabetes is correlated with the presence of multiple islet autoantibodies. Currently, a "staging" model of type 1 diabetes proposes discrete components consisting of normal blood glucose but at least two islet autoantibodies (Stage 1), abnormal blood glucose with at least two islet autoantibodies (Stage 2), and clinical diagnosis (Stage 3). While these stages may, in fact, not be discrete and vary by individual, the format suggests important applications of precision medicine to diagnosis, prevention, prognosis, treatment and monitoring. In this paper, applications of precision medicine in type 1 diabetes are discussed, with both opportunities and barriers to global implementation highlighted. Several groups have implemented components of precision medicine, yet the integration of the necessary steps to achieve both short- and long-term solutions will need to involve researchers, patients, families, and healthcare providers to fully impact and reduce the burden of type 1 diabetes.

High-Precision Monitoring of Average Molecular Weight of Polyethylene Wax from Waste High-Density Polyethylene.

High-density polyethylene (HDPE) is a major component of polyethylene waste, yet only under 29.9% of waste HDPE is recycled. As an important additive, polyethylene wax (PEW) is increasingly used in many industries such as plastics, dyes, and paints. The preparation of PEW has received considerable interest because recycling and precisely controllable production can bring huge economic benefits. In this study, to recycle waste HDPE, a single screw extruder was innovatively combined with a connecting pipe to prepare PEW from the pyrolysis of waste HDPE. Using a test platform, PEWs were prepared under different pyrolysis temperatures and screw speeds, and corresponding number-average molecular weights (NAMWs) of PEWs were measured. To precisely monitor NAMW of PEW, a program was developed in MATLAB. First, the relationship between NAMW and pyrolysis ratio was obtained, and a measure-point-independence verification was conducted. Then, modified Arrhenius equations and time-dependent pyrolysis temperature were for the first time introduced into the HDPE pyrolysis model. Furthermore, the screw-speed-dependent inverse method was proposed and validated for high-precision monitoring of NAMW of PEW from the pyrolysis of waste HDPE by extrusion. PEW of desired molecular weight was able to be precisely obtained from waste HDPE.

Technical note: validation of a system for monitoring individual behavior in beef heifers.

The objectives of the 2 studies conducted were to validate the accuracy of an automated monitoring device (AMD; HR-LDn tags, SCR Engineers Ltd., Netanya, Israel) for different types of behaviors or cow-states (side lying, resting, medium activity, high activity, rumination, grazing, walking, and panting) in beef heifers and to determine if the total time per cow-state recorded by the AMD corresponds to the total time per cow-state recorded by instantaneous observations. Cow-state is recorded every second and, within 1 min, the most prevalent cow-state is considered to be the behavior presented by the animal during that interval. Study personnel (n = 2) observed heifers (n = 10) for 20 min from 0800 to 1140 h and 10 min from 1500 to 1640 h during 4 consecutive days and recorded continuously each cow-state at started and ended. Thus, study personnel were able to determine within a 1-min interval, which cow-state was most prevalent and represented the heifer's behavior. Because the proprietary machine learning algorithm prioritizes certain behaviors over others based on their contribution to the understanding of generalized bovine behavior patterns, we also determined the most prevalent behavior observed in 5-min intervals. Test characteristics (sensitivity, specificity, accuracy, and negative and positive predicted values) were calculated using the observer as the gold standard. In study 2, heifer behavior was scanned by observers (n = 2) every 5 min from 0800 to 1100 h and 1500 to 1800 h for 3 consecutive days. Total minutes per cow-state according to the observer were compared with the total minutes per cow-state according to the AMD during the same period to determine the correlation coefficient. In study 1, test characteristics were high (low ≤ 40%, moderate = 41 to 74%, high ≥ 75%) for rumination (≥ 89.7%), grazing (≥ 76.5%), and side lying (≥ 81.8%), and moderate for resting (≥ 48.8%). In study 2, the correlation coefficient for rumination (R2 = 0.92) and grazing (R2 = 0.90) were high and the correlation coefficient for resting (R2 = 0.66) and walking (R2 = 0.33) were moderate. We conclude that the AMD used in this study showed high accuracy when measuring rumination and grazing, but it was subpar when measuring resting and walking. The algorithms employed by the AMD used need to be improved for determination of walking and resting behaviors of beef cattle.