Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India.

BACKGROUND: Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. RESULTS: 903 smMIPs were designed to target exon and exon-intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. CONCLUSION: We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

Can the introduction of a 12-lead ECG help reduce mortality in those presenting with foot ulceration to multidisciplinary diabetic foot clinics? An observational evaluation of a real-world implementation pilot in England.

AIMS/HYPOTHESIS: The risk of dying within 2 years of presentation with diabetic foot ulceration is over six times the risk of amputation, with CVD the major contributor. Using an observational evaluation of a real-world implementation pilot, we aimed to assess whether for those presenting with diabetic foot ulceration in England, introducing a 12-lead ECG into routine care followed by appropriate clinical action was associated with reduced mortality. METHODS: Between July 2014 and December 2017, ten multidisciplinary diabetic foot services in England participated in a pilot project introducing 12-lead ECGs for new attendees with foot ulceration. Inception coincided with launch of the National Diabetes Footcare Audit (NDFA), whereby all diabetic footcare services in England were invited to enter data on new attendees with foot ulceration. Poisson regression models assessed the mortality RR at 2 and 5 years following first assessment of those receiving care in a participating pilot unit vs those receiving care in any other unit in England, adjusting for age, sex, ethnicity, deprivation, type and duration of diabetes, ulcer severity, and morbidity in the year prior to first assessment. RESULTS: Of the 3110 people recorded in the NDFA at a participating unit during the pilot, 33% (1015) were recorded as having received an ECG. A further 25,195 people recorded in the NDFA had attended another English footcare service. Unadjusted mortality in the pilot units was 16.3% (165) at 2 years and 37.4% (380) at 5 years for those who received an ECG, and 20.5% (430) and 45.2% (950), respectively, for those who did not receive an ECG. For people included in the NDFA at other units, unadjusted mortality was 20.1% (5075) and 42.6% (10,745), respectively. In the fully adjusted model, mortality was not significantly lower for those attending participating units at 2 (RR 0.93 [95% CI 0.85, 1.01]) or 5 years (RR 0.95 [95% CI 0.90, 1.01]). At participating units, mortality in those who received an ECG vs those who did not was lower at 5 years (RR 0.86 [95% CI 0.76, 0.97]), but not at 2 years (RR 0.87 [95% CI 0.72, 1.04]). Comparing just those that received an ECG with attendees at all other centres in England, mortality was lower at 5 years (RR 0.87 [95% CI 0.78, 0.96]), but not at 2 years (RR 0.86 [95% CI 0.74, 1.01]). CONCLUSIONS/INTERPRETATION: The evaluation confirms the high mortality seen in those presenting with diabetic foot ulceration. Overall mortality at the participating units was not significantly reduced at 2 or 5 years, with confidence intervals just crossing parity. Implementation of the 12-lead ECG into the routine care pathway proved challenging for clinical teams-overall a third of attendees had one, although some units delivered the intervention to over 60% of attendees-and the evaluation was therefore underpowered. Nonetheless, the signals of potential mortality benefit among those who had an ECG suggest that units in a position to operationalise implementation may wish to consider this. DATA AVAILABILITY: Data from the National Diabetes Audit can be requested through the National Health Service Digital Data Access Request Service process at: https://digital.nhs.uk/services/data-access-request-service-dars/dars-products-and-services/data-set-catalogue/national-diabetes-audit-nda.

Clinical perspectives on sampling and processing approaches for the management of infection in diabetic foot ulceration: A qualitative study.

Diabetic foot ulcers (DFUs) often become infected and are treated with antimicrobials, with samples collected to inform care. Swab samples are easier than tissue sampling but report fewer organisms. Compared with culture and sensitivity (C&S) methods, molecular microbiology identifies more organisms. Clinician perspectives on sampling and processing are unknown. We explored clinician perspectives on DFU sampling-tissue samples/wound swabs-and on processing techniques, culture and sensitivity or molecular techniques. The latter provides information on organisms which have not survived transport to the laboratory for culture. We solicited feedback on molecular microbiology reports. Qualitative study using semi-structured interview, with analysis using a Framework approach. CODIFI2 clinicians from UK DFU clinics. Seven consultants agreed to take part. They reported, overall, a preference for tissue samples over swabbing. Clinicians were not confident replacing C&S with molecular microbiology as the approach to reporting was unfamiliar. The study was small and did not recruit any podiatrists or nurses, who may have discipline-specific attitudes or perspectives on DFU care. Both sampling approaches appear to be used by clinicians. Molecular microbiology reports would not be, at present, suitable for replacement of traditional culture and sensitivity.

Xylitol production by Pseudomonas gessardii VXlt-16 from sugarcane bagasse hydrolysate and cost analysis.

Xylitol is a well-known sugar alcohol with exponentially rising market demand due to its diverse industrial applications. Organic agro-industrial residues (OAIR) are economic alternative for the cost-effective production of commodity products along with addressing environmental pollution. The present study aimed to design a process for xylitol production from OAIR via microbial fermentation with Pseudomonas gessardii VXlt-16. Parametric analysis with Taguchi orthogonal array approach resulted in a conversion factor of 0.64 g xylitol/g xylose available in untreated sugarcane bagasse hydrolysate (SBH). At bench scale, the product yield increased to 71.98/100 g (0.66 g/L h). 48.49 g of xylitol crystals of high purity (94.56%) were recovered after detoxification with 2% activated carbon. Cost analysis identified downstream operations as one of the cost-intensive parts that can be countered by adsorbent recycling. Spent carbon, regenerated with acetic acid washing can be reused for six cycles effectively and reduced downstream cost by about ≈32%. The strategy would become useful in the cost-effective production of several biomass-dependent products like proteins, enzymes, organic acids, as well.

Improved Glycemic Control Following Transition to Tubeless Insulin Pump Therapy in Adults With Type 1 Diabetes.

Continuous subcutaneous insulin infusion (CSII) treatment may improve long-term glycemic outcomes and enhance quality of life compared with a multiple daily injection (MDI) insulin regimen for people with type 1 diabetes. As the number of people treated with CSII via a tubeless insulin pump is increasing, there is growing interest in the long-term glycemic outcomes of this treatment option across diverse populations. This multicenter, retrospective study evaluated glycemic control in 156 adults with type 1 diabetes initiating tubeless insulin pump therapy following transition from either MDI or CSII with a tubed insulin pump. In this study, use of the tubeless insulin pump over 12 months was associated with significant improvement in A1C in adults with type 1 diabetes, most notably in those with an A1C ≥9.0% and those previously treated with MDI.

Erratum. Establishment of the T1D Exchange Quality Improvement Collaborative (T1DX-QI). Clinical Diabetes 2020;38:141-151 (DOI: 10.2337/cd19-0032).

[This corrects the article on p. 141 in vol. 38, PMID: 32327886.].

Establishment of the T1D Exchange Quality Improvement Collaborative (T1DX-QI).

The T1D Exchange established a learning platform by evaluating the current state of care and engaging 10 diabetes clinics in collaborative quality improvement (QI) activities. Participating clinics are sharing data and best practices to improve care delivery for people with type 1 diabetes. This article describes the design and initial implementation of this platform, known as the T1D Exchange Quality Improvement Collaborative. This effort has laid a foundation for learning from variation in type 1 diabetes care delivery via QI methodology and has demonstrated success in improving processes through iterative testing cycles and transparent sharing of data.

Identification of novel variants in a large cohort of children with Tay-Sachs disease: An initiative of a multicentric task force on lysosomal storage disorders by Government of India.

Tay-Sachs disease (TSD) (OMIM) is a neurodegenerative lysosomal storage disorder caused due to mutations in the HEXA gene. To date, nearly 190 mutations have been reported in HEXA gene. Here, we have characterized 34 enzymatically confirmed TSD families to investigate the presence of novel as well as known variants in HEXA gene. Overall study detected 25 variants belonging to 31 affected TSD patients and 3 carrier couples confirmed by enzyme study. Of these 17 patients harbors 15 novel variants, including seven missense variants [p.V206L, p.Y213H, p.R252C, p.F257S, p.C328G, p.G454R, and p.P475R], four nonsense variant [p.S9X, p.E91X, p.W420X, and p.W482X], two splice site variants [c.347-1G>A and c.460-1G>A], and two small deletion [c.1349delC (p.A450VfsX3) and c.52delG (p.G18Dfs*82)]. While remaining 17 patients harbors 10 previously reported variants that includes six missense variants [p.M1T, p.R170Q, p.D322Y, p.D322N, p.E462V, and p.R499C], one nonsense variant [p.Q106X], two splice site variants [c.1073+1G>A and c.459+4A>G] and one 4 bp insertion [c.1278insTATC (p.Y427IfsX5)]. In conclusion, Indian infantile TSD patients provide newer insight into the molecular heterogeneity of the TSD. Combining present study and our earlier studies, we have observed that 67% genotypes found in Indian TSD patients are novel, which are associated with severe infantile phenotypes, while rest 33% genotypes found in our cohort were previously reported in various populations. In addition, higher frequency of the p.E462V and c.1278insTATC mutations in the present study further support and suggest the prevalence of p.E462V mutation in the Indian population.

Real-world opportunity of empagliflozin to improve blood pressure control in African American patients with type 2 diabetes: A National Cardiovascular Data Registry "research-to-practice" project from the diabetes collaborative registry.

The 1245.29 Trial recently showed that empaglifozin improved both blood pressure and glucose control in African American (AA) patients with type 2 diabetes (T2D) and hypertension. Using the Diabetes Collaborative Registry, a large-scale US registry of outpatients with diabetes recruited from primary care, cardiology and endocrinology practices, we sought to understand the potential impact of these observations in routine clinical practice. Among 74 290 AA patients with T2D from 368 US clinics, 60.4% had hypertension, of whom 34.5% had systolic blood pressure ≥ 140 mm Hg (20.8% of the total AA T2D population). Only 1.7% of this eligible population had been prescribed a sodium-glucose co-transporter two inhibitor. The mean estimated 5-year risk of cardiovascular death was 7.7%, which could be reduced to 6.2% when modelling the antihypertensive effect of empagliflozin across the eligible population (based on an 8-mm Hg blood pressure reduction). These findings may represent a potential opportunity for better management of cardiovascular risk factors and improved outcomes in this vulnerable cohort.

Identification of deletion-duplication in HEXA gene in five children with Tay-Sachs disease from India.

BACKGROUND: Tay-Sachs disease (TSD) is a sphingolipid storage disorder caused by mutations in the HEXA gene. To date, nearly 170 mutations of HEXA have been described, including only one 7.6 kb large deletion. METHODS: Multiplex Ligation-dependent Probe Amplification (MLPA) study was carried out in 5 unrelated patients for copy number changes where heterozygous and/or homozygous disease causing mutation/s could not be identified in the coding region by sequencing of HEXA gene. RESULTS: The study has identified the presence of a homozygous deletion of exon-2 and exon-3 in two patients, two patient showed compound heterozygosity with exon 1 deletion combined with missense mutation p.E462V and one patient was identified with duplication of exon-1 with novel variants c.1527-2A > T as a second allele. CONCLUSION: This is the first report of deletion/duplication in HEXA gene providing a new insight into the molecular basis of TSD and use of MLPA assay for detecting large copy number changes in the HEXA gene.

IMPROVEMENTS IN METABOLIC CONTROL IN ADULTS WITH TYPE 2 DIABETES FOLLOWING REFERRAL TO A DIABETES CENTER, 2005-2010.

OBJECTIVE: We aimed to compare metabolic control in adults with diabetes in the general population to those newly referred to a diabetes center and after 1 year of specialty care. METHODS: We performed a retrospective comparison of adults with diabetes aged ≥20 years data from the National Health and Nutrition Examination Survey (NHANES, n = 1,674) and a diabetes center (n = 3,128) from 2005-2010. NHANES participants represented the civilian, non-institutionalized U.S. POPULATION: Diabetes center referrals lived primarily around eastern Massachusetts. The proportion attaining targets for glycated hemoglobin A1c (A1c), blood pressure (BP), low-density lipoprotein (LDL) cholesterol, or all 3 (ABC control) and the proportion prescribed medications to lower A1c, BP, or cholesterol were evaluated. RESULTS: Compared to the general sample, a smaller proportion of new diabetes center referrals had A1c <7% (<53 mmol/mol, 24% vs. 53%, P<.001), BP <130/80 mm Hg (38% vs. 50%, P<.001), and ABC control (5.6% vs. 17%, P<.001) but not LDL<100 mg/dL (<2.6 mmol/L, 54% vs. 53%, P = .65). After 1 year, more diabetes center referrals attained targets for A1c (40%), BP (38%), LDL (67%), and ABC control (15%) (P<.001 for all versus baseline). ABC control was not different between the general sample and diabetes center referrals at 1 year (P = .16). After 1 year, a greater percentage of diabetes center referrals compared to the general sample were prescribed medications to lower glucose (95% vs. 72%), BP (79% vs. 64%), and cholesterol (77% vs. 54%)(all P<.001). CONCLUSION: Compared to the general population, glycemic control was significantly worse for adults newly referred to the diabetes center. Within 1 year of specialty care, ABC control increased 270% in the setting of significant therapy escalation. ABBREVIATIONS: A1c = glycated hemoglobin A1c ABC = composite of A1c, blood pressure, and cholesterol ACEi = angiotensin-converting enzyme inhibitor ARB = angiotensin receptor blocker BMI = body mass index BP = blood pressure EHR = electronic health record LDL = low-density lipoprotein NCHS = National Center for Health Statistics NHANES = National Health and Nutrition Examination Survey PCP = primary care provider.

Improving dietary quality in youth with type 1 diabetes: randomized clinical trial of a family-based behavioral intervention.

BACKGROUND: Diets of children with type 1 diabetes are low in fruits, vegetables, and whole grains, and high in foods of minimal nutritional value, increasing risk for future adverse health outcomes. This 18-month randomized clinical trial tested the effect of a family-based behavioral intervention integrating motivational interviewing, active learning, and applied problem-solving on the primary outcomes of dietary intake and glycemic control among youth with type 1 diabetes. METHODS: A parallel-group study with equal randomization was conducted at an outpatient, free-standing, multidisciplinary tertiary diabetes center in the United States. Eligible youth were those age 8-16 years with type 1 diabetes diagnosis ≥1 year and hemoglobin A1c (HbA1c) ≥6.5% and ≤10.0%. Participants were 136 parent-youth dyads (treatment n = 66, control n = 70). The intervention consisted of 9 in-clinic sessions delivered to the child and parent; control condition comprised equivalent assessments and number of contacts without dietary advice. Dietary intake was assessed using 3-day diet records at 6 time points across the 18-month study. Dietary outcomes included the Healthy Eating Index-2005 (HEI2005; index measuring conformance to the 2005 United States Dietary Guidelines for Americans) and Whole Plant Food Density (WPFD; number of cup or ounce equivalents per 1000 kcal of whole grains, whole fruit, vegetables, legumes, nuts, and seeds consumed). HbA1c was obtained every 3 months. Overall comparison of outcome variables between intervention and usual care groups was conducted using permutation tests. RESULTS: There was a positive intervention effect across the study duration for HEI2005 (p = .015) and WPFD (p = .004). At 18 months, HEI2005 was 7.2 greater (mean ± SE 64.6 ± 2.0 versus 57.4 ± 1.6), and WPFD was 0.5 greater (2.2 ± 0.1 versus 1.7 ± 0.1) in the intervention group versus control. There was no difference between groups in HbA1c across the study duration. CONCLUSIONS: This behavioral nutrition intervention improved dietary quality among youth with type 1 diabetes, but did not impact glycemic control. Findings indicate the potential utility of incorporating such strategies into clinical care, and suggest that improvement in diet quality can be achieved in families living with this burdensome disease. TRIAL REGISTRATION: Clinicaltrials.gov registration number: NCT00999375.

Effects of Macronutrient Intake and Number of Meals on Glycemic Outcomes Over 1 Year in Youth with Type 1 Diabetes.

Objective: Insulin bolus doses derive from glucose levels and planned carbohydrate intake, although fat and protein impact glycemic excursions. We examined the impact of macronutrients and number of daily meals/snacks on glycemic outcomes in youth with type 1 diabetes. Methods: Youth (N = 136, ages 8-17) with type 1 diabetes completed 3-day food records, wore 3-day masked continuous glucose monitoring, and had A1c measurements every 3 months for 1 year. Diet data were analyzed using Nutrition Data System for Research. Longitudinal mixed models assessed effects of macronutrient intake and number of meals/snacks on glycemic outcomes. Results: At baseline, youth (48% male) had mean age of 12.8 ± 2.5 years and diabetes duration of 5.9 ± 3.1 years; 73% used insulin pumps. Baseline A1c was 8.1% ± 1.0%, percent time in range 70-180 mg/dL (%TIR) was 49% ± 17%, % time below range <70 mg/dL (%TBR) was 6% ± 8%, % time above range >180 mg/dL (%TAR) was 44% ± 20%, and glycemic variability as coefficient of variation (CV) was 41% ± 8%; macronutrient intake included 48% ± 5% carbohydrate, 36% ± 5% fat, and 16% ± 2% protein. Most youth (56%) reported 3-4 meals/snacks daily (range 1-9). Over 1 year, greater carbohydrate intake was associated with lower A1c (P = 0.0003), more %TBR (P = 0.0006), less %TAR (P = 0.002), and higher CV (P = 0.03). Greater fat intake was associated with higher A1c (P = 0.006), less %TBR (P = 0.002), and more %TAR (P = 0.005). Greater protein intake was associated with higher A1c (P = 0.01). More daily meals/snacks were associated with lower A1c (P = 0.001), higher %TIR (P = 0.0006), and less %TAR (P = 0.0001). Conclusions: Both fat and protein impact glycemic outcomes. Future automated insulin delivery systems should consider all macronutrients for timely insulin provision. The present research study derived from secondary analysis of the study registered under NCT00999375.

Two Years with a Tubeless Automated Insulin Delivery System: A Single-Arm Multicenter Trial in Children, Adolescents, and Adults with Type 1 Diabetes.

Background: The Omnipod® 5 Automated Insulin Delivery (AID) System was shown to be safe and effective following 3 months of use in people with type 1 diabetes (T1D); however, data on the durability of these results are limited. This study evaluated the long-term safety and effectiveness of Omnipod 5 use in people with T1D during up to 2 years of use. Materials and Methods: After a 3-month single-arm, multicenter, pivotal trial in children (6-13.9 years) and adolescents/adults (14-70 years), participants could continue system use in an extension phase. HbA1c was measured every 3 months for up to 15 months; continuous glucose monitor metrics were collected for up to 2 years. Results: Participants (N = 224) completed median (interquartile range) 22.3 (21.7, 22.7) months of AID. HbA1c was reduced in the pivotal trial from 7.7% ± 0.9% in children and 7.2% ± 0.9% in adolescents/adults to 7.0% ± 0.6% and 6.8% ± 0.7%, respectively, (P < 0.0001), and was maintained at 7.2% ± 0.7% and 6.9% ± 0.6% after 15 months (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 52.4% ± 15.6% in children and 63.6% ± 16.5% in adolescents/adults at baseline to 67.9% ± 8.0% and 73.8% ± 10.8%, respectively, during the pivotal trial (P < 0.0001) and was maintained at 65.9% ± 8.9% and 72.9% ± 11.3% during the extension (P < 0.0001 from baseline). One episode of diabetic ketoacidosis and seven episodes of severe hypoglycemia occurred during the extension. Children and adolescents/adults spent median 96.1% and 96.3% of time in Automated Mode, respectively. Conclusion: Our study supports that long-term use of the Omnipod 5 AID System can safely maintain improvements in glycemic outcomes for up to 2 years of use in people with T1D. Clinical Trials Registration Number: NCT04196140.

Relationships among parent and youth healthful eating attitudes and youth dietary intake in a cross-sectional study of youth with type 1 diabetes.

BACKGROUND: Constructs based on Social Cognitive Theory have shown utility in understanding dietary behavior; however, little research has examined these relations in youth and parents concurrently. Unique demands of dietary management among families of youth with type 1 diabetes (T1D) suggest the importance of investigation in this population. The purpose of this study was to develop and evaluate youth and parent measures of self-efficacy, outcome expectations, and barriers for healthful eating, and parent modeling of healthful eating, in a sample of youth with type 1 diabetes and their parents. METHODS: Youth (n=252) ages 8-18 years with diabetes duration ≥1 year and parents completed self-report measures of healthful eating attitudes including self-efficacy, perceived barriers, positive and negative outcome expectations; youth reported parent modeling of healthful eating. Youth dietary intake from 3-day diet records was used to calculate the Healthy Eating Index 2005 and the Nutrient Rich Foods 9.3 index, measures of overall diet quality. The relations among parent and youth healthful eating attitudes, parent modeling, and youth diet quality were examined using structural equation modeling. RESULTS: Internal consistency and test-retest reliability of the measures were acceptable. The structural equation model demonstrated acceptable fit (CFI/TLI=0.94/0.94; RMSEA=0.03), and items loaded the hypothesized factors. Parent modeling ß^=.27,p=.02 and attitudes toward healthful eating (latent variable comprised of self-efficacy, barriers, outcome expectations) ß^=.16,p=.04 had direct effects on youth diet quality. Parent modeling had a direct effect on youth attitudes ß^=.49,p<.001; parent attitudes had an indirect effect on youth attitudes through parent modeling ß^=.12,p,<.001. Youth attitudes were not associated with youth diet quality. Overall, the model accounted for 20% of the variance in child diet quality. CONCLUSIONS: Parent diet-related behaviors demonstrated an impact on youth attitudes and diet quality, suggesting the importance of family-based clinical and public health efforts to improve diet.

An "All-Data-on-Hand" Deep Learning Model to Predict Hospitalization for Diabetic Ketoacidosis in Youth With Type 1 Diabetes: Development and Validation Study.

BACKGROUND: Although prior research has identified multiple risk factors for diabetic ketoacidosis (DKA), clinicians continue to lack clinic-ready models to predict dangerous and costly episodes of DKA. We asked whether we could apply deep learning, specifically the use of a long short-term memory (LSTM) model, to accurately predict the 180-day risk of DKA-related hospitalization for youth with type 1 diabetes (T1D). OBJECTIVE: We aimed to describe the development of an LSTM model to predict the 180-day risk of DKA-related hospitalization for youth with T1D. METHODS: We used 17 consecutive calendar quarters of clinical data (January 10, 2016, to March 18, 2020) for 1745 youths aged 8 to 18 years with T1D from a pediatric diabetes clinic network in the Midwestern United States. The input data included demographics, discrete clinical observations (laboratory results, vital signs, anthropometric measures, diagnosis, and procedure codes), medications, visit counts by type of encounter, number of historic DKA episodes, number of days since last DKA admission, patient-reported outcomes (answers to clinic intake questions), and data features derived from diabetes- and nondiabetes-related clinical notes via natural language processing. We trained the model using input data from quarters 1 to 7 (n=1377), validated it using input from quarters 3 to 9 in a partial out-of-sample (OOS-P; n=1505) cohort, and further validated it in a full out-of-sample (OOS-F; n=354) cohort with input from quarters 10 to 15. RESULTS: DKA admissions occurred at a rate of 5% per 180-days in both out-of-sample cohorts. In the OOS-P and OOS-F cohorts, the median age was 13.7 (IQR 11.3-15.8) years and 13.1 (IQR 10.7-15.5) years; median glycated hemoglobin levels at enrollment were 8.6% (IQR 7.6%-9.8%) and 8.1% (IQR 6.9%-9.5%); recall was 33% (26/80) and 50% (9/18) for the top-ranked 5% of youth with T1D; and 14.15% (213/1505) and 12.7% (45/354) had prior DKA admissions (after the T1D diagnosis), respectively. For lists rank ordered by the probability of hospitalization, precision increased from 33% to 56% to 100% for positions 1 to 80, 1 to 25, and 1 to 10 in the OOS-P cohort and from 50% to 60% to 80% for positions 1 to 18, 1 to 10, and 1 to 5 in the OOS-F cohort, respectively. CONCLUSIONS: The proposed LSTM model for predicting 180-day DKA-related hospitalization was valid in this sample. Future research should evaluate model validity in multiple populations and settings to account for health inequities that may be present in different segments of the population (eg, racially or socioeconomically diverse cohorts). Rank ordering youth by probability of DKA-related hospitalization will allow clinics to identify the most at-risk youth. The clinical implication of this is that clinics may then create and evaluate novel preventive interventions based on available resources.

Lung Imaging in COPD Part 2: Emerging Concepts.

The diagnosis, prognostication, and differentiation of phenotypes of COPD can be facilitated by CT scan imaging of the chest. CT scan imaging of the chest is a prerequisite for lung volume reduction surgery and lung transplantation. Quantitative analysis can be used to evaluate extent of disease progression. Evolving imaging techniques include micro-CT scan, ultra-high-resolution and photon-counting CT scan imaging, and MRI. Potential advantages of these newer techniques include improved resolution, prediction of reversibility, and obviation of radiation exposure. This article discusses important emerging techniques in imaging patients with COPD. The clinical usefulness of these emerging techniques as they stand today are tabulated for the benefit of the practicing pulmonologist.

Evaluation of 1,5-anhydroglucitol, hemoglobin A1c, and glucose levels in youth and young adults with type 1 diabetes and healthy controls.

BACKGROUND AND OBJECTIVE: Serum 1,5-anhydroglucitol (1,5-AG) is a marker of hyperglycemic excursions in adults with diabetes and hemoglobin A1c (HbA1c) < 8%. We compared 1,5-AG levels among youth and young adults with and without type 1 diabetes (T1D) and investigated the utility of 1,5-AG in the assessment of glycemic status in pediatric T1D. METHODS: We compared 1,5-AG, HbA1c, and plasma glucose levels in 138 patients with T1D (duration ≥1 yr) and 136 healthy controls, aged 10-30 yr. Within each group, we investigated associations between 1,5-AG and clinical characteristics, HbA1c and random plasma glucose. For patients with T1D, 1,5-AG was further analyzed according to HbA1c strata: <8, 8-9, and >9%. RESULTS: Compared to controls, patients with T1D had higher HbA1c (8.5 ± 1.6 vs. 5.1 ± 0.4%, p < 0.0001), lower 1,5-AG (4.0 ± 2.0 vs. 24.7 ± 6.4 µg/mL, p < 0.0001), and higher glucose (11.1 ± 5.2 vs. 5.1 ± 0.9 mmol/L, p < 0.0001). Males had higher 1,5-AG than females within patients (4.5 ± 2.3 vs. 3.4 ± 1.6 µg/mL, p = 0.003) and controls (26.0 ± 6.6 vs. 23.5 ± 6.0 µg/mL, p = 0.02). 1,5-AG was not correlated with glucose in either group. 1,5-AG was significantly correlated to HbA1c in patients, but not controls. For patients with HbA1c < 8%, 1,5-AG demonstrated the widest range and was not predicted by HbA1c; 1,5-AG levels were narrowly distributed among patients with HbA1c ≥ 8%. CONCLUSIONS: Youth and young adults with T1D demonstrate similar 1,5-AG levels which are distinct from controls. 1,5-AG assessment may provide unique information beyond that provided by HbA1c in the mid-term assessment of glycemic control in young patients with T1D and HbA1c < 8%.

Caring for Young Adults With Diabetes in the Adult Care Setting: Summary of a Multidisciplinary Roundtable.

Aims: A multidisciplinary team of clinicians and researchers, patients and family members, and representative from national advocacy groups and research organization met to review the literature, highlight gaps, and identify best practices to improve adult care delivery for young adults (YA) with diabetes. Methods: The participants prepared presentations in advance, rotated through sessions, and contributed to group discussions in three areas: physical health, mental health, and quality of life (QoL). Session moderators and scribes used thematic analysis to summarize discussions for each topic. Results: Thematic analysis revealed four foci for addressing physical health, mental health and QoL: 1) best practices to facilitate the process of transfer; 2) age-specific curricula and guidelines for prevention and management of comorbidities and complications; 3) collaboration with behavioral health clinicians to address diabetes distress and mental health disorders; and 4) research on the impact of diabetes on QoL in YA. Conclusion: There was substantial interest and need among adult clinicians to work in concert with pediatric and mental health professionals to identify best practices and future directions to improve healthcare process and diabetes-related outcome measures in YA with diabetes.