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Coronavirus infection can cause a range of syndromes, which in dogs can include mild-to-severe enteritis that generally resolves rapidly. Fatalities can occur from coinfection with other pathogens, including canine parvovirus. Between late December 2019 and April 2020, canine coronavirus (CCoV) was detected in Australian racing Greyhounds that displayed signs of gastrointestinal disease. The CCoV was genotyped using high-throughput sequencing, recovering 98.3% of a type IIb CCoV, generally thought to cause a mild but highly contagious enteric disease. The Australian CCoV was almost identical (99.9%, whole-genome sequence) to another CCoV associated with an outbreak of severe vomiting in dogs in the United Kingdom at the same time (December 2019–March 2020).

Summary Background Insertion of a ventriculoperitoneal shunt for hydrocephalus is one of the commonest neurosurgical procedures worldwide. Infection of the implanted shunt affects up to 15% of these patients, resulting in prolonged hospital treatment, multiple surgeries, and reduced cognition and quality of life. Our aim was to determine the clinical and cost-effectiveness of antibiotic (rifampicin and clindamycin) or silver shunts compared with standard shunts at reducing infection. Methods In this parallel, multicentre, single-blind, randomised controlled trial, we included patients with hydrocephalus of any aetiology undergoing insertion of their first ventriculoperitoneal shunt irrespective of age at 21 regional adult and paediatric neurosurgery centres in the UK and Ireland. Patients were randomly assigned (1:1:1 in random permuted blocks of three or six) to receive standard shunts (standard shunt group), antibiotic-impregnated (0·15% clindamycin and 0·054% rifampicin; antibiotic shunt group), or silver-impregnated shunts (silver shunt group) through a randomisation sequence generated by an independent statistician. All patients and investigators who recorded and analysed the data were masked for group assignment, which was only disclosed to the neurosurgical staff at the time of operation. Participants receiving a shunt without evidence of infection at the time of insertion were followed up for at least 6 months and a maximum of 2 years. The primary outcome was time to shunt failure due the infection and was analysed with Fine and Gray survival regression models for competing risk by intention to treat. This trial is registered with ISRCTN 49474281. Findings Between June 26, 2013, and Oct 9, 2017, we assessed 3505 patients, of whom 1605 aged up to 91 years were randomly assigned to receive either a standard shunt (n=536), an antibiotic-impregnated shunt (n=538), or a silver shunt (n=531). 1594 had a shunt inserted without evidence of infection at the time of insertion (533 in the standard shunt group, 535 in the antibiotic shunt group, and 526 in the silver shunt group) and were followed up for a median of 22 months (IQR 10–24; 53 withdrew from follow-up). 32 (6%) of 533 evaluable patients in the standard shunt group had a shunt revision for infection, compared with 12 (2%) of 535 evaluable patients in the antibiotic shunt group (cause-specific hazard ratio [csHR] 0·38, 97·5% CI 0·18–0·80, p=0·0038) and 31 (6%) of 526 patients in the silver shunt group (0·99, 0·56–1·74, p=0·96). 135 (25%) patients in the standard shunt group, 127 (23%) in the antibiotic shunt group, and 134 (36%) in the silver shunt group had adverse events, which were not life-threatening and were mostly related to valve or catheter function. Interpretation The BASICS trial provides evidence to support the adoption of antibiotic shunts in UK patients who are having their first ventriculoperitoneal shunt insertion. This practice will benefit patients of all ages by reducing the risk and harm of shunt infection. Funding UK National Institute for Health Research Health Technology Assessment programme.

The purpose of this study was to assess the pain control methods in use by patients who have Ehlers-Danlos Syndrome (EDS), a group of connective tissue disorders, and their perceived effectiveness.This descriptive study involved 1179 adults diagnosed with EDS who completed an anonymous on-line survey. The survey consisted of demographics information, the Patient Reported Outcomes Measurement Information System (PROMIS) Pain-Behavior, PROMIS Pain-Interference, and Neuro QOL Satisfaction with Social Roles and Activities scales, as well as a modified version of the Pain Management Strategies Survey.Respondents reported having to seek out confirmation of their EDS diagnosis with multiple healthcare providers, which implies the difficulty many people with EDS face when trying to gain access to appropriate treatment. Patients with EDS experience higher levels of pain interference and lower satisfaction with social roles and activities compared to national norms. Among the treatment modalities in this study, those perceived as most helpful for acute pain control were opioids, surgical interventions, splints and braces, avoidance of potentially dangerous activities and heat therapy. Chronic pain treatments rated as most helpful were opioids, splints or braces and surgical interventions. For methods used for both acute and chronic pain, those perceived as most helpful were opioids, massage therapies, splints or braces, heat therapy and avoiding potentially dangerous activities.EDS is a complex, multi-systemic condition that can be difficult to diagnose and poses challenges for healthcare practitioners who engage with EDS patients in holistic care. Improved healthcare provider knowledge of EDS is needed, and additional research on the co-occurring diagnoses with EDS may assist in comprehensive pain management for EDS patients.Ehlers-Danlos Syndrome (EDS) is a group of connective tissue disorders associated with defective production of collagen, which can dramatically reduce musculoskeletal functioning by symptoms of joint laxity and frequent dislocations eventually leading to disability. Respondents to an on-line survey reported having to seek out confirmation of their EDS diagnosis with multiple physicians, which implies the difficulty many people with EDS face when trying to gain access to appropriate treatment. Participants with EDS reported the most helpful methods for managing acute pain were opioids, surgical interventions, splints and braces, heat therapy, nerve blocks and physical therapy, while chronic pain was treated most effectively with opioids, heat therapy, splints or braces and surgical interventions.

We evaluated the safety and efficacy of closed-loop therapy with meal announcement during reduction and omission of meal insulin boluses in adolescents with type 1 diabetes (T1D). Twelve adolescents with T1D [six male; mean (s.d.) age 15.9 (1.8) years; mean (s.d.) glycated haemoglobin (HbA1c) 77 (27) mmol/mol] were studied in a randomized crossover study comparing closed-loop therapy with meal announcement with conventional pump therapy over two 24-h stays at a clinical research facility. Identical meals were given on both occasions. The evening meal insulin bolus was calculated to cover half of the carbohydrate content of the meal and no bolus was delivered for lunch. Plasma glucose levels were in the target range of 3.9–10 mmol/l for a median [interquartile range (IQR)] of 74 (55,86)% of the time during closed-loop therapy with meal announcement and for 62 (49,75)% of the time during conventional therapy (p = 0.26). Median (IQR) time spent with plasma glucose levels > 10 mmol/l [23 (13,39) vs. 27 (10,50)%; p = 0.88] or

Accurate real-time continuous glucose measurements may improve glucose control in the critical care unit. We evaluated the accuracy of the FreeStyle(®) Navigator(®) (Abbott Diabetes Care, Alameda, CA) subcutaneous continuous glucose monitoring (CGM) device in critically ill adults using two methods of calibration.In a randomized trial, paired CGM and reference glucose (hourly arterial blood glucose [ABG]) were collected over a 48-h period from 24 adults with critical illness (mean±SD age, 60±14 years; mean±SD body mass index, 29.6±9.3 kg/m(2); mean±SD Acute Physiology and Chronic Health Evaluation score, 12±4 [range, 6-19]) and hyperglycemia. In 12 subjects, the CGM device was calibrated at variable intervals of 1-6 h using ABG. In the other 12 subjects, the sensor was calibrated according to the manufacturer's instructions (1, 2, 10, and 24 h) using arterial blood and the built-in point-of-care glucometer.In total, 1,060 CGM-ABG pairs were analyzed over the glucose range from 4.3 to 18.8 mmol/L. Using enhanced calibration median (interquartile range) every 169 (122-213) min, the absolute relative deviation was lower (7.0% [3.5, 13.0] vs. 12.8% [6.3, 21.8], P0.001), and the percentage of points in the Clarke error grid Zone A was higher (87.8% vs. 70.2%).Accuracy of the Navigator CGM device during critical illness was comparable to that observed in non-critical care settings. Further significant improvements in accuracy may be obtained by frequent calibrations with ABG measurements.

OBJECTIVE To compare two validated closed-loop (CL) algorithms versus patient self-control with CSII in terms of glycemic control. RESEARCH DESIGN AND METHODS This study was a multicenter, randomized, three-way crossover, open-label trial in 48 patients with type 1 diabetes mellitus for at least 6 months, treated with continuous subcutaneous insulin infusion. Blood glucose was controlled for 23 h by the algorithm of the Universities of Pavia and Padova with a Safety Supervision Module developed at the Universities of Virginia and California at Santa Barbara (international artificial pancreas [iAP]), by the algorithm of University of Cambridge (CAM), or by patients themselves in open loop (OL) during three hospital admissions including meals and exercise. The main analysis was on an intention-to-treat basis. Main outcome measures included time spent in target (glucose levels between 3.9 and 8.0 mmol/L or between 3.9 and 10.0 mmol/L after meals). RESULTS Time spent in the target range was similar in CL and OL: 62.6% for OL, 59.2% for iAP, and 58.3% for CAM. While mean glucose level was significantly lower in OL (7.19, 8.15, and 8.26 mmol/L, respectively) (overall P = 0.001), percentage of time spent in hypoglycemia ( CONCLUSIONS Both CAM and iAP algorithms provide safe glycemic control.

OBJECTIVE To describe activity patterns in pregnant women with type 1 diabetes and evaluate the impact of increased structured physical activity on glucose control. RESEARCH DESIGN AND METHODS Physical activity energy expenditure (PAEE) and glucose levels (continuous glucose monitoring) were measured in 10 pregnant women with type 1 diabetes (age 33.2 years, gestation 20 weeks, BMI 27.9 kg/m2, diabetes duration 16.6 years, HbA1c 6.5% [48 mmol/mol], insulin pump duration 2.4 years) during a day at home (free-living) and during a 24-h visit incorporating controlled diet and structured physical activity with light intensity activity (three 20-min self-paced walks) and moderate intensity activity (two 50-min sessions of brisk treadmill walking). PAEE was evaluated through individually calibrated combined heart rate and movement sensing. RESULTS Free-living PAEE was comparable to that under controlled study conditions (3.8 and 5.1 kcal/kg/day, P = 0.241), with women achieving near to the recommended 30 min of moderate physical activity (median 27 min [interquartile range 14–68]). During the free-living period, more time was spent in light activity (10.3 vs. 7.2 h, P = 0.005), with less sedentary time (13.0 vs. 14.9 h, P = 0.047) and less moderate activity (27 vs. 121 min, P = 0.022). The free-living 24-h mean glucose levels by continuous glucose monitoring were significantly higher (7.7 vs. 6.0 mmol/L, P = 0.028). The effect of controlled diet and exercise persisted overnight, with significantly less time spent hyperglycemic (19 vs. 0%, P = 0.028) and less glucose variability (glucose SD 1.3 vs. 0.7 mmol/L, P = 0.022). CONCLUSIONS A controlled diet and structured physical activity program may assist women with type 1 diabetes in achieving optimal glucose control during pregnancy.

OBJECTIVE We evaluated the safety and efficacy of closed-loop basal insulin delivery during sleep and after regular meals and unannounced periods of exercise. RESEARCH DESIGN AND METHODS Twelve adolescents with type 1 diabetes (five males; mean age 15.0 [SD 1.4] years; HbA1c 7.9 [0.7]%; BMI 21.4 [2.6] kg/m2) were studied at a clinical research facility on two occasions and received, in random order, either closed-loop basal insulin delivery or conventional pump therapy for 36 h. During closed-loop insulin delivery, pump basal rates were adjusted every 15 min according to a model predictive control algorithm informed by subcutaneous sensor glucose levels. During control visits, subjects’ standard infusion rates were applied. Prandial insulin boluses were given before main meals (50–80 g carbohydrates) but not before snacks (15–30 g carbohydrates). Subjects undertook moderate-intensity exercise, not announced to the algorithm, on a stationary bicycle at a 140 bpm heart rate in the morning (40 min) and afternoon (20 min). Primary outcome was time when plasma glucose was in the target range (71–180 mg/dL). RESULTS Closed-loop basal insulin delivery increased percentage time when glucose was in the target range (median 84% [interquartile range 78–88%] vs. 49% [26–79%], P = 0.02) and reduced mean plasma glucose levels (128 [19] vs. 165 [55] mg/dL, P = 0.02). Plasma glucose levels were in the target range 100% of the time on 17 of 24 nights during closed-loop insulin delivery. Hypoglycemia occurred on 10 occasions during control visits and 9 occasions during closed-loop delivery (5 episodes were exercise related, and 4 occurred within 2.5 h of prandial bolus). CONCLUSIONS Day-and-night closed-loop basal insulin delivery can improve glucose control in adolescents. However, unannounced moderate-intensity exercise and excessive prandial boluses pose challenges to hypoglycemia-free closed-loop basal insulin delivery.

Performance of continuous glucose monitors (CGMs) may be lower when glucose levels are changing rapidly, such as occurs during physical activity. Our aim was to evaluate accuracy of a current-generation CGM during moderate-intensity exercise in type 1 diabetes (T1D) pregnancy.As part of a study of 24-h closed-loop insulin delivery in 12 women with T1D (disease duration, 17.6 years; glycosylated hemoglobin, 6.4%) during pregnancy (gestation, 21 weeks), we evaluated the Freestyle Navigator(®) sensor (Abbott Diabetes Care, Alameda, CA) during afternoon (15:00-18:00 h) and morning (09:30-12:30 h) exercise (55 min of brisk walking on a treadmill followed by a 2-h recovery), compared with sedentary conditions (18:00-09:00 h). Plasma (reference) glucose, measured at regular 15-30-min intervals with the YSI Ltd. (Fleet, United Kingdom) model YSI 2300 analyzer, was used to assess CGM performance.Sensor accuracy, as indicated by the larger relative absolute difference (RAD) between paired sensor and reference glucose values, was lower during exercise compared with rest (median RAD, 11.8% vs. 18.4%; P0.001). These differences remained significant when correcting for plasma glucose relative rate of change (P0.001). Analysis by glucose range showed lower accuracy during hypoglycemia for both sedentary (median RAD, 24.4%) and exercise (median RAD, 32.1%) conditions. Using Clarke error grid analysis, 96% of CGM values were clinically safe under resting conditions compared with only 87% during exercise.Compared with sedentary conditions, accuracy of the Freestyle Navigator CGM was lower during moderate-intensity exercise in pregnant women with T1D. This difference was particularly marked in hypoglycemia and could not be solely explained by the glucose rate of change associated with physical activity.

Objective To evaluate an ambulatory, portable prototype, overnight automated closed-loop (CL) system and to explore optimal time of CL initiation. Methods We performed a randomized crossover study and compared automated overnight glucose control started at the time of an evening-meal or at bedtime. Eight young people with type 1 diabetes (T1D) on insulin pump therapy [M = 4; age = 14.3 (1.7) yr; HbA1c = 8.2 (1.3)%; mean (SD)] were studied on two occasions at clinical research facility. A standardized self-selected evening meal [70 (11)g CHO] and snack [22 (4)g CHO] accompanied by prandial insulin boluses were given at 18:00 and 21:00 hours, respectively. In random order, automated CL was started at 18:00 or 21:00 hours and ran until 8:00 hours the next day. Basal insulin delivery was automatically adjusted by a model predictive control algorithm based on real-time continuous glucose monitor readings. Results Overnight plasma glucose levels (between 21:00 and 08:00 hours) were within the target range (71–145 mg/dL) for 82 (59, 98)% of time when CL started at 18:00 hours and 64 (48, 70)% when CL started at 21:00 hours [median (IQR), p = 0.036]. Time spent above 180 mg/dL [8 (0, 17) vs. 13 (3, 26)%, p = 0.310] or below 70 mg/dL [0 (0,7) vs. 0 (0, 8)%, p = 1.000] did not differ between the two occasions. Mean overnight glucose [121 (14) vs. 137 (13) mg/dL, p = 0.731) was also similar. Overnight insulin infusion rates were comparable [0.8 (0.5, 1.3) vs. 0.8 (0.6, 1.4) U/h, p = 0.263]. No interruptions to CL delivery were observed. Conclusion Automated CL delivery can be applied reliably and safely to control glucose levels overnight in young people with T1D. Tighter glucose levels may be achieved with an earlier time of CL initiation.

Counselors may encounter clients who wish to make such lifestyle changes as healthy eating and weight management. Mindfulness, defined here as the practice of nonjudgmentally attending to the present moment while monitoring reactivity, has been adapted for use in treating many self-regulation disorders; mindfulness-based eating approaches support intuitive or attuned eating, an approach to weight management that helps individuals recognize internal cues in support of enhanced self-regulation. One program for developing mindfulness skills in individuals who want to maintain weight loss is the Enhancing Mindfulness for the Prevention of Weight Regain (EMPOWER) Program. Participants report changes in eating behavior, thinking patterns, emotional reactions, and physical activity and increased acceptance of personal responsibility for making choices, planning, asserting needs, and accomplishing personal goals. The article reviews key mindfulness skills for clinical practice.

This study examined whether mindfulness increased through participation in movement-based courses and whether changes in self-regulatory self-efficacy, mood, and perceived stress mediated the relationship between increased mindfulness and better sleep.166 college students enrolled in the 2007-2008 academic year in 15 week classes in Pilates, Taiji quan, or GYROKINESIS.At beginning, middle, and end of the semester, participants completed measures of mindfulness, self-regulatory self-efficacy, mood, perceived stress, and sleep quality.Total mindfulness scores and mindfulness subscales increased overall. Greater changes in mindfulness were directly related to better sleep quality at the end of the semester after adjusting for sleep disturbance at the beginning. Tiredness, Negative Arousal, Relaxation, and Perceived Stress mediated the effect of increased mindfulness on improved sleep.Movement-based courses can increase mindfulness. Increased mindfulness accounts for changes in mood and perceived stress, which explain, in part, improved sleep quality.

This study evaluated the impact ofan extended shelter-based child development/family therapy intervention, called Building Blocks, on the development of children of substance- abusing homeless mothers. The homeless children had greater than expected percentages ofdevelopmental deficits in a number of the developmental domains. Those children who participated in the extended child development/family therapy services were one fourth as likely to have a developmental deficit at 12 months compared to children who did not receive these services. Interventions must be intensive and long-term to improve the developmental outcomes of children with multiple risks ofpoverty, homelessness, and family substance abuse.

OBJECTIVE To evaluate the safety and efficacy of closed-loop insulin delivery in well-controlled pregnant women with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS A total of 12 women with type 1 diabetes (aged 32.9 years, diabetes duration 17.6 years, BMI 27.1 kg/m2, and HbA1c 6.4%) were randomly allocated to closed-loop or conventional CSII. They performed normal daily activities (standardized meals, snacks, and exercise) for 24 h on two occasions at 19 and 23 weeks’ gestation. Plasma glucose time in target (63–140 mg/dL) and time spent hypoglycemic were calculated. RESULTS Plasma glucose time in target was comparable for closed-loop and conventional CSII (median [interquartile range]: 81 [59–87] vs. 81% [54–90]; P = 0.75). Less time was spent hypoglycemic ( CONCLUSIONS Closed-loop insulin delivery was as effective as conventional CSII, with less time spent in extreme hypoglycemia.

CONTEXT: Discontinuation of anti-hyperglycemic oral agents and initiation of insulin is recommended in certain clinical situations for inpatients with type 2 diabetes (T2D). The effects on glucose turnover when these agents are acutely withdrawn are poorly understood and may be of importance when insulin therapy is initiated.OBJECTIVE: Our objective was to investigate alterations in glucose turnover after acute withdrawal of noninsulin therapy.DESIGN AND SETTING: This was a randomized crossover study at a clinical research facility.PARTICIPANTS: Participants included 12 insulin-naive subjects with T2D.METHODS: Subjects attended two 24-hour visits. Standard therapy was discontinued and replaced by closed-loop insulin delivery during the intervention visit. Usual anti-hyperglycemic therapy was continued during the control visit. Systemic glucose appearance (Ra) and glucose disposal (Rd) were measured using a tracer dilution technique with iv [6,6-(2)H2]glucose.RESULTS: Plasma glucose profiles during both visits were comparable (P = .48). Glucose Ra increased during the day (21.4 [19.5, 23.5] vs 18.6 [17.0, 21.6) μmol/kg/min, P = .019) and decreased overnight (9.7 [8.5, 11.4] vs 11.6 [10.3, 12.9] μmol/kg/min, P = .004) when the usual therapy was discontinued and replaced with insulin. Increased daytime glucose Rd (21.2 [19.4, 23.9] vs 18.8 [18.3, 21.7] μmol/kg/min, P = .002) and decreased overnight Rd (10.4 [9.1, 12.0] vs 11.8 [10.7, 13.7] μmol/kg/min, P = .005) were observed when the usual therapy was discontinued, whereas daytime peripheral insulin sensitivity was reduced (47.8 [24.8, 66.1] vs 62.5 [34.8, 75.8] nmol/kg/min per pmol/L, P = .034).CONCLUSION: In T2D, acute discontinuation of anti-hyperglycemic therapy and replacement with insulin increases postprandial Ra and reduces peripheral insulin sensitivity. Insulin dose initiation may need to compensate for these alterations.

© 2015 Elsevier Inc. All rights reserved. Context Integrative medicine (IM) is a rapidly growing field whose providers report clinical success in treating significant stress, chronic pain, and depressive and anxiety symptoms. While IM therapies have demonstrated efficacy for numerous medical conditions, IM for psychological symptoms has been slower to gain recognition in the medical community. Objective and Design This large, cross-sectional study is the first of its kind to document the psychosocial profiles of 4182 patients at 9 IM clinics that form the BraveNet Practice-Based Research Network (PBRN). Results IM patients reported higher levels of perceived stress, pain, and depressive symptoms, and lower levels of quality of life compared with national norms. Per provider reports, 60% of patients had at least one of the following: stress (9.3%), fatigue (10.2%), anxiety (7.7%), depression (7.2%), and/or sleep disorders (4.8%). Pain, having both physiological and psychological components, was also included and is the most common condition treated at IM clinics. Those with high stress, psychological conditions, and pain were most frequently treated with acupuncture, IM physician consultation, exercise, chiropractic services, diet/nutrition counseling, and massage. Conclusion With baseline information on clinical presentation and service utilization, future PBRN studies can examine promising interventions delivered at the clinic to treat stress and psychological conditions.

OBJECTIVE To evaluate feasibility, safety, and efficacy of overnight closed-loop insulin delivery in free-living youth with type 1 diabetes. RESEARCH DESIGN AND METHODS Overnight closed loop was evaluated at home by 16 pump-treated adolescents with type 1 diabetes aged 12–18 years. Over a 3-week period, overnight insulin delivery was directed by a closed-loop system, and on another 3-week period sensor-augmented therapy was applied. The order of interventions was random. The primary end point was time when adjusted sensor glucose was between 3.9 and 8.0 mmol/L from 2300 to 0700 h. RESULTS Closed loop was constantly applied over at least 4 h on 269 nights (80%); sensor data were collected over at least 4 h on 282 control nights (84%). Closed loop increased time spent with glucose in target by a median 15% (interquartile range −9 to 43; P < 0.001). Mean overnight glucose was reduced by a mean 14 (SD 58) mg/dL (P < 0.001). Time when glucose was CONCLUSIONS Unsupervised home use of overnight closed loop in adolescents with type 1 diabetes is safe and feasible. Glucose control was improved during the day and night with fewer episodes of nocturnal hypoglycemia.

Insulin aspart, lispro, or glulisine are recommended in pump-treated type 1 diabetes (T1D). Aspart pharmacokinetics has been studied (1), but little is known about its reproducibility and associations with anthropometric and clinical factors. We analyzed retrospectively data collected in 70 pump-treated subjects with T1D, comprising 39 females, 46 young, with mean (SD) BMI 22.7 (4.2) kg/m2, A1C 8.1% (1.3) (65.3 [14.4] mmol/mol), and total daily insulin 0.8 (0.3) units/kg/day, who were undergoing investigations, with ethical approval, of closed-loop insulin delivery. Participants/guardians signed consent/assent as appropriate. Participants were admitted twice to the research facility, 1–6 weeks apart, for 15–37 h, and consumed 1–4 meals accompanied by prandial insulin aspart. Basal aspart was delivered using closed-loop insulin delivery or conventional pump therapy. Venous blood samples were collected every 30–60 min to measure plasma insulin (Invitron, Monmouth, U.K.). From 5,804 plasma insulin measurements, we estimated, using a two-compartment model, the time-to-peak plasma insulin concentration (tmax [min]), the metabolic clearance rate of insulin (MCR in mL/kg/min), and the background residual plasma insulin concentration (mU/L). Results are presented in Table 1. Sex differences in aspart kinetics were not observed. Aspart pharmacokinetics was weakly influenced by common clinical and anthropometric factors, because less than 20% of intersubject variability was explained by sex, BMI, total daily dose, A1C, and diabetes duration.

OBJECTIVE Closed-loop insulin delivery offers a promising treatment option, but to date, it has only been evaluated in type 1 diabetes. Our aim was to evaluate the feasibility of fully closed-loop subcutaneous insulin delivery in insulin-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Twelve subjects (seven males, age 57.2 years, BMI 30.5 kg/m2) with noninsulin-treated type 2 diabetes (HbA1c 8.4% [68 mmol/mol], diabetes duration 7.6 years) underwent two 24-h visits (closed-loop and control) in a randomized crossover design. During closed-loop visits, the subjects’ routine diabetes therapy was replaced with model predictive control algorithm-driven subcutaneous insulin pump delivery based on real-time continuous glucose monitoring. Meals were unannounced, and no additional insulin was administered for carbohydrates consumed. During control visits, the usual diabetes regimen was continued (metformin 92%, sulfonylureas 58%, dipeptidyl peptidase-4 inhibitors 33%). On both visits, subjects consumed matched 50- to 80-g carbohydrate meals and optional 15-g carbohydrate snacks and remained largely sedentary. Plasma glucose measurements evaluated closed-loop performance. RESULTS Compared with conventional therapy, 24 h of closed-loop insulin delivery increased overall the median time in target plasma glucose (3.9–8.0 mmol/L) from 24 to 40% (P = 0.016), despite sensor under-reading by a median of 1.2 mmol/L. The benefit of the closed-loop system was more prominent overnight, with greater time in target glucose (median 78 vs. 35%; P = 0.041) and less time in hyperglycemia (22 vs. 65%; P = 0.041). There was no hypoglycemia during either intervention. CONCLUSIONS A closed-loop system without meal announcement and using subcutaneous insulin delivery in insulin-naïve patients with type 2 diabetes appears feasible and safe. Improvement in postprandial glucose control may require further optimization of system performance.

We evaluated the clinical and numerical accuracy of the Freestyle Navigator continuous glucose monitoring (CGM) system, in critically ill adults using two different methods of calibration. Studies looking at intensive glucose control have yielded conflicting results with increased rates of iatrogenic hypoglycemia. Availability of accurate real-time glucose information may improve safety and efficacy of glucose control in the critical care unit.

INTRODUCTION: Closed-loop (CL) systems modulate insulin delivery according to glucose levels without nurse input. In a prospective randomized controlled trial, we evaluated the feasibility of an automated closed-loop approach based on subcutaneous glucose measurements in comparison with a local sliding-scale insulin-therapy protocol. METHODS: Twenty-four critically ill adults (predominantly trauma and neuroscience patients) with hyperglycemia (glucose, ≥10 mM) or already receiving insulin therapy, were randomized to receive either fully automated closed-loop therapy (model predictive control algorithm directing insulin and 20% dextrose infusion based on FreeStyle Navigator continuous subcutaneous glucose values, n = 12) or a local protocol (n = 12) with intravenous sliding-scale insulin, over a 48-hour period. The primary end point was percentage of time when arterial blood glucose was between 6.0 and 8.0 mM. RESULTS: The time when glucose was in the target range was significantly increased during closed-loop therapy (54.3% (44.1 to 72.8) versus 18.5% (0.1 to 39.9), P = 0.001; median (interquartile range)), and so was time in wider targets, 5.6 to 10.0 mM and 4.0 to 10.0 mM (P ≤ 0.002), reflecting a reduced glucose exposure >8 and >10 mM (P ≤ 0.002). Mean glucose was significantly lower during CL (7.8 (7.4 to 8.2) versus 9.1 (8.3 to 13.0] mM; P = 0.001) without hypoglycemia (