A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial).

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. Design: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. Setting: Neurosurgical units in the UK. Participants: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. Interventions: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. Main outcome measures: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0-3) or an unfavourable (score of 4-6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Results: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (-8.2%, 95% confidence interval -13.3% to -3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be -£97.19. Conclusions: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group. Future work and limitations: A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study. Trial registration: This trial is registered as ISRCTN80782810. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.

Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an 'old' collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma.

Promoting Smoking Cessation Among Lesbian and Bisexual Women: Lessons Learned From a Location-Based Media Campaign in Western North Carolina.

Despite well-documented inequities in tobacco use for lesbian, gay, bisexual, and transgender populations, there is little practical guidance for local public health officials on developing and implementing media campaigns that prioritize lesbian, gay, bisexual, transgender, and queer (LGBTQ) communities. In this practice note article, we describe the development and lessons learned from a location-based media campaign to promote tobacco use cessation and raise awareness of QuitlineNC among lesbian and bisexual women in Western North Carolina. The campaign used a digital approach based on cell phone locations and marketing profiles to deliver messages across 4 years (2018-2021). Considerations for practitioners include how our project required messaging adaptation to meet Google's restrictions against using the word "yours" and the importance of addressing privacy protection concerns with state officials to enable collection of outcome evaluation measures via a conversion pixel (code for capturing metrics).

The in vivo metabolism of Jungle Warfare in greyhounds.

Δ6-Methyltestosterone was reported as the main active ingredient of the purported "dietary supplement" Jungle Warfare. This compound is structurally similar to 17α-methyltestosterone, containing an additional Δ6 double bond, and is reported to possess notable androgenic activity, raising concerns over the potential for abuse of Jungle Warfare in sport. The in vivo metabolism of Δ6-methyltestosterone in greyhounds was investigated. Urinary phase I (unconjugated) and phase II (glucuronide) metabolites were detected following oral administration using liquid chromatography-mass spectrometry. No phase II sulfate metabolites were detected. The major phase I metabolite was confirmed as 16α,17ß-dihydroxy-17α-methylandrosta-4,6-dien-3-one by comparison with a synthetically-derived reference material. Minor amounts of the parent drug were also confirmed. Glucuronide conjugated metabolites were also observed, but were found to be resistant to hydrolysis using the Escherichia coli ß-glucuronidase enzyme. Qualitative excretion profiles, limits of detection, and extraction recoveries were determined for the parent drug and the major phase I metabolite. These results provide a method for the detection of Jungle Warfare abuse in greyhounds suitable for incorporation into routine screening methods conducted by anti-doping laboratories.

Epidemiological Study of Multiple Zoonotic Mosquito-Borne Alphaviruses in Horses in Queensland, Australia (2018-2020).

The increased frequency of extreme weather events due to climate change has complicated the epidemiological pattern of mosquito-borne diseases, as the host and vector dynamics shift to adapt. However, little is known about the seroprevalence of common mosquito-borne virus infections in horses in Australia. In this study, serological surveys for multiple alphaviruses were performed on samples taken from 622 horses across two horse populations (racehorses and horses residing on The University of Queensland (UQ) campus) in Queensland using the gold standard virus neutralization test. As is the case in humans across Australia, Ross River virus (RRV) is the most common arbovirus infection in horses, followed by Barmah Forest virus, with an overall apparent seroprevalence of 48.6% (302/622) and 4.3% (26/607), respectively. Horses aged over 6 years old (OR 1.86, p = 0.01) and residing at UQ (OR 5.8, p < 0.001) were significantly associated with seroconversion to RRV. A significant medium correlation (r = 0.626, p < 0.001) between RRV and Getah virus (GETV) neutralizing antibody titers was identified. Collectively, these results advance the current epidemiological knowledge of arbovirus exposure in a susceptible host in Australia. The potential use of horses as sentinels for arbovirus monitoring should be considered. Furthermore, since GETV is currently exotic to Australia, antibodies cross-reactivity between RRV and GETV should be further investigated for cross-protection, which may also help to inform vaccine developments.

Advancing Commercial Tobacco Control and Health Equity Through Policy, Systems, and Environmental Change.

Commercial tobacco products have been protected from regulation, yet are designed to addict, are deadly, and are promoted to young people whose brains are not yet fully developed. Until everyone is protected from addiction and exposure, we must keep working toward fairness and value-based policy, systems, and environmental change.

Identification of a canine coronavirus in Australian racing Greyhounds.

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).

The in vivo metabolism of Furazadrol in greyhounds.

Samples of the 'dietary supplement' Furazadrol sourced through the internet have been reported to contain the designer anabolic androgenic steroids [1',2']isoxazolo[4',5':2,3]-5α-androstan-17ß-ol (furazadrol F) and [1',2']isoxazolo[4',3':2,3]-5α-androstan-17ß-ol (isofurazadrol IF). These steroids contain an isoxazole fused to the A-ring and were designed to offer anabolic activity while evading detection, raising concerns over the potential for abuse of this preparation in sports. The metabolism of Furazadrol (F:IF, 10:1) was studied by in vivo methods in greyhounds. Urinary phase II Furazadrol metabolites were detected as glucuronides after a controlled administration. These phase II metabolites were subjected to enzymatic hydrolysis by Escherichia coli ß-glucuronidase to afford the corresponding phase I metabolites. Using a library of synthetically derived reference materials, the identities of seven urinary Furazadrol metabolites were confirmed. Major confirmed metabolites were isofurazadrol IF, 4α-hydroxyfurazadrol 4α-HF and 16α-hydroxy oxidised furazadrol 16α-HOF, whereas the minor confirmed metabolites were furazadrol F, 4ß-hydroxyfurazadrol 4ß-HF, 16ß-hydroxyfurazadrol 16ß-HF and 16ß-hydroxy oxidised furazadrol 16ß-HOF. One major hydroxyfurazadrol and two dihydroxyfurazadrol metabolites remained unidentified. Qualitative excretion profiles, limits of detection and extraction recoveries were established for furazadrol F and major confirmed metabolites. These investigations identify the key urinary metabolites of Furazadrol following oral administration, which can be incorporated into routine screening by anti-doping laboratories to aid the regulation of greyhound racing.

Trial of Dexamethasone for Chronic Subdural Hematoma.

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).

Engaging Patients in their Health Care: Lessons From a Qualitative Study on the Processes Health Coaches Use to Support an Active Learning Paradigm.

BACKGROUND: While recent health-care trends rely on activated patients, few studies report direct observations of how to engage and activate patients to be full participants in their own health care. The interpersonal processes and communication strategies used in integrative health coaching (IHC) may offer important insight into how clinicians can help patients step into a more active learning model rather than more typical passive roles. OBJECTIVE: This study uses verbatim transcripts of medical patients' first few IHC sessions to identify the actual processes used to help patients embrace this more active learning role. METHODS: A thematic analysis was conducted of 72 verbatim transcripts from IHC sessions of 26 patients with severe dysfunction from tinnitus. The patients participated in 6 months of IHC as part of a larger integrative intervention in a randomized, controlled pilot designed to assess feasibility for a larger randomized, controlled trial on the clinical effectiveness of an integrative intervention. RESULTS: Four themes emerged: (1) Describing the Health Coaching Process to patients; (2) Using Key Procedures for Action Planning-optimal health future self-visualization, Wheel of Health, and exploration of the gap between current and desired states to help patients set goals for themselves; (3) Supporting Action and Building Momentum-the creation and support of action steps with frequent reinforcement of self-efficacy; and (4) Active Listening and Inviting the Patient to Articulate Learning-coaches' active listening process included reflection, clarifying questions, turning patient questions back to the patients, highlighting values, identifying potential barriers and resources, and inviting patients to articulate what they were learning. CONCLUSION: The processes identified in IHC incorporate key principles of adult learning theory and engage patients' innate resources of goal orientation, self-direction, and intrinsic motivation. These interpersonal processes help patients embrace a more active learning role, with implications for patient engagement in other clinical contexts.

Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase.

The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.

Correction to: Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial.

After publication of the original article [1], the authors notified that that one of the BNTRC institutional collaborator names was misspelled.

Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common neurosurgical condition, typically treated with surgical drainage of the haematoma. However, surgery is associated with mortality and morbidity, including up to 20% recurrence of the CSDH. Steroids, such as dexamethasone, have been identified as a potential therapy for reducing recurrence risk in surgically treated CSDHs. They have also been used as a conservative treatment option, thereby avoiding surgery altogether. The hypothesis of the Dex-CSDH trial is that a two-week course of dexamethasone in symptomatic patients with CSDH will lead to better functional outcome at six months. This is anticipated to occur through reduced number of hospital admissions and surgical interventions. METHODS: Dex-CSDH is a UK multi-centre, double-blind randomised controlled trial of dexamethasone versus placebo for symptomatic adult patients diagnosed with CSDH. A sample size of 750 patients has been determined, including an initial internal pilot phase of 100 patients to confirm recruitment feasibility. Patients must be recruited within 72 h of admission to a neurosurgical unit and exclusions include patients already on steroids or with steroid contraindications, patients who have a cerebrospinal fluid shunt and those with a history of psychosis. The decision regarding surgical intervention will be made by the clinical team and patients can be included in the trial regardless of whether operative treatment is planned or has been performed. The primary outcome measure is the modified Rankin Scale (mRS) at six months. Secondary outcomes include the number of CSDH-related surgical interventions during follow-up, length of hospital stay, mRS at three months, EQ-5D at three and six months, adverse events, mortality and a health-economic analysis. DISCUSSION: This multi-centre trial will provide high-quality evidence as to the effectiveness of dexamethasone in the treatment of CSDH. This has implications for patient morbidity and mortality as well as a potential economic impact on the overall health service burden from this condition. TRIAL REGISTRATION: ISRCTN, ISRCTN80782810 . Registered on 7 November 2014. EudraCT, 2014-004948-35 . Registered on 20 March 2015. Dex-CSDH trial protocol version 3, 27 Apr 2017. This protocol was developed in accordance with the SPIRIT checklist. Available as a separate document on request.

Integrative Medicine Strategies for Changing Health Behaviors: Support for Primary Care.

Until system reforms allow adequate time and reimbursement for primary care providers to focus on lifestyle change to prevent and mitigate chronic disease, primary care providers need a manageable, defined role to support lifestyle change. The authors suggest this role is to serve as a catalyst, priming the patient for change; educating and pointing the patient to appropriate, evidence-based resources for additional guidance and hands-on support; and providing ongoing encouragement throughout the long journey of change while patients work more intensely with health coaches or allied health providers.

Effects of tai chi chuan on anxiety and sleep quality in young adults: lessons from a randomized controlled feasibility study.

OBJECTIVE: To determine feasibility and estimate the effect of a 10-week tai chi chuan (TCC) intervention on anxiety and sleep quality in young adults. PARTICIPANTS: Seventy-five adults (18-40 years) from a predominately undergraduate midsized university. METHODS: This was an assessor blinded, randomized feasibility trial, and participants were randomized into one of three groups: 10 weeks of TCC meeting 2 times per week, 10 weeks of TCC with a DVD of the curriculum, and control group receiving a handout on anxiety management. Anxiety and sleep quality were assessed 4 times: baseline, 4 weeks, 10 weeks (immediate post-intervention), and 2 months post-intervention. Retention was defined as a participant attending the baseline assessment and at least one other assessment. Adherence to the intervention was set a priori as attendance at 80% of the TCC classes. RESULTS: Eighty-five percent of participants were retained during the intervention and 70% completed the 2 month follow-up assessments. To increase statistical power, the two TCC groups were combined in the analyses of anxiety and sleep quality measures. No significant changes in anxiety were found in the control group, while levels of anxiety decreased significantly over time in the two TCC groups. Sleep quality scores improved across time for all three groups, but adherent TCC participants reported greater improvement than control participants. CONCLUSION: TCC may be an effective nonpharmaceutical means of improving anxiety and poor sleep quality in young adults.

Pain control methods in use and perceived effectiveness by patients with Ehlers-Danlos syndrome: a descriptive study.

PURPOSE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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. IMPLICATIONS FOR REHABILITATION: 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.

Integrative Medicine Patients Have High Stress, Pain, and Psychological Symptoms.

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.

Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial.

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 <70 mg/dL was low in both groups, but nights with glucose <63 mg/dL for at least 20 min were less frequent during closed loop (10 vs. 17%; P = 0.01). Despite lower total daily insulin doses by a median 2.3 (interquartile range -4.7 to 9.3) units (P = 0.009), overall 24-h glucose was reduced by a mean 9 (SD 41) mg/dL (P = 0.006) during closed loop. 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.

Feasibility of closed-loop insulin delivery in type 2 diabetes: a randomized controlled study.

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.

Accuracy of subcutaneous continuous glucose monitoring in critically ill adults: improved sensor performance with enhanced calibrations.

OBJECTIVE: 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. SUBJECTS AND METHODS: 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. RESULTS: 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], P<0.001), and the percentage of points in the Clarke error grid Zone A was higher (87.8% vs. 70.2%). CONCLUSIONS: 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.

Day and night closed-loop control in adults with type 1 diabetes: a comparison of two closed-loop algorithms driving continuous subcutaneous insulin infusion versus patient self-management.

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 (<3.9 mmol/L) was almost threefold reduced during CL (6.4%, 2.1%, and 2.0%) (overall P = 0.001) with less time ≤2.8 mmol/L (overall P = 0.038). There were no significant differences in outcomes between algorithms. CONCLUSIONS: Both CAM and iAP algorithms provide safe glycemic control.