UK's Association of British Clinical Diabetologist's Diabetes Technology Network (ABCD-DTN): Best practice guide for hybrid closed-loop therapy.

This best practice guide is written with the aim of providing an overview of current hybrid closed-loop (HCL) systems in use within the United Kingdom's (UK) National Health Service (NHS) and to provide education and advice for their management on both an individual and clinical service level. The environment of diabetes technology, and particularly HCL systems, is rapidly evolving. The past decade has seen unprecedented advances in the development of HCL systems. These systems improve glycaemic outcomes and reduce the burden of treatment for people with type 1 diabetes (pwT1D). It is anticipated that access to these systems will increase in England as a result of updates in National Institute of Health and Care Excellence (NICE) guidance providing broader support for the use of real-time continuous glucose monitoring (CGM) for pwT1D. NICE is currently undertaking multiple-technology appraisal into HCL systems. Based on experience from centres involved in supporting advanced technologies as well as from the recent NHS England HCL pilot, this guide is intended to provide healthcare professionals with UK expert consensus on the best practice for initiation, optimisation and ongoing management of HCL therapy.

Association of crystalloid fluid infusion with intravascular hemolysis and organ dysfunction in hematopoietic stem cell transplant patients.

Endothelial cell activation and injury is common after hematopoietic stem cell transplant (HSCT) and is associated with many post-transplant complications. An underexplored mechanism of endothelial cell damage in this population is the infusion of normal saline (NS, 0.9 % sodium chloride) and other crystalloids, as NS use is associated with adverse outcomes in other patient populations. We hypothesized that the infusion of unbalanced crystalloids during HSCT may lead to changes in biomarkers commonly associated with red blood cell (RBC) hemolysis in patients before and after infusion, and that markers of endothelial and end-organ damage during admission may be associated with markers of hemolysis and total crystalloid use. Samples were collected from 97 patients. From pre-fluid infusion to post-fluid infusion, mean haptoglobin decreased (11.7 ug/ml vs 8.4 ug/ml; p < 0.0001), hemopexin decreased (549 vs 512 µg/ml; p = 0.005), and red cell distribution width (RDW) decreased (15.7 vs 15.6; p = 0.0009). During admission (mean 19.4 days, SD 9.9), all markers of tissue and organ damage, including mean creatinine, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), total bilirubin, AST, and ALT, increased from admission to peak levels (p < 0.0001). On linear regression, fluid volume (ml/kg) of crystalloid infusion positively predicted post-fluid infusion cell-free hemoglobin (r(96) = 0.34, p < 0.0001), free heme (r(96) = 0.36, p < 0.0001), and peak LDH during admission (r(75) = 0.23, p = 0.041), and negatively predicted post-fluid infusion hemopexin (r(96) = - 0.34, p < 0.0001). Unbalanced crystalloids may contribute to hemolysis and endothelial damage in HSCT patients. Alternatives such as buffered crystalloid solutions (PlasmaLyte, Lactated Ringer's) may be worth investigating in this population.

Lonely older adults are more likely to delay or avoid medical care during the coronavirus disease 2019 pandemic.

OBJECTIVES: To examine the relationship between loneliness and self-reported delay or avoidance of medical care among community-dwelling older adults during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Analyses of data from a nationally representative survey administered in June of 2020, in COVID-19 module of the Health and Retirement Study. Bivariate and multivariable analyses determined associations of loneliness with the likelihood of, reasons for, and types of care delay or avoidance. RESULTS: The rate of care delay or avoidance since March of 2020 was 29.1% among all respondents (n = 1997), and 10.1% higher for lonely (n = 1,150%, 57.6%) versus non-lonely respondents (33.5% vs. 23.4%; odds ratio = 1.59, p = 0.003 after covariate adjustment). The differences were considerably larger among several subgroups such as those with emotional/psychiatric problems. Lonely older adults were more likely to cite "Decided it could wait," "Was afraid to go," and "Couldn't afford it" as reasons for delayed or avoided care. Both groups reported dental care and doctor's visit as the two most common care delayed or avoided. CONCLUSIONS: Loneliness is associated with a higher likelihood of delaying or avoiding medical care among older adults during the pandemic.

Impact of Pharmacist Involvement on the Utility of a Gram-Negative Blood Culture Identification Panel on Antimicrobial Usage.

Background: A rapid molecular diagnostic test (MDT) is a test used to identify several different species of gram-negative bacteria and their genetic resistance markers. However, the impact of rapid MDT has not been established when combined with pharmacist involvement. Objective: To determine the impact of pharmacy involvement on patient outcomes when using rapid MDT. The primary outcome is the time from gram stain result to the first dose of the targeted antibiotic. Methods: This is a single-center, quasi-experimental, 1-group pretest-posttest design study of patients with gram-negative bacteremia in a community hospital. Hospitalized patients 18 years or older were included if they had a gram-negative blood culture. Patients were excluded if they were discharged or expired prior to culture results. Outcomes were compared between patients prior to and after implementation of the automated MDT. This research was determined to be exempt from institutional review board oversight consistent with West Florida Healthcare and in accordance with institutional policy. Results: The use of rapid MDT combined with pharmacist intervention resulted in a statistically significant decrease in the time to targeted antibiotic therapy (pre-intervention group, n = 77, 44.8 ± 17.8 hours versus post-intervention group, n= 80, 4.4 ± 5.8 hours; P ≤.001). There was no significant difference found between secondary outcomes. Limitations included small sample size as well as inconsistent documentation. Conclusions: The use of rapid MDT combined with pharmacist intervention resulted in a statistically significant decrease in the time to targeted antibiotic therapy.

No Differences in Clinical, Functional, or Patient-Reported Outcomes Following Trial of Nonoperative Management Before Open Reduction and Internal Fixation of Humeral Shaft Fractures.

OBJECTIVES: To test the hypothesis that primary osteosynthesis of humeral shaft fractures may lead to more favorable clinical, functional, and patient-reported outcomes than fixation following a trial of nonoperative management. DESIGN: Retrospective cohort review. SETTING: Academic level I trauma center. PATIENT SELECTION CRITERIA: Adult patients who presented with humeral shaft fractures and ultimately underwent open reduction and internal fixation (ORIF) from May 2011 to May 2021. Patients who underwent ORIF within 2 weeks of injury were grouped into the primary osteosynthesis cohort, and patients who underwent ORIF >4 weeks from the date of injury were grouped into the trial of nonoperative cohort. OUTCOME MEASURES AND COMPARISONS: Postoperative complications, elbow arc of motion, time to radiographic union, and patient-reported outcomes were investigated and compared between the primary osteosynthesis and trial of nonoperative management cohorts. RESULTS: One hundred twenty-seven patients fit the study criteria, 84 underwent primary osteosynthesis and 43 trialed initial nonoperative treatment. No differences were found in patient demographics between the primary osteosynthesis and trial of nonoperative management cohorts, including age (53 ± 19 vs. 57 ± 18; P = 0.25), sex (39% vs. 44% male, 61% vs. 56% female; P = 0.70), and Body Mass Index (BMI) (30 ± 6 vs. 32 ± 9; P = 0.38). The average time to operative intervention in the primary osteosynthesis group was 4 days (0-14 days) and 105 days (28-332 days) in the trial of nonoperative treatment group ( P < 0.01). No differences were found with regard to intraoperative blood loss, total operative time, time to radiographic union (determined using the Radiographic Union Scores for Humeral scoring system), or overall complication rates, including primary and secondary radial nerve injuries ( P = 0.23 and 0.86, respectively). Patients reported similar patient-reported outcomes measurement information system pain interference ( P = 0.73), depression (D) ( P = 0.99), and physical function ( P = 0.66) scores at their 6-month postsurgical follow-up visits. CONCLUSIONS: Patients who attempted a trial of nonoperative management for humeral shaft fractures before ORIF had similar clinical, functional, and patient-reported outcomes as those who underwent primary osteosynthesis. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Rare Radiographic Changes in a Cervicomedullary Spinal Ependymoma After Biopsy and Drainage of an Intratumoral Cyst: A Staged Approach.

Spinal ependymomas are the most common intramedullary spinal tumor, with a large proportion containing a small intratumoral cyst. Although the signal intensity varies, spinal ependymomas are generally well-demarcated, are not associated with a pre-syrinx, and do not extend above the foramen magnum. Our case demonstrates unique radiographic findings of a cervical ependymoma with a staged approach to diagnosis and resection. The patient is a 19-year-old female who presented with a three-year history of neck pain, progressive arm and leg weakness, falls, and functional decline. MRI revealed an expansile dorsal and centrally located T2 hypointense cervical lesion with a large intratumoral cyst extending from the foramen magnum to the C7 pedicle. Contrasted T1 scans showed an irregular enhancement pattern along the superior tumoral border down to the C3 pedicle. She underwent a C1 laminectomy for open biopsy and cysto-subarachnoid shunt. Postoperative MRI revealed a well-demarcated enhancing mass extending from the foramen magnum to C2. Pathology revealed Grade II ependymoma. She underwent an occipital to C3 laminectomy with gross total resection. Postoperatively she experienced weakness and orthostatic hypotension that improved remarkably upon discharge. Initial imaging was concerning for a higher-grade tumor, with holocervical cord involvement and cervical kyphosis. Given concern for grade and possible extensive C1-7 laminectomy and fusion for resection, a smaller surgery involving drainage of the cyst and biopsy was performed. Postoperative MRI revealed regression of the pre-syrinx, improved tumoral definition, and improvement of cervical kyphosis. This staged approach spared the patient unnecessary surgical intervention such as extensive laminectomy and fusion. We conclude that in cases of a large intratumoral cyst in an extensive intramedullary spinal cord lesion, open biopsy and drainage followed by resection in a staged fashion should be considered. Radiographic changes from the first procedure may affect the surgical approach for ultimate resection.

Crisis of confidence averted: Impairment of exercise economy and performance in elite race walkers by ketogenic low carbohydrate, high fat (LCHF) diet is reproducible.

INTRODUCTION: We repeated our study of intensified training on a ketogenic low-carbohydrate (CHO), high-fat diet (LCHF) in world-class endurance athletes, with further investigation of a "carryover" effect on performance after restoring CHO availability in comparison to high or periodised CHO diets. METHODS: After Baseline testing (10,000 m IAAF-sanctioned race, aerobic capacity and submaximal walking economy) elite male and female race walkers undertook 25 d supervised training and repeat testing (Adapt) on energy-matched diets: High CHO availability (8.6 g∙kg-1∙d-1 CHO, 2.1 g∙kg-1∙d-1 protein; 1.2 g∙kg-1∙d-1 fat) including CHO before/during/after workouts (HCHO, n = 8): similar macronutrient intake periodised within/between days to manipulate low and high CHO availability at various workouts (PCHO, n = 8); and LCHF (<50 g∙d-1 CHO; 78% energy as fat; 2.1 g∙kg-1∙d-1 protein; n = 10). After Adapt, all athletes resumed HCHO for 2.5 wk before a cohort (n = 19) completed a 20 km race. RESULTS: All groups increased VO2peak (ml∙kg-1∙min-1) at Adapt (p = 0.02, 95%CI: [0.35-2.74]). LCHF markedly increased whole-body fat oxidation (from 0.6 g∙min-1 to 1.3 g∙min-1), but also the oxygen cost of walking at race-relevant velocities. Differences in 10,000 m performance were clear and meaningful: HCHO improved by 4.8% or 134 s (95% CI: [207 to 62 s]; p < 0.001), with a trend for a faster time (2.2%, 61 s [-18 to +144 s]; p = 0.09) in PCHO. LCHF were slower by 2.3%, -86 s ([-18 to -144 s]; p < 0.001), with no evidence of superior "rebound" performance over 20 km after 2.5 wk of HCHO restoration and taper. CONCLUSION: Our previous findings of impaired exercise economy and performance of sustained high-intensity race walking following keto-adaptation in elite competitors were repeated. Furthermore, there was no detectable benefit from undertaking an LCHF intervention as a periodised strategy before a 2.5-wk race preparation/taper with high CHO availability. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry: ACTRN12619000794101.

Correction: Crisis of confidence averted: Impairment of exercise economy and performance in elite race walkers by ketogenic low carbohydrate, high fat (LCHF) diet is reproducible.

[This corrects the article DOI: 10.1371/journal.pone.0234027.].

Do-It-Yourself Artificial Pancreas Systems in Type 1 Diabetes: Perspectives of Two Adult Users, a Caregiver and Three Physicians.

Advances in continuous glucose monitoring and insulin pumps have allowed people with type 1 diabetes (T1D) and caregivers to accurately and continuously measure their glucose levels and make adjustments to insulin infusion. In recent years, algorithms for subcutaneous insulin dosing have been developed that can respond to changes in glucose in an automated fashion and "close the loop". At present, a first-generation 'hybrid closed-loop', 'artificial pancreas' or 'automated insulin dosing' system, Medtronic 670G, is available commercially. Further systems are in clinical trials. Frustrated by the slow pace of innovation, people affected by diabetes have united online under the hashtag '#WeAreNotWaiting,' to disseminate open-source diabetes technologies. One dimension of #WeAreNotWaiting is "looping" with a do-it-yourself artificial pancreas. Here we provide the perspectives of two adults with T1D, the parent of a child with T1D and three physicians who detail their experience with these systems. These personal and clinical perspectives highlight very clear metabolic and psychological benefits of these systems in real-world settings.

Teleneurology and mobile technologies: the future of neurological care.

Neurological disorders are the leading cause of global disability. However, for most people around the world, current neurological care is poor. In low-income countries, most individuals lack access to proper neurological care, and in high-income countries, distance and disability limit access. With the global proliferation of smartphones, teleneurology - the use of technology to provide neurological care and education remotely - has the potential to improve and increase access to care for billions of people. Telestroke has already fulfilled this promise, but teleneurology applications for chronic conditions are still in their infancy. Similarly, few studies have explored the capabilities of mobile technologies such as smartphones and wearable sensors, which can guide care by providing objective, frequent, real-world assessments of patients. In low-income settings, teleneurology can increase the capacity of local care systems through professional development, diagnostic support and consultative services. In high-income settings, teleneurology is likely to promote the expansion and migration of neurological care away from institutions, incorporate systems of asynchronous communication (such as e-mail), integrate clinicians with diverse skill sets and reach new populations. Inertia, outdated policies and social barriers - especially the digital divide - will slow this progress at considerable cost. However, a future increasingly will be possible in which neurological care can be accessed by anyone, anywhere. Here, we examine the emerging evidence regarding the benefits of teleneurology for chronic conditions, its role and risks in low-income countries and the promise of mobile technologies to measure disease status and deliver care. We conclude by discussing the future trends, barriers and timing for the adoption of teleneurology.

Safety, tolerance, and efficacy of posaconazole therapy in patients with nonmeningeal disseminated or chronic pulmonary coccidioidomycosis.

BACKGROUND: Coccidioidomycosis can be difficult to treat with available therapies, particularly in patients with progressive or disseminated disease. Posaconazole is a new azole antifungal with potent activity against Coccidioides species, the causative agent of coccidioidomycosis. METHODS: Twenty patients with chronic pulmonary or nonmeningeal disseminated coccidioidomycosis were enrolled in a multicenter trial to study the safety and tolerability of posaconazole therapy, with efficacy as a secondary end point. Patients received posaconazole (400 mg/day) in capsule formulation for up to 6 months. Safety was evaluated on the basis of the occurrence of adverse events. A satisfactory efficacy response was defined as a >or=50% reduction in the Mycoses Study Group score from baseline. RESULTS: Seventeen (85%) of 20 patients had a satisfactory response to treatment. The median duration of treatment was 173 days. Paired baseline and end-of-treatment culture results for Coccidioides species were available for 4 patients, all of whom converted from being positive to being negative for Coccidioides species. Relapse was experienced by 3 of 9 patients who did not receive antifungal therapy during the follow-up period. In general, posaconazole therapy was well tolerated, with 12 of 20 patients reporting adverse events that were possibly or probably related to treatment. The most common adverse events were dry mouth (in 5 patients [25%]) and headache (in 3 patients [15%]). CONCLUSIONS: Courses of posaconazole therapy that were up to 6 months in duration were well tolerated in patients with coccidioidomycosis. Although this study was limited by the number of patients enrolled, it clearly demonstrates that posaconazole shows promise in the treatment of patients with coccidioidomycosis and warrants additional investigation in a full-scale clinical trial.

Is Continuous Glucose Monitoring Underappreciated in the UK?

INTRODUCTION: Information about continuous glucose monitoring (CGM) use in the UK is limited. We conducted an online survey of a representative sample of current CGM users in England, Scotland and Wales to address this deficit. METHODS: The 29-item online survey was conducted between 29 December 2016 and 25 January 2017. Persons with type 1 diabetes (T1D) and caregivers of T1D children/adolescents were recruited from mailing lists, using Nielsen and Harris Polling databases. RESULTS: 315 patients and caregivers responded to the survey - 170 adult patients and 145 caregivers. Among respondents, 144 received full funding for CGM use, 72 received partial funding and 83 received no funding. Most reported improvements in glycated haemoglobin (HbA1c) (67.0%), fewer hypoglycaemia episodes (70.2%), improved hypoglycaemia awareness (77.5%) and better diabetes management (92.4%). Self-funders reported significantly higher CGM use (76.1%) than those who were fully funded (58.9%) and/or partially funded (65.9%), p=0.0008. Fewer than 50% of all respondents reported receiving guidance in interpreting CGM data from their diabetes care team; 30.1% of self-funders reported receiving no CGM support from their diabetes team compared with fully funded (2.8%) and partially funded (1.4%) respondents, p<0.0001. CONCLUSIONS: Patients with T1D and their caregivers are realising benefits from CGM use but are largely unsupported by the UK healthcare system.

Real-time continuous glucose monitoring in type 1 diabetes: a qualitative framework analysis of patient narratives.

OBJECTIVE: This study analyzed narratives about experiences of real-time continuous glucose monitoring (CGM) in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: People with type 1 diabetes using CGM and caregivers completed an online survey. Questions included duration of CGM, frequency of sensor wear, funding, and a free narrative about experiences or views about CGM. We used qualitative framework analysis to analyze 100 responses; 50% of participants were aged ≥ 18 years. RESULTS: Most participants (87%) used CGM with insulin pump therapy, 71% used sensors ≥ 75% of the time, and 66% received funding for CGM from the National Health Service. Four themes were identified: 1) metabolic control, 2) living with CGM (work and school, sleep, exercise, nutrition, frequency of self-monitoring of blood glucose [SMBG]), 3) psychological issues and patient/caregiver attitudes, and 4) barriers to CGM use (technical issues, financial issues, attitudes of healthcare professionals toward CGM). Despite some hassles, experiences were overwhelmingly positive, with improved glycemic control, diet and exercise management, quality of life, and physical and psychological well-being, as well as reduced frequency of SMBG. Technical problems included sensor inaccuracy and unreliability, and "alarm fatigue." The advantages of CGM used with an insulin pump with automatic suspension of insulin delivery during hypoglycemia were recorded by several participants, noting reduced hypoglycemia frequency and fear of nocturnal hypoglycemia. CONCLUSIONS: Patient and caregiver narratives indicate that CGM is a valuable addition to diabetes care for many with type 1 diabetes.

Evaluation of array comparative genomic hybridization for genetic analysis of chorionic villus sampling from pregnancy loss in comparison to karyotyping and multiplex ligation-dependent probe amplification.

OBJECTIVE: The aim of this study was to evaluate the use of array comparative genomic hybridization (aCGH) for genetic analysis of chorionic villus sampling (CVS) from pregnancy loss. aCGH results were compared with results from karyotyping and multiplex ligation-dependent probe amplification (MLPA) analysis to assess the suitability of aCGH as a method for detecting a variety of known chromosomal abnormalities. It was determined which technique gave the most valuable information. METHOD: Twenty anonymised samples from CVS were analyzed by aCGH, MLPA, and karyotyping. RESULTS: Ten cases were identified as normal by all three methods. Aneuploidy was detected in four cases by all three methods. Partial deletion and duplication was detected in two cases by aCGH and karyotyping but missed by MLPA. In addition, mosaicism was detected by aCGH in 3 of 20 cases missed by MLPA and karyotyping. CONCLUSION: aCGH is a rapid, automated, reliable, high-resolution technique to diagnose unbalanced chromosomal abnormalities. In this study, aCGH analysis accurately identified all chromosomal abnormalities in CVS from pregnancy loss, suggesting that it is suitable in the clinical setting for prenatal diagnosis.