Real-world outcomes of Omnipod DASH system use in people with type 1 diabetes: Evidence from the Association of British Clinical Diabetologists (ABCD) study.

AIMS: To evaluate real-world outcomes in people with Type 1 Diabetes (PwT1D) initiated on Omnipod DASH® Insulin Management System. METHODS: Anonymized clinical data were submitted to a secure web-based tool within the National Health Service network. Hemoglobin A1c (HbA1c), sensor-derived glucometrics, total daily dose of insulin (TDD), and patient-reported outcome changes between baseline and follow-up were assessed. Individuals were classified to "new-to-pump" (switched from multiple daily injections) and "established-on-pump" (switched from a tethered insulin pump) groups. RESULTS: 276 individuals from 11 centers [66.7 % female; 92 % White British; median age 41 years (IQR 20-50); diabetes duration 20 years (IQR 11-31); 49.3 % within "new-to-pump" group] were included. Baseline HbA1c was 8.0 ± 1.3 % (64 ± 14 mmol/mol). At follow-up [3 years (IQR 1.5-3.2)], HbA1c reduced by 0.3 % [(3 mmol/mol); p = 0.002] across the total population, 0.4 % [(5 mmol/mol); p = 0.001] in those "new-to-pump" and remained unchanged in those "established-on-pump". TDD decreased in the "new-to-pump" cohort (baseline:44.9 ± 21.0units vs follow-up:38.1 ± 15.4units, p = 0.002). Of those asked, 141/143 (98.6 %) stated Omnipod DASH had a positive impact on quality of life. CONCLUSIONS: Omnipod DASH was associated with improvements in HbA1c in PwT1D "new-to-pump" and maintained previous HbA1c levels in those "established-on-pump". User satisfaction in all groups and TDD reduction in those "new-to-pump" were reported.

Hybrid Closed-Loop Therapy in Adults With Type 1 Diabetes and Above-Target HbA1c: A Real-world Observational Study.

OBJECTIVE: We explored longitudinal changes associated with switching to hybrid closed-loop (HCL) insulin delivery systems in adults with type 1 diabetes and elevated HbA1c levels despite the use of intermittently scanned continuous glucose monitoring (isCGM) and insulin pump therapy. RESEARCH DESIGN AND METHODS: We undertook a pragmatic, preplanned observational study of participants included in the National Health Service England closed-loop pilot. Adults using isCGM and insulin pump across 31 diabetes centers in England with an HbA1c ≥8.5% who were willing to commence HCL therapy were included. Outcomes included change in HbA1c, sensor glucometrics, diabetes distress score, Gold score (hypoglycemia awareness), acute event rates, and user opinion of HCL. RESULTS: In total, 570 HCL users were included (median age 40 [IQR 29-50] years, 67% female, and 85% White). Mean baseline HbA1c was 9.4 ± 0.9% (78.9 ± 9.1 mmol/mol) with a median follow-up of 5.1 (IQR 3.9-6.6) months. Of 520 users continuing HCL at follow-up, mean adjusted HbA1c reduced by 1.7% (95% CI 1.5, 1.8; P < 0.0001) (18.1 mmol/mol [95% CI 16.6, 19.6]; P < 0.0001). Time in range (70-180 mg/dL) increased from 34.2 to 61.9% (P < 0.001). Individuals with HbA1c of ≤58 mmol/mol rose from 0 to 39.4% (P < 0.0001), and those achieving ≥70% glucose time in range and <4% time below range increased from 0.8 to 28.2% (P < 0.0001). Almost all participants rated HCL therapy as having a positive impact on quality of life (94.7% [540 of 570]). CONCLUSIONS: Use of HCL is associated with improvements in HbA1c, time in range, hypoglycemia, and diabetes-related distress and quality of life in people with type 1 diabetes in the real world.

Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review.

Background: Intraepidermal nerve fiber density (IENFD) has become an important biomarker for neuropathy diagnosis and research. The consequences of reduced IENFD can include sensory dysfunction, pain, and a significant decrease in quality of life. We examined the extent to which IENFD is being used as a tool in human and mouse models and compared the degree of fiber loss between diseases to gain a broader understanding of the existing data collected using this common technique. Methods: We conducted a scoping review of publications that used IENFD as a biomarker in human and non-human research. PubMed was used to identify 1,004 initial articles that were then screened to select articles that met the criteria for inclusion. Criteria were chosen to standardize publications so they could be compared rigorously and included having a control group, measuring IENFD in a distal limb, and using protein gene product 9.5 (PGP9.5). Results: We analyzed 397 articles and collected information related to publication year, the condition studied, and the percent IENFD loss. The analysis revealed that the use of IENFD as a tool has been increasing in both human and non-human research. We found that IENFD loss is prevalent in many diseases, and metabolic or diabetes-related diseases were the most studied conditions in humans and rodents. Our analysis identified 74 human diseases in which IENFD was affected, with 71 reporting IENFD loss and an overall average IENFD change of -47%. We identified 28 mouse and 21 rat conditions, with average IENFD changes of -31.6 % and - 34.7% respectively. Additionally, we present data describing sub-analyses of IENFD loss according to disease characteristics in diabetes and chemotherapy treatments in humans and rodents. Interpretation: Reduced IENFD occurs in a surprising number of human disease conditions. Abnormal IENFD contributes to important complications, including poor cutaneous vascularization, sensory dysfunction, and pain. Our analysis informs future rodent studies so they may better mirror human diseases impacted by reduced IENFD, highlights the breadth of diseases impacted by IENFD loss, and urges exploration of common mechanisms that lead to substantial IENFD loss as a complication in disease.

Disordered sleep and its association with academic performance and functioning.

Sleep disorders are prevalent among college students and are associated with poor academic performance. Few studies have included a clinical interview to comprehensively assess sleep disorder diagnostic criteria or assessed academic functioning (e.g., class attendance). College students (n = 277) were recruited to complete sleep questionnaires, a sleep diary for two weeks and, if indicated, a semi-structured clinical interview. Based on questionnaire data, students were categorized as being at risk versus not at risk for a sleep disorder. Based on the semi-structured clinical interview, students were categorized as meeting versus not meeting diagnostic criteria for a sleep disorder. Academic performance and functioning were assessed in all students to determine the association between the presence of sleep disorders and academic performance and functioning. In models adjusted for age, sex, race, and credit hours completed, students at risk for a sleep disorder (38.6% of the sample) reported missing more classes due to oversleeping (p = 0.001) and illness (p = 0.014), and fell asleep in class more often (p = 0.030) than their peers not at risk. Students with a sleep disorder (24.8% of the sample) reported missing more classes due to illness (p = 0.024) than those without a sleep disorder. There were no differences in grade point average between students at risk versus not at risk or with versus without a sleep disorder. Sleep disorder symptoms and diagnoses were significantly associated with worse academic functioning but not performance. Assessment and treatment of sleep disorders early in college students' career may be important for optimal academic functioning. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00423-3.

Use of a Mylar filter to eliminate vacuum ultraviolet pulse pileup in low-energy x-ray measurements.

We describe a method to reduce vacuum ultraviolet (VUV) pulse pileup (PPU) in x-ray pulse-height Silicon Drift Detector (SDD) signals. An Amptek FAST SDD, with C1 (Si3N4) window, measures bremsstrahlung emitted from PFRC-2 plasma to extract the electron temperature (Te) and density (ne). The C1 window has low transmissivity for photons with energy below 200 eV though will transmit some VUV and soft x-ray photons, which PFRC-2 plasmas abundantly emit. Multi-VUV-photon PPU contaminates the interpretation of x rays with energy > 100 eV, particularly in a low-energy exponential tail. The predicted low transmissivity of ∼1 µm thick Mylar [polyethylene terephthalate (PET)] to photons of energy <100 eV led to the selection of Mylar as the candidate filter to reduce VUV PPU. Experiments were conducted on an x-ray tube with a graphite target and on a quasi-Maxwellian tenuous plasma (ne ∼ 109 cm-3) with effective temperatures reaching 1500 eV. A Mylar filter thickness of 850 nm is consistent with the results. The Mylar-filter-equipped SDD was then used on the PFRC-2 plasma, showing a substantial reduction in the low-energy x-ray signal, supporting our hypothesis of the importance of VUV PPU. We describe the modeling and experiments performed to characterize the effect of the Mylar filter on SDD measurements.

An update on oral cavity cancer: epidemiological trends, prevention strategies and novel approaches in diagnosis and prognosis.

In the UK, the incidence of oral cavity cancer continues to rise, with an increase of around 60% over the past 10 years. Many patients still present with advanced disease, often resulting in locoregional recurrence and poor outcomes, which has not changed significantly for over four decades. Changes in aetiology may also be emerging, given the decline of smoking in developed countries. Therefore, new methods to better target prevention, improve screening and detect recurrence are needed. High-throughput 'omics' technologies appear promising for future individual-level diagnosis and prognosis. However, given this is a relatively rare cancer with significant intra-tumour heterogeneity and variation in patient response, reliable biomarkers have been difficult to elucidate. From a public health perspective, implementing these novel technologies into current services would require substantial practical, financial and ethical considerations. This may be difficult to justify and implement at present, therefore focus remains on early detection using new patient-led follow-up strategies. This paper reviews the latest evidence on epidemiological trends in oral cavity cancer to help identify at risk groups, population-based approaches for prevention, in addition to potential cutting-edge approaches in the diagnosis and prognosis of this disease.

Injectable semaglutide and reductions in HbA1c and weight in the real world in people switched from alternative glucagon-like peptide-1 receptor agonists.

The ABCD semaglutide audit was designed to capture the routine clinical outcomes of people commenced on semaglutide in the UK. Previous work showed differential reductions in HbA1c and weight dependent on previous glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure. The analysis, in this research letter, shows that decreases in HbA1c and weight associated with semaglutide occur irrespective of previous GLP-1RA use. However, HbA1c reductions were less if switched from dulaglutide or liraglutide and weight changes were attenuated if switched from dulaglutide or exenatide, potentially suggesting differing potencies between GLP-1RAs. Dedicated studies with head-to-head comparisons are needed to confirm these findings.

Association of British Clinical Diabetologists, Diabetes Technology Network UK and Association of Children's Diabetes Clinicians Survey of UK Healthcare Professional Attitudes Towards Open-Source Automated Insulin Delivery Systems.

INTRODUCTION: Automated insulin delivery (AID) systems can enable improved glycaemic outcomes with reduced mental burden. Open-source AID (OS-AID) systems overcome some of the developmental and access barriers enabling a wider use of these systems. Limited data are available on healthcare professional (HCP) opinions and current practice regarding these systems. The aim of this survey was to gain insight into HCP perceptions and practices around OS-AID. METHODS: This survey was developed collaboratively with OS-AID users and distributed to adult and children's teams, using an online survey tool. Results were received between February and April 2019. Responses were assessed using simple descriptive statistics with analyses stratified by respondent characteristics. RESULTS: 317 responses were obtained from a range of HCPs in both adult and paediatric services. Key results include: HCP perception of OS-AID as "risky in the wrong hands" (43%); 91% felt uncomfortable initiating discussions around OS-AID because of lack of regulation (67%) and/or their own lack of knowledge (63%). Half of HCPs (47%) reported that they would choose OS-AID if they themselves had type 1 diabetes. CONCLUSIONS: HCPs are generally supportive of OS-AID users but many feel uncomfortable with the technicalities of the systems given the lack of approval. Knowledge around the use of these systems was limited. Re-assessment of HCP perceptions should be performed in the future given the evolving landscape of diabetes technology, recent consensus statements and emerging ethical and legal perspectives.

Open-source automated insulin delivery systems are an increasingly encountered diabetes technology. These involve a small glucose sensor and an insulin delivery device called an insulin pump. These two devices interact to allow adjustment of insulin delivery to maintain glucose levels in a desirable range. The computer codes which drive these systems are developed by people with diabetes or their families rather than by device companies; as such, they have not been through formal approval processes and therefore there is limited formal evidence concerning whether they are safe or beneficial to use. Users report high satisfaction with these devices and improvements in their diabetes management. This survey was performed to assess the opinions of UK healthcare professionals and their usual practice. Key results include: UK healthcare professionals would not routinely recommend the use of these devices and there was concern about the medicolegal implications of use. However, UK healthcare professionals were generally supportive of those who chose to use the devices. Interestingly, almost half of the healthcare professionals would use the systems if they had diabetes.

Safety and effectiveness of do-it-yourself artificial pancreas system compared with continuous subcutaneous insulin infusions in combination with free style libre in people with type 1 diabetes.

AIMS: The use of do-it-yourself artificial pancreas systems (DIYAPS) among people with type 1 diabetes is increasing. At present, it is unclear how DIYAPS compares with other technologies such as FreeStyle Libre (FSL) and continuous subcutaneous insulin infusion (CSII). The aim of this analysis is to compare safety, effectiveness and quality-of-life outcomes of DIYAPS use with the addition of FSL to CSII. METHOD: Data from two large UK hospitals were extracted from the Association of British Clinical Diabetologists (ABCD) DIYAPS and FSL audits. Outcomes included HbA1c , glucose TBR (time-below-range), TIR (time-in-range), Diabetes Distress Score (DDS), and Gold hypoglycaemia score. Any adverse events were noted. Changes at follow-up were assessed using paired t-tests and ANOVA in Stata; TIR/TBR at follow-up assessed using unpaired t-tests; chi-square tests assessed the change in frequency of health utilisation (e.g. hospital admissions). RESULTS: DIYAPS (n = 35) and FSL+CSII (n = 149) users, with median follow-up duration of 1.4 (IQR 0.8-2.1) and 1.3 (IQR 0.7-1.8) years, respectively, were included. HbA1c with DIYAPS use changed by -10 mmol/mol [0.9%] (p < 0.001, 95% CI 5, 14 [0.5, 1.3%]) significantly lower (p < 0.001) than in the FSL+CSII group -3 mmol/mol [0.25%] (p < 0.001, 95% CI 1, 4 [0.1, 0.4%]). TIR was higher and TBR was lower in the DIYAPS group. Adverse events were rare in both groups and no significant differences were observed in the frequency of healthcare utilisation. CONCLUSION: DIYAPS use was associated with a lower HbA1c levels, higher TIR and lower TBR compared with FSL+CSII. There was no significant increase in adverse events, although this should be interpreted cautiously given the low numbers of users. Full results from the ABCD DIYAPS audit are awaited.

Suboptimal sleep and incident cardiovascular disease among African Americans in the Jackson Heart Study (JHS).

BACKGROUND: Suboptimal sleep, including insufficient/long sleep duration and poor sleep quality, is a risk factor for cardiovascular disease (CVD) common but there is little information among African Americans, a group with a disproportionate CVD burden. The current study examined the association between suboptimal sleep and incident CVD among African Americans. METHODS: This study included 4,522 African Americans without CVD at baseline (2000-2004) of the Jackson Heart Study (JHS). Self-reported sleep duration was defined as very short (<6 h/night), short (6 h/night), recommended (7-8 h/night), and long (≥9 h/night). Participants' self-reported sleep quality was defined as "high" and "low" quality. Suboptimal sleep was defined by low quality sleep and/or insufficient/long sleep duration. Incident CVD was a composite of incident coronary heart disease and stroke. Associations between suboptimal sleep and incident CVD were examined using Cox proportional hazards models over 15 follow-up years with adjustment for predictors of CVD risk and obstructive sleep apnea. RESULTS: Sample mean age was 54 years (SD = 13), 64% female and 66% reported suboptimal sleep. Suboptimal sleep was not associated with incident CVD after covariate adjustment [HR(95% CI) = 1.18(0.97-1.46)]. Long [HR(95%CI) = 1.32(1.02-1.70)] and very short [HR(95% CI) = 1.56(1.06-2.30)] sleep duration were associated with incident CVD relative to recommended sleep duration. Low quality sleep was not associated with incident CVD (p = 0.413). CONCLUSIONS: Long and very short self-reported sleep duration but not self-reported sleep quality were associated with increased hazard of incident CVD.

Evidence for interaction between genetic liability and childhood trauma in the development of psychotic symptoms.

PURPOSE: Whilst childhood trauma (CT) is a known risk factor across the spectrum of psychosis expression, little is known about possible interplay with genetic liability. METHODS: The TwinssCan Study collected data in general population twins, focussing on expression of psychosis at the level of subthreshold psychotic experiences. A multilevel mixed-effects linear regression analysis was performed including 745 subjects to assess the interaction between genetic liability and CT. The Symptom Checklist-90 (SCL-90-R) score of the co-twin was used as an indirect measure of genetic liability to psychopathology, while the Childhood Trauma Questionnaire Short-Form (CTQ-SF) was used to assess CT in the domains of physical, emotional and sexual abuse, as well as physical and emotional neglect. The Community Assessment of Psychic Experience (CAPE) questionnaire was used to phenotypically characterize psychosis expression. RESULTS: In the model using the CAPE total score, the interaction between CT and genetic liability was close to statistical significance (χ2 = 5.6, df = 2, p = 0.06). Analyses of CAPE subscales revealed a significant interaction between CT and genetic liability (χ2 = 8.8, df = 2, p = 0.012) for the CAPE-negative symptoms subscale, but not for the other two subscales (i.e. positive and depressive). CONCLUSION: The results suggest that the impact of CT on subthreshold expression of psychosis, particularly in the negative subdomain, may be larger in the co-presence of significant genetic liability for psychopathology.

Autosegmentation of the rectum on megavoltage image guidance scans.

Autosegmentation of image guidance (IG) scans is crucial for streamlining and optimising delivered dose calculation in radiotherapy. By accounting for interfraction motion, daily delivered dose can be accumulated and incorporated into automated systems for adaptive radiotherapy. Autosegmentation of IG scans is challenging due to poorer image quality than typical planning kilovoltage computed tomography (kVCT) systems, and the resulting reduction of soft tissue contrast in regions such as the pelvis makes organ boundaries less distinguishable. Current autosegmentation solutions generally involve propagation of planning contours to the IG scan by deformable image registration (DIR). Here, we present a novel approach for primary autosegmentation of the rectum on megavoltage IG scans acquired during prostate radiotherapy, based on the Chan-Vese algorithm. Pre-processing steps such as Hounsfield unit/intensity scaling, identifying search regions, dealing with air, and handling the prostate, are detailed. Post-processing features include identification of implausible contours (nominally those affected by muscle or air), 3D self-checking, smoothing, and interpolation. In cases where the algorithm struggles, the best estimate on a given slice may revert to the propagated kVCT rectal contour. Algorithm parameters were optimised systematically for a training cohort of 26 scans, and tested on a validation cohort of 30 scans, from 10 patients. Manual intervention was not required. Comparing Chan-Vese autocontours with contours manually segmented by an experienced clinical oncologist achieved a mean Dice Similarity Coefficient of 0.78 (SE < 0.011). This was comparable with DIR methods for kVCT and CBCT published in the literature. The autosegmentation system was developed within the VoxTox Research Programme for accumulation of delivered dose to the rectum in prostate radiotherapy, but may have applicability to further anatomical sites and imaging modalities.

Human papillomavirus (HPV) and its vaccine: awareness and opinions of clinical dental students in a UK dental school.

Introduction: Dental clinicians are in a position to educate their patients on the subject of HPV as part of a primary healthcare multidisciplinary team and to detect HPV-related disease. Attention needs to be paid to dental undergraduate teaching on the topic. This study aims to ascertain awareness and opinions of our dental undergraduate students about HPV, its relation to oral health and its vaccine. Method: A questionnaire was distributed to undergraduate dental students in clinical years 3, 4 and 5 of the BDS programme at Bristol Dental School. Results: Dental students demonstrated an understanding of HPV and oropharyngeal cancer and expressed that they felt dentists should play a role in health promotion in relation to oropharyngeal cancers. They also wished for more teaching on the subject and suggested topic areas that they wished to know more about. Conclusion: New teaching strategies on the topic of HPV should be considered for inclusion into undergraduate dental programmes and encompass both knowledge and communication skills training to prepare future dentists for their role in confronting this preventable disease.

Core information set for informed consent to surgery for oral or oropharyngeal cancer: A mixed-methods study.

OBJECTIVES: To develop a core information set for informed consent to surgery for oral/oropharyngeal surgery. A core information set is baseline information rated important by patients and surgeons and is intended to improve patients' understanding of the intended procedure. DESIGN: A mixed-methods study. Systematic reviews of scientific and written healthcare literature, qualitative interviews and observations, Delphi surveys, and group consensus meetings identified information domains of importance for consent. SETTING: A regional head and neck clinic in the United Kingdom. Questionnaire participants were recruited from around the UK. PARTICIPANTS: Patients about to undergo, or who had previously undergone, surgery for oral/oropharyngeal cancer. Healthcare professionals involved in the management of head and neck cancer. MAIN OUTCOME MEASURES: The main outcome was a core information set. RESULTS: Systematic reviews, interviews and consultation observations yielded 887 pieces of information that were categorised into 87 information domains. Survey response rates were 67% (n = 50) and 71% (n = 52) for patient and healthcare professional groups in round one. More than 90% responded in each group in the second round. Healthcare professionals were more likely to rate information about short-term or peri-operative events as important while patients rated longer term issues about survival and quality of life. The consensus-building process resulted in an agreed core information set of 13 domains plus two procedure-specific domains about tracheostomy and free-flap surgery. CONCLUSION: This study produced a core information set for surgeons and patients to discuss before surgery for oral/oropharyngeal cancer. Future work will optimise ways to integrate core information into routine consultations.