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The Australian Medical Journal is important to Australian anaesthesia in that, as well as associated editorials, it recorded the first use of ether for surgical operations. Though it survived from 1 August 1846 until 1 October 1847, its first issue was surrounded with mystery, referring to an earlier publication. Proof of this earlier issue of April 1846 has been discovered though no copy remains extant. [ABSTRACT FROM AUTHOR]

Background: Frailty is a clinical state of increased vulnerability and is common in patients with cirrhosis. The liver frailty index (LFI) is a validated tool to evaluate frailty in cirrhosis, comprising of grip strength, chair stands, and balance tests. The chair-stand test is an easy to conduct frailty subcomponent that does not require specialized equipment and may be valuable to predict adverse clinical outcomes in cirrhosis. The objective of this study was to determine if the chair-stand test is an independent predictor of mortality and hospitalization in cirrhosis., Methods: A retrospective review of 787 patients with cirrhosis was conducted. Chair-stand times were collected at baseline in person and divided into three groups: <10 seconds ( n = 276), 10-15 seconds ( n = 290), and >15 seconds ( n = 221). Fine-Gray proportional hazards regression models were used to evaluate the association between chair-stand times and the outcomes of mortality and non-elective hospitalization., Results: The hazard of mortality (HR 3.21, 95% CI 2.16%-4.78%, p <0.001) and non-elective hospitalization (HR 2.24, 95% CI 1.73%-2.91%, p <0.001) was increased in group 3 in comparison to group 1. A chair-stand test time >15 seconds had increased all-cause mortality (HR 2.78, 95% CI 2.01%-3.83%, p <0.001) and non-elective hospitalizations (HR 1.84, 95% CI 1.48%-2.29%, p <0.001) compared to <15 seconds., Conclusions: A chair-stand test time of >15 seconds is independently associated with mortality and non-elective hospitalizations. This test holds promise as a rapid prognostication tool in cirrhosis. Future work will include external validation and virtual assessment in this population., (© Canadian Association for the Study of the Liver, 2023.)

Aims: This cross-sectional analysis explored the relationships between periodontal disease (PD) and subclinical CVD in a cohort of patients with type 1 diabetes and non-diabetic controls., Methods: Data were collected from adults enrolled in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study or enrolled through the Barbara Davis Center for Diabetes Adult Clinic. A clinical periodontal exam measured attachment loss and probing depth. Brachial artery distensibility (brachD), carotid intima-media thickness (cIMT), and pulse wave velocity (PWV) were assessed as measures of subclinical cardiovascular structure and function., Results: 144 participants with T1D and 148 non-diabetics were enrolled. Compared to non-diabetic controls, T1D participants had a higher probing depth (2.6 mm vs. 2.5 mm; p = 0.04), higher attachment loss (2.7 mm vs. 2.4 mm; p < 0.01), lower brachD (mean 5.8 vs. 6.4 mmHg; p < 0.01), a higher cIMT (mean 0.68 vs. 0.64 mm; p < 0.01), and a higher PWV (mean 8.3 vs. 7.8 m/s; p < 0.01). There were no significant associations between PD and CVD metrics., Conclusions: Periodontal and cardiovascular health was worse in participants with T1D compared to non-diabetics. No significant associations between PD measures and CVD were identified., Competing Interests: Declaration of competing interest RB, AS, JKS, BRB, SC, LJ, and AA have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: The purpose of this study was to evaluate outcomes of Descemet stripping automated endothelial keratoplasty comparing exchange with fresh intermediate-term cold storage solution after lenticule preparation versus reuse of the original solution in the Cornea Preservation Time Study., Methods: In the Cornea Preservation Time Study, 508 donor corneas had lenticules prepared by the eye bank with fresh solution exchange (Fresh group) and 283 with reuse of the original solution (Original group). Storage time for all donors was ≤11 days. Graft success rates, central endothelial cell loss at 3 years, and frequency of positive donor rim cultures were compared between the 2 groups., Results: The 3-year graft success rate (95% confidence interval) was 93.4% (90.7%-95.3%) in the Fresh group and 95.2% (91.8%-97.2%) in the Original group (adjusted hazard ratio for graft failure = 0.64, 95% confidence interval, 0.33-1.24, P = 0.19). The mean percentage endothelial cell loss was significantly greater in the Fresh group versus Original group (45% ± 22% vs. 38% ± 20%, respectively, P = 0.004). Cultures were positive in 4 (1.5%) of 267 donor rims (3 fungal and 1 bacterial) in the Fresh group and in 4 (2.5%) of 158 in the Original group ( P = 0.57). There were 2 postoperative infections in the Original group and none in the Fresh group., Conclusions: The use of the original intermediate-term cold storage solution did not reduce the 3-year graft success rate compared with exchanging with fresh solution after lenticule preparation for Descemet stripping automated endothelial keratoplasty, while the frequency of positive donor rim cultures did not significantly differ between groups., Competing Interests: The following authors have financial disclosures with companies that manufacture corneal storage solutions (considered relevant to this work): M. Terry (Bausch & Lomb) and W. B. Lee (Bausch & Lomb) (part of CPTS Study Group but not authors on this paper). These authors are employed by eye banks: M. Soper (VisionFirst), and M. S. Titus (Eversight). J. H. Lass is a voluntary board member of Eversight and the Cleveland Eye Bank Foundation. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

The Medtronic advanced hybrid closed-loop (AHCL) and MiniMed™ 670G hybrid closed-loop (HCL) systems provide the option to temporarily increase the glucose target to 150 mg/dL (8.3 mmol/L). This analysis investigated the efficacy of the AHCL compared with that of the HCL after the use of this setting. Data from 60 participants in the Fuzzy Logic Automated Insulin Regulation (FLAIR) study were used to compare the AHCL and HCL systems after the use of the temporary target (TT), and during analogous periods where this setting was not used. Differences in time in range 70-180 mg/dL between the systems were similar after the use of the TT setting and during analogous non-TT periods (interaction P  = 0.87). Similar trends were observed for mean glucose, percentage time >180 mg/dL, and percentage time >250 mg/dL. Differences between AHCL and HCL systems were similar after the use of the TT setting compared with those of non-TT periods. ClinicalTrials.gov NCT03040414.

Background: Psychological stress negatively impacts inflammatory bowel disease (IBD) outcomes. Patients have prioritized access to online interventions; yet, the data on these have been limited by mixed in-person/online interventions, low adherence, and non-randomized controlled trial (RCT) design., Objectives: We assessed the efficacy of and adherence to a 12-week online multicomponent stress reduction intervention in IBD., Design: This is a RCT., Methods: Adult participants on stable IBD medical therapy with elevated stress levels from four centers were randomized to intervention or control groups. Intervention participants received a 12-week online program including a weekly yoga, breathwork and meditation video (target 2-3 times/week), a weekly cognitive behavioral therapy/positive psychology informed video activity, and weekly 10-min check-ins by a study team member. Control participants received weekly motivational messages by email. All patients received standard of care IBD therapy. The primary outcome was Cohen's Perceived Stress Scale (PSS). Secondary outcomes evaluated mental health, resilience, health-related quality of life (HRQoL), symptom indices, acceptability, adherence, and inflammatory biomarkers. Analysis of covariance was used to determine between-group differences., Results: Of 150 screened patients, 101 were randomized to the intervention ( n  = 49) and control ( n  = 52) groups (mean age: 42.5 ± 14.1 years; M:F 1:3, 48% with ulcerative colitis and 52% with Crohn's disease). The between-group PSS improved by 22.4% (95% confidence interval, 10.5-34.3, p  < 0.001). Significant improvements were seen in mental health, resilience, and HRQoL measures, with a median satisfaction score of 89/100 at the end of the 12 weeks. In the 44/49 patients who completed the intervention, 91% achieved program adherence targets., Conclusion: This 12-week online intervention improved perceived stress, mental health, and HRQoL, but did not impact IBD symptom indices or inflammatory biomarkers. The program was readily adopted and adhered to by participants with high retention rates. After iterative refinement based on participant feedback, future studies will evaluate the impact of a longer/more intense intervention on disease course., Registration: ClinicalTrials.gov Identifier NCT03831750., Plain Language Summary: An online stress reduction intervention in inflammatory bowel disease patients improves stress, mental health, and quality of life People with inflammatory bowel disease (IBD) have high levels of stress, anxiety, and depression. Although IBD patients have expressed the need for online mental wellness interventions, the existing data to support these interventions in IBD are limited. In this trial, 101 IBD patients had the chance to participate in a 12-week online stress reduction intervention. In those patients randomly selected to participate in the online intervention, each week they received the following: a 20- to 30-min yoga, breathwork, and meditation video that they were asked to do 2-3 times a week, a 10- to 20-min mental wellness activity they were asked to do once during the week, and a 10-min telephone check-in with a study team member. Participants who were not selected to use the online intervention received a weekly motivational message by email. In all, 90 of the 101 participants (89%) completed the study with the mean age of participants being 43 years and the majority being females (75%). Ninety-one percent of participants who completed the intervention met the program target of doing the yoga, breathwork, and meditation video at least 2 times per week. Significant improvements were seen in perceived stress (by 22.4%), depression (by 29.5%), anxiety (by 23.7%), resilience (by 10.6%), and quality of life (by 8.9%). No changes were seen in IBD severity or in blood markers of inflammation. In conclusion, this study demonstrates evidence that a 12-week online stress reduction intervention had low dropout rates, high adherence and beneficial effects on stress, mental health, and quality of life measures. Continued feedback will be sought from study participants and our IBD patient partners to refine the intervention and assess the impact in future studies of patients with active IBD, as well as the impact of a longer/more intense intervention., (© The Author(s), 2022.)

Current methods for segmenting eye imagery into skin, sclera, pupil, and iris cannot leverage information about eye motion. This is because the datasets on which models are trained are limited to temporally non-contiguous frames. We present Temporal RIT-Eyes, a Blender pipeline that draws data from real eye videos for the rendering of synthetic imagery depicting natural gaze dynamics. These sequences are accompanied by ground-truth segmentation maps that may be used for training image-segmentation networks. Temporal RIT-Eyes relies on a novel method for the extraction of 3D eyelid pose (top and bottom apex of eyelids/eyeball boundary) from raw eye images for the rendering of gaze-dependent eyelid pose and blink behavior. The pipeline is parameterized to vary in appearance, eye/head/camera/illuminant geometry, and environment settings (indoor/outdoor). We present two open-source datasets of synthetic eye imagery: sGiW is a set of synthetic-image sequences whose dynamics are modeled on those of the Gaze in Wild dataset, and sOpenEDS2 is a series of temporally non-contiguous eye images that approximate the OpenEDS-2019 dataset. We also analyze and demonstrate the quality of the rendered dataset qualitatively and show significant overlap between latent-space representations of the source and the rendered datasets.

Background: Primary biliary cholangitis (PBC) is a rare, chronic autoimmune, cholestatic liver disease affecting approximately 318 per million Canadians. There is limited information regarding the characterization of this patient population in Canada. Consequently, we aim to describe a cohort of PBC patients managed across liver centres serving this type of population., Methods: A cross-sectional examination of 1,125 PBC patient charts at 15 liver centres across Canada was conducted between January 2016 and September 2017., Results: Data from 1,125 eligible patients were collected from 7 Canadian provinces. The patient population was largely female (90.2%), had a median overall age of 61.3 years, and a median overall time since diagnosis of 6.4 years. Of the patients included in the study, 89% were on ursodeoxycholic acid (UDCA) therapy at a median dose of 14.0 mg/kg/day and 4.4% were previously treated with UDCA, whereas 6.6% were never treated with UDCA. Of the patients with available data (n = 1067), 289 (27.1%) presented with alkaline phosphatase (ALP) levels ≥200 IU/L and/or total bilirubin levels ≥21 µmol/L. Assessment of UDCA treatment response revealed that 26.6% and 38.3% of patients were inadequate responders according to the Toronto and Paris-II criteria, respectively. Mortality occurred in 1.2% (14) of patients, with liver-related adverse outcomes being more commonly observed in patients who discontinued UDCA compared to those who are currently on treatment (36.3% and 19.6%, respectively)., Conclusion: This study showed that Canadian PBC patients present with demographics and features commonly reported in the literature for this disease. Over one third of PBC patients had inadequate response to UDCA treatment or were not currently being treated with UDCA. Consequently, there is a significant unmet therapeutic need in this Canadian PBC population., Competing Interests: EM Yoshida has received an unrestricted research grant from Paladin Laboartories and clinical trials sponsorship from Gilead Sciences, Intercept, Abbvie, Merck, Genfit, Pfizer, Celgene, Allergan, and Madrigal. He has also received honoraria for CME/Ad Board lectures from Intercept, Gilead, and Merck. He is President of the Vancouver Medical Dental Allied Staff Association; C Tsien received grants/contracts from Lupin, and payment or honoraria for lectures, presentations, speaker bureaus, or educational events from Abbvie and Intercept; MG Swain received grants/contracts for research studies from Gilead, Intercept, CymaBay, Genkyotex, GSK, Genfit, Novartis, Pfizer, Celgene, AstraZeneca, AbbVie, and Novo Nordisk, payment or honoraria for lectures and presentations from Gilead, Intercept, and AbbVie, and participated on the advisory boards for Gilead, Novartis, and Intercept; KM Peltekian participated on the advisory board for Intercept and has held a leadership or fiduciary role on the Canadian Liver Foundation board; MA Puglia has received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Intercept as well as support from them for attending meetings and/or travel and participating on their advisory board; M Elkhashab has received consulting fees and payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AbbVie, Gilead, and Merck, as well as participated on the advisory boards for AbbVie, Gilead, and Merck; M O’Brien has received payment or honoraria for lectures, presentations, speaker bureaus, or educational events from Intercept; HH Ko has received payment or honoraria for lectures, presentations, speaker bureaus, or educational events from Intercept and has held a leadership or fiduciary role on the Intercept advisory board; E Tam has received consulting fees from Intercept as well as payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Intercept; A Ramji has received grants/contracts from AbbVie, Allergan, Assembly, Galmed, Gilead, Janssen, Intercept, Novartis, and Merck, as well as payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AbbVie, Allergan, Amgen, Celgene, Gilead, Intercept, Amgen, Janssen, Novartis, and Merck. He has participated on advisory board for AbbVie, Gilead, Janssen, Intercept, Novartis, Merck, and Novo Nordisk; the other authors have nothing to disclose., (Copyright © 2022 Canadian Association for the Study of the Liver.)

Given the ongoing dilemma for college counseling centers to meet steady increases in demand for services, this study outlines the implementation of an adapted stepped care model in a university counseling center. Our adapted model focused, as do other stepped care models, on treatment planning and lower-intensity interventions, with the addition of the intensive therapy option being provided on a weekly basis. We adopted our stepped care model across a large center and hypothesized that after implementation we would be able to serve a similar number of clients as our previous model and that treatment outcomes for these clients would improve. Descriptive data and regression analyses demonstrated support for our hypotheses, including an increased likelihood of clinically significant improvement for clients postimplementation. Implications for adapting service delivery models using practice-based evidence are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: We recently reported that use of an "advanced" hybrid closed-loop system reduced hyperglycemia without increasing hypoglycemia compared to a first-generation system. The aim of this analysis was to evaluate whether this improved performance was specifically related to better mealtime glycemic control. Methods: We conducted a secondary analysis of postprandial glycemic control in an open-label, multinational, randomized crossover trial of 112 participants with type 1 diabetes, aged 14-29, of the Medtronic MiniMed™ 670G hybrid closed-loop system (670G) versus the Medtronic advanced hybrid closed-loop (AHCL) system, for 12 weeks each. We compared glycemic and insulin delivery metrics over a 3 h horizon across all meals to assess system performance and outcomes. Results: Overall meal size and premeal insulin on board were similar during run-in and between 670G and AHCL arms. Compared with 670G arm, premeal, peak, and mean glucose levels were numerically lower in the AHCL arm (167 ± 23, 231 ± 23, and 177 ± 20 mg/dL vs. 175 ± 23, 235 ± 23, and 180 ± 19 mg/dL, respectively), with a trend to lower hyperglycemia level 2 in AHCL arm. Adjusting for premeal glucose level, all postmeal outcomes between 670G and AHCL were statistically similar. Prandial insulin delivery also was similar in both treatment arms (21 ± 9 vs. 23 ± 10 U), with a shift in basal/bolus ratio from 28%/71% in 670G arm to 20%/80% in AHCL arm. Conclusions: Reduced hyperglycemia with AHCL compared to 670G was not related to early postprandial glycemic excursions after adjusting for premeal glucose level (<3 h after meal), but likely to later (>3 h) postprandial or overnight improvements. Further refinements to mealtime bolus algorithms and strategies may more optimally control prandial glycemic excursions.

With increasing demand for psychotherapy services, clinicians are carrying increasingly large caseloads (Bailey et al., 2020). As the number of new intakes exceeds the number of clinical hours available each week in some settings, psychotherapy is delivered on an attenuated schedule for returning clients (rather than the traditional weekly frequency); there is, however, little support for the efficacy of this practice. The present study explored the effect of session frequency on psychotherapy outcomes using a quasi-randomized controlled design. In a working university counseling center, we assigned therapists to either a treatment-as-usual (TAU) group (attenuated session frequency) or an experimental group (weekly session frequency). Clients were randomly assigned to a therapist in either condition. Using hierarchical linear modeling and survival analyses, we examined psychotherapy outcomes (measured by session-by-session Outcome Questionnaire 45 scores) for 1,322 clients (3,919 individual sessions). We found no differences between groups when examining the full sample, but also found limited fidelity in the experimental group. When identifying individuals who were seen weekly in at least the first three sessions after intake (sensitivity analysis), we found the following: (a) weekly therapy resulted in faster trajectories of change over time, (b) weekly therapy resulted in a greater likelihood of achieving recovery, and (c) weekly therapy resulted in a greater likelihood of achieving recovery sooner . We discuss the importance of including session frequency when considering the dose of therapy, as well as the implication that prioritizing weekly therapy may increase therapy efficacy and efficiency in routine practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objectives: The prevalence and effects of anxiety on health-related quality of life and clinical outcomes in cirrhosis are not well understood. This is increasingly relevant during COVID-19. Our aim was to use the Mini-International Neuropsychiatric Interview (MINI) to determine the prevalence of anxiety, its association with clinical outcomes in cirrhosis and to develop a rapid cirrhosis-specific anxiety screening nomogram., Methods: Adults with a diagnosis of cirrhosis were prospectively recruited as outpatients at three tertiary care hospitals across Alberta and followed for up to 6 months to determine the association with unplanned hospitalization/death. The Hospital Anxiety and Depression scale (HADS) was used as a screening tool as it is free of influence from somatic symptoms. Anxiety was diagnosed using the MINI., Results: Of 304 patients, 17% of patients had anxiety by the MINI and 32% by the HADS. Anxious patients had lower health-related quality of life as assessed by the chronic liver disease questionnaire (P < 0.001) and EuroQol Visual Analogue Scale (P < 0.001), and also had higher levels of frailty using the Clinical Frailty score (P = 0.004). Multivariable analysis revealed smoking and three HADS subcomponents as independent predictors of anxiety. These were used to develop a rapid screening nomogram., Conclusion: A formal diagnosis of anxiety was made in approximately one in five patients with cirrhosis, and it was associated with worse HrQoL and frailty. The use of a 4-question nonsomatic symptom-based nomogram requires validation but is promising as a rapid screen for anxiety in cirrhosis., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Loop is an open-source automated insulin dosing system that allows users unrivaled control over system settings that affect future glucose prediction. Thousands use Loop, but little is known about those who discontinue. Methods: In a large observational study, 874 Loop participants completed surveys and provided glycemic data, 46 (5.3%) of those self-identified as discontinuing Loop use during the observation window, 45 completed a discontinued use survey, 22 provided system settings data, and 19 participated in semistructured interviews about their discontinuation. Qualitative data were transcribed, coded, and analyzed. Results: Older age and not trusting Loop were associated with discontinued use, although no other demographic or clinical characteristics were significant correlates. The most endorsed reasons were "I decided to try something else" (27.8%) followed by "It just didn't help as much as I thought it would" (22.2%). Qualitative analyses revealed prominent themes centered upon mental and emotional burden and adjusting settings. Other reasons for discontinued use included fear of disapproval of Loop use from diabetes provider, barriers to acquiring component devices, a desire to try new/different technologies, concerns that Loop could not accommodate specific exercise or low insulin dose regimens, and worry about Loop use during pregnancy. It was noted that burdens might be alleviated by enhanced technical assistance and expert guidance. Conclusions: Although the majority of individuals in the Loop observational study continued use, those who discontinued reported similar challenges. Technical support and education specific to setting calculations could expand Loop benefits, alleviate burden, and support sustained use among new Loop users. Clinical Trial Registration: clinicaltrials.gov (NCT03838900).

Background and Aims: The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease., Approach and Results: Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI < 3.2), prefrail (LFI 3.2-4.5), and frail (LFI > 4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5 ± 6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis., Conclusions: Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty., (© 2021 American Association for the Study of Liver Diseases.)

Background: Primary sclerosing cholangitis (PSC) is an immune-mediated biliary disorder of unknown etiology with no effective treatment. The purpose of this study was to better prognosticate the development of cirrhosis, decompensation, and requirement for liver transplantation (LT) in PSC patients based on serum immunoglobulin G4 (IgG4) levels., Methods: A retrospective chart review was conducted on PSC patients seen at the University of Alberta Hospital between 2002 and 2017. PSC patients were categorized as high IgG4 group (≥70 mg/dL) or normal IgG4 group (<70 mg/dL). Laboratory parameters, clinical characteristics, and outcomes were compared between the groups., Results: One hundred and ten patients were followed over a mean period of 7.3 (SD 5) years. Seventy-two patients (66%) were male, the mean age at diagnosis of PSC was 35 (SD 15) years, and inflammatory bowel disease (IBD) was present in 80 patients (73%). High IgG4 levels were found in 37 patients (34%). PSC patients with high IgG4 had a shorter mean cholangitis-free survival time (5.3 versus 10.4 years, p = 0.02), cirrhosis-free survival time (8.7 versus 13.0 years, p = 0.02), and LT-free survival time (9.3 years versus 18.9 years, p <0.001). IgG4 ≥70 mg/dL was independently associated with liver decompensation and LT-free outcomes. A cut-off IgG4 value of ≥70 mg/dL performed better than a cut-off value of ≥140 mg/dL to predict time to LT (area under the curve [AUC] 0.68, p = 0.03, sensitivity 72%, specificity 78%)., Conclusions: Serum IgG4 ≥70 mg/dL in PSC predicts a shorter time to cirrhosis decompensation and LT., Competing Interests: F Peerani affirms that the manuscript, including related data, figures, and tables has not been previously published and that the manuscript is not under consideration elsewhere. AJ Montano-Loza has received a Canadian Liver Foundation grant, and participated on the Intercept and Gilead advisory boards. The other authors have nothing to disclose., (Copyright © 2022 Canadian Association for the Study of the Liver.)

This article reports on the lived experience of Medtronic advanced hybrid closed-loop (AHCL) in comparison to first generation hybrid closed-loop (HCL) in a randomized, open-label, two-period crossover trial. Patient-reported outcome (PROs) measures were administered before randomization and at the end of each study period in 113 adolescents and young adults with type 1 diabetes. Glucose monitoring satisfaction subscales for emotional burden and behavioral burden improved significantly ( P  < 0.01) over time with use of AHCL versus HCL and co-occurred with glycemic improvements (reduced percent time above 180 mg/dL during the day and no change in % time less than 54 mg/dL across 24 h) and greater time in Auto Mode. PROs, including distress, technology attitudes, and hypoglycemia confidence, were not different. AHCL use was associated with improved glucose monitoring satisfaction. Satisfaction was greater in those participants who had more appreciable glycemic benefit and stayed in Auto Mode more often. Clinical Trial Registration number: NCT03040414.

As demand increased for mental health services, especially in university counseling centers, providers have seen increasing numbers of clients. The effect of this increase on therapist caseloads is explored, with a recognition that past research on therapist caseloads lacks direct and fluctuating measures of caseload that reflect practice in naturalistic settings. Using a large dataset from a counseling center ( N = 18,322), therapist caseload was conceptualized dynamically over rolling 30-day periods, using within-therapist counts of therapy sessions, unique clients seen, and the proportion of unique clients to sessions. Analysis of variance was used first to test for differences in caseload between months, years, then to test for differences between therapists ( n = 173). Hierarchical linear models were constructed to examine the relationship between changes in therapist caseload across time and client outcome. Logistic and ordinal regression approaches were used to further examine this relationship for clinically significant change. Results included finding a small, but significant, effect of therapist caseload on outcome, with this finding discussed in the context of the effect sizes in the literature on therapist effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

There is a rapidly evolving need for e-health to support chronic disease self-management and connect patients with their healthcare teams. Patients with cirrhosis have a high symptom burden, significant comorbidities, and a range of psychological and cognitive issues. Patients with cirrhosis were assessed for their readiness and interest in e-health. Adults attending one of two outpatient cirrhosis clinics in Alberta were recruited. Eligible participants were not required to own or have experience with digital technologies or the Internet. Medical history, socioeconomic status, and attitudes regarding e-health, the Computer Proficiency Questionnaire, and the Mobile Device Proficiency Questionnaire were used to describe participants' knowledge and skills. Of the 117 recruited patients, 68.4% owned a computer and 84.6% owned a mobile device. Patients had mean proficiency scores of 72.8% (SD 25.9%) and 69.3% (SD 26.4%) for these devices, respectively. In multiple regression analyses, significant predictors of device proficiency were age, education, and household income. Most patients (78.7%) were confident they could participate in videoconferencing after training and most (61.5%) were interested in an online personalized health management program. This diverse group of patients with cirrhosis had technology ownership, proficiency, and online behaviours similar to the general population. Moreover, the patients were very receptive to e-health if training was provided. This promising data is timely given the unique demands of COVID-19 and its influence on self-management and healthcare delivery to a vulnerable population.

Objective: To evaluate the safety and effectiveness of the Loop Do-It-Yourself automated insulin delivery system. Research Design and Methods: A prospective real-world observational study was conducted, which included 558 adults and children (age range 1-71 years, mean HbA1c 6.8% ± 1.0%) who initiated Loop either on their own or with community-developed resources and provided data for 6 months. Results: Mean time-in-range 70-180 mg/dL (TIR) increased from 67% ± 16% at baseline (before starting Loop) to 73% ± 13% during the 6 months (mean change from baseline 6.6%, 95% confidence interval [CI] 5.9%-7.4%; P  < 0.001). TIR increased in both adults and children, across the full range of baseline HbA1c, and in participants with both high- and moderate-income levels. Median time <54 mg/dL was 0.40% at baseline and changed by -0.05% (95% CI -0.09% to -0.03%, P  < 0.001). Mean HbA1c was 6.8% ± 1.0% at baseline and decreased to 6.5% ± 0.8% after 6 months (mean difference = -0.33%, 95% CI -0.40% to -0.26%, P  < 0.001). The incidence rate of reported severe hypoglycemia events was 18.7 per 100 person-years, a reduction from the incidence rate of 181 per 100 person-years during the 3 months before the study. Among the 481 users providing Loop data at 6 months, median continuous glucose monitoring use was 96% (interquartile range [IQR] 91%-98%) and median time Loop modulating basal insulin was at least 83% (IQR 73%-88%). Conclusions: The Loop open source system can be initiated with community-developed resources and used safely and effectively by adults and children with type 1 diabetes.

Ellipse fitting, an essential component in pupil or iris tracking based video oculography, is performed on previously segmented eye parts generated using various computer vision techniques. Several factors, such as occlusions due to eyelid shape, camera position or eyelashes, frequently break ellipse fitting algorithms that rely on well-defined pupil or iris edge segments. In this work, we propose training a convolutional neural network to directly segment entire elliptical structures and demonstrate that such a framework is robust to occlusions and offers superior pupil and iris tracking performance (at least 10% and 24% increase in pupil and iris center detection rate respectively within a two-pixel error margin) compared to using standard eye parts segmentation for multiple publicly available synthetic segmentation datasets.

Context: Glycemic control in adolescents with type 1 diabetes is poor; yet, it typically improves during early adulthood. Factors related to improvement of glycemic control are unclear., Objective: This work examines how demographic and clinical variables may affect trajectories of glycemic control over time., Methods: This retrospective, observational study comprised 1775 participants ages 18 to 30 years at enrollment in the T1D Exchange clinic registry. Latent class trajectory modeling was used to determine subgroups following a similar glycated hemoglobin A1c (HbA1c) trajectory over time., Results: Five distinct trajectories of HbA1c classes were identified: "low-decline" and "moderate-decline" groups had low or moderate HbA1c with a gradual decline, the "high-stable" group had high HbA1c and remained stable, and the "very high-rapid decline" and "very high-slow decline" groups had very high HbA1c with rapid or gradual decline. Compared with the "high-stable" group, the "low-decline" and "moderate-decline" groups were more likely to be male (P = .009), White non-Hispanic (P = .02), nonsmokers (P < .001), check self-monitoring blood glucose (SMBG) more frequently (P < .001), and have higher education (P < .001), lower body mass index (P = .02), and lower daily insulin dose (P < .001). Compared with the "very high-rapid decline" and "very high-slow decline" groups, the "low-decline" and "moderate-decline" groups were more likely to be male (P = .02), have higher education (P < .001), use insulin pumps (P = .01), be nonsmokers (P < .001), and have a higher number of SMBG checks per day at enrollment (P < .001)., Conclusion: We determined 5 distinct patterns of glycemic control from early adulthood into adulthood. Further evaluation into the modifiable factors associated with a declining HbA1c trajectory would aid in the development of targeted interventions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Due to the limitations of bone autografts, we aimed to develop new composite biomaterials with pro-angiogenic and osteogenic properties to be used as scaffolds in bone tissue engineering applications. We used a porous, cross-linked and slowly biodegradable fibrin/alginate scaffold originally developed in our laboratory for wound healing, throughout which deposits of calcium phosphate (CaP) were evenly incorporated using an established biomimetic method. Material characterisation revealed the porous nature and confirmed the deposition of CaP precursor phases throughout the scaffolds. MC3T3-E1 cells adhered to the scaffolds, proliferated, migrated and differentiated down the osteogenic pathway during the culture period. Chick chorioallantoic membrane (CAM) assay results showed that the scaffolds were pro-angiogenic and biocompatible. The work presented here gave useful insights into the potential of these pro-angiogenic and osteogenic scaffolds for bone tissue engineering and merits further research in a pre-clinical model prior to its clinical translation., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Dr Vaibhav Sharma and Dr Elena García-Gareta provided services to Smart Matrix Ltd (SML), established to take the humanised version of fibrin/alginate dermal replacement scaffold through the development stage and onto patients. Dr Sharma and Dr García-Gareta did not get directly paid for these services. The RAFT Institute, which invented and developed fibrin/alginate, had a service agreement with SML and the time that these two authors spent on services for SML were reimbursed to The RAFT Institute., (© The Author(s) 2021.)

Background: Management of type 1 diabetes is challenging. We compared outcomes using a commercially available hybrid closed-loop system versus a new investigational system with features potentially useful for adolescents and young adults with type 1 diabetes., Methods: In this multinational, randomised, crossover trial (Fuzzy Logic Automated Insulin Regulation [FLAIR]), individuals aged 14-29 years old, with a clinical diagnosis of type 1 diabetes with a duration of at least 1 year, using either an insulin pump or multiple daily insulin injections, and glycated haemoglobin (HbA 1c ) levels of 7·0-11·0% (53-97 mmol/mol) were recruited from seven academic-based endocrinology practices, four in the USA, and one each in Germany, Israel, and Slovenia. After a run-in period to teach participants how to use the study pump and continuous glucose monitor, participants were randomly assigned (1:1) using a computer-generated sequence, with a permuted block design (block sizes of two and four), stratified by baseline HbA 1c and use of a personal MiniMed 670G system (Medtronic) at enrolment, to either use of a MiniMed 670G hybrid closed-loop system (670G) or the investigational advanced hybrid closed-loop system (Medtronic) for the first 12-week period, and then participants were crossed over with no washout period, to the other group for use for another 12 weeks. Masking was not possible due to the nature of the systems used. The coprimary outcomes, measured with continuous glucose monitoring, were proportion of time that glucose levels were above 180 mg/dL (>10·0 mmol/L) during 0600 h to 2359 h (ie, daytime), tested for superiority, and proportion of time that glucose levels were below 54 mg/dL (<3·0 mmol/L) calculated over a full 24-h period, tested for non-inferiority (non-inferiority margin 2%). Analysis was by intention to treat. Safety was assessed in all participants randomly assigned to treatment. This trial is registered with ClinicalTrials.gov, NCT03040414, and is now complete., Findings: Between June 3 and Aug 22, 2019, 113 individuals were enrolled into the trial. Mean age was 19 years (SD 4) and 70 (62%) of 113 participants were female. Mean proportion of time with daytime glucose levels above 180 mg/dL (>10·0 mmol/L) was 42% (SD 13) at baseline, 37% (9) during use of the 670G system, and 34% (9) during use of the advanced hybrid closed-loop system (mean difference [advanced hybrid closed-loop system minus 670G system] -3·00% [95% CI -3·97 to -2·04]; p<0·0001). Mean 24-h proportion of time with glucose levels below 54 mg/dL (<3·0 mmol/L) was 0·46% (SD 0·42) at baseline, 0·50% (0·35) during use of the 670G system, and 0·46% (0·33) during use of the advanced hybrid closed-loop system (mean difference [advanced hybrid closed-loop system minus 670G system] -0·06% [95% CI -0·11 to -0·02]; p<0·0001 for non-inferiority). One severe hypoglycaemic event occurred in the advanced hybrid closed-loop system group, determined to be unrelated to study treatment, and none occurred in the 670G group., Interpretation: Hyperglycaemia was reduced without increasing hypoglycaemia in adolescents and young adults with type 1 diabetes using the investigational advanced hybrid closed-loop system compared with the commercially available MiniMed 670G system. Testing an advanced hybrid closed-loop system in populations that are underserved due to socioeconomic factors and testing during pregnancy and in individuals with impaired awareness of hypoglycaemia would advance the effective use of this technology FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Atopic dermatitis (eczema) is a widespread disorder, with researchers constantly looking for more efficacious treatments. Natural oils are reported to be an effective therapy for dry skin, and medical textiles can be used as an alternative or supporting therapy. In this study, fibrous membranes from poly(vinyl butyral-co-vinyl alcohol-co-vinyl acetate) (PVB) with low and high molecular weights were manufactured to obtain nano- and micrometer fibers via electrospinning for the designed patches used as oil carriers for atopic skin treatment. The biocompatibility of PVB patches was analyzed using proliferation tests and scanning electron microscopy (SEM), which combined with a focused ion beam (FIB) allowed for the 3D visualization of patches. The oil spreading tests with evening primrose, black cumin seed, and borage were verified with cryo-SEM, which showed the advantage nanofibers have over microfibers as carriers for low-viscosity oils. The skin tests expressed the usability and the enhanced oil delivery performance for electrospun patches. We demonstrate that through the material nano- and microstructure, commercially available polymers such as PVB have great potential to be deployed as a biomaterial in medical applications, such as topical treatments for chronic skin conditions., Competing Interests: The authors declare no competing financial interest.