Liver fibrosis markers and all cause mortality in people with type 2 diabetes: A population based study (The Ayrshire Diabetes Outcomes Cohort (ADOC) Study).

AIMS: To describe the distribution of the biomarker scores Fibrosis-4 (FIB4), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI), and the associations between risk categories and all-cause mortality. MATERIALS AND METHODS: This was a retrospective cohort study of 12 589 patients, with follow-up from January 2012 until November 2021. The cut-off points used to identify low risk were: FIB4 <1.3 if aged <65 years or <2.0 if aged ≥65 years; NFS < -1.455 if aged <65 years or <0.12 if aged ≥ 65 years; APRI <1 (independent of age). High-risk cut-off points were FIB4 >2.67, NFS >0.676 and APRI ≥1 (all independent of age). Multivariable Cox regression analysis was performed to assess the association between liver fibrosis scores and all-cause mortality. RESULTS: The mean ± standard deviation age was 65.2 ± 12.1 years, 54.5% were men and the median (interquartile range) diabetes duration was 5.8 (2.8-9.3) years. The prevalence of high-risk categories was 6.1% for FIB4, 23.5% for NFS and 1.6% for APRI. During a median follow-up of 9.8 years, 3925 patients (31.1%) died, resulting in a crude mortality rate of 40.4 per 1000 person-years. The overall adjusted all-cause mortality hazard ratios (95% confidence intervals [CIs]) in the high- compared with low-fibrosis-risk groups were 3.69 (1.95-2.75) for FIB4, 2.32 (2.88-4.70) for NFS, and 3.92 (2.88-5.34) for APRI. Stratified adjusted all-cause mortality hazard ratios for individuals under 65 years and people over 65 years of age at cohort entry were 3.89 (95% CI 2.99-5.05) and 1.44 (95% CI 1.28-1.61) for FIB4, 2.50 (95% CI 1.89-3.18) and 1.35 (95% CI 1.24-1.48) for NFS and 3.74 (95% CI 2.73-5.14) and 1.64 (95% CI 1.24-2.17) for APRI. CONCLUSIONS: All three fibrosis risk scores were positively associated with all-cause mortality in people with type 2 diabetes, with higher relative risks in younger than older people. Effective interventions are required to minimize excess mortality in people at high risk of liver fibrosis.

How effective is public health policy in Scotland on vitamin D deficiency during pregnancy?

OBJECTIVE: To evaluate the uptake of universal vitamin D supplementation during pregnancy, its effectiveness in preventing vitamin D deficiency and the factors associated with these. DESIGN: The regional public health organisation in Ayrshire, Scotland has a policy of universal provision of vitamin D supplements (10 µg/d) to all pregnant women for the duration of their pregnancy. Pregnant women in this area were recruited at their 12-week antenatal appointment. Blood samples were collected at the 12-week and 34-week appointments. To account for the seasonal variation, women were recruited in two cohorts: summer and winter. Telephone interviews were conducted at 34 weeks to assess the uptake of vitamin D supplements during pregnancy. Other variables were obtained from medical records. SETTING: The study was conducted in the NHS Ayrshire and Arran Health Board in Scotland. PARTICIPANTS: 612 pregnant women (aged 15-44 years) living in Ayrshire (latitude 55°), Scotland. RESULTS: Sixty-six percentage took supplementation as recommended. Consumption of supplementation was significantly associated with a higher median serum 25-hydroxyvitamin D concentrations at 34 weeks. Despite this at 34 weeks, 33 % of the summer cohort had insufficient or deficient vitamin D status, while 15 % of the winter cohort had insufficient or deficient status. In multivariable analysis, only adherence and season were independent predictors of vitamin D status. CONCLUSIONS: While supplementation improved and maintained vitamin D status during pregnancy, it was not adequate to ensure all those insufficient at 12 weeks achieved sufficient status at the end of pregnancy.

Maximizing donors' gifts: A comparison of actual and expected solid organ yield among VCA donors.

Vascularized Composite Allograft (VCA) transplantation provides life-changing transplants, but VCA adds complexity to the donation process and timing, possibly impeding solid organ donation. Expanding upon descriptive analyses, this study examines risk-adjusted predictions versus the observed number of organs donated by VCA donors. Our cohort included VCA donors in the United States during January 1, 2008-December 31, 2017 (n = 51), using OPTN Deceased Donor Registration Form data and the Scientific Registry of Transplant Recipients (SRTR) donor yield models to calculate observed-to-expected (O:E) yield ratios. Almost all VCA donors' livers (48/51; 94.1%) and kidneys (92/102; 90.2%) were transplanted, with fewer hearts (28/51; 54.9%), lungs (46/102; 45.1%), pancreata (15/51; 29.4%), and intestines (3/51; 5.9%) transplanted. O:E ratios for overall organ yield were slightly greater than expected for VCA donors (1.10; 95% CI: 1.02-1.17). Liver (1.17: 1.08-1.27) and lung yields (1.38: 1.07-1.68) were both greater than expected, while kidney, heart, and pancreas yields were similar to expected. Across VCA types, bilateral upper limb and abdominal wall donors had better-than-expected yields while uterus, face, and unilateral upper limb donors all had similar-to-expected yields. Solid organ yield among VCA donors was as good or better than predicted, suggesting that VCA donation does not compromise recovery and transplantation of lifesaving organs.

Material Properties of the Medial Elbow During Passive Valgus and Self-Initiated Varus Torques.

Shear wave elastography imaging of the ulnar collateral ligament (UCL) is used to help understand changes in material properties of the ligament. Ensuring that the wrist flexors are relaxed is essential as muscle contractions can alter the alignment of the medial elbow. The purpose of this study was to determine how the structural and material properties of the medial elbow respond to various elbow torques. The medial elbows of 20 healthy adults, free from upper extremity disorders, were imaged in 3 of the following torque conditions: (1) neutral relaxed, (2) passive valgus, and (3) active varus. Structural properties (ulnohumeral gap and UCL length) using B-mode and material properties (UCL and flexor muscle stiffness) using shear wave were measured. Passive valgus torque opened the ulnohumeral gap (P < .001), and increased UCL (P < .001) and wrist flexor stiffness (P = .001), compared with the neutral condition. Under an active varus contraction, the gap returned back to the neutral position, but UCL (P < .008) and wrist flexor stiffness (P < .004) remained elevated compared with neutral, meaning low-intensity torques can influence structural and material properties of the medial elbow. Therefore, effort should be taken to minimize muscle activation during imaging in order to accurately measure medial elbow properties.

Scaling PatientsLikeMe via a "Generalized Platform" for Members with Chronic Illness: Web-Based Survey Study of Benefits Arising.

BACKGROUND: Launched in 2006 for patients with amyotrophic lateral sclerosis, PatientsLikeMe is an online community offering patient-reported outcomes, symptom tracking, and social features. Every member of the site can see all the data reported by every other member, view aggregated reports, identify "patients like them," and learn about treatment options in order to live better with their condition. In previous studies, members reported benefits such as improved condition knowledge, increased medication adherence, and better management of side effects. However, the site evolved in 2011 from condition-specific "vertical" communities consisting only of people with the same disease to a "generalized platform," in which every patient could connect with every other patient regardless of condition and with generic, rather than condition-specific, data tools. Some, but not all, communities received further custom tracking tools. OBJECTIVE: We aimed to understand (1) whether members of PatientsLikeMe using the generalized platform still reported similar benefits and (2) assess factors associated with benefits, such as community customization, site use, and patient activation. METHODS: A cross-sectional retrospective custom survey was fielded to 377,625 members between 2016 and 2017 including the Patient Activation Measure (PAM). A benefit index was developed for comparability across conditions. RESULTS: The invitation was viewed by 26,048 members of whom 11,915 did not respond, 5091 opted out, 1591 provided partial data, and 17 were screened out. Complete responses were received from 7434 participants. Users perceived greatest benefit in understanding how their condition may affect them (4530/6770, 66.91% participants, excluding "does not apply" answers), understanding what might help them live better with their condition (4247/6750, 62.92%), which treatments were available (4143/6898, 60.06%), understanding treatment side effects (4182/6902, 60.59%), and important factors in making treatment decisions (3919/6813, 57.52%). The benefit index was 29% higher for the "most activated" patients (PAM level 4 vs PAM level 1; relative risk [RR]=1.29, P<.001), 21% higher for conditions with some community customization versus none (RR=1.21, P<.001), and 11% higher in those using the site most often versus least (RR=1.11, P<.001). CONCLUSIONS: Members of the generalized platform reported a range of benefits related to improved knowledge and understanding of their condition and treatment management. Condition-specific customization may improve their experience still further. Future studies will explore longitudinal changes to patient activation.

SARS-CoV-2 Antibody Serology Testing in a 3-Month-Old Organ Donor: A Case Report and Review of Available Literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a highly prevalent infectious disease. Currently, organs are not being transplanted from donors who are SARS-CoV-2 positive. It remains unclear as to how to differentiate active from recovered patients. We report our recent experience of a 3-month-old deceased organ donor who died as the result of an anoxic brain injury after a cardiopulmonary arrest (presumed sudden infant death syndrome). The child was born to a mother presumed to have coronavirus disease 2019. The donor tested negative for SARS-CoV-2 reverse transcriptase-polymerase chain reaction and positive for SARS-CoV-2 immunoglobulin A antibodies. We suspect this is the first known report of its kind and noteworthy for the organ donation and transplantation community.

Patient perceptions of their glycemic control and its influence on type 2 diabetes outcomes: an international survey of online communities.

PURPOSE: This study aimed to assess awareness of glycated hemoglobin (A1C) testing and targets, perceived level of glycemic control and risk of complications, attitudes toward medications and self-management, and regimen-related distress in an international sample of patients with type 2 diabetes (T2D). METHODS: The descriptive study used a single time-point survey of adults in online health communities in the USA, Canada, the UK, Germany, Spain, and Mexico, who self-reported T2D diagnosed by a physician. RESULTS: In total, 661 patients participated. Awareness of their A1C value at last test varied considerably between countries (42%-89%), as did awareness of having an A1C target (26%- 70%). Self-reported A1C values were similar across US, Canadian, and European respondents (mean, 6.8%-7.3%). Approximately two-thirds of respondents from these countries (66%-71%) reported that their T2D was very or fairly well controlled, and few (5%-15%) expected to experience serious complications within 1 year. However, many respondents expected to experience microvascular (rather than macrovascular) complications in this time frame (eg, nerve pain, 5%-47%). Self-reported adherence to oral medication was generally high, with most respondents (86%-98%) taking their pills or tablets as directed by their healthcare provider, although for insulin injections adherence was lower in the USA (71%) and Mexico (78%) than in the other countries (86%-95%). The majority of respondents across countries (71%-79%) reported that taking injectable medications was not at all or a little burdensome. Respondents across countries appeared to be reasonably confident that they could adequately manage their blood sugar levels; despite this, a sizeable minority (21%-35%) had clinically significant levels of regimen-related distress. CONCLUSION: Limited patient awareness of their A1C value and the potential complications of poorly controlled T2D, particularly regarding cardiovascular complications, may be a widespread problem. Furthermore, greater patient support may be needed to improve self-management of T2D and to reduce regimen-related distress.

Mobility assessment using wearable technology in patients with late-onset Pompe disease.

Late-onset Pompe disease (LOPD) is a rare genetic disorder due to the absence or deficiency of acid alpha-glucosidase enzyme resulting in slowly progressing reduction of muscle strength, causing difficulties with mobility and respiration. Wearable technologies offer novel options to evaluate mobility in a real-world setting. LOPD patients self-reporting LOPD, ≥18 years, US residents, walking (with or without aid), and not on invasive ventilation were recruited for a 6- to 8-week wearable study via patient organizations. Eligible patients were shipped a wearable tracker (Fitbit One™) and completed self-assessment questionnaires. Mobility outcome measures were median step count and peak 1-min activity. In the analyses cohort (N = 29), engagement in data sharing was high (94% of patients uploaded data for more than half the study days). Mean age was 43 years, 90% were females, and 93% were diagnosed in adulthood. Mean delay in diagnosis was 10 years; most had disease onset for ≥10 years (55%); some required walking aid (17%) and breathing assistance (38%). Mean step count differed by age (20-39 years: 4071 vs. 40-69 years: 2394, p < 0.01), diagnostic delay (<10 years: 3584 vs. ≥10 years: 2232, p < 0.05), disease duration (<10 years: 4219 vs. ≥10 years: 2462, p < 0.05), and ambulatory status (aided: 1883 vs. unaided: 3408, p < 0.05). Patient-reported "fatigue and pain" score was inversely correlated with step count (Pearson's r = -0.42, p < 0.05) and peak 1-min activity (Pearson's r = -0.49, p < 0.01). This study illustrates a new approach to measure mobility in LOPD patients and establishes a framework for future outcomes data collection.

Patient Perspective of Cognitive Symptoms in Major Depressive Disorder: Retrospective Database and Prospective Survey Analyses.

BACKGROUND: Major depressive disorder (MDD) is a common and burdensome condition. The clinical understanding of MDD is shaped by current research, which lacks insight into the patient perspective. OBJECTIVE: This two-part study aimed to generate data from PatientsLikeMe, an online patient network, on the perception of cognitive symptoms and their prioritization in MDD. METHODS: A retrospective data analysis (study 1) was used to analyze data from the PatientsLikeMe community with self-reported MDD. Information on patient demographics, comorbidities, self-rated severity of MDD, treatment effectiveness, and specific symptoms of MDD was analyzed. A prospective electronic survey (study 2) was emailed to longstanding and recently active members of the PatientsLikeMe MDD community. Study 1 analysis informed the objectives of the study 2 survey, which were to determine symptom perception and prioritization, cognitive symptoms of MDD, residual symptoms, and medication effectiveness. RESULTS: In study 1 (N=17,166), cognitive symptoms were frequently reported, including "severe" difficulty in concentrating (28%). Difficulty in concentrating was reported even among patients with no/mild depression (80%) and those who considered their treatment successful (17%). In study 2 (N=2525), 23% (118/508) of patients cited cognitive symptoms as a treatment priority. Cognitive symptoms correlated with depression severity, including difficulty in making decisions, concentrating, and thinking clearly (rs=0.32, 0.36, and 0.34, respectively). Cognitive symptoms interfered with meaningful relationships and daily life tasks and had a profound impact on patients' ability to work and recover from depression. CONCLUSIONS: Patients acknowledge that cognitive dysfunction in MDD limits their ability to recover fully and return to a normal level of social and occupational functioning. Further clinical understanding and characterization of MDD for symptom prioritization and relapse risk due to residual cognitive impairment are required to help patients return to normal cognitive function and aid their overall recovery.

Patient attitudes toward and goals for MDD treatment: a survey study.

Background/Objectives: Major depressive disorder (MDD) is a highly prevalent disorder, frequently diagnosed and treated in a primary care setting; however, little information is available about the treatment decision-making process between MDD patients and their providers. A shared decision-making and goal attainment approach to establishing and tracking progress toward treatment goals that are meaningful to individual patients is explored in this survey study. In addition, information about patient perspectives on setting treatment goals, medication selection/switching, and engaging patients with their health care professionals was also collected and evaluated. Methods: A 50-question online survey was administered to members of the PatientsLikeMe community who indicated an MDD diagnosis and a switch in antidepressant medications within the past 2 years. Follow-up interviews were also conducted with a small subset of these participants. Results: Of the 200 participants who completed the survey, 42% reported currently having goals for MDD treatment. These goals were typically in the areas of physical health (62.7%), cognitive functioning (60.2%), and social aspects of life (57.8%). A majority of survey participants (61%) believed the goal attainment approach would be helpful to set and evaluate treatment goals. Conclusions: The data provide important insights into patient perspectives on the development of formal treatment plans and goals for MDD. In addition, the data also support the use of a patient-centric approach to shared decision-making by using a goal attainment scale to establish and track progress toward treatment goals that are meaningful to MDD patients in real-world clinical practice. The results of this study can be used to inform best practices in patient-clinician communication when developing an MDD treatment plan and goals.

Morphodynamic evolution following sediment release from the world's largest dam removal.

Sediment pulses can cause widespread, complex changes to rivers and coastal regions. Quantifying landscape response to sediment-supply changes is a long-standing problem in geomorphology, but the unanticipated nature of most sediment pulses rarely allows for detailed measurement of associated landscape processes and evolution. The intentional removal of two large dams on the Elwha River (Washington, USA) exposed ~30 Mt of impounded sediment to fluvial erosion, presenting a unique opportunity to quantify source-to-sink river and coastal responses to a massive sediment-source perturbation. Here we evaluate geomorphic evolution during and after the sediment pulse, presenting a 5-year sediment budget and morphodynamic analysis of the Elwha River and its delta. Approximately 65% of the sediment was eroded, of which only ~10% was deposited in the fluvial system. This restored fluvial supply of sand, gravel, and wood substantially changed the channel morphology. The remaining ~90% of the released sediment was transported to the coast, causing ~60 ha of delta growth. Although metrics of geomorphic change did not follow simple time-coherent paths, many signals peaked 1-2 years after the start of dam removal, indicating combined impulse and step-change disturbance responses.

Direct Single-Enzyme Biomineralization of Catalytically Active Ceria and Ceria-Zirconia Nanocrystals.

Biomineralization is an intriguing approach to the synthesis of functional inorganic materials for energy applications whereby biological systems are engineered to mineralize inorganic materials and control their structure over multiple length scales under mild reaction conditions. Herein we demonstrate a single-enzyme-mediated biomineralization route to synthesize crystalline, catalytically active, quantum-confined ceria (CeO2-x) and ceria-zirconia (Ce1-yZryO2-x) nanocrystals for application as environmental catalysts. In contrast to typical anthropogenic synthesis routes, the crystalline oxide nanoparticles are formed at room temperature from an otherwise inert aqueous solution without the addition of a precipitant or additional reactant. An engineered form of silicatein, rCeSi, as a single enzyme not only catalyzes the direct biomineralization of the nanocrystalline oxides but also serves as a templating agent to control their morphological structure. The biomineralized nanocrystals of less than 3 nm in diameter are catalytically active toward carbon monoxide oxidation following an oxidative annealing step to remove carbonaceous residue. The introduction of zirconia into the nanocrystals leads to an increase in Ce(III) concentration, associated catalytic activity, and the thermal stability of the nanocrystals.

Intensive care unit extubation does not preclude extrarenal organ recovery from donors after cardiac death.

BACKGROUND: We have sought to increase the utilization of both renal and extrarenal organs from donors after cardiac death (DCD), including DCD donors with ICU extubation. METHODS: Extubation occurred in the intensive care unit (ICU; n=15) and operating room (OR; n=5). The charts of donors were reviewed for demographics, cause of death, time of asystole and cold perfusion. Recipient's charts were reviewed for graft function, length of hospitalization, serum creatinine (Cr) at discharge and last follow-up. Peak transaminases, amylase, and lipase for liver and pancreas recipients were also reviewed. Data are presented as means+/-SEM. RESULTS: From December 2002 until December 2004, 20 DCD donors were utilized yielding 34 kidney transplants (33 recipients), five liver (1 liver-kidney), and two pancreas (SPK) transplants. Mean follow-up overall is 260 days. ICU extubation occurred in 26/33 (78.8%) kidneys, 3/5(60%) livers and 1/2 (50%) pancreata performed. Time from extubation to asystole was 15.9+/-1.9 min and overall warm ischemia time was 12.5+/-1.0 min. Serum Cr at discharge and at last follow-up for renal grafts are 4.3+/-0.5 and 1.9+/-0.3 mg/dl, respectively. Peak AST and ALT levels after OLTx were 3620+/-951 and 1955+/-266 i.u., respectively. Peak and discharge total bilirubin were 8.1+/-0.9 and 2.5+/-0.5 mg/dl. Length of hospitalization was 9.6+/-1.0 and 15.8+/-2.3 days for kidney and liver recipients, respectively. Both pancreas recipients were insulin free after transplant. CONCLUSIONS: ICU extubation should not eliminate extrarenal organs from consideration and may be preferable to OR extubation by improving family support and eliminating OR staff concerns about their role in end-of-life care.