Flux and fluence effects on the vacuum-UV photodesorption and photoprocessing of CO2 ices.

CO2 is a major component of the icy mantles surrounding dust grains in planet and star formation regions. Understanding its photodesorption is crucial for explaining gas phase abundances in the coldest environments of the interstellar medium irradiated by vacuum-UV (VUV) photons. Photodesorption yields determined experimentally from CO2 samples grown at low temperatures (T = 15 K) have been found to be very sensitive to experimental methods and conditions. Several mechanisms have been suggested for explaining the desorption of CO2, O2 and CO from CO2 ices. In the present study, the cross-sections characterizing the dynamics of photodesorption as a function of photon fluence (determined from released molecules in the gas phase) and of ice composition modification (determined in situ in the solid phase) are compared for the first time for different photon flux conditions (from 7.3 × 1012 photon per s cm-2 to 2.2× 1014 photon per s cm-2) using monochromatic synchrotron radiation in the VUV range (on the DESIRS beamline at SOLEIL). This approach reveals that CO and O2 desorptions are decorrelated from that of CO2. CO and O2 photodesorption yields depend on photon flux conditions and can be linked to surface chemistry. In contrast, the photodesorption yield of CO2 is independent of the photon flux conditions and can be linked to bulk ice chemical modification, consistently with indirect desorption induced by an electronic transition (DIET) process.

Socioeconomic representativeness of Australian, Canadian and British cohorts from the paediatric diabetes AdDIT study: comparisons to regional and national data.

BACKGROUND: Given limited data regarding the involvement of disadvantaged groups in paediatric diabetes clinical trials, this study aimed to evaluate the socioeconomic representativeness of participants recruited into a multinational clinical trial in relation to regional and national type 1 diabetes reference populations. METHODS: Retrospective, cross-sectional evaluation of a subset of adolescent type 1 diabetes cardiorenal intervention trial (AdDIT) participants from Australia (n = 144), Canada (n = 312) and the UK (n = 173). Validated national measures of deprivation were used: the Index of Relative Socioeconomic Disadvantage (IRSD) 2016 (Australia), the Material Resources (MR) dimension of the Canadian Marginalisation index 2016 (Canada) and the Index of Multiple Deprivation (IMD) 2015 (UK). Representativeness was assessed by comparing the AdDIT cohort's distribution of deprivation quintiles with that of the local paediatric type 1 diabetes population (regional), and the broader type 1 diabetes population for which the trial's intervention was targeted (national). RESULTS: Recruited study cohorts from each country had higher proportions of participants with higher SES, and significant underrepresentation of lower SES, in relation to their national references. The socioeconomic make-up in Australia mirrored that of the regional population (p = 0.99). For Canada, the 2nd least deprived (p = 0.001) and the most deprived quintiles (p < 0.001) were over- and under-represented relative to the regional reference, while the UK featured higher regional and national SES bias with over-representation and under-representation from the least-deprived and most-deprived quintiles (p < 0.0001). CONCLUSIONS: Significant national differences in trial participation of low SES participants were observed, highlighting limitations in access to clinical research and the importance of reporting sociodemographic representation in diabetes clinical trials. TRIAL REGISTRATION: NCT01581476. Registered on 20 April 2012.

Alcohol use disorder conceptualizations and diagnoses reflect their sociopolitical context.

The present paper highlights how alcohol use disorder (AUD) conceptualizations and resulting diagnostic criteria have evolved over time in correspondence with interconnected sociopolitical influences in the United States. We highlight four illustrative examples of how DSM-defined alcoholism, abuse/dependence, and AUD have been influenced by sociopolitical factors. In doing so, we emphasize the importance of recognizing and understanding such sociopolitical factors in the application of AUD diagnoses. Last, we offer a roadmap to direct the process of future efforts toward the improved diagnosis of AUD, with an emphasis on pursuing falsifiability, acknowledging researchers' assumptions about human behavior, and collaborating across subfields. Such efforts that center the numerous mechanisms and functions of behavior, rather than signs or symptoms, have the potential to minimize sociopolitical influences in the development of diagnostic criteria and maximize the treatment utility of diagnoses.

Risk for Suicidal Behavior After Psychiatric Hospitalization Among Sexual and Gender Minority Patients.

Importance: The months following inpatient psychiatric hospitalization are a period of high risk for suicidal behavior. Sexual and gender minority (SGM) individuals have elevated risk for suicidal behavior, but no prior research has examined whether SGM inpatients have disproportionate risk for suicidal behavior following discharge from psychiatric hospitalization. Objectives: To evaluate whether SGM patients have elevated risk for suicidal behavior following discharge from psychiatric hospitalization compared with heterosexual and cisgender patients and to examine whether differences in risk across groups were accounted for by demographic characteristics and clinical factors known to be associated with suicidal behavior. Design, Setting, and Participants: This prospective cohort study was conducted from August 2017 to July 2021 among inpatients aged 18 to 30 years who were voluntarily enrolled during psychiatric hospitalization. The study was conducted at an inpatient psychiatric hospital, with prospective data collected via follow-up visits and electronic health records. Main Outcomes and Measures: Onset and/or recurrence of suicidal behavior following discharge from psychiatric hospitalization, assessed at follow-up visits and through electronic health records. Results: A total of 160 patients were included, with 56 sexual minority (SM) and 15 gender minority (GM) patients. The median (IQR) age of the patients was 23.5 (20.4-27.6) years, 77 (48%) reported male sex assigned at birth, and 114 (71%) identified their race as White. During the follow-up period, 33 suicidal behavior events occurred (among 21% of patients). SM (hazard ratio [HR], 2.02; 95% CI, CI, 1.02-4.00; log-rank P = .04) and GM (HR, 4.27; 95% CI, 1.75-10.40; log-rank P < .001) patients had significantly higher risk for suicidal behavior compared with their heterosexual and cisgender counterparts, respectively, in bivariable analyses. Risk between SM and heterosexual patients was not different after controlling for demographic characteristics and clinical factors associated with suicidal behavior. GM patients exhibited elevated risk during the 100 days following discharge even after controlling for demographic and clinical characteristics (HR, 3.80; 95% CI, 1.18-11.19; P = .03). Conclusions and Relevance: Within this cohort study of psychiatric patients, SGM patients had higher risk for suicidal behavior than non-SGM patients following discharge. While SM patients' risk was accounted for by clinical characteristics, GM patients' risk for suicidal behavior was not accounted for by their acute psychiatric state on admission. Future studies with larger subsamples of GM individuals are needed, and inpatient clinicians must attend to the unique needs of SGM individuals to ensure they receive affirming services.

Mediating Effects of Technology-Based Therapy on the Relationship Between Socioeconomic Status and Glycemic Management in Pediatric Type 1 Diabetes.

Background: Socioeconomic disparities exist related to accessibility and uptake of diabetes technologies that impact glycemic management. The aims of this study were to describe diabetes technology use (continuous subcutaneous insulin infusion [CSII] and continuous glucose monitoring [CGM]) in children with type 1 diabetes (T1D) and assess the mediating effects of each technology on the relationship between socioeconomic status (SES) and glycemic management. Methods: Single-center retrospective cross-sectional study of children aged 0-18 years (n = 813) with T1D and valid postal codes between 2018 and 2020. Extracted data were linked to validated census-based material deprivation (MD) quintiles. Exposures included MD and technology use (CSII, CGM), whereas the primary outcome was glycemic management (HbA1c). Results: Of 813 patients included, 379 (46.6%) and 246 (30.3%) individuals used CGM and CSII, respectively. Real-time CGM (rtCGM) and CSII were associated with both MD and HbA1c, but intermittently scanned CGM (isCGM) was not. There was a difference in HbA1c of +1.17% between patients from the most (Q5) and least deprived (Q1) MD quintile (P < 0.0001), and significant mediating effects for rtCGM and CSII use, but not isCGM. rtCGM use and CSII use accounted for 0.14% (P < 0.0001) and 0.25% (P < 0.0001) of the difference in HbA1c between patients from Q1 and Q5 quintiles (indirect effects), representing 12.0% and 23.1% of this difference, respectively. Conclusions: CSII and rtCGM use partially mediated the significant discrepancies observed with SES and glycemic management, highlighting potential benefits of broader access to these technologies to improve diabetes outcomes and help mitigate the negative impact of deprivation on diabetes management.

Comparative Effectiveness of Postdischarge Smoking Cessation Interventions for Hospital Patients: The Helping HAND 4 Randomized Clinical Trial.

Importance: Smoking cessation interventions for hospitalized patients must continue after discharge to improve long-term tobacco abstinence. How health systems can best deliver postdischarge tobacco treatment is uncertain. Objective: To determine if health system-based tobacco cessation treatment after hospital discharge produces more long-term tobacco abstinence than referral to a community-based quitline. Design, Setting, and Participants: This randomized clinical trial was conducted September 2018 to November 2020 in 3 hospitals in Massachusetts, Pennsylvania, and Tennessee. Cigarette smokers admitted to a study hospital who received brief in-hospital tobacco treatment and wanted to quit smoking were recruited for participation and randomized for postdischarge treatment to health system-based Transitional Tobacco Care Management (TTCM) or electronic referral to a community-based quitline (QL). Both multicomponent interventions offered smoking cessation counseling and nicotine replacement therapy (NRT) for up to 3 months. Data were analyzed from February 1, 2021, to April 25, 2022. Interventions: TTCM provided 8 weeks of NRT at discharge and 7 automated calls with a hospital-based counselor call-back option. The QL intervention sent referrals from the hospital electronic health record to the state quitline, which offered 5 counseling calls and an NRT sample. Main Outcomes and Measures: The main outcome was biochemically verified past 7-day tobacco abstinence at 6 months. Self-reported point-prevalence and continuous tobacco abstinence and tobacco treatment utilization were assessed 1, 3, and 6 months after discharge. Results: A total of 1409 participants (mean [SD] age, 51.7 [12.6] years; 784 [55.6%] women; mean [SD] 16.4 [10.6] cigarettes/day) were recruited, including 706 randomized to TTCM and 703 randomized to QL. Participants were comparable at baseline, including 216 Black participants (15.3%), 82 Hispanic participants (5.8%), and 1089 White participants (77.3%). At 1 and 3 months after discharge, more TTCM participants than QL participants used cessation counseling (1 month: 245 participants [34.7%] vs 154 participants [21.9%]; 3 months: 248 participants [35.1%] vs 123 participants [17.5%]; P < .001) and pharmacotherapy (1 month: 455 participants [64.4%] vs 324 participants [46.1%]; 3 months: 367 participants [52.0%] vs 264 participants [37.6%]; P < .001). More TTCM than QL participants reported continuous abstinence for 3 months (RR, 1.30; 95% CI, 1.06-1.58) and point-prevalence abstinence at 1 month (RR, 1.22; 95% CI, 1.08-1.35) and 3 months (RR, 1.23; 95% CI, 1.09-1.37) but not at 6 months (RR, 1.14; 95% CI, 0.99-1.29). The primary outcome, biochemically verified point-prevalence abstinence at 6 months, was not statistically significantly different between groups (19.9% vs 16.9%; RR, 1.18; 95% CI, 0.92-1.50). Conclusions and Relevance: In this randomized clinical trial, biochemically verified tobacco abstinence rates were not significantly different between groups at the 6-month follow-up. However, the health system-based model was superior to the community-based quitline model throughout the 3 months of active treatment. A longer duration of postdischarge treatment may sustain the superiority of the health system-based model. Trial Registration: ClinicalTrials.gov Identifier: NCT03603496.

COVID-19 Vaccine Hesitancy, Acceptance, and Promotion Among Healthcare Workers: A Mixed-Methods Analysis.

Even with vaccine mandates, COVID-19 vaccine hesitancy remains a concern among healthcare workers, in part due to their role in promoting vaccination among patients and communities. To examine COVID-19 vaccine hesitancy, acceptance, and promotion among healthcare workers, we conducted a mixed-methods analysis of (1) survey responses about COVID-19 vaccination and (2) Twitter messages (i.e., tweets) relevant to COVID-19 vaccination and healthcare. A total of 540 hospital employees completed the survey. Those that completed less than 80% of the survey or did not endorse employment at the hospital were excluded, resulting in a total of 511 valid responses; 93.2% reported receiving at least one dose of a COVID-19 vaccine. Approximately 1/3 of vaccinated individuals indicated they posted about receiving the vaccine on social media. Simultaneously, we analyzed a sample of 3845 tweets; 2299 (60%) were relevant to COVID-19 vaccination and 1863 (81%) were coded as authored by an individual. Of tweets authored by an individual, 6% (n = 106) were authored by a healthcare provider/health sciences student. Among relevant tweets, the most frequent code across all sentiment categories was related to the pharmaceutical industry (n = 529 tweets, 28%; n = 33, 31% of tweets authored by healthcare workers). Triangulation of results found themes including vaccine access, trust, and vaccine safety or negative health impacts. Results suggest that promoting the sharing of COVID-19 vaccine personal narratives on social media, combined with interventions targeting specific reasons for COVID-19 vaccine hesitancy and emphasizing freedom from fear once vaccinated could be effective at reducing COVID-19 vaccine hesitancy among this population.

Motivational Interviewing Strategies for Addressing COVID-19 Vaccine Hesitancy.

Severe acute respiratory syndrome coronavirus 2, or coronavirus disease 2019 (COVID-19), vaccine hesitancy, defined as a behavioral phenomenon whereby individuals neither fully accept nor fully reject the COVID-19 vaccine, presents a major health threat in the midst of the current pandemic. Traditional approaches for addressing vaccine hesitancy in health care lack empirical support and, in some instances, have actually increased vaccine hesitancy. Thus, there is an urgent need for approaches that effectively address COVID-19 vaccine hesitancy, especially in health care settings. The current article highlights the need for and importance of motivational interviewing (MI), which emphasizes collaborative communication between physicians and patients, in addressing vaccine hesitancy. We describe a 3-step process for addressing COVID-19 vaccine hesitancy that includes using a guiding style, using the MI toolbox, and responding mindfully and skillfully to the individual's degree of hesitancy. The discussion concludes with a consideration of possible challenges in implementing these steps when addressing and resolving COVID-19 vaccine hesitancy.

Gastrointestinal Symptoms in Type 1 Diabetes: Relationship With Autoimmune and Microvascular Complications.

PURPOSE: To assess reported rates of gastrointestinal (GI) symptoms and their association with autoimmune diseases and microvascular complications in adults and children with type 1 diabetes. METHODS: The Gastrointestinal Symptom Scale was used to assess GI symptom type and severity in 2370 patients with type 1 diabetes aged 8 to 45 years evaluated as part of a clinical trial screening for celiac disease (CD). The presence and severity of GI symptoms and relationships with demographic, clinical, and other diabetes-related factors were evaluated. RESULTS: Overall, 1368 adults (57.7%) aged 19 to 45 years and 1002 (42.3%) pediatric patients aged 8 to 18 years were studied. At least 1 GI symptom was reported in 34.1% of adults as compared with 21.7% of children (P < 0.0001). Common symptoms in children included upper and lower abdominal pain while adults more frequently reported lower GI symptoms. Participants with GI symptoms had higher hemoglobin A1c (HbA1c) levels (68 ±â€…14mmol/mol; 8.35 ±â€…1.37%) than those without symptoms (66 ±â€…15mmol/mol; 8.22 ±â€…1.40%; P = 0.041). Patients with microvascular complications (nephropathy, retinopathy, and/or neuropathy) were 1.8 times more likely to report GI symptoms (95% CI: 1.26-2.60; P < 0.01) after adjusting for age and sex. No association was observed between GI symptoms and the presence of autoimmune conditions, including thyroid and biopsy-confirmed CD (odds ratio = 1.1; 95% CI: 0.86-1.42; P = 0.45). MAIN CONCLUSIONS: These results highlight that GI symptoms are an important clinical morbidity and are associated with increasing age, duration of type 1 diabetes, HbA1c, and microvascular complications but not with autoimmune comorbidities including CD.

Characteristics and treatment preferences of individuals with opioid use disorder seeking to transition from buprenorphine to extended-release naltrexone in a residential setting.

BACKGROUND AND OBJECTIVES: Treatment for individuals receiving medication for opioid use disorder (MOUD) should follow an informed patient-centered approach. To better support patient autonomy in the decision-making process, clinicians should be aware of patient preferences and be prepared to educate and assist patients in transitioning from one MOUD to another, when clinically indicated. This posthoc analysis describes the characteristics of clinical trial participants (NCT02696434) with a history of opioid use disorder (OUD) seeking to transition from buprenorphine (BUP) to extended-release naltrexone (XR-NTX). METHODS: The posthoc analysis included adults with OUD currently receiving BUP (≤8 mg/day) and seeking transition to XR-NTX (N = 101) in a residential setting. Baseline participant characteristics and OUD treatment history were reviewed. All patients completed a screening questionnaire that asked about their reasons for seeking transition to XR-NTX and for choosing BUP. RESULTS: The most common reasons for initiating a transition to XR-NTX were "Seeking to be opioid-free" (63.4%) and "Tired of daily pill taking" (25.7%). Positive predictors of transition included a more extensive BUP treatment history and a history of prescription opioid abuse. Most participants stated they were not aware of XR-NTX as a treatment option when initiating BUP (78.2%). DISCUSSIONS AND CONCLUSIONS: Patients' reasons for seeking XR-NTX transition, more extensive BUP treatment history, and a history of prescription opioid abuse, may positively predict outcomes. SCIENTIFIC SIGNIFICANCE: These findings may assist clinicians in optimizing outcomes of the BUP to XR-NTX transition and supporting patients to make better informed MOUD decisions.

Patterns of withdrawal in patients with opioid use disorder (OUD) transitioning from untreated OUD or buprenorphine treatment to extended-release naltrexone.

BACKGROUND: Pharmacologic treatment is recommended for many individuals with opioid use disorder (OUD). For patients who select opioid antagonist treatment, effective management of opioid withdrawal symptoms during transition to antagonist treatment requires consideration of the patient experience. OBJECTIVES: To compare patterns of opioid withdrawal between those withdrawing from untreated opioid use and those withdrawing from buprenorphine. METHODS: We performed a post hoc, cross-study comparison of the temporal pattern of opioid withdrawal during 1-week induction onto extended-release naltrexone by similar protocols enrolling two participant populations: participants with OUD entering a study with untreated opioid use (N = 378, NCT02537574) or on stable buprenorphine (BUP) treatment (N = 101, NCT02696434). RESULTS: The temporal pattern of withdrawal from induction day 1 through day 7 differed between the two participant populations for Clinical Opiate Withdrawal Score (COWS) and Subjective Opiate Withdrawal Score (SOWS): participants with untreated OUD prior to study entry were more likely to experience an earlier relative peak in opioid withdrawal followed by a gradual decline, whereas participants on stable BUP treatment prior to study entry were more likely to experience a relatively later, though still mild, peak opioid withdrawal. The peak COWS was reached at a mean (standard deviation) of 1.9 (1.5) days for participants with untreated OUD and 5.0 (1.5) days for participants on stable BUP. Daily peak cravings were generally higher for participants with untreated OUD than participants on stable BUP. CONCLUSION: Awareness of population-specific variations in the patient experience of opioid withdrawal may help clinicians anticipate the expected course of withdrawal.

Racial inequity in medication treatment for opioid use disorder: Exploring potential facilitators and barriers to use.

BACKGROUND: Despite evidence that individuals with opioid use disorder (OUD) have a lower risk of mortality when using evidence-based medications for OUD (MOUD), only 20 % of people with OUD receive MOUD. Black patients are significantly less likely than White patients to initiate MOUD. We measured the association between various facilitators and barriers to initiation, including criminal justice, human services, and health care factors, and variation in initiation of MOUD by race. METHODS: We used data from a comprehensive, linked data set of health care, human services, and criminal justice programs from Allegheny County in Western Pennsylvania to measure disparities in MOUD initiation by race in the first 180 days after an OUD diagnosis, as well as mediation by potential facilitators and barriers to treatment, among Medicaid enrollees. This is a cross-sectional analysis. RESULTS: Among 6374 Medicaid enrollees who met study criteria, Black enrollees were 18.2 percentage points less likely than White enrollees to start MOUD after controlling for gender, age, and Medicaid eligibility (95 % CI: -21.5 % - -14.8 %). Each day in the emergency department or county jail was associated with a decrease in the likelihood of initiation, as was the presence of a non-OUD substance use disorder diagnosis or participation in intensive non-MOUD treatment. Mediators accounted for approximately one-fifth of the variation in initiation related to race. CONCLUSIONS: Acute care facilities and settings in which people with OUD are incarcerated may have an opportunity to increase the use of MOUD overall and close the racial gap in initiation.

Pathological lesions of the digestive tract in free-ranging mountain gorillas (Gorilla beringei beringei).

The finding of parasites and bacterial pathogens in mountain gorilla feces and oral lesions in gorilla skeletal remains has not been linked to pathological evidence of morbidity or mortality. In the current study, we conducted a retrospective study of digestive tracts including oral cavity, salivary glands, esophagus, stomach, intestines (gastrointestinal tract [GI]), liver, and pancreas of 60 free-ranging mountain gorillas from Uganda, Rwanda, and the Democratic Republic of Congo that died between 1985 and 2007. We reviewed clinical histories and gross pathology reports and examined histological sections. On histology, enteritis (58.6%), gastritis (37.3%), and colitis (29.3%) were the commonest lesions in the tracts. Enteritis and colitis were generally mild, and judged likely to have been subclinical. Gastritis was often chronic and proliferative or ulcerative, and associated with nematodiasis. A gastro-duodenal malignancy (carcinoid) was present in one animal. A number of incidental lesions were identified throughout the tract and cestodes and nematodes were frequently observed grossly and/or histologically. Pigmentation of teeth and tongue were a common finding, but periodontitis and dental attrition were less common than reported from past studies of skeletal remains. Despite observing numerous GI lesions and parasites in this study of deceased free-living mountain gorillas, we confirmed mortality attributable to gastroenteritis in just 8% (5/60) cases, which is less than that described in captive gorillas. Other deaths attributed to digestive tract lesions included cleft palate in an infant, periodontal disease causing systemic infection in an older adult and gastric cancer. Of all the parasitic infections observed, only hepatic capillariasis and gastric nematodiasis were significantly associated with lesions (hepatitis and gastritis, respectively). Understanding GI lesions in this endangered species is key in the management of morbidity associated with GI ailments.

Accuracy of Screening Tests for Celiac Disease in Asymptomatic Patients With Type 1 Diabetes.

INTRODUCTION: To evaluate the diagnostic performance of celiac serologic tests in asymptomatic patients with type 1 diabetes (T1D). METHODS: Patients with T1D asymptomatic for celiac disease were prospectively screened with immunoglobulin A anti-tissue transglutaminase. Test characteristics were calculated and optimal cutoffs for a positive screen determined. RESULTS: Two thousand three hundred fifty-three patients were screened and 101 proceeded to biopsy. The positive predictive value of immunoglobulin A anti-tissue transglutaminase at the assay referenced upper limit of normal (30CU) was 85.9%, and the sensitivity and specificity were 100% and 38%, respectively. DISCUSSION: Thresholds extrapolated from the general population for the diagnostic evaluation of celiac disease are not suitable for use in asymptomatic T1D patients. Population-specific screening cutoffs are required.

Impact of a Gluten-Free Diet on Quality of Life and Health Perception in Patients With Type 1 Diabetes and Asymptomatic Celiac Disease.

CONTEXT: Celiac disease (CD) is a common comorbidity seen in patients with type 1 diabetes (T1D) and is frequently asymptomatic. As chronic conditions requiring significant lifestyle changes, there are limited reports assessing changes in health-related quality of life (HRQoL) during transition to a gluten-free diet (GFD) in patients with T1D who are asymptomatic for CD. OBJECTIVE: This work aims to prospectively assess HRQoL and health perception in children and adults with T1D and asymptomatic CD after random assignment to GFD vs usual diet. METHODS: Patients with T1D aged 8 to 45 years without CD symptoms were serologically screened for CD, with positive results confirmed with intestinal biopsy. Participants were randomly assigned in an open-label fashion to a GFD or gluten-containing diet (GCD) for 12 months. Generic and diabetes-specific HRQoL and self-perceived wellness (SPW) were assessed longitudinally. RESULTS: A total of 2387 T1D patients were serologically screened. CD was biopsy-confirmed in 82 patients and 51 participants were randomly assigned to a GFD (N = 27) or GCD (N = 24). Excellent adherence to the assigned diets was observed. Overall, no changes in generic (P = .73) or diabetes-specific HRQoL (P = .30), or SPW (P = .41) were observed between groups over 12 months. Hemoglobin A1c (HbA1c) and gastrointestinal symptoms were consistent predictors of HRQoL and SPW. CONCLUSION: HRQoL and SPW were not significantly affected by the adoption of a GFD over 12 months, but worsened with symptom onset and increased HbA1c. Our findings indicate that transition to a GFD can be made successfully in this population without adversely affecting quality of life.

Founder Mutation in N Terminus of Cardiac Troponin I Causes Malignant Hypertrophic Cardiomyopathy.

BACKGROUND: Cardiac troponin I (TNNI3) gene mutations account for 3% of hypertrophic cardiomyopathy and carriers have a heterogeneous phenotype, with increased risk of sudden cardiac death (SCD). Only one mutation (p.Arg21Cys) has been reported in the N terminus of the protein. In model organisms, it impairs PKA (protein kinase A) phosphorylation, increases calcium sensitivity, and causes diastolic dysfunction. The phenotype of this unique mutation in patients with hypertrophic cardiomyopathy remains unknown. METHODS: We sequenced 29 families with hypertrophic cardiomyopathy enriched for pediatric-onset disease and identified 5 families with the TNNI3 p.Arg21Cys mutation. Using cascade screening, we studied the clinical phenotype of 57 individuals from the 5 families with TNNI3 p.Arg21Cys-related cardiomyopathy. We performed survival analysis investigating the age at first SCD in carriers of the mutation. RESULTS: All 5 families with TNNI3 p.Arg21Cys were from South Lebanon. TNNI3 p.Arg21Cys-related cardiomyopathy manifested a malignant phenotype-SCD occurred in 30 (53%) of 57 affected individuals at a median age of 22.5 years. In select carriers without left ventricular hypertrophy on echocardiogram, SCD occurred, myocyte disarray was found on autopsy heart, and tissue Doppler and cardiac magnetic resonance imaging identified subclinical disease features such as diastolic dysfunction and late gadolinium enhancement. CONCLUSIONS: The TNNI3 p.Arg21Cys mutation has a founder effect in South Lebanon and causes malignant hypertrophic cardiomyopathy with early SCD even in the absence of hypertrophy. Genetic diagnosis with this mutation may be sufficient for risk stratification for SCD.

Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, N = 1,298] vs. 4.7% [95% CI 3.4-5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI -0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4-2.7; P = 0.014) emerged with a GFD. CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

Assessing Allied Health-Care Professional Time in Pediatric Type 1 Diabetes: Associations With Clinical Factors, Technology and Social Determinants.

OBJECTIVES: The factors associated with allied health-care professional (HCP) time spent face-to-face with patients in clinic have not been well described in type 1 diabetes (T1D) given the introduction of resource-intensive technologies and gaps in socioeconomic circumstances. The objective of this study was to evaluate clinical and social factors associated with nonphysician HCP time in a pediatric T1D practice. METHODS: Nonphysician HCP workload data, including time spent in direct clinical care over a 1-year period and nonclinic contacts, were linked to data from 723 pediatric subjects with T1D and evaluated in relation to key demographic, social and diabetes treatment factors. RESULTS: HCPs spent 145.7 min per patient on a median of 3 clinic visits, with certified diabetes educators (CDEs) being responsible for most clinic interactions compared with psychosocial staff. CDE time varied considerably according to T1D duration, with new-onset patients (≤1 year) taking a median of 392.0 min compared with 114.5 min for their established counterparts (p<0.0001). Among the established group (n=629), CDE time was strongly associated with continuous subcutaneous insulin infusion therapy initiation, psychosocial service use, glycated hemoglobin (A1C) and degree of marginalization (p<0.0001). Overall, CDE time increased by 8.6 min for each 1.0% increase in A1C (p=0.022) and by 16.3 min for each 1-U increase in marginalization (p=0.01). CONCLUSIONS: We observed HCP time was associated with multiple clinical factors in addition to overall marginalization. Although initial investments in education and continuous subcutaneous insulin infusion training were considerable, our results suggest that these lead to a decrease in time spent in clinic over time, and is largely driven by lower A1C.