Cost-Effectiveness of Closed-Loop Automated Insulin Delivery Using the Cambridge Hybrid Algorithm in Children and Adolescents with Type 1 Diabetes: Results from a Multicenter 6-Month Randomized Trial.

BACKGROUND/OBJECTIVE: The main objective of this study is to evaluate the incremental cost-effectiveness (ICER) of the Cambridge hybrid closed-loop automated insulin delivery (AID) algorithm versus usual care for children and adolescents with type 1 diabetes (T1D). METHODS: This multicenter, binational, parallel-controlled trial randomized 133 insulin pump using participants aged 6 to 18 years to either AID (n = 65) or usual care (n = 68) for 6 months. Both within-trial and lifetime cost-effectiveness were analyzed. Analysis focused on the treatment subgroup (n = 21) who received the much more reliable CamAPS FX hardware iteration and their contemporaneous control group (n = 24). Lifetime complications and costs were simulated via an updated Sheffield T1D policy model. RESULTS: Within-trial, both groups had indistinguishable and statistically unchanged health-related quality of life, and statistically similar hypoglycemia, severe hypoglycemia, and diabetic ketoacidosis (DKA) event rates. Total health care utilization was higher in the treatment group. Both the overall treatment group and CamAPS FX subgroup exhibited improved HbA1C (-0.32%, 95% CI: -0.59 to -0.04; P = .02, and -1.05%, 95% CI: -1.43 to -0.67; P < .001, respectively). Modeling projected increased expected lifespan of 5.36 years and discounted quality-adjusted life years (QALYs) of 1.16 (U.K. tariffs) and 1.52 (U.S. tariffs) in the CamAPS FX subgroup. Estimated ICERs for the subgroup were £19 324/QALY (United Kingdom) and -$3917/QALY (United States). For subgroup patients already using continuous glucose monitors (CGM), ICERs were £10 096/QALY (United Kingdom) and -$33 616/QALY (United States). Probabilistic sensitivity analysis generated mean ICERs of £19 342/QALY (95% CI: £15 903/QALY to £22 929/QALY) (United Kingdom) and -$28 283/QALY (95% CI: -$59 607/QALY to $1858/QALY) (United States). CONCLUSIONS: For children and adolescents with T1D on insulin pump therapy, AID using the Cambridge algorithm appears cost-effective below a £20 000/QALY threshold (United Kingdom) and cost saving (United States).

Cost-effectiveness analysis of individual-level obesity treatment in paediatrics: A scoping review.

OBJECTIVES: This scoping review informs a health economics perspective on the treatment of paediatric obesity. The results detail recently published research findings on the cost-effectiveness of paediatric obesity treatments and identify key characteristics of cost-effective interventions. METHODS: A structured search was applied to six databases with no data restriction through March 2023: Medline, Embase, Cochrane CENTRAL, CINAHL, and PsycINFO. Studies that included a cost analysis of an individual level, weight management intervention (behavioural, pharmacotherapy, and surgical) in youth, with obesity, ages 2 to 21 years were eligible for inclusion. RESULTS: Of the 4371 records identified in the initial search, 353 underwent full-text review, 39 studies met the pre-specified inclusion criteria. The majority were published after 2010 (n = 36/39, 92%) and applied to high-income countries (n = 39/39, 100%). Thirty-five of the studies assessed the cost-effectiveness of lifestyle interventions (90%), and four studies assessed surgical outcomes (10%). No pharmacotherapy studies met eligibility criteria. Although the outcome measures differed across the studies, all four surgical interventions were reported to be cost-effective. Thirty of the 35 (85%) lifestyle modification studies were reported to be cost-effective compared to the study comparator examined. CONCLUSIONS: There is a small amount of evidence that individual-level paediatric obesity treatment interventions are cost-effective and, in some cases cost-saving, with most of this work conducted on behavioural interventions. The economic evaluation of paediatric obesity interventions poses various methodologic challenges, which should be addressed in future research to fully use the potential of economic evaluation as an aid to decision-making.

Modelling structural colour from helicoidal multi-layer thin films with natural disorder.

A coupled mode theory based on Takagi-Taupin equations describing electromagnetic scattering from distorted periodic arrays is applied to the problem of light scattering from beetles. We extend the method to include perturbations in the permittivity tensor to helicoidal arrays seen in many species of scarab beetle and optically anisotropic layered materials more generally. This extension permits analysis of typical dislocations arising from the biological assembly process and the presence of other structures in the elytra. We show that by extracting structural information from transmission electron microscopy data, including characteristic disorder parameters, good agreement with spectral specular and non-specular reflectance measurements is obtained.

A perspective on In vitro developmental neurotoxicity test assay results: An expert panel review.

For decades, there has been increasing concern about the potential developmental neurotoxicity (DNT) associated with chemicals. Regulatory agencies have historically utilized standardized in vivo testing to evaluate DNT. Owing to considerations including higher-throughput screening for DNT, reduction in animal use, and potential cost efficiencies, the development of alternative new approach methods (NAMs) occurred; specifically, the advent of the DNT in vitro test battery (DNT IVB). SciPinion convened an expert panel to address specific questions related to the interpretation of in vitro DNT test data. The consensus of the expert panel was that the DNT IVB might be used during initial screening, but it is not presently a complete or surrogate approach to determine whether a chemical is a DNT in humans. By itself, the DNT IVB does not have the ability to capture nuances and complexity of the developing nervous system and associated outcomes including behavioral ontogeny, motor activity, sensory function, and learning/memory. Presently, such developmental landmarks cannot be adequately assessed in the DNT IVB or by other NAMs. The expert panel (all who serve as co-authors of this review) recommended that additional data generation and validation is required before the DNT IVB can be considered for application within global regulatory frameworks for decision-making.

Virtual Peer Groups Reduce HbA1c and Increase Continuous Glucose Monitor Use in Adolescents and Young Adults with Type 1 Diabetes.

Background: Adolescents and young adults (AYA) from diverse and marginalized backgrounds with type 1 diabetes (T1D) generally have higher hemoglobin A1c (HbA1c) levels and less frequent continuous glucose monitor (CGM) use than AYA from more privileged backgrounds. Further, scant data address the impact of virtual peer groups (VPG) on health-related outcomes for ethnically and racially diverse AYA with T1D. Methods: CoYoT1 to California was a 15-month randomized controlled trial for AYA aged 16-25 years. In this study, AYA were randomized to receive standard care (n = 28), or CoYoT1 care (n = 40), which consisted of person-centered provider visits and bimonthly VPG. VPG were AYA-driven discussions. AYA completed the Diabetes Distress Scale (DDS), Center for Epidemiologic Studies Depression (CES-D), and Diabetes Empowerment Scale-Short Form (DES-SF) scales at baseline and all study visits. Results: Participants were 50% Latinx and 75% publicly insured. Among CoYoT1 care participants, 19 attended at least 1 VPG session (VPG attendees) and 21 did not attend any VPG sessions. VPG attendees participated in 4.1 VPG sessions on average. VPG attendees had a relative reduction in HbA1C (treatment effect -1.08%, effect sizes values [ES] = -0.49, P = 0.04) and increase in CGM use (treatment effect +47%, ES = 1.00, P = 0.02) compared to standard care. VPG participation was not associated with statistically significant changes in DDS, CES-D, and DES-SF scores. Conclusions: In a 15-month randomized controlled trial, AYA with T1D who participated in VPG reported significant improvements in HbA1c and CGM use. Peer interactions may support unmet needs of AYA with T1D from diverse and marginalized backgrounds. ClinicalTrials.gov Identifier: NCT03793673.

Greater Telehealth Use Results in Increased Visit Frequency and Lower Physician Related-Distress in Adolescents and Young Adults With Type 1 Diabetes.

BACKGROUND: Type one diabetes (T1D) management is challenging for adolescents and young adults (AYAs) due to physiological changes, psychosocial challenges, and increasing independence, resulting in increased diabetes distress and hemoglobin A1c (HbA1c). Alternative care models that engage AYAs and improve diabetes-related health outcomes are needed. METHODS: A 15-month study evaluated an adaptation of the Colorado Young Adults with T1D (CoYoT1) Care model. CoYoT1 Care includes person-centered care, virtual peer groups, and physician training delivered via telehealth. AYAs (aged 16-25 years) were partially randomized to CoYoT1 or standard care, delivered via telehealth or in-person. As the study was ending, the COVID-19 pandemic forced all AYAs to transition to primarily telehealth appointments. This secondary analysis compares changes in clinic attendance, T1D-related distress, HbA1c, and device use between those who attended more than 50% of diabetes clinic visits via telehealth and those who attended more sessions in-person throughout the course of the study. RESULTS: Out of 68 AYA participants, individuals (n = 39, 57%) who attended most (>50%) study visits by telehealth completed more diabetes care visits (3.3 visits) than those (n = 29, 43%) who primarily attended visits in-person (2.5 visits; P = .007). AYAs who primarily attended visits via telehealth maintained stable physician-related distress, while those who attended more in-person visits reported increases in physician-related distress (P = .03). CONCLUSIONS: Greater usage of telehealth improved AYA engagement with their care, resulting in increased clinic attendance and reduced physician-related diabetes distress. A person-centered care model delivered via telehealth effectively meets the needs of AYAs with T1D.

An addiction-based digital weight loss intervention: A multi-centre randomized controlled trial.

OBJECTIVE: This randomized clinical trial tested the effectiveness of an addiction-based digital weight-loss intervention, focusing on withdrawal/abstinence from self-identified problem foods, snacking and excessive amounts at meals, and discomfort displacement, with and without coaching, compared to an in-person, multi-disciplinary, care model among adolescents with obesity. We hypothesized that the digital intervention with coaching would yield greater weight loss and lower delivery burden than the standard clinical arm, and greater participant engagement than the digital arm without coaching. METHODS: Adolescents were randomized to app intervention, with or without coaching, or in-person multidisciplinary obesity intervention for 6 months. The primary outcome was change in %BMIp95 at weeks 12 and 24. A mixed-effects linear regression model was used to assess the association between change in %BMIp95 and intervention arm. We were also interested in assessing delivery burden, participant engagement and evaluating the relationships between weight change and demographic characteristics, mood, executive function and eating behaviours. RESULTS: All adolescents (n = 161; BMI ≥95th%, age 16 ± 2.5 year; 47% Hispanic, 65% female, 59% publicly insured) lost weight over 24-weeks (-1.29%, [-1.82, -0.76], p < 0.0001), with no significant weight loss difference between groups (p = 0.3). Girls lost more weight than boys, whereas binge eating behaviour at baseline was associated with increase in %BMIp95 when controlling for other covariates. There was no association between ethnicity, mood, timing of intervention in relation to the pandemic, or executive function and change in %BMIp95 . CONCLUSIONS: Contrary with our hypothesis, our results showed no difference in the change in BMI status between treatment arms. Since efficacy of this digital intervention was not inferior to in-person, multi-disciplinary care, this could offer a reasonable weight management option for clinicians, based on youth and family specific characteristics, such as accessibility, resources, and communication styles. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT035008353.

Lived experience of CamAPS FX closed loop system in youth with type 1 diabetes and their parents.

AIM: To examine changes in the lived experience of type 1 diabetes after use of hybrid closed loop (CL), including the CamAPS FX CL system. MATERIALS AND METHODS: The primary study was conducted as an open-label, single-period, randomized, parallel design contrasting CL versus insulin pump (with or without continuous glucose monitoring). Participants were asked to complete patient-reported outcomes before starting CL and 3 and 6 months later. Surveys assessed diabetes distress, hypoglycaemia concerns and quality of life. Qualitative focus group data were collected at the completion of the study. RESULTS: In this sample of 98 youth (age range 6-18, mean age 12.7 ± 2.8 years) and their parents, CL use was not associated with psychosocial benefits overall. However, the subgroup (n = 12) using the CamAPS FX system showed modest improvements in quality of life and parent distress, reinforced by both survey (p < .05) and focus group responses. There were no negative effects of CL use reported by study participants. CONCLUSIONS: Closed loop use via the CamAPS FX system was associated with modest improvements in aspects of the lived experience of managing type 1 diabetes in youth and their families. Further refinements of the system may optimize the user experience.

Exposure to corticosteroids in the first trimester is associated with an increased risk of urogenital congenital anomalies.

STUDY QUESTION: Does maternal exposure to first trimester corticosteroids in IVF/ICSI treatment result in an increased risk of congenital anomalies? SUMMARY ANSWER: Children born with the aid of IVF/ICSI whose mothers were treated with adjuvant corticosteroids during the first trimester had an increased risk of cryptorchidism, hypospadias and talipes. WHAT IS KNOWN ALREADY: Maternal exposure to corticosteroids may increase the risk of congenital anomalies such as cleft palate and neural tube defects. However, the existing studies have conflicting outcomes, are underpowered, and do not study a population undergoing IVF/ICSI, a group known to be at increased risk of abnormalities. STUDY DESIGN, SIZE, DURATION: This retrospective cohort analysis covering Monash IVF fertility clinics in Melbourne, Australia assessed the outcomes of 12 426 live births from both fresh and frozen embryo transfers between 2010 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 618 live births included in our study group of mothers exposed to corticosteroids (oral prednisolone or dexamethasone) during their IVF/ICSI treatment, with the remainder of births not exposed to steroids (control, n = 11 808). The primary outcome measured was the presence of congenital anomalies and secondary outcomes were birth weight and gestation length. Multivariate binary logistic regression was used to assess the independent effects of corticosteroid exposure and the freezing of embryos, with adjustment for maternal age at oocyte retrieval, smoking status, number of cycles taken, BMI, etiology of the infertility and the use of ICSI. Results are presented as incidence rate ratios (IRRs) with 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE: Amongst 12 426 live births, and 597 birth defects, multivariate logistic regression demonstrated there was an increased incidence in talipes equinovarus (1.33% vs 0.32%, adjusted IRR = 4.30, 95% CI = 1.93, 9.58; P < 0.001), hypospadias (0.66% vs 0.18%, adjusted IRR = 5.90, 95% CI = 2.09, 16.69; P = 0.001) and cryptorchidism (0.83% vs 0.19%, adjusted IRR = 5.53, 95% CI = 1.91, 15.42; P = 0.001) in the offspring of mothers exposed to corticosteroids compared to those who were unexposed. The incidence of neither neural tube defects nor cleft palate were significantly increased in babies exposed to corticosteroids. The sex ratio of infants exposed to corticosteroids during a fresh embryo transfer cycle significantly favored males but reverted to the normal sex ratio in infants conceived in frozen embryo transfer cycles. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective observational cohort study using administrative datasets with the potential for measurement error and unobserved confounding. Missing outcome data were obtained from patients using self-report leading to possible ascertainment bias. Given the rare incidence of some of the anomalies assessed, the study was underpowered to identify differences in abnormality rates for some specific anomalies. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study, the largest of its kind, suggest that caution should be heeded when prescribing corticosteroids to women undergoing IVF/ICSI, given that this study has now identified three previously unassociated serious neonatal complications (talipes, hypospadias and cryptorchidism), plus a potential alteration in sex ratio. Physicians should be careful in using corticosteroids in the critical first trimester and should counsel patients regarding the potential risks of this treatment. STUDY FUNDING/COMPETING INTEREST(S): There was no funding sought or obtained for this study. K.T., V.T., B.V. and D.Z.-F. are employees or contractors to Monash IVF and hold a minority stock position in Monash IVF. R.J.W. reports no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial.

BACKGROUND: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. METHODS: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6-18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0-10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. FINDINGS: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference -3·5 mmol/mol (95% CI -6·5 to -0·5 [-0·32 percentage points, -0·59 to -0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26-53]), but consistently high with CamAPS FX (93% [88-96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. INTERPRETATION: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.

Can a Behavioral Weight-Loss Intervention Change Adolescents' Food Addiction Severity?

Objective: This study examines changes in the Yale Food Addiction Scale symptom count over a 24-week, weight-loss mobile Health (mHealth) intervention incorporating elements of addiction medicine. Methods: Adolescents (n = 117) with obesity (15.5 ± 1.3 years; 66% Hispanic) were randomized to the following: (1) mHealth intervention (AppAlone), (2) mHealth intervention+coaching (AppCoach), or (3) in-person intervention (Control). A multivariate mixed Poisson regression model was used to evaluate changes in symptom counts across intervention arms after adjusting for sex, age, depressive symptomatology, stress, and executive function. Results: After the intervention, 57% of adolescents showed a decrease in symptom count (median change: -0.3 [0 to -1.5]), with a significant change by intervention arm in the intention-to-treat analysis (p = 0.045). There was a positive linear relationship between change in symptom count and change in depressive symptomatology (p < 0.01) and stress (p < 0.01), with no association with change in weight (p = 0.3). Discussion: Both mHealth and in-person obesity interventions seemed to confer benefits in food addiction symptomatology associated with change in mood and stress. Clinical Trial Registration number: NCT035008353.

Clinical aspects and outcomes of patients with malaria at Chris Hani Baragwanath Academic Hospital,Johannesburg, South Africa.

BACKGROUND: South Africa (SA) is currently experiencing a significant increase in malaria cases despite having shifted focus from malaria control towards malaria elimination. The clinical features of malaria are nonspecific, but their relative frequency on presentation are not well described. HIV and malaria are both independently associated with high mortality in sub-Saharan Africa. There are important interactions between HIV and malaria. OBJECTIVES: To describe the population characteristics of patients with malaria at Chris Hani Baragwanath Academic Hospital, Johannesburg, SA, clinical and biochemical features of severity, the proportion of patients with HIV infection, management and outcomes. METHODS: A prospective observational study was conducted whereby patients with a confirmed laboratory diagnosis of malaria were identified, approached and consented for study inclusion over the time period January 2017 - January 2018. Clinical and biochemical data were collected at the time of consent and later analysed. RESULTS: The mean (standard deviation) age was 35.7 (12.98) years, and 72 (70.6%) of the 102 patients were male. Peak admissions for malaria were in January, with 58 patients (56.9%) admitted during January 2017 and 2018. All malaria cases were imported, with 74.5% associated with travel to Mozambique. The majority of the patients (61.8%) were expatriates living in SA. The most common presenting symptoms were chills (95.1%), weakness (94.1%), fever (91.2%), headache (90.2%) and lethargy (88.2%). The most common clinical signs were dehydration (31.4%), prostration (19.6%) and jaundice (13.7%). Among the 40 patients (39.2%) who had severe malaria, prostration was the most common feature of severity (19.6%), 8 (7.8%) were admitted to an intensive care unit, and 6 (5.9%) required haemodialysis. The median (interquartile range) duration of hospital stay was 5 (3 -6) (range 2 - 35) days. HIV status was known in 83 patients (81.4%), of whom 32 (38.6%) were HIV-positive. Malaria prophylaxis had been taken by only 8 patients. The all-cause mortality rate was 4.9%, and mortality attributable to malaria 3.9%. CONCLUSIONS: There was a high proportion of complicated malaria cases, particularly in January. The majority of patients were young expatriate males with a history of travel to southern Mozambique or Limpopo Province, with very few taking malaria prophylaxis. Most clinical signs and symptoms were constitutional and nonspecific. A large number of patients were found to be HIV-positive, and most were newly diagnosed. Mortality was high, at around five times the national average, and may have been an underestimate.

Use of continuous glucose monitoring in obesity research: A scoping review.

BACKGROUND: This scoping review provides a timely synthesis of the use of continuous glucose monitoring in obesity research with considerations to adherence to continuous glucose monitor devices and metrics most frequently reported. METHODS: This scoping review was conducted adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Eligible studies (n = 31) evaluated continuous glucose monitor use in research on participants, of all ages, with overweight or obesity. RESULTS: Reviewed studies varied in duration from one to 84 days (mean: 8.74 d, SD 15.2, range 1-84 d) with 889 participants total (range: 11-118 participants). Across all studies, the mean percent continuous glucose monitor wear time (actual/intended wear time in days) was 92% (numerator - mean: 266.1 d, SD: 452, range: 9-1596 d/denominator - mean: 271.6 d, SD: 451.5, range: 9-1596 d). Continuous glucose monitoring was utilized to provide biofeedback (n = 2, 6%), monitor dietary adherence (n = 2, 6%), and assess glycemic variability (n = 29, 93%). The most common variability metrics reported were standard deviation (n = 19, 62%), area under the curve (n = 12, 39%), and glycemic range (n = 12, 39%). CONCLUSIONS: Available evidence suggests that continuous glucose monitoring is a well-tolerated and versatile tool for obesity research in pediatric and adult patients. Future investigation is needed to substantiate the feasibility and utility of continuous glucose monitors in obesity research and maximize comparability across studies.

Executive Functioning, Depressive Symptoms, and Intervention Engagement in a Sample of Adolescents Enrolled in a Weight Management Program.

Purpose: This study examines how baseline demographics, psychosocial characteristics, and intervention delivery predict engagement among adolescents with overweight and obesity seeking treatment. Methods: Data originates from a multisite randomized control trial evaluating the efficacy of an app-based weight loss intervention, compared with standard in-clinic model in adolescents with overweight and obesity. Participants were randomized to one of the three arms: (1) AppCoach, (2) AppAlone, or (3) Control. Demographic, executive functioning (EF), and depression questionnaires were completed at baseline. Percent engagement was compared within and between groups defined by demographics and depressive symptoms. Quantile regression was used to evaluate the association between age and EF on percent engagement. Results: Baseline demographics were not associated with engagement within or between groups. Neither baseline self-reported depressive symptoms (p = 0.244) nor deficits in EF (p = 0.34) were predictors of engagement. Univariate analysis found that the control arm had the highest engagement (83%) compared with AppCoach (63.5%) and AppAlone (22.5%, p = 0.02). Hispanic ethnicity was predictive of higher engagement in the control arm (p = 0.02). On multivariate quartile regression no other baseline characteristics were significant predictors of engagement. Conclusion: Baseline demographics and individual psychosocial characteristics were not related to engagement in this cohort. The intervention arm that required parental involvement resulted in the greatest engagement suggesting that family involvement may overshadow individual behavioral phenotype and thus promote better engagement. Further investigation is needed to understand how program delivery can be leveraged to optimize treatment engagement and outcomes in adolescence. Clinical Trial Registration number: NCT03500835.

Recent Developments in Species Sensitivity Distribution Modeling.

The species sensitivity distribution (SSD) is a statistical approach that is used to estimate either the concentration of a chemical that is hazardous to no more than x% of all species (the HCx) or the proportion of species potentially affected by a given concentration of a chemical. Despite a significant body of published research and critical reviews over the past 20 yr aimed at improving the methodology, the fundamentals remain unchanged. Although there have been some recent suggestions for improvements to SSD methods in the literature, in general, few of these suggestions have been formally adopted. Furthermore, critics of the approach can rightly point to the fact that differences in technical implementation can lead to marked differences in results, thereby undermining confidence in SSD approaches. Despite the limitations, SSDs remain a practical tool and, until a demonstrably better inferential framework is available, developments and enhancements to conventional SSD practice will and should continue. We therefore believe the time has come for the scientific community to decide how it wants SSD methods to evolve. The present study summarizes the current status of, and elaborates on several recent developments for, SSD methods, specifically, model averaging, multimodality, and software development. We also consider future directions with respect to the use of SSDs, with the ultimate aim of helping to facilitate greater international collaboration and, potentially, greater harmonization of SSD methods. Environ Toxicol Chem 2021;40:293-308. © 2020 SETAC.

Team clinic: Expansion of a multidisciplinary care model for adolescents with type 1 diabetes.

BACKGROUND: Adolescent and young adults (AYA) with Type 1 Diabetes (T1D) experience more difficulty with glycemic control than patients in all other age groups. The shared medical appointment (SMA) model has been effective in multiple healthcare populations, but the feasibility and effectiveness of SMA in AYA patients with T1D is unclear. METHODS: This research leverages the team's multidisciplinary expertise to develop an engaging intervention toolkit and test the implementation of the Team Clinic care model for the treatment of T1D among middle school adolescents in a large urban children's hospital serving an economically, racially and ethnically diverse population. In Phase 1, the team will manualize the Team Clinic care model into an engaging, age-appropriate educational and intervention toolkit. In Phase 2, the team will conduct a randomized clinical trial to test the feasibility and usability of the toolkit from the provider perspective (team member satisfaction; clinical efficiency; compliance with American Diabetes Association, American Association of Diabetes Educators, and California Children's Services standards; and payor-level cost data) and the preliminary efficacy of the intervention toolkit on patient- and family-level outcomes (attendance, acceptability/satisfaction with care, patient-level cost data, diabetes outcomes, diabetes family conflict, diabetes distress, and depression). DISCUSSION: AYA patients with T1D often receive care in clinics and institutions with limited resources and time. This research tests the feasibility and efficacy of an innovative and potentially cost-effective SMA model to address the unique needs of underserved populations, while meeting national and state clinical standards. Trial registration The study is registered with ClinicalTrials.gov (Protocol Record: NCT04190368).

Effect of Continuous Glucose Monitoring on Hypoglycemia in Older Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes. Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes. Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100). Main Outcomes and Measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate. Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8). Conclusions and Relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT03240432.

Real-world evidence on impact of a pharmacist-led transitional care program on 30- and 90-day readmissions after acute care episodes.

PURPOSE: Recent evidence suggests that improving the transitional care process may reduce 30-day readmissions and hospital length of stay (LOS). The objective of this study was to evaluate the impact of a pharmacist-led transitions-of-care (TOC) program on 30- and 90-day all-cause readmissions and LOS for patients discharged from the hospital acute care setting. METHODS: A retrospective cohort study was conducted using a difference-in-difference (DID) approach. Patients who were at least 18 years old with any of the following primary diagnoses were included: acute myocardial infarction, chronic obstructive pulmonary disease, congestive heart failure (CHF), and pneumonia. Outcome measures were all-cause 30- and 90-day readmission and LOS for the index admission. RESULTS: From October 2013 through September 2017, 1,776 patients were discharged from the intervention site, and 2,969 patients were discharged from 3 control sites. Only 33.3% of eligible patients at the intervention site actually received the intervention. The DID analysis showed that the odds ratio (OR) for 30-day readmission was 0.65 [P = 0.035] at the intervention site following TOC program initiation. The OR for 90-day readmission was 0.75 [P = 0.070]. Among all diagnosis groups, the CHF subgroup had the highest proportion of patients who actually received the TOC intervention (57.2%). Within that CHF subgroup, the ORs for 30- and 90-day readmissions were 0.52 [P = 0.056] and 0.47 [P = 0.005], respectively. The mean LOS did not change significantly in either analysis. CONCLUSION: This pharmacist-led transitional care intervention was associated with significantly decreased inpatient readmissions. The analysis indicates that pharmacist interventions can significantly reduce 30-day readmissions for high-risk populations and 90-day readmissions in patients with CHF.

Computed tomography colonography: Radiographer independent preliminary clinical evaluation for intraluminal pathology.

INTRODUCTION: We evaluated the reporting competency of radiographers providing preliminary clinical evaluations (PCE) for intraluminal pathology of computed tomography colonography (CTC). METHOD: Following validation of a suitable tool, audit was undertaken to compare radiographer PCE against radiology reports. A database was designed to capture radiographer and radiologist report data. The radiographer's PCE of intraluminal pathology was given a score, the "pathology discrepancy and significance" (PDS) score based on the pathology present, any discrepancy between the PCE and the final report, and the significance of that discrepancy on the management of the patient. Agreement was assessed using percentage agreement and Kappa coefficient. Significant discrepancies between findings were compared against endoscopy and pathology reports. RESULTS: There was agreement or insignificant discrepancy between the radiographer PCE and the radiology report for 1736 patients, representing 97.0% of cases. There was a significant discrepancy between findings in 2.8% of cases and a major discrepancy recorded for 0.2% of cases. There was a 98.4% agreement in the 229 cases where significant pathologies were present. CONCLUSION: From a database of 1815 studies acquired over three years and representing work done in a clinical environment, this study indicates a potential for trained radiographers to provide a PCE of intraluminal pathology.

Combinations of geoenvironmental data underline coastal aquifer anthropogenic nitrate legacy through groundwater vulnerability mapping methods.

Groundwater quality is strongly dependent on land use. Past and current anthropogenic activities can lead to the diffusion of contaminants in aquifers. This diffusion can threaten the resource exploitation for decades, thereby endangering the ecological health of groundwater dependent ecosystems. Thus, groundwater stakeholders need methods for long-term management which integrate groundwater vulnerability. This study was conducted on the shallow alluvial aquifer of the groundwater-dependent Biguglia lagoon on Corsica Island, France. The aquifer is exposed to anthropogenic contamination for many decades with nitrate contamination legacy linked to agricultural activities, uncontrolled urbanization and sewage leakages. In most cases, vulnerability mapping is done in the objective of comparing groundwater situation regarding an on-going contamination process. But the question is still pending for aquifers where contamination is inherited from past practices or contaminations and where anthropogenic influences have changed through time. To propose an effective and innovative method for territorial management in Mediterranean alluvial aquifers, four index-based groundwater vulnerability mapping methods were tested and compared: two intrinsic vulnerability mapping methods (DRASTIC and SINTACS) and two specific vulnerability mapping methods (Modified-DRASTIC and SI), the latter integrating land use in the accuracy of groundwater vulnerability. Novelty is coming from the comparison between vulnerability maps and their application and validation in a hydrosystem affected by nitrate legacy-type contamination. The specific vulnerability mapping methods are more likely to represent the current pressures to which groundwater are subject. Thus, specific vulnerability methods such as the SI one revealed here very relevant to assess groundwater quality and to react retrospectively. The comparison between groundwater nitrate legacy and intrinsic groundwater vulnerability methods appeared also useful to define priority protection areas in long-term territorial management planning (EU Water Framework Direction). In this sense, the SINTACS method seems to be the more appropriate in the Mediterranean and alluvial context of this study.