Internalizing Psychiatric Symptoms in People with Mosaicism for Trisomy 21.

People with mosaicism for trisomy 21 have been shown to exhibit the many of same phenotypic traits present in people with non-mosaic Down syndrome, but with varying symptom severity. However, the behavioral phenotype of people with mosaic Down syndrome (mDS) has not been well characterized. This study aimed to examine the prevalence of self-report and caregiver-report symptoms of depression and anxiety among a sample of 62 participants with mDS aged 12 - 46, and assess their association with the percentage of trisomy 21 in blood and/or buccal mucosa cells. The results showed that 53% of the participants reported clinically significant depression symptoms and 76% reported clinically significant anxiety symptoms. No clear associations were observed between the percentage of trisomic cells and total anxiety or depression, but a significant positive association between the proband-reported specific fears subscale and the percentage of trisomic cells in buccal specimens was detected (r = .43, p = .007). This study highlights the high occurrence of depression and anxiety symptoms in individuals with mDS and the need for routine assessment to optimize their care. It also demonstrates the ability of people with mDS to complete these evaluations, thereby supporting their inclusion in research studies/clinical trials.

Confidence of Emergency Department doctors in managing ophthalmic emergencies: a systematic review.

BACKGROUND: Eye emergencies constitute a significant portion of attendances to general Emergency Departments (EDs) in the UK, therefore it is important to assess the confidence of doctors who work in this setting in managing these potentially sight- and life-threatening presentations. This systematic review aims to assess the confidence of UK doctors working in general EDs in managing ophthalmic emergencies. METHODS: MEDLINE (Ovid), EMBASE (Ovid), ProQuest Central and Web of Science databases and grey literature were searched from inception to 1 October 2022 for publications that (1) featured doctors working in UK general EDs, (2) assessed doctors' confidence in managing ophthalmic emergencies, (3) contained original data, (4) were full-text, and (5) written in English. Methodological quality was assessed using the AXIS tool. RESULTS: 462 articles were screened, and 7 papers included for data extraction, which collectively assessed the confidence of 956 doctors working in EDs in managing ophthalmic emergencies. There was a widespread lack of confidence amongst foundation doctors, which has worsened over time. Most doctors lacked confidence in performing funduscopy and using the slit-lamp, and considered formal ophthalmology training received in EDs to be inadequate. CONCLUSIONS: Evidence suggests a lack of confidence amongst foundation doctors in managing ophthalmic emergencies. High-quality evidence investigating the confidence amongst more experienced Emergency Medicine (EM) physicians was lacking. It is important to assess why foundation doctors feel so ill-prepared to manage eye emergencies and develop further ophthalmic training for doctors working in EDs. Further investigation exploring the confidence of EM trainees and consultants is required.

Factors Associated With Attainment of Glycemic Targets Among Adults With Type 1 and Type 2 Diabetes in Canada: A Cross-sectional Study Using Primary and Specialty Care Electronic Medical Record Data.

OBJECTIVE: Using a new database combining primary and specialty care electronic medical record (EMR) data in Canada, we determined attainment of glycemic targets and associated predictors among adults with diabetes. METHODS: We conducted a cross-sectional observational study combining primary and specialty care EMR data in Canada. Adults with diabetes whose primary care provider contributed to the National Diabetes Repository or who were assessed at a diabetes specialty clinic (LMC Diabetes and Endocrinology) between July 3, 2015, and June 30, 2019, were included. Diabetes type was categorized as type 2 diabetes (T2D) not prescribed insulin, T2D prescribed insulin, and type 1 diabetes (T1D). Covariates were age, sex, income quintile, province, rural/urban location, estimated glomerular filtration rate, medications, and insulin pump use. Associations between predictors and the outcome (glycated hemoglobin [A1C] of ≤7.0%) were assessed by multivariable logistic regressions. RESULTS: Among 122,106 adults, consisting of 91,366 with T2D not prescribed insulin, 25,131 with T2D prescribed insulin, and 5,609 with T1D, attainment of an A1C of ≤7.0% was 60%, 25%, and 23%, respectively. Proportions with an A1C of ≤7.5% and ≤8.0% were 75% and 84% for those with T2D not prescribed insulin, 41% and 57% for those with T2D prescribed insulin, and 37% and 53% for those with T1D. Highest vs lowest income quintile was associated with greater odds of meeting the A1C target (adjusted odds ratio [95% confidence interval] for each diabetes category: 1.15 [1.10 to 1.21], 1.21 [1.10 to 1.33], and 1.29 [1.04 to 1.60], respectively). Individuals in Alberta and Manitoba had less antihyperglycemic medication use and attainment of A1C target than other provinces. CONCLUSIONS: Attainment of glycemic targets among adults with diabetes was poor and differed by income and geographic location, which must be addressed in national diabetes strategies.

Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.

Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.

Predicting Participation Willingness in Ecological Momentary Assessment of General Population Health and Behavior: Machine Learning Study.

BACKGROUND: Ecological momentary assessment (EMA) is widely used in health research to capture individuals' experiences in the flow of daily life. The majority of EMA studies, however, rely on nonprobability sampling approaches, leaving open the possibility of nonrandom participation concerning the individual characteristics of interest in EMA research. Knowledge of the factors that predict participation in EMA research is required to evaluate this possibility and can also inform optimal recruitment strategies. OBJECTIVE: This study aimed to examine the extent to which being willing to participate in EMA research is related to respondent characteristics and to identify the most critical predictors of participation. METHODS: We leveraged the availability of comprehensive data on a general young adult population pool of potential EMA participants and used and compared logistic regression, classification and regression trees, and random forest approaches to evaluate respondents' characteristic predictors of willingness to participate in the Decades-to-Minutes EMA study. RESULTS: In unadjusted logistic regression models, gender, migration background, anxiety, attention deficit hyperactivity disorder symptoms, stress, and prosociality were significant predictors of participation willingness; in logistic regression models, mutually adjusting for all predictors, migration background, tobacco use, and social exclusion were significant predictors. Tree-based approaches also identified migration status, tobacco use, and prosociality as prominent predictors. However, overall, willingness to participate in the Decades-to-Minutes EMA study was only weakly predictable from respondent characteristics. Cross-validation areas under the curve for the best models were only in the range of 0.56 to 0.57. CONCLUSIONS: Results suggest that migration background is the single most promising target for improving EMA participation and sample representativeness; however, more research is needed to improve prediction of participation in EMA studies in health.

Immunotherapy responsiveness and risk of relapse in Down syndrome regression disorder.

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9-12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, P = 0.001), abnormal MRI (χ2 = 7.78, P = 0.005), and abnormal LP (χ2 = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.

Respondent characteristics associated with adherence in a general population ecological momentary assessment study.

OBJECTIVES: Ecological momentary assessment (EMA) has seen an explosion in popularity in recent years; however, an improved understanding of how to minimise (selective) non-adherence is needed. METHODS: We examined a range of respondent characteristics predictors of adherence (defined as the number of EMA surveys completed) in the D2M EMA study. Participants were a sample of n = 255 individuals drawn from the longitudinal z-proso cohort who completed up to 4 EMA surveys per day for a period of 2 weeks. RESULTS: In unadjusted analyses, lower moral shame, lower self-control, lower levels of self-injury, and higher levels of aggression, tobacco use, psychopathy, and delinquency were associated with lower adherence. In fully adjusted analyses with predictors selected using lasso, only alcohol use was related to adherence: beer and alcopops to higher adherence and spirits to lower adherence. CONCLUSIONS: These findings provide potential insights into some of the psychological mechanisms that may underlie adherence in EMA. They also point to respondent characteristics for which additional or tailored efforts may be needed to promote adherence.

Exploring the effect of ADHD traits on the moment-to-moment interplay between provocation and aggression: Evidence from dynamic structural equation modeling.

The relation between attention deficit hyperactivity disorder (ADHD) symptoms and aggression is well documented; however, the processes that account for higher levels of aggression associated with ADHD in the course of daily life are little understood. The current study used ecological momentary assessment to explore how ADHD traits relate to individual differences in perceiving provocation from others and the resultant aggressive behaviors; and the strengths of the links between provocation and aggression in the flow of daily life. A dynamic structural equation model was fit using data from a subpopulation of young adults involved in the longitudinal z-proso study (n = 259, median-age 20). Data on provocation and aggression was collected at four quasi-random time periods per day over a 14-day period. Individuals with higher ADHD trait levels reported higher instances of provocation and aggression, with ADHD traits significantly moderating aggression inertia such that those with higher levels of ADHD traits showed greater persistence of aggressive behavior over time. However, ADHD trait levels did not significantly moderate any of the observed cross-lagged effects. Our findings suggest that individuals with higher levels of ADHD traits are at greater risk of exposure to interpersonal interactions involving interpersonal provocation, show higher levels of aggressive behavior in daily life, and find it more difficult to reduce their aggression once triggered. These findings support the importance of targeting factors such as social skills and emotion regulation that may underpin the increased difficulties in interpersonal interactions often experienced by individuals with high levels of ADHD symptoms.

Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder.

Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean off therapy after 9-12 months of treatment. Baseline, on therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, p = 0.001), abnormal MRI (χ2 = 7.78, p = 0.005), and abnormal LP (χ2 = 5.45, p = 0.02), and a personal history of autoimmunity (OR: 6.11, p < 0.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.

Psychometric evaluation of an adapted version of the perceived stress scale for ecological momentary assessment research.

Ecological momentary assessment (EMA) methodologies are commonly used to illuminate the predictors and impacts of experiencing subjective stress in the course of daily life. The validity of inferences from this research is contingent on the availability of measures of perceived momentary stress that can provide valid and reliable momentary stress scores. However, studies of the development and validation of such measures have been lacking. In this study, we use an EMA data collection design to examine the within- and between- person reliability and criterion validity and between-person gender measurement invariance of a brief EMA-adapted measure of a widely used trait measure of stress: the Perceived Stress Scale (PSS). Scores showed high internal consistency reliability and significant correlations with a range of criterion validity measures at both the within- and between-person level. Gender measurement invariance up to the scalar level also held for scores. Findings support the use of the EMA-adapted PSS presented in the current study for use in community-ascertained samples to address research questions relating to the influences on and effects of momentary stress and their gender differences.

The role of moment-to-moment dynamics of perceived stress and negative affect in co-occurring ADHD and internalising symptoms.

A maladaptive response to stress in individuals with high ADHD traits may be a key factor explaining co-occurring ADHD symptoms and internalising problems. The current study investigates whether between-person differences in ADHD traits are associated with differences in the within-person moment-to-moment coupling of stress and negative affect; and whether these can explain between-person differences in internalising problems (N = 262, median-age 20). Results of a dynamic structural equation model indicated that between-person differences in ADHD traits significantly moderated the daily life coupling between stress and negative affect. Further, higher ADHD traits were associated with stronger stress carry-over and higher mean levels of negative affect. Stress carry-over and mean levels of negative affect mediated the association between ADHD traits and internalising problems.

IMpact of flash glucose Monitoring in pEople with type 2 Diabetes Inadequately controlled with non-insulin Antihyperglycaemic ThErapy (IMMEDIATE): A randomized controlled trial.

AIM: To examine the efficacy and patient satisfaction of intermittently scanned continuous glucose monitoring (isCGM) in adults using non-insulin therapies for the management of type 2 diabetes. MATERIALS AND METHODS: The IMMEDIATE study was a multisite, open label, randomized controlled trial with follow-up at 16 weeks. Adults with type 2 diabetes using at least one non-insulin therapy, with an HbA1c of 7.5% or higher (≥ 58 mmol/mol), were randomized 1:1 to receive an isCGM device plus diabetes self-management education (isCGM + DSME) or DSME alone. Enrolment occurred from 8 September 2020 to 24 December 2021. The primary outcome was percentage mean time in range (TIR), in the final 2-week period, measured via blinded CGM. RESULTS: One hundred and sixteen participants were randomized (mean age, 58 years; diabetes duration, 10 years; mean HbA1c, 8.6% [70 mmol/mol]). At 16 weeks of follow-up, the isCGM and DSME arm had a significantly greater mean TIR by 9.9% (2.4 hours) (95% CI, -17.3% to -2.5%; P < .01), significantly less time above range by 8.1% (1.9 hours) (95% CI, 0.5% to 15.7%; P = .037), and a greater reduction in mean HbA1c by 0.3% (3 mmol/mol) (95% CI, 0% to 0.7%; P = .048) versus the DSME arm. Time below range was low and not significantly different between groups and hypoglycaemic events were few in both groups. Glucose monitoring satisfaction was higher among isCGM users (adjusted difference -0.5 [95% CI, -0.7 to -0.3], P < .01). CONCLUSIONS: The IMMEDIATE study has shown that among non-insulin-treated individuals with type 2 diabetes, use of isCGM is associated with an improvement in glycaemic outcomes.

Prompt-level predictors of compliance in an ecological momentary assessment study of young adults' mental health.

BACKGROUND: Ecological momentary assessment (EMA) has become a popular method of gathering information about participants as they go about their daily lives. However, participant non-compliance, especially non-random compliance, in EMA is a concern. Better knowledge of the moment-to-moment factors that predict prompt non-response can inform the design of strategies to mitigate it. METHOD: We used data from a general population young adult (n = 260) EMA study, 'decades-to-minutes' (D2M) and fitted dynamic structural equation models (DSEMs) to explore a range of candidate momentary predictors of missing the next prompt. RESULTS: We found that higher levels of stress, overall negative affect, and the specific negative affective state of 'upset' at a given prompt predicted a greater likelihood of missing the next prompt. However, no other specific affective states, alcohol use, experiencing social provocations nor aggressive behaviour predicted missing the next prompt. LIMITATIONS: The primary limitation of the present study was a lack of information on predictors concurrent with missed prompts. CONCLUSIONS: Findings point to the potential value of gathering information on momentary negative affect (especially feeling upset) and stress to help inform strategies that intervene to prevent application disengagement at optimal moments and to feed into strategies to mitigate bias due to non-random non-response in EMA studies.

Phenotypic continuum of NFU1-related disorders.

Bi-allelic variants in Iron-Sulfur Cluster Scaffold (NFU1) have previously been associated with multiple mitochondrial dysfunctions syndrome 1 (MMDS1) characterized by early-onset rapidly fatal leukoencephalopathy. We report 19 affected individuals from 10 independent families with ultra-rare bi-allelic NFU1 missense variants associated with a spectrum of early-onset pure to complex hereditary spastic paraplegia (HSP) phenotype with a longer survival (16/19) on one end and neurodevelopmental delay with severe hypotonia (3/19) on the other. Reversible or irreversible neurological decompensation after a febrile illness was common in the cohort, and there were invariable white matter abnormalities on neuroimaging. The study suggests that MMDS1 and HSP could be the two ends of the NFU1-related phenotypic continuum.

Real-world glycaemic outcomes in adult persons with type 1 diabetes using a real-time continuous glucose monitor compared to an intermittently scanned glucose monitor: A retrospective observational study from the Canadian LMC diabetes registry (REAL-CGM-T1D).

Real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM) have both been shown to improve glycaemic outcomes in people with T1D. The aim of this study was to compare real-world glycaemic outcomes at 6-12 months in a propensity score matched cohort of CGM naïve adults with T1D who initiated a rtCGM or an isCGM. Among the matched rtCGM and isCGM cohorts (n = 143/cohort), rtCGM users had a significantly greater HbA1c benefit compared to isCGM users (adjusted difference, -3 mmol/mol [95% CI, -5 to -1]; -0.3% [95% CI, -0.5 to -0.1]; p = 0.01). There was a significantly greater lowering of HbA1c for rtCGM compared to isCGM when baseline HbA1c was <69 mmol/mol (8.5%) (adjusted difference, -4 mmol/mol [95% CI, -7 mmol/mol to -2 mmol/mol]; -0.4% [95% CI, -0.6% to -0.2%]; p < 0.001), and in MDI users (adjusted difference, -3 mmol/mol [95% CI, -6 mmol/mol to -0 mmol/mol]; -0.3% [95% CI -0.5% to 0.0%], p = 0.04). The rtCGM cohort had significantly greater time in range (58.3 ± 16.1% vs. 54.5 ± 17.1%, p = 0.03), lower time below range (2.1 ± 2.7% vs. 6.1 ± 5.0%, p < 0.001) and lower glycaemic variability compared to the isCGM cohort. In this real-world analysis of adults with T1D, rtCGM users had a significantly greater reduction in HbA1c at 6-12 months compared to isCGM, and significantly greater time in range, lower time below range and lower glycaemic variability, compared to a matched cohort of isCGM users.

Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus.

Objective: To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome. Background: There are no consensus criteria for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets. Lack of standardized assessment tools has slowed research in this clinical area. Methods: The authors performed a two-round traditional Delphi method survey of an international group of clinicians with experience in treating Down syndrome to develop a standardized approach to clinical care and research in this area. Thirty-eight potential panelists who had either previously published on neurocognitive regression in Down syndrome or were involved in national or international working groups on this condition were invited to participate. In total, 27 panelists (71%) represented nine medical specialties and six different countries reached agreement on preliminary standards in this disease area. Moderators developed a proposed nomenclature, diagnostic work up and diagnostic criteria based on previously published reports of regression in persons with Down syndrome. Results: During the first round of survey, agreement on nomenclature for the condition was reached with 78% of panelists agreeing to use the term Down Syndrome Regression Disorder (DSRD). Agreement on diagnostic work up and diagnostic criteria was not reach on the first round due to low agreement amongst panelists with regards to the need for neurodiagnostic testing. Following incorporation of panelist feedback, diagnostic criteria were agreed upon (96% agreement on neuroimaging, 100% agreement on bloodwork, 88% agreement on lumbar puncture, 100% agreement on urine studies, and 96% agreement on "other" studies) as were diagnostic criteria (96% agreement). Conclusions: The authors present international consensus agreement on the nomenclature, diagnostic work up, and diagnostic criteria for DSRD, providing an initial practical framework that can advance both research and clinical practices for this condition.