Branched-chain α-ketoacid dehydrogenase deficiency (maple syrup urine disease): Treatment, biomarkers, and outcomes.

Over the past three decades, we studied 184 individuals with 174 different molecular variants of branched-chain α-ketoacid dehydrogenase activity, and here delineate essential clinical and biochemical aspects of the maple syrup urine disease (MSUD) phenotype. We collected data about treatment, survival, hospitalization, metabolic control, and liver transplantation from patients with classic (i.e., severe; n = 176), intermediate (n = 6) and intermittent (n = 2) forms of MSUD. A total of 13,589 amino acid profiles were used to analyze leucine tolerance, amino acid homeostasis, estimated cerebral amino acid uptake, quantitative responses to anabolic therapy, and metabolic control after liver transplantation. Standard instruments were used to measure neuropsychiatric outcomes. Despite advances in clinical care, classic MSUD remains a morbid and potentially fatal disorder. Stringent dietary therapy maintains metabolic variables within acceptable limits but is challenging to implement, fails to restore appropriate concentration relationships among circulating amino acids, and does not fully prevent cognitive and psychiatric disabilities. Liver transplantation eliminates the need for a prescription diet and safeguards patients from life-threatening metabolic crises, but is associated with predictable morbidities and does not reverse pre-existing neurological sequelae. There is a critical unmet need for safe and effective disease-modifying therapies for MSUD which can be implemented early in life. The biochemistry and physiology of MSUD and its response to liver transplantation afford key insights into the design of new therapies based on gene replacement or editing.

Video Telehealth Access and Changes in HbA1c Among People With Diabetes.

INTRODUCTION: Video telehealth can offer people convenient, real-time access to clinicians without arranging transportation or time off work. Among people with diabetes, this study examines the association between video telehealth access and changes in HbA1c. METHODS: This longitudinal cohort study (2016-2019) used linear regression with person-level fixed effects, stratified by baseline HbA1c (last value in 2015), to examine the association between video visit access and changes in HbA1c. HbA1c values were categorized into 3 periods of video visit exposure: (1) before any video visit, (2) during video visit transition year (calendar year of the first video visit), and (3) after video visits. The model compared changes in HbA1c values collected before the patient had any video visits with those collected after the transition year. Analyses were conducted in September 2020. RESULTS: Among 204,301 people with diabetes, video visit access was associated with a statistically significant reduction of 0.15 (95% CI= -0.19, -0.11) percentage points in HbA1c, with greater reductions among patients with an elevated baseline HbA1c value (-0.22 percentage points, 95% CI= -0.32, -0.11) and with no baseline HbA1c measurement (-0.39 percentage points, 95% CI= -0.71, -0.07). CONCLUSIONS: Gaining access to video telehealth was associated with reductions in HbA1c among people with diabetes. Video telehealth offers people with chronic conditions a new, convenient way to access health care, is not associated with worsening HbA1c, and may support better disease management, particularly among patients with higher baseline HbA1c.

Poor performance on cognitive tasks in depression: Doing too much or not enough?

Depressed people perform poorly on cognitive tasks. It is unclear whether these deficits are due to decreased devotion of task-related resources or to increased attention to non-task-related information. In the present study, we examined the degree to which depressed and healthy adults displayed pupillary motility that varied at the frequency of presented stimuli on a cognitive task, which we interpreted as task-related processing, and at other frequencies, which we interpreted as reflecting intrinsic processing. Depressed participants made more consecutive errors than did controls. More pupillary motility at other frequencies was associated with poorer performance, whereas more pupillary motility at the frequency of presented stimuli was associated with better performance. Depressed participants had more pupillary motility at other frequencies, which partially mediated observed deficits in cognitive performance. These findings support the hypothesis that allocating cognitive resources to intrinsic processing contributes to observed cognitive deficits in depression.

Association of Mobile Patient Portal Access With Diabetes Medication Adherence and Glycemic Levels Among Adults With Diabetes.

Importance: Online patient portals support self-management, and mobile devices expand portal access, but whether this translates to improvements in diabetes outcomes is unclear. Objective: To examine the association of adding mobile patient portal access with diabetes medication adherence and glycemic levels among adults with diabetes. Design, Setting, and Participants: This retrospective cohort study included patients with diabetes treated at Kaiser Permanente Northern California, a large, integrated health care delivery system, from April 1, 2015, to December 31, 2017. Inclusion criteria were adults with diabetes with an oral diabetes prescription at baseline and no insulin use. Data were analyzed from March 2018 to March 2019. Exposures: Patient portal access status for each calendar month from April 2015 to December 2017, categorized as never used, used from a computer only, used from a mobile device only, or used from both computer and mobile device. Main Outcomes and Measures: Medication adherence, measured by monthly percentage of days covered (PDC), and glycemic levels, measured by changes in glycated hemoglobin A1c (HbA1c) levels. The association of portal access with study outcomes was assessed using linear regression with patient-level fixed effects and adjusting for time-changing variables, stratified by baseline HbA1c level. Results: Among 111 463 included patients (mean [SD] age, 63.79 [12.93] years; 59 918 [53.76%] men), the number of patients using the portal from both a computer and mobile device increased over time from 38 371 patients (34.42%) in April 2015 to 57 920 patients (61.71%) in December 2017. Among patients with no prior portal access, adding computer-only portal access was associated with an increase in PDC of 1.16 (95% CI, 0.63 to 1.70) percentage points and a change of -0.06 (95% CI, -0.08 to -0.03) percentage points in HbA1c level, and adding both mobile and computer portal access was associated with an increase in PDC of 1.67 (95% CI, 1.10 to 2.23) percentage points and a change of -0.13 (95% CI, -0.16 to -0.10) percentage points in HbA1c level. Among patients with higher baseline HbA1c level (>8.0%), changing from no portal access to both computer and mobile access was associated with an increase in PDC of 5.09 (95% CI, 3.78 to 6.40) percentage points and a change of -0.19 (95% CI, -0.27 to -0.15) percentage points in HbA1c level. Conclusions and Relevance: These findings suggest that providing patients with computer patient portal access and combining it with mobile patient portal access are associated with significantly improved diabetes medication adherence and glycemic control, with greater benefits among patients with more clinical need. Convenient access to portal self-management tools through a mobile device could significantly improve diabetes management.

Biochemical correlates of neuropsychiatric illness in maple syrup urine disease.

Maple syrup urine disease (MSUD) is an inherited disorder of branched chain amino acid metabolism presenting with neonatal encephalopathy, episodic metabolic decompensation, and chronic amino acid imbalances. Dietary management enables survival and reduces risk of acute crises. Liver transplantation has emerged as an effective way to eliminate acute decompensation risk. Psychiatric illness is a reported MSUD complication, but has not been well characterized and remains poorly understood. We report the prevalence and characteristics of neuropsychiatric problems among 37 classical MSUD patients (ages 5-35 years, 26 on dietary therapy, 11 after liver transplantation) and explore their underlying mechanisms. Compared with 26 age-matched controls, MSUD patients were at higher risk for disorders of cognition, attention, and mood. Using quantitative proton magnetic resonance spectroscopy, we found lower brain glutamate, N-acetylaspartate (NAA), and creatine concentrations in MSUD patients, which correlated with specific neuropsychiatric outcomes. Asymptomatic neonatal course and stringent longitudinal biochemical control proved fundamental to optimizing long-term mental health. Neuropsychiatric morbidity and neurochemistry were similar among transplanted and nontransplanted MSUD patients. In conclusion, amino acid dysregulation results in aberrant neural networks with neurochemical deficiencies that persist after transplant and correlate with neuropsychiatric morbidities. These findings may provide insight into general mechanisms of psychiatric illness.