Vitamin E improves serum markers and histology in adults with metabolic dysfunction-associated steatotic liver disease: Systematic review and meta-analysis.

BACKGROUND AND AIM: Multiple clinical trials have been conducted to study the potential benefits of vitamin E for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Despite available evidence, vitamin E is not widely used. This study aimed to assess the effect of vitamin E on serum markers of liver inflammation, specifically serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and histology, including resolution of metabolic dysfunction-associated steatohepatitis (MASH), in adult patients with MASLD. METHODS: A systematic literature search on randomized controlled trials published in English was conducted using electronic databases. Standardized mean difference (SMD) and mean difference (MD) were used for continuous outcomes, while risk ratio (RR) was used for dichotomous outcomes, with corresponding 95% confidence interval (CI). RESULTS: A total of eight studies were included in the qualitative synthesis while seven studies were included in the meta-analysis. Vitamin E significantly reduced serum ALT and AST levels with SMD of -0.82 (95% CI, -1.13 to -0.51) and -0.68 (95% CI, -0.94 to -0.41), respectively. Vitamin E significantly reduced steatosis, lobular inflammation, and hepatocyte ballooning with a MD of -0.60 (95% CI, -0.83 to -0.37), -0.34 (95% CI, -0.53 to -0.16), -0.32 (95% CI, -0.53 to -0.12), and increased MASH resolution with a RR of 1.9 (95%CI, 1.20 to 3.02). However, vitamin E did not reduce fibrosis, with a MD of -0.23 (95% CI, -0.51 to 0.05). CONCLUSION: Vitamin E resulted in significant improvement in serum markers of liver inflammation and histology in patients with MASLD.

Risk of renal impairment in atypical antipsychotics: a systematic review and meta-analysis.

PURPOSE: Atypical antipsychotics are associated with several adverse effects including metabolic syndrome, weight gain, QTc interval prolongation, and extrapyramidal effects. This study aims to investigate the risk of renal impairment in patients receiving atypical antipsychotics. METHODS: A systematic literature search was conducted via PubMed and Ovid SP and Web of Science to retrieve studies reporting the risk of renal impairment in patients receiving atypical antipsychotic treatment. The pooled risk ratio (RR) of renal impairment and the subgroup analysis was calculated using the random-effects generic inverse variance method in Cochrane Review Manager. RESULTS: A total of 4 studies involving 514,710 patients (221, 873 patients on atypical antipsychotics/CKD and 292, 837 controls) were included in this meta-analysis. Patients on atypical antipsychotics exhibited an increased risk of renal impairment, with a pooled risk ratio of 1.34 (95%CI 1.23-1.47). Subgroup analysis demonstrated that atypical antipsychotic use was associated with an increased risk of both acute kidney injury (AKI) (RR 1.51, 95%CI 1.34-1.71) and chronic kidney disease (CKD) (RR: 1.23, 95%CI 1.12-1.35). CONCLUSION: Patients receiving atypical antipsychotics have an increased risk of renal impairment. Quetiapine carries the highest risk of renal impairment encompassing both AKI and CKD.

Performance of wearable sleep trackers during nocturnal sleep and periods of simulated real-world smartphone use.

GOAL AND AIMS: To test sleep/wake transition detection of consumer sleep trackers and research-grade actigraphy during nocturnal sleep and simulated peri-sleep behavior involving minimal movement. FOCUS TECHNOLOGY: Oura Ring Gen 3, Fitbit Sense, AXTRO Fit 3, Xiaomi Mi Band 7, and ActiGraph GT9X. REFERENCE TECHNOLOGY: Polysomnography. SAMPLE: Sixty-three participants (36 female) aged 20-68. DESIGN: Participants engaged in common peri-sleep behavior (reading news articles, watching videos, and exchanging texts) on a smartphone before and after the sleep period. They were woken up during the night to complete a short questionnaire to simulate responding to an incoming message. CORE ANALYTICS: Detection and timing accuracy for the sleep onset times and wake times. ADDITIONAL ANALYTICS AND EXPLORATORY ANALYSES: Discrepancy analysis both including and excluding the peri-sleep activity periods. Epoch-by-epoch analysis of rate and extent of wake misclassification during peri-sleep activity periods. CORE OUTCOMES: Oura and Fitbit were more accurate at detecting sleep/wake transitions than the actigraph and the lower-priced consumer sleep tracker devices. Detection accuracy was less reliable in participants with lower sleep efficiency. IMPORTANT ADDITIONAL OUTCOMES: With inclusion of peri-sleep periods, specificity and Kappa improved significantly for Oura and Fitbit, but not ActiGraph. All devices misclassified motionless wake as sleep to some extent, but this was less prevalent for Oura and Fitbit. CORE CONCLUSIONS: Performance of Oura and Fitbit is robust on nights with suboptimal bedtime routines or minor sleep disturbances. Reduced performance on nights with low sleep efficiency bolsters concerns that these devices are less accurate for fragmented or disturbed sleep.

Subtype Identification of Surgically Curable Primary Aldosteronism During Treatment With Mineralocorticoid Receptor Blockade.

BACKGROUND: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment. METHODS: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and ß-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated. RESULTS: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents (P=0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P=0.022) and adrenalectomy (72% versus 54%; P=0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. CONCLUSIONS: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.

Selecting a sleep tracker from EEG-based, iteratively improved, low-cost multisensor, and actigraphy-only devices.

AIMS: Evaluate the performance of 6 wearable sleep trackers across 4 classes (EEG-based headband, research-grade actigraphy, iteratively improved consumer tracker, low-cost consumer tracker). FOCUS TECHNOLOGY: Dreem 3 headband, Actigraph GT9X, Oura Ring Gen3, Fitbit Sense, Xiaomi Mi Band 7, Axtro Fit3. REFERENCE TECHNOLOGY: In-lab polysomnography with 3-reader, consensus sleep scoring. SAMPLE: Sixty participants (26 males) across 3 age groups (18-30, 31-50, and 51-70years). DESIGN: Overnight in a sleep laboratory from habitual sleep time to wake time. CORE ANALYTICS: Discrepancy and epoch-by-epoch analyses for sleep/wake (2-stage) and sleep-stage (4-stage; wake/light/deep/rapid eye movement) classification (devices vs. polysomnography). CORE OUTCOMES: EEG-based Dreem performed the best (2-stage kappa=0.76, 4-stage kappa=0.76-0.86) with the lowest total sleep time, sleep efficiency, sleep onset latency, and wake after sleep onset discrepancies vs. polysomnography. This was followed by the iteratively improved consumer trackers: Oura (2-stage kappa=0.64, 4-stage kappa=0.55-0.70) and Fitbit (2-stage kappa=0.58, 4-stage kappa=0.45-0.60) which had comparable total sleep time and sleep efficiency discrepancies that outperformed accelerometry-only Actigraph (2-stage kappa=0.47). The low-cost consumer trackers had poorest overall performance (2-stage kappa<0.31, 4-stage kappa<0.33). IMPORTANT ADDITIONAL OUTCOMES: Proportional biases were driven by nights with poorer sleep (longer sleep onset latencies and/or wake after sleep onset). CORE CONCLUSION: EEG-based Dreem is recommended when evaluating poor quality sleep or when highest accuracy sleep-staging is required. Iteratively improved non-EEG sleep trackers (Oura, Fitbit) balance classification accuracy with well-tolerated, and economic deployment at-scale, and are recommended for studies involving mostly healthy sleepers. The low-cost trackers, can log time in bed but are not recommended for research use.

Comparison of three analgesic regimens in women undergoing cervical brachytherapy.

PURPOSE: Effective periprocedural analgesia is an important aspect of cervical brachytherapy delivery, with implications for patient comfort and attendance for subsequent fractions. We compared the efficacy and safety of three analgesic modalities: intravenous patient-controlled analgesia (IV-PCA), continuous epidural infusion (CEI) and programmed-intermittent epidural bolus with patient-controlled epidural analgesia (PIEB-PCEA). METHODS AND MATERIALS: Ninety-seven brachytherapy episodes involving 36 patients between July 2016 and June 2019 in a single tertiary center were retrospectively reviewed. Episodes were divided into two key phases: Phase 1 (while applicator remained in situ) and Phase 2 (following applicator removal until discharge or 4 h). For the primary endpoint, pain scores were retrieved and analyzed by analgesic modality with respect to median score and an internally defined "unacceptable" pain experience (>20% of scores being ≥4/10; i.e., moderate or greater). Total nonepidural oral morphine equivalent dose (OMED) and toxicity/complication events were reported as secondary endpoints. RESULTS: In Phase 1, there was a significantly higher median pain score (p < 0.001) and more episodes with unacceptable pain scores (46%) in the IV-PCA group compared with either epidural modality (6-14%; p < 0.001). In Phase 2, we observed a greater median pain score (p = 0.007) and higher proportion of patient episodes with unacceptable pain scores (38%) in the CEI group compared with both the IV-PCA (13%) and PIEB-PCEA (14%) groups (p = 0.001). There was a significant difference in median OMED used throughout all phases across the PIEB-PCEA (0 mg), IV-PCA (70 mg), and CEI (15 mg) groups (p < 0.001). CONCLUSIONS: PIEB-PCEA is safe and offers superior analgesia compared to IV-PCA or CEI for pain control after applicator placement in cervical brachytherapy.

Unilaterally Selective Adrenal Vein Sampling for Identification of Surgically Curable Primary Aldosteronism.

BACKGROUND: Adrenal venous sampling is recommended for the identification of unilateral surgically curable primary aldosteronism but is often clinically useless, owing to failed bilateral adrenal vein cannulation. OBJECTIVES: To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal. METHODS: Among 1625 patients consecutively submitted to adrenal vein sampling in tertiary referral centers, we selected those with selective adrenal vein sampling results in at least one side; we used surgically cured unilateral primary aldosteronism as gold reference. The accuracy of different values of the relative aldosterone secretion index (RASI), which estimates the amount of aldosterone produced in each adrenal gland corrected for catheterization selectivity, was examined. RESULTS: We found prominent differences in RASI values distribution between patients with and without unilateral primary aldosteronism. The diagnostic accuracy of RASI values estimated by the area under receiver operating characteristic curves was 0.714 and 0.855, respectively, in the responsible and the contralateral side; RASI values >2.55 and ≤0.96 on the former and the latter side furnished the highest accuracy for detection of surgically cured unilateral primary aldosteronism. Moreover, in the patients without unilateral primary aldosteronism, only 20% and 16% had RASI values ≤0.96 and >2.55. CONCLUSIONS: With the strength of a large real-life data set and use of the gold reference entailing an unambiguous diagnosis of unilateral primary aldosteronism, these results indicate the feasibility of identifying unilateral primary aldosteronism using unilaterally selective adrenal vein sampling results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01234220.

Saline suppression to distinguish the primary aldosteronism subtype: a diagnostic study.

OBJECTIVES: The saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA), while adrenal vein sampling (AVS) is used to subtype PA as unilateral or bilateral. Criteria that can accurately identify those with bilateral PA based on SST results could reduce the need for AVS. We previously demonstrated that a combination of plasma aldosterone concentration (PAC) < 300 pmol L-1 and a reduction in aldosterone-to-renin ratio (ARR) following recumbent SST had high specificity for predicting bilateral PA in an Australian cohort of 92 patients with PA who have undergone AVS. We sought to validate our predictive criteria in larger, independent cohorts of patients with PA. DESIGN: An international, multi-centre cohort study. METHODS: Data from 55 patients at Monash Health, Victoria, Australia, 106 patients from the First Affiliated Hospital of Chongqing Medical University, China, and 105 patients from Nihon University Itabashi Hospital, Japan were analysed. RESULTS: A combination of PAC <300 pmol L-1 and a reduction in ARR following recumbent SST predicted bilateral PA with specificities of 88.2%, 97.0%, and 100.0% in Australian, Chinese, and Japanese cohorts, respectively. This criterion could allow 22%-38% of patients with PA to bypass AVS and proceed directly to medical treatment. CONCLUSION: In patients undergoing the recumbent SST, a post-saline PAC <300 pmol L-1 together with a reduction in ARR can predict bilateral PA with high specificity and may allow targeted treatment to be commenced without AVS in up to a third of patients.

An automated heart rate-based algorithm for sleep stage classification: Validation using conventional polysomnography and an innovative wearable electrocardiogram device.

Background: The rapid advancement in wearable solutions to monitor and score sleep staging has enabled monitoring outside of the conventional clinical settings. However, most of the devices and algorithms lack extensive and independent validation, a fundamental step to ensure robustness, stability, and replicability of the results beyond the training and testing phases. These systems are thought not to be feasible and reliable alternatives to the gold standard, polysomnography (PSG). Materials and methods: This validation study highlights the accuracy and precision of the proposed heart rate (HR)-based deep-learning algorithm for sleep staging. The illustrated solution can perform classification at 2-levels (Wake; Sleep), 3-levels (Wake; NREM; REM) or 4- levels (Wake; Light; Deep; REM) in 30-s epochs. The algorithm was validated using an open-source dataset of PSG recordings (Physionet CinC dataset, n = 994 participants, 994 recordings) and a proprietary dataset of ECG recordings (Z3Pulse, n = 52 participants, 112 recordings) collected with a chest-worn, wireless sensor and simultaneous PSG collection using SOMNOtouch. Results: We evaluated the performance of the models in both datasets in terms of Accuracy (A), Cohen's kappa (K), Sensitivity (SE), Specificity (SP), Positive Predictive Value (PPV), and Negative Predicted Value (NPV). In the CinC dataset, the highest value of accuracy was achieved by the 2-levels model (0.8797), while the 3-levels model obtained the best value of K (0.6025). The 4-levels model obtained the lowest SE (0.3812) and the highest SP (0.9744) for the classification of Deep sleep segments. AHI and biological sex did not affect scoring, while a significant decrease of performance by age was reported across the models. In the Z3Pulse dataset, the highest value of accuracy was achieved by the 2-levels model (0.8812), whereas the 3-levels model obtained the best value of K (0.611). For classification of the sleep states, the lowest SE (0.6163) and the highest SP (0.9606) were obtained for the classification of Deep sleep segment. Conclusion: The results of the validation procedure demonstrated the feasibility of accurate HR-based sleep staging. The combination of the proposed sleep staging algorithm with an inexpensive HR device, provides a cost-effective and non-invasive solution deployable in the home environment and robust across age, sex, and AHI scores.

Impact of Intraprocedural Sedation on Adrenal Vein Sampling without Corticotropin Stimulation.

See also the editorial by Georgiades in this issue.

Multi-Night at-Home Evaluation of Improved Sleep Detection and Classification with a Memory-Enhanced Consumer Sleep Tracker.

Purpose: To evaluate the benefits of applying an improved sleep detection and staging algorithm on minimally processed multi-sensor wearable data collected from older generation hardware. Patients and Methods: 58 healthy, East Asian adults aged 23-69 years (M = 37.10, SD = 13.03, 32 males), each underwent 3 nights of PSG at home, wearing 2nd Generation Oura Rings equipped with additional memory to store raw data from accelerometer, infra-red photoplethysmography and temperature sensors. 2-stage and 4-stage sleep classifications using a new machine-learning algorithm (Gen3) trained on a diverse and independent dataset were compared to the existing consumer algorithm (Gen2) for whole-night and epoch-by-epoch metrics. Results: Gen 3 outperformed its predecessor with a mean (SD) accuracy of 92.6% (0.04), sensitivity of 94.9% (0.03), and specificity of 78.5% (0.11); corresponding to a 3%, 2.8% and 6.2% improvement from Gen2 across the three nights, with Cohen's d values >0.39, t values >2.69, and p values <0.01. Notably, Gen 3 showed robust performance comparable to PSG in its assessment of sleep latency, light sleep, rapid eye movement (REM), and wake after sleep onset (WASO) duration. Participants <40 years of age benefited more from the upgrade with less measurement bias for total sleep time (TST), WASO, light sleep and sleep efficiency compared to those ≥40 years. Males showed greater improvements on TST and REM sleep measurement bias compared to females, while females benefitted more for deep sleep measures compared to males. Conclusion: These results affirm the benefits of applying machine learning and a diverse training dataset to improve sleep measurement of a consumer wearable device. Importantly, collecting raw data with appropriate hardware allows for future advancements in algorithm development or sleep physiology to be retrospectively applied to enhance the value of longitudinal sleep studies.

Cortical thinning and sleep slow wave activity reductions mediate age-related improvements in cognition during mid-late adolescence.

STUDY OBJECTIVES: Gains in cognitive test performance that occur during adolescence are associated with brain maturation. Cortical thinning and reduced sleep slow wave activity (SWA) are markers of such developmental changes. Here we investigate whether they mediate age-related improvements in cognition. METHODS: 109 adolescents aged 15-19 years (49 males) underwent magnetic resonance imaging, polysomnography (PSG), and a battery of cognitive tasks within a 2-month time window. Cognitive tasks assessed nonverbal intelligence, sustained attention, speed of processing and working memory and executive function. To minimize the effect of sleep history on SWA and cognitive performance, PSG and test batteries were administered only after at least 8 nights of 9-h time-in-bed (TIB) sleep opportunity. RESULTS: Age-related improvements in speed of processing (r = 0.33, p = 0.001) and nonverbal intelligence (r = 0.24, p = 0.01) domains were observed. These cognitive changes were associated with reduced cortical thickness, particularly in bilateral temporoparietal regions (rs = -0.21 to -0.45, ps < 0.05), as well as SWA (r = -0.35, p < 0.001). Serial mediation models found that ROIs in the middle/superior temporal cortices, together with SWA mediated the age-related improvement observed on cognition. CONCLUSIONS: During adolescence, age-related improvements in cognition are mediated by reductions in cortical thickness and sleep SWA.

Reopening after lockdown: the influence of working-from-home and digital device use on sleep, physical activity, and wellbeing following COVID-19 lockdown and reopening.

STUDY OBJECTIVES: COVID-19 lockdowns drastically affected sleep, physical activity, and wellbeing. We studied how these behaviors evolved during reopening the possible contributions of continued working from home and smartphone usage. METHODS: Participants (N = 198) were studied through the lockdown and subsequent reopening period, using a wearable sleep/activity tracker, smartphone-delivered ecological momentary assessment (EMA), and passive smartphone usage tracking. Work/study location was obtained through daily EMA ascertainment. RESULTS: Upon reopening, earlier, shorter sleep and increased physical activity were observed, alongside increased self-rated stress and poorer evening mood ratings. These reopening changes were affected by post-lockdown work arrangements and patterns of smartphone usage. Individuals who returned to work or school in-person tended toward larger shifts to earlier sleep and wake timings. Returning to in-person work/school also correlated with more physical activity. Contrary to expectation, there was no decrease in objectively measured smartphone usage after reopening. A cluster analysis showed that persons with relatively heavier smartphone use prior to bedtime had later sleep timings and lower physical activity. CONCLUSIONS: These observations indicate that the reopening after lockdown was accompanied by earlier sleep timing, increased physical activity, and altered mental wellbeing. Moreover, these changes were affected by work/study arrangements and smartphone usage patterns.

Drug-resistant hypertension in primary aldosteronism patients undergoing adrenal vein sampling: the AVIS-2-RH study.

AIMS: We aimed at determining the rate of drug-resistant arterial hypertension in patients with an unambiguous diagnosis of primary aldosteronism (PA). Moreover, we sought for investigating the diagnostic performance of adrenal vein sampling (AVS), and the effect of adrenalectomy on blood pressure (BP) and prior treatment resistance in PA patients subtyped by AVS in major referral centres. METHODS AND RESULTS: The Adrenal Vein Sampling International Study-2 (AVIS-2) was a multicentre international study that recruited consecutive PA patients submitted to AVS, according to current guidelines, during 15 years. The patients were over 18 years old with arterial hypertension and had an unambiguous diagnosis of PA. The rate of resistant hypertension was assessed at baseline and after adrenalectomy using the American Heart Association (AHA) 2018 definition. Information on presence or absence of resistant hypertension was available in 89% of the 1625 enrolled PA patients. Based on the AHA 2018 criteria, resistant hypertension was found in 20% of patients, of which about two-thirds (14%) were men and one-third (6%) women (χ2 = 17.1, P < 1*10-4) with a higher rate of RH in men than in women (23% vs. 15% P < 1*10-4). Of the 292 patients with resistant hypertension, 98 (34%) underwent unilateral AVS-guided adrenalectomy, which resolved BP resistance to antihypertensive treatment in all. CONCLUSIONS: (i) Resistant hypertension is a common presentation in patients seeking surgical cure of PA; (ii) AVS is key for the optimal management of patients with PA due to resistant hypertension; and (iii) AVS-guided adrenalectomy allowed resolution of treatment-resistant hypertension.

Feasibility of Imaging-Guided Adrenalectomy in Young Patients With Primary Aldosteronism.

Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy. Among 1625 patients with PA submitted to adrenal vein sampling in a multicenter multiethnic international study, 473 were ≤45 years of age; 231 of them had exhaustive imaging and follow-up data. Fifty-three percentage had a unilateral adrenal nodule, 43% had no nodules, and 4% bilateral nodules. Fifty-six percentage (n=131) received adrenalectomy and 128 were unambiguously diagnosed as unilateral PA. A unilateral adrenal nodule on imaging and hypokalemia were the strongest predictors of unilateral PA at regression analysis. Accordingly, imaging allowed correct identification of the responsible adrenal in 95% of the adrenalectomized patients with a unilateral nodule. The rate raised to 100% in the patients with hypokalemia, who comprised 29% of the total, but fell to 88% in those without hypokalemia. Therefore, a unilateral nodule and hypokalemia could be used to identify unilateral PA in patients ≤45 years of age if adrenal vein sampling is not easily available. However, adrenal vein sampling remains indispensable in 71% of the young patients, who showed no nodules/bilateral nodules at imaging and/or no hypokalemia. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.

Identification of Surgically Curable Primary Aldosteronism by Imaging in a Large, Multiethnic International Study.

CONTEXT: Adrenal gland imaging is recommended by the current guidelines for the workup of primary aldosteronism (PA). However, its diagnostic performance has not been established in large, multiethnic cohorts of patients who undergo adrenal vein sampling (AVS) and adrenalectomy. OBJECTIVE: This work aims to assess the diagnostic accuracy of cross-sectional adrenal imaging. METHODS: This international multicenter study took place in tertiary referral centers. A total of 1625 PA patients seeking surgical cure were enrolled in an international study involving 19 centers in North America, Europe, Asia, and Australia. Of these, 1311 (81%) had imaging data available and 369 (23%), who received a final diagnosis of surgically cured unilateral PA, were examined. Patients underwent AVS and imaging by computed tomography and/or magnetic resonance imaging. The accuracy of detection of unilateral PA at imaging was estimated by the area under the receiver operator characteristics curve using cure (biochemical and/or full clinical success) as the reference at follow-up after unilateral adrenalectomy. RESULTS: In the cohort of 1311 patients with imaging data available, 34% and 7% of cases showed no detectable or bilateral nodules, respectively. Imaging did not detect the culprit adrenal in 28% of the surgically cured unilateral PA patients. Moreover, the clinical outcome did not differ significantly between the imaging-positive and imaging-negative patients. CONCLUSION: Cross-sectional imaging did not identify a lateralized cause of disease in around 40% of PA patients and failed to identify the culprit adrenal in more than one-fourth of patients with unilateral PA.

Trait-like nocturnal sleep behavior identified by combining wearable, phone-use, and self-report data.

Using polysomnography over multiple weeks to characterize an individual's habitual sleep behavior while accurate, is difficult to upscale. As an alternative, we integrated sleep measurements from a consumer sleep-tracker, smartphone-based ecological momentary assessment, and user-phone interactions in 198 participants for 2 months. User retention averaged >80% for all three modalities. Agreement in bed and wake time estimates across modalities was high (rho = 0.81-0.92) and were adrift of one another for an average of 4 min, providing redundant sleep measurement. On the ~23% of nights where discrepancies between modalities exceeded 1 h, k-means clustering revealed three patterns, each consistently expressed within a given individual. The three corresponding groups that emerged differed systematically in age, sleep timing, time in bed, and peri-sleep phone usage. Hence, contrary to being problematic, discrepant data across measurement modalities facilitated the identification of stable interindividual differences in sleep behavior, underscoring its utility to characterizing population sleep and peri-sleep behavior.

Multi-Night Validation of a Sleep Tracking Ring in Adolescents Compared with a Research Actigraph and Polysomnography.

BACKGROUND: Wearable devices have tremendous potential for large-scale longitudinal measurement of sleep, but their accuracy needs to be validated. We compared the performance of the multisensor Oura ring (Oura Health Oy, Oulu, Finland) to polysomnography (PSG) and a research actigraph in healthy adolescents. METHODS: Fifty-three adolescents (28 females; aged 15-19 years) underwent overnight PSG monitoring while wearing both an Oura ring and Actiwatch 2 (Philips Respironics, USA). Measurements were made over multiple nights and across three levels of sleep opportunity (5 nights with either 6.5 or 8h, and 3 nights with 9h). Actiwatch data at two sensitivity settings were analyzed. Discrepancies in estimated sleep measures as well as sleep-wake, and sleep stage agreements were evaluated using Bland-Altman plots and epoch-by-epoch (EBE) analyses. RESULTS: Compared with PSG, Oura consistently underestimated TST by an average of 32.8 to 47.3 minutes (Ps < 0.001) across the different TIB conditions; Actiwatch 2 at its default setting underestimated TST by 25.8 to 33.9 minutes. Oura significantly overestimated WASO by an average of 30.7 to 46.3 minutes. It was comparable to Actiwatch 2 at default sensitivity in the 6.5, and 8h TIB conditions. Relative to PSG, Oura significantly underestimated REM sleep (12.8 to 19.5 minutes) and light sleep (51.1 to 81.2 minutes) but overestimated N3 by 31.5 to 46.8 minutes (Ps < 0.01). EBE analyses demonstrated excellent sleep-wake accuracies, specificities, and sensitivities - between 0.88 and 0.89 across all TIBs. CONCLUSION: The Oura ring yielded comparable sleep measurement to research grade actigraphy at the latter's default settings. Sleep staging needs improvement. However, the device appears adequate for characterizing the effect of sleep duration manipulation on adolescent sleep macro-architecture.

Memory performance following napping in habitual and non-habitual nappers.

STUDY OBJECTIVES: Afternoon naps benefit memory but this may depend on whether one is a habitual napper (HN; ≥1 nap/week) or non-habitual napper (NN). Here, we investigated whether a nap would benefit HN and NN differently, as well as whether HN would be more adversely affected by nap restriction compared to NN. METHODS: Forty-six participants in the nap condition (HN-nap: n = 25, NN-nap: n = 21) took a 90-min nap (14:00-15:30 pm) on experimental days while 46 participants in the Wake condition (HN-wake: n = 24, NN-wake: n = 22) remained awake in the afternoon. Memory tasks were administered after the nap to assess short-term topographical memory and long-term memory in the form of picture encoding and factual knowledge learning respectively. RESULTS: An afternoon nap boosted picture encoding and factual knowledge learning irrespective of whether one habitually napped (main effects of condition (nap/wake): ps < 0.037). However, we found a significant interaction for the hippocampal-dependent topographical memory task (p = 0.039) wherein a nap, relative to wake, benefitted habitual nappers (HN-nap vs HN-wake: p = 0.003) compared to non-habitual nappers (NN-nap vs. NN-wake: p = 0.918). Notably for this task, habitual nappers' performance significantly declined if they were not allowed to nap (HN-wake vs NN-wake: p = 0.037). CONCLUSIONS: Contrary to concerns that napping may be disadvantageous for non-habitual nappers, we found that an afternoon nap was beneficial for long-term memory tasks even if one did not habitually nap. Naps were especially beneficial for habitual nappers performing a short-term topographical memory task, as it restored the decline that would otherwise have been incurred without a nap. CLINICAL TRIAL INFORMATION: NCT04044885.