Impact of preovulatory follicle maturity on oocyte metabolism and embryo development.

Improved oocyte competence for embryo development and pregnancy was observed following ovulation of preovulatory follicles with greater physiological maturity, as indicated by estradiol production, prior to the gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) surge. It was hypothesized that follicular fluid from preovulatory follicles of greater maturity better supports the maturing oocyte's metabolic requirements and improves embryo development. The objective was to determine if differences in preovulatory follicular fluid due to follicle maturity influence oocyte metabolism during in vitro maturation (IVM) and affect embryo development. Bovine preovulatory follicular fluid was collected 18 h after a GnRH-induced LH surge. Serum estradiol concentration at GnRH administration categorized follicles as greater or lesser maturity. Immature bovine oocytes were submitted to 24 h IVM in medium supplemented with 20% follicular fluid from preovulatory follicles of greater or lesser maturity. Embryo development was recorded. Oocyte maturation media and media conditioned by developing embryos were submitted for metabolomics. A randomized block design was utilized to determine differences in embryo development and media metabolites (P ≤ 0.05). Blastocysts from oocytes matured in greater vs. lesser maturity follicular fluid had a more moderate rate of development (P = 0.01). At the conclusion of 24 h IVM, abundance of 66 metabolites differed between greater and lesser follicle maturity treatments. Nine metabolites differed in media conditioned by developing embryos. Metabolome results suggest improved amino acid, purine, and glucose metabolism, followed by a more efficient rate of embryo development, in oocytes matured in greater vs lesser maturity follicular fluid.

Association between monoclonal antibody therapy, vaccination, and longer-term symptom resolution after acute COVID-19.

Effective therapies for reducing post-acute sequelae of COVID-19 (PASC) symptoms are lacking. Evaluate the association between monoclonal antibody (mAb) treatment or COVID-19 vaccination with symptom recovery in COVID-19 participants. The longitudinal survey-based cohort study was conducted from April 2021 to January 2022 across a multihospital Colorado health system. Adults ≥18 years with a positive SARS-CoV-2 test were included. Primary exposures were mAb treatment and COVID-19 vaccination. The primary outcome was time to symptom resolution after SARS-CoV-2 positive test date. The secondary outcome was hospitalization within 28 days of a positive SARS-CoV-2 test. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. COVID-19 vaccination, but not mAb therapy, was associated with a shorter time to symptom resolution. Both were associated with lower 28-day hospitalization.

Neurodevelopmental outcomes at 18 months of children diagnosed with CHD compared to children born very preterm.

OBJECTIVE: To compare neurodevelopmental outcomes and parent behaviour ratings of children born term with CHD to children born very preterm. METHODS: A clinical research sample of 181 children (CHD [n = 81]; very preterm [≤32 weeks; n = 100]) was assessed at 18 months. RESULTS: Children with CHD and born very preterm did not differ on Bayley-III cognitive, language, or motor composite scores, or on expressive or receptive language, or on fine motor scaled scores. Children with CHD had lower ross motor scaled scores compared to children born very preterm (p = 0.047). More children with CHD had impaired scores (<70 SS) on language composite (17%), expressive language (16%), and gross motor (14%) indices compared to children born very preterm (6%; 7%; 3%; ps < 0.05). No group differences were found on behaviours rated by parents on the Child Behaviour Checklist (1.5-5 years) or the proportion of children with scores above the clinical cutoff. English as a first language was associated with higher cognitive (p = 0.004) and language composite scores (p < 0.001). Lower median household income and English as a second language were associated with higher total behaviour problems (ps < 0.05). CONCLUSIONS: Children with CHD were more likely to display language and motor impairment compared to children born very preterm at 18 months. Outcomes were associated with language spoken in the home and household income.

Screening for Anxiety and Depression Symptoms Using Concussion Symptom Scales Among Varsity Athletes.

OBJECTIVE: This study examined associations between Sport Concussion Assessment Tool-5 (SCAT-5) symptom reporting and gold-standard measures of anxiety and depression, and explored the utility SCAT-5 symptom subscales to identify anxiety and depression symptomology. DESIGN: Prospective cross-sectional study. SETTING: York University in Toronto, Canada. PARTICIPANTS: Preseason data were collected for varsity athletes (N = 296) aged between 17 and 25 years ( M = 20.01 years, SD = 1.69 years; 52% male). MAIN OUTCOME MEASURES: The SCAT-5 symptom evaluation scale was used to assess baseline symptoms. The Generalized Anxiety Disorder Index-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess symptoms of anxiety and depression, respectively. RESULTS: Endorsement of SCAT-5 symptoms of feeling anxious, sadness, irritability, and feeling more emotional had the strongest correlations with the GAD-7 ( r' s > 0.400; P' s < 0.001). Sadness, trouble falling asleep, concentration problems, feeling slowed down, anxious, irritability, mental fog, fatigue, and memory problems had the highest correlations with the PHQ-9 ( r' s >0 .400; P' s < 0.001). The Emotional subscale from the SCAT-5 predicted mild to severe anxiety on the GAD-7 ( P < 0.001). The Sleep, Cognitive, and Emotional subscales predicted mild to severe depression on the PHQ-9 ( P' s < 0.05). CONCLUSIONS: These findings provide better delineation of symptoms endorsed on the SCAT-5 symptoms that aid in identification of athletes with symptoms of anxiety or depression who may be at risk for developing a clinical disorder or experiencing persistent symptoms after a concussion.

Social Determinants of Health Screening at an Urban Emergency Department Urgent Care During COVID-19.

INTRODUCTION: Social determinants of health (SDoH) impact patients' health outcomes, yet screening methods in emergency departments (ED) are not consistent or standardized. The SDoH-related health disparities may have widened during the coronavirus 2019 (COVID-19) pandemic, especially among patients who primarily receive their medical care in EDs. We sought to identify SDoH among ED urgent care patients during the COVID-19 pandemic at an urban safety-net hospital, assess the impact of the pandemic on their SDoH, study the feasibility of SDoH screening and resource referrals, and identify preferred methods of resource referrals and barriers to accessing resources. METHODS: Research assistants screened ED urgent care patients using a validated SDoH screener, inquiring about the impact of COVID-19 on their SDoH. A printed resource guide was provided. Two weeks later, a follow-up telephone survey assessed for barriers to resource connection and patients' preferred methods for resource referrals. This study was deemed exempt by our institutional review board. RESULTS: Of the 418 patients presented with a screener, 414 (99.0%) patients completed the screening. Of those screened, 296 (71.5%) reported at least one adverse SDoH, most commonly education (38.7%), food insecurity (35.3%), and employment (31.0%). Housing insecurity was reported by 21.0%. Over half of patients (57.0%) endorsed COVID-19 affecting their SDoH. During follow-up, 156 of 234 (67%) attempted calls were successful and 36/156 (23.1%) reported attempting to connect with a resource, with most attempts made for stable housing (11.0%) and food (7.7%). Reasons for not contacting the provided resources included lack of time (37.8%) and forgetting to do so (26.3%). Patients preferred resource guides to be printed (34.0%) and sent via text message to their mobile devices (25.6%). CONCLUSION: Many urgent care patients of this urban ED reported at least one adverse SDoH, the majority of which were exacerbated by the COVID-19 pandemic. This finding further emphasizes the need to allocate more resources to standardize and expand SDoH screening in EDs. Additionally, hospitals should increase availability of printed or electronic SDoH resource guides, resource navigators, and interpreters both during and after ED visits.

Recent innovations in adaptive trial designs: A review of design opportunities in translational research.

Clinical trials are constantly evolving in the context of increasingly complex research questions and potentially limited resources. In this review article, we discuss the emergence of "adaptive" clinical trials that allow for the preplanned modification of an ongoing clinical trial based on the accumulating evidence with application across translational research. These modifications may include terminating a trial before completion due to futility or efficacy, re-estimating the needed sample size to ensure adequate power, enriching the target population enrolled in the study, selecting across multiple treatment arms, revising allocation ratios used for randomization, or selecting the most appropriate endpoint. Emerging topics related to borrowing information from historic or supplemental data sources, sequential multiple assignment randomized trials (SMART), master protocol and seamless designs, and phase I dose-finding studies are also presented. Each design element includes a brief overview with an accompanying case study to illustrate the design method in practice. We close with brief discussions relating to the statistical considerations for these contemporary designs.

Metabolite abundance in bovine preovulatory follicular fluid is influenced by follicle developmental progression post estrous onset in cattle.

Introduction: Preovulatory follicle response to the luteinizing hormone (LH) surge leads to metabolic, molecular, and functional changes in the oocyte and somatic follicular cells from the onset of estrus to ovulation. Follicular fluid contains metabolites, miRNAs, proteins, and hormones that are byproducts of follicular metabolism and support cellular processes of oocyte, cumulus, and granulosa constituents. Numerous studies have highlighted the importance of follicular fluid composition to support fertility, but critical gaps exist toward understanding dynamic modifications in the follicular fluid metabolome from estrous onset to ovulation. The hypothesis was that abundance of follicular fluid metabolites is dependent on follicle progression post LH surge and variability in follicular fluid metabolome profiles indicate key processes required for preparation of the follicle and oocyte for optimal fertility. The objective was to generate preovulatory follicular fluid metabolome profiles and discern differences in the metabolome of preovulatory follicular fluid samples collected at onset of estrus, 11 h post estrous onset, and 18 h post estrous onset. Methods: Estrus was synchronized in non-lactating Jersey cows (n=40) and follicular fluid was collected immediately after the first observed standing mount (hr 0) or at approximately h 11 or 18 after the first standing mount. Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry was performed on preovulatory follicular fluid samples (n = 9 collected at hr 0, 9 at h 11, and 10 at h 18) and a multiple linear model was performed to determine if time post estrous onset impacted metabolite abundance. Results: Metabolites influenced by time post estrous onset were tested for enrichment in KEGG pathways. Ninety metabolites were identified in follicular fluid samples. Twenty metabolites differed in abundance among timepoints post estrous onset (p ≤ 0.05). Pathways corresponding to amino acid and energy metabolism were enriched with metabolites impacted by time post estrous onset (FDR ≤ 0.10). Discussion: Results from the current study indicate early response to the LH surge to increase bioavailability of amino acids and metabolites used by the cumulus and granulosa cells for energy production and shuttled into the oocyte to support meiotic maturation. Such metabolites may later be used by the ovulatory follicle for protein production.

Siphophage 0105phi7-2 of Bacillus thuringiensis: Novel Propagation, DNA, and Genome-Implied Assembly.

Diversity of phage propagation, physical properties, and assembly promotes the use of phages in ecological studies and biomedicine. However, observed phage diversity is incomplete. Bacillus thuringiensis siphophage, 0105phi-7-2, first described here, significantly expands known phage diversity, as seen via in-plaque propagation, electron microscopy, whole genome sequencing/annotation, protein mass spectrometry, and native gel electrophoresis (AGE). Average plaque diameter vs. plaque-supporting agarose gel concentration plots reveal unusually steep conversion to large plaques as agarose concentration decreases below 0.2%. These large plaques sometimes have small satellites and are made larger by orthovanadate, an ATPase inhibitor. Phage head-host-cell binding is observed by electron microscopy. We hypothesize that this binding causes plaque size-increase via biofilm evolved, ATP stimulated ride-hitching on motile host cells by temporarily inactive phages. Phage 0105phi7-2 does not propagate in liquid culture. Genomic sequencing/annotation reveals history as temperate phage and distant similarity, in a virion-assembly gene cluster, to prototypical siphophage SPP1 of Bacillus subtilis. Phage 0105phi7-2 is distinct in (1) absence of head-assembly scaffolding via either separate protein or classically sized, head protein-embedded peptide, (2) producing partially condensed, head-expelled DNA, and (3) having a surface relatively poor in AGE-detected net negative charges, which is possibly correlated with observed low murine blood persistence.

Implementation of total laparoscopic hysterectomy as day case surgery.

Elective surgeries within the National Health Service are frequently cancelled due to shortages of inpatient beds due to acute emergency admissions, and more recently, the COVID-19 pandemic. The aim of this quality improvement project was to initiate a day case hysterectomy pathway, prospectively collecting data on a group of selected motivated patients to assess its feasibility and safety. Interventions to maximise the chance of same day discharge included preoperative education and hydration, alterations in anaesthetic and surgical techniques and collaborative working between surgeons and recovery nurses to safely discharge patients. In change cycle 1, 93% of patients were discharged on the same day as surgery. In change cycle 2, 100% of patients were discharged on the same day as surgery. In a patient questionnaire, 90% of patients would recommend a day case hysterectomy to their friends or family. Day case hysterectomy was safely introduced to our unit, through leaders actively encouraging contributions and feedback throughout the initiation of the pathway from different components of the multidisciplinary team, from conception to roll out of the guideline for use by other gynaecological surgical teams within the trust.

Fabrication-robust silicon photonic devices in standard sub-micron silicon-on-insulator processes.

Perturbations to the effective refractive index from nanometer-scale fabrication variations in waveguide geometry plague high index-contrast photonic platforms; this includes the ubiquitous sub-micron silicon-on-insulator (SOI) process. Such variations are particularly troublesome for phase-sensitive devices, such as interferometers and resonators, which exhibit drastic changes in performance as a result of these fabrication-induced phase errors. In this Letter, we propose and experimentally demonstrate a design methodology for dramatically reducing device sensitivity to silicon width variations. We apply this methodology to a highly phase-sensitive device, the ring-assisted Mach-Zehnder interferometer (RAMZI), and show comparable performance and footprint to state-of-the-art devices, while substantially reducing stochastic phase errors from etch variations. This decrease in sensitivity is directly realized as energy savings by significantly reducing the required corrective thermal tuning power, providing a promising path toward ultra-energy-efficient large-scale silicon photonic circuits.

Building I-INTERACT-North: Participatory Action Research Design of an Online Transdiagnostic Parent-Child Interaction Therapy Program to Optimize Congenital and Neurodevelopmental Risk.

To adapt an existing virtual family-based mental health intervention learning platform (I-InTERACT-North), using participatory action research design, to meet the needs of parents and children with congenital, neonatal, and neurodevelopmental conditions that impact development. A purposive sample of parent knowledge users recruited from a large pediatric hospital (n = 21) and clinician stakeholders (n = 16) participated in one interview. An iterative process was adopted to implement feedback in the adaption of the learning platform. Qualitative thematic analysis was used to examine themes across participant feedback. Initial satisfaction with the adapted website was high. Qualitative results revealed four themes: acceptability, usability, recommendations, and dissatisfaction. Addressed with iterations, technical difficulties, wanting more information on content, resources, and intended audience were areas of dissatisfaction. This study reflects the importance of participatory action research methods in informing virtual mental health interventions. Future directions to improve the learning platform are discussed.

Intraoperative Embolization during Inferior Vena Cava Tumor Thrombectomy for Renal Cell Carcinoma.

Intraoperative tumor thrombus embolization is a potentially lethal complication during inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC). Intraoperative embolization is uncommonly encountered because IVC thrombectomy surgical technique is focused on avoiding this complication. Nonetheless, early recognition of embolization is essential so that emergent management can be instituted. When available, cardiopulmonary bypass (CPB) and embolectomy should be considered the gold standard for the management of intraoperative embolization. Several novel endovascular techniques are also available for selective use. We present the case of a 71-year-old female with a right renal mass and level II (retrohepatic) IVC tumor thrombus. During cytoreductive nephrectomy and IVC thrombectomy, tumor embolization was diagnosed during a period of hypotension based on transesophageal echocardiographic finding of new thrombus within the right atrium. This prompted sternotomy, CPB, and pulmonary artery embolectomy. The patient survived this embolization event and has a complete response to systemic therapy 9 months postoperatively. This case serves as the framework for a discussion on management considerations surrounding intraoperative embolization during IVC thrombectomy.

"All of the things to everyone everywhere": A mixed methods analysis of community perspectives on equitable access to monoclonal antibody treatment for COVID-19.

BACKGROUND: Neutralizing monoclonal antibody (mAb) treatment for COVID-19 prevents hospitalization and death but is underused, especially in racial/ethnic minority and rural populations. Reasons for underuse and inequity may include community member lack of awareness or healthcare access barriers, among others. This study assessed mAbs community awareness and opportunities for improving equitable mAb access. METHODS: A concurrent mixed methods study including surveys and focus groups with adults with high-risk conditions or their proxy decision-makers. Surveys and focus group guides addressed diffusion of innovation theory factors. Descriptive statistics and Fisher's exact method was used to report and compare survey findings by race and ethnicity. Rapid qualitative methods were used for focus group analysis. RESULTS: Surveys from 515 individuals (460 English, 54 Spanish, 1 Amharic), and 8 focus groups (6 English, 2 Spanish) with 69 participants, completed June 2021 to January 2022. Most survey respondents (75%) had heard little or nothing about mAbs, but 95% would consider getting mAb treatment. Hispanic/Latino and Non-Hispanic People of Color (POC) reported less awareness, greater concern about intravenous infusions, and less trust in mAb safety and effectiveness than White, Non-Hispanic respondents. Focus group themes included little awareness but high interest in mAb treatment and concerns about cost and access barriers such as lacking established sources of care and travel from rural communities. Focus groups revealed preferences for broad-reaching but tailored messaging strategies using multiple media and trusted community leaders. CONCLUSIONS: Despite unfamiliarity with mAb treatment, most respondents were open to receiving mAbs or recommending mAbs to others. While mAb messaging should have broad reach "to everyone everywhere," racial and geographic disparities in awareness and trust about mAbs underscore need for tailored messaging to promote equitable access. Care processes should address patient-level barriers like transportation, insurance, or primary care access. COVID-19 treatment dissemination strategies should promote health equity.

A machine-learning algorithm for diagnosis of multisystem inflammatory syndrome in children and Kawasaki disease in the USA: a retrospective model development and validation study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease that was identified during the COVID-19 pandemic and is characterised by systemic inflammation following SARS-CoV-2 infection. Early detection of MIS-C is a challenge given its clinical similarities to Kawasaki disease and other acute febrile childhood illnesses. We aimed to develop and validate an artificial intelligence algorithm that can distinguish among MIS-C, Kawasaki disease, and other similar febrile illnesses and aid in the diagnosis of patients in the emergency department and acute care setting. METHODS: In this retrospective model development and validation study, we developed a deep-learning algorithm called KIDMATCH (Kawasaki Disease vs Multisystem Inflammatory Syndrome in Children) using patient age, the five classic clinical Kawasaki disease signs, and 17 laboratory measurements. All features were prospectively collected at the time of initial evaluation from patients diagnosed with Kawasaki disease or other febrile illness between Jan 1, 2009, and Dec 31, 2019, at Rady Children's Hospital in San Diego (CA, USA). For patients with MIS-C, the same data were collected from patients between May 7, 2020, and July 20, 2021, at Rady Children's Hospital, Connecticut Children's Medical Center in Hartford (CT, USA), and Children's Hospital Los Angeles (CA, USA). We trained a two-stage model consisting of feedforward neural networks to distinguish between patients with MIS-C and those without and then those with Kawasaki disease and other febrile illnesses. After internally validating the algorithm using stratified tenfold cross-validation, we incorporated a conformal prediction framework to tag patients with erroneous data or distribution shifts. We finally externally validated KIDMATCH on patients with MIS-C enrolled between April 22, 2020, and July 21, 2021, from Boston Children's Hospital (MA, USA), Children's National Hospital (Washington, DC, USA), and the CHARMS Study Group consortium of 14 US hospitals. FINDINGS: 1517 patients diagnosed at Rady Children's Hospital between Jan 1, 2009, and June 7, 2021, with MIS-C (n=69), Kawasaki disease (n=775), or other febrile illnesses (n=673) were identified for internal validation, with an additional 16 patients with MIS-C included from Connecticut Children's Medical Center and 50 from Children's Hospital Los Angeles between May 7, 2020, and July 20, 2021. KIDMATCH achieved a median area under the receiver operating characteristic curve during internal validation of 98·8% (IQR 98·0-99·3) in the first stage and 96·0% (95·6-97·2) in the second stage. We externally validated KIDMATCH on 175 patients with MIS-C from Boston Children's Hospital (n=50), Children's National Hospital (n=42), and the CHARMS Study Group consortium of 14 US hospitals (n=83). External validation of KIDMATCH on patients with MIS-C correctly classified 76 of 81 patients (94% accuracy, two rejected by conformal prediction) from 14 hospitals in the CHARMS Study Group consortium, 47 of 49 patients (96% accuracy, one rejected by conformal prediction) from Boston Children's Hospital, and 36 of 40 patients (90% accuracy, two rejected by conformal prediction) from Children's National Hospital. INTERPRETATION: KIDMATCH has the potential to aid front-line clinicians to distinguish between MIS-C, Kawasaki disease, and other similar febrile illnesses to allow prompt treatment and prevent severe complications. FUNDING: US Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Heart, Lung, and Blood Institute, US Patient-Centered Outcomes Research Institute, US National Library of Medicine, the McCance Foundation, and the Gordon and Marilyn Macklin Foundation.

Acute Effects of Concussion in Adolescent Athletes With High Preseason Anxiety.

OBJECTIVE: To examine associations between pre-existing anxiety symptoms, and symptoms and cognitive functioning acutely following a suspected concussion. DESIGN: Nested case-control study. SETTING: High schools in Maine, USA. PARTICIPANTS: Participants were identified from a dataset of 46 920 student athletes ages 13 to 18 who received baseline preseason testing. A subset of 4732 underwent testing following a suspected concussion. Of those, 517 were assessed within 72 hours after their suspected concussion and met other inclusion criteria. Nineteen injured athletes endorsed anxiety-like symptoms on the Post-Concussion Symptom Scale (PCSS) during baseline testing and were placed in the high anxiety group. Each athlete was matched to 2 injured athletes who did not endorse high levels of anxiety-like symptoms (N = 57). MAIN OUTCOME MEASURES: Immediate Post-Concussion Assessment and Cognitive Testing cognitive composite scores, PCSS total score, and symptom endorsement. RESULTS: Cognitive composite scores were similar between groups across testing times ( = 0.004-0.032). The high anxiety group endorsed a greater number of symptoms than the low anxiety group ( = 0.452) and rated symptoms as more severe ( = 0.555) across testing times. Using a modified symptom score that excluded anxiety-like symptoms, a mixed analysis of variance indicated a group by injury interaction ( = 0.079); the high anxiety group reported greater increases in overall symptom severity following injury. CONCLUSIONS: Adolescent athletes who have an anxious profile at baseline are likely to experience greater symptom burden following injury. Consideration of pre-injury anxiety may inform clinical concussion management by tailoring intervention strategies (eg, incorporating mental health treatments) to facilitate concussion recovery.

Sleep deprivation as a treatment for major depressive episodes: A systematic review and meta-analysis.

Sleep deprivation, alone or in combination with pharmacological treatment and as part of a chronotherapy package, is of potential use for people with major depressive episodes, however the evidence base is still conflicting. The aim of this systematic review and meta-analysis is to assess the clinical effects of sleep deprivation in comparison to any other intervention for the acute and long-term treatment of mood disorders. We searched electronic databases and trial registries (last update: 16th October 2021) for published and unpublished randomised controlled trials recruiting participants with a major depressive episode in unipolar or bipolar affective disorder. The clinical outcomes of interest were the reduction in depressive symptoms at different timepoints and the number of participants experiencing at least one side effect. Overall, 29 trials (1246 participants) were included. We did not find any difference in change in symptoms or all-cause discontinuation between interventions including SD compared to a control of the same intervention except without SD. In the included studies there were no available data for adverse events. Using the most methodologically rigorous approach, we did not find evidence that the addition of sleep deprivation to treatment packages leads to enhanced depressive outcomes.

Epidemiological and Clinical Features of Kawasaki Disease During the COVID-19 Pandemic in the United States.

Importance: Public health measures implemented during the COVID-19 pandemic had widespread effects on population behaviors, transmission of infectious diseases, and exposures to environmental pollutants. This provided an opportunity to study how these factors potentially influenced the incidence of Kawasaki disease (KD), a self-limited pediatric vasculitis of unknown etiology. Objectives: To examine the change in KD incidence across the United States and evaluate whether public health measures affected the prevalence of KD. Design, Setting, and Participants: This multicenter cohort study included consecutive, unselected patients with KD who were diagnosed between January 1, 2018, and December 31, 2020 (multicenter cohort with 28 pediatric centers), and a detailed analysis of patients with KD who were diagnosed between January 1, 2002, and November 15, 2021 (Rady Children's Hospital San Diego [RCHSD]). Main Outcomes and Measures: For the multicenter cohort, the date of fever onset for each patient with KD was collected. For RCHSD, detailed demographic and clinical data as well as publicly available, anonymized mobile phone data and median household income by census block group were collected. The study hypothesis was that public health measures undertaken during the pandemic would reduce exposure to the airborne trigger(s) of KD and that communities with high shelter-in-place compliance would experience the greatest decrease in KD incidence. Results: A total of 2461 KD cases were included in the multicenter study (2018: 894; 2019: 905; 2020: 646), and 1461 cases (median [IQR] age, 2.8 years [1.4-4.9 years]; 900 [61.6%] males; 220 [15.1%] Asian, 512 [35.0%] Hispanic, and 338 [23.1%] White children) from RCHSD between 2002 and 2021 were also included. The 28.2% decline in KD cases nationally during 2020 (646 cases) compared with 2018 (894 cases) and 2019 (905 cases) was uneven across the United States. For RCHSD, there was a disproportionate decline in KD cases in 2020 to 2021 compared with the mean (SD) number of cases in earlier years for children aged 1 to 5 years (22 vs 44.9 [9.9]; P = .02), male children (21 vs 47.6 [10.0]; P = .01), and Asian children (4 vs 11.8 [4.4]; P = .046). Mobility data did not suggest that shelter-in-place measures were associated with the number of KD cases. Clinical features including strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation were decreased during 2020 compared with the baseline period (strawberry tongue: 39% vs 63%; P = .04; enlarged lymph node: 21% vs 32%; P = .09; periungual desquamation: 47% vs 58%; P = .16). School closures, masking mandates, decreased ambient pollution, and decreased circulation of respiratory viruses all overlapped to different extents with the period of decreased KD cases. KD in San Diego rebounded in the spring of 2021, coincident with lifting of mask mandates. Conclusions and Relevance: In this study of epidemiological and clinical features of KD during the COVID-19 pandemic in the United States, KD cases fell and remained low during the period of masking and school closure. Mobility data indicated that differential intensity of sheltering in place was not associated with KD incidence. These findings suggest that social behavior is associated with exposure to the agent(s) that trigger KD and are consistent with a respiratory portal of entry for the agent(s).

Long-term health outcomes in young adults after Kawasaki disease.

Background: We compared the long-term health of adults with prior Kawasaki disease (KD) to controls and determined whether outcomes varied by coronary artery (CA) status. Methods: We conducted a prospective cohort study of 258 KD subjects (mean 19 ± 9 years since KD) and 148 age-similar controls who completed extensive health questionnaires. KD subjects were divided into 2 groups, Cohort 1: 109 subjects followed since KD diagnosis at our institution; Cohort 2: 149 KD subjects diagnosed elsewhere. Results: KD subjects and controls were of similar age at the time of questionnaire completion (p = 0.50). Overall, 128 subjects (including 60 in Cohort 1) reported normal CAs during and after KD. Compared to controls, KD subjects with normal CAs reported several medical conditions with increased prevalence including migraine headaches, shortness of breath, and leg pain with walking, among others. When limited to Cohort 1, KD subjects were significantly more likely to report chest pain (47% vs 16%, p < 0.001) or palpitations (23% vs 10%, p = 0.01) compared to controls. Prevalence of depression was similar (7% vs 5%, p = 0.73). Conclusions: Despite always having normal CAs in the acute and subacute phases of KD, young adults with a history of KD with normal coronaries were more likely than controls to experience cardiovascular symptoms. These differences could be influenced by anxiety or depression, but report of depression was similar between groups. Whether these health differences reflect a heightened awareness of symptoms among KD subjects, or underlying vascular pathology (i.e. vasospasm, microvascular dysfunction, other) merits further study.

Attention and executive control in varsity athletes engaging in strategic and static sports.

Examining non-sport-related cognitive tasks of attention and executive control in skilled athletes may provide insight into the acquisition of highly specific skills developed in experts as well as help identify successful performance in sport. Through a cross-sectional design, this study examined performance on aspects of attention and executive control among varsity athletes playing soccer (strategic sport) or track & field (static sport) using a computerized test of attention and executive control. Ninety-seven university athletes participating in soccer (n = 50) or track and field (n = 47) were included in the study. Domains of attention and executive control were examined using the Attention Network Test-Interactions (ANT-I). Mean reaction time (RT) and intra-individual variability (IIV) were compared between groups as measures of performance speed and performance stability respectively. Soccer players demonstrated overall faster RTs (p = 0.0499; ηp2 = .04) and higher response accuracy (p = .021, d = .48) on the ANT-I compared to track and field athletes. Faster RTs were observed for soccer players when presented with an alerting tone (p = .029, d = .45), valid orienting cue (p = .019, d = .49) and incongruent flanker (p = .031, d = .45). No significant group differences were observed in IIV (p = .083, d = .36). Athletes engaging in strategic sports (i.e., soccer) demonstrated faster performance under test conditions that required higher vigilance and conflict resolution. These findings suggest that engagement in strategic sports is associated with enhanced performance on non-sport-related cognitive tasks of attention and executive control.