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Approximately, 1.7 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). This has disproportionately impacted adults, but many children have been infected and hospitalised as well. To date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here, we share the approach to the cardiac workup and monitoring utilised at a large congenital heart centre in New York City, the epicentre of the COVID-19 pandemic in the United States.
While negative affect reliably predicts binge eating, it is unknown how this association may decrease or ‘de-couple’ during treatment for binge eating disorder (BED), whether such change is greater in treatments targeting emotion regulation, or how such change predicts outcome. This study utilized multi-wave ecological momentary assessment (EMA) to assess changes in the momentary association between negative affect and subsequent binge-eating symptoms during Integrative Cognitive Affective Therapy (ICAT-BED) and Cognitive Behavior Therapy Guided Self-Help (CBTgsh). It was predicted that there would be stronger de-coupling effects in ICAT-BED compared to CBTgsh given the focus on emotion regulation skills in ICAT-BED and that greater de-coupling would predict outcomes.
Adults with BED were randomized to ICAT-BED or CBTgsh and completed 1-week EMA protocols and the Eating Disorder Examination (EDE) at pre-treatment, end-of-treatment, and 6-month follow-up (final N = 78). De-coupling was operationalized as a change in momentary associations between negative affect and binge-eating symptoms from pre-treatment to end-of-treatment.
There was a significant de-coupling effect at follow-up but not end-of-treatment, and de-coupling did not differ between ICAT-BED and CBTgsh. Less de-coupling was associated with higher end-of-treatment EDE global scores at end-of-treatment and higher binge frequency at follow-up.
Both ICAT-BED and CBTgsh were associated with de-coupling of momentary negative affect and binge-eating symptoms, which in turn relate to cognitive and behavioral treatment outcomes. Future research is warranted to identify differential mechanisms of change across ICAT-BED and CBTgsh. Results also highlight the importance of developing momentary interventions to more effectively de-couple negative affect and binge eating.
Hydrogen lithography has been used to template phosphine-based surface chemistry to fabricate atomic-scale devices, a process we abbreviate as atomic precision advanced manufacturing (APAM). Here, we use mid-infrared variable angle spectroscopic ellipsometry (IR-VASE) to characterize single-nanometer thickness phosphorus dopant layers (δ-layers) in silicon made using APAM compatible processes. A large Drude response is directly attributable to the δ-layer and can be used for nondestructive monitoring of the condition of the APAM layer when integrating additional processing steps. The carrier density and mobility extracted from our room temperature IR-VASE measurements are consistent with cryogenic magneto-transport measurements, showing that APAM δ-layers function at room temperature. Finally, the permittivity extracted from these measurements shows that the doping in the APAM δ-layers is so large that their low-frequency in-plane response is reminiscent of a silicide. However, there is no indication of a plasma resonance, likely due to reduced dimensionality and/or low scattering lifetime.
Thick thermal oxide films on Si are usually obtained by oxidation at high temperatures; e. g., 1 μm of thermal oxide is obtained at 1000°C after 5 hr in water vapor. Such a long oxidation step is unattractive from a Si processing viewpoint; also, defects have been observed to occur in wafers subjected to such a procedure. A porous Si film may be comparably oxidized in 3 to 4 min.
Porous Si is obtained by anodizing Si in HF solution. The growth and porosity of the porous layer depend on the type and resistivity of the Si, HF concentration, and anodizing time. Microstructural characterization shows that “pores” in Si, depending on conditions, vary from a few tens of angstroms to microns.
The transmission electron microscopic study of thin metal film interconnections on electronic integrated circuits requires a sophisticated in-situ capability. Electromigration, particularly, cannot be investigated solely by viewing static heat-treated or electrically stressed specimens ex-situ. The key to the early electromigration studies by Blech, and others, was the in-situ observation of material movement in anelectrical-powering-stage equipped TEM. Blech's approach was insensitive to structure effects because of an absence of heating capability; he therefore relied on joule heating and temperature gradient effects.
Lizards in captivity are commonly afflicted with an osteodystrophy related to dietary imbalances in calcium, phosphorus and vitamin D. Young green iguanas (Iguana iguana) were fed beef heart based diets either low (0.2%) in calcium (experimental group) or adequate (2.7%) in calcium (control group). Both diets were unsupplemented with vitamin D and contained 1.1% P, 82% protein and 14% fat on a dry weight basis. Beginning with the sixth month iguanas of the experimental group developed progressive hypocalcemia (8.0 to 3.2 mg/100 ml plasma) resulting in secondary hyperparathyroidism. Progressive osteoporosis, detected radiographically,with osteomalacia was apparent from the seventh month until termination of the experiment at 9 months.
Parathyroid chief cells of iguanas in the experimental group were primarily in the active stage of the secretory cycle. Lamellar and circular aggregations of rough endoplasmic reticulum were extensive and Golgi apparatuses were prominent (Fig. 1). Mitochondria often were displaced peripherally in chief cells by the large arrays of endoplasmic reticulum.
It remains poorly understood how negative symptoms are experienced in the daily lives of individuals in the early stages of psychosis. We aimed to investigate whether altered affective experience, anhedonia, social anhedonia, and asociality were more pronounced in individuals with an at-risk mental state for psychosis (ARMS) and individuals with first-episode psychosis (FEP) than in controls.
We used the experience sampling methodology (ESM) to assess negative symptoms, as they occurred in the daily life of 51 individuals with FEP and 46 ARMS, compared with 53 controls.
Multilevel linear regression analyses showed no overall evidence for a blunting of affective experience. There was some evidence for anhedonia in FEP but not in ARMS, as shown by a smaller increase of positive affect (BΔat−risk v. FEP = 0.08, p = 0.006) as the pleasantness of activities increased. Against our expectations, no evidence was found for greater social anhedonia in any group. FEP were more often alone (57%) than ARMS (38%) and controls (35%) but appraisals of the social situation did not point to asociality.
Overall, altered affective experience, anhedonia, social anhedonia and asociality seem to play less of a role in the daily life of individuals in the early stages of psychosis than previously assumed. With the experience of affect and pleasure in daily life being largely intact, changing social situations and appraisals thereof should be further investigated to prevent development or deterioration of negative symptoms.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
Innovation Concept: Dizziness is an increasingly common presenting complaint in the emergency department (ED), accounting for >2% of visits annually or almost 30% of visits in patients aged over 65. Approximately half of all cases of dizziness in older adults are caused by benign paroxysmal positional vertigo (BPPV). The use of computerized tomography (CT) to rule out serious but rare underlying central nervous system (CNS) causes in patients with dizziness in the ED is increasing despite guidelines supporting the use of clinical exam maneuvers such as the Dix-Hallpike test and therapeutic canalith repositioning maneuvers. Evidence indicates that these clinical tools are underutilized due to clinician discomfort or lack of understanding in performing and interpreting the maneuvers, supporting brief and accessible clinical resources that incorporate video examples to address this. Methods: Through an iterative process the authors have developed a smartphone app that is designed to facilitate the clinical diagnosis of BPPV and provide treatment maneuvers where appropriate. The app is being tested by clinicians practicing emergency medicine or primary care in Northern Ontario. Curriculum, Tool, or Material: The BPPV Tool is designed as a step-wise guide to diagnose BPPV. Clinicians will be prompted to perform specific exam maneuvers based on clinical findings, and can follow short example videos or written directions. Potentially precipitated nystagmus is described along with example videos. Provocative tests include the Dix-Hallpike and Supine Roll. If appropriate, the clinician will be prompted to perform therapeutic repositioning maneuvers such as the Epley or Gufoni, with associated sample videos, descriptions, and billing information where available. If at any point a clinician's exam findings are not in keeping with a diagnosis of BPPV, they will be alerted to this and stop progressing through the app. Conclusion: The BPPV Tool is an accessible and easily disseminated smartphone app designed to improve clinician comfort in reliably diagnosing BPPV. Diagnosing this common condition clinically is supported in the literature and can reduce the number of unnecessary CT scans performed, which would reduce healthcare costs and ED length of stay for these visits, and could reduce the number of patient transfers from peripheral sites for imaging.
First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups.
We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010–2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.
Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5).
FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.
This study presents two years of characterization of a warm temperate rhodolith bed in order to analyse how certain environmental changes influence the community ecology. The biomass of rhodoliths and associated species were analysed during this period and in situ experiments were conducted to evaluate the primary production, calcification and respiration of the dominant species of rhodoliths and epiphytes. The highest total biomass of rhodoliths occurred during austral winter. Lithothamnion crispatum was the most abundant rhodolith species in austral summer. Epiphytic macroalgae occurred only in January 2015, with Padina gymnospora being the most abundant. Considering associated fauna, the biomass of Mollusca increased from February 2015 to February 2016. Population densities of key reef fish species inside and around the rhodolith beds showed significant variations in time. The densities of grouper (carnivores/piscivores) increased in time, especially from 2015 to 2016. On the other hand, grunts (macroinvertebrate feeders) had a modest decrease over time (from 2014 to 2016). Other parameters such as primary production and calcification of L. crispatum were higher under enhanced irradiance, yet decreased in the presence of P. gymnospora. Community structure and physiological responses can be explained by the interaction of abiotic and biotic factors, which are driven by environmental changes over time. Biomass changes can indicate that herbivores play a role in limiting the growth of epiphytes, and this is beneficial to the rhodoliths because it decreases competition for environmental resources with fleshy algae.
The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
People with severe enduring mental illness (SMI) are at least twice as likely to die from cardiovascular disease (CVD) than the general population, with 60% of excess mortality rate attributable to physical illness.
We report implementation in primary care of screening and intervention for cardiometabolic risk factors in SMI in Cheshire, UK. Data search was performed through the EMIS software provider.
453 patients (55.8% male 44.2% female) on the SMI Register in Cheshire, UK were screened for dysglycaemia (screening rate 57.3 %) and dyslipidaemia (screening rate 36.2%). There were no differences in BMI by gender, but a greater proportion of women (25% vs 20%) were obese (BMI ≥ 30 kg/m2). Fasting glucose was in the impaired fasting glycaemia range (6.1-6.9mM) in 6.5% of those screened and at or above the threshold for type 2 diabetes (7.0mM) in 17.3% of the group. Fasting serum cholesterol was high at >5mmol/L in 62.8% of those screened for whom the mean cholesterol was 6.2±0.8 mmol/L). Despite high rates of dysglycaemia and dyslipidaemia, systolic blood pressure was greater than 140mmHg in only 13% of those examined. 61% were active smokers.
Multivariate linear regression analyses revealed a direct relation between fasting glucose levels and BMI (beta = 0.22, p< 0.001) independent of age, gender, systolic blood pressure and fasting cholesterol and triglycerides.
There is scope for cardiometabolic risk reduction in patients with severe mental illness. Measures to encourage weight reduction and smoking cessation would be vital in risk reduction strategies.
There is increasing evidence for a neurobiological basis of antisocial personality disorder (ASPD), includinggenetic liability, aberrant serotonergic function, neuropsychological deficits and structural and functional brain abnormalities. However, few functional brain imaging studies have been conducted using tasks of clinically relevant functions such as impulse control and reinforcement processing. Here we report on a study investigating the neural basis of behavioural inhibition and reward sensitivity in ASPD using functional magnetic resonance imaging (fMRI).
17 medication-free male individuals with DSM IV ASPD and 14 healthy controls were included. All subjects were screened for Axis I pathology and substance misuse. Scanner tasks included two block design tasks: one Go/No-Go task and one reward task. Scanning was carried out on a 1.5T Phillips system. Whole brain coverage was achieved using 40 axial slices with 3.5mm spacing a TR of 5 seconds. Data were analysed using SPM5 using random effects models.
Results of the Go/No-Go task confirmed brain activation previously described in the processing of impulse inhibition, namely in the orbitofrontal and dorsolateral prefrontal cortex and the anterior cingulate, and these were enhanced in the PD group. The reward task was associated with BOLD response changes in the reward network in both groups. However, these BOLD responses were reduced in the ASPD group, particularly in prefrontal areas.
Our results further support the notion of prefrontal dysfunction in ASPD. However, contrary to previous studies suggesting “hypofrontality” in this disorder, we found task specific increased and decreased BOLD responses.
Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo.
This is a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. 210 treatment-seekers with DSM-IV diagnosis of cocaine dependence consented and enrolled. 72 participants were randomized to placebo, 69 to modafinil 200mg, and 69 to modafinil 400mg, taken once daily on awakening. Participants attended the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy once per week. The primary outcome was the increase in weekly percentage of non-use days. Secondary outcomes included: decrease in the weekly median log of urine benzoylecgonine, subgroup analyses of balancing factors and co-morbid conditions, self-report of alcohol use, addiction severity, craving, and risk behaviors for HIV.
125 participants completed 12 weeks of treatment (60%). The GEE regression analysis showed that for the total sample, the difference between modafinil groups and placebo in the weekly percentage of cocaine non-use days over the 12-week treatment period was not statistically significant (p=0.95). A post-hoc analysis showed a significant effect for modafinil, only in the subgroup of cocaine patients without alcohol dependence. Modafinil 200mg also showed significant effects of an increase in the total number of consecutive non-use days for cocaine (p=0.02), and a reduction in craving (p=0.04).
These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing craving.
Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for treatment of attention-deficit/hyperactivity disorder (ADHD).
Review efficacy and safety data from two double-blind, randomized trials (SPD489-325 and SPD489-326) in patients with ADHD aged 6–17 years.
In SPD489-325, patients received placebo or optimized doses of LDX or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH) for ≤7 weeks. The primary efficacy measure was ADHD Rating Scale IV (ADHD-RS-IV) total score. Statistical comparison of LDX versus OROS-MPH was not pre-specified. In SPD489-326, a ≥26-week open-label LDX period preceded a 6-week, placebo-controlled, randomized-withdrawal period (RWP). The primary endpoint was treatment failure (50% increase in ADHD-RS-IV total score and ≥2-point increase in Clinical Global Impressions-Severity score from RWP baseline). Efficacy was assessed in the full analysis sets.
In SPD489-325 (N=317), placebo-adjusted least-squares-mean changes in ADHD-RS-IV total score from baseline to endpoint were: LDX, –18.6 (95% confidence interval [CI]: –21.5, –15.7; p<0.001; effect size 1.80) and OROS MPH, –13.0 (–15.9, –10.2; p<0.001; 1.26). In SPD489-326 (N=262, open-label period; N=153, RWP), 15.8% and 67.5% of patients receiving LDX and placebo, respectively, met treatment failure criteria at RWP endpoint (differen –51.7%; 95% CI: –65.0%, –38.5%; p<0.001). The most common treatment-emergent adverse events in LDX-treated patients were decreased appetite, headache and decreased weight.
Short-term LDX treatment improved symptoms of ADHD in children and adolescents. Continued LDX treatment was associated with maintenance of efficacy compared with placebo. The safety profile of LDX was generally consistent with that of stimulant therapy.
In a European, phase 3 study (SPD489-325), lisdexamfetamine dimesylate (LDX) and osmotic-release oral system methylphenidate (OROS-MPH) were more effective than placebo in improving core symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
Objectives and aims
To compare post hoc the efficacy of LDX and OROS-MPH in study SPD489-325.
This 7-week, randomized, double-blind, parallel-group, dose-optimized, placebo-controlled trial enrolled patients aged 6-17 years with ADHD of at least moderate severity. Patients were randomized (1:1:1) to receive a once-daily dose of LDX (30, 50, 70 mg/day), OROS-MPH (18, 36, 54 mg/day) or placebo. Efficacy was assessed using the ADHD Rating Scale version IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Endpoint was defined as the last ontherapy treatment visit with a valid assessment.
The full analysis set comprised 317 patients (LDX, n=104; placebo, n=106; OROS-MPH, n=107). The difference between LDX and OROS-MPH in least squares mean change (95% confidence interval [CI]) in ADHD-RS-IV total score from baseline to endpoint was statistically significant in favour of LDX (-5.6 [-8.4, -2.7]; p < 0.001; effect size, 0.541). The difference (LDX minus OROS-MPH) in the percentage of patients (95% CI) with an improved CGI-I score at endpoint was also statistically significant in favour of LDX (17.4 [5.0, 29.8]; p < 0.05).
This post hoc analysis indicated that LDX is significantly more effective than OROS-MPH in improving core symptoms and global functioning in children and adolescents with ADHD.