Background
First‐line treatments for pediatric obsessive–compulsive disorder (OCD) include exposure‐based cognitive‐behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). No ...studies have thus far identified distinct classes and associated predictors of long‐term symptom severity during and after treatment. Yet, these could form the basis for more personalized treatment in pediatric OCD.
Method
The study included 269 OCD patients aged 7−17 years from the Nordic Long‐term OCD Treatment Study (NordLOTS). All participants received stepped‐care treatment starting with 14 weekly sessions of manualized CBT. Nonresponders were randomized to either prolonged CBT or SSRIs. Symptom severity was assessed using the Children's Yale‐Brown Obsessive‐Compulsive Scale at seven time points from pre‐ to post‐treatment and over a three‐year follow‐up. Latent class growth analysis (LCGA) was performed to identify latent classes of symptom severity trajectories. Univariate and multivariate analyses were used to detect differences between classes and identify predictors of trajectory class membership including several clinical and demographic variables. Trial registry: Nordic Long‐term Obsessive‐Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119.
Results
Three LCGA classes were identified: (a) acute, sustained responders (54.6%); (b) slow, continued responders (23.4%); and (c) limited long‐term responders (21.9%). Class membership was predicted by distinct baseline characteristics pertaining to age, symptom severity, contamination/cleaning and anxiety symptoms.
Conclusions
The LCGA suggests three distinct trajectory classes of long‐term symptom severity during and after treatment in pediatric OCD with different clinical profiles at pretreatment. The results point to required clinical attention for adolescent patients with contamination/cleaning and anxiety symptoms who do not show convincing responses to first‐line treatment even though they may have reached the established cutoff for treatment response.
Obesity is a risk factor for poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19).
To investigate the relationship between prior metabolic surgery and the severity of COVID-19 ...in patients with severe obesity.
Cleveland Clinic Health System in the United States.
Among 4365 patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between March 8, 2020 and July 22, 2020 in the Cleveland Clinic Health System, 33 patients were identified who had a prior history of metabolic surgery. The surgical patients were propensity matched 1:10 to nonsurgical patients to assemble a cohort of control patients (n = 330) with a body mass index (BMI) ≥ 40 kg/m
at the time of SARS-CoV-2 testing. The primary endpoint was the rate of hospital admission. The exploratory endpoints included admission to the intensive care unit (ICU), need for mechanical ventilation and dialysis during index hospitalization, and mortality. After propensity score matching, outcomes were compared in univariate and multivariate regression models.
The average BMI of the surgical group was 49.1 ± 8.8 kg/m
before metabolic surgery and was down to 37.2 ± 7.1 at the time of SARS-CoV-2 testing, compared with the control group's BMI of 46.7 ± 6.4 kg/m
. In the univariate analysis, 6 (18.2%) patients in the metabolic surgery group and 139 (42.1%) patients in the control group were admitted to the hospital (P = .013). In the multivariate analysis, a prior history of metabolic surgery was associated with a lower hospital admission rate compared with control patients with obesity (odds ratio, 0.31; 95% confidence interval, 0.11-0.88; P = .028). While none of the 4 exploratory outcomes occurred in the metabolic surgery group, 43 (13.0%) patients in the control group required ICU admission (P = .021), 22 (6.7%) required mechanical ventilation, 5 (1.5%) required dialysis, and 8 (2.4%) patients died.
Prior metabolic surgery with subsequent weight loss and improvement of metabolic abnormalities was associated with lower rates of hospital and ICU admission in patients with obesity who became infected with SARS-CoV-2. Confirmation of these findings will require larger studies.
Aims.Based on a new set of sulphur abundances in very metal-poor stars and an improved analysis of previous data, we aim at resolving current discrepancies on the trend of S/Fe vs. Fe/H and thereby ...gain better insight into the nucleosynthesis of sulphur. The trends of Zn/Fe and S/Zn will also be studied. Methods.High resolution VLT/UVES spectra of 40 main-sequence stars with -3.3 < Fe/H < -1.0 are used to derive S abundances from the weak λ 8694.6 $\ion{S}{i}$ line and the stronger $\lambda \lambda$ 9212.9,9237.5 pair of $\ion{S}{i}$ lines. For one star, the S abundance is also derived from the $\ion{S}{i}$ triplet at 1.046 μm recently observed with the VLT infrared echelle spectrograph CRIRES. Fe and Zn abundances are derived from lines in the blue part of the UVES spectra, and effective temperatures are obtained from the profile of the Hβ line. Results.Comparison of sulphur abundances from the weak and strong $\ion{S}{i}$ lines provides important constraints on non-LTE effects. The high sulphur abundances reported by others for some metal-poor stars are not confirmed; instead, when taking non-LTE corrections into account, the Galactic halo stars distribute around a plateau at S/Fe ~ +0.2 dex with a scatter of 0.07 dex only. Zn/Fe is close to zero for metallicities in the range -2.0 < Fe/H < -1.0 but increases to a level of Zn/Fe ~ +0.1 to +0.2 dex in the range -2.7< Fe/H < -2.0. At still lower metallicities Zn/Fe rises steeply to a value of Zn/Fe ~ +0.5 dex at Fe/H = -3.2. Conclusions.The trend of S/Fe vs. Fe/H corresponds to the trends of Mg/Fe, Si/Fe, and Ca/Fe and indicates that sulphur in Galactic halo stars has been made by α-capture processes in massive SNe. The observed scatter in S/Fe is much smaller than predicted from current stochastic models of the chemical evolution of the early Galaxy, suggesting that either the models or the calculated yields of massive SNe should be revised. We also examine the behaviour of S/Zn and find that departures from the solar ratio are significantly reduced at all metallicities if non-LTE corrections to the abundances of these two elements are adopted. This effect, if confirmed, would reduce the usefulness of the S/Zn ratio as a diagnostic of past star-formation activity, but would bring closer together the values measured in damped Lyman-alpha systems and in Galactic stars.
Within the last several years, previously rare liver tumors have been seen in young women using oral contraceptive steroids. The Registry for Liver Tumors Associated with Oral Contraceptives at the ...University of California, Irvine, has clearly identified 27 cases. The recent literature contains 44 case reports. Common to these 71 cases has been a histopathologic diagnosis of focal nodular hyperplasia, adenoma, hamartoma, and hepatoma. Significant statistical etiologic factors include prolonged uninterrupted usage of oral contraceptive steroids. Eight deaths and liver rupture in 18 patients attest to the seriousness of this new potentially lethal adverse phenomenon.
Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality of life for millions of people. Familial Hemiplegic Migraine type 2 (FHM2) is a ...subtype of migraine with aura and co-morbidities like epilepsy/seizures, cognitive impairments and psychiatric manifestations, such as obsessive-compulsive disorder (OCD). FHM2 disease-mutations locate to the ATP1A2 gene encoding the astrocyte-located α2-isoform of the sodium-potassium pump (α2Na(+)/K(+)-ATPase). We show that knock-in mice heterozygous for the FHM2-associated G301R-mutation (α2(+/G301R)) phenocopy several FHM2-relevant disease traits e.g., by mimicking mood depression and OCD. In vitro studies showed impaired glutamate uptake in hippocampal mixed astrocyte-neuron cultures from α2(G301R/G301R) E17 embryonic mice, and moreover, induction of cortical spreading depression (CSD) resulted in reduced recovery in α2(+/G301R) male mice. Moreover, NMDA-type glutamate receptor antagonists or progestin-only treatment reverted specific α2(+/G301R) behavioral phenotypes. Our findings demonstrate that studies of an in vivo relevant FHM2 disease knock-in mouse model provide a link between the female sex hormone cycle and the glutamate system and a link to co-morbid psychiatric manifestations of FHM2.
Professional medical associations (PMAs) play an essential role in defining and advancing health care standards. Their conferences, continuing medical education courses, practice guidelines, ...definitions of ethical norms, and public advocacy positions carry great weight with physicians and the public. Because many PMAs receive extensive funding from pharmaceutical and device companies, it is crucial that their guidelines manage both real and perceived conflict of interests. Any threat to the integrity of PMAs must be thoroughly and effectively resolved. Current PMA policies, however, are not uniform and often lack stringency. To address this situation, the authors first identified and analyzed conflicts of interest that may affect the activities, leadership, and members of PMAs. The authors then went on to formulate guidelines, both short-term and long-term, to prevent the appearance or reality of undue industry influence. The recommendations are rigorous and would require many PMAs to transform their mode of operation and perhaps, to forgo valuable activities. To maintain integrity, sacrifice may be required. Nevertheless, these changes are in the best interest of the PMAs, the profession, their members, and the larger society.
Field studies were conducted in Colorado, Kansas, and Wyoming to compare the use of quinclorac plus 2,4-D with picloram plus 2,4-D, dicamba plus 2,4-D, a glyphosate plus 2,4-D premix, and 2,4-D alone ...for control of field bindweed (Convolvulus arvensis) in a winter wheat (Triticum aestivum)-fallow rotation. Treatments were applied in late summer or fall each year for two, three, or four consecutive years at the beginning and end of each fallow period. Evaluations were taken 10 to 12 mo after treatment each year. Quinclorac plus 2,4-D and picloram plus 2,4-D consistently performed as well as or better than 2,4-D, dicamba plus 2,4-D, and glyphosate plus 2,4-D. Wheat yields increased when field bindweed was controlled during the fallow period. Strong correlations (r > -0.85) were obtained among visual field bindweed evaluation, biomass, and stand count data.
Summary
Objective
In one third of patients, seizures remain after epilepsy surgery, meaning that improved preoperative evaluation methods are needed to identify the epileptogenic zone. A potential ...framework for such a method is network theory, as it can be applied to noninvasive recordings, even in the absence of epileptiform activity. Our aim was to identify the epileptogenic zone on the basis of hub status of local brain areas in interictal magnetoencephalography (MEG) networks.
Methods
Preoperative eyes‐closed resting‐state MEG recordings were retrospectively analyzed in 22 patients with refractory epilepsy, of whom 14 were seizure‐free 1 year after surgery. Beamformer‐based time series were reconstructed for 90 cortical and subcortical automated anatomic labeling (AAL) regions of interest (ROIs). Broadband functional connectivity was estimated using the phase lag index in artifact‐free epochs without interictal epileptiform abnormalities. A minimum spanning tree was generated to represent the network, and the hub status of each ROI was calculated using betweenness centrality, which indicates the centrality of a node in a network. The correspondence of resection cavity to hub values was evaluated on four levels: resection cavity, lobar, hemisphere, and temporal versus extratemporal areas.
Results
Hubs were localized within the resection cavity in 8 of 14 seizure‐free patients and in zero of 8 patients who were not seizure‐free (57% sensitivity, 100% specificity, 73% accuracy). Hubs were localized in the lobe of resection in 9 of 14 seizure‐free patients and in zero of 8 patients who were not seizure‐free (64% sensitivity, 100% specificity, 77% accuracy). For the other two levels, the true negatives are unknown; hence, only sensitivity could be determined: hubs coincided with both the resection hemisphere and the resection location (temporal versus extratemporal) in 11 of 14 seizure‐free patients (79% sensitivity).
Significance
Identifying hubs noninvasively before surgery is a valuable approach with the potential of indicating the epileptogenic zone in patients without interictal abnormalities.
Abdominal obesity is associated with metabolic abnormalities and increased risk of atherosclerotic cardiovascular disease. However, no obesity management strategy has demonstrated the ability to slow ...progression of coronary disease.
To determine whether weight loss and metabolic effects of the selective cannabinoid type 1 receptor antagonist rimonabant reduces progression of coronary disease in patients with abdominal obesity and the metabolic syndrome.
Randomized, double-blinded, placebo-controlled, 2-group, parallel-group trial (enrollment December 2004-December 2005) comparing rimonabant with placebo in 839 patients at 112 centers in North America, Europe, and Australia.
Patients received dietary counseling, were randomized to receive rimonabant (20 mg daily) or matching placebo, and underwent coronary intravascular ultrasonography at baseline (n = 839) and study completion (n = 676).
The primary efficacy parameter was change in percent atheroma volume (PAV); the secondary efficacy parameter was change in normalized total atheroma volume (TAV).
In the rimonabant vs placebo groups, PAV (95% confidence interval CI) increased 0.25% (-0.04% to 0.54%) vs 0.51% (0.22% to 0.80%) (P = .22), respectively, and TAV decreased 2.2 mm3 (-4.09 to -0.24) vs an increase of 0.88 mm3 (-1.03 to 2.79) (P = .03). In the rimonabant vs placebo groups, imputing results based on baseline characteristics for patients not completing the trial, PAV increased 0.25% (-0.04% to 0.55%) vs 0.57% (0.29% to 0.84%) (P = .13), and TAV decreased 1.95 mm3 (-3.8 to -0.10) vs an increase of 1.19 mm3 (-0.73 to 3.12) (P = .02). Rimonabant-treated patients had a larger reduction in body weight (4.3 kg -5.1 to -3.5 vs 0.5 kg -1.3 to 0.3) and greater decrease in waist circumference (4.5 cm -5.4 to -3.7 vs 1.0 cm -1.9 to -0.2) (P < .001 for both comparisons). In the rimonabant vs placebo groups, high-density lipoprotein cholesterol levels increased 5.8 mg/dL (4.9 to 6.8) (22.4%) vs 1.8 mg/dL (0.9 to 2.7) (6.9%) (P < .001), and median triglyceride levels decreased 24.8 mg/dL (-35.4 to -17.3) (20.5%) vs 8.9 mg/dL (-14.2 to -1.8) (6.2%) (P < .001). Rimonabant-treated patients had greater decreases in high-sensitivity C-reactive protein (1.3 mg/dL -1.7 to -1.2 50.3% vs 0.9 mg/dL -1.4 to -0.5 30.9%) and less increase in glycated hemoglobin levels (0.11% 0.02% to 0.20% vs 0.40% 0.31% to 0.49%) (P < .001 for both comparisons). Psychiatric adverse effects were more common in the rimonabant group (43.4% vs 28.4%, P < .001).
After 18 months of treatment, the study failed to show an effect for rimonabant on disease progression for the primary end point (PAV) but showed a favorable effect on the secondary end point (TAV). Determining whether rimonabant is useful in management of coronary disease will require additional imaging and outcomes trials, which are currently under way.
clinicaltrials.gov Identifier: NCT00124332.
PDF
