How effective has the Spanish lockdown been to battle COVID-19? A spatial analysis of the coronavirus propagation across provinces

This paper examines the propagation of COVID-19 across the Spanish provinces and assesses the effectiveness of the Spanish lockdown of the population implemented on March 14, 2020 in order to battle this pandemic. To achieve these objectives, a standard spatial econometric model used in economics is adapted to resemble the popular reproduction models employed in the epidemiological literature. In addition, we introduce a counterfactual exercise that allows us to examine the Gross domestic product (GDP) gains of bringing forward the date of the Spanish Lockdown. We find that the number of COVID-19 cases would have been reduced by 70.4% in the absence of spatial propagation between the Spanish provinces. We also determine that the lockdown prevented the propagation of the virus within and between provinces. As such, the Spanish lockdown reduced the number of potential COVID-19 cases by 82.8%. However, the number of coronavirus cases would have been reduced by an additional 11.6% if the lockdown had been brought forward to March 7, 2020. Finally, an earlier lockdown would have saved approximately 26,900,000,000 euros.     

Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

A French survey on the lockdown consequences of COVID-19 pandemic in Parkinson's disease. The ERCOPARK study

BackgroundIn 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March – mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP).MethodsPwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life.Results2653 PwP were included: 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group.ConclusionsThe first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. .     

Prefrontal theta modulates sensorimotor gamma networks during the reorienting of attention

The ability to execute a motor plan involves spatiotemporally precise oscillatory activity in primary motor (M1) regions, in concert with recruitment of “higher order” attentional mechanisms for orienting toward current task goals. While current evidence implicates gamma oscillatory activity in M1 as central to the execution of a movement, far less is known about top‐down attentional modulation of this response. Herein, we utilized magnetoencephalography (MEG) during a Posner attention‐reorienting task to investigate top‐down modulation of M1 gamma responses by frontal attention networks in 63 healthy adult participants. MEG data were evaluated in the time–frequency domain and significant oscillatory responses were imaged using a beamformer. Robust increases in theta activity were found in bilateral inferior frontal gyri (IFG), with significantly stronger responses evident in trials that required attentional reorienting relative to those that did not. Additionally, strong gamma oscillations (60–80 Hz) were detected in M1 during movement execution, with similar responses elicited irrespective of attentional reorienting. Whole‐brain voxel‐wise correlations between validity difference scores (i.e., attention reorienting trials—nonreorienting trials) in frontal theta activity and movement‐locked gamma oscillations revealed a robust relationship in the contralateral sensorimotor cortex, supplementary motor area, and right cerebellum, suggesting modulation of these sensorimotor network gamma responses by attentional reorienting. Importantly, the validity difference effect in this distributed motor network was predictive of overall motor function measured outside the scanner and further, based on a mediation analysis this relationship was fully mediated by the reallocation response in the right IFG. These data are the first to characterize the top‐down modulation of movement‐related gamma responses during attentional reorienting and movement execution.     

Relationship of Hip and Trunk Muscle Function with Single Leg Step-Down Performance: Implications for Return to Play Screening and Rehabilitation

ObjectivesEvaluate the relationship of hip and trunk muscle function with the Single Leg Step-Down test (SLSD).Study designLaboratory study.SettingBiomechanics Laboratory.Participants71 healthy participants with no history of anterior cruciate ligament (ACL) or lower extremity injury in the last 3 months completed this study (38 males, 33 females; mean 25.49 ± 0.62 years).Main outcomesHip abduction (HABD), external rotation (HER), and extension (HEXT) peak isometric force were measured. Trunk endurance was measured with plank (PL) and side plank (SPL) tests. SLSD repetitions in 60-s and dynamic knee valgus (VAL) were recorded.ResultsPL, SPL, HABD, HER, and HEXT were positively correlated with SLSD repetitions. PL (r = 0.598, p < 0.001) was most correlated with SLSD repetitions, and regression demonstrated that PL (p = 0.001, R² = 0.469) was a predictor of SLSD repetitions. VAL trended toward negative correlation with PL and SPL. Sex-specific differences were present, with PL, SPL, HABD, and HER showing stronger relationships with SLSD in females.ConclusionHip and trunk muscle function were positively correlated with SLSD performance, and these relationships were strongest in females. PL predicted performance on the SLSD. Further research is needed to investigate the utility of SLSD as a screening or return-to-play test for lower extremity conditions such as ACL injury and patellofemoral pain.     

Automated Delineation of the Normal Urinary Bladder on Planning CT and Cone Beam CT

PurposeTo quantify the volumetric effect of delineation variability when using manual versus semiautomated tools to contour the normal bladder on planning computed tomography (CT) and cone beam CT.MethodsFollowing research ethics board approval, 10 prostate cancer patients were selected. For each patient, one pretreatment cone beam CT (CBCT) was randomly selected from the first treatment week and registered to the planning CT (planCT). Model-based auto adaptation was used to delineate the outer bladder (OB) surface for the planCT. That contour was then propagated and manually adapted onto the CBCT. A second observer delineated OB for the planCT and CBCT using typical manual methods. These delineation procedures were repeated four times on each image set, with observers blinded to the previous contours. Metrics of volumetric, geometric, and overlap concordance were used to compare the manual and automated OB contours.ResultsThe mean pairwise difference between the manual and model-based planCT volumes was 4 cm³ (2%), and the model-based contours exhibited approximately half the observer variation of the manual ones (3 cm³, 2%). The mean of pairwise differences between the manual and propagated CBCT volumes was 13 cm³ (8%), but the propagated contours exhibited approximately half the observer related volume variation (11 cm³, 6%). Small CBCT bladder volumes displayed larger observer variation with manual methods (r², −0.640). Variability between the automated contours was significantly smaller than for the corresponding manual observations (P = .004 and .002, respectively). Metrics of three-dimensional overlap concordance indicated excellent agreement within and between the delineation methods. Automated CBCT contours were significantly smoother than the manual ones (surface sphericity index, 1.29 vs. 1.35; P = .03).ConclusionsVolumetric, geometric, and overlap metrics all indicated that planCT and CBCT automated OB contours fell within the range of manually delineated contours. The CBCT propagated contours were significantly smoother and associated with smaller intraobserver variability, compared with manual contours. Importantly, the findings from this research suggest that contour propagation may be more robust than manual delineation, especially in the presence of poor image quality.     

Subharmonic,Non-linear Fundamental and Ultraharmonic Imaging of Microbubble Contrast at High Frequencies

There is increasing use of ultrasound contrast agent in high-frequency ultrasound imaging. However, conventional contrast detection methods perform poorly at high frequencies. We performed systematic in vitro comparisons of subharmonic, non-linear fundamental and ultraharmonic imaging for different depths and ultrasound contrast agent concentrations (Vevo 2100 system with MS250 probe and MicroMarker ultrasound contrast agent, VisualSonics, Toronto, ON, Canada). We investigated 4-, 6- and 10-cycle bursts at three power levels with the following pulse sequences: B-mode, amplitude modulation, pulse inversion and combined pulse inversion/amplitude modulation. The contrast-to-tissue (CTR) and contrast-to-artifact (CAR) ratios were calculated. At a depth of 8 mm, subharmonic pulse-inversion imaging performed the best (CTR = 26 dB, CAR = 18 dB) and at 16 mm, non-linear amplitude modulation imaging was the best contrast imaging method (CTR = 10 dB). Ultraharmonic imaging did not result in acceptable CTRs and CARs. The best candidates from the in vitro study were tested in vivo in chicken embryo and mouse models, and the results were in a good agreement with the in vitro findings.