An analytic model for the flow induced in syringomyelia cavities.

A simple two-dimensional fluid-structure-interaction problem, involving viscous oscillatory flow in a channel separated by an elastic membrane from a fluid-filled slender cavity, is analyzed to shed light on the flow dynamics pertaining to syringomyelia, a neurological disorder characterized by the appearance of a large tubular cavity (syrinx) within the spinal cord. The focus is on configurations in which the velocity induced in the cavity, representing the syrinx, is comparable to that found in the channel, representing the subarachnoid space surrounding the spinal cord, both flows being coupled through a linear elastic equation describing the membrane deformation. An asymptotic analysis for small stroke lengths leads to closed-form expressions for the leading-order oscillatory flow, and also for the stationary flow associated with the first-order corrections, the latter involving a steady distribution of transmembrane pressure. The magnitude of the induced flow is found to depend strongly on the frequency, with the result that for channel flow rates of non-sinusoidal waveform, as those found in the spinal canal, higher harmonics can dominate the sloshing motion in the cavity, in agreement with previous in vivo observations. Under some conditions, the cycle-averaged transmembrane pressure, also showing a marked dependence on the frequency, changes sign on increasing the cavity transverse dimension (i.e. orthogonal to the cord axis), underscoring the importance of cavity size in connection with the underlying hydrodynamics. The analytic results presented here can be instrumental in guiding future numerical investigations, needed to clarify the pathogenesis of syringomyelia cavities.

Effects of buoyancy on the dispersion of drugs released intrathecally in the spinal canal.

This paper investigates the transport of drugs delivered by direct injection into the cerebrospinal fluid (CSF) that fills the intrathecal space surrounding the spinal cord. Because of the small drug diffusivity, the dispersion of neutrally buoyant drugs has been shown in previous work to rely mainly on the mean Lagrangian flow associated with the CSF oscillatory motion. Attention is given here to effects of buoyancy, arising when the drug density differs from the CSF density. For the typical density differences found in applications, the associated Richardson number is shown to be of order unity, so that the Lagrangian drift includes a buoyancy-induced component that depends on the spatial distribution of the drug, resulting in a slowly evolving cycle-averaged flow problem that can be analysed with two-time scale methods. The asymptotic analysis leads to a nonlinear integro-differential equation for the spatiotemporal solute evolution that describes accurately drug dispersion at a fraction of the cost involved in direct numerical simulations of the oscillatory flow. The model equation is used to predict drug dispersion of positively and negatively buoyant drugs in an anatomically correct spinal canal, with separate attention given to drug delivery via bolus injection and constant infusion.

Effect of switch from flash glucose monitoring to flash glucose monitoring with real-time alarms on hypoglycaemia in people with type 1 diabetes mellitus.

We aimed to evaluate the utility of the FreeStyle Libre 2 device for reducing time below range level 1 and level 2 compared with the Freestyle Libre device (without alarms) in people with type 1 diabetes mellitus. We conducted longitudinal observational follow-up study of a cohort of 100 people with type 1 diabetes mellitus who had switched from FreeStyle Libre to FreeStyle Libre 2 as part of routine clinical practice. Three months after switching to FreeStyle Libre 2, compared with results with FreeStyle Libre, there were a significant improvements in time below range level 1 (p = 0.02) and level 2 (p <0.001), time in range (p <0.001), time above range level 1 (p = 0.002), glucose management indicator (p= 0.04) and mean glucose (p= 0.04) during follow-up. Furthermore there was a significant direct association between age and change in TIR with a coefficient of 0.23, and a significant inverse association between age and change in TAR-1 with a coefficient of 0.11. Switching to a flash glucose monitoring system with alarms improves time below range, time in range and coefficient of variation in people with type 1 diabetes mellitus.

Stationary flow driven by non-sinusoidal time-periodic pressure gradients in wavy-walled channels.

The classical problem of secondary flow driven by a sinusoidally varying pressure gradient is extended here to address periodic pressure gradients of complex waveform, which are present in many oscillatory physiological flows. A slender two-dimensional wavy-walled channel is selected as a canonical model problem. Following standard steady-streaming analyses, valid for small values of the ratio ε of the stroke length of the pulsatile motion to the channel wavelength, the spatially periodic flow is described in terms of power-law expansions of ε, with the Womersley number assumed to be of order unity. The solution found at leading order involves a time-periodic velocity with a zero time-averaged value at any given point. As in the case of a sinusoidal pressure gradient, effects of inertia enter at the following order to induce a steady flow in the form of recirculating vortices with zero net flow rate. An improved two-term asymptotic description of this secondary flow is sought by carrying the analysis to the following order. It is found that, when the pressure gradient has a waveform with multiple harmonics, the resulting velocity corrections display a nonzero flow rate, not present in the single-frequency case, which enables stationary convective transport along the channel. Direct numerical simulations for values of ε of order unity are used to investigate effects of inertia and delineate the range of validity of the asymptotic limit ε≪1. The comparisons of the time-averaged velocity obtained numerically with the two-term asymptotic description reveals that the latter remains remarkably accurate for values of ε exceeding 0.5. As an illustrative example, the results of the model problem are used to investigate the cerebrospinal-fluid flow driven along the spinal canal by the cardiac and respiratory cycles, characterized by markedly non-sinusoidal waveforms.

Oscillating viscous flow past a streamwise linear array of circular cylinders.

This paper addresses the viscous flow developing about an array of equally spaced identical circular cylinders aligned with an incompressible fluid stream whose velocity oscillates periodically in time. The focus of the analysis is on harmonically oscillating flows with stroke lengths that are comparable to or smaller than the cylinder radius, such that the flow remains two-dimensional, time-periodic and symmetric with respect to the centreline. Specific consideration is given to the limit of asymptotically small stroke lengths, in which the flow is harmonic at leading order, with the first-order corrections exhibiting a steady-streaming component, which is computed here along with the accompanying Stokes drift. As in the familiar case of oscillating flow over a single cylinder, for small stroke lengths, the associated time-averaged Lagrangian velocity field, given by the sum of the steady-streaming and Stokes-drift components, displays recirculating vortices, which are quantified for different values of the two relevant controlling parameters, namely, the Womersley number and the ratio of the inter-cylinder distance to the cylinder radius. Comparisons with results of direct numerical simulations indicate that the description of the Lagrangian mean flow for infinitesimally small values of the stroke length remains reasonably accurate even when the stroke length is comparable to the cylinder radius. The numerical integrations are also used to quantify the streamwise flow rate induced by the presence of the cylinder array in cases where the periodic surrounding motion is driven by an anharmonic pressure gradient, a problem of interest in connection with the oscillating flow of cerebrospinal fluid around the nerve roots located along the spinal canal.

The role of multiparametric magnetic resonance in active surveillance of a low-risk prostate cancer cohort from clinical practice.

INTRODUCTION: Active surveillance (AS) is considered a suitable management practice for those patients with low-risk prostate cancer (PCa). At present, however, the role of multiparametric magnetic resonance imaging (mpMRI) in AS protocols has not yet been clearly established. OUTCOMES: To determine the role of mpMRI and its ability to detect significant prostate cancer (SigPCa) in PCa patients enrolled in AS protocols. MATERIALS AND METHODS: There were 229 patients enrolled in an AS protocol between 2011 and 2020 at Reina Sofía University Hospital. MRI interpretation was based on PIRADS v.1 or v.2/2.1 classification. Demographics, clinical, and analytical data were collected and analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for mpMRI in different scenarios. We defined SigPCa and reclassification/progression as a Gleason score (GS) ≥ 3 + 4, a clinical stage ≥T2b, or an increase in PCa volume. Kaplan-Meier and log-rank tests were used to estimate progression-free survival time. RESULTS: Median age was 69.02 (±7.73) at diagnosis, with a 0.15 (±0.08) PSA density (PSAD). Eighty-six patients were reclassified after confirmatory biopsy, with a suspicious mpMRI an indication for a clear reclassification and risk-predictor factor in disease progression (p < 0.05). During follow-up, 46 patients were changed from AS to active treatment mainly due to disease progression. Ninety patients underwent ≥2mpMRI during follow-up, with a median follow-up of 29 (15-49) months. Thirty-four patients had a baseline suspicious mpMRI (at diagnostic or confirmatory biopsy): 14 patients with a PIRADS 3 and 20 patients with ≥PIRADS 4. From 14 patients with a PIRADS 3 baseline mpMRI, 29% progressed radiologically, with a 50% progression rate versus 10% (1/10 patients) for those with similar or decreased mpMRI risk. Of the 56 patients with a non-suspicious baseline mpMRI (PIRADS < 2), 14 patients (25%) had an increased degree of radiological suspicion, with a detection rate of SigPCa of 29%. The mpMRI NPV during follow-up was 0.91. CONCLUSION: A suspicious mpMRI increases the reclassification and disease progression risk during follow-up and plays an important role in monitoring biopsies. In addition, a high NPV at mpMRI follow-up can help to decrease the need to monitor biopsies during AS.

[Factors associated with dissatisfaction with pharmacological treatment in patients with type 2 diabetes mellitus: A cross-sectional study]. / Factores asociados a la insatisfacción con el tratamiento farmacológico en pacientes con diabetes mellitus tipo 2: estudio transversal.

BACKGROUND AND OBJECTIVES: Diabetes is a chronic disease with a high impact on both health and Quality of Life Related to Health (QLRH). To evaluate the satisfaction of treatment in patients with type 2 diabetes mellitus through the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and its relationship with sociodemographic variables, with antidiabetic medication and clinical-analytical variables. MATERIALS AND METHODS: This cross-sectional study was conducted in General University Hospital of San Juan de Alicante between September 2016 and December 2017. Two hundred thirty-two patients diagnosed with type 2 diabetes mellitus at least 1 year before inclusion, treated with antidiabetic medication were included. The Spanish version of the DTSQ scale was used to measure satisfaction with treatment. Factors associated with low satisfaction were analyzed by applying the Chi-square test for qualitative variables and Student-T for quantitative variables. To estimate magnitudes of association, logistic models were adjusted. RESULTS: Two hundred thirty-two patients were included in this study. 21.5% of the patients presented low satisfaction with the treatment. Patients who presented low satisfaction with treatment were associated with medications that could cause hypoglycemia (OR: 2.872 [1.195-6.903]), HbA1c levels higher than 7% (OR: 2.260 [1.005-5.083]) and drugs administered by the route oral (OR: 2.749 [1.233-6.131]). CONCLUSIONS: Patients with type 2 diabetes mellitus who had a lower score on the DTSQ questionnaire were associated with medications that produced hypoglycaemia, and with higher levels of HbA1c higher than 7%, and those who took oral medication.

Hábitos de vida y mortalidad cardiovascular de las mujeres menopáusicas: estudio de cohortes de base poblacional / Lifestyle and cardiovascular mortality in menopausal women: a population-based cohort study

Introducción y objetivos: Existen modelos de predicción de riesgo cardiovascular en población general, pero no se ha estudiado de modo específico la predicción del riesgo de las mujeres posmenopáusicas. El objetivo de este estudio es conocer los hábitos de vida y las enfermedades crónicas asociados con mayor riesgo cardiovascular en mujeres menopáusicas, así como construir una escala de riesgo. Métodos: Estudio de cohortes retrospectivo de base poblacional cuya fuente de datos es la Encuesta Nacional de Salud de España de 2011. Se incluyó a mujeres de edad ≥ 50 años. Se recogieron las características que mejor definían los hábitos de vida de las mujeres del estudio, así como su estado de salud y los antecedentes médicos declarados por ellas en el momento de la encuesta. Se realizó seguimiento de la mortalidad de las mujeres del estudio desde 2011 hasta 2017. Resultados: Se incluyó a 5.953 mujeres con una media de edad de 66,4±11,4 años. La incidencia de mortalidad cardiovascular en el periodo de seguimiento fue del 4%. Se relacionaron con la mortalidad cardiovascular el consumo de verduras menor de 1 vez/semana (HR=1,758), el tabaquismo (HR=1,816) el exceso de horas de sueño (≥ 9 h/día, HR=1,809) o tener actividad principal diaria sentada la mayor parte del tiempo (HR=2,757). El modelo predictivo presenta un estadístico C «sincero» en muestra de prueba de 0,8407 (IC95%, 0,8025-0,8789). Conclusiones: Hábitos de vida como el consumo de verduras, la actividad principal diaria, las horas de sueño o el tabaquismo son factores de riesgo de mortalidad cardiovascular de gran relevancia entre las mujeres menopáusicas. Se aporta una sencilla escala de riesgo autorreferida a 6 años con elevada capacidad predictiva (AU)

Introduction and objectives: There are models for cardiovascular risk prediction in the general population, but the prediction of risk in postmenopausal women has not been specifically studied. This study aimed to determine the association of lifestyle habits and chronic diseases with cardiovascular risk in menopausal women, as well as to build a risk scale. Methods: Retrospective population-based cohort study using data from the 2011 National Health Survey of Spain as a data source, Women ≥ 50 years were included. The characteristics that best defined the life habits of the study women were collected, as well as their health status and self-reported medical history at the time of the survey. Follow-up data on all-cause mortality were obtained from participants from 2011 to 2017. Results: A total of 5953 women ≥ 50 years of age were included, with a mean age of 66.4 ± 11.4 years. The incidence of cardiovascular mortality in the follow-up period was 4%. Vegetable consumption less than 1 time/week (HR, 1.758), smoking (HR, 1.816) or excess hours of sleep (≥ 9h/day, HR, 1.809), or o have main daily activity sitting most of the time (HR, 2.757) were related to cardiovascular mortality. The predictive model presents an honest C-index in test sample of 0.8407 (95%CI, 0.8025-0.8789). Conclusions: Life habits such as the consumption of vegetables, daily main activity, sleeping hours or smoking are risk factors for cardiovascular mortality of great relevance among menopausal women. A simple 6-year self-reported risk scale with high predictive capacity is provided (AU)

[Analysis of two health attendance models for the non-hospital emergencies in Gipuzkoa: Retrospective study]. / Análisis de dos modelos asistenciales para la atención de las emergencias extrahospitalarias en Guipúzcoa: Estudio retrospectivo.

BACKGROUND AND OBJECTIVE: Out-of-hospital medical emergency services are defined as a functional organization that performs a set of sequential human and material activities. The objective of this study was to compare the mortality of patients attended by the out-of-hospital medical emergency services in 2 neighboring Spanish regions with different models of healthcare transport assistance for emergency care. MATERIAL AND METHOD: Retrospective observational cohort study, done between June 1, 2007 and December 31, 2008 in 2 regions of Gipuzkoa, Alto Deba (AD) and Bajo Deba (BD). The study variables were age, sex and place of exposure (AD/BD), heart rate, blood pressure, initial reason for the call defined by the European Resuscitation Council, unconsciousness and digestive bleeding. 3452 subjects were analyzed. RESULTS: The risk of in situ mortality in BD was 1.31 times higher than in AD (P=.050), that of hospital mortality in BD was 0.71 times lower than in AD (P=.011) and the risk of mortality at one year between counties and the combined mortality (in situ+hospital) did not contribute significant differences. CONCLUSIONS: Mortality (in situ+in-hospital, and one year aftercare) of patients treated by the out-of-hospital emergency medical services in AD (non-medicalized healthcare transport model) was similar to that of the BD region (mixed healthcare transport model).

Buoyancy-modulated Lagrangian drift in wavy-walled vertical channels as a model problem to understand drug dispersion in the spinal canal.

This paper investigates flow and transport in a slender wavy-walled vertical channel subject to a prescribed oscillatory pressure difference between its ends. When the ratio of the stroke length of the pulsatile flow to the channel wavelength is small, the resulting flow velocity is known to include a slow steady-streaming component resulting from the effect of the convective acceleration. Our study considers the additional effect of gravitational forces in configurations with a non-uniform density distribution. Specific attention is given to the slowly evolving buoyancy-modulated flow emerging after the deposition of a finite amount of solute whose density is different from that of the fluid contained in the channel, a relevant problem in connection with drug dispersion in intrathecal drug delivery (ITDD) processes, involving the injection of the drug into the cerebrospinal fluid that fills the spinal canal. It is shown that when the Richardson number is of order unity, the relevant limit in ITDD applications, the resulting buoyancy-induced velocities are comparable to those of steady streaming. As a consequence, the slow time-averaged Lagrangian motion of the fluid, involving the sum of the Stokes drift and the time-averaged Eulerian velocity, is intimately coupled with the transport of the solute, resulting in a slowly evolving problem that can be treated with two-time-scale methods. The asymptotic development leads to a time-averaged, nonlinear integro-differential transport equation that describes the slow dispersion of the solute, thereby circumventing the need to describe the small concentration fluctuations associated with the fast oscillatory motion. The ideas presented here can find application in developing reduced models for future quantitative analyses of drug dispersion in the spinal canal.

Incubation period of COVID-19: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. METHODS: For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. RESULTS: We included seven studies (n=792) in the meta-analysis. The heterogeneity (I2 83.0%, p<0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2-6.0) to 6.7 days (95% CI: 6.0-7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. CONCLUSION: Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns.

Retrospective study of gross and histopathologic lesions associated with closed chest cardiopulmonary resuscitation in dogs.

OBJECTIVES: To investigate and characterise the incidence of iatrogenic complications secondary to closed chest cardiopulmonary resuscitation in dogs. MATERIALS AND METHODS: Necropsy reports and histologic sections of tissues were retrospectively examined from 180 dogs that had received closed chest cardiopulmonary resuscitation to determine lesions associated with resuscitation. RESULTS: The most common complication was pulmonary haemorrhage (81/163, 49.7%, 95% confidence interval: 42.1 to 57.3), although only nine dogs had pulmonary haemorrhage of at least moderate severity. Liver fractures occurred in 16 of 180 cases (8.9%, 95% confidence interval: 5.5 to 14.0). Blood loss of >15% of blood volume into the abdomen and/or thorax occurred in 13 of 180 cases (7.2%, 95% confidence interval: 4.2 to 12.1). CLINICAL SIGNIFICANCE: Significant haemorrhage secondary to cardiopulmonary resuscitation may decrease the chances of achieving the return of spontaneous circulation or may cause or compound ischemic damage to critical organs if the return of spontaneous circulation is achieved. Following successful cardiopulmonary resuscitation, animals should be screened for cavitary or pulmonary haemorrhage, as significant haemorrhage could be a factor in recurrence of cardiac arrest.

Carotid atherosclerosis in virologically suppressed HIV patients: comparison with a healthy sample and prediction by cardiovascular risk equations.

OBJECTIVES: To compare the prevalence of carotid atherosclerosis in virologically suppressed HIV patients with that of a community sample, and to evaluate the capacity of various cardiovascular risk (CVR) equations for predicting carotid atherosclerosis. METHODS: This was a cross-sectional study with two randomly selected groups: HIV patients from an HIV unit and a control group drawn from the community. Participants were matched by age (30-80 years) and sex without history of cardiovascular disease. Carotid plaque, common carotid intima-media thickness (cc-IMT) and subclinical atherosclerosis (carotid plaque and/or cc-IMT > 75th percentile) were assessed by carotid ultrasound. The Systematic Coronary Risk Evaluation (SCORE), Framingham, REGICOR, reduced Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D), and COMVIH equations were applied, and their abilities to predict carotid plaque were compared using the area under the curve (AUC). RESULTS: Each group included 379 subjects (77.8% men, age 49.7 years). Duration of antiretroviral therapy was 15.5 years. There were no differences between the groups for carotid plaque (HIV, 33.2%; control, 31.3%), mean cc-IMT (HIV, 0.63 mm; control, 0.61 mm) or subclinical atherosclerosis (HIV, 42.9%; control, 47.9%). Thymidine analogues were independently associated with subclinical atherosclerosis in HIV-infected patients. CVR equations revealed AUCs between 0.715 and 0.807 for prediction of carotid plaque; prediction was better in the control group and did not improve when HIV-adapted scales were used. CONCLUSIONS: The features of carotid atherosclerosis did not differ between the HIV-infected and the control group, although CVR equations were more predictive for carotid plaque in controls than in HIV-infected patients. HIV-specific equations did not improve prediction.

Período de incubación de la COVID-19: revisión sistemática y metaanálisis / Incubation period of COVID-19: A systematic review and meta-analysis

Antecedentes y objetivo El período de incubación de la COVID-19 ayuda a determinar la duración óptima del período de cuarentena y a crear modelos predictivos de curvas de incidencia. Se han reportado resultados variables en recientes estudios y, por ello, el objetivo de esta revisión sistemática es proporcionar una estimación más precisa del período de incubación de la COVID-19. Métodos Se realizó una búsqueda bibliográfica en las bases de datos de Pubmed, Scopus/EMBASE y la Cochrane Library, incluyendo todos los estudios observacionales y experimentales que reportaban un período de incubación y que se habían publicado entre el 1 de enero y el 21 de marzo de 2020. Se estimó la media y el percentil 95 del período de incubación mediante metaanálisis, teniendo en cuenta la heterogeneidad entre los estudios y el análisis con variables moderadoras. Resultados Se incluyeron siete estudios (n = 792) en el metaanálisis. La heterogeneidad (I2 83,0%, p < 0,001) disminuyó significativamente cuando se tuvo en cuenta la calidad del estudio y el modelo estadístico utilizado como variables moderadoras (I2 15%). El período medio de incubación oscilaba entre 5,6 (IC 95%: 5,2 a 6,0) y 6,7 días (IC 95%: 6,0 a 7,4), según el modelo estadístico utilizado. El percentil 95 fue de 12,5 días cuando la edad media de los pacientes era de 60 años, aumentando un día por cada 10 años de edad. Conclusión Según los datos publicados sobre el período de incubación de la COVID-19, el tiempo medio entre la exposición y la aparición de los síntomas clínicos depende del modelo estadístico utilizado y el percentil 95, de la edad media de los pacientes. Se recomienda registrar el sexo y la edad en la recogida de los datos para poder analizar los posibles patrones diferenciales (AU)

Background and objective The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. Methods For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. Results We included seven studies (n = 792) in the meta-analysis. The heterogeneity (I2 83.0%, p < 0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2 to 6.0) to 6.7 days (95% CI: 6.0 to 7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. Conclusion Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns (AU)

[Incubation period of COVID-19: A systematic review and meta-analysis]. / Período de incubación de la COVID-19: revisión sistemática y metaanálisis.

BACKGROUND AND OBJECTIVE: The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. METHODS: For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. RESULTS: We included seven studies (n = 792) in the meta-analysis. The heterogeneity (I2 83.0%, p < 0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2 to 6.0) to 6.7 days (95% CI: 6.0 to 7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. CONCLUSION: Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns.

Report on G4-Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group.

BACKGROUND: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. AIMS: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. MATERIALS AND METHODS: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. RESULTS: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. DISCUSSION: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. CONCLUSION: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

Impact of patients' perception of COPD and treatment on adherence and health-related quality of life in real-world: Study in 53 community pharmacies.

BACKGROUND: Patient adherence to treatment in chronic obstructive pulmonary disease (COPD) is essential to optimize disease management. We aimed to assess the impact of patients' perception of their treatment and disease on adherence and Health-Related Quality of Life (HRQL) in patients attending a community pharmacy, where usually subjects have a better condition than those in clinical settings. METHODS: We performed a cross-sectional study of 318 patients with COPD in treatment with inhalers in the last 3 months from 53 community pharmacies. We assessed HRQL with St George's Respiratory Questionnaire (SGRQ). Persistence was assessed from the three previous refills and adherence through the Test of Adherence to Inhalers test. RESULTS: Persistence was achieved by 78.6% of the patients and 58.5% had good adherence. Patients having a multidose DPI and those with MDI showed a 2.8-fold and 4.1-fold increased association, respectively, with intermediate/poor adherence in comparison with those having a single dose DPI. Those patients who did not have knowledge about COPD (aOR 2.106, p = 0.006) and those who thought that the inhaler effectiveness was fair/poor (aOR 2.361, p = 0.006) were more likely to have intermediate/poor adherence. Overall SGRQ score was significantly worse in patients with intermediate/poor adherence (p = 0.036) and in those who thought the inhaler's effectiveness was fair/poor (p < 0.001). CONCLUSIONS: The type of inhaler and patients' knowledge and perceptions of their disease and treatment were associated with good adherence and higher HRQL. Clinicians should promote shared-decision making in the choice of inhaler depending on patients' individual abilities and beliefs.

Incubation period of COVID-19: A systematic review and meta-analysis. / Período de incubación de la COVID-19: revisión sistemática y metaanálisis.

BACKGROUND AND OBJECTIVE: The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. METHODS: For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. RESULTS: We included seven studies (n = 792) in the meta-analysis. The heterogeneity (I2 83.0%, p < 0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2 to 6.0) to 6.7 days (95% CI: 6.0 to 7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. CONCLUSION: Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns.

A randomized controlled double-blind study of rotigotine on neuropsychiatric symptoms in de novo PD.

Management of apathy, depression and anxiety in Parkinson's disease (PD) represents a challenge. Dopamine agonists have been suggested to be effective. This multicenter, randomized (1:1), double-blind study assessed the 6-month effect of rotigotine versus placebo on apathy, depression and anxiety in de novo PD. The primary outcome was the change of apathy, measured with the LARS. The secondary outcomes were the change in depression and anxiety, measured with BDI-2 and STAI-trait and state. Forty-eight drug-naive PD patients were included. The primary outcome was not reached, with a surprisingly high placebo effect on apathy (60%). There was no significant difference in the change of depression at 6 months between rotigotine and placebo. Trait-anxiety was significantly improved by rotigotine compared to placebo (p = 0.04). Compared to placebo, low dose rotigotine significantly improved trait anxiety, but not apathy and depression. The major placebo effect on apathy points towards the importance of a multidisciplinary and tight follow-up in the management of neuropsychiatric symptoms.

Neutron Capture on the s-Process Branching Point

The neutron capture cross sections of several unstable nuclides acting as branching points in the s process are crucial for stellar nucleosynthesis studies. The unstable ^{171}Tm (t_{1/2}=1.92 yr) is part of the branching around mass A∼170 but its neutron capture cross section as a function of the neutron energy is not known to date. In this work, following the production for the first time of more than 5 mg of ^{171}Tm at the high-flux reactor Institut Laue-Langevin in France, a sample was produced at the Paul Scherrer Institute in Switzerland. Two complementary experiments were carried out at the neutron time-of-flight facility (n_TOF) at CERN in Switzerland and at the SARAF liquid lithium target facility at Soreq Nuclear Research Center in Israel by time of flight and activation, respectively. The result of the time-of-flight experiment consists of the first ever set of resonance parameters and the corresponding average resonance parameters, allowing us to make an estimation of the Maxwellian-averaged cross sections (MACS) by extrapolation. The activation measurement provides a direct and more precise measurement of the MACS at 30 keV: 384(40) mb, with which the estimation from the n_TOF data agree at the limit of 1 standard deviation. This value is 2.6 times lower than the JEFF-3.3 and ENDF/B-VIII evaluations, 25% lower than that of the Bao et al. compilation, and 1.6 times larger than the value recommended in the KADoNiS (v1) database, based on the only previous experiment. Our result affects the nucleosynthesis at the A∼170 branching, namely, the ^{171}Yb abundance increases in the material lost by asymptotic giant branch stars, providing a better match to the available pre-solar SiC grain measurements compared to the calculations based on the current JEFF-3.3 model-based evaluation.