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Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), but initial outcomes can be modest.
Aims
To compare SSRI dose optimisation with four alternative second-line strategies in MDD patients unresponsive to an SSRI.
Method
Of 257 participants, 51 were randomised to SSRI dose optimisation (SSRI-Opt), 46 to lithium augmentation (SSRI+Li), 48 to nortriptyline combination (SSRI+NTP), 55 to switch to venlafaxine (VEN) and 57 to problem-solving therapy (SSRI+PST). Primary outcomes were week-6 response/remission rates, assessed by blinded evaluators using the 17-item Hamilton Depression Rating Scale (HDRS-17). Changes in HDRS-17 scores, global improvement and safety outcomes were also explored. EudraCT No. 2007-002130-11.
Results
Alternative second-line strategies led to higher response (28.2% v. 14.3%, odds ratio = 2.36 [95% CI 1.0–5.6], p = 0.05) and remission (16.9% v. 12.2%, odds ratio = 1.46, [95% CI 0.57–3.71], p = 0.27) rates, with greater HDRS-17 score reductions (−2.6 [95% CI −4.9 to −0.4], p = 0.021]) than SSRI-Opt. Significant/marginally significant effects were only observed in both response rates and HDRS-17 decreases for VEN (odds ratio = 2.53 [95% CI 0.94–6.80], p = 0.067; HDRS-17 difference: −2.7 [95% CI −5.5 to 0.0], p = 0.054) and for SSRI+PST (odds ratio = 2.46 [95% CI 0.92 to 6.62], p = 0.074; HDRS-17 difference: −3.1 [95% CI −5.8 to −0.3], p = 0.032). The SSRI+PST group reported the fewest adverse effects, while SSRI+NTP experienced the most (28.1% v. 75%; p < 0.01), largely mild.
Conclusions
Patients with MDD and insufficient response to SSRIs would benefit from any other second-line strategy aside from dose optimisation. With limited statistical power, switching to venlafaxine and adding psychotherapy yielded the most consistent results in the DEPRE'5 study.
Before a binary system enters into a common envelope (CE) phase, accretion from the primary star onto the companion star through Roche Lobe overflow (RLOF) will lead to the formation of an accretion disk, which may generate jets. Accretion before and during the CE may alter the outcome of the interaction. Previous studies have considered different aspects of this physical mechanism. Here we study the properties of an accretion disk formed via 3D hydrodynamic simulations of the RLOF mass transfer between a 7 M$_{\odot}$, red supergiant star and a 1.4 M$_{\odot}$, neutron star companion. We simulate only the volume around the companion for improved resolution. We use a 1D implicit mesa simulation of the evolution of the system during 30 000 yr between the on-set of the RLOF and the CE to guide the binary parameters and the mass-transfer rate, while we simulate only 21 yr of the last part of the RLOF in 3D using an ideal gas quasi-isothermal equation of state. We expect that a pre-CE disk under these parameters will have a mass of $\sim 5\times 10^{-3}$ M$_{\odot}$ and a radius of $\sim40\ R_\odot$ with a scale height of $\sim 5\ R$$_{\odot}$. The temperature profile of the disk is shallower than that predicted by the formalism of Shakura and Sunyaev, but more reasonable cooling physics would need to be included. We stress test these results with respect to a number of physical and numerical parameters, as well as simulation choices, and we expect them to be reasonable within a factor of a few for the mass and 15% for the radius. We also contextualise our results within those presented in the literature, in particular with respect to the dimensionality of simulations and the adiabatic index. We discuss the measured accretion rate in the context of the Shakura and Sunyaev formalism and debate the viscous mechanisms at play, finishing with a list of prospects for future work.
Migration and forced displacement are remodeling cities and countries. The number of people being displaced due to war, persecution, serious human rights violations and disturbance in social and political order has increased exponentially. Colombia is a vivid example of a massive mixed migration crisis, receiving refugees from Venezuela, crossed by migrants of various origins and a protracted internal displacement affecting mostly its Pacific Region.
Objectives:
The purpose of this study is to showcase the field experience of the Colombian EMT Hospital Barco San Raffaele through its response to two forced displacement crises: (1) in Colombia’s Pacific Region, and (2) Venezuelan refugees, aiming at providing evidence for the improvement of EMTs Type1 Standards of care.
Method/Description:
Mix method case study methodology is employed to describe a complex phenomenon of mixed-migration. Data is gathered from response reports, program activities, clinical presentations; data will be analyzed using triangulation method, allowing comparison between adaption of health services, configuration of teams, legal frameworks, using the surge capacity components (4S) and current standards of care for Type1 EMTs.
Results/Outcomes:
Preliminary analysis shows the need to adapt services and configure teams to respond to volatile contexts; collaboration, negotiation, coordination, interoperability with local institutions, organizations and community leaders prove to be key to ensure credibility, access, and quality of care.
Conclusion:
Enabling factors such as legal frameworks have a major impact/influence in ensuring access to care to displaced populations, facilitating or preventing responses. EMTs Type 1 Standards of care must be adapted if teams are to respond to this worldwide phenomenon.
In individuals with severe mental illness (SMI), low muscle strength heightens the risk of mortality and chronic disease development. Routine muscle strength assessments could identify vulnerabilities, thereby reducing the growing burden associated with SMI. However, integration into clinical settings faces obstacles because of limited resources and inadequate healthcare staff training. The 5 sit-to-stand (5-STS) test offers an alternative for measuring muscle strength compared with more complex or demanding tests. Nevertheless, its validity in individuals with SMI remains unexplored.
Aims
This study aimed to analyse the criterion validity of the 5-STS test in SMI, considering potential age, gender and body mass index influences.
Method
In a cross-sectional study following the ‘STrengthening the Reporting of OBservational studies in Epidemiology’ (STROBE) guidelines, 82 adults with SMI (aged 18–65, 24 women) were assessed. Participants underwent both the 5-STS test and the isometric knee extension strength (KES) test.
Results
Analysis revealed a significant moderate correlation coefficient and intraclass correlation coefficient (−0.58 for both) for all participants, indicating that the measures are valid and assess related aspects of the same construct. Strong agreement was observed in women and the older age groups. The 5-STS test demonstrated accuracy, with a standard error of estimate lower than the within-subject variability on the KES test. Bland–Altman plots showed limits of agreement values of −3.39 and 3.52 for the entire sample, and heteroscedasticity analyses indicated consistent differences between the 5-STS and KES tests across all groups analysed, except in the women's group.
Conclusions
The 5-STS test seems to be a valid test for assessing muscle strength in individuals with SMI, supporting its usefulness for routine assessment in clinical settings, facilitating detection and intervention in critical situations.
We introduce a versatile high-repetition-rate solid tape target system suitable for relativistic laser-plasma driven secondary sources. We demonstrate the operation and stability monitoring based on a petawatt laser focused at 1 Hz. Experiments were carried out at the VEGA-3 laser system of the Centro de Láseres Pulsados facility where results for different tape materials and thicknesses are presented. Experimental proton spectra were recorded by a Thomson parabola spectrometer and a time-of-flight detector. In addition, non-invasive detectors, such as a target charging monitor and ionization chamber detectors, were tested as metrology for the stability of the source. Degradation of the proton signal at high-repetition-rate operation was observed and it was solved by online optimization of the relative focus position of the target and laser beam parameters. We report the use of the tape target for bursts of 1000 shots at 1 Hz with mean cut-off energies of about 10 MeV in optimized interaction conditions.
Burkitt lymphoma (BL) is a rare and highly aggressive subtype of non-Hodgkin’s lymphoma. Several studies have identified prognostic factors (PFs) for disease progression and mortality among adults with BL. However, there is no consensus on risk stratification based on PFs. This study aims to identify, critically assess, and synthesize the available evidence on PFs for survival in adults with BL.
Methods
A systematic review of the literature was conducted. MEDLINE, Embase, and CENTRAL were searched from inception to 22 February 2022. Randomized or non-randomized clinical trials and longitudinal observational studies were eligible for inclusion. Reference screening, data extraction, and risk-of-bias assessment using the Quality in Prognosis Studies (QUIPS) tool for prognostic factor studies were conducted independently and in duplicate. Publication bias was examined by visual inspection of funnel plots. Effect measures and the corresponding 95% confidence intervals were pooled with an indirect variance estimation in meta-analyses using Review Manager 5, and sensitivity analyses were conducted. Certainty of evidence was assessed using GRADE.
Results
The search identified 1,119 references after duplicate removal. Of these, 76 potentially relevant papers were selected for full-text assessment and 36 studies (N=10,882) reported in 39 articles were eligible for inclusion. Older age, higher performance status, and central nervous system involvement were associated with poorer overall survival (OS) and progression-free survival (PFS). Black patients exhibited significantly lower OS and relative survival. Bone marrow involvement and higher albumin levels were associated with poorer OS. Treatment with rituximab and treatment with methotrexate were associated with better OS and PFS. No significant differences in survival were found for HIV status, sex, and risk stratification.
Conclusions
This study, framed within a collaboration with European Reference Network EuroBloodNet, provides a comprehensive and methodologically rigorous evidence review on PFs in adults with BL. Several significant associations of PFs and survival estimates were observed, providing data to inform treatment decisions and to improve patient care.
Electroanatomic mapping (EAM) has been shown to be an alternative procedure to fluoroscopy for the implantation of conduction system pacing (His-bundle pacing [HBP] and left bundle branch pacing [LBBP]) in patients with severe bradyarrhythmias, mainly those vulnerable to ionizing radiation. However, the evidence of its beneficial and harmful effects has not been assessed in a systematic review (SR).
Methods
An SR of the available scientific literature was conducted on the safety, effectiveness, and cost-effectiveness of implantation of the HBP and LBBP using EAM system versus fluoroscopy in patients with bradycardia with an indication for pacing therapy. Cochrane methodology and PRISMA statement for reporting were followed. A partial economic evaluation was carried out to compare the costs of both pacemaker implantation strategies from the perspective of the Spanish National Health System. A budget impact analysis was also conducted with a five-year horizon.
Results
Seven comparative observational studies (N=259) analyzing the use of EAM versus fluoroscopy were selected. Statistically significant differences were observed in total fluoroscopy time: −9.87 minutes (95% confidence interval [CI]: −14.20, −5.53; p<0.01; I2=95%; k=7; n=231); His-lead fluoroscopic time: −8.08 minutes (95% CI: −10.36, −5.81; p<0.01; I2=0%; k=2; n=50); and His-lead radiation dose: −17.21 mGy (95% CI: −24.08, −10.34; p<0.01; k=1; n=20). No differences in total radiation dose, procedural success, immediate procedure-related complications, electrode revision, or device infection were found. The use of EAM represents an increase of EUR1,397.81 (USD1,513.88) per patient and a net budget impact of EUR1.63 million (USD1.77 million).
Conclusions
No differences between EAM and fluoroscopy in terms of procedure success and safety were found. Therefore, EAM is a valuable alternative for patients who should not be exposed to ionizing radiation. The inclusion of EAM systems, for the indication under study, in routine clinical practice would mean an increase in costs for the Spanish National Health System.
While a clear human presence may be recognised in the Andes by 12 000–11 000 cal BP, most archaeological research has focused on occupation of the Andean highlands. To understand the initial occupation of inland areas of South America, the authors consider regional connections and spatial exploitation strategies of hunter-gatherers highlighted in a recent survey of Andean sites. Focusing on north-central Chile, artefacts and radiocarbon dates from three rock shelters suggest sporadic and brief occupation during the Terminal Pleistocene–Early Holocene. Co-occurrence of marine and montane resources, the authors argue, demonstrates a strategy of high mobility and local adaptation in early Andean occupation, using rock shelters as landmarks to navigate and learn new landscapes.
TwinsMX registry is a national research initiative in Mexico that aims to understand the complex interplay between genetics and environment in shaping physical and mental health traits among the country’s population. With a multidisciplinary approach, TwinsMX aims to advance our knowledge of the genetic and environmental mechanisms underlying ethnic variations in complex traits and diseases, including behavioral, psychometric, anthropometric, metabolic, cardiovascular and mental disorders. With information gathered from over 2800 twins, this article updates the prevalence of several complex traits; and describes the advances and novel ideas we have implemented such as magnetic resonance imaging. The future expansion of the TwinsMX registry will enhance our comprehension of the intricate interplay between genetics and environment in shaping health and disease in the Mexican population. Overall, this report describes the progress in the building of a solid database that will allow the study of complex traits in the Mexican population, valuable not only for our consortium, but also for the worldwide scientific community, by providing new insights of understudied genetically admixed populations.
Astigmatism and myopia are two common ocular refractive errors that can impact daily life, including learning and productivity. Current knowledge suggests that the etiology of these conditions is the result of a complex interplay between genetic and environmental factors. Studies in populations of European ancestry have demonstrated a higher concordance of refractive errors in monozygotic (MZ) twins compared to dizygotic (DZ) twins. However, there is a lack of studies on genetically informative samples of multi-ethnic ancestry. This study aimed to estimate the genetic contribution to astigmatism and myopia in the Mexican population. A sample of 1399 families, including 243 twin pairs and 1156 single twins, completed a medical questionnaire about their own and their co-twin’s diagnosis of astigmatism and myopia. Concordance rates for astigmatism and myopia were estimated, and heritability and genetic correlations were determined using a bivariate ACE Cholesky decomposition method, decomposed into A (additive genetic), C (shared environmental) and E (unique environmental) components. The results showed a higher concordance rate for astigmatism and myopia for MZ twins (.74 and .74, respectively) than for DZ twins (.50 and .55). The AE model, instead of the ACE model, best fitted the data. Based on this, heritability estimates were .81 for astigmatism and .81 for myopia, with a cross-trait genetic correlation of rA = .80, nonshared environmental correlation rE = .89, and a phenotypic correlation of rP = .80. These results are consistent with previous findings in other populations, providing evidence for a similar genetic architecture of these conditions in the multi-ethnic Mexican population.
The aim of this contribution is to provide a new methodology regarding the use of photogrammetry and 3D modelling in the classroom. By means of a practicum taught at Complutense University of Madrid and a survey conducted afterwards, we show the different steps of the activity, as well as the reception of the students, who learnt to elaborate 3D figures.
Conflicts are increasingly analysed as exhibiting a stealth complexity in which triggers and consequences are intricately linked to climate, environmental degradation and the struggle to control a finite pool of natural resources. The climate crisis is a multifaceted reality and, against this background, many pressing priorities compete with each other. The disruptive effect of climate variability and change on food systems is particularly acute and constitutes a direct and tangible threat to livelihoods globally. The objective of this paper is to demonstrate and discuss the importance of food systems under a climate crisis in exacerbating conflicts in the Sahelian region and propose interventions beyond and complementary to the usual military and security solutions. We demonstrate for the Sahel that (i) climate hazards are frequent and exposure to climate variability is high, (ii) hotspots of high climate variability and conflict exist, and (iii) impact pathways by which climate exacerbates food systems that can lead to conflicts are documented in the literature. While these three findings suggest clear links between conflict and climate, we find that (iv) current peace indices do not include climate and food systems indicators and therefore provide an uncomplete picture, and (v) food systems programming for climate adaptation has so far not explicitly considered peace and security outcomes. Furthermore, we propose that food systems programming that truly tackles the climate crisis should take more explicit account of peace and security outcomes in conflict-affected areas.
El Niño cave, located on the south-eastern border of the Spanish Meseta, hosts a discontinuous sequence including Middle Palaeolithic and Neolithic levels, along with Upper Palaeolithic and Levantine style paintings. It is a key site for understanding human occupations of inland Iberia during the Palaeolithic and early prehistory. This paper summarises the main results of a multidisciplinary project aimed at defining the prehistoric human occupations at the site.
A late Pleistocene glaciolacustrine record was studied at Fagnano Lake (54°35´S, 67°20´W), central Isla Grande de Tierra del Fuego, southernmost South America. Two profiles from the Río Valdéz outcrop were collected for isotopic, geochemical, sedimentological, and geophysical analyses. The sedimentological characteristics, such as rhythmites, presence of dropstones, absence of fossil record, and scarce presence of organic matter, suggest deposition in an ice-contact lake, possibly dammed by the Fagnano paleoglacier. Organic matter of C3 plant origin suggests certain cold and wet conditions. A chronology of the late Pleistocene outcrop was obtained from five 14C ages resulting in an age-depth model. The time span covered 49.01 cal ka BP to 32.14 cal ka BP. Based on the thickness of the deposit and the calculated average sedimentation rate, the glacial environment could have been present in the study area prior to the last glacial maximum, in agreement with the Inútil-San Sebastián paleoglacier. Both glaciers flowed from the same mountain ice sheet in the Darwin Cordillera, which makes it possible to infer a different behavior of this ice cap from those of the Patagonian Andes, perhaps forced by different atmospheric dynamics and proximity to the wet and cold subantarctic air masses.
This study aimed to identify clinical and cognitive factors associated with increased risk for difficult-to-treat depression (DTD) or treatment-resistant depression (TRD).
Methods.
A total of 229 adult outpatients with major depression were recruited from the mental health unit at a public hospital. Participants were subdivided into resistant and nonresistant groups according to their Maudsley Staging Model score. Sociodemographic, clinical, and cognitive (objective and subjective measures) variables were compared between groups, and a logistic regression model was used to identify the factors most associated with TRD risk.
Results.
TRD group patients present higher verbal memory impairment than the nonresistant group irrespective of pharmacological treatment or depressive symptom severity. Logistic regression analysis showed that low verbal memory scores (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.38–2.95) together with high depressive symptom severity (OR: 1.29; CI95%: 1.01–1.65) were associated with TRD risk.
Conclusions.
Our findings align with neuroprogression models of depression, in which more severe patients, defined by greater verbal memory impairment and depressive symptoms, develop a more resistant profile as a result of increasingly detrimental neuronal changes. Moreover, our results support a more comprehensive approach in the evaluation and treatment of DTD in order to improve illness course. Longitudinal studies are warranted to confirm the predictive value of verbal memory and depression severity in the development of TRD.
A thermo-tolerant diatom species has been isolated from Tunisian hot spring water (40°C). The isolated diatom has been molecularly identified and classified into the genus Halamphora. The growth kinetics, lipid content and distribution of fatty acids were assessed at 20 and 30°C temperature levels and constant irradiance in controlled batch cultures (11 days). Halamphora sp. showed better growth (μ = 0.53 day−1) and a higher lipid yield (25% of the dry weight) at a higher temperature (30°C). Under the two temperatures tested, the highest lipid and fatty acid contents were mainly reached during the stationary growth phase. The fatty acid profile showed a significant content of two essential fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (AA, 20:4n-6), reaching ~15% and ~21% of the total fatty acids, respectively, at 20°C and 30°C. The distribution of the different components of the fatty acids showed that EPA and AA were mainly located in the neutral lipid fraction in the stationary phase.
How non-spherical particles orient as they settle in a flow has important practical implications in a number of scientific and engineering problems. In a quiescent fluid, a slowly settling particle orients so that it settles with its broad side first. This is an effect of the torque due to convective inertia of the fluid that is set in motion by the settling particle, which maximises the drag experienced by the particle. Turbulent fluid-velocity gradients, on the other hand, tend to randomise the particle orientation. Recently the settling of non-spherical particles in turbulence was analysed neglecting the effect of convective fluid inertia, but taking into account the effect of the turbulent fluid-velocity gradients on the particle orientation. These studies reached the opposite conclusion, namely that the particle tends to settle with its narrow edge first, therefore minimising the drag on the particle. Here, we consider both effects, the convective inertial torque as well as the torque due to fluctuating fluid-velocity gradients. We ask under which circumstances either one or the other dominates. To this end we estimate the ratio of the magnitudes of the two torques. Our estimates suggest that the fluid-inertia torque prevails in high-Reynolds-number flows. In this case non-spherical particles tend to settle with orientations maximising drag. But when the Reynolds number is small, then the torque due to fluid-velocity gradients may dominate, causing the particle to settle with its narrow edge first, minimising the drag.
This project is designed for children under 18 years that have to frequently visit hospitals or that have to endure long-term hospital stays. The aims are to entertain these children and their families, to increase their scientific culture, and to promote scientific vocations. So far we have visited one hospital in Mexico City bringing astronomy to the patients and their families. We have developed five hands-on activities and one musical activity that ensures that all the children can participate independently of their conditions. We plan to expand this project to other hospitals and other cities in the country. Our next challenge is to start virtual visits to hospitals.
In cases of mass-casualty incidents (MCIs), triage represents a fundamental tool for the management of and assistance to the wounded, which helps discriminate not only the priority of attention, but also the priority of referral to the most suitable center.
Hypothesis/Problem:
The objective of this study was to evaluate the capacity of different prehospital triage systems based on physiological parameters (Shock Index [SI], Glasgow-Age-Pressure Score [GAP], Revised Trauma Score [RTS], and National Early Warning Score 2 [NEWS2]) to predict early mortality (within 48 hours) from the index event for use in MCIs.
Methods:
This was a longitudinal prospective observational multi-center study on patients who were attended by Advanced Life Support (ALS) units and transferred to the emergency department (ED) of their reference hospital. Collected were: demographic, physiological, and clinical variables; main diagnosis; and data on early mortality. The main outcome variable was mortality from any cause within 48 hours.
Results:
From April 1, 2018 through February 28, 2019, a total of 1,288 patients were included in this study. Of these, 262 (20.3%) participants required assistance for trauma and injuries by external agents. Early mortality within the first 48 hours due to any cause affected 69 patients (5.4%). The system with the best predictive capacity was the NEWS2 with an area under the curve (AUC) of 0.891 (95% CI, 0.84-0.94); a sensitivity of 79.7% (95% CI, 68.8-87.5); and a specificity of 84.5% (95% CI, 82.4-86.4) for a cut-off point of nine points, with a positive likelihood ratio of 5.14 (95% CI, 4.31-6.14) and a negative predictive value of 98.7% (95% CI, 97.8-99.2).
Conclusion:
Prehospital scores of the NEWS2 are easy to obtain and represent a reliable test, which make it an ideal system to help in the initial assessment of high-risk patients, and to determine their level of triage effectively and efficiently. The Prehospital Emergency Medical System (PhEMS) should evaluate the inclusion of the NEWS2 as a triage system, which is especially useful for the second triage (evacuation priority).