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Background and Objectives: Data on care home admission and survival rates of patients with syndromes associated with frontotemporal lobar degeneration (FTLD) are limited. However, their estimation is essential to plan trials and assess the efficacy of intervention. Population-based registers provide unique samples for this estimate. The aim of this study was to assess care home admission rate, survival rate, and their predictors in incident patients with FTLD-associated syndromes from the European FRONTIERS register-based study., Methods: We conducted a prospective longitudinal multinational observational registry study, considering incident patients with FTLD-associated syndromes diagnosed between June 1, 2018, and May 31, 2019, and followed for up to 5 years till May 31, 2023. We enrolled patients fulfilling diagnosis of the behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS), and FTD with motor neuron disease (FTD-MND). Kaplan-Meier analysis and Cox multivariable regression models were used to assess care home admission and survival rates. The survival probability score (SPS) was computed based on independent predictors of survivorship., Results: A total of 266 incident patients with FTLD were included (mean age ± SD = 66.7 ± 9.0; female = 41.4%). The median care home admission rate was 97 months (95% CIs 86-98) from disease onset and 57 months (95% CIs 56-58) from diagnosis. The median survival was 90 months (95% CIs 77-97) from disease onset and 49 months (95% CIs 44-58) from diagnosis. Survival from diagnosis was shorter in FTD-MND (hazard ratio [HR] 4.59, 95% CIs 2.49-8.76, p < 0.001) and PSP/CBS (HR 1.56, 95% CIs 1.01-2.42, p = 0.044) compared with bvFTD; no differences between PPA and bvFTD were found. The SPS proved high accuracy in predicting 1-year survival probability (area under the receiver operating characteristic curve = 0.789, 95% CIs 0.69-0.87), when defined by age, European area of residency, extrapyramidal symptoms, and MND at diagnosis., Discussion: In FTLD-associated syndromes, survival rates differ according to clinical features and geography. The SPS was able to predict prognosis at individual patient level with an accuracy of ∼80% and may help to improve patient stratification in clinical trials. Future confirmatory studies considering different populations are needed.

Large-scale studies of gene expression are commonly influenced by biological and technical sources of expression variation, including batch effects, sample characteristics, and environmental impacts. Learning the causal relationships between observable variables may be challenging in the presence of unobserved confounders. Furthermore, many high-dimensional regression techniques may perform worse. In fact, controlling for unobserved confounding variables is essential, and many deconfounding methods have been suggested for application in a variety of situations. The main contribution of this article is the development of a two-stage deconfounding procedure based on Bow-free Acyclic Paths (BAP) search developed into the framework of Structural Equation Models (SEM), called SEMbap(). In the first stage, an exhaustive search of missing edges with significant covariance is performed via Shipley d-separation tests; then, in the second stage, a Constrained Gaussian Graphical Model (CGGM) is fitted or a low dimensional representation of bow-free edges structure is obtained via Graph Laplacian Principal Component Analysis (gLPCA). We compare four popular deconfounding methods to BAP search approach with applications on simulated and observed expression data. In the former, different structures of the hidden covariance matrix have been replicated. Compared to existing methods, BAP search algorithm is able to correctly identify hidden confounding whilst controlling false positive rate and achieving good fitting and perturbation metrics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Grassi, Tarantino. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality., Patients and Methods: In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014., Results: Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26)., Discussion and Conclusion: The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Ciccone reports grants from Daiichi-Sankyo; grants from Italfarmaco; and grants from Alexion Pharmaceuticals.Dr Paciaroni reports compensation from SANOFI-AVENTIS U.S. LLC for other services; compensation from PFIZER CANADA INC for other services; compensation from iRhythm Technologies for other services; compensation from Daiichi Sankyo Europe GmbH for other services; and compensation from Bristol-Myers Squibb for other services.The other Authors have nothing to disclose.

Background: Oral anticoagulation is becoming more common with the aging population, which raises concern for the risk of invasive procedures that can cause bleeding, such as chest tube placement (thoracostomy). With the increase in CT imaging, more pneumothoraces and hemothoraces are being identified. The relative risk of thoracostomy in the presence of anticoagulation is not well-established. The objective of this study was to determine whether pre-injury anticoagulation affects the relative risk of tube thoracostomy following significant chest trauma., Methods: This retrospective cohort study used data from the 2019 American College of Surgeons-Trauma Quality Program (ACS-TQP) database using R version 4.2.2. Data from the database was filtered based on inclusion and exclusion criteria. Outcomes were then assessed with the population of interest. Demographics, vitals, comorbidities, and injury parameters were also collected for each patient. This study included all adult patients (≥18 years) presenting with traumatic hemothorax, pneumothorax, or hemopneumothorax. Patients with missing data in demographics, vitals, comorbidities, injury parameters, or outcomes, as well as those with no signs of life upon arrival, were excluded from the study. Patients were stratified into groups based on whether they had pre-injury anticoagulation and whether they had a chest tube placed in the hospital. The primary outcome was mortality, and the secondary outcome was hospital length of stay (LOS). Logistic and standard regressions were used by a statistician to control for age, sex, and Injury Severity Score (ISS)., Results: Our study population included 72,385 patients (4250 with pre-injury anticoagulation and 68,135 without pre-injury anticoagulation). Pre-injury anticoagulation and thoracostomy were each independently associated with increased mortality and LOS. However, there was a non-significant interaction term between pre-injury anticoagulation and thoracostomy for both outcomes, indicating that their combined effects on mortality and LOS did not differ significantly from the sum of their individual effects., Conclusion: This study suggests that both pre-injury anticoagulation and thoracostomy are risk factors for mortality and increased LOS in adult patients presenting with hemothorax, pneumothorax, or hemopneumothorax, but they do not interact with each other. We recommend further study of this phenomenon to potentially improve clinical guidelines., Level of Evidence: Therapeutic, Level III., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Whether statin use after spontaneous intracerebral haemorrhage (ICH) increases the risk of recurrent ICH is uncertain., Methods: In the setting of the Multicentric Study on Cerebral Haemorrhage in Italy we followed up a cohort of 30-day ICH survivors, consecutively admitted from January 2002 to July 2014, to assess whether the use of statins after the acute event is associated with recurrent cerebral bleeding., Results: 1623 patients (mean age, 73.9±10.3 years; males, 55.9%) qualified for the analysis. After a median follow-up of 40.5 months (25th to 75th percentile, 67.7) statin use was not associated with increased risk of recurrent ICH either in the whole study group (adjusted HR, 0.99; 95% CI 0.64 to 1.53) or in the subgroups defined by haematoma location (deep ICH, adjusted HR, 0.74; 95% CI 0.35 to 1.57; lobar ICH, adjusted HR, 1.09; 95% CI 0.62 to 1.90), intensity of statins (low-moderate intensity statins, adjusted HR, 0.93; 95% CI 0.58 to 1.49; high-intensity statins, adjusted HR, 1.48; 95% CI 0.66 to 3.31) and use of statins before the index event (adjusted HR, 0.66; 95% CI 0.38 to 1.17)., Conclusions: Statin use appears to be unrelated to the risk of ICH recurrence., Competing Interests: Competing interests: AC reports grants from Daiichi-Sankyo; grants from Italfarmaco; and grants from Alexion Pharmaceuticals. MP reports compensation from SANOFI-AVENTIS US LLC for other services; compensation from PFIZER CANADA for other services; compensation from iRhythm Technologies for other services; compensation from Daiichi Sankyo Europe GmbH for other services; and compensation from Bristol-Myers Squibb for other services. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The identification of patients surviving an acute intracerebral hemorrhage who are at a long-term risk of arterial thrombosis is a poorly defined, crucial issue for clinicians., Methods: In the setting of the MUCH-Italy (Multicenter Study on Cerebral Haemorrhage in Italy) prospective observational cohort, we enrolled and followed up consecutive 30-day intracerebral hemorrhage survivors to assess the long-term incidence of arterial thrombotic events, to assess the impact of clinical and radiological variables on the risk of these events, and to develop a tool for estimating such a risk at the individual level. Primary end point was a composite of ischemic stroke, myocardial infarction, or other arterial thrombotic events. A point-scoring system was generated by the β-coefficients of the variables independently associated with the long-term risk of arterial thrombosis, and the predictive MUCH score was calculated as the sum of the weighted scores., Results: Overall, 1729 patients (median follow-up time, 43 months [25th to 75th percentile, 69.0]) qualified for inclusion. Arterial thrombotic events occurred in 169 (9.7%) patients. Male sex, diabetes, hypercholesterolemia, atrial fibrillation, and personal history of coronary artery disease were associated with increased long-term risk of arterial thrombosis, whereas the use of statins and antithrombotic medications after the acute intracerebral hemorrhage was associated with a reduced risk. The area under the receiver operating characteristic curve of the MUCH score predictive validity was 0.716 (95% CI, 0.56-0.81) for the 0- to 1-year score, 0.672 (95% CI, 0.58-0.73) for the 0- to 5-year score, and 0.744 (95% CI, 0.65-0.81) for the 0- to 10-year score. C statistic for the prediction of events that occur from 0 to 10 years was 0.69 (95% CI, 0.64-0.74)., Conclusions: Intracerebral hemorrhage survivors are at high long-term risk of arterial thrombosis. The MUCH score may serve as a simple tool for risk estimation., Competing Interests: Disclosures Dr Ciccone reports grants from Daiichi Sankyo, Italfarmaco, and Alexion Pharmaceuticals. Dr Paciaroni reports compensation from Sanofi-Aventis U.S. LLC, Pfizer Canada, Inc, iRhythm Technologies, Daiichi Sankyo Europe GmbH, and Bristol Myers Squibb for other services. The other authors report no conflicts.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive disease for which no curative treatment is currently available., Objective: This study aimed to investigate whether cortico-spinal transcranial direct current stimulation (tDCS) could mitigate symptoms in ALS patients via a randomized, double-blind, sham-controlled trial, followed by an open-label phase., Methods: Thirty-one participants were randomized into two groups for the initial controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS), while Group 2 received cortico-spinal stimulation (real tDCS) for five days/week for two weeks (T1), with an 8-week (T2) follow-up (randomized, double-blind, sham-controlled phase). At the 24-week follow-up (T3), all participants (Groups 1 and 2) received a second treatment of anodal bilateral motor cortex and cathodal spinal stimulation (real tDCS) for five days/week for two weeks (T4). Follow-up evaluations were performed at 32-weeks (T5) and 48-weeks (T6) (open-label phase). At each time point, clinical assessment, blood sampling, and intracortical connectivity measures using transcranial magnetic stimulation (TMS) were evaluated. Additionally, we evaluated survival rates., Results: Compared to sham stimulation, cortico-spinal tDCS significantly improved global strength, caregiver burden, and quality of life scores, which correlated with the restoration of intracortical connectivity measures. Serum neurofilament light levels decreased among patients who underwent real tDCS but not in those receiving sham tDCS. The number of completed 2-week tDCS treatments significantly influenced patient survival., Conclusions: Cortico-spinal tDCS may represent a promising therapeutic and rehabilitative approach for patients with ALS. Further larger-scale studies are necessary to evaluate whether tDCS could potentially impact patient survival., Clinical Trial Registration: NCT04293484., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Motivation: With the exponential growth of expression and protein-protein interaction (PPI) data, the identification of functional modules in PPI networks that show striking changes in molecular activity or phenotypic signatures becomes of particular interest to reveal process-specific information that is correlated with cellular or disease states. This requires both the identification of network nodes with reliability scores and the availability of an efficient technique to locate the network regions with the highest scores. In the literature, a number of heuristic methods have been suggested. We propose SEMtree(), a set of tree-based structure discovery algorithms, combining graph and statistically interpretable parameters together with a user-friendly R package based on structural equation models framework., Results: Condition-specific changes from differential expression and gene-gene co-expression are recovered with statistical testing of node, directed edge, and directed path difference between groups. In the end, from a list of seed (i.e. disease) genes or gene P-values, the perturbed modules with undirected edges are generated with five state-of-the-art active subnetwork detection methods. The latter are supplied to causal additive trees based on Chu-Liu-Edmonds' algorithm (Chow and Liu, Approximating discrete probability distributions with dependence trees. IEEE Trans Inform Theory 1968;14:462-7) in SEMtree() to be converted in directed trees. This conversion allows to compare the methods in terms of directed active subnetworks. We applied SEMtree() to both Coronavirus disease (COVID-19) RNA-seq dataset (GEO accession: GSE172114) and simulated datasets with various differential expression patterns. Compared to existing methods, SEMtree() is able to capture biologically relevant subnetworks with simple visualization of directed paths, good perturbation extraction, and classifier performance., Availability and Implementation: SEMtree() function is implemented in the R package SEMgraph, easily available at https://CRAN.R-project.org/package=SEMgraph., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022., Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1-4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models' predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models' forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models' past predictive performance., Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models' forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models' forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models' forecasts of deaths (N=763 predictions from 20 models). Across a 1-4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models., Conclusions: Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks., Funding: AA, BH, BL, LWa, MMa, PP, SV funded by National Institutes of Health (NIH) Grant 1R01GM109718, NSF BIG DATA Grant IIS-1633028, NSF Grant No.: OAC-1916805, NSF Expeditions in Computing Grant CCF-1918656, CCF-1917819, NSF RAPID CNS-2028004, NSF RAPID OAC-2027541, US Centers for Disease Control and Prevention 75D30119C05935, a grant from Google, University of Virginia Strategic Investment Fund award number SIF160, Defense Threat Reduction Agency (DTRA) under Contract No. HDTRA1-19-D-0007, and respectively Virginia Dept of Health Grant VDH-21-501-0141, VDH-21-501-0143, VDH-21-501-0147, VDH-21-501-0145, VDH-21-501-0146, VDH-21-501-0142, VDH-21-501-0148. AF, AMa, GL funded by SMIGE - Modelli statistici inferenziali per governare l'epidemia, FISR 2020-Covid-19 I Fase, FISR2020IP-00156, Codice Progetto: PRJ-0695. AM, BK, FD, FR, JK, JN, JZ, KN, MG, MR, MS, RB funded by Ministry of Science and Higher Education of Poland with grant 28/WFSN/2021 to the University of Warsaw. BRe, CPe, JLAz funded by Ministerio de Sanidad/ISCIII. BT, PG funded by PERISCOPE European H2020 project, contract number 101016233. CP, DL, EA, MC, SA funded by European Commission - Directorate-General for Communications Networks, Content and Technology through the contract LC-01485746, and Ministerio de Ciencia, Innovacion y Universidades and FEDER, with the project PGC2018-095456-B-I00. DE., MGu funded by Spanish Ministry of Health / REACT-UE (FEDER). DO, GF, IMi, LC funded by Laboratory Directed Research and Development program of Los Alamos National Laboratory (LANL) under project number 20200700ER. DS, ELR, GG, NGR, NW, YW funded by National Institutes of General Medical Sciences (R35GM119582; the content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the National Institutes of Health). FB, FP funded by InPresa, Lombardy Region, Italy. HG, KS funded by European Centre for Disease Prevention and Control. IV funded by Agencia de Qualitat i Avaluacio Sanitaries de Catalunya (AQuAS) through contract 2021-021OE. JDe, SMo, VP funded by Netzwerk Universitatsmedizin (NUM) project egePan (01KX2021). JPB, SH, TH funded by Federal Ministry of Education and Research (BMBF; grant 05M18SIA). KH, MSc, YKh funded by Project SaxoCOV, funded by the German Free State of Saxony. Presentation of data, model results and simulations also funded by the NFDI4Health Task Force COVID-19 (https://www.nfdi4health.de/task-force-covid-19-2) within the framework of a DFG-project (LO-342/17-1). LP, VE funded by Mathematical and Statistical modelling project (MUNI/A/1615/2020), Online platform for real-time monitoring, analysis and management of epidemic situations (MUNI/11/02202001/2020); VE also supported by RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), the CETOCOEN EXCELLENCE (CZ.02.1.01/0.0/0.0/17-043/0009632), RECETOX RI project (CZ.02.1.01/0.0/0.0/16-013/0001761). NIB funded by Health Protection Research Unit (grant code NIHR200908). SAb, SF funded by Wellcome Trust (210758/Z/18/Z)., Competing Interests: KS, HG, RG, HJ, RN, BP, FS, JD, DW, SA, AU, GG, ER, NR, DS, YW, NW, LW, JT, GO, TS, DT, LP, EK, JM, MB, NL, JM, JS, JW, JF, BL, IR, JB, RW, IV, VT, MS, MZ, CP, BR, NB, SM, LC, GF, IM, DO, PA, AM, VE, AK, DK, LP, BD, ML, SS, JD, SM, VP, GR, BB, GA, NP, GZ, WB, SH, TH, DS, MG, JA, DM, SA, EA, DL, CP, JB, AR, TZ, AK, JZ, FP, FD, MC, GL, PG, BT, FB, GJ, MM, AF, AS, PM, AA, BH, BL, MM, PP, SV, RB, FD, AG, KG, MG, BK, AM, KN, JN, MR, FR, MS, ES, JZ, JK, BP, KH, YK, MS, BP, MB, MF, RI, TK, TO, JB, SF No competing interests declared, PB, HG, SS, BS Affiliated with IEM, Inc. The author has no financial interests to declare

Background: The COVID-19 pandemic is commonly believed to have increased common mental disorders (CMD, i.e., depression and anxiety), either directly due to COVID-19 contractions (death of near ones or residual conditions), or indirectly by increasing stress, economic uncertainty, and disruptions in daily life resulting from containment measure. Whereas studies reporting on initial changes in self-reported data frequently have reported increases in CMD, pandemic related changes in CMD related to primary care utilization are less well known. Analyzing time series of routinely and continuously sampled primary healthcare data from Sweden, Norway, Netherlands, and Latvia, we aimed to characterize the impact of the pandemic on CMD recorded prevalence in primary care. Furthermore, by relating these changes to country specific time-trajectories of two classes of containment measures, we evaluated the differential impact of containment strategies on CMD rates. Specifically, we wanted to test whether school restrictions would preferentially affect age groups corresponding to those of school children or their parents., Methods: For the four investigated countries, we collected time-series of monthly counts of unique CMD patients in primary healthcare from the year 2015 (or 2017) until 2021. Using pre-pandemic timepoints to train seasonal Auto Regressive Integrated Moving Average (ARIMA) models, we predicted healthcare utilization during the pandemic. Discrepancies between observed and expected time series were quantified to infer pandemic related changes. To evaluate the effects of COVID-19 measures on CMD related primary care utilization, the predicted time series were related to country specific time series of levels of social distancing and school restrictions., Results: In all countries except Latvia there was an initial (April 2020) decrease in CMD care prevalence, where largest drops were found in Sweden (Prevalence Ratio, PR = 0.85; 95% CI 0.81-0.90), followed by Netherlands (0.86; 95% CI 0.76-1.02) and Norway (0.90; 95% CI 0.83-0.98). Latvia on the other hand experienced increased rates (1.25; 95% CI 1.08-1.49). Whereas PRs in Norway and Netherlands normalized during the latter half of 2020, PRs stayed low in Sweden and elevated in Latvia. The overall changes in PR during the pandemic year 2020 was significantly changed only for Sweden (0.91; 95% CI 0.90-0.93) and Latvia (1.20; 95% CI 1.14-1.26). Overall, the relationship between containment measures and CMD care prevalence were weak and non-significant. In particular, we could not observe any relationship of school restriction to CMD care prevalence for the age groups best corresponding to school children or their parents., Conclusion: Common mental disorders prevalence in primary care decreased during the initial phase of the COVID-19 pandemic in all countries except from Latvia, but normalized in Norway and Netherlands by the latter half of 2020. The onset of the pandemic and the containment strategies were highly correlated within each country, limiting strong conclusions on whether restriction policy had any effects on mental health. Specifically, we found no evidence of associations between school restrictions and CMD care prevalence. Overall, current results lend no support to the common belief that the pandemic severely impacted the mental health of the general population as indicated by healthcare utilization, apart from in Latvia. However, since healthcare utilization is affected by multiple factors in addition to actual need, future studies should combine complementary types of data to better understand the mental health impacts of the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Flodin, Sörberg Wallin, Tarantino, Cerchiello, Mladá, Kuklová, Kondrátová, Parimbelli, Osika, Hollander and Dalman.)

The COVID-19 pandemic has highlighted the importance of reliable statistical models which, based on the available data, can provide accurate forecasts and impact analysis of alternative policy measures. Here we propose Bayesian time-dependent Poisson autoregressive models that include time-varying coefficients to estimate the effect of policy covariates on disease counts. The model is applied to the observed series of new positive cases in Italy and in the United States. The results suggest that our proposed models are capable of capturing nonlinear growth of disease counts. We also find that policy measures and, in particular, closure policies and the distribution of vaccines, lead to a significant reduction in disease counts in both countries., (© 2022 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

Motivation: With the advent of high-throughput sequencing in molecular biology and medicine, the need for scalable statistical solutions for modeling complex biological systems has become of critical importance. The increasing number of platforms and possible experimental scenarios raised the problem of integrating large amounts of new heterogeneous data and current knowledge, to test novel hypotheses and improve our comprehension of physiological processes and diseases., Results: Combining network analysis and causal inference within the framework of structural equation modeling (SEM), we developed the R package SEMgraph. It provides a fully automated toolkit, managing complex biological systems as multivariate networks, ensuring robustness and reproducibility through data-driven evaluation of model architecture and perturbation, which is readily interpretable in terms of causal effects among system components., Availability and Implementation: SEMgraph package is available at https://cran.r-project.org/web/packages/SEMgraph., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pathway enrichment analysis is extensively used in high-throughput experimental studies to gain insight into the functional roles of pre-defined subsets of genes, proteins and metabolites. Methods that leverages information on the topology of the underlying pathways outperform simpler methods that only consider pathway membership, leading to improved performance. Among all the proposed software tools, there's the need to combine high statistical power together with a user-friendly framework, making it difficult to choose the best method for a particular experimental environment., Results: We propose SEMgsa, a topology-based algorithm developed into the framework of structural equation models. SEMgsa combine the SEM p values regarding node-specific group effect estimates in terms of activation or inhibition, after statistically controlling biological relations among genes within pathways. We used SEMgsa to identify biologically relevant results in a Coronavirus disease (COVID-19) RNA-seq dataset (GEO accession: GSE172114) together with a frontotemporal dementia (FTD) DNA methylation dataset (GEO accession: GSE53740) and compared its performance with some existing methods. SEMgsa is highly sensitive to the pathways designed for the specific disease, showing low p values ([Formula: see text]) and ranking in high positions, outperforming existing software tools. Three pathway dysregulation mechanisms were used to generate simulated expression data and evaluate the performance of methods in terms of type I error followed by their statistical power. Simulation results confirm best overall performance of SEMgsa., Conclusions: SEMgsa is a novel yet powerful method for identifying enrichment with regard to gene expression data. It takes into account topological information and exploits pathway perturbation statistics to reveal biological information. SEMgsa is implemented in the R package SEMgraph, easily available at https://CRAN.R-project.org/package=SEMgraph ., (© 2022. The Author(s).)

Purpose: To improve resiliency and reduce burnout in nurses through implementation of the Healing Pathways program (University of Maryland School of Medicine, Baltimore). Aims of this study include assessment of feasibility and acceptability and to explore changes in stress, coping, burnout, and mindfulness., Design: A single-group, pre-, posttest design of an 8-week program in which participants attended weekly sessions that included Reiki, yoga, and meditation. Sample included 8 nurses with 1 advanced practice nurse, all female, ages ranging from 22 to 49 years, experience levels ranging from <1 year to 26 years., Methods: Participants completed the Perceived Stress Scale, Coping Self-Efficacy Scale, Maslach Burnout Inventory, and Mindful Attention Awareness Scale before intervention, at last session, and 1 month after last session. Data were analyzed using one-way analysis of variance and qualitative narrative inquiry., Findings: Improvements were noted in perceived stress, coping, burnout exhaustion subscale, and mindfulness., Conclusion: Healing Pathways was effective at reducing stress and improving coping and mindfulness in nurses., Implications: Nurses who invest time in self-care techniques including Reiki, yoga, and meditation improve their overall wellbeing and may provide higher-quality patient care. Implementation of an 8-week program in integrative self-care is feasible and important for the health of nurses.

Stress, fatigue, and burnout are common maladies among healthcare employees. To address this problem, a holistic integrative self-care program for healthcare practitioners was designed, implemented, and evaluated. A total of 84 participants, recruited via presentations, flyers, and word of mouth, completed the 8-week program. The experiential course, entitled Healing Pathways, combined training in Reiki, guided imagery, yoga, toning, meditation, intuitive scanning, creative expression, and mentorship to foster more empowered and resilient individuals. We measured the effectiveness of the program via mixed methods consisting of qualitative interviews providing in-depth feedback and quantitative analysis demonstrating statistically significant benefit. Participants reported significantly lower levels of stress and significantly increased confidence in their ability to cope at treatment conclusion (8 weeks) and long-term follow-up (12 months). These findings suggest that an integrative wellness and resiliency program, coupled with individual mentorship, may improve coping, decrease stress, and improve functioning and well-being for nurses and other health care providers., (Published by Elsevier Inc.)

Introduction: Fournier's gangrene (FG) is a rapidly developing necrotizing fasciitis that originates in genital and perineal region. The mortality rate is high and requires prompt diagnosis, antibiotic treatment and extensive necrosectomy with derivative colostomy. Vacuum Assisted Closure (VAC) is a wound care system of paramount importance in the treatment of complex wounds, including the perineum., Materials and Methods: We evaluated 6 cases of FG (males, mean age: 54.6 yrs) of the last 3 years (February 2008-August 2010). All patients were diabetics. We used intravenous antibiotic treatment and early surgical debridement with colostomy, followed by immediate positioning of a VAC device (NP 125-200 mmHg). The dressing changes were done every 3-4 days. Hyperbaric oxygen therapy (HBOT) was given only to one patient. Microbiological etiology was assessed by multiple cultures to tailor the antimicrobial treatment., Results: The VAC therapy reduces the number of dressings and the hospital length of stay (LOS), in agreement with the literature; in one of the cases a secondary reconstructive surgical intervention was possible. The colostomy was reversed in all patients within 3 months., Conclusions: Negative pressure is a time saving device, reducing days of hospitalization, patient's discomfort and number of medications. The possibility of a early reconstructive surgery improves significantly quality of life.