Validation of a Model Estimating the Budget Impact of Video Capsule Endoscopy for Surveillance of Crohn's Disease in an Italian Center.

Background: Crohn's disease is a chronic ailment affecting the gastrointestinal tract. Mucosal healing, a marker of reduced disease activity, is currently assessed in the colonic sections using ileocolonoscopy and magnetic resonance enteroscopy. Video capsule endoscopy (VCE) offers visualization of the entire GI mucosae. Objective: To validate a Crohn's disease model estimating the budget impact of VCE compared with the standard of care (SOC) in Italy. Methods: A patient-level, discrete-event simulation was developed to estimate the budget impact of VCE compared with SOC for Crohn's disease surveillance over 5 years in the Italian setting. Input data were sourced from a physician-initiated study from Sant'Orsola-Malpighi Hospital in Bologna, Italy, and the literature. The care pathway followed hospital clinical practice. Comparators were the current SOC (ileocolonoscopy, with or without magnetic resonance enteroscopy) and VCE. Sensitivity analysis was performed using 500-patient bootstraps. A comparative analysis regarding clinical outcomes (biologics use, surgical interventions, symptom remission) was performed to explore the validity of the model compared with real-world data. Cumulative event incidences were compared annually and semi-annually. Bayesian statistical analysis further validated the model. Results: Implementing VCE yielded an estimated €67 savings per patient per year, with savings in over 55% of patients, compared with SOC. While annual costs are higher up to the second year, VCE becomes cost saving from the third year onward. The real-world validation analysis proved a good agreement between the model and real-world patient records. The highest agreement was found for biologics, where Bayesian analysis estimated an 80.4% probability (95% CI: 72.2%-87.5%) that a decision maker would accept the result as an actual reflection of real-world data. Even where trend data diverged (eg, for surgery [43.1% likelihood of acceptance, 95% CI: 33.7%-52.8%]), the cumulative surgery count over 5 years was within the margin of error of the real-world data. Conclusions: Implementing VCE in the surveillance of patients with Crohn's disease and small bowel involvement may be cost saving in Italy. The congruence between model predictions and real-world patient records supports using this discrete-event simulation to inform healthcare decisions.

PEG hydrogel sealant versus fibrin glue in posterior fossa surgery: an economic comparison across five European countries.

Aim: Posterior cranial fossa (PCF) surgery is associated with complications, including cerebrospinal fluid (CSF) leakage. Dural sealants such as polyethylene glycol (PEG)-based hydrogels and fibrin glue can prevent CSF leaks, with evidence suggesting PEG hydrogels may outperform fibrin glue. However, the budget impact of using PEG hydrogels in PCF surgeries in Europe is unclear. Materials & methods: A decision tree was developed based on a previous US model, to assess the budget impact of switching from fibrin glue to PEG hydrogel in PCF surgery across five European countries. Input costs were derived from published sources for the financial year 2022/2023. Health outcomes, including CSF leaks, were considered. Results: The model predicted that using PEG hydrogel instead of fibrin glue in PCF surgery can lead to cost savings in five European countries. Cost savings per patient ranged from EUR 419 to EUR 1279, depending on the country. Sensitivity analysis showed that the incidence of CSF leaks and pseudomeningoceles had a substantial impact on the model's results. Conclusion: PEG hydrogels may be a cost-effective alternative to fibrin glue in PCF surgery. The model predicted that cost savings would be mainly driven by a reduction in the incidence of postoperative CSF leaks, resulting in reduced reliance on lumbar drains, reparative surgery and shortened hospital stays.

Homocysteine potentiates amyloid ß $$ \upbeta $$ -induced death receptor 4- and 5-mediated cerebral endothelial cell apoptosis, blood brain barrier dysfunction and angiogenic impairment.

Cerebrovascular dysfunction has been implicated as a major contributor to Alzheimer's Disease (AD) pathology, with cerebral endothelial cell (cEC) stress promoting ischemia, cerebral-blood flow impairments and blood-brain barrier (BBB) permeability. Recent evidence suggests that cardiovascular (CV)/cerebrovascular risk factors, including hyperhomocysteinemia (Hhcy), exacerbate AD pathology and risk. Yet, the underlying molecular mechanisms for this interaction remain unclear. Our lab has demonstrated that amyloid beta 40 (Aß40) species, and particularly Aß40-E22Q (AßQ22; vasculotropic Dutch mutant), promote death receptor 4 and 5 (DR4/DR5)-mediated apoptosis in human cECs, barrier permeability, and angiogenic impairment. Previous studies show that Hhcy also induces EC dysfunction, but it remains unknown whether Aß and homocysteine function through common molecular mechanisms. We tested the hypotheses that Hhcy exacerbates Aß-induced cEC DR4/5-mediated apoptosis, barrier dysfunction, and angiogenesis defects. This study was the first to demonstrate that Hhcy specifically potentiates AßQ22-mediated activation of the DR4/5-mediated extrinsic apoptotic pathway in cECs, including DR4/5 expression, caspase 8/9/3 activation, cytochrome-c release and DNA fragmentation. Additionally, we revealed that Hhcy intensifies the deregulation of the same cEC junction proteins mediated by Aß, precipitating BBB permeability. Furthermore, Hhcy and AßQ22, impairing VEGF-A/VEGFR2 signaling and VEGFR2 endosomal trafficking, additively decrease cEC angiogenic capabilities. Overall, these results show that the presence of the CV risk factor Hhcy exacerbates Aß-induced cEC apoptosis, barrier dysfunction, and angiogenic impairment. This study reveals specific mechanisms through which amyloidosis and Hhcy jointly operate to produce brain EC dysfunction and death, highlighting new potential molecular targets against vascular pathology in comorbid AD/CAA and Hhcy conditions.

Prevalence of Critical Congenital Heart Disease Detected in the Pulse Oximetry Test in Asymptomatic Newborns, ≥35 Gestational Weeks, in a Maternity in Southern Brazil

Abstract Background Congenital heart diseases (CHD) are one of the most prevalent malformations, and the screening tests to identify critical congenital heart disease (CCHD) is the pulse oximetry test, with subsequent investigation and treatment. Objective To quantify positive pulse oximetry tests and verify the prevalence of CCHD detected by it in asymptomatic newborns, ≥35 gestational weeks, in a Brazilian maternity hospital. Methodology This is an observational, retrospective, quantitative, analytical and cross-sectional study, conducted from October 2020 to May 2022, in a maternity hospital in southern Brazil, through the collection of records of positive oximetry pulse tests, following the norms of screening CCHD test of the Brazilian Society of Pediatrics (SBP), after they were evaluated with echocardiography for confirmation or exclusion of CHD. Results A total of 5,667 newborns were evaluated in this study, according to the inclusion criteria; 0.17% (n = 10) had a positive pulse oximetry test. Regarding the results of the echocardiography of the neonates with a positive test, two were normal, seven were cases of patent foramen ovale (PFO), and one was a case (0,017%) with interatrial communication (IAC) diagnosis. In the same period, five neonates with CCHD were born, symptomatic, diagnosed by physical examination, and referred to neonatal intensive care units (NICU) before taking the neonatal cardiac screening (< 24 hours of life). Conclusion The prevalence of positive pulse oximetry tests was 0.17% and none CCHD was detected. Five cases of CCHD were born in this period, but they were diagnosed before the recommend time to perform the screening test.

A Health Economic Analysis Exploring the Cost Consequence of Using a Surgical Site Infection Prevention Bundle for Hip and Knee Arthroplasty in Germany.

Background: According to the European Centre for Disease Prevention and Control, surgical site infections (SSIs) constitute over 50% of all hospital-acquired infections. Reducing SSIs can enhance healthcare efficiency. Objective: This study explores the cost consequences of implementing an SSI prevention bundle (SPB) in total hip and knee arthroplasty (THKA). Methods: A health-economic model followed a cohort of THKA patients from admission to 90 days postdischarge. The perioperative process was modeled using a decision tree, and postoperative recovery and potential SSI evaluated using a Markov model. The model reflects the hospital payers' perspective in Germany. The SPB includes antimicrobial incision drapes, patient warming, and negative pressure wound therapy in high-risk patients. SSI reduction associated with these interventions was sourced from published meta-analyses. An effectiveness factor of 70% was introduced to account for potential overlap of effectiveness when interventions are used in combination. Sensitivity analyses were performed to assess the robustness of model outcomes. Results: The cost with the SPB was €4274.32 per patient, €98.27, or 2.25%, lower than that of the standard of care (€4372.59). Sensitivity analyses confirmed these findings, indicating a median saving of 2.22% (95% credible interval: 1.00%-3.79%]). The SPB also reduced inpatient SSI incidence from 2.96% to 0.91%. The break-even point for the SPB was found when the standard of care had an SSI incidence of 0.938%. Major cost drivers were the cost of inpatient SSI care, general ward, and operating room, and the increased risk of an SSI associated with unintended, intraoperative hypothermia. Varying the effectiveness factor from 10% to 130% did not substantially impact model outcomes. Conclusions: Introducing the SPB is expected to reduce care costs if the inpatient SSI rate (superficial and deep combined) in THKA procedures exceeds 1%. Research into how bundles of measures perform together is required to further inform the results of this computational analysis.

Tunable birefringence and elliptical polarization eigenmodes in a biplate of two quarter-wave plates.

Birefringence of elliptical polarization eigenmodes can be conceptualized as a composite system comprising two distinct media: one with linear polarization eigenmodes and the other with circular polarization eigenmodes. However, the practical realization of such a system often involves the combination of two birefringent quarter-wave plates (QWPs). In this study, our objective is to characterize the variable retardation and variable elliptical polarization eigenmodes exhibited by a biplate consisting of two quarter-wave plates. Additionally, we aim to analyze the geometric properties of the transformation of one state of polarization on the Poincaré sphere, employing the emerging state's curve. This curve corresponds to the intersection between the Poincaré sphere and a cone. The outcomes of our study are presented as a function of the angle between the fast axes of the two QWPs. The findings have the potential to contribute to the configuration of q-plates and facilitate the development of quantum communication protocols.

Prevalence of depressive disorder in the adult population of Latin America: a systematic review and meta-analysis.

Background: Depressive disorder is one of the leading causes of disability worldwide; however its prevalence and association with inequality and crime is poorly characterised in Latin America. This study aimed to: i. systematically review population-based studies of prevalence of ICD/DSM depressive disorder in Latin America, ii. report pooled regional, country, and sex-specific prevalence estimates, and iii. test its association with four country-level development indicators: human development (HDI), income (Gini) and gender inequality (GII), and intentional homicide rate (IHR). Methods: We conducted a systematic review and meta-analysis of population-based studies reporting primary data on the prevalence of ICD/DSM depressive disorder in Latin America from 1990 to 2023, irrespective of language. We searched PubMed, PsycINFO, Cochrane Library, SciELO (regional database), LILAC (regional database), and available grey literature. Study quality was assessed using JBI's critical appraisal tools. We generated pooled estimates using random-effects meta-analysis; heterogeneity was assessed using the I2 statistic. Meta-regression analyses were used to test associations of depression prevalence with indicators of inequality and human development. The study was registered with PROSPERO (CRD42019143054). Findings: Using data from 40 studies in Latin America, lifetime, 12-month, and current prevalence of ICD/DSM depressive disorder were calculated at 12.58% (95% CI 11.00%-14.16%); 5.30% (4.55-6.06%), and 3.12% (2.22-4.03), respectively. Heterogeneity was high across lifetime, 12-month, and current prevalence, sex, and countries. 12-month and current prevalence was associated with higher Gini and GII, 12-month prevalence with lower HDI, and current prevalence with higher IHR. Interpretation: We found a high prevalence of ICD/DSM depressive disorders in Latin America, and a statistically significant association with inequality and development indicators. The high heterogeneity found across prevalence periods and the major gaps in country representation underscore the need to escalate efforts to improve mental health access and research capabilities in Latin America. Systematic, comparable prevalence estimates would inform more effective decision-making in the region. Funding: Pfizer Independent Medical Education Grant.

Patient Safety during Propofol Sedation before and after Implementation of Capnography Monitoring.

Endoscopic procedures are routinely applied to cancer screening programs and surveillance. The preferred technique is usually deep sedation with propofol being a convenient agent allowing for a quicker patient recovery while maintaining a similar safety profile compared to traditional agents. However, adverse events, including respiratory depression and consequent undesirable cardiovascular side effects, may occur. The goal of this work is to evaluate the patient safety impact of adding capnography during endoscopic procedures under deep propofol sedation. Data were retrospectively collected from patients undergoing deep, procedural sedation for gastrointestinal (GI) endoscopy in October 2019 to January 2021 in a single Turkish university hospital. Included in the analysis were all adult patients classified by the American Society of Anesthesiologists (ASA) as I-IV, who were scheduled for GI endoscopy utilizing propofol alone or in combination. Data on 1840 patients were collected, of whom 1610 (730 pre- and 880 post-capnography implemention) met inclusion criteria. The primary outcome was a change in the composite incidence of mild oxygen desaturation (SpO2 75-90% for <60 s), severe oxygen desaturation (SpO2 < 75% anytime or <90% for >60 s), bradycardia (<60 ppm), and tachycardia (>25% from baseline). Without capnography, on average, 7.5 events of the primary endpoint were observed per 100 procedures and 2.9 with additional capnography monitoring (p < 0.001). A significant reduction was observed for mild oxygen desaturation, with a resulting odds ratio of 0.25 (95% CI 0.14 to 0.46). ASA I patients had the highest difference in combined incidence of any oxygen desaturation of 5.85% in the pre-capnography group and 0.64% in the post-capnography group. Although procedural sedation using propofol is not associated with severe adverse events, the incidence of composite adverse events could be reduced with the addition of capnography monitoring.

Amyloid ß induces cardiac dysfunction and neuro-signaling impairment in the heart of an Alzheimer's disease model.

Aims: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by cerebral amyloid ß (Aß) deposition and tau pathology. The AD-mediated degeneration of the brain neuro-signaling pathways, together with a potential peripheral amyloid accumulation, may also result in the derangement of the peripheral nervous system, culminating in detrimental effects on other organs, including the heart. However, whether and how AD pathology modulates cardiac function, neurotrophins, innervation, and amyloidosis is still unknown. Here, we report for the first time that cardiac remodeling, amyloid deposition, and neuro-signaling dysregulation occur in the heart of Tg2576 mice, a widely used model of AD and cerebral amyloidosis. Methods ad Results: Echocardiographic analysis showed significant deterioration of left ventricle function, evidenced by a decline of both ejection fraction and fraction shortening percentage in 12-month-old Tg2576 mice compared to age-matched WT littermates. Tg2576 mice hearts exhibited an accumulation of amyloid aggregates, including Aß, an increase in interstitial fibrosis and severe cardiac nervous system dysfunction. The transgenic mice also showed a significant decrease in cardiac nerve fiber density, including both adrenergic and regenerating nerve endings. This myocardial denervation was accompanied by a robust reduction in NGF and BDNF protein expression as well as GAP-43 expression (regenerating fibers) in both the brain and heart of Tg2576 mice. Accordingly, cardiomyocytes and neuronal cells challenged with Aß oligomers showed significant downregulation of BDNF and GAP-43, indicating a causal effect of Aß on the loss of cardiac neurotrophic function. Conclusions: Overall, this study uncovers possible harmful effects of AD on the heart, revealing cardiac degeneration induced by Aß through fibrosis and neuro-signaling pathway deregulation for the first time in Tg2576 mice. Our data suggest that AD pathology can cause deleterious effects on the heart, and the peripheral neurotrophic pathway may represent a potential therapeutic target to limit these effects.

Prevalence and Clinical Factors Associated With Pes Planus Among Children and Adults: A Population-Based Synthesis and Systematic Review.

Estimates of pes planus ("flatfoot") prevalence vary considerably across studies. Moreover, there is uncertainty over which factors are associated with the pes planus prevalence. We aimed to systematically review the prevalence and clinical factors associated with flatfoot among children and adults. We searched Web of Science, PubMed/MEDLINE, and Google Scholar databases reporting population-based flatfoot prevalence. Two reviewers independently extracted the data and assessed the qualities of the studies. Subgroup analysis was conducted to analyze the associated factors on flatfoot prevalence. Frequencies, odds ratios (OR), and 95% confidence intervals (CI) were performed using descriptive analysis and chi-square test accounting for heterogeneity. Any conflict in the data analysis was discussed by all the reviewers. Twelve studies including 2509 flatfoot cases were analyzed (overall prevalence 15.6%, n = 16,000). The subgroup analysis indicated that male gender (OR = 1.26, 95% CI: 1.15-1.37), age groups 3 to 5 years (OR = 2.02, 95% CI: 1.78-2.30) and 11 to 17 years (OR = 1.91, 95% CI: 1.64-2.22), Asian race (OR = 2.34, 95% CI: 2.10-2.60), and obesity (OR = 2.62, 95% CI: 2.06-3.32) were more associated with flatfoot (p < .001). Conversely, female gender (OR = 0.44, 95% CI: 0.40-0.48) and White race (OR = 0.52, 95% CI: 0.47-0.57) were less associated with flatfoot (p < .001). Our findings may be valuable for clinical/surgical settings, particularly, for those modifiable findings and targeted populations. However, we suggest that future studies estimating flatfoot should consider prospective/multicenter designs using a common screening methods in random samples populations.

Stigmatic aspherical refracting surfaces from Cartesian ovoids.

A theory for Descartes ovoids has been developed in terms of four form parameters, (GOTS). This theory allows the design of optical imaging systems that, in addition to a rigorous stigmatism, exhibit the property of aplanatism, necessary for the proper imaging of extended objects. As a decisive step for the production of these systems, in this work, we propose a formulation of Descartes ovoids in the form of standard aspherical surfaces (ISO 10110-12: 2019), by means of explicit formulas for the corresponding aspheric coefficients. Thus, with these results, the designs developed with Descartes ovoids are finally translated into the language of aspherical surfaces for their production, inheriting the aspherical surfaces of all optical properties of Cartesian surfaces. Consequently, these results make this optical design methodology viable for the development of technological solutions using the current optical fabrication capabilities of the industry.

Definition of a second-order degree of polarization in terms of the complex degree of coherence.

The classical theory of random electric fields and polarization formalism has been formulated considering the Stokes parameters' auto-correlations. However, in this work, the need to consider the Stokes parameters' cross-correlations to obtain a complete description of the polarization dynamics of a light source is explained. We propose a general expression for the Stokes parameters' degree of correlation using both auto-correlations and cross-correlations, which we derive from the application of Kent's distribution in the statistical study of Stokes parameter dynamics on Poincaré's sphere. Additionally, from the proposed degree of correlation, we obtain a new expression for the degree of polarization (DOP) in terms of the complex degree of coherence, which is a generalization of the well-known Wolf's DOP. The new DOP is tested using a depolarization experiment in which partially coherent light sources propagate through a liquid crystal variable retarder. The experimental results show that our generalization for the DOP improves the theoretical description of a new depolarization phenomenon that Wolf's DOP cannot describe.

Hyperspectral camera as a compact payload architecture for remote sensing applications.

Monitoring and observation over the surface of the Earth have been a matter of global interest. In this path, recent efforts aim to develop a spatial mission to perform remote sensing applications. Mainly, CubeSat nanosatellites have emerged as a standard for developing low-weight and small-sized instruments. In terms of payloads, state-of-the-art optical systems for CubeSats are expensive and designed to work in general use cases. To overcome these limitations, this paper presents a 1.4 U compact optical system to acquire spectral images from a CubeSat standard satellite at the height of 550 km. To validate the proposed architecture, optical simulations using ray tracing simulation software are presented. Because the performance of computer vision tasks is highly related to data quality, we compared the optical system in terms of the classification performance on a real remote sensing application. The performances of the optical characterization and land cover classification show that the proposed optical system achieves a compact instrument, operating at a spectral range from 450 nm to 900 nm discretized on 35 spectral bands. The optical system has an overall f-number of 3.41 with a ground sampling distance of 52.8 m and a swath of 40 km. Additionally, the design parameters for each optical element are publicly available for validation, repeatability, and reproducibility of the results.

FDA-approved carbonic anhydrase inhibitors reduce amyloid ß pathology and improve cognition, by ameliorating cerebrovascular health and glial fitness.

INTRODUCTION: Cerebrovascular pathology is an early and causal hallmark of Alzheimer's disease (AD), in need of effective therapies. METHODS: Based on the success of our previous in vitro studies, we tested for the first time in a model of AD and cerebral amyloid angiopathy (CAA), the carbonic anhydrase inhibitors (CAIs) methazolamide and acetazolamide, Food and Drug Administration-approved against glaucoma and high-altitude sickness. RESULTS: Both CAIs reduced cerebral, vascular, and glial amyloid beta (Aß) accumulation and caspase activation, diminished gliosis, and ameliorated cognition in TgSwDI mice. The CAIs also improved microvascular fitness and induced protective glial pro-clearance pathways, resulting in the reduction of Aß deposition. Notably, we unveiled that the mitochondrial carbonic anhydrase-VB (CA-VB) is upregulated in TgSwDI brains, CAA and AD+CAA human subjects, and in endothelial cells upon Aß treatment. Strikingly, CA-VB silencing specifically reduces Aß-mediated endothelial apoptosis. DISCUSSION: This work substantiates the potential application of CAIs in clinical trials for AD and CAA.

Measuring Fatigue and Fatigability in Spinal Muscular Atrophy (SMA): Challenges and Opportunities.

Fatigue, a common symptom, together with the characteristic of performance fatigability, are well-documented features of SMA that impact quality of life and function. Importantly, establishing associations between multidimensional self-reported fatigue scales and patient performance has proven difficult. This review was conducted to evaluate the various patient-reported fatigue scales applied in SMA, with the objective of considering the limitations and advantages of each measure. Variable use of fatigue-related nomenclature, including conflicting terminology interpretation, has affected assessment of physical fatigue attributes, specifically perceived fatigability. This review encourages the development of original patient-reported scales to enable perceived fatigability assessment, providing a potential complementary method of evaluating treatment response.

Stress Testing the Cardiac Catheterization Laboratory: A Novel Use of In Situ Simulation to Identify and Mitigate Latent Safety Threats During Acute Airway Management.

INTRODUCTION: Although uncommon, cardiac arrests in the cardiac catheterization laboratory (CCL) are often catastrophic and likely to increase with rising case complexity. In situ simulation (ISS) has been used to identify latent safety threats (LSTs) in inpatient units but has not yet been studied in the CCL. METHODS: Three Plan-Do-Study-Act (PDSA) cycles leveraging ISS were conducted focused on acute airway management. Data collected through debriefs focused on (1) airway management, (2) equipment availability, and (3) interdepartmental communication. The LSTs were subcategorized and plotted on the Survey Analysis for Evaluating Risk (SAFER)-Matrix. A SAFER score was calculated based on quantifying the likelihood of harm, scope, and the number of times a threat was identified during simulation. Time to definitive airway was collected as a secondary measure. Interventions were developed using cause and effect and driver diagrams between PDSA cycles. RESULTS: Eleven total simulations through 3 PDSA cycles were conducted between January and December 2021 (5 in PDSA 1, 4 in PDSA 2, and 2 in PDSA 3). One hundred one LSTs were identified with 14 total subcategories. The mean SAFER score decreased from 5.37 in PDSA 1, to 2.96 in PDSA 2, and to 1.00 in PDSA 3. Bivariate regression analysis showed a decrease in SAFER score of 2.19 for every PDSA cycle (P = 0.011). Ordinary least squares regression had a decrease of 1.65 in airway-related threats every PDSA cycle (P < 0.01) as well as an increase in intubation time of 35.0 seconds for every 1-unit increase in communication threat identified (P = 0.037). CONCLUSIONS: This study successfully leveraged ISS and existing quality improvement initiatives in the CCL, resulting in a decrease in airway-related threats as measured through simulation.

In Situ Simulation as a Tool to Longitudinally Identify and Track Latent Safety Threats in a Structured Quality Improvement Initiative for SARS-CoV-2 Airway Management: A Single-Center Study.

BACKGROUND: In situ simulation has emerged as a powerful tool for identifying latent safety threats (LSTs). After the first wave of the SARS-CoV-2 pandemic, an urban community emergency department (ED) identified opportunities for improvement surrounding acute airway management and particularly focused on infection control precautions, equipment availability, and interprofessional communication during acute resuscitation. Using the Model for Improvement, a hybrid in situ/quality improvement initiative was implemented using Plan-Do-Study-Act (PDSA) cycles to enhance systems for intubating patients with SARS-CoV-2. METHODS: Three PDSA cycles consisting of 10 simulations each were conducted from June 2020 through February 2021. Latent safety threats (LST) were identified through an in situ simulation scenario involving a patient with SARS-CoV-2 in acute respiratory failure. LSTs were collected through structured debriefs focused on (1) infection control, (2) equipment availability, and (3) communication. The SAFER-Matrix was used to score LSTs according to frequency and likelihood of harm by members of the ED QI team (SAFER score). The research team worked with the same QI leaders to implement action plans based on scored threats using cause-and-effect and driver diagrams. The Donabedian model was used to conceptually evaluate the quality of interventions upon conclusion of the third PDSA cycle. RESULTS: The median SAFER score decreased from 10.94 in PDSA cycle 1 to 6.77 in PDSA cycle 2 to 4.71 in PDSA cycle 3. Across all identified LSTs, the SAFER score decreased by 3.114 for every additional PDSA cycle ( P = 0.0167). When evaluating for threats identified as being primarily structure based, there was a decrease in SAFER score of 1.28 per every additional PDSA cycle ( P = 0.001). There was a decrease in total count of LST of 0.20 per additional simulation run ( P = 0.02) after controlling for shift type, census, perceived workload, team size, and prior attendance in simulations across all PDSA cycles. CONCLUSIONS: This study presents a blueprint for the utilization of in situ simulation through multiple waves of the SARS-CoV-2 pandemic to identify LSTs and use the SAFER score as a surrogate marker to monitor the impact of interventions for a safer environment for both medical staff and patients.

Capsule endoscopy in Crohn's disease surveillance: A monocentric, retrospective analysis in Italy.

Background: Crohn's disease (CD) is a potentially debilitating condition that burdens Italian healthcare substantially. The symptomatic management relies on prompt therapy adjustment to reduce flares and follow-up diagnostic inputs to maximise remission. Capsule endoscopy (CE) has introduced advantages in CD diagnostics, allowing the direct inspection of the entire gastrointestinal mucosa. The diagnostic procedure is comparable in effort to standard ileocolonoscopy (IC) but requires no anaesthesia. Whether CE follow-up improves clinical outcomes remains to be defined. Objectives: To provide a preliminary evaluation of CE in terms of clinical outcomes with respect to the standard of care ileocolonoscopy/MRE in Italy. Methods: This retrospective analysis utilises anonymised, monocentric data from the S. Orsola-Malpighi Hospital IBD database in Bologna, Italy, collected between 1999 and 2019. Out of 421 adult patient records, 100 were included in the analysis (50 per arm, matched per demographic and clinical characteristics). The CE represented the intervention arm, whereas ileocolonoscopy/magnetic resonance enterography was the standard of care. The use of biologics, symptomatology course, and surgery were the outcomes. Results: The two techniques performed similarly overall. In general, no significant difference emerged in the use of biologics. The use of biologics appears reduced in the CE group, only in L4 patients after the first follow-up year. Similarly, surgery was seemingly less frequent among L4 patients in the CE group. No difference was found between groups in flare occurrence and duration. CE patients might have experienced longer and earlier first remissions, but no long-term difference persisted. Conclusions: The CE group showed an apparent reduction in biologics and surgery, limiting to L4 diagnoses. More extensive, prospective, multicentre, randomised studies must corroborate these preliminary findings.

The Validity and Reliability of the PHQ-9 and PHQ-2 on Screening for Major Depression in Spanish Speaking Immigrants in Chile: A Cross-Sectional Study.

BACKGROUND: The study aimed to explore the psychometric properties of two versions of the Patient Health Questionnaires (PHQ-9 and PHQ-2) on screening for Major Depressive Disorder (MDD) among Spanish-speaking Latin American adult immigrants in Santiago, and to explore factors associated with a higher risk of occurrence of MDD among them. METHODS: A representative sample of 897 Spanish-speaking immigrants completed the PHQ-9. The Composite International Diagnostic Interview (CIDI) was employed to evaluate MDD. Internal consistency and structural validity were evaluated using Cronbach's α coefficient and confirmatory factor analysis (CFA). Convergent validity with the 7-item General Anxiety Disorder Scale (GAD-7) was assessed using Spearman's correlations. Sensitivity, specificity, positive predictive values, and area under the receiver operating characteristic (ROC) curve were calculated for different cut-off points. Logistic regression analysis was used to identify factors associated with the risk of MDD. RESULTS: Cronbach's α coefficient of the PHQ-9 was 0.90; item-total correlation coefficients ranged from 0.61 to 0.76 and correlation with the GAD-7 was moderate (r = 0.625; p < 0.001). CFA on three alternative models suggests a plausible fit in the overall sample and among two of the subsamples: Peruvians and Venezuelans. Taking the results of CIDI as the gold standard for MDD, the area under the ROC curve was 0.91 (95% confidence interval (CI): 0.83~1.0). When the cut-off score was equal to 5, values of sensitivity, specificity, and Youden's index were 0.85, 0.90, and 0.75, respectively. Multivariate logistic regression analyses showed that the influence of having three or more children (OR = 3.91, 95% CI: 1.20~12.81; p < 0.05), residency in Chile of up to three years (OR = 1.79, 95% CI: 1.07~3.00; p < 0.05), active debt (OR = 2.74, 95% CI: 1.60~4.70; p < 0.001), a one (OR = 2.01, 95% CI: 1.03~3.94; p < 0.05) and two or more events of adversity during childhood (OR = 5.25, 95% CI: 1.93~14.3; p < 0.01) on the occurrence of MDD was statistically significant. Reliability (α = 0.62), convergent (r = 0.534; p < 0.01) and criterion (AUC = 0.85, 95% CI: 0.67~1.00) validity coefficients of the PHQ-2 were weaker than for the PHQ-9. CONCLUSIONS: The PHQ-2 and the PHQ-9 are reliable and valid instruments for use as screeners for MDD among Spanish-speaking populations of Latin America.

Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease that leads to motor impairment due to a chronic inflammatory process in the central nervous system (CNS). However, the HAM/TSP pathogenesis is not completely clear, and biomarkers to define the disease prognosis are still necessary. Thus, we aimed to identify biomarkers for HAM/TSP and potential mechanisms involved in disease development. To that end, the concentrations of VILIP-1, BDNF, VEGF, ß-NGF, TGF-ß1, fractalkine/CX3CL1, IL-6, IL-18, and TNF-α, and the soluble forms of TREM-1, TREM-2, and RAGE, were assessed using a multiplex bead-based immunoassay in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n = 20), asymptomatic HTLV-1 carriers (AC) (n = 13), and HTLV-1-seronegative individuals (n = 9), with the results analyzed according to the speed of HAM/TSP progression. HAM/TSP patients had elevated fractalkine in the serum but not in the CSF, particularly those with low neuroinflammatory activity (CSF/serum ratio of neopterin <1 and of CXCL10 < 2). HAM/TSP patients with normal CSF levels of neurofilament light chain (NfL) showed elevated ß-NGF in serum, and serum BDNF levels were increased in HTLV-1-infected individuals, particularly in HTLV-1 AC. Both HTLV-1 AC and HAM/TSP patients had lower TGF-ß1 levels in CSF compared to uninfected individuals, and HAM/TSP patients with active CNS inflammation showed higher CSF levels of IL-18, which correlated with markers of inflammation, neuronal death, and blood−brain-barrier permeability. Although none of the factors evaluated were associated with the speed of HAM/TSP progression, reduced TGF-ß1 levels in CSF suggest that suppressive responses to control subclinical and/or active neurodegeneration are impaired, while increased CSF IL-18 indicates the involvement of inflammasome-mediated mechanisms in HAM/TSP development.