Drug-Associated Acute Kidney Disease: Data From a World Pharmacovigilance Database.

Background Drugs are a frequent cause of nephrotoxicity, especially in the context of acute kidney disease (AKD), with a significant number of cases being drug-associated. The WHO's VigiBase is a powerful tool for identifying drugs described and associated with the development of AKD. Methods We retrieved data from the period 1968 to 2022 regarding notifications of adverse drug reactions (ADR). The extracted medications were evaluated for their nephrotoxicity based on the bibliographic score (BS) developed through pre-selected references. The main medications involved were classified as 'non-nephrotoxic', 'potentially nephrotoxic', and 'nephrotoxic'. We utilized the IC025 and reporting odds ratio (ROR) disproportionality indexes to study the relationship between medications and the odds of being included in an AKD notification. Results During the period, a total of 33,932,051 notifications were obtained, revealing 435,677 cases related to drug-associated AKD following MedDRA term filtering, predominantly affecting males aged 45-64. We identified 8,991 active ingredients or suspected combinations associated with AKD development, with the ATC class A - Alimentary Tract and Metabolism being the most frequently described. Among the medications most strongly associated with this phenotype, classes J and N stood out. Among the most notable medications collected, 8.3% were classified as "non-nephrotoxic," 16.7% as "potentially nephrotoxic," and 75% as "known nephrotoxic." Notable active ingredients included cobicistat + elvitegravir + emtricitabine + tenofovir disoproxil (IC025 8.7; ROR 786.96), inotersen (IC025 7.7; ROR 604.57), emtricitabine + tenofovir disoproxil (IC025 7.9; ROR 432.36), esomeprazole (IC025 6.8; ROR 184.23), and pantoprazole (IC025 6.3; ROR 109.86), with proton pump inhibitors dominating the top four positions among the most frequently involved medications. Conclusion AKD is a frequent adverse reaction in VigiBase, with a significantly high reported mortality rate. Evaluation of the notifications revealed medications with a high disproportionality index and a strong association with AKD. We also highlight the potential nephrotoxic role of less suspected medications. This study emphasizes the need to consider AKD as a condition potentially associated with iatrogenic etiology, highlighting various medications and their respective involvement in the various possible manifestations of AKD.

Identification of Novel DNA Methylation Prognostic Biomarkers for AML With Normal Cytogenetics.

PURPOSE: AML is a hematologic cancer that is clinically heterogeneous, with a wide range of clinical outcomes. DNA methylation changes are a hallmark of AML but are not routinely used as a criterion for risk stratification. The aim of this study was to explore DNA methylation markers that could risk stratify patients with cytogenetically normal AML (CN-AML), currently classified as intermediate-risk. MATERIALS AND METHODS: DNA methylation profiles in whole blood samples from 77 patients with CN-AML in The Cancer Genome Atlas (LAML cohort) were analyzed. Individual 5'-cytosine-phosphate-guanine-3' (CpG) sites were assessed for their ability to predict overall survival. The output was validated using DNA methylation profiles from bone marrow samples of 79 patients with CN-AML in a separate data set from the Gene Expression Omnibus. RESULTS: In the training set, using DNA methylation data derived from the 450K array, we identified 2,549 CpG sites that could potentially distinguish patients with CN-AML with an adverse prognosis (intermediate-poor) from those with a more favorable prognosis (intermediate-favorable) independent of age. Of these, 25 CpGs showed consistent prognostic potential across both the 450K and 27K array platforms. In a separate validation data set, nine of these 25 CpGs exhibited statistically significant differences in 2-year survival. These nine validated CpGs formed the basis for a combined prognostic biomarker panel, which includes an 8-CpG Somatic Panel and the methylation status of cg23947872. This panel displayed strong predictive ability for 2-year survival, 2-year progression-free survival, and complete remission in the validation cohort. CONCLUSION: This study highlights DNA methylation profiling as a promising approach to enhance risk stratification in patients with CN-AML, potentially offering a pathway to more personalized treatment strategies.

Zebrafish Avatar-test forecasts clinical response to chemotherapy in patients with colorectal cancer.

Cancer patients often undergo rounds of trial-and-error to find the most effective treatment because there is no test in the clinical practice for predicting therapy response. Here, we conduct a clinical study to validate the zebrafish patient-derived xenograft model (zAvatar) as a fast predictive platform for personalized treatment in colorectal cancer. zAvatars are generated with patient tumor cells, treated exactly with the same therapy as their corresponding patient and analyzed at single-cell resolution. By individually comparing the clinical responses of 55 patients with their zAvatar-test, we develop a decision tree model integrating tumor stage, zAvatar-apoptosis, and zAvatar-metastatic potential. This model accurately forecasts patient progression with 91% accuracy. Importantly, patients with a sensitive zAvatar-test exhibit longer progression-free survival compared to those with a resistant test. We propose the zAvatar-test as a rapid approach to guide clinical decisions, optimizing treatment options and improving the survival of cancer patients.

Fatigue and Mental Illness Symptoms in Long COVID: Protocol for a Prospective Cohort Multicenter Observational Study.

BACKGROUND: The aftermath of the COVID-19 pandemic continues to affect millions worldwide, resulting in persisting postvirus complaints and impacting peoples' quality of life. Long COVID, characterized by lingering symptoms like fatigue and mental illness, can extend beyond a few months, necessitating further research to understand its implications. OBJECTIVE: This study aims to quantify the degree of physical and psychological fatigue in patients following COVID-19 infection and examine its correlation with mental health disorders. METHODS: Using a consecutive nonrandom sampling technique, we will conduct a prospective cohort multicenter observational study in 5 Portuguese hospitals. Symptomatic adult patients with previous COVID-19 attending follow-up consultations will be enrolled. We will include patients who had mild, moderate, and severe acute disease. We will assess clinical outcomes related to COVID-19, including the type of respiratory support such as high-flow nasal cannula, noninvasive ventilation, and invasive mechanical ventilation. The exclusion criteria will include previous severe psychiatric disorders confirmed by a psychiatrist; refusal or inability to respond to the questionnaire; concomitant neurological disorder; persistent fatigue symptoms during the 6 months before infection; and the need for invasive mechanical ventilation during COVID-19 infection due to a high prevalence of postintensive care syndrome. Our primary outcome is the prevalence of fatigue in patients with post-COVID-19 depression and/or anxiety, as measured by the Chalder Fatigue Scale (CFQ-11) and the Hospital Anxiety and Depression Scale (HADS). The secondary outcomes will include an assessment of health-related quality of life via the EQ-5D questionnaire and an exploration of the prevalence of symptoms of posttraumatic stress disorder (PTSD) using the 14-item Posttraumatic Stress Scale (PTSS-14). We will also examine the association between mental health symptoms and the severity of acute COVID-19. The post-COVID-19 data will be collected at least 6 months after the positive test and no longer than 9 months during the clinical appointment. RESULTS: We expect our multicenter study on patients post COVID-19 to reveal a significant link between mental illness symptoms and both physical and psychological fatigue. Patients with heightened depression and anxiety may report increased levels of fatigue. Additionally, we expect to find persistent PTSD symptoms in a subset of participants, indicating the enduring psychological impact of the virus. CONCLUSIONS: This study may underscore the need for integrated care addressing physical and mental health in patients post COVID-19. The observed connections emphasize the importance of considering mental well-being for long-term health outcomes. Despite study limitations, our findings contribute valuable insights for future treatment strategies and highlight the necessity for comprehensive mental health support in post-COVID-19 care. This research provides valuable insights into the mental health implications of COVID-19 and its impact on post-COVID-19 fatigue and the overall well-being of affected individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT05323318; https://clinicaltrials.gov/study/NCT05323318. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51820.

Neutrophil-to-leukocyte ratio and admission glycemia as predictors of short-term death in very old elderlies with lobar intracerebral hemorrhage.

BACKGROUND: The incidence of spontaneous intracerebral hemorrhage (SICH) is highest in very old elderlies (≥75 years). The increasing use of antithrombotic drugs is shifting the epidemiology of SICH towards predominance of lobar subtype, suggesting an incremented propensity of bleeding associated with underlying cerebral amyloid angiopathy. With population aging and antithrombotic use, a parallel raise of proportion of lobar SICH is occurring. Improvement of prognostication in this specific age group and SICH type is needed. Routine blood biomarkers can contribute to prediction of short-term mortality after SICH. OBJECTIVE: Our aim was to investigate the contribution of routine blood biomarkers for short-term mortality (30-days) in elderly patients with lobar SICH. METHODS: Retrospective analysis of consecutive 130 patients with ≥ 75 years and lobar SICH. The outcome was 30-day mortality. Logistic regression analysis was used to investigate whether admission routine biomarkers can be used as predictors. RESULTS: The case fatality was 40.8%. Admission glycaemia level, neutrophil to lymphocyte ratio and mean platelet volume were significantly different between groups (p = 0.001, p = 0.024, p = 0.038, respectively). There was no significant difference in all other routine biomarkers. On multivariate analysis, admission higher mean BG level (odds ratio [OR]: 1.010, 95% confidence interval [CI]: 1.001-1.019, p = 0.026) and neutrophil to lymphocyte ratio (OR: 1.070, 95% CI: 1.008-1.136, p = 0.027) emerged as predictors. CONCLUSION: In very old patients with lobar SICH, higher BG level and neutrophil to lymphocyte ratio are associated with increased risk of short-term death.

Type I Diabetes in Zebrafish Reduces Sperm Quality and Increases Insulin and Glucose Transporter Transcripts.

Type I diabetes is a prominent human pathology with increasing incidence in the population; however, its cause is still unknown. This disease promotes detrimental effects on reproduction, such as lower sperm motility and DNA integrity. Hence, the investigation of the underlying mechanisms of this metabolic disturbance in reproduction and its transgenerational consequences is of the utmost importance. The zebrafish is a useful model for this research considering its high homology with human genes as well as its fast generation and regeneration abilities. Therefore, we aimed to investigate sperm quality and genes relevant to diabetes in the spermatozoa of Tg(ins:nfsb-mCherry) zebrafish, a model for type I diabetes. Diabetic Tg(ins:nfsb-mCherry) males showed significantly higher expression of transcripts for insulin a (insa) and glucose transporter (slc2a2) compared to controls. Sperm obtained from the same treatment group showed significantly lower sperm motility, plasma membrane viability, and DNA integrity compared to that from the control group. Upon sperm cryopreservation, sperm freezability was reduced, which could be a consequence of poor initial sperm quality. Altogether, the data showed similar detrimental effects related to type I diabetes in zebrafish spermatozoa at the cellular and molecular levels. Therefore, our study validates the zebrafish model for type I diabetes research in germ cells.

R2CHA2DS2-VA Predictsthe Cardiovascular Risk after Carotid Endarterectomy.

BACKGROUND: R2CHA2DS2-VA score has been used to predict short and long-term outcomes in many cardiovascular diseases. This study aims to validate the R2CHA2DS2-VA score as a long-term major adverse cardiovascular events (MACE) predictor after carotid endarterectomy (CEA). Secondary outcomes were also assessed regarding the incidence of all-cause mortality, acute myocardial infarction (AMI), major adverse limb events (MALE), and acute heart failure (AHF). METHODS: From January 2012 to December 2021, patients (n = 205) from a Portuguese tertiary care and referral center that underwent CEA with regional anesthesia (RA) for carotid stenosis (CS) were selected from a previously collected prospective database, and a posthoc analysis was performed. Demographics and comorbidities were registered. Clinical adverse events were assessed 30 days after the procedure and in the subsequent long-term surveillance period. Statistical analysis was performed by the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: Of the patients enrolled, 78.5% were males with a mean age of 70.44 ± 8.9 years. Higher scores of R2CHA2DS2-VA were associated with long-term MACE (adjusted hazard ratio (aHR) 1.390; 95% confidence interval (CI) 1.173-1.647); and mortality (aHR 1.295; 95% CI 1.08-1.545). CONCLUSIONS: This study demonstrated the potential of the R2CHA2DS2-VA score to predict long-term outcomes, such as AMI, AHF, MACE, and all-cause mortality, in a population of patients submitted to carotid endarterectomy.

Benefits of Tranexamic Acid in Total Knee Arthroplasty: A Classification and Regression Tree Analysis in Function of Instrumentation, BMI, and Gender.

Tranexamic acid (TXA) is an antifibrinolytic drug that reduces blood loss in patients that undergo Total knee arthroplasty (TKA). Few studies compare its effect on conventional instrumentation (CI) versus patient-specific instrumentation (PSI). The main objective of this study was to understand analytically how TXA usage in both instrumentations influenced blood loss in TKA differently and see if the differences seen could be explained by the patient's body mass index (BMI) and gender. This nonrandomized retrospective study sample consisted of 688 TKA procedures performed on patients who had symptomatic arthrosis resistant to conservative treatment. Descriptive analysis was used to evaluate blood loss using hemoglobin (Hb) mean values and mean variation (%). The Classification and Regression Tree (CRT) method was applied to understand how the independent variables affected the dependent variable. Comparing patients submitted to the same instrumentation, where some received TXA and others did not, patients that received TXA had lower blood loss. Comparing patients who underwent TKA with different instrumentations and without the use of TXA, it was found that patients who underwent TKA with PSI had lower blood loss than those who underwent TKA with CI. However, when these same instruments were compared again, but associated with the use of TXA, the opposite was true with patients undergoing TKA with PSI showing greater blood loss than patients undergoing TKA with CI. TXA usage in TKA is significantly beneficial in minimizing blood loss and regardless of instrumentation. When using TXA, the lowest blood loss was obtained in patients with higher BMI and submitted to TKA with CI. This is most likely explained by the synergistic antifibrotic effect of TXA with adipokines, such as plasminogen activator inhibitor-1 (PAI-1), found in the femoral bone marrow which is perforated using CI. If, however, TXA wasn't used, the lowest blood loss was obtained in patients submitted to TKA with PSI.

Relapsed Ovarian Cancer Patients with Ascites and/or Pleural Effusion Still Benefit from Treatment: A Real-Life Study.

(1) Background: Relapsed HGSOC with ascites and/or pleural effusion is a poor-prognostic population and poorly represented in clinical studies. We questioned if these patients are worth treating. In other words, if these patients received the most effective treatment, would it change the course of this disease? To our knowledge this is the first real-life study to evaluate this question in this low-survival population. (2) Methods: To tackle this question we performed a retrospective, multi-centric, real-life study, that reviewed relapsed HGSOC patients with ascites and/or pleural effusion. Our rationale was to compare the OS of two groups of patients: responders, i.e., patients who had an imagological response to treatment (complete/partial response/stable disease, RECIST criteria) versus non-responders (no response/progression upon treatment). We evaluated the predictive value of clinical variables that are available in a real-life setting (e.g., staging, chemotherapy, surgery, platinum-sensitivity). Multivariate logistic regression and survival analysis was conducted. A two-step cluster analysis SPSS tool was used for subgroup analysis. Platinum sensitivity/resistance was also analyzed, as well as multivariate and cluster analysis. (3) Results: We included 57 patients, 41.4% first line responders and 59.6% non-responders. The median OS of responders was 23 months versus 8 months in non-responders (p < 0.001). This difference was verified in platinum-sensitive (mOS 28 months vs. 8 months, p < 0.001) and platinum-resistant populations (mOS 16 months vs. 7 months, p < 0.001). Thirty-one patients reached the second line, of which only 10.3% responded to treatment. Three patients out of thirty-one who did not respond in the first line of relapse, responded in the second line. In the second line, the mOS for the responders' group vs. non-responders was 31 months versus 13 months (p = 0.02). The two step cluster analysis tool found two different subgroups with different prognoses based on overall response rate, according to consolidation chemotherapy, neoadjuvant chemotherapy, FIGO staging and surgical treatment. Cluster analysis showed that even patients with standard clinical and treatment variables associated with poor prognosis might achieve treatment response (the opposite being also true). (4) Conclusions: Our data clearly show that relapsed HGSOC patients benefit from treatment. If given an effective treatment upfront, this can lead to a ~3 times increase in mOS for these patients. Moreover, this was irrespective of patient disease and treatment characteristics. Our results highlight the urgent need for a sensitivity test to tailor treatments and improve efficacy rates in a personalized manner.

The Gupta Perioperative Risk for Myocardial Infarct or Cardiac Arrest (MICA) Calculator as an Intraoperative Neurologic Deficit Predictor in Carotid Endarterectomy.

BACKGROUND: Patients undergoing carotid endarterectomy (CEA) may experiment intraoperative neurologic deficits (IND) during carotid cross-clamping. This work aimed to assess the impact of the Gupta Perioperative Myocardial Infarct or Cardiac Arrest (MICA) risk calculator in the IND. METHODS: From January 2012 to April 2021, patients undergoing CEA with regional anaesthesia for carotid stenosis with IND and consecutively control operated patients without IND were selected. A regressive predictive model was created, and a receiver operating characteristic (ROC) curve was applied for comparison. A multivariable dependence analysis was conducted using a classification and regression tree (CRT) algorithm. RESULTS: A total of 97 out of 194 included patients developed IND. Obesity showed aOR = 4.01 (95% CI: 1.66-9.67) and MICA score aOR = 1.21 (1.03-1.43). Higher contralateral stenosis showed aOR = 1.29 (1.08-1.53). The AUROC curve was 0.656. The CRT algorithm differentiated obese patients with a MICA score ≥ 8. Regarding non-obese patients, the model identified the presence of contralateral stenosis ≥ 55% with a MICA ≥ 10. CONCLUSION: MICA score might play an additional role in stratifying patients for IND in CEA. Obesity was determined as the best discrimination factor, followed by a score ≥ 8. A higher ipsilateral stenosis degree is suggested to have a part in avoiding procedure-related IND. Larger studies might validate the benefit of MICA score regarding the risk of IND.

Determinants of health-related quality of life in spondyloarthritis and rheumatoid arthritis - data from the COMOSPA and COMORA studies.

OBJECTIVES: To assess the hierarchy of outcomes contributing to health-related quality of life (HRQoL) in spondyloarthritis (SpA) and rheumatoid arthritis (RA). METHODS: Data from the international cross-sectional COMOSPA and COMORA studies were used. HRQoL was assessed using the EuroQOL 5-dimension 3-level (EQ-5D-3 L). First, multivariable linear regression models were used to identify associations between EQ-5D-3 L (dependent variable) and several demographic and clinical variables (independent variables). Second, a decision tree was built using Chi-square Automatic Interaction Detector, a method of unbiased hierarchical multivariable analysis (dependent variable: EQ-5D-3 L). RESULTS: In total, 3984 patients with SpA and 3920 patients with RA were included. In SpA, HRQoL was associated with BASFI (adjusted B=-0.006; 95%CI=-0.007 to -0.005), ASDAS (-0.052; -0.071 to -0.033), work productivity loss score (-0.002; -0.003 to -0.002), NSAID treatment (-0.052; -0.083 to -0.020), bDMARD treatment (-0.051; -0.082 to -0.021), university education (-0.051; -0.075 to -0.027) and radiographic sacroiliitis (0.035; 0.004 to 0.030). In RA, HRQoL was associated with modified Health Assessment Questionnaire (MHAQ) (-0.220, -0.253 to -0.188), DAS28-CRP-3v (-0.027, -0.036 to -0.018), work productivity loss score (-0.003, -0.003 to -0.002), presence of erosions (-0.042, -0.065 to -0.020), alcohol consumption ≥3 units/day (0.012, 0.001 to 0.024)) and csDMARD treatment (0.034, 0.001 to 0.066). The decision tree revealed BASFI and MHAQ as first variables with the most discriminative power on EQ-5D-3 L, followed by work productivity loss and disease activity, in both SpA and RA cohorts. CONCLUSION: In SpA and RA, physical function is the main contributor to HRQoL measured by EQ-5D-3 L, followed by disease activity and work productivity loss.

Predictors of pneumonia in patients with acute spontaneous intracerebral hemorrhage in Algarve, Southern Portugal.

INTRODUCTION: Following the hyperacute phase of spontaneous intracerebral hemorrhage (SICH), the severest form of stroke, pneumonia emerges as the leading cause of morbidity and mortality. Prevention of stroke associated pneumonia (SAP) is fundamental to improve the prognosis of SICH patients. AIM: Identify clinical, sociodemographic and process of care factors associated with occurrence of SAP after SICH in Algarve, southern Portugal. METHODS: Observational, retrospective study of community representative consecutive case series of patients with SICH admitted to the sole public hospital in the region. Logistic regression was used to identify predictors of SAP after SICH. RESULTS: A total of 525 patients were included. The mean age was 71 ( ± 13) years and 64% were men. SAP occurred in 165 (31.5%). Lower Glasgow Coma Scale score (GCS score): ≤ 8 (OR= 2.087; 95% CI= [1.027;4.424]; p = 0.042) and GCS 9-12 (OR= 1.775; 95% CI= [1.030;3.059]; p = 0.039); prolonged emergency room stay (OR= 8.066; 95%CI=[3.082;21.113]; p < 0.001) and hyperactive delirium (OR=2.860; 95% CI= [1.661;4.925]; p < 0.001) increased the likelihood of SAP. Being younger, ≤ 59 years (OR= 0.391; 95% CI= [0.168; 0.911]; p = 0.029) and 60-71 years (OR= 0.389; 95% CI= [0.185; 0.818]; p = 0.013); and having less severe SICH/intracerebral hemorrhage score (ICH score) ≤ 2 (OR=0.601; 95% CI= [0.370; 0.975]; p = 0.039), decreased the risk of SAP. CONCLUSION: After SICH, SAP occurs in approximately a third of patients. Non preventable (admission severity, ageing) and potentially preventable (prolonged emergency room stay, hyperactive delirium) determine the occurrence of SAP. Intensification of preventive intervention in high-risk patients, delirium prevention and improvement of the process of care can potentially reduce the occurrence of SAP after SICH.

Impact of process of care in the short-term mortality in non-severe intracerebral hemorrhage in southern Portugal.

INTRODUCTION: Patients with spontaneous intracerebral hemorrhage (SICH) face the worse functional and vital prognosis among all stroke subtypes. In cases of severe SICH, therapeutic inertia or nihilism complicates meaningful identification of outcome predictors. Therefore, we sought to investigate clinic-radiological and process of care predictors of short-term mortality in patients with mild to moderate SICH. PATIENTS AND METHODS: Observational retrospective community representative consecutive case series of patients from Algarve, southern Portugal. Logistic regression was used to identify predictors of short-term (30-day) death. RESULTS: Mortality was 23.9% (111/464). Most important predictors of death were unconsciousness at admission (OR = 12.392, 95% CI = 3.816-40.241, p < 0.001), hospital arrival ≥ 6 h after stroke onset (OR = 2.842, 95% CI = 1.380-5.852, p =.005), hematoma volume > 30 cc/cm3 (OR = 3.295, 95% CI 0 1.561-6.953, p =.002), intraventricular extension (OR = 2.885, 95% CI = 1.457-5.712, p =.002) and ≥ 24 h in the Emergency Department (OR = 19.675, 95% CI = 3.682-34.125, p =.009). Stroke Unit (SU) admission reduced the likelihood of death (OR = 0.293, 95% CI = 0.137-0.682, p =.002). CONCLUSION: The observed mortality is high. Apart from the traditional clinic-radiological factors, in mild to moderate SICH, process of care related factors have strong impact on mortality. These results highlight the need of continuous improvement of SICH care to improve the prognosis.

Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant.

PIK3CA mutations are the most common in breast cancer, particularly in the estrogen receptor-positive cohort, but the benefit of PI3K inhibitors has had limited success compared with approaches targeting other less common mutations. We found a frequent allelic expression imbalance between the missense mutant and wild-type PIK3CA alleles in breast tumors from the METABRIC (70.2%) and the TCGA (60.1%) projects. When considering the mechanisms controlling allelic expression, 27.7% and 11.8% of tumors showed imbalance due to regulatory variants in cis, in the two studies respectively. Furthermore, preferential expression of the mutant allele due to cis-regulatory variation is associated with poor prognosis in the METABRIC tumors (P = 0.031). Interestingly, ER-, PR-, and HER2+ tumors showed significant preferential expression of the mutated allele in both datasets. Our work provides compelling evidence to support the clinical utility of PIK3CA allelic expression in breast cancer in identifying patients of poorer prognosis, and those with low expression of the mutated allele, who will unlikely benefit from PI3K inhibitors. Furthermore, our work proposes a model of differential regulation of a critical cancer-promoting gene in breast cancer.

The impact of small-group virtual patient simulator training on perceptions of individual learning process and curricular integration: a multicentre cohort study of nursing and medical students.

BACKGROUND: The COVID-19 pandemic has precipitated rapid changes in medical education to protect students and patients from the risk of infection. Virtual Patient Simulators (VPS) provide a simulated clinical environment in which students can interview and examine a patient, order tests and exams, prioritize interventions, and observe response to therapy, all with minimal risk to themselves and their patients. Like high-fidelity simulators (HFS), VPS are a tool to improve curricular integration. Unlike HFS, VPS require limited infrastructure investment and can be used in low-resource settings. Few studies have examined the impact of VPS training on clinical education. This international, multicenter cohort study was designed to assess the impact of small-group VPS training on individual learning process and curricular integration from the perspective of nursing and medical students. METHODS: We conducted a multi-centre, international cohort study of nursing and medical students. Baseline perceptions of individual learning process and curricular integration were assessed using a 27-item pre-session questionnaire. Students subsequently participated in small-group VPS training sessions lead by a clinical tutor and then completed a 32-item post-session questionnaire, including 25 paired items. Pre- and post-session responses were compared to determine the impact of the small-group VPS experience. RESULTS: Participants included 617 nursing and medical students from 11 institutions in 8 countries. At baseline, nursing students reported greater curricular integration and more clinical and simulation experience than did medical students. After exposure to small-group VPS training, participants reported significant improvements in 5/6 items relating to individual learning process and 7/7 items relating to curricular integration. The impact of the VPS experience was similar amongst nursing and medical students. CONCLUSIONS: In this multi-centre study, perceptions of individual learning process and curricular integration improved after exposure to small-group VPS training. Nursing and medical students showed similar impact. Small-group VPS training is an accessible, low-risk educational strategy that can improve student perceptions of individual learning process and curricular integration.

Determining the Profile of People with Fall Risk in Community-Living Older People in Algarve Region: A Cross-Sectional, Population-Based Study.

One in three people aged 65 years or older falls every year. Injuries associated with this event among the older population are a major cause of pain, disability, loss of functional autonomy and institutionalization. This study aimed to assess mobility and fall risk (FR) in community-living older people and to determine reliable and independent measures (health, social, environmental and risk factors) that can predict the mobility loss and FR. In total, 192 participants were included, with a mean age of 77.93 ± 8.38. FR was assessed by EASY-Care (EC) Standard 2010, the Tinetti Test and the Modified Falls Efficacy Scale (MFES). An exploratory analysis was conducted using the divisive non-hierarchical cluster method, aiming to identify a differentiator and homogeneous group of subjects (optimal group of variables) and to verify if that group shows differences in fall risk. Individually, the health, social, environmental and risk factor categories were not found to be an optimal group; they do not predict FR. The most significant predictor variables were a mix of the different categories, namely, the presence of pain, osteoarthritis (OA), and female gender. The finding of a profile that allows health professionals to be able to quickly identify people at FR will enable a reduction in injuries and fractures resulting from falls and, consequently, the associated costs.

Out-of-hospital cardiac arrest in the Algarve region of Portugal: a retrospective registry trial with outcome data.

BACKGROUND AND IMPORTANCE: Out-of-hospital cardiac arrest is a leading cause of death in Europe. An understanding of region-specific factors is essential for informing strategies to improve survival. DESIGN: This retrospective observational study included all out-of-hospital cardiac arrest patients attended by the Emergency Medical Service of the Algarve in 2019. Outcome data were derived from hospital records. MAIN RESULTS: In 2019, there were 850 out-of-hospital cardiac arrests treated with cardiopulmonary resuscitation in the Algarve, representing a population incidence of 189/100 000. Return of spontaneous circulation occurred in 83 patients (9.8%), of whom 17 (2.0%) had survival to hospital discharge and 15 (1.8%) had survival with good neurologic outcome. Among patients in the Utstein comparator group, survival to hospital discharge was 21.4%. Predictors of return of spontaneous circulation were age, witnessed arrest, initial shockable rhythm, time of year, time to cardiopulmonary resuscitation, and time to advanced life support. Predictors of survival to hospital discharge were age, initial shockable rhythm, time to rhythm analysis, and time to advanced life support. Predictors of survival with good neurologic outcome were age, initial shockable rhythm, and time to return of spontaneous circulation. CONCLUSIONS: The incidence of out-of-hospital cardiac arrest with cardiopulmonary resuscitation in the Algarve was higher than in other jurisdictions while return of spontaneous circulation, survival to hospital discharge, and survival with good neurologic outcome were comparatively low. An aging population, a geographically diverse region, and a low incidence of bystander cardiopulmonary resuscitation may have contributed to these outcomes. These results confirm the importance of early cardiopulmonary resuscitation, early rhythm assessment, and early advanced life support, all of which are potentially modifiable through public education, broadening of the defibrillator network and increased availability of advanced life support teams.

Long-Term Association Between Disease Activity and Disability in Early Axial Spondyloarthritis: Results From a Prospective Observational Study of Inflammatory Back Pain.

OBJECTIVE: Our primary objective was to study the long-term association between disease activity and disability in axial spondyloarthritis (SpA). Our secondary objective was to define patient profiles according to their level of disability. METHODS: We analyzed data collected during the first 5 years of follow-up of a large early axial SpA cohort, the Devenir des Spondylarthropathies Indifferénciées Récentes (DESIR) cohort. Multivariable models were built to study the association between the Health Assessment Questionnaire for Ankylosing Spondylitis (HAQ-AS) and the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), adjusting for potential confounders. Hierarchical multivariable analysis was conducted using the chi-square automatic interaction detector (CHAID) method, to help determine how variables best cluster to explain HAQ-AS. RESULTS: Data from 644 patients and 5,152 visits were analyzed. HAQ-AS was longitudinally, independently, and positively associated with ASDAS-CRP (adjusted B [adjB] 0.205 [95% confidence interval (95% CI) 0.187, 0.222]), the enthesitis score (adjB 0.011 [95% CI 0.008, 0.015]), the Bath Ankylosing Spondylitis Metrology Index (adjB 0.087 [95% CI 0.069, 0.105]), and female sex (adjB 0.172 [95% CI 0.120, 0.225]). The CHAID decision tree revealed ASDAS-CRP as the first variable with discriminative power on HAQ-AS. The cutoffs that separated different patient disability profiles were obtained. CONCLUSION: Disease activity contributes longitudinally to disability and is hierarchically superior to any other variable in explaining this health domain. Enthesitis and spinal mobility are also key drivers of disability in early axial SpA. ASDAS-CRP cutoffs that separated different patient disability profiles largely mimicked the cutoffs previously defined for ASDAS-CRP disease activity states.