Enhancing Ecological Validity: Virtual Reality Assessment of Executive Functioning in Children and Adolescents with ADHD.

BACKGROUND: SmartAction-VR uses virtual reality to simulate daily life tasks and assess cognitive performance based on the multi-errand paradigm. This study explored whether this new task could provide insights into the executive functioning of children and adolescents with ADHD in their everyday activities. METHODS: A cross-sectional study was conducted between November 2021 and December 2022. It consisted of one session and was divided into two parts (cognitive tests; and SmartAction-VR). The sample comprised 76 children and adolescents with a median age (IQR) of 13 (11-14) years and an age range of 9-17 years. Of these participants, 60.50% (n = 46) were males. Out of this sample, 40 participants were in the ADHD group and 36 were in the neurotypical group. The following instruments were used: Waisman Activities of Daily Living Scale, Assessment of Sensory Processing and Executive Functioning, Pediatric Simulator Disease Questionnaire, Digit span subtest, Stroop test, NEPSY-II Subtest of Auditory Attention and Cognitive Flexibility, Trail Making Test, Zoo Map Test, and SmartAction-VR. RESULTS: The ADHD group demonstrated lower accuracy (U = 406, p = 0.010), higher values for total errors (U = 292, p = 0.001), more commissions (U = 417, p = 0.003), new actions (U = 470, p = 0.014), and forgetting actions (U = 406, p = 0.010), as well as fewer perseverations compared to the neurotypical group (U = 540.5, p = 0.029). Additionally, participants who forgot more actions were found to have lower independence in daily life (r = -0.281, p = 0.024). CONCLUSIONS: The correlations between the results of SmartAction-VR and activities of daily living, as well as cognitive tests, suggest that this new task could be useful for evaluating executive functioning in daily life.

Use of diagnostic tests in elderly patients consulting the emergency department. Analysis of the emergency department and elder needs cohort (EDEN-8).

OBJECTIVE: Analyse the association between the use of diagnostic tests and the characteristics of older patients 65 years of age or more who consult the emergency department (ED). METHODS: We performed an analysis of the EDEN cohort that includes patients who consulted 52 Spanish EDs. The association of age, sex, and ageing characteristics with the use of diagnostic tests (blood tests, electrocardiogram (ECG), microbiological cultures, X-ray, computed tomography, ultrasound, invasive techniques) was studied. The association was analysed by calculating the adjusted odds ratios (aOR) and their 95 % confidence intervals (CI) using a logistic regression model. RESULTS: A total of 25,557 patients were analysed. There was an increase in the use of diagnostic tests based on age, with an aOR for blood test of 1.805 (95 %CI 1.671 - 1.950), ECG 1.793 (95 %CI 1.664 - 1.932) and X-ray 1.707 (95 %CI 1.583 - 1.840) in the group of 85 years or more. The use of diagnostic tests is lower in the female population. Most ageing characteristics (cognitive impairment, previous falls, polypharmacy, dependence, and comorbidity) were independently associated with increased use of diagnostic tests. CONCLUSIONS: Age, and the characteristics of ageing itself are generally associated with a greater use of diagnostic tests in the ED.

Overnight stay in Spanish emergency departments and mortality in older patients.

To assess whether older adults who spend a night in emergency departments (ED) awaiting admission are at increased risk of mortality. This was a retrospective review of a multipurpose cohort that recruited all patients ≥ 75 years who visited ED and were admitted to hospital on April 1 to 7, 2019, at 52 EDs across Spain. Study groups were: patients staying in ED from midnight until 8:00 a.m. (ED group) and patients admitted to a ward before midnight (ward group). The primary endpoint was in-hospital mortality, truncated at 30 days, and secondary outcomes assessed length of stay for the index episode. The sample comprised 3,243 patients (median [IQR] age, 85 [81-90] years; 53% women), with 1,096 (34%) in the ED group and 2,147 (66%) in the ward group. In-hospital mortality for patients spending the night in the ED the ED group was 10.7% and 9.5% for patients transferred to a ward bed before midnight the ward group (adjusted OR: 1.12, 95%CI: 0.80-1.58). Sensitivity analyses rendered similar results (ORs ranged 1.06-1.13). Interaction was only detected for academic/non-academic hospitals (p < 0.001), with increased mortality risk for the latter (1.01, 0.33-3.09 vs 2.86, 1.30-6.28). There were no differences in prolonged hospitalization (> 7 days), with adjusted OR of 1.16 (0.94-1.43) and 1.15 (0.94-1.42) depending on whether time spent in the ED was or was not taken into consideration. No increased risk of in-hospital mortality or prolonged hospitalization was found in older patients waiting overnight in the ED for admission. Nonetheless, all estimations suggest a potential harmful effect of staying overnight, especially if a proper bedroom and hospitalist ward bed and hospitalized care are not provided.

Use of resources in elderly patients consulting the emergency department: analysis of the Emergency Department and Elder Needs Cohort (EDEN-21).

The elderly population frequently consults the emergency department (ED). This population could have greater use of EDs and hospital health resources. The EDEN cohort of patients aged 65 years or older visiting the ED allowed this association to be investigated. To analyse the association between healthcare resource use and the characteristics of patients over 65 years of age who consult hospital EDs. We performed an analysis of the EDEN cohort, a retrospective, analytical, and multipurpose registry that includes patients over 65 years of age who consulted in 52 Spanish EDs. The impact of age, sex, and characteristics of ageing on the following outcomes was studied: need for hospital admission (primary outcome) and need for observation, stay in the ED > 12 h, prolonged hospital stay > 7 days, need for intensive care unit (ICU) and return to the ED at 30 days related to the index visit (secondary outcomes). The association was analysed by calculating the adjusted odds ratios (aOR) and their 95% confidence intervals (CI), using a logistic regression model. A total of 25,557 patients with a mean age of 78.3 years were analysed, 45% were males. Of note was the presence of comorbidity, a Charlson index ≥ 3 (33%), and polypharmacy (66%). Observation in the ED was required by 26%, 25.4% were admitted to the hospital, and 0.9% were admitted to the ICU. The ED stay was > 12 h in 12.5% and hospital stay > 7 days in 13.5% of cases. There was a progressive increase in healthcare resource use based on age, with an aOR for the need for observation of 2.189 (95% CI 2.038-2.352), ED stay > 12 h 2.136 (95% CI 1.942-2.349) and hospital admission 2.579 (95% CI 2.399-2.772) in the group ≥ 85 years old. Most of the characteristics inherent to ageing (cognitive impairment, falls in the previous 6 months, polypharmacy, functional dependence, and comorbidity) were associated with significant increases in the use of healthcare resources, except for ICU admission, which was less in all the variables studied. Age and the characteristics inherent to ageing are associated with greater use of structural healthcare resources.

Older Adult Patients in the Emergency Department: Which Patients should be Selected for a Different Approach?

BACKGROUND: While multidimensional and interdisciplinary assessment of older adult patients improves their short-term outcomes after evaluation in the emergency department (ED), this assessment is time-consuming and ill-suited for the busy environment. Thus, identifying patients who will benefit from this strategy is challenging. Therefore, this study aimed to identify older adult patients suitable for a different ED approach as well as independent variables associated with poor short-term clinical outcomes. METHODS: We included all patients ≥65 years attending 52 EDs in Spain over 7 days. Sociodemographic, comorbidity, and baseline functional status data were collected. The outcomes were 30-day mortality, re-presentation, hospital readmission, and the composite of all outcomes. RESULTS: During the study among 96,014 patients evaluated in the ED, we included 23,338 patients ≥65 years-mean age, 78.4±8.1 years; 12,626 (54.1%) women. During follow-up, 5,776 patients (24.75%) had poor outcomes after evaluation in the ED: 1,140 (4.88%) died, 4,640 (20.51) returned to the ED, and 1,739 (7.69%) were readmitted 30 days after discharge following the index visit. A model including male sex, age ≥75 years, arrival by ambulance, Charlson Comorbidity Index ≥3, and functional impairment had a C-index of 0.81 (95% confidence interval, 0.80-0.82) for 30-day mortality. CONCLUSION: Male sex, age ≥75 years, arrival by ambulance, functional impairment, or severe comorbidity are features of patients who could benefit from approaches in the ED different from the common triage to improve the poor short-term outcomes of this population.

Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving ß-blockers+ligation to prevent re-bleeding.

BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

Hyperactive delirium during emergency department stay: analysis of risk factors and association with short-term outcomes.

To investigate factors related to the development of hyperactive delirium in patients during emergency department (ED) stay and the association with short-term outcomes. A secondary analysis of the EDEN (Emergency Department and Elderly Needs) multipurpose multicenter cohort was performed. Patients older than 65 years arriving to the ED in a calm state and who developed confusion and/or psychomotor agitation requiring intravenous/intramuscular treatment during their stay in ED were assigned to delirium group. Patients with psychiatric and epileptic disorders and intracranial hemorrhage were excluded. Thirty-four variables were compared in both groups and outcomes were adjusted for age, sex, Charlson Comorbidity Index, Barthel Index and polypharmacy. Hyperactive delirium that needed treatment were developed in 301 out of 18,730 patients (1.6%). Delirium was directly associated with previous episodes of delirium (OR: 2.44, 95% CI 1.24-4.82), transfer to the ED observation unit (1.62, 1.23-2.15), chronic treatment with opiates (1.51, 1.09-2.09) and length of ED stay longer than 12 h (1.41, 1.02-1.97) and was indirectly associated with chronic kidney disease (0.60, 0.37-0.97). The 30-day all-cause mortality was 4.0% in delirium group and 2.9% in non-delirium group (OR: 1.52, 95% CI 0.83-2.78), need for hospitalization 25.6% and 25% (1.09, 0.83-1.43), in-hospital mortality 16.4% and 7.3% (2.32, 1.24-4.35), prolonged hospitalization 54.5% and 48.6% (1.27, 0.80-2.00), respectively, and 90-day post-discharge combined adverse event 36.4% and 35.8%, respectively (1.06, 0.82-2.00). Patients with previous episodes of delirium, treatment with opioids and longer stay in ED more frequently develop delirium during ED stay and preventive measures should be taken to minimize the incidence. Delirium is associated with in-hospital mortality during the index event.

Ten Issues to Update in Nosocomial or Hospital-Acquired Pneumonia: An Expert Review.

Nosocomial pneumonia, or hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) are important health problems worldwide, with both being associated with substantial morbidity and mortality. HAP is currently the main cause of death from nosocomial infection in critically ill patients. Although guidelines for the approach to this infection model are widely implemented in international health systems and clinical teams, information continually emerges that generates debate or requires updating in its management. This scientific manuscript, written by a multidisciplinary team of specialists, reviews the most important issues in the approach to this important infectious respiratory syndrome, and it updates various topics, such as a renewed etiological perspective for updating the use of new molecular platforms or imaging techniques, including the microbiological diagnostic stewardship in different clinical settings and using appropriate rapid techniques on invasive respiratory specimens. It also reviews both Intensive Care Unit admission criteria and those of clinical stability to discharge, as well as those of therapeutic failure and rescue treatment options. An update on antibiotic therapy in the context of bacterial multiresistance, in aerosol inhaled treatment options, oxygen therapy, or ventilatory support, is presented. It also analyzes the out-of-hospital management of nosocomial pneumonia requiring complete antibiotic therapy externally on an outpatient basis, as well as the main factors for readmission and an approach to management in the emergency department. Finally, the main strategies for prevention and prophylactic measures, many of them still controversial, on fragile and vulnerable hosts are reviewed.

Benefits of MR-proADM-guided decision-making in the emergency department: clinical and economic evaluation in Italy, Germany, Spain, and the UK.

AIM: In a randomized control trial mid-regional proadrenomedullin (MR-proADM)-guided decision-making has been proven to safely reduce hospital admissions based on an accurate assessment of disease severity in the Emergency Department (ED). This study aimed to assess the impact of a MR-proADM-Guided Triage (MR-GT) versus standard Hospital Triage (HT) on clinical and economic outcomes in ED patients with suspected infection in Spain, Italy, Germany, and the UK, using Patient-Level Data (PLD) from two observational studies. METHODS: PLD was collected from patients enrolled at a Spanish hospital during two observational studies. Logistic regression was used to identify predictors of hospitalization. A patient-level simulation model was subsequently developed to evaluate the clinical and economic impact of MR-GT versus HT using results from the statistical analysis and country-specific cost data from the published literature. Probabilistic and deterministic sensitivity analyses were carried out. RESULTS: Four hundred seventy-three patients were enrolled in this study. MR-proADM had the strongest association with hospital admission, followed by age and National Early Warning Score (NEWS). In the simulation model, MR-GT was associated with an overall reduction in hospitalization relative to HT, equal to 22.6 percentage points (40.9 vs. 63.5%). In addition, the use of MR-GT would reduce the total hospital cost per patient presenting to the ED with suspected infection by roughly 30%, with a mean cost saving per patient of €626, €1,484, €1,154, and £1,113 in Spain, Italy, Germany, and the UK, respectively. The robustness of these findings was confirmed by sensitivity analyses. LIMITATIONS: The statistical analyses were not performed on the same population simulated in the model. Clinical input parameters were assumed to be the same for all countries. CONCLUSIONS: MR-proADM showed to be the main predictor of hospitalization. An MR-proADM decision algorithm provides cost savings in Spain, Italy, Germany, and the UK.

Sialolitiasis, sialoadenitis y sialoadenosis. Revisión de literatura y reporte de un caso clínico / Sialolithiasis, sialadenitis and sialadenosis. Review of literature and report of a clinical case

Introducción: la formación de sialolitos se considera la alteración más común en las glándulas salivales. Su origen aún no es claro en cuanto a qué provoca la obstrucción parcial o total del sistema de conductos salivales, con una predilección significativa en las glán - dulas submandibulares, lo que permite un desplazamiento retrógrado de bacterias a través del conducto salival hacia la glándula afectada, el cual se traducirá clínicamente como inflamación unilateral o bila - teral. El tratamiento para la sialolitiasis y sialoadenitis puede variar desde un manejo conservador hasta tratamientos que implican la remoción de la glándula salival afectada. La sialoadenosis difiere de las anteriores en su origen, ya que ésta no se considera inflamatoria ni neoplásica y no afecta la función glandular de excretar saliva. Presentación de caso clínico: se trata de paciente masculino con diagnósticos presuntivos de sialoadenitis y sialolitiasis, al cual se le realizó biopsia escisional de la glándula afectada, su estudio histo- patológico corroboró los diagnósticos mencionados anteriormente que además confirmó un diagnóstico de sialoadenosis. Conclusio- nes: la escisión de la glándula salival involucrada se realizará en casos diagnosticados de sialoadenitis y sialolitiasis con sialolitos de gran tamaño y procesos supurativos crónicos que no resuelven con antibioticoterapia (AU)

Utilidad del modelo 5MPB-Toledo para predecir bacteriemia en el paciente anciano / Usefulness of the 5MPB-Toledo model to predict bacteremia in the elderly patient

Resumen Objetivo: Analizar la utilidad del modelo predictivo de bacteriemia (5MPB-Toledo) en los mayores de 65 años atendidos por infección en el servicio de urgencias (SU). Material y Método: Estudio observacional prospectivo y multicéntrico de los hemocultivos (HC) obtenidos en pacientes mayores de 65 años atendidos por infección en 66 SU españoles desde el 1 de diciembre de 2019 hasta el 30 de abril de 2020. Se analizó la capacidad predictiva del modelo con el área bajo la curva (ABC) de la característica operativa del receptor (COR) y se calculó el rendimiento diagnóstico de los puntos de corte (PC) del modelo elegido con los cálculos de la sensibilidad, la especificidad, el valor predictivo positivo y el valor predictivo negativo. Resultados: Se incluyeron 2.401 episodios de HC extraídos. De ellos, se consideró como bacteriemia verdadera a 579 (24,11%) y como HC negativo a 1.822 (75,89%). Entre los negativos, 138 (5,74%) se consideraron contaminados. Se categorizó a los pacientes en bajo (0-2 puntos), moderado (3-5 puntos) y alto (6-8 puntos) riesgo, con una probabilidad de bacteriemia de 1,2%, 18,1% y 80,7%, respectivamente. El ABC-COR del modelo tras remuestreo fue de 0,908 (IC 95%: 0,897-0,924). El rendimiento diagnóstico del modelo, considerando un PC ≥ 5 puntos, obtiene una sensibilidad de 94% (IC 95%:92-96), especificidad de 77% (IC 95%:76-79) y un valor predictivo negativo de 97% (IC 95%:96-98). Conclusión: El modelo 5MPB-Toledo es de utilidad para predecir bacteriemia en los mayores de 65 años atendidos en el SU por un episodio de infección.

Abstract Objective: To analyse a risk score to predict bacteremia (MPB5-Toledo) in the patients aged older 65 years seen in the emergency departments (ED) due to infections. Patients and Methods: Prospective and multicenter observational cohort study of the blood cultures (BC) ordered in 66 Spanish ED for patients aged older 65 years seen from December 1, 2019, to April 30, 2020. The predictive ability of the model was analyzed with the area under the Receiver Operating Characteristic curve (AUC-ROC). The prognostic performance for true bacteremia was calculated with the cut-off values chosen for getting the sensitivity, specificity, positive predictive value and negative predictive value. Results: A total of 2.401 blood samples wered cultured. True cases of bacteremia were confirmed in 579 (24.11%). The remaining 1.822 cultures (75.89%) wered negative. And, 138 (5.74%) were judged to be contaminated. Low risk for bacteremia was indicated by a score of 0 to 2 points, intermediate risk by 3 to 5 points, and high risk by 6 to 8 points. Bacteremia in these 3 risk groups was predicted for 1.2%, 18.1%, and 80.7%, respectively. The model´s area under the receiver ope rating characteristic curve was 0.908 (95% CI, 0.897-0.924). The prognostic performance with a model´s cut-off value of ≥ 5 points achieved 94% (95% CI: 92-96) sensitivity, 77% (95% CI: 76-79) specificity, and negative predictive value of 97% (95% CI: 96-98). Conclusion: The 5MPB-Toledo score is useful for predicting bacteremia in the patients aged older 65 years seen in the emergency departments due to infections.

Can axillary lymphadenectomy be avoided in breast cancer with positive sentinel lymph node biopsy? Predictors of non-sentinel lymph node metastasis.

PURPOSE: Completion axillary lymph node dissection (cALND) can currently be avoided in those patients with a low tumor load (LTL) and/or a low-risk profile that tested with positive sentinel lymph node biopsy (SLNB). Our objective is to identify prognostic factors that significantly influence axillary lymph node involvement to identify patients who could benefit from surgery without axillary lymphadenectomy. METHODS: This is an observational retrospective study of consecutive patients diagnosed and operated of breast cancer between 2000 and 2014 at University Hospital La Ribera (UHR). RESULTS: The size of the sample was 1641 patients, from which 1174 underwent SLNB. In the multivariate analysis, we objectify a raise of risk of positive sentinel lymph node (SLN) up to 5.2% for every millimeter of increase. The risk of positive SLNB when showing lymphovascular invasion seems to be 2.80 times greater but becomes lower when SLN involvement appears in luminal A, luminal B and triple-negative types, regarding HER2. In case of triple negatives, the difference is statistically significant. 16.7% present affected additional lymph nodes. The proportion of patients with affected additional lymph nodes increase dramatically above OSNA values of 12,000 copies/µl of CK19 mRNA and it depends on tumor size and lymphovascular infiltration. CONCLUSIONS: Tumors smaller than 5 cm whose OSNA SLNB analysis is less than 12,000 copies/µl of CK19 mRNA have a low chance to develop additional affected lymph nodes, thus cALND can be avoided.

The utility of the Barthel index as an outcome predictor in older patients with acute infection attending the emergency department.

BACKGROUND: Functional decline and frailty are common in older adults and influence the risk of adverse outcomes. We aimed to assess the value of a Barthel index at the Emergency Department (ED-BI) score in predicting 30-day mortality and ED reconsultation among older patients with acute infection. METHODS: We performed a prospective multicentre cohort study of older patients (≥75 years) diagnosed with acute infection in 69 Spanish EDs. Demographic, comorbidities, functional status, clinical and analytical data were collected. Unadjusted and adjusted logistic regression models were used to assess the association between ED-BI score, mortality and ED reconsultation. RESULTS: In total 1596 patients with a mean age of 84.7 years were included in the study and 51.7% female. The most frequent focus of infection was respiratory in 918 patients (57.5%). Patients with an ED-BI< 60 points were significantly older, predominantly female, more likely institutionalized and more urinary infections. When comparing patients with an ED-BI score ≥ 60 points with those< 60 points no differences were found in ED reconsultation but in the latter group mortality at 30-days was higher (p < 0.001). CONCLUSION: An ED-BI score< 60 points appears to be a strong predictor of mortality at the 30-day follow up in older patients with acute infection. DATA AVAILABILITY: The data used to support the findings of this study are included within the article.

Platelet number and function alterations in preclinical models of sterile inflammation and sepsis patients: implications in the pathophysiology and treatment of inflammation.

Platelets are the blood cells in charge of maintaining the body hemostasis, recognising the damaged vessel wall, and providing the appropriate cellular surface for the coagulation cascade to act locally. Additionally, platelets are active immunomodulators. At the crossroads of hemostasis and inflammation, platelets may exert either beneficial actions or participate in pathological manifestations, and have been associated with the prothrombotic nature of multi-organ failure in systemic inflammation. Platelet number alterations have been reported in septis, and platelet transfusions are given to thrombocytopenic patients. However, the risk to develop transfusion related acute lung injury (TRALI) is higher in sepsis patients. In this manuscript we show that platelets produced during inflammation in preclinical mouse models of sterile inflammation display lower aggregation capacity when stimulating certain receptors, while responses through other receptors remain intact, and we name them "inflammation-conditioned" platelets. In a cohort of sepsis patients, we observed, as previously reported, alterations in the number of platelets and platelet hyperreactivity. Furthermore, we identified a receptor-wise platelet aggregation response disbalance in these patients, although not similar to platelets from preclinical models of sterile inflammation. Interestingly, we generated evidence supporting the notion that platelet aggregation capacity disbalance was partially triggered by plasma components from sepsis patients. Our findings have implications in the indication of platelet transfusions in sepsis patients: Are fully functional platelets suitable for transfusion in sepsis patients? Current Clinical Trials (RESCUE) will answer whether platelet production stimulation with thrombopoietin receptor agonists (TPO-RAs) could be a substitute of platelet transfusions.

Incidence, Clinical Characteristics, Risk Factors and Outcomes of Acute Coronary Syndrome in Patients With COVID-19: Results of the UMC-19-S1010.

BACKGROUND: There is a lack of knowledge about the real incidence of acute coronary syndrome (ACS) in patients with COVID-19, their clinical characteristics, and their prognoses. OBJECTIVE: We investigated the incidence, clinical characteristics, risk factors, and outcomes of ACS in patients with COVID-19 in the emergency department. METHODS: We retrospectively reviewed all COVID-19 patients diagnosed with ACS in 62 Spanish emergency departments between March and April 2020 (the first wave of COVID-19). We formed 2 control groups: COVID-19 patients without ACS (control A) and non-COVID-19 patients with ACS (control B). Unadjusted comparisons between cases and control subjects were performed regarding 58 characteristics and outcomes. RESULTS: We identified 110 patients with ACS in 74,814 patients with COVID-19 attending the ED (1.48% [95% confidence interval {CI} 1.21-1.78%]). This incidence was lower than that observed in non-COVID-19 patients (3.64% [95% CI 3.54-3.74%]; odds ratio [OR] 0.40 [95% CI 0.33-0.49]). The clinical characteristics of patients with COVID-19 associated with a higher risk of presenting ACS were: previous coronary artery disease, age ≥60 years, hypertension, chest pain, raised troponin, and hypoxemia. The need for hospitalization and admission to intensive care and in-hospital mortality were higher in cases than in control group A (adjusted OR [aOR] 6.36 [95% CI 1.84-22.1], aOR 4.63 [95% CI 1.88-11.4], and aOR 2.46 [95% CI 1.15-5.25]). When comparing cases with control group B, the aOR of admission to intensive care was 0.41 (95% CI 0.21-0.80), while the aOR for in-hospital mortality was 5.94 (95% CI 2.84-12.4). CONCLUSIONS: The incidence of ACS in patients with COVID-19 attending the emergency department was low, around 1.48%, but could be increased in some circumstances. Patients with COVID-19 with ACS had a worse prognosis than control subjects with higher in-hospital mortality.

Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study.

BACKGROUND: There is a need for more convenient, less frequent treatment to help address challenges associated with daily oral HIV treatment in people living with HIV, including stigma, pill burden, drug-food interactions, and adherence. The phase 3 ATLAS and FLAIR studies showed non-inferiority of long-acting cabotegravir and rilpivirine dosed every 4 weeks compared with standard oral therapy for the maintenance of virological suppression in adults with HIV-1 over 48 weeks. We present the 96-week findings. METHODS: FLAIR is a randomised, phase 3, open-label, multicentre study done in 11 countries investigating whether switching to long-acting cabotegravir and rilpivirine is non-inferior to daily dolutegravir, abacavir, and lamivudine in virologically suppressed adults living with HIV-1. Antiretroviral therapy (ART)-naive participants received induction therapy with daily oral dolutegravir (50 mg), abacavir (600 mg), and lamivudine (300 mg) for 20 weeks. After 16 weeks, participants with less than 50 HIV-1 RNA copies per mL were randomly assigned (1:1) to continue the standard of care regimen (standard care group) or switch to receive daily oral cabotegravir 30 mg and rilpivirine 25 mg for at least 4 weeks followed by long-acting cabotegravir 400 mg and rilpivirine 600 mg, administered as two 2 mL intramuscular injections, every 4 weeks for at least 96 weeks (long-acting group). Randomisation was stratified by baseline (preinduction) HIV-1 RNA (<100 000 or ≥100 000 copies per mL) and sex at birth and used GlaxoSmithKline-verified randomisation software (RandAll NG, version 1.3.3) for treatment assignment. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies per mL or more assessed as per the US Food and Drug Administration (FDA) Snapshot algorithm at week 48, which has been reported previously. Here, we report the proportion of participants with 50 or more HIV-1 RNA copies per mL using the FDA Snapshot algorithm at week 96 (intention-to-treat population; non-inferiority margin 6%). The trial is registered with ClinicalTrials.gov, NCT02938520. FINDINGS: Between Oct 27, 2016, and March 24, 2017, 809 participants were screened. 631 (78%) participants entered the induction phase and 566 (70%) were randomly assigned to either the standard care group (283 [50%] participants) or the long-acting group (283 [50%]). Median age was 34 years (IQR 29 to 43), 62 (11%) were 50 years or older, 127 (22%) were women (sex at birth), and 419 (74%) were white. At week 96, nine (3%) participants in each arm had 50 or more HIV-1 RNA copies per mL, with an adjusted difference of 0·0 (95% CI -2·9 to 2·9), consistent with non-inferiority established at week 48. Across both treatment groups, adverse events leading to withdrawal were infrequent (14 [5%] participants in the long-acting group and four [1%] in the standard care group). Injection site reactions were the most common adverse event, reported by 245 (88%) participants in the long-acting group; their frequency decreased over time. Median injection site reaction duration was 3 days (IQR 2 to 4), and 3082 (99%) of 3100 reactions were grade 1 or 2. No deaths occurred during the maintenance phase. INTERPRETATION: The 96-week results reaffirm the 48-week results, showing long-acting cabotegravir and rilpivirine continued to be non-inferior compared with continuing a standard care regimen in adults with HIV-1 for the maintenance of viral suppression. These results support the durability of long-acting cabotegravir and rilpivirine, over an almost 2-year-long period, as a therapeutic option for virally suppressed adults with HIV-1. FUNDING: ViiV Healthcare and Janssen Research and Development.

Mid-regional pro-adrenomedullin as a supplementary tool to clinical parameters in cases of suspicion of infection in the emergency department.

INTRODUCTION: Mid-regional proadrenomedullin (MR-proADM), a novel biomarker, has recently gained interest particularly with regards to its potential in assisting clinicians' decision making in patients with suspicion of infection in the emergency department (ED). A group of international experts, with research and experience in MR-proADM applications, produced this review based on their own experience and the currently available literature. AREAS COVERED: The review provides evidence related to MR-proADM as a triaging tool in avoiding unnecessary admissions to hospital and/or inadequate discharge, and identifying patients most at risk of deterioration. It also covers the use of MR-proADM in the context of COVID-19. Moreover, the authors provide a proposal on how to incorporate MR-proADM into patients' clinical pathways in an ED setting. EXPERT OPINION: The data we have so far on the application of MR-proADM in the ED is promising. Incorporating it into clinical scoring systems may aid the clinician's decision making and recognizing the 'ill looking well' and the 'well looking ill' sooner. However there are still many gaps in our knowledge especially during the ongoing COVID-19 waves. There is also a need for cost-effectiveness analysis studies especially in the era of increasing cost pressures on health systems globally.

How are rapid diagnostic tests for infectious diseases used in clinical practice: a global survey by the International Society of Antimicrobial Chemotherapy (ISAC).

Novel rapid diagnostic tests (RDTs) offer huge potential to optimise clinical care and improve patient outcomes. In this study, we aim to assess the current patterns of use around the world, identify issues for successful implementation and suggest best practice advice on how to introduce new tests. An electronic survey was devised by the International Society of Antimicrobial Chemotherapy (ISAC) Rapid Diagnostics and Biomarkers working group focussing on the availability, structure and impact of RDTs around the world. It was circulated to ISAC members in December 2019. Results were collated according to the UN human development index (HDI). 81 responses were gathered from 31 different countries. 84% of institutions reported the availability of any test 24/7. In more developed countries, this was more for respiratory viruses, whereas in high and medium/low developed countries, it was for HIV and viral hepatitis. Only 37% of those carrying out rapid tests measured the impact. There is no 'one-size fits all' solution to RDTs: the requirements must be tailored to the healthcare setting in which they are deployed and there are many factors that should be considered prior to this.

Lowering Portal Pressure Improves Outcomes of Patients With Cirrhosis, With or Without Ascites: A Meta-Analysis.

BACKGROUND & AIMS: In unselected patients with cirrhosis, those with reductions in hepatic venous pressure gradient (HVPG) to below a defined threshold (responders) have a reduced risk of variceal hemorrhage (VH) and death. We performed a meta-analysis to compare this effect in patients with vs without ascites. METHODS: We collected data from 15 studies of primary or secondary prophylaxis of VH that reported data on VH and death in responders vs nonresponders. We included studies in which data on ascites at baseline and on other relevant outcomes during follow-up evaluation were available. We performed separate meta-analyses for patients with vs without ascites. RESULTS: Of the 1113 patients included in the studies, 968 patients (87%) had been treated with nonselective ß-blockers. In 993 patients (89%), HVPG response was defined as a decrease of more than 20% from baseline (>10% in 11% of patients) or to less than 12 mm Hg. In the 661 patients without ascites, responders (n = 329; 50%) had significantly lower odds of events (ascites, VH, or encephalopathy) than nonresponders (odds ratio [OR], 0.35; 95% CI, 0.22-0.56). Odds of death or liver transplantation were also significantly lower among responders than nonresponders (OR, 0.50, 95% CI, 0.32-0.78). In the 452 patients with ascites, responders (n = 188; 42%) had significantly lower odds of events (VH, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome) than nonresponders (OR, 0.27; 95% CI, 0.16-0.43). Overall, odds of death or liver transplantation were lower among responders (OR, 0.47; 95% CI, 0.29-0.75). No heterogeneity was observed among studies. CONCLUSIONS: In a meta-analysis of clinical trials, we found that patients with cirrhosis with and without ascites who respond to treatment with nonselective ß-blockers (based on reductions in HVPG) have a reduced risk of events, death, or liver transplantation.