Development and external validation of a model to predict multidrug-resistant bacterial infections in patients with cirrhosis.

With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. METHODS: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture-positive and culture-negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism-adjusted model using calibration and discrimination statistics and evaluated its clinical utility. RESULTS: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD-Na, use of vasopressors, acute-on-chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI .48-1.05), and the area under the ROC curve was .68 (95% CI .61-.73). The application of the model significantly changed the post-test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community-acquired infections at significant risk (36%). CONCLUSION: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies.

Towards evidence-based empiric antibiotic recommendations for spontaneous infections in patients with cirrhosis.

BACKGROUND: With the emergence of multidrug-resistant infections, healthcare professionals must evaluate the effectiveness of empiric antibiotic treatments. AIMS: To assess the antibiotic susceptibility patterns of microorganisms causing spontaneous infections in patients with cirrhosis and to evaluate the suitability of empiric antibiotic treatments based on major clinical guidelines. METHODS: This cross-sectional study utilized two datasets from prospective studies of patients with cirrhosis and culture-positive spontaneous bacterial infections in Argentina and Uruguay. We estimated susceptibility to commonly used antibiotics and assessed coverage following European and American recommendations. RESULTS: We analyzed 238 episodes of culture-positive spontaneous infections in 229 patients. When implementing the recommendations for empiric treatment of community-acquired spontaneous infections, ceftazidime would result in 39 % coverage, whereas ceftriaxone would reach 70 %. Cefepime, which is not included in the recommendations, would have provided coverage of 74 %. Using ertapenem for nosocomial infections would have only covered 56 % of these episodes, whereas meropenem or imipenem reached 73 % coverage. Only the combination of meropenem or imipenem plus vancomycin would achieve a coverage surpassing 85 % in healthcare-associated or nosocomial spontaneous bacterial infections. CONCLUSIONS: Our study uncovers inadequate coverage in specific clinical scenarios when adhering to recommendations, underscoring the necessity of guidelines based on local epidemiological data.

Closing the gap: prognostic and predictive biomarker validation for personalized care in a Latin American hormone-dependent breast cancer cohort.

BACKGROUND: Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort. METHODS: The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers. RESULTS: Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively). CONCLUSION: In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.

Comparing Bispectral Index Monitoring vs Clinical Assessment for Deep Sedation in the ICU: Effects on Delirium Reduction and Sedative Drug Doses-A Randomized Trial.

BACKGROUND: Sedative overdoses pose a risk of delirium among patients in the ICU, with potential mitigation through the use of a processed EEG monitor (the bispectral index [BIS]) to guide depth of sedation. RESEARCH QUESTION: Can BIS-guided deep sedation (Richmond Agitation Sedation Scale RASS score, -4 or -5) reduce sedative dosage and increase delirium-free and coma-free (DFCF) days? STUDY DESIGN AND METHODS: A randomized controlled trial was conducted in a tertiary mixed ICU, enrolling patients requiring deep sedation for > 8 h. Patients were assigned randomly to either the clinical assessment (CA) or BIS groups (BIS range, 40-60). Both groups used a BIS sensor, whereas the CA group's screen remained covered. After deep sedation, BIS sensors were removed, and delirium was assessed twice daily by researchers masked to the randomization. The primary outcome was the number of DFCF days within 14 days after deep sedation. Additionally, we compared doses of sedative drugs and BIS values during deep sedation. RESULTS: Ninety-nine patients were included in the study. We found no significant difference in DFCF days (P = .1) between CA and BIS arms, but propofol doses were significantly lower in the BIS group (CA group, 1.77 mg/kg/h [95% CI, 1.60-1.93] vs BIS group, 1.44 mg/kg/h [95% CI, 1.04-1.83]; P = .03). During deep sedation, the CA group spent 46% of the total hours (95% CI, 35%-57%) with BIS values of < 40, whereas the BIS group spent 32% (95% CI, 25%-40%; P = .03). Subgroup analysis focusing on patients sedated for > 24 h revealed an increase in DFCF days in the BIS group (CA group: median, 1 day [interquartile range (IQR), 0-9 days] vs BIS group: median, 8 days [IQR, 0-13 days]; P = .04). INTERPRETATION: BIS-guided deep sedation did not improve DFCF days, but did reduce sedative drug use. In patients requiring sedation for > 24 h, it showed an improvement in DFCF days. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03840577; URL: www. CLINICALTRIALS: gov.

Comparison of rivaroxaban and low molecular weight heparin in the treatment of cancer-associated venous thromboembolism: a Swedish national population-based register study.

BACKGROUND: Treating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk. OBJECTIVES: To compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT. METHODS: We developed a cohort study using Swedish national registers 2013-2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated. RESULTS: We included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0-109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9-102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43-1.35). The IR for major bleeding was 23.5 (95% CI 8.6-51.1) for rivaroxaban versus 49.2 (95% CI 42.3-56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26-1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9-201.5) for rivaroxaban and 565.6 (95% CI 541.8-590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34-0.67). CONCLUSIONS: Rivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding. TRIAL REGISTRATION NUMBER: NCT05150938 (Registered 9 December 2021).

Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Validation of diagnoses of liver disorders in users of systemic azole antifungal medication in Sweden.

BACKGROUND: Liver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment. METHODS: Data from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group. RESULTS: Among the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4-73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4-74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3-99.9%). CONCLUSION: Among patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower.

Incidence of SARS-CoV-2 infection in patients with multiple sclerosis who received SARS-CoV-2 vaccines and are under treatment with high-efficacy therapies in Argentina.

We aimed to evaluate the incidence of SARS-CoV-2 breakthrough infection of SARS-CoV-2 vaccines in people with MS (PwMS) on high-efficacy disease-modifying therapies (HET) included in the national MS registry in Argentina (RelevarEM). METHODS: Non-interventional, retrospective cohort study that collected information directly from RelevarEM. Adult PwMS who had been treated for at least 6 months with a HET (ocrelizumab, natalizumab, alemtuzumab, cladribine) who had received at least two doses of SARS-CoV-2 vaccines available in Argentina were included. Full course of vaccination was considered after the second dose of the corresponding vaccines. Cumulative incidence of SARS-CoV-2 infection was reported for the whole cohort by Kaplan-Meier survival curves (which is expressed in percentage) as well as incidence density (which is expressed per 10.000 patients/day with 95% CI). RESULTS: Two hundred twenty-eight PwMS were included. Most frequent first and second dose received was AstraZeneca vaccine, followed by Sputnik vaccine. Most frequent HETs used in included patients were cladribine in 79 (34.8%). We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina. We described the incidence rate after vaccination for every HET used, it being significantly higher for ocrelizumab compared with other HETs (p = 0.005). Only five patients presented a relapse during the follow-up period with no differences regarding the pre-vaccination period. CONCLUSIONS: We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina.

Association Between Selective Serotonin Reuptake Inhibitors Prevalent Use and COVID-19-Related Mortality: A Retrospective Cohort Study.

PURPOSE/BACKGROUND: Since the emergence of the coronavirus disease 2019 (COVID-19), many efforts have been made to prevent and to treat the disease. In this line, the anti-inflammatory effect of selective serotonin reuptake inhibitors (SSRI) as alternatives for treating chronic inflammatory diseases has been studied. There is previous evidence of the usefulness of these drugs for reducing COVID-19 impact. METHODS/PROCEDURES: We conducted a retrospective single-center cohort study of adult patients with a positive reverse transcriptase-polymerase chain reaction for COVID-19, evaluating the association between SSRI use and in-hospital mortality. FINDINGS/RESULTS: Of 1689 included patients, 182 (10.8%) were exposed to SSRI. A total of 291 patients died during the hospitalization, representing an in-hospital mortality of 17.2% (95% confidence interval [CI], 15.4%-19.0%): 44 (24.2%) of the exposed to SSRIs versus 247 (16.4%) of those not exposed to SSRIs (crude odds ratio [OR], 1.62; 95% CI, 1.12-2.34; P = 0.009). No independent effect of SSRIs on in-hospital mortality was found when applying either the inverse probability of treatment weighting (OR, 1.15; 95% CI, 0.71-1.89; P = 0.56) or with conventional multivariable analysis 0.81 (95 % CI: 0.28-2.31, P = 0.69). IMPLICATIONS/CONCLUSIONS: In the present retrospective study of patients hospitalized for COVID-19, prior use of SSRIs did not reduce mortality.

Clinical and microbiological characteristics of bacterial infections in patients with cirrhosis. A prospective cohort study from Argentina and Uruguay.

INTRODUCTION AND OBJECTIVES: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. MATERIALS AND METHODS: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. RESULTS: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. CONCLUSIONS: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032).

Parental sensitivity and specificity to recognize shunt malfunction in their child: a single-center prospective study.

OBJECTIVE: The objective of this study was to estimate the diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) for recognizing ventriculoperitoneal shunt (VPS) failure in the parents of patients 0-18 years of age who attended the hospital's emergency room (ER). The second objective was to identify the factors associated with the parents' ability to recognize the shunt blockage (true positives). METHODS: A prospective cohort study was conducted between 2021 and 2022 including all patients 0-18 years of age who had a VPS and attended the hospital's ER with symptoms that could correspond to VPS blockage. Parents were interviewed on admission and patients were assessed over time to discover potential VPS malfunction by surgery or follow-up. Consent was obtained from all participants. RESULTS: Ninety-one patients were surveyed, and 59.3% showed evidence of a confirmed VPS blockage. Parental sensitivity was 66.7%, with a specificity of 21.6%. An association was found between parents who could correctly identify their child's shunt block and the number of symptoms of shunt failure that the parent could name (OR 2.4, p < 0.05) as well as parents who reported vomiting and headache as symptoms of shunt malfunction (OR 6, p < 0.05). Parents who knew the first and last name of their primary neurosurgeon (OR 3.5, p < 0.05) also had better diagnostic sensitivity. CONCLUSIONS: Parents who are more knowledgeable of their child's disease, as well as parents who have good communication with their neurosurgeon, were found to have better diagnostic sensitivity.

Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections.

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.

Temporal trends in hematopoietic stem cell transplantation in Argentina between 2009 and 2018: A collaborative study by GATMO-TC and INCUCAI.

INTRODUCTION: Hematopoietic stem cell transplantation is the only curative treatment for many disorders and international data shows a growing trend. METHOD: We aimed to evaluate the temporal trends in HSCT transplant rates in Argentina. A time-series analysis was performed for the period 2009 to 2018 using the national database from the National Central Coordinating Institute for Ablations and Implants. Crude and standardized transplant rates were calculated. A permutation joinpoint regression model analysis was used to identify significant changes over time. RESULTS: Altogether, 8,474 transplants were reported to INCUCAI by 28 centers (autologous 67.5%); the main indication was multiple myeloma (30%). The WHO age-sex standardized HSCT rates for the entire country were 153.3 HSCT/10 million inhabitants (95% CI 141.7-165.8) in 2009 and 260.1 HSCT/10 million inhabitants (95% CI 245.5-275.5) in 2018. There was a large gap in HSCT rates among the states and regions. The transplant rate was higher for autologous transplants throughout the years. Within the allogeneic group, the related donor transplant rate was higher than the unrelated donor transplant rate. The joinpoint regression analysis of HSCT rates for the whole country over time showed an observed annual percentage change of 6.3% (95% CI 5.4-7.3; p < 0.01). No changes were observed for unrelated donors during the study period. CONCLUSIONS: Age-sex standardized HSCT rates in Argentina are increasing, mainly due to autologous and family donor allogeneic transplants. A wide variation across the country was found, demonstrating differences in the access to transplantation among Argentine regions.

Bleeding events among patients concomitantly treated with direct oral anticoagulants and macrolide or fluoroquinolone antibiotics.

Fluoroquinolones and macrolides may, due to a potential drug-drug interaction, increase the concentration of any concomitantly administered direct oral anticoagulant (DOAC) and thereby increase the risk of severe bleeding. However, clinical evidence for such an effect is scarce. The present study aimed to evaluate the association between the use of fluoroquinolones or macrolides and bleeding events in patients with concomitant DOAC use. This was a nationwide cohort study including 19 288 users of DOACs in 2008-2018 using information from Swedish national health registers. We compared the incidence of bleeding events associated with use of fluoroquinolones or macrolides using doxycycline as a negative control. Cox regression was used to calculate crude and adjusted hazard ratios (aHRs) in time windows of various length of follow-up after the start of antibiotic use. The incidence rates for fluoroquinolones and macrolides ranged from 12 to 24 and from 12 to 53 bleeding events per 100 000 patients in the investigated time windows. The aHRs (95% confidence interval) for use of fluoroquinolones and macrolides were 1.29 (0.69-2.44) and 2.60 (0.74-9.08) at the concomitant window, 1.31 (0.84-2.03) and 1.79 (0.75-4.29) at 30 days, and 1.34 (0.99-1.82) and 1.28 (0.62-2.65) at 150 days, respectively. With regard to fluoroquinolones, the present study suggests that the risk of bleeding when combined with DOACs, if any, is small. Codispensation of macrolides in patients on DOACs was not associated with an increased risk of bleeding. However, due to the small number of macrolide users, the results must be interpreted with caution.

Development and validation of nonattendance predictive models for scheduled adult outpatient appointments in different medical specialties.

INTRODUCTION: Nonattendance is a critical problem that affects health care worldwide. Our aim was to build and validate predictive models of nonattendance in all outpatients appointments, general practitioners, and clinical and surgical specialties. METHODS: A cohort study of adult patients, who had scheduled outpatient appointments for General Practitioners, Clinical and Surgical specialties, was conducted between January 2015 and December 2016, at the Italian Hospital of Buenos Aires. We evaluated potential predictors grouped in baseline patient characteristics, characteristics of the appointment scheduling process, patient history, characteristics of the appointment, and comorbidities. Patients were divided between those who attended their appointments, and those who did not. We generated predictive models for nonattendance for all appointments and the three subgroups. RESULTS: Of 2,526,549 appointments included, 703,449 were missed (27.8%). The predictive model for all appointments contains 30 variables, with an area under the ROC (AUROC) curve of 0.71, calibration-in-the-large (CITL) of 0.046, and calibration slope of 1.03 in the validation cohort. For General Practitioners the model has 28 variables (AUROC of 0.72, CITL of 0.053, and calibration slope of 1.01). For clinical subspecialties, the model has 23 variables (AUROC of 0.71, CITL of 0.039, and calibration slope of 1), and for surgical specialties, the model has 22 variables (AUROC of 0.70, CITL of 0.023, and calibration slope of 1.01). CONCLUSION: We build robust predictive models of nonattendance with adequate precision and calibration for each of the subgroups.

Temporal trends in hematopoietic stem cell transplantation in Argentina between 2009 and 2018: A collaborative study by GATMO-TC and INCUCAI

Special Article Introduction Hematopoietic stem cell transplantation is the only curative treatment for many disorders and international data shows a growing trend. Method We aimed to evaluate the temporal trends in HSCT transplant rates in Argentina. A time-series analysis was performed for the period 2009 to 2018 using the national database from the National Central Coordinating Institute for Ablations and Implants. Crude and standardized transplant rates were calculated. A permutation joinpoint regression model analysis was used to identify significant changes over time. Results Altogether, 8,474 transplants were reported to INCUCAI by 28 centers (autologous 67.5%); the main indication was multiple myeloma (30%). The WHO age-sex standardized HSCT rates for the entire country were 153.3 HSCT/10 million inhabitants (95% CI 141.7-165.8) in 2009 and 260.1 HSCT/10 million inhabitants (95% CI 245.5-275.5) in 2018. There was a large gap in HSCT rates among the states and regions. The transplant rate was higher for autologous transplants throughout the years. Within the allogeneic group, the related donor transplant rate was higher than the unrelated donor transplant rate. The joinpoint regression analysis of HSCT rates for the whole country over time showed an observed annual percentage change of 6.3% (95% CI 5.4-7.3; p< 0.01). No changes were observed for unrelated donors during the study period. Conclusions Age-sex standardized HSCT rates in Argentina are increasing, mainly due to autologous and family donor allogeneic transplants. A wide variation across the country was found, demonstrating differences in the access to transplantation among Argentine regions.

Monitoreo serológico y psicológico en personal de salud durante el comienzo de la pandemia COVID-19 / Serological and psychological monitoring of healthcare workers during the start of the COVID-19 pandemic

Introducción: el personal de salud (PdS) es esencial en la lucha contra el COVID-19. Al inicio de la pandemia, el riesgo de adquirir la enfermedad en este grupo era desconocido. Buscamos estimar incidencia y prevalencia de anticuerpos anti-SARS-CoV-2, y prevalencia de burnout en una cohorte de PdS durante la pandemia COVID-19, así como valorar la prevalencia de burnout y depresión en la cohorte. Materiales y métodos: cohorte prospectiva conformada por médicos que atendían pacientes COVID-19 desde marzo de 2020 hasta enero de 2021, en un hospital de alta complejidad de la ciudad de Buenos Aires. Se evaluó IgM e IgG anti-SARS-CoV-2 quincenalmente durante 3 meses, así como la presencia de síntomas compatibles y factores asociados a la exposición. Se remitió a participantes con alteraciones de la esfera psíquica a contacto con el equipo de salud mental del hospital. Resultados: se incluyeron 52 participantes; de ellos, 31 eran mujeres; mediana de edad 32 años (rango 25-58). La mediana de horas semanales de trabajo autoinformadas fue 48 (IIC [intervalo intercuartil] 40-69,5). Inicialmente todos fueron PCR SARS-CoV-2 negativos en hisopado nasal; 11 (21,50% IC 95%; 9,62-32,53%) tuvieron COVID-19 sintomático con anticuerpos positivos. Los factores con mayor asociación a riesgo de COVID-19 fueron anosmia/disgeusia OR 403,33 (IC 95%; 47,60-3417,02), fiebre OR 172,53 (IC 95%; 28,82-1032,65), mialgias OR 41,97 (IC 95%; 8,08-217,84), conviviente con COVID-19 OR 28,17 (IC 95%; 5,67-179,97). Cerca del 40% presentaba alteraciones en las escalas de medición de burnout o depresión. Discusión: la incidencia hallada coincide con las cifras informadas acerca de personal de salud en la etapa inicial de la pandemia en la Argentina. Otro aspecto similar fue una mayoría de infecciones de curso leve, sin ningún paciente hospitalizado. No obstante, se halló una elevada incidencia de alteraciones de la esfera psíquica, tanto al comienzo como al final del seguimiento. Conclusiones: la incidencia de positivización de anticuerpos anti-SARS-CoV-2 fue cercana al 20%. No evidenciamos infecciones presintomáticas o asintomáticas. En cambio, la prevalencia de burnout y depresión fue elevada. La salud mental es un componente del personal de salud que debe ser priorizado en situaciones futuras de impacto similar. (AU)

Introduction: healthcare personnel are essential in the response against COVID-19. At the beginning of the pandemic the risk of acquiring the disease in this group was unknown. We sought to estimate incidence and prevalence of anti SARS-CoV-2 antibodies, as well as burnout prevalence in a cohort of healthcare staff during the pandemic, as well as assessing the prevalence of burnout and depression in this group. Materials and methods: prospective cohort formed by physicians tending to COVID-19 patients from march 2020 to january 2021 in a high-complexity hospital in the city of Buenos Aires. We evaluated anti SARS-CoV-2 IgM and IgG each 15 days for 3 months as well as the presence of compatible symptoms and factors associated to exposition to the virus. Patients showing signs of burnout and/or depression were referred to proper care by the mental health team in the hospital. Results: we included 52 patients, 31 women, median age was 32 years (range 25 - 58). Median amount of self-reported hours worked each week was 48 (IQR 40 - 69.5). Initially all participants had a negative COVID-19 PCR nasopharyngeal swab; 11 (21.50% CI95% 9.62 - 32.53%) had symptomatic COVID-19 with positive antibodies. Factors showing stronger association with testing positive were anosmia/dysgeusia OR 403.33 (CI95% 47.60-3417.02), fever OR 172.53 (CI95% 28.82 - 1032.65), myalgia OR 41.97 (CI95% 8.08 - 217.84), cohabitation with confirmed COVID-19 case OR 28.17 (CI95% 5.67 - 179.97). Near 40% showed alterations in burnout or depression scales. Discussion: the incidence rate we found was like reported values in the initial stages of the pandemic in Argentina. Another similarity was that all cases were mild; no hospitalization was required for any participant. We found an elevated incidence of alterations in the psychic sphere, both at the beginning and end of the follow up period. Conclusions:the incidence of positive SARS-CoV-2 antibodies was around 20%. No pre or asymptomatic cases were identified. Burnout and depression incidence was high. Mental health is a component that should never be overlooked in similar situations to come. (AU)

Safety and effectiveness of RBD-specific polyclonal equine F(ab´)2 fragments for the treatment of hospitalized patients with severe Covid-19 disease: A retrospective cohort study.

BACKGROUND: Passive immunotherapy has been evaluated as a therapeutic alternative for patients with COVID-19 disease. Equine polyclonal immunotherapy for COVID-19 (EPIC) showed adequate safety and potential efficacy in a clinical trial setting and obtained emergency use authorization in Argentina. We studied its utility in a real world setting with a larger population. METHODS: We conducted a retrospective cohort study at "Hospital de Campaña Escuela-Hogar" (HCEH) in Corrientes, Argentina, to assess safety and effectiveness of EPIC in hospitalized adults with severe COVID-19 pneumonia. Primary endpoints were 28-days all-cause mortality and safety. Mortality and improvement in modified WHO clinical scale at 14 and 21 days were secondary endpoints. Potential confounder adjustment was made by logistic regression weighted by the inverse of the probability of receiving the treatment (IPTW) and doubly robust approach. FINDINGS: Subsequent clinical records of 446 non-exposed (Controls) and 395 exposed (EPIC) patients admitted between November 2020 and April 2021 were analyzed. Median age was 58 years and 56.8% were males. Mortality at 28 days was 15.7% (EPIC) vs. 21.5% (Control). After IPTW adjustment the OR was 0.66 (95% CI: 0.46-0.96) P = 0.03. The effect was more evident in the subgroup who received two EPIC doses (complete treatment, n = 379), OR 0.58 (95% CI 0.39 to 0.85) P = 0.005. Overall and serious adverse events were not significantly different between groups. CONCLUSIONS: In this retrospective cohort study, EPIC showed adequate safety and effectiveness in the treatment of hospitalized patients with severe SARS-CoV-2 disease.

Método de captura y recaptura: una experiencia de su aplicación para determinar la incidencia de diabetes gestacional / Capture and recapture method: anexperience of itsapplication to estimatetheincidence of gestational diabetes

Los métodos de captura y recaptura (MCR) se emplean en la estimación de poblaciones mediante la utilización de diferentes fuentes de datos, disponibles e incompletas, que registran por separado un mismo evento. En esta metodología, las fuentes son utilizadas para extrapolar el número de individuos no registrados, usando la información recopilada sobre los individuos sí registrados. Este artículo describe todos los pasos de su aplicación práctica, a partir de un ejemplo de estimación de la incidencia de diabetes gestacional en una institución, a partir de cinco fuentes documentales. (AU)

Capture-recapture (CRM) methods are widely used to estimate populations by using different data sources, available and incomplete, that record the same event separately. In these methods, the available sources are used to extrapolate the number of unregistered individuals, using the information collected on the individuals that are registered. This article describes all the steps of its practical application, based on an example of estimating the incidence of gestational diabetes in an institution based on five documentary sources. (AU)