Venous thromboembolism prophylaxis in inflammatory bowel disease inpatients - Systematic review and meta-analysis.

INTRODUCTION: Inflammatory bowel disease (IBD) patients are three-times more likely to develop venous thromboembolism (VTE), and guidelines recommend prophylaxis during all hospitalizations. In this systematic review we sought to assess for the benefits and risks of VTE prophylaxis in hospitalized IBD patients. METHODS: We performed a systematic review and meta-analysis. We searched MEDLINE and others up to 2/2022, for studies on IBD inpatients treated with prophylactic anti-coagulation during hospitalization, compared to no prophylaxis. Primary efficacy and safety outcomes were any VTE and major bleeding, respectively. Results were pooled using random-effects models, calculating odds-ratios (OR) and 95% confidence-intervals (CI). The ROBINS-I tool was used to assess bias. RESULTS: We extracted data from 18 observational studies, and two randomized-trial subgroups. The studies were highly variable regarding the included populations, interventions, and outcome definitions. Meta-analysis of all studies showed a non-significant effect of prophylaxis on VTEs (OR 0.97[95%CI 0.49-1.95]). An analysis of eight lower-risk-of-bias studies showed a significant reduction in VTEs (OR 0.27[95%CI 0.13-0.55), number needed to treat(NNT) 34.8[95%CI 26.8-49.8]. A significant protective effect persisted in several subgroups. Major-bleeding was reported in three studies and showed a significant increase with prophylaxis (OR 2.02[95%CI 1.11-3.67], number needed to harm(NNH) 113.6[95%CI 40.7-very-large-number]). CONCLUSIONS: In studies with lower-risk-of-bias, a significant reduction in VTEs was shown in patients treated with VTE prophylaxis (NNT=35), which should be carefully considered against an increased major-bleeding risk (NNH=114). However current data is limited and randomized trials dedicated to IBD inpatients would aid in understating whether universal prophylaxis should be recommended.

The Contribution of 18F FDG PET-CT for the Investigation of Fever of Unknown Origin and Inflammation of Unknown Origin.

BACKGROUND: Fever of unknown origin and inflammation of unknown origin are highly challenging diagnostic conditions. The current practice for evaluating patients is to conduct a positron emission tomography-computed tomography (PET-CT) scan as either a first- or a second-line modality. We aimed to assess the contributory effect of PET-CT to the diagnosis and compare it with the contributory effect of CT alone. METHODS: We performed a systematic review and meta-analysis. We included all cohorts that examined the contribution of PET-CT to the investigation of classical fever of unknown origin and inflammation of unknown origin. The primary outcome was the contribution of PET-CT to the final diagnosis. Secondary outcomes were sensitivity and specificity of PET-CT and CT scans, and contribution of a CT scan. We pooled the results of all studies and calculated the pooled contributory effect of PET-CT. RESULT: Thirty-six studies (3516 patients) were included in the systematic review. The pooled contribution of PET-CT was 75.4%. The compiled sensitivity and specificity values for all studies were 85.9% and 59.5%, respectively. Five studies (405 patients) compared between the PET-CT component and the total body CT component. The pooled contribution of a CT scan was 68%. The summed sensitivity and specificity values of a CT scan for all studies were 63.1% and 84.4%, respectively. CONCLUSIONS: PET-CT has a contributory effect of 75% for the diagnosis of fever of unknown origin and inflammation of unknown origin. PET-CT had superior sensitivity and inferior specificity vs the CT scan.

Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies.

BACKGROUND: Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE). We conducted a systematic review and a meta-analysis to compare the efficacy and safety of rivaroxaban versus apixaban in the treatment of VTE. METHODS: We conducted an electronic search for studies that directly compared treatment with rivaroxaban and apixaban in adult patients with VTE. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled using a fixed-effect model unless significant heterogeneity was present (I2 > 40%), then random-effects model was used. The primary efficacy and safety outcomes were recurrent VTE (rVTE) and major bleeding events, respectively. RESULTS: Nine observational studies were included in our meta-analysis, assessing 24,156 patients for apixaban and 38,847 for rivaroxaban. Pooling of data for our primary efficacy outcome showed a trend towards lower risk of rVTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57-1.04, I2 = 53%). Analysis of our primary safety outcome showed a significantly lower risk of major bleeding with apixaban compared to rivaroxaban (RR 0.68, 95% CI 0.61-0.76, I2 = 0%). Apixaban was associated with significantly decreased risk of net clinical harm, clinically relevant non major bleeding (CRNMB) and any bleeding, compared to rivaroxaban (RR 0.75, 95% CI 0.61-0.92, I2 = 50%; RR 0.58, 95% CI 0.50-0.67, I2 = 7%; RR 0.64, 95% CI 0.59-0.70, I2 = 0%, respectively). CONCLUSIONS: Apixaban is associated with a significantly lower risk of major bleeding compared to rivaroxaban for treatment of VTE. Given the limitations of the existing evidence, further interventional studies comparing the two drugs are needed.

Screening for Latent Tuberculosis Infection in Solid Organ Transplant Recipients to Predict Active Disease: A Systematic Review and Meta-Analysis of Diagnostic Studies.

Background: This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients. Methods: Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2. Results: A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; P = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB. Conclusions: We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.

The Impact of Thrombocytopenia and Lymphopenia on Mortality in Patients Infected with Influenza Virus: A Retrospective Cohort Study.

INTRODUCTION: Influenza virus causes significant global annual morbidity and mortality. Thrombocytopenia is recognized as a poor prognostic factor in sepsis and is associated with mortality, while lymphopenia has been established as a poor prognostic factor in other viral infections. We aimed to assess the incidence of thrombocytopenia and lymphopenia in seasonal influenza and their effect on clinical outcomes. METHODS: This single-center, retrospective, cohort study included consecutive adult patients, hospitalized in Rabin Medical Center between October 2017 and April 2018, with laboratory-confirmed influenza. Patients were grouped according to blood counts on admission: (1) thrombocytopenia (<150 K/mL), (2) lymphopenia (<0.5 K/mL), and (3) both thrombocytopenia and lymphopenia. Patients without thrombocytopenia and lymphopenia were designated as controls. The primary outcome was 30-day all-cause mortality. Risk factors were identified by univariable and multivariable analyses, using logistic regression and reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 625 patients were included, 112 (18%) had thrombocytopenia, 98 (15.6%) had lymphopenia, and 107 (17%) had both. The crude 30-day all-cause mortality was 7.6% (48/625). Mortality rates were 7.1% (8/112) for the thrombocytopenia group, 11.2% (11/98) for the lymphopenia group, and 14.9% (16/107) for patients with both versus 4.2% (13/308) in the control (p = 0.000 for all). In a multivariable regression model, significant thrombocytopenia (<100 K/µL) [OR 5.07 (95% CI 1.5-16.2)], age [OR 1.07 (95% CI 1.02-1.11)], time to oseltamivir [OR 1.006 (95% CI 1.002-1.11)], and significant respiratory support [OR 8.85 (3.4-22.6)] were associated with 30-day all-cause mortality. CONCLUSION: Patients hospitalized with seasonal influenza and thrombocytopenia <100 K/mL on admission, have an increased 30-day all-cause mortality.

Ceftriaxone 1 g versus 2 g per day, for the treatment of community-acquired pneumonia: a retrospective cohort study.

Guidelines recommend intravenous (IV) ceftriaxone at a dose of 1-2 g/d as empirical treatment in adults hospitalized with community acquired pneumonia (CAP), with the addition of macrolide. We examined whether 1 g/d of IV ceftriaxone is associated with similar clinical outcomes to those of 2 g/d. This is a single-center, retrospective, cohort study of all adult patients hospitalized at Rabin Medical Center between 2015 and 2018 with CAP. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 2045 patients were treated with IV ceftriaxone 1 g/d and were and compared to 1944 patients who were treated with 2 g/d. The groups were comparable in their baseline characteristics and their clinical presentation. The 30-day all-cause mortality rate was similar between the groups (301/2045 (14.7%) for 1 g/d vs. 312/1944 (16.0%) for 2 g/d, p = 0.24). The rate of C. difficile infection (CDI) was significantly decreased with 1 g/d compared to 2 g/d (4/2045 (0.2%) vs. 12/1944 (0.6%), p = 0.03) and the length of stay was significantly shorter (median 4 days interquartile range (IQR) 3-7 vs. 5 days IQR 3-8, p = 0.02). None of the blood isolates of Streptococcus pneumoniae were penicillin or ceftriaxone resistant. For hospitalized patients with CAP, IV ceftriaxone 1 g/d was associated with similar mortality rates as IV ceftriaxone 2 g/d, with a decreased rate of CDI and shorter length of stay. Ceftriaxone 1 g/d may be sufficient to treat patients with CAP in countries with low prevalence of drug resistant Streptococcus pneumoniae.

Is there a 'weekend effect' on mortality among hospitalised patients in an internal medicine ward? A retrospective study.

BACKGROUND: Previous studies demonstrated a 'weekend effect' and a 'night effect' of increased mortality among patients admitted during weekends or night shifts, presumably due to understaffing. AIMS: To examine whether death during hospitalisation follows a similar effect regardless of admission time. METHODS: A retrospective cohort study among deceased patients hospitalised in the internal medicine wing of a tertiary medical centre in Israel, between 2019 and 2020. Demographic and medical data were retrieved from electronic medical charts. Causes of death were specifically categorised. We applied statistical models to test for differences in mortality using incidence rate ratio (IRR) according to the day, time and cause of death. RESULTS: One thousand, two hundred and seventy-eight deceased patients were included. All-cause mortality was similar between weekends and weekdays. When sepsis was the cause of death, higher IRR were demonstrated on Fridays in comparison with weekdays (IRR 1.4; 95% confidence interval (CI) 1.1-1.9; P < 0.05). Other causes of death were not consistent with a 'weekend effect'. Mortality during night shifts was higher in comparison with the afternoon (IRR 1.5; 95% CI 1.3-4.7) and similar to the morning (IRR 1; 95% CI 0.9-1.2). CONCLUSION: Our study did not find a pattern of 'weekend effect' or 'night effect' on all-cause mortality among hospitalised patients in internal medicine wards. Our findings suggest that perhaps specifically death from sepsis, and not all-cause mortality, can be used as a surrogate for the measurement of understaffing or quality of care in the internal ward.

Predictors for spontaneous resolution of classical FUO in patients undergoing PET-CT.

Spontaneous resolution is common in patients with classic fever of unknown origin (FUO). Identifying predictors of spontaneous resolution could reduce the usage of unnecessary, invasive tests or empirical therapy, and furthermore reduce patient anxiety. Identify predictors associated with spontaneous resolution of FUO. A single center, retrospective, cohort study. All hospitalized patients who underwent an [18F] FDG PET-CT scan for the investigation of classical FUO between 1/2012 and 1/2020 were included. We compared patients with spontaneous resolution of fever and clinical symptoms, to those who were diagnosed with a specific etiology of FUO (subdivided to infectious diseases, non-infectious inflammatory diseases (NIID), and malignancies). Epidemiologic characteristics as well as laboratory and PETCT study results were compared. Variables that were found to be associated with spontaneous resolution of FUO on univariate analysis (p < 0.1) were entered into a multivariable regression analysis. The results are reported as odds ratios (OR) and 95% confidence intervals (CI). A total of 303 patients were hospitalized for the investigation of classical FUO and underwent complete assessment. Fever resolved without a diagnosis in 84/303 patients (28%). Variables that were associated with spontaneous resolution of FUO on multivariable analysis included: no anemia, no hypoalbuminemia and no pathological FDG uptake on PET-CT. In 17.8% (15/84) of studies, PET-CT yielded false-positive results that led to additional unnecessary, invasive investigation. Patients without anemia or hypoalbuminemia, and those without uptake on PET-CT are more likely to have spontaneous resolution of classical FUO.

Ceftriaxone versus ampicillin for the treatment of community-acquired pneumonia. A propensity matched cohort study.

OBJECTIVES: Ceftriaxone is recommended as first-line antibiotic treatment (with the addition of macrolide) for hospitalised adults with community acquired pneumonia (CAP). Narrower-spectrum ß-lactam as ampicillin, may be associated with comparable clinical outcomes, with less emergence of resistant pathogens or Clostridioides difficile infection (CDI). We aimed to examine whether ampicillin and ceftriaxone (with the addition of macrolides for both arms) are comparable for the treatment of hospitalized adults due to CAP. METHODS: This was a single center, observational cohort study. We included adult patients who were hospitalized in internal medicine wards due to CAP and were treated with either ceftriaxone or ampicillin with the addition of macrolide. A propensity-score model was used. The primary outcome was 30-day all-cause mortality. A multivariable logistic regression analysis and Kaplan-Meier survival analysis was performed. We performed subgroup analyses for the main outcome based on CURB-65 score and age. RESULTS: A total of 1586 patients fulfilled the inclusion criteria. There was no difference in 30-day mortality rate in the total cohort (28/233 vs. 208/1353 in ampicillin and ceftriaxone arm, respectively; p = 0.184). In the propensity matched cohort (197 in ampicillin and 394 in ceftriaxone arm), there was no significant difference in 30-day all-cause mortality between treatment groups in multivariable analysis of the main model (OR 0.67, 95% CI, 0.37-1.2; p = 0.189) and Kaplan-Meier survival analysis (p = 0.108). Thirty-day mortality rate was (19/197 vs. 57/394, in ampicillin and ceftriaxone arms, respectively; p = 0.108) Patients who were treated with ampicillin experienced significantly lower rates of CDI (0/197, 0% vs. 8/394, 2%; p = 0.044). DISCUSSION: Ampicillin was associated with comparable clinical outcomes in comparison to ceftriaxone for patients who were hospitalized due to CAP. Ampicillin was associated with significantly lower rate of CDI. Results need to be confirmed by more robust study designs.

Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The pathophysiology of cancer-related anemia is multifactorial, including that of chemotherapy-induced anemia (CIA). The guidelines are not consistent in their approach to the use of intravenous (IV) iron in patients with cancer as part of the clinical practice. Materials and methods: All randomized controlled trials that compared IV iron with either no iron or iron taken orally for the treatment of CIA were included. We excluded trials if erythropoiesis-stimulating agents (ESAs) were used. The primary outcome was the percentage of patients requiring a red blood cell (RBC) transfusion during the study period. The secondary outcomes included the hematopoietic response (an increase in the Hb level by more than 1 g/dL or an increase above 11 g/dL), the iron parameters and adverse events. For the dichotomous data, risk ratios (RRs) with 95% confidence intervals (Cis) were estimated and pooled. For the continuous data, the mean differences were calculated. A fixed effect model was used, except in the event of significant heterogeneity between the trials (p < 0.10; I2 > 40%), in which we used a random effects model. Results: A total of 8 trials published between January 1990 and July 2021 that randomized 1015 patients fulfilled the inclusion criteria. Of these, 553 patients were randomized to IV iron and were compared with 271 patients randomized to oral iron and 191 to no iron. IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (RR 0.72; 95% CI 0.55−0.95) with a number needed to treat of 20 (95% CI 11−100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01−1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88−1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76−1.57; 8 trials). Conclusions: IV iron resulted in a decrease in the need for RBC transfusions, with no difference in adverse events in patients with CIA. IV iron for the treatment of CIA should be considered in clinical practice.

Chronic aspirin use and survival following sepsis-A propensity-matched, observational cohort study.

OBJECTIVES: The use of antiplatelet agents is postulated to lead to improved outcomes in sepsis. We aimed to evaluate whether chronic, pre-hospitalization aspirin use leads to improved outcomes in patients with sepsis. METHODS: We conducted an observational cohort study among patients with sepsis, hospitalized in internal medicine wards in a single university-affiliated medical center. A propensity-score model was used to match and compare patients on chronic aspirin use to non-users. Patients with established cardiovascular disease were excluded. The primary outcome was survival rates at 30 days. Secondary outcomes included survival rates at 90 days, days of fever, length of hospital stay, and hospital readmission within 90 days. RESULTS: A total of 1671 patients fulfilled the inclusion criteria. 533 chronic aspirin users were matched to 533 aspirin non-users. Survival rates were significantly higher among patients on chronic aspirin use (hazard ratio (HR) 0.67; 95% CI, 0.51-0.89)). This effect was highlighted in several subgroups of patients, as patients with chronic obstructive pulmonary disease (COPD) or those with chronic use of beta blockers showed the greatest survival benefit with aspirin use. Patients in the aspirin group also showed significantly higher 90 days survival rates (HR 0.69; 95% CI, 0.57-0.92; p = 0.006) and experienced less days of fever in comparison to the control group. DISCUSSION: Pre-hospitalization treatment with aspirin for patients without established cardiovascular disease may be associated with mortality reduction, as shown in this is hypothesis-generating single center observational study.

Does accepted definition of Clostridioides difficile infection (CDI) severity predict poor outcomes in older adults?

BACKGROUND: Advanced age is an important factor affecting Clostridioides difficile infection (CDI) risk and outcome. While fever and leukocytosis are prominent findings in young individuals with CDI, they are usually blunted in the elderly. Furthermore, chronic kidney disease often exists among this population prior to the CDI episode onset. AIM: We aimed to examine whether the accepted definition of severe CDI (leukocytosis ≥ 15,000 cells/µl or serum creatinine > 1.5 mg/dl) predicts poor outcomes in the elderly. METHODS: All CDI hospitalized individuals between January-2013 and May-2020 were included. The study population was dichotomized into older group (≥ 65 years) and younger group (< 65 years). Primary composite outcome was 30-day mortality, colectomy due to severe colitis, or intensive care unit admission. The older group was divided according to the primary outcome to evaluate the effect of CDI severity criteria. RESULTS: The study included 853 patients. Of them, 571 were in the older group and 282 in the younger one. The primary outcome was significantly more common in the older group (93/571, 16% vs. 31/282, 11%; p = 0.04). Ninety days mortality was significantly higher in the older group [116/571, 20% vs. 30/282, 11%; p < 0.01]. In multivariate analysis, accepted CDI severity criteria were not significantly associated with poor outcomes (odds ratio [OR] = 1.2, 95% confidence interval [CI] 0.7-2.2, p = 0.5). Advanced dementia and low serum albumin were significant predictors of poor outcomes (OR = 3, 95%CI 1.5-6, p = 0.002 and OR = 3.1, 95%CI 1.7-5.8, p < 0.01). CONCLUSION: The accepted definition of CDI severity was not useful in predicting CDI poor outcomes in older adults. In this population, we suggest advanced dementia and low albumin among others as CDI severity markers.

The Importance of Abnormal Platelet Count in Patients with Clostridioides difficile Infection.

BACKGROUND: Clostridium difficile infection (CDI) causes morbidity and mortality. Platelets have been increasingly recognized as an important component of innate and adaptive immunity. We aimed to assess the incidence of thrombocytopenia and thrombocytosis in CDI and the effect of an abnormal platelet count on clinical outcomes. METHODS: This single-center, retrospective cohort study consisted of all adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression. RESULTS: A total of 527 patients with CDI were included. Among them 179 (34%) had an abnormal platelet count: 118 (22%) had thrombocytopenia and 61 (11.5%) had thrombocytosis. Patients with thrombocytosis were similar to control patients other than having a significantly higher white blood cell count at admission. Patients with thrombocytopenia were younger than control patients and were more likely to suffer from malignancies, immunosuppression, and hematological conditions. In a multivariable analysis, both thrombocytosis (OR 1.89, 95% CI 1.01-3.52) and thrombocytopenia (OR 1.70, 95% CI 1.01-2.89) were associated with 30-days mortality, as well as age, hypoalbuminemia, acute kidney injury, and dependency on activities of daily living. A sensitivity analysis restricted for patients without hematological malignancy or receiving chemotherapy revealed increased mortality with thrombocytosis but not with thrombocytopenia. CONCLUSIONS: In this retrospective study of hospitalized patients with CDI, we observed an association between thrombocytosis on admission and all-cause mortality, which might represent a marker for disease severity. Patients with CDI and thrombocytopenia also exhibited increased mortality, which might reflect their background conditions and not the severity of the CDI. Future studies should assess thrombocytosis as a severity marker with or without the inclusion of the WBC count.

The impact of obesity on seasonal influenza: a single-center, retrospective study conducted in Israel.

Obesity is associated with an increased susceptibility to infections. Several studies have reported adverse clinical outcomes of influenza among obese individuals. Our aim was to examine the association between obesity and the clinical outcomes of hospitalized adult patients ill with seasonal influenza. Consecutive hospitalized adult patients between 10/2017 and 4/2018 with laboratory confirmed influenza A and B were divided into an obese group (body mass index (BMI) ≥ 30 kg/m2) and controls. The primary outcome was a composite endpoint of 30-day all-cause mortality, vasopressor use, mechanical ventilation, ICU admission, and severe influenza complication (myocarditis and encephalitis). Secondary outcomes encompassed all the components of the primary outcome, 90-day all-cause mortality, occurrence of pneumonia, length of hospital stay, and 90-day readmission rates. The study comprised 512 hospitalized adults diagnosed with laboratory-confirmed influenza A (195/512) and B (317/512). Within this group, 17% (86/512) were classified obese; the remaining 83% (426/512) were controls. Results of the composite outcome (7/85, 8% vs. 45/422, 11%; p=0.5) and the crude 30-day all-cause mortality rate (5/86, 6% vs. 34/426, 8%, p=0.5) were similar between the two groups. The multivariate analysis demonstrated that obesity was not a significant risk factor for influenza adverse events (OR=1.3, CI 95% 0.3-3.3; p=0.5), whereas advanced age, chronic kidney disease, and hypoalbuminemia were significant risk factors (OR=1.03, OR=2.7, and OR=5.4, respectively). Obesity was not associated with influenza-related morbidity and mortality among the hospitalized adults during the 2017-2018 influenza season. Further studies researching different influenza seasons are essential.

ß-Blockers, Tachycardia, and Survival Following Sepsis: An Observational Cohort Study.

BACKGROUND: Sepsis is associated with excessive release of catecholamines, which causes tachycardia and is correlated with poor clinical outcome. ß-Blockers (BBs) may blunt this effect on heart rate (HR). The objective of this study is to assess whether long-term BB therapy is associated with better clinical outcomes in patients with sepsis admitted to internal medicine wards. METHODS: We performed a single-center, observational cohort study. We included adult patients who were hospitalized in medicine departments due to sepsis. A propensity score model for BB therapy was used to match patients. The primary outcome was the 30-day all-cause mortality rate. A multivariate analysis was performed to identify risk factors for an adverse outcome. Patients were stratified according to absolute tachycardia (HR ≥100/min) or relative tachycardia at presentation (tachycardia index above the third quartile, with tachycardia index defined as the ratio of HR to temperature). RESULTS: A total of 1186 patients fulfilled the inclusion criteria. In the propensity-matched cohort patients given BB treatment were younger (median age [interquartile range], 74 [62-82] vs 81 [68-87] years; P ≤ .001). BB treatment was associated with reduction in 30-day mortality rates for patients with absolute tachycardia (odds ratio, 0.406; 95% confidence interval, .177-.932). Final model with interaction variable of BB treatment with HR was associated with short-term survival (odds ratio, 0.38; 95% confidence interval, .148-.976). Selective BB therapy had a stronger protective effect than nonselective BB therapy. CONCLUSIONS: Long-term BB therapy was associated with decreased mortality rate in patients hospitalized with sepsis in internal medicine wards exhibiting absolute and relative tachycardia.

Morbidity and mortality of respiratory syncytial virus infection in hospitalized adults: Comparison with seasonal influenza.

INTRODUCTION: Respiratory syncytial virus (RSV) is considered a major pathogen that causes acute influenza-like illness. The objective of this study was to compare the clinical outcomes of patients with laboratory-confirmed RSV and patients with influenza infection. METHODS: Adults hospitalized in Beilinson Hospital (October 2017-April 2018) with laboratory-confirmed RSV or influenza were included. The primary outcome was the composite of RSV/influenza complications: 30-day mortality, pneumonia, mechanical ventilation, vasopressor support, intensive care unit admission, and myocarditis/encephalitis. Secondary outcomes were individual components of the primary outcome, 90-day mortality, 90-day readmission, and length of hospital stay. RESULTS: A total of 639 patients with RSV (n = 113) and influenza (n = 526) were included. The composite primary outcome was 21.4% (136/633), and was higher in RSV patients (30% (34/113) vs 19% (102/526), p = 0.002). Pneumonia was more common in RSV patients (21.2% (24/113) vs 9.1% (48/526), p = 0.001). On multivariable analysis, hypoalbuminemia (odds ratio (OR) 3.3, 95% confidence interval (CI) 2.1-5.3, p < 0.001), reduced room-air saturation (OR 1.1, 95% CI 1.02-1.1, p = 0.001), and infection with RSV (OR 1.67, 95% CI 1.01-2.76, p = 0.046) were predictors of complications. CONCLUSIONS: RSV infection in hospitalized adults resulted in serious respiratory illness with complications that are comparable to those caused by influenza.

The Effect of ß-Blockers for Burn Patients on Clinical Outcomes: Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the effects and safety of ß-blockers in hospitalized patients with burns. METHODS: A systematic review and meta-analysis of the literature. A broad search was conducted to identify all randomized controlled trials (RCTs) comparing ß-blockers to control in hospitalized patients with burns. The primary outcome was 3-month all-cause mortality. Secondary outcomes were clinical patient-relevant end points. We subgrouped results by children/adults and burn severity. Risk of bias was assessed using the individual domain approach. RESULTS: Four RCTs reported in 11 publications were included. Primary outcome of mortality was assessed in children (2 trials, n = 424) and adults (2 trials, n = 148) with severe burns. No significant difference was found between propranolol and control for mortality (risk ratio [RR] = 0.82, 95% CI = 0.48-1.39, 4 trials with broad confidence intervals in adults and children), sepsis (RR = 0.81, 95% CI = 0.46-1.43, 2 trials), and survivors' length of stay (absolute mean difference = 2.53, 95% CI = -2.58-7.63, 3 trials). There was no significant difference in bradycardia (RR = 1.33, 95% CI = 0.77-2.3, 2 trials), hypotension (RR = 1.26, 95% CI = 0.73-2.17, 3 trials), or cardiac arrhythmia (RR: 2.97, 95% CI: 0.12-71.87, 1 trial). The evidence was graded as very low certainty, due to trial's internal risk of bias, imprecision, and possible selective reporting. CONCLUSIONS: No sufficient evidence was found to support or refute an advantage for ß-blocker use in children or adults after burns. Additional studies are needed to create a consensus and formulate practice guidelines on the optimal ß-blocker to use, indications for initiation, and duration of treatment.

The significance of acute kidney injury in Clostridioides difficile infection.

OBJECTIVE: Clostridioides difficile infection (CDI) may present as sepsis with acute kidney injury (AKI). Herein, we aimed to evaluate the clinical outcomes of patients with AKI complicating CDI. METHODS: All consecutive adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI, were included in the study. Subjects were divided into two groups: patients with AKI and controls. Primary outcome was all-cause mortality at 30 days after the CDI episode. Secondary outcomes included number of patients with deteriorating renal functions at 90 days, 90-day all-cause mortality, length of hospital stay and readmission rates. A multivariable analysis adjusted for other risk factors for mortality and renal function deterioration was conducted. An analysis of subgroups based on baseline kidney function and AKI stage was also performed. Results are reported as odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: A total of 527 patients were included, amongst them 140 patients with AKI and 387 controls. Patients with AKI were significantly older, had more comorbidities, and more of them had chronic kidney disease (CKD) at any stage at baseline. On multivariable analysis, 30 days all-cause mortality was significantly higher in patients with AKI, OR 1.67, 95% CI 1.05-2.66. Mortality was also significantly associated with advanced age and baseline CKD. Among patients alive at 90 days, deterioration of renal function was significantly more common in patients with AKI (27/63 (42.8%) vs 22/191 (11.5%), P = .000). In a multivariable analysis, deterioration of renal function at 90 days was associated with AKI at presentation (OR 4.67, 95% CI 1.05-20.6). Early (at discharge) renal function recovery was not associated with protection from further deterioration of renal function at day 90. CONCLUSIONS: CDI patients with AKI have an increased risk of mortality and further deterioration of renal function. Early renal function recovery does not infer protection from further deterioration of renal function at 3 months. Caution and nephrology follow-up should be considered after discharge for all patients who developed AKI during CDI, regardless of discharge creatinine levels.

A systematic review assessing the under-representation of elderly adults in COVID-19 trials.

BACKGROUND: Coronavirus disease (COVID-19) has caused a pandemic threatening millions of people worldwide. Yet studies specifically assessing the geriatric population are scarce. We aimed to examine the participation of elderly patients in therapeutic or prophylactic trials on COVID-19. METHODS: In this review, randomized controlled trials (RCTs; n = 12) comparing therapeutic or prophylactic interventions registered on preprint repositories and/or published since December 2019 were analyzed. We searched in PubMed, leading journals websites, and preprint repositories for RCTs and large observational studies. We aimed to describe the age of included patients, the presence of an upper age limit and of adjusted analyses on age, any exclusion criteria that could limit participation of elderly adults such as comorbidities, cognitive impairment, limitation of life expectancy; and the assessment of long-term outcomes such as the need of rehabilitation or institutionalization. Mean participant ages were reported and compared with observational studies. RESULTS: Twelve RCTs assessing drug therapy for COVID-19 were included. Mean age of patients included in RCTs was 56.3 years. An upper age limit was applied in three published trials (25%) and in 200/650 (31%) trials registered at clinicaltrials.gov . One trial reported a subgroup analysis in patients ≥65. Patients were excluded for liver-function abnormalities in eight trials, renal disease in six, cardiac disease or risk of torsade de pointes in five, and four for cognitive or mental criteria, which are frequent comorbidities in the oldest patients. Only three trials allowed a family member to provide consent. Patients enrolled in RCTs were on average 20 years younger than those included in large (n ≥ 1000) observational studies. Seven studies had as their primary outcome a clinical endpoint, but none reported cognitive, functional or quality of life outcomes or need for rehabilitation or long-term care facility placement. CONCLUSIONS: Elderly patients are clearly underrepresented in RCTs, although they comprise the population hardest hit by the COVID-19 pandemic. Long-term outcomes such as the need of rehabilitation or institutionalization were not reported. Future investigations should target specifically this vulnerable population.