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Background: Venous thromboembolism (VTE) is considered a preventable cause of mortality. The evidence for the benefit of VTE prophylaxis in acute medical patients is non-conclusive. Meta-analysis of RCTs failed to demonstrate reduction of all-cause mortality, while showing higher risk of bleeding. The Israeli Ministry of Health has instructed to assess all acute medical patients for the risk for VTE using the Padua Prediction Score, without mandating prophylaxis. Aim: To evaluate the effect of filling the Padua score on clinical outcomes and VTE prophylaxis rates. Methods: Retrospective Study was performed in Israel during the years 2014–2017. The participants were divided to Padua compliance vs non-compliance group. Primary outcome: 30-day mortality. Secondary outcomes: 90-day incidence of VTE and suspected major bleeding. A propensity-weighted logistic multiple regression was performed. Results: 18,890 patients were included in the study. The fulfillment of the Padua score was associated with an increased use of VTE prophylaxis, OR 1.66 (95% CI 1.49–1.84). However, there was no reduction of mortality or VTE events, OR 1.13 (95% CI 0.97–1.31) and OR 1.22 (95% CI 0.79–1.8) respectively. Hospitalizations related to hemoglobin decrease were not statistically different between the two groups. Conclusions: Padua score for the assessment of VTE risk in medical wards was associated with higher administration of pharmacological prophylaxis without reduction in VTE or mortality rate. Its usage should be reassessed as a performance measure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to assess the natural annual trends in the levels of haemoglobin, haematocrit, and mean corpuscular volume (MCV) in a population of adults, together with the influence of different clinical parameters on these trends. Methods: A retrospective analysis was carried out on data from a large cohort of subjects attending a screening centre in Israel. For each subject, the yearly average change of haemoglobin, haematocrit, and MCV was calculated. Statistical analysis was performed for the whole cohort and for different subgroups. Results: The study included 3,551 subjects. The average annual rates of decline were found to be −0.0550 g/dL (95% confidence interval [CI] −0.0590 g/dL to −0.0503 g/dL) and −0.097% (95% CI −0.112% to −0.083%) for haemoglobin and haematocrit, respectively. An average annual increase in the MCV level by 0.184 fL (95% CI 0.168 fL–0.200 fL) was found. Among men, the rate of decline in haemoglobin was found to be twice as high compared with women −0.06 g/dL versus −0.03 g/dL, respectively (p = 0.0063). In a multivariate analysis, gender remained the only parameter significantly associated with the annual decline of haemoglobin (p = 0.0001). Conclusion: An annual average decrease in the levels of haemoglobin and haematocrit together with an annual increase in MCV was found. These changes were more prominent in men. [ABSTRACT FROM AUTHOR]

Background: In adults, post-liver transplantation anemia (PLTA) is common, but its characteristics and long-term influence on major outcomes have yet to be elucidated.Aim: We aimed to assess prevalence, characteristics, predictors, and outcomes of PLTA at 6 months (early PLTA) and at 2 years (late PLTA).Methods: A single-center retrospective cohort study using prospectively collected data from liver transplantations in adults during January 2007-December 2015. PLTA impact on various long-term outcomes was assessed, including mortality, composites of mortality or graft failure, cardiovascular outcomes, and malignancy occurrences.Results: Hundred and fifty liver transplanted individuals were included. There was a 79% prevalence of anemia pre-transplantation, whereas early and late PLTA were evident in 58% and 40% of patients, respectively. Pre-transplantation anemia was associated with development of early PLTA which was associated with late PLTA. In a multivariate analysis, early PLTA was significantly associated with mortality or graft failure at a follow-up of 3 years (odds ratio 3.838, 95% CI 1.114-13.226). Late PLTA was not significantly associated with worse long-term outcomes.Conclusions: Early and late PLTA are prevalent among liver transplanted patients. Early PLTA is associated with long-term mortality or graft failure. [ABSTRACT FROM AUTHOR]

Euvolemic hyponatremia results from either the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, or adrenal insufficiency. Furthermore, the criteria for diagnosis of SIADH entail the exclusion of hypothyroidism and hypoadrenalism. We aim to assess the yield of euvolemic hyponatremia workup focusing on underlying endocrinopathies in a real-world setting. A single-center retrospective study includes all patients diagnosed with euvolemic hyponatremia in a tertiary hospital between 1.1.2007 and 1.1.2013. Demographic, clinical, and laboratory data were collected from medical charts. Euvolemic hyponatremia was detected in 564 patients. Thyroid function was tested in 69% (391/564) and adrenal function was assessed in 29% (164/564) of cases. Endocrinopathy-induced euvolemic hyponatremia was diagnosed in nine (1.6%) patients: three patients were diagnosed with hypothyroidism-induced hyponatremia, three with adrenal insufficiency as an underlying cause, and three with central hypothyroidism and central hypoadrenalism. All nine had medical history and symptoms suggestive of endocrine deficiencies other than the hyponatremia, which resolved within 1-3 days after administration of hormone replacement therapy. Yield of performed workup for hypothyroidism and hypoadrenalism in euvolemic hyponatremia was low. However, in this real-world study, only a limited number of patients underwent a full ascertainment of hypoadrenalism and hypothyroidism, which was diagnosed only in patients with additional findings supportive of these endocrinopathies; a higher rate of undiagnosed endocrinopathies cannot be ruled out. As both hypoadrenalism and hypothyroidism are easily treatable, potentially life-threatening conditions, there are insufficient data to change current recommendation for their universal evaluation in patients with euvolemic hyponatremia. [ABSTRACT FROM AUTHOR]

Serum lactate dehydrogenase (LDH) levels may help to distinguish ischemic acute tubular necrosis (ATN) from acute rejection after kidney transplantation.~Background~Background~All kidney biopsies performed in the years 2010 to 2012 were reviewed. Serum LDH, creatinine level, clinical variables, and presence of donor-specific antibodies were recorded before the biopsy.~Methods~Methods~Overall 150 biopsies were included. Ischemic ATN was diagnosed in 45 biopsies and acute cellular-mediated rejection and/or antibody-mediated rejection in 59 biopsies, 38 of which were accompanied by ATN. Serum LDH was elevated in 23 (51%) of 45 cases with ischemic ATN versus 15 (14%) of 105 cases with other diagnoses ( P < .0001). Median serum LDH was 478 U/L (range 277-2018) for ischemic ATN and 372 U/L (range 191-748) for all other diagnoses ( P < .001). When delayed graft function or primary nonfunctioning grafts were caused by ischemic ATN, serum LDH was elevated in 58% of cases, but when caused by acute rejection, LDH was normal in 88% of cases ( P = .02).~Results~Results~There is a strong association between elevated serum LDH 1 to 3 days before performing kidney biopsy and the diagnosis of ischemic ATN after kidney transplantation, especially at the immediate posttransplantation period. Normal serum LDH at this period should raise a suspicion of acute rejection.~Conclusions~Conclusions [ABSTRACT FROM AUTHOR]

Incorporation of novel biological agents has become the cornerstone of treatment in multiple myeloma. For the last 4 years we have adopted the more intensified approach, previously published as total therapy 3 by the Arkansas group and used it with local modifications. This study aims to evaluate the efficacy and safety of the Arkansas protocol-based treatment outside clinical trial in a tertiary medical center in Israel. We retrospectively analyzed 23 patients. Seventy-three percent of the patients achieved very good partial remission (VGPR) before autologous stem cell transplantation (ASCT). Eighty-six percent of the patients achieved at least VGPR after tandem ASCT. Two-year overall survival was estimated as 70%. Four patients died during treatment, one as a result of disease progression. We conclude that this protocol is effective and rather safe. Further clinical trials should assess which subgroups of patients would benefit most from this approach. [ABSTRACT FROM AUTHOR]

Objective: Current guidelines recommend pharmacologic prophylaxis for medical patients at high risk for venous thromboembolism. We aimed to assess the benefit and safety of venous thromboembolism prophylaxis in acutely ill medical patients hospitalized.Methods: We prepared a retrospective cohort study in a tertiary hospital in Israel with patients hospitalized in medical departments with an admission lasting more than 48 hours during 2014-2017.Primary Outcome: 30-day mortality.Secondary Outcomes: 90-day incidence of pulmonary embolism, symptomatic deep vein thrombosis, and major bleeding. Propensity-weighted logistic multivariate analysis was performed.Results: A total of 18,890 patient-unique episodes were included in the analysis. Of them, 3206 (17.0%) received prophylaxis. A total of 1309 (6.9%) died, 540/3206 (16.8%) of those who received venous thromboembolism prophylaxis and 769/15,864 (4.9%) of those who did not. Prophylaxis was not associated with a reduction in mortality, multivariable-adjusted odds ratio propensity-weighted (OR) 0.99 (95% confidence interval [CI], 0.84-1.14). One hundred forty-two patients (0.7%) developed venous thromboembolism, 44/3206 (1.4%) of those who received prophylaxis and 98/15,864 (0.6%) of those who did not. Prophylaxis was not associated with reduction in venous thromboembolism in the whole cohort, multivariable-adjusted propensity-weighted OR 1.09 (95% CI, 0.52-2.29). Prophylaxis was associated with an increase in major bleeding (multivariable-adjusted propensity-weighted OR 1.24; 95% CI, 1.04-1.48).Conclusion: The current practice of routinely administering venous thromboembolism prophylaxis to medically ill patients considered at high risk for thrombosis resulted in a high risk for bleeding without a clear clinical benefit, and should be reassessed. [ABSTRACT FROM AUTHOR]

A multi-center retrospective analysis of a cohort of patients in Israel treated with any bendamustine containing regimen between 2010-2014 was performed in order to determine the incidence and predictors for infection. The Kaplan Meier Model, employing log rank analysis, was used to assess time-to-infection. The Cox Proportional Hazards model was used to analyze multivariate effects of risk and 234 patients were included in the analysis. One hundred and nine (46.6%) developed at least one infection and 33.76% had severe infections. Seventy-six (41.5%) developed bacterial infection, nine (3.8%) fungal infection and 26 (11.5%) had viral infections. Factors significantly associated with time to infection on multivariable analysis were: bendamustine-combinations [hazard ratio (HR) = 0.589 (95% CI = 0.374-0.926), p = 0.022], Hb level [HR = 0.791 (95% CI = 0.716-0.875), p < 0.0001] and ischemic heart disease [HR = 1.828 (95% CI = 1.165-2.868), p = 0.009]. Infections were associated with a higher mortality and hospitalization rate.

Purpose: To determine the distribution of etiologies for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients and to characterize patients according to the different etiologies., Methods: A single-center retrospective study including all patients diagnosed with SIADH in a large community hospital and tertiary center between 1.1.2007 and 1.1.2013. Two physicians reviewed every patient's medical file for predetermined relevant clinical data., Results: The study cohort included 555 patients. The most common etiologies were malignancies and medication-induced SIADH, followed by idiopathic SIADH, pulmonary infections, pain and nausea, and central nervous system (CNS) disorders. Subgroup analysis according to etiology showed that CNS disorders were associated with more severe episodes of SIADH. Patients with idiopathic SIADH were older than patients with a specific diagnosis, had a lower urine osmolality, and required less treatment with hypertonic saline. Long-term survival was determined primarily by SIADH etiology rather than hyponatremia severity, with hazard ratios for death of up to 7.31 (95% CI 4.93-10.82, p<0.001) for patients with malignancy-associated SIADH as compared to patients with idiopathic SIADH. Hyponatremia grade at short-term follow-up was also predictive for long-term survival (HR 1.42 per grade, 95% CI 1.21-1.66, p<0.001)., Conclusions: Patients with SIADH have different characteristics and a different prognosis according to SIADH etiology. Serum sodium concentration at short-term follow-up is predictive of long-term survival. These findings might have diagnostic and treatment-related implications., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: We aimed to find predictors for development of anemia in a large cohort of adults., Patients and Methods: Cohort study of a large health database from a screening center at the Rabin Medical Center in Israel, between the years 2000-2013. We asked which variables, known at the first visit, would predict anemia at the last visit. Multivariable analysis was conducted using stepwise logistic regression analysis. Odds ratios (ORs) for anemia with 95% confidence intervals (CIs) were calculated., Results: Our cohort included 10,577 people. At baseline 4.4% were diagnosed with anemia and excluded. Therefore, 10,093 subjects, with a mean age of 42.3 ± 9 years comprised our study sample. At the end of follow-up of 4.7 ± 3.1 years, 307 developed anemia (3%). In men, independent predictors for development of anemia were diabetes mellitus (OR 3.00, 95% CI 1.41-6.39), age (OR 1.03, 95% CI 1.03-1.05, for 1 year increment), low MCV (OR 0.92, 95% CI 0.89-0.96, for every 1 fL unit increment) and elevated platelet count (OR 1.004, 95% CI 1.00-1.01 for 1000/μL unit increment). For women, high total serum protein level was a strong predictor for anemia (OR 3.44, 95% CI 2.33-5.08 for 1mg/dL increment) as well as low triglycerides (OR 0.996, 95% CI 0.993-1.000 for 1mg/dL increment)., Conclusions: Subgroups who are prone to develop anemia include men with diabetes, and women with an elevated serum protein level and low triglycerides., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the association between inflammatory markers and mortality in patients with systemic lupus erythematosus (SLE)., Methods: A retrospective cohort analysis of 143 patients with SLE followed between 1991 and 2010 in a Lupus Clinic in Israel. High sensitivity CRP (hsCRP) level and ESR were recorded at baseline. We compared outcomes of patients with elevation of either ESR or hsCRP to outcomes of patients without any elevation of inflammatory markers at start of follow-up. Risk factors for mortality were identified using univariate and multivariate analyses (Cox regression analysis)., Results: Of the 143 patients, 93 patients had an inflammatory marker and 50 had no inflammatory marker. There were no differences between the two groups in terms of lupus criteria, disease activity parameters or damage index. Survival was lower for patients in the inflammatory group, 24 deaths of 93 patients (25.8%), 1393 patients-years, versus five deaths of 50 patients (10%), 692 patient-years, in the non-inflammatory group, log rank P=0.031. On multivariate analysis, inflammatory markers at baseline remained an independent risk factor for death, hazard ratio 2.72 (95% CI, 1.3-7.2)., Conclusions: SLE patients with elevation of inflammatory markers at baseline are at higher risk of death., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Hypomethylating agents have become the standard therapy for patients with high-risk myelodysplastic syndrome (MDS). In Israel, azacitidine (AZA) is routinely used. Yet, infectious complications are common during AZA therapy. The current study was aimed to evaluate the incidence and predisposing risk factors for infections in AZA-treated patients. This retrospective study included patients treated with AZA in 18 Israeli medical institutions between 2008 and 2011. Data on 184 patients [157 high-risk MDS and 27 acute myeloid leukemia (AML)], with a median age of 71.6 (range 29-92) were recorded. Overall, 153 infectious events were reported during 928 treatment cycles (16.5%) administered to 100 patients. One hundred fourteen, 114/153 (75%) events required hospitalization and 30 (19.6%) were fatal. In a univariate analysis, unfavorable cytogenetics, low neutrophil, hemoglobin (Hb) and platelet (PLT) counts were found to be associated with infections (24.4% vs. 12.9%, P < 0.0001; 27% vs. 13.5%, P < 0.0001; 20.4% vs. 11%, P < 0.0001 and 29.2% vs. 14.2%, P < 0.0001, respectively). In multivariate analysis, only low Hb level, low PLT count, and unfavorable cytogenetics remained significant. Prior to therapy, poor cytogenetics, PLT count below 20 × 10⁹/L and neutrophil count below 0.5 × 10⁹/L were predictive of the risk of infection during the first two cycles of therapy. In conclusion, patients with unfavorable cytogenetics, presenting with low neutrophil and PLT counts, are susceptible to infections. Evaluation of infection risk should be repeated prior to each cycle. Patients with poor cytogenetics in whom AZA is prescribed despite low PLT count are particularly at high risk for infections and infection prophylaxis may be considered., (Copyright © 2012 Wiley Periodicals, Inc.)

Surveys of bacterial infections among neutropenic cancer patients frequently report pooled antibiotic susceptibility data. Management guidelines address initial antibiotic regimens for febrile neutropenia. In this study, rates of bacterial infection and antibiotic susceptibilities among initial and subsequent or breakthrough episodes of fever were analysed. Prospective surveillance of fever of unknown origin (FUO), clinically documented infection and microbiologically documented infection (MDI) was conducted in the haemato-oncology and haematopoietic stem cell transplantation wards in a single cancer centre in Israel. Subsequent infections were defined as those developing during or after broad-spectrum antibiotic treatment. A total of 567 febrile episodes were documented among 271 patients. Bacterial MDIs were documented in 104/162 (64%) initial febrile episodes and 75/405 (19%) subsequent episodes and Gram-negative bacteria predominated (64% and 71%, respectively). Escherichia coli was the most common species isolated. Higher antibiotic susceptibilities were observed for initial compared with subsequent MDIs for Gram-negative bacteria [ceftazidime 80% vs. 45%, piperacillin/tazobactam (TZP) 86% vs. 40% and meropenem 95% vs.76%] and Gram-positive bacteria. TZP monotherapy was the most commonly used antibiotic and its susceptibility decreased to 22.2% following its use. Appropriate empirical antibiotic treatment was administered in 71/97 (73%) initial and 40/74 (54%) subsequent episodes (P=0.009) and was significantly associated with mortality (adjusted odds ratio=0.4, 95% confidence interval 0.18-0.87). We conclude that previous antibiotic exposure significantly impacts antibiotic susceptibility and that pooled reporting of all infections can be misleading. Treatment guidelines should address the antibiotic treatment of breakthrough fever., (Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Background: Monitoring the rate of infections in individual centers that treat patients with hematological malignancies is of major importance. However, there are no uniform guidelines for infection surveillance., Objectives: To describe the epidemiology of bacterial and fungal infections in a single hematology ward and to compare methods for reporting surveillance and infection rates in other centers in Israel., Methods: We conducted a prospective surveillance of all patients admitted to our hematology ward, applying standard definitions for invasive fungal infections and adapting definitions for non-fungal infections. Incidence rates were calculated using patients, admissions, hospital days and neutropenia days. We performed a search for other reported surveillance studies in Israel. ,, Results: We detected 79 infectious episodes among 159 patients admitted to the hematology ward during 1 year. Using neutropenia days as the denominator for calculation of incidence discriminated best between patients at high and low risk for infection. The incidence of invasive fungal infections was 7, 10 and 18 per 1000 neutropenia days, among all patients, those with acute leukemia and those with acute leukemia undergoing induction therapy, respectively. Only 10 reports from Israel were identified, 6 of which were prospective. Our data could not be compared to these reports because of the varying definitions and denominators used., Conclusions: Hematology centers should monitor infection rates and report them in a uniform methodology.

Background: The epidemiology of bacteremic febrile neutropenia differs between locations and constitutes the basis for selection of empiric antibiotic therapy for febrile neutropenia., Objectives: To describe the epidemiology of bacteremia among patients with neutropenia in a single center in Israel., Methods: We conducted a prospective data collection on all patients with neutropenia (< 500/mm3) and clinically significant bacteremia or fungemia during the period 1988-2004., Results: Among adults (462 episodes) the most common bloodstream isolate was Escherichia coli. Gram-negative bacteria predominated throughout the study period and the ratio between Gram-negative and Gram-positive bacteremia increased from 1.7 to 2.3. Among children (752 episodes), the ratio between Gram-negative and Gram-positive bacteremia reversed from 1.2 to 0.7, due to increasing prevalence of coagulase-negative staphylcoccal bacteremia. Both among adults and children, the length of hospital stay prior to bacteremia had a major impact on the pathogens causing bacteremia and their antibiotic susceptibilities. The prevalence of E. coli decreased with time in hospital, while the rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp., Acinetobacter spp., Enterococcus spp. and Candida spp. increased. Resistance to broad-spectrum empiric monotherapy in our center was observed in > 40% of Gram-negative bacteria when bacteremia was acquired after 14 days in hospital., Conclusions: Improved infection-control measures for neutropenic cancer patients in our center are needed. Empiric antibiotic treatment should be tailored to patients' risk for multidrug-resistant organisms. Individual hospitals should monitor infection epidemiology among cancer patients to guide empiric antibiotic treatment.