A Longitudinal Assessment of the Natural Change in Haemoglobin, Haematocrit, and Mean Corpuscular Volume with Age.

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.

A possible increased risk of metamizole-associated neutropenia among COVID-19 patients.

Metamizole is commonly used as analgesic and antipyretic drug. The use of metamizole is prohibited in several countries due to its rare side effect of neutropenia and even agranulocytosis. Among the many symptoms of COVID-19, fever and diffuse pain predominant and therefore it can be assumed that metamizole may be widely used in the current epidemic period. So far, there have been no reports on the safety of metamizole in COVID-19 patients. We describe a series of 3 patients who developed severe neutropenia under metamizole treatment, raising a concern of a possible increased risk of this side effect among COVID-19 patients.

Sex Differences in Folate Levels: A Cross Sectional Study of a Large Cohort from Israel.

BACKGROUND: Low folate levels are associated with megaloblastic anemia, neural tube defects, and an increased risk of cancer. Data are scarce regarding the sex aspect of this deficiency. OBJECTIVES: To assess sex differences in folate levels in a large cohort of patients and to investigate the effect of low folate levels on homocysteine concentrations. METHODS: Data were collected from medical records of patients examined at a screening center in Israel between 2000 and 2014. Cross sectional analysis was conducted on 9214 males and 4336 females. RESULTS: The average age was 48.4 ± 9.5 years for males and 47.6 ± 9.4 years for females. Average folate levels were 19.2 ± 8.6 and 22.4 ±10.3 nmol/L in males and females, respectively (P < 0.001). The prevalence of folate levels below 12.2 nmol/L was 19.5% in males compared to 11.6% in females (P < 0.001). In patients with low folate levels and normal B12 levels, homocysteine levels above 15 µmol/L were found in 32.4% of males and 11.4% of females (P < 0.001). Males had a significantly higher odds ratio (OR) of having folate levels below 12.2 nmol/L: OR 1.84 (95% confidence interval [95%CI] 1.66-2.05) in a non-adjusted model, and OR 2.02 (95%CI 1.82-2.27) adjusted for age, smoking status, body mass index, kidney function, albumin, and triglycerides levels. CONCLUSIONS: Folate levels are lower in males compared to females, which may contribute to the higher homocysteine levels found in males and thus to their increased risk of developing atherosclerosis and coronary artery disease.

Nocardia colonization in contrast to nocardiosis: a comparison of patients' clinical characteristics.

Information on Nocardia colonization of the lower respiratory tract is scarce. The current study is aimed at comparing clinical characteristics between individuals with Nocardia colonization and those with nocardiosis. All patients with Nocardia isolation between 2007 and 2018 at a tertiary hospital in Israel were included. Nocardia isolation was based on biochemical tests together with phenotypic susceptibility and resistance patterns until 2011 and on matrix-assisted laser desorption/ionization time-of-flight mass spectrometer from 2012. We defined nocardiosis as a clinically evident infection related to the isolation of the bacteria, which required antibiotic therapy. We defined colonization as Nocardia isolation with no clinical evidence of disease. The medical charts of all included individuals were independently reviewed by an infectious disease specialist to ensure adequate classification. Logistic regression models were fitted to compare clinical characteristics between the groups. Fifteen (20%) of the 75 Nocardia isolations met the criteria for colonization. Of those, 13 (87%) had background illnesses. Having a chronic pulmonary disease was associated with increased likelihood of Nocardia colonization, in contrast to nocardiosis (adjusted odds ratio [OR] 4.06, 95% confidence interval [CI] 1.06-15.48, p = 0.040), while an inverse association was found with corticosteroid therapy (adjusted OR 0.21, 95% CI 0.06-0.74, p = 0.015). Nocardia colonization of the lower respiratory tract accounts for a substantial proportion of all Nocardia isolations. Individuals colonized with Nocardia typically have chronic pulmonary disease and are less frequently treated with corticosteroid than patients with nocardiosis.

Reconsidering the relation between serum homocysteine and red blood cell distribution width: a cross-sectional study of a large cohort.

PURPOSE: In a recent small sample study, red blood cell distribution width (RDW) was suggested as a predictor of homocysteine levels. The current study was aimed to reexamine this association in a large scale sample. METHODS: A retrospective cross-sectional study of healthy adults, conducted at Rabin Medical Center, during 2000-2014. Data were retrieved from the medical charts and a logistic regression controlling for interfering factors was carried out. Sensitivity analysis was implemented by exclusion of individuals with anaemia. RESULTS: Five thousand, five hundred fifty-four healthy individuals were included. Mean serum homocysteine level was 10.10 (SD 2.72) µmol/L. 34.4% of the study population had a homocysteine level higher than the upper limit of normal (10.8 µmol/L). Homocysteine showed no association with RDW (OR 1.00; 95% CI 0.97-1.03), but increased with age (OR 1.05; 95% CI 1.04-1.06) and decreased with a rise in haemoglobin (OR 0.77; 95% CI 0.71-0.83), and in the mean corpuscular volume (OR 0.86; 95% CI 0.85-0.88). Exclusion of individuals with anaemia did not reveal an association between homocysteine and RDW but found a somewhat smaller association between haemoglobin and RDW [OR 0.82; 95% CI 0.73-0.91]. CONCLUSIONS: In our large scale sample we did not find an association between RDW and serum homocysteine.

Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort.

BACKGROUND: Vitamin B12 deficiency is associated with hematological, neurological, and cardiovascular consequences. Epidemiologic data on these related illnesses indicate gender differences. METHODS: A cross-sectional study was designed to examine gender differences in vitamin B12 deficiency among a healthy population. Data from healthy individuals aged 18-65, who were provided with a routine medical evaluation during 2000-2014, were retrieved from the medical charts. Individuals with background illnesses and those who had used medications or nutritional supplements were excluded. Vitamin B12 deficiency was defined by 2 cutoff values (206 and 140 pmol/L). The multivariate analysis was adjusted for age, body mass index, estimated glomerular filtration rate, hyperhomocysteinemia, folate deficiency, albumin, and transferrin saturation. Sensitivity analyses were implemented by excluding individuals with anemia, hyperhomocysteinemia, or folate deficiency and by age stratification. RESULTS: In all, 7,963 individuals met the inclusion criteria. Serum vitamin B12 mean levels were 312.36 and 284.31 pmol/L for women and men respectively (p < 0.001). Deficiency prevalence was greater for men (25.5%) in comparison with women (18.9%; p < 0.001). Men were strongly associated with severe deficiency (adjusted OR 2.26; 95% CI 1.43-3.56). CONCLUSIONS: Among the healthy population, men are susceptible to vitamin B12 deficiency. This can be explained by neither diet habits nor estrogen effects. Genetic variations are therefore hypothesized to play a role.

Infective endocarditis in the setting of renal transplantation: Case report and review of the literature.

The potent immunosuppressive drugs used by transplant recipients place them at risk of infections. Data on infective endocarditis (IE) in the setting of renal transplantation (RT) are sparse. We describe a 36-year-old woman referred to a tertiary medical center for evaluation of elevated creatinine levels 1 month after a second RT. Work-up revealed the presence of all four of Duke's criteria: fever, persistent bacteremia, new-onset tricuspid regurgitation, and masses suspected to be vegetation attached to the tricuspid annulus. Symptoms resolved with antibiotic treatment and fluids. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed hypermetabolic absorption in the femoral vascular graft that had been used for hemodialysis prior to transplantation. The graft was removed by open surgery, and the patient was discharged home in good condition with continued antibiotic treatment. Review of the literature yielded 73 previously reported cases of IE in renal transplant recipients. Several differences were noted from IE in the general population: lower male predominance, younger age (<60 years), absence in most cases of a preexisting structural cardiac anomaly, and more variable causative pathogens. Our case also highlights the importance of FDG-PET/CT for detecting the source of IE and alerts clinicians to the sometimes unexpected course of the disease in renal transplant recipients.

The Relationship between Cigarette Smoking and Renal Function: A Large Cohort Study.

BACKGROUND: Both cigarette smoking and chronic kidney disease (CKD) are linked to cardiovascular morbidity and development of atherosclerosis. However, the relationship between cigarette smoking and renal function is not clearly understood. OBJECTIVES: To investigate the relationship between cigarette smoking and renal function, and determine whether the intensity of cigarette smoking influences renal function. METHODS: We conducted a retrospective analysis of subjects attending the screening center at the Rabin Medical Center. Subjects were classified as smokers, non-smokers and past smokers. Renal function was evaluated by means of the CKD-EPI equation for estimating glomerular filtration rate (eGFR). Multivariate and gender-based analyses were performed. RESULTS: The study population comprised 24,081 participants, of whom 3958 (17%) were classified current smokers, and 20,123 non-smokers of whom 4523 were classified as past smokers. Current smokers presented a higher eGFR compared to the non-smoking group (100.8 vs. 98.7, P < 0.001) as well as higher rates of proteinuria (15.3% vs. 9.3%, P < 0.001). The difference in eGFR between smokers and non-smokers was more significant in males than in females. Past smokers had the lowest eGFR of all groups, this difference remained significant after age adjustments (P = 0.005). CONCLUSIONS: Cigarette smoking is associated with higher eGFR compared to non-smoking. This difference was more pronounced in males than females, implying a gender-based difference. The higher prevalence of proteinuria in smokers suggests a mechanism of hyperfiltration, which might result in future progressive renal damage.

The real-world safety of sacubitril / valsartan among older adults (≥75): A pharmacovigilance study from the FDA data.

BACKGROUND: Heart failure is a major cause of morbidity and mortality among older adults. Sacubitril-Valsartan (Sac/Val) has been shown to improve patients' outcomes; however, its safety profile among older adults has not been adequately examined. We therefore aimed to examine its safety profile among this population. METHODS: We conducted a retrospective pharmacovigilance study utilizing the FDA's database of safety reports (FAERS). We employed disproportionality analysis comparing Sac/Val to angiotensin receptor blockers (ARBs). We aim to evaluate the reporting of pre-defined adverse events associated with Sac/Val (hypotension, acute kidney injury (AKI), hyperkalemia and angioedema) in two age groups: adults (< 75 years) and older adults (≥ 75). For each subgroup, we calculated reporting odds ratio (ROR) and compared them by calculating P for interaction. RESULTS: The FAERS database encompassed 18,432 unique reports of Sac/Val. Of them, 12,630 (68.5%) subjects were adults (< 75 years), and 5802 (31.5%) were older adults (≥ 75 years), with a median age (IQR) of 68 (59-77). When compared to ARBs, Sac/Val was associated with higher reporting of hypotension, lower reporting of acute kidney injury (AKI) and hyperkalemia, and similar reporting of angioedema. Notably, we did not observe a significant interaction between the age subgroups and the risk estimates (AKI: Pinteraction = 0.72, hyperkalemia: Pinteraction = 0.94, hypotension: Pinteraction = 0.31, and angioedema: Pinteraction = 0.61). CONCLUSIONS: In this postmarking study, none of the prespecified adverse events was reported more frequently in older adults. These findings provide reassurance for safety use of Sac/Val in older adults.

Association between the body mass index and chronic kidney disease in men and women. A population-based study from Israel.

BACKGROUND: Any association between the body mass index (BMI) and chronic kidney disease (CKD) has so far proved inconclusive. Most studies have estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation. This has recently been replaced by the more accurate Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. METHODS: In a cross-sectional study, data from a screening centre in Israel, n = 21880 (32% women) were used to assess the prevalence of CKD defined as eGFR < 60 mL/min/1.73 m(2) in relation to BMI categories. The CKD-EPI equation was used to assess the eGFR. RESULTS: CKD was found in 167 men and 45 women. Subjects with a BMI of 25-29.9 kg/m(2), compared with those with a BMI of <25 kg/m(2), had an odds ratio (OR; 95% confidence intervals) for CKD of 1.8 (1.2-2.7) and 3.4 (1.5-7.7) for men and women, respectively. Subjects with a BMI of 30-35 kg/m(2) had an OR of 2.5 (1.6-4.0) and 4.5 (1.7-11.7) for men and women, respectively. In comparable data, for subjects with a BMI > 35 kg/m(2) the OR was 2.7 (1.3-5.5) and 15.4 (6.4-36.7) for men and women, respectively. After multivariate adjustment for age, hypertension and diabetes mellitus, no association was found in men yet it persisted for women. This correlation in women, between the BMI and CKD, was attributed to the subcategory of severely obese women with a BMI of >35 kg/m(2). CONCLUSIONS: Our study is the first to suggest that morbid obesity may be an independent factor related to CKD in women.

Anti-GalNAcß: a novel anti-glycan autoantibody associated with pregnancy loss in women with antiphospholipid syndrome and in a mouse experimental model.

OBJECTIVES: We evaluated the presence of anti-glycan antibodies (aGA) in patients with antiphospholipid syndrome (APS), and associations between aGA and clinical features of the disease. METHODS: Sera from APS patients and healthy controls were analyzed for aGA levels by ELISA. Analysis of the association of specific aGA with clinical manifestations of APS was performed. Selected aGA were affinity-purified and injected intravenously into naive mice which were tested for fetal loss. Matrigel invasion assay was performed for detection of choriocarcinoma cells (JAR) invasion and proliferation in the presence of selected aGA. Culture fluid of JAR invasion assays was analyzed for the presence of MMP2 and MMP9. RESULTS: High levels of several aGA were found in APS sera, of which anti-GalNAc-ß was significantly associated with recurrent pregnancy loss. Naive mice infused intravenously with anti-GalNAc-ß developed increased fetal loss. Anti-GalNAc-ß significantly inhibited the in-vitro percentage of JAR invasiveness and the secretion of MMP2 and MMP9 by human JAR cells. CONCLUSIONS: APS sera contain significant levels of aGA directed against several glycans. Anti-GalNAc-ß Ab is specifically associated with recurrent pregnancy loss both in human patients and experimental mouse model. The pathogenic effects of anti-GalNAc-ß include inhibition of JAR cells invasiveness accompanied by decreased MMP2 and MMP9 secretion.

Hyperuricemia and metabolic syndrome: lessons from a large cohort from Israel.

BACKGROUND: There is a striking increase in the number of people with metabolic syndrome (MetS) as a result of the global epidemic of obesity and diabetes. Increasing evidence suggests that uric acid may play a role in MetS. OBJECTIVES: To assess the prevalence of MetS in a large cohort from Israel and its association with hyperuricemia using the latest three definitions of MetS. METHODS: We conducted a retrospective analysis of the database from a screening center in Israel, using the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF) and the Harmonizing definitions of MetS, to assess 12,036 subjects with an age range of 20-80 years. RESULTS: The mean age of the study sample was 46.1 +/- 10.2 years and 69.8% were male. The prevalence of MetS was 10.6%, 18.2% and 20.2% in the revised NCEP ATP III, the IDF and the Harmonizing definitions respectively. The prevalence of hyperuricemia in subjects with MetS, for all three MetS definitions, was similar: 20.0%, 19.9% and 19.1% respectively. There was a graded increase in the prevalence of MetS among subjects with increasing levels of uric acid. The increasing trend persisted after stratifying for age and gender and after multivariate analysis (P for trend (0.001). CONCLUSIONS: This large cohort shows a high prevalence of MetS in Israel, but is still lower than the prevalence in western countries. Hyperuricemia is common in those subjects and might be considered a potential clinical parameter in the definition of MetS.

Proton pump inhibitor use and its effect on vitamin B12 and homocysteine levels among men and women: A large cross-sectional study.

BACKGROUND: Previous studies have demonstrated an association between proton pump inhibitors (PPI) use and vitamin B12 deficiency. However, data regarding PPI use and elevated serum homocysteine level, an important marker of vitamin B12 deficiency, are scant. METHODS: Data were collected from medical records of subjects examined at a screening center in Israel. Cross sectional analysis was conducted on 25,953 subjects. Levels of vitamin B12 and homocysteine were compared between subjects who consumed PPI medications and those who did not. RESULTS: The mean age of the study population was 45 years and 33% were females. Subjects who received PPI medications had a minor higher vitamin B12 levels (320 pmol/L vs 300 pmol/L, p=0.024). Levels of vitamin B12 remained higher in females receiving PPI medications after performing a stratified analysis according to subjects' gender. Homocysteine levels were higher in subjects receiving PPI medications as compared to those who did not (12.0 µmol/L vs 11.6 0 µmol/L, p<0.001). Levels remained higher in female subjects after performing a stratified analysis according to subjects' sex. There was no statistically significant difference in the prevalence of vitamin B12 deficiency (according to two cutoffs: vitamin B12≤200 or ≤140 pmol/L) as well as the prevalence of hyperhomocysteinemia (defined as homocysteine >15.0 µmol/L) between the two groups. CONCLUSIONS: According to our study, no association was found between PPI medication use and vitamin B12 deficiency or hyperhomocysteinemia. Patients receiving PPI medications had slightly higher levels of vitamin B12 and homocysteine, however these differences were too small to have any clinical relevance.

Markers of Chronic Inflammation in Overweight and Obese Individuals and the Role of Gender: A Cross-Sectional Study of a Large Cohort.

OBJECTIVE: During the last decade, obesity has become an epidemic. As obesity is now considered a state of low-grade inflammation, the purpose of this study was to assess the prevalence of four common elements of inflammation, in individuals with increased BMI. These findings were compared to those of subjects with normal BMI. The effect of gender was also noted. METHODS: Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000-2014. Cross-sectional analysis was carried out on 7526 men and 3219 women. White blood cell count (WBC); platelet (PLT) count; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were assessed in four BMI categories: normal, overweight, obese and morbidly obese. RESULTS: Mean (SD) age of the study sample was 47.5 (9.7) and 46.7 (9.8) years for men and women, respectively. The prevalence of each inflammatory marker increased significantly when comparing abnormal to normal BMI (p<0.0001). The odds ratio (OR) of the prevalence of increased inflammatory markers was compared between subjects with overweight, obese and morbid obesity and subjects with normal BMI. This study showed that the higher the BMI, the higher the OR. For those in the morbid obesity group, the OR for the different inflammatory markers adjusting for age, diabetes mellitus hypertension and kidney function were as follows: WBC levels, 5.1 (2.9-8.7) and 4.7 (2.4-9.1) for men and women, respectively; PLT levels, 1.7 (0.3-8.5) and 2.0 (0.6-7.2) for men and women, respectively; ESR levels, 4.2 (3.2-5.4) and 4.6 (3.2-6.6) for men and women, respectively, and CRP levels, 13.4 (10.0-18.2) and 19.2 (12.9-28.6) for men and women, respectively. CONCLUSION: Inflammatory markers are significantly higher in subjects with abnormal compared to normal BMI. This difference was found to be greater in women than in men.

Streptococcus gallolyticus endocarditis on a prosthetic tricuspid valve: a case report and review of the literature.

BACKGROUND: Streptococcus gallolyticus subspecies gallolyticus is a known pathogen that causes infective endocarditis, and most cases involve the left heart valves. We present the first reported case of prosthetic tricuspid valve endocarditis caused by this microorganism. Relevant literature is reviewed. CASE PRESENTATION: A 67-year-old Jewish female with a history of a prosthetic tricuspid valve replacement was admitted to the emergency department because of nonspecific complaints including effort dyspnea, fatigue, and a single episode of transient visual loss and fever. No significant physical findings were observed. Laboratory examinations revealed microangiopathic hemolytic anemia and a few nonspecific abnormalities. Transesophageal echocardiogram demonstrated a vegetation attached to the prosthetic tricuspid valve. The involved tricuspid valve was replaced by a new tissue valve, and Streptococcus gallolyticus subspecies gallolyticus was grown from its culture. Prolonged antibiotic treatment was initiated. CONCLUSIONS: Based on this report and the reviewed literature, Streptococcus gallolyticus should be considered as a rare but potential causative microorganism in prosthetic right-sided valves endocarditis. The patient's atypical presentation emphasizes the need for a high index of suspicion for the diagnosis of infective endocarditis.

Global Academic Productivity in the Field of Internal Medicine and Its Correlation to National Economic Indicators: A Bibliometric Analysis of 24 Years.

BACKGROUND: Previous studies have demonstrated a correlation between national economic indicators and academic productivity. However, such a relationship has not been studied in the field of internal medicine (IM). METHODS: The number of documents published, number of citable documents, number of citations, citations per document and the h index between 1996 and 2019 in the field of IM among the Organisation for Economic Co-operation and Development (OECD) countries were analysed. Data were derived from the The Scimago Journal and Country rank source. We analysed the correlation between these indicators to the gross domestic product (GDP) per capita, health spending as percent of GDP and gross domestic expenditure on research and development as percent of GDP (GERD). Economic data were collected from the OECD websites. RESULTS: A significant correlation was found between health expenditure and h index (r = 0.75, P < 0.001), number of citations (r = 0.72, P < 0.001), number of documents (r = 0.62, P < 0.001) and number of citable documents (r = 0.61, P < 0.001); between GERD and number of citations (r = 0.6, P < 0.001), h index (r = 0.6, P < 0.001), number of documents published (r = 0.53, P = 0.001) and citable documents (r = 0.51, P = 0.001); between the GDP per capita and number of citations (r = 0.46, P = 0.005), citations per document (r = 0.54, P = 0.001) and h index (r = 0.5, P = 0.002). CONCLUSIONS: This study demonstrated a positive correlation between academic productivity in the field of IM and economic indicators of the OECD countries, mainly health expenditure, implying the advantage of domestic investment in health.

COVID-19 in a patient receiving adjuvant breast cancer chemotherapy with granulocyte olony-stimulating factor (G-CSF) support: A case report.

Patients receiving chemotherapy are at high risk for severe infections and complications such as acute respiratory syndrome. The most commonly used adjuvant chemotherapy protocols (docetaxel-cyclophosphamide every 3 weeks or the dose-dense regimen, doxorubicin-cyclophosphamide every 2 weeks followed by paclitaxel) incorporate granulocyte-colony stimulating factor (G-CSF). G-CSF is routinely administered to prevent chemotherapy-associated neutropenia but often results in significant neutrophilia. The present case describes a patient with breast cancer who was successfully treated for severe COVID-19 respiratory syndrome while under adjuvant chemotherapy (docetaxel-cyclophosphamide) treatment and long-term G-CSF support. In addition, the potential effect of G-CSF on the respiratory deterioration of the patient given its cardinal role in innate inflammation and, accordingly, the cytokine storm associated with COVID-19 was described. The case described in the present study indicated how solutions to the immunity challenges faced when treating a patient with chemotherapy may be the source of a larger problem within the coronavirus COVID-19 pandemic.

Risk of stroke and other thromboembolic complications after interruption of DOAC therapy compared with warfarin therapy in patients with atrial fibrillation: a retrospective cohort analysis.

Direct oral anticoagulants (DOACs) have become the treatment of choice in thromboembolism prophylaxis for non-valvular atrial fibrillation, surpassing warfarin. While interruption of DOAC therapy for various reasons is a common eventuality, the body of data from real-world clinical practice on the implications of such interruptions in different clinical settings is still limited. We assessed complication rates from DOAC (apixaban, rivaroxaban, dabigatran) interruption compared with warfarin in hospitalized patients. We performed a retrospective cohort analysis of electronic records of patients hospitalized in Rabin Medical Center between 2010 and 2017. Incidents of anticoagulation interruptions for various reasons (including unintended interruptions) were collected. DOAC-treated patients were excluded if they reported non-compliance, and warfarin-treated patients were excluded if their international normalized ratio measurement on admission was subtherapeutic. Outcomes included ischemic stroke, systemic thromboembolism, myocardial infarction, and all-cause mortality within 90 days of anticoagulation interruption. The median CHA2DS2-VASc score was 5.0 (IQR 4.0-6.0) in both treatment groups. The associated risk of stroke, thromboembolic complications, myocardial infarction, and all-cause mortality after interruption of anticoagulation was not significantly different between the 2 treatment groups. Selective comparison of patients who were well balanced on warfarin before treatment interruption to DOAC-treated patients did not significantly influence the outcomes. This study did not find a significant difference in the complication rate after interruption of DOAC therapy compared with interruption of warfarin therapy in hospitalized patients with a high risk of thromboembolism.

Secondary bacterial infection in COVID-19 patients is a stronger predictor for death compared to influenza patients.

Secondary bacterial infections are a potentially fatal complication of influenza infection. We aimed to define the impact of secondary bacterial infections on the clinical course and mortality in coronavirus disease 2019 (COVID-19) patients by comparison with influenza patients. COVID-19 (n = 642) and influenza (n = 742) patients, admitted to a large tertiary center in Israel and for whom blood or sputum culture had been taken were selected for this study. Bacterial culture results, clinical parameters, and death rates were compared. COVID-19 patients had higher rates of bacterial infections than influenza patients (12.6% vs. 8.7%). Notably, the time from admission to bacterial growth was longer in COVID-19 compared to influenza patients (4 (1-8) vs. 1 (1-3) days). Late infections (> 48 h after admission) with gram-positive bacteria were more common in COVID-19 patients (28% vs. 9.5%). Secondary infection was associated with a higher risk of death in both patient groups 2.7-fold (1.22-5.83) for COVID-19, and 3.09-fold (1.11-7.38) for Influenza). The association with death remained significant upon adjustment to age and clinical parameters in COVID-19 but not in influenza infection. Secondary bacterial infection is a notable complication associated with worse outcomes in COVID-19 than influenza patients. Careful surveillance and prompt antibiotic treatment may benefit selected patients.