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.

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.

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.

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.

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.

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.

A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary centre in Israel.

OBJECTIVES: The effectiveness of remdesivir, a Food and Drug Administration-approved drug for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been repeatedly questioned during the current coronavirus disease 2019 (COVID-19) pandemic. Most of the recently reported studies were randomized controlled multicentre clinical trials. Our goal was to test the efficiency of remdesivir in reducing nasopharyngeal viral load and hospitalization length in a real-life setting in patients admitted to a large tertiary centre in Israel. METHODS: A total of 142 COVID-19 patients found to have at least three reported SARS-CoV-2 quantitative RT-PCR tests during hospitalization were selected for this study. Of these, 29 patients received remdesivir, while the remaining non-treated 113 patients served as controls. RESULTS: Among the tested parameters, the control and remdesivir groups differed significantly only in the intubation rates. Remdesivir treatment did not significantly affect nasopharyngeal viral load, as determined by comparing the differences between the first and last cycle threshold values of the SARS-CoV-2 quantitative RT-PCR tests performed during hospitalization (cycle threshold 7.07 ± 6.85 vs. 7.08 ± 7.27, p 0.977 in the control and treated groups, respectively). Remdesivir treatment shortened hospitalization length by less than a day compared with non-treated controls and by 3.1 days when non-intubated patients from both groups were compared. These differences, however, were not statistically significant, possibly because of the small size of the remdesivir group. DISCUSSION: Remdesivir was not associated with nasopharyngeal viral load changes, but our study had a significant disease severity baseline imbalance and was not powered to detect viral load or clinical differences.

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.

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.

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.

Clinical correlates of nocardiosis.

Nocardia is an opportunistic pathogen that most frequently affects the lungs. Evidence is limited regarding the risk factors for nocardiosis. The current study assessed clinical correlates of nocardiosis. A retrospective study was conducted based on medical records of consecutive adult patients (N = 60) with nocardiosis hospitalized during 2007-2018 at a tertiary hospital in central Israel. A matched comparison group of 120 patients was randomly selected among hospitalized patients with community-acquired pneumonia. Multivariable conditional logistic regression models were fitted. Immunosuppressive pharmacotherapy was positively associated with nocardiosis (matched odds ratio [OR] 4.40, 95% confidence interval [CI] 2.25-8.62, p < 0.001), particularly corticosteroid therapy (matched OR 4.69, 95% CI 2.45-8.99, p < 0.001). Systemic corticosteroid therapy was strongly associated with pulmonary nocardiosis (matched OR 5.90, 95% CI 2.75-12.66, p < 0.001). The positive association between solid organ transplantation and nocardiosis was attenuated following adjustment for systemic corticosteroids in a multivariable model. The association between corticosteroid therapy and nocardiosis appeared stronger in patients with chronic pulmonary disease (OR 5.74, 95% CI 2.75-12.66, p < 0.001) than in the pooled analysis of all nocardiosis cases. In conclusion, corticosteroid therapy was strongly correlated with nocardiosis, particularly among individuals with chronic pulmonary disease and in pulmonary nocardiosis.

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.

The relationship between the concentration of plasma homocysteine and chronic kidney disease: a cross sectional study of a large cohort.

BACKGROUND: High concentrations of homocysteine are considered a risk factor for developing atherosclerosis and coronary artery disease. The aim of this study was to assess the concentrations of homocysteine in subjects with chronic kidney disease (CKD). 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 17,010 subjects; 67% were men. RESULTS: Significant differences were observed between four quartiles of homocysteine concentrations and estimated glomerular filtration rate (eGFR)-the higher the homocysteine concentration, the lower the eGFR (p < 0.0001). In subjects with CKD, homocysteine plasma levels were correlated with the stage of renal impairment. Mean (SD) homocysteine concentrations in subjects with eGFR < 60 mL/min per 1.73 m2 compared to subjects with eGFR ≥ 60 mL/min per 1.73 m2 were: 16.3 (5.9) vs. 11.5 (5.5) µmol/L respectively. These findings remained significant after adjustment for age, smoking status, body mass index, hypertension and diabetes mellitus (p < 0.0001). Compared to subjects with homocysteine concentrations less than 15 µmol/L, those with homocysteine concentrations equal and above 15 µmol/L, had a significantly higher odds ratio (95% CI) of having an eGFR < 60 mL/min per 1.73 m2; non adjusted model, 8.30 (6.17-11.16); adjusted model for age smoking status, body mass index, hypertension and diabetes mellitus, 7.43 (5.41-10.21). CONCLUSION: Plasma homocysteine concentrations are higher in subjects with CKD. This may contribute to an increased risk for developing atherosclerosis and coronary artery disease in these patients.

Gender as an Independent Risk Factor for the Components of Metabolic Syndrome Among Individuals Within the Normal Range of Body Mass Index.

Background: Overweight and obesity are more common in men than in women. This explains the higher prevalence of risk factors for metabolic syndrome (MetS) found in men. We aimed to assess whether gender, per se, might be an independent risk factor for the components of MetS in a large cohort of subjects within the normal range of body mass index (BMI). Materials and Methods: Cross-sectional analysis was carried out on 9976 men and women, aged 18 to 70 years, with a BMI between 18.5 and 25.0 kg/m2 attending a screening center in Israel between the years 2000 and 2014. Results: Mean (SD) age of the study sample was 43.3 (9.6) years, 54.5% were men. Prevalence of MetS components in men and women was hypertension 5.3% and 3.0%, impaired fasting glucose (IFG) 18.1% and 7.9%, diabetes mellitus (DM) 2.4% and 1.3%, high triglyceride levels 17.7% and 9.4%, and low high-density lipoprotein (HDL) cholesterol levels 13.6% and 17.0%, respectively, P < 0.001 for all. Increased waist circumference was <1% in both genders. Multivariate analysis showed male gender to be an independent risk factor for IFG [odds ratio (OR) 2.43, 95% confidence interval (CI) 2.12-2.79], hypertriglyceridemia (OR 1.86, 95% CI 1.63-2.12), DM (OR 1.80, 95% CI 1.29-2.50), and hypertension (OR 1.46, 95% CI 1.16-1.83) but not for low HDL levels (OR 0.59, 95% CI 0.52-0.67). Conclusion: This study, on a cross-sectional sample of subjects with a normal BMI, showed male gender to be an independent risk factor for all components of the MetS, apart from the low HDL risk factor that was found to be higher in women.

Impaired fasting glucose is associated with lower glomerular filtration rate decline among men but not women -a large cohort study from Israel.

OBJECTIVES: Early stages of diabetes are associated with an increased glomerular filtration rate (GFR). Little is known, however, about the change in GFR among patients with impaired fasting glucose (IFG). We aimed to evaluate the yearly decline rate of GFR among IFG patients. METHODS: A retrospective analysis of a large cohort of subjects attending a medical screening center in Israel. Patients with diabetes mellitus and patients with decreased estimated GFR (eGFR) were excluded. We divided the cohort into 2 subgroups; Healthy controls and impaired fasting control subjects. For each group, we calculated the average yearly estimated GFR decline (ΔeGFR). The results were adjusted for age, BMI, hypertension and smoking status. RESULTS: 8176 subjects met the inclusion criteria. The median follow up time was 4.8 years (range 2.0 to 13.4). For the whole cohort (men and women), yearly ΔeGFR was -0.68 among healthy controls, and - 0.47 among IFG patients (p = .003). Among men, average yearly ΔeGFR in healthy controls and IFG patients was -0.7 and - 0.4, respectively (p = .0002). All results remained significant after adjusting for age, BMI, hypertension, smoking status and level of HDL and triglycerides. In contrast, among IFG women there was no significant difference in ΔeGFR in comparison with healthy women. CONCLUSIONS: Impaired fasting glucose is associated with a decreased rate of GFR reduction compared with healthy subjects. This effect is gender dependent - observed in men but not in women. A mechanism of glomerular hyperfiltration might be involved.

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.

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.

Relationship between hematocrit levels and intraocular pressure in men and women: A population-based cross-sectional study.

To assess a possible relationship between hematocrit level and intraocular pressure (IOP) in both men and women.Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000 and 2013. Hematocrit levels were categorized as low, normal, and high and by sex; IOP values were categorized as < 18 mmHg and ≥18 mmHg.Cross-sectional analysis was performed on 18,424 subjects of mean (standard deviation) age 46 (10) years (68% male). Normal-range hematocrit for men was 42% to 52% and 37% to 47% for women. In men, mean [95% confidence interval CI)] IOP values by hematocrit level were as follows: below-normal hematocrit, 13.3 mmHg (13.2-13.3), normal hematocrit, 13.5 mmHg (13.4-13.5), above-normal hematocrit, 14.3 mmHg (13.5-15.2) (P < .001). Corresponding values in women were 12.9 mmHg (12.8-13.0), 13.0 mmHg (13.0-13.1), and 14.2 mmHg (12.9-15.6) (P = .014). The difference remained significant for men (P < .001) after adjustment for age, hypertension, diabetes, and body mass index. Men (but not women) with a low hematocrit were found to have a significantly lower odds ratio (95% CI) of having IOP ≥18 mmHg than men with normal hematocrit: nonadjusted model, 0.761 (0.631-0.919); adjusted model, 0.771 (0.638-0.932) (P < .01).It is possible that a raised hematocrit level may also contribute to an elevated IOP in men in addition to the classic risk factors.