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.

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.

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.

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.

Relationship Between Serum Glucose Levels and Intraocular Pressure, a Population-based Cross-sectional Study.

PURPOSE: The purpose of this study is to assess the relationship between serum glucose levels and intraocular pressure (IOP) both in subjects with impaired fasting glucose (IFG) as well as in subjects with diabetes mellitus (DM). MATERIALS AND METHODS: Data of a cross-sectional sample of 18,406 subjects who underwent routine annual screening at a tertiary medical center in 2000 to 2013 were analyzed. RESULTS: Mean (SD) age of the subjects was 46 (10) years; 68% were male. Mean (95% confidence interval) IOP measured 13.1 (13.0-13.1) mm Hg in subjects with normal glucose levels, 13.7 (13.6-13.8) mm Hg in subjects with IFG, and 14.3 (14.1-14.4) mm Hg in subjects with diabetes. The difference in IOP between subjects with normal and abnormal (DM or IFG) serum glucose levels were significant, even after adjusting for age, body mass index, and hypertension (P<0.0001). There was a positive linear correlation between serum glucose levels and IOP in both men (r=0.12; P<0.0001) and women (r=0.17; P<0.0001). For every 10 mg/dL increase in fasting serum glucose, IOP increased by 0.09 mm Hg in men and by 0.11 mm Hg in women. CONCLUSIONS: This study demonstrated that similar to subjects with DM, subjects with IFG also have IOP levels that are higher than those with normal serum glucose. Moreover, there is a direct correlation between fasting serum glucose levels and changes in IOP. These findings highlight another end-organ effect of uncontrolled glucose levels.

Relationship between homocysteine and intraocular pressure in men and women: A population-based study.

The relationship between homocysteine levels and glaucoma has been questioned in previous studies without conclusive results. In the current study, we assessed the relationship between homocysteine levels and intraocular pressure which is one of the main factors in the development of glaucoma in men and women.A retrospective cross-sectional analysis of a database from a screening center in Israel which assessed 11,850 subjects, within an age range 20 to 80 years. The relationship between homocysteine and intraocular pressure has been investigated by comparing intraocular pressure in subjects with elevated and normal homocysteine and by comparing homocysteine levels in subjects with elevated and normal intraocular pressure. In addition, we compared the levels of homocysteine in subjects with and without a confirmed diagnosis of glaucoma.The mean IOP (±SD) in subjects with normal homocysteine levels(≤15 µmol/L) was 13.2 ±â€Š2.3 mm Hg and 13.4 ±â€Š2.4 mm Hg in those with high homocysteine levels (>15 µmol/L) (P < 0.008, 95% confidence interval [CI] 0.3-0.09).Nonetheless, after multivariate adjustment for age, gender, vitamin B12, and folic acid statistical significance was no longer demonstrated (P = 0.37). Mean homocysteine levels (±SD) in subjects with normal intraocular pressure of ≤ 21 mm Hg was 11.7 ±â€Š5.5 µmol/L and 12.09 ±â€Š3.43 µmol/L in those with elevated intraocular pressure (P = 0.4, 95%CI 1.1-1.8). Mean homocysteine levels (±SD) in subjects with glaucoma were 11.2 ±â€Š3.5 µmol/L compared to 11.7 ±â€Š5.5 µmol/L in subjects without glaucoma and normal intraocular pressure ≤ 21 mm Hg (P = 0.4, 95% CI 1.2-2.1).The current study displays no clinical correlation between the homocysteine level and the intraocular pressure. Homocysteine may not be used as a predictive parameter to recognize those subjects prone to develop elevated intraocular pressure.

Factors Affecting the Upper Limit of the Methotrexate (MTX) CSF Levels Achievable in Children With Brain Tumors Treated With High-dose Intravenous MTX.

BACKGROUND: Little has been published in the medical literature on serum and cerebrospinal fluid (CSF) methotrexate (MTX) levels in children with brain tumors. METHODS: Matched 24-hour serum and CSF MTX levels were studied after 113 treatments in 35 brain tumors patients. RESULTS: A correlation between the 24-hour serum levels of MTX and MTX dosage was observed after 113 treatments in all 35 patients (r=0.39, P<0.001) but no statistical difference was found between CSF MTX levels in the irradiated and nonirradiated groups (P=0.12). Nonirradiated children received a lower dose of MTX (12.3±4.8 cf 14.8±3.7) (P=0.002). The 24-hour MTX CSF levels of these 2 groups were also found to be different (the nonirradiated group 7.6±9.8 cf 12.5±0.15.3). Using the Levene test for variances we found that these variances were not equal and therefore we used the Welch test which resulted in a P-value of 0.04. However, when an analysis of covariance was performed looking at evidence of CSF disease and MTX dose the radiation difference was no longer significant (P=0.15). The 24-hour CSF MTX levels in children without evidence of active CSF disease were consistently lower than those with active disease using a mixed-model analysis (P=0.002). Although a 24-hour CSF MTX level of at least 1 µM was observed after infusions of >5 g/m MTX in previously irradiated children and after infusion of ≥10 g/m in nonirradiated children this difference did not reach statistical significance. CSF MTX levels plateau at doses of MTX 15 g/m putting in doubt the value of administering even higher doses of MTX. CONCLUSIONS: The 24-hour MTX CSF levels are higher in patients with active CSF disease. Doses of <10 gm/m in children with brain tumors may not achieve a guaranteed 24-hour MTX CSF level of 1 µM. There may be little value in a given dose of >15 g/m MTX as CSF levels plateau at this dose.

Triglyceride levels and risk of type 2 diabetes mellitus: a longitudinal large study.

The relationship between triglyceridemia and diabetes mellitus remains unclear. This study evaluated the risk of diabetes and impaired fasting glucose associated with a wide range of triglyceride levels. A longitudinal retrospective study was carried out employing data from a screening center between the years 2000 and 2012. Inclusion criteria were absence of diabetes at baseline and attendance at the center at least twice over a 5-year period. Participants were divided by fasting blood glucose level (normal/impaired) at the first visit. A total of 5085 participants were eligible for the study. Of the 4164 normoglycemic participants at baseline, 40 (0.96%) had diabetes and 998 (24%) had impaired fasting glucose by the end of the study. On stepwise logistic regression analysis, every 10 mg/dL increase in triglyceride level significantly increased the risk of diabetes by 4% and of impaired fasting glucose by 2% (p<0.001). This association held true even when rising triglyceride levels remained within the accepted normal range (<150 mg/dL, p<0.001). Sustained increments in serum triglyceride level, even within the accepted normal range, are an independent risk factor for diabetes mellitus and impaired fasting glucose in normoglycemic participants.

Relationship Between Body Mass Index and Intraocular Pressure in Men and Women: A Population-based Study.

PURPOSE: To assess the possibility of a relationship between body mass index (BMI) and intraocular pressure (IOP) in both men and women. MATERIALS AND METHODS: A retrospective cross-sectional analysis of a database from a screening center in Israel which assessed 18,575 subjects, within an age range 20 to 80 years. RESULTS: The mean (±SD) age of the study sample was 46 (±10) years, 68% were men. A positive linear correlation was found between BMI and IOP for both men and women (r=0.166, P<0.0001 in men and r=0.202, P<0.0001 in women). Mean (95% confidence interval) IOP in subjects with BMI<25 kg/m(2) was 12.8 mm Hg (range, 12.7 to 12.9 mm Hg) and increased significantly to 13.4 (range, 13.3 to 13.5 mm Hg); 13.9 mm Hg (range, 13.8 to14.0 mm Hg), and 14.3 mm Hg (range, 14.1 to 14.5 mm Hg) for BMI subcategories 25 to 29.9, 30 to 35, and >35 kg/m(2), respectively (P<0.0001). These differences remained significant after multivariate adjustment for age, hypertension, and diabetes mellitus (P<0.0001). Similar multivariate adjustments showed that the coefficient factors for BMI (95% confidence interval) affecting IOP were 0.087 (range, 0.076 to 0.098) P<0.0001 and 0.070 (range, 0.058 to 0.082) P<0.0001 for men and women respectively, indicating that in men and women, the changes in IOP associated with a 10 kg/m(2) increase in BMI were 0.9 and 0.7 mm Hg, respectively. Subjects with abnormal BMI compared with subjects with normal BMI had increased odds ratio of having IOP≥18 mm Hg after adjusting for confounding factors (P<0.001). CONCLUSIONS: This study shows that obesity is an independent risk factor for increasing IOP in both men and women. We consider this finding particularly pertinent in the context of the current obesity epidemic.

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.