Robin Mukherjee - Academia.edu (original) (raw)

Papers by Robin Mukherjee

Research paper thumbnail of Beurteilung der wirkung von eplerenon in der subgruppe der EPHESUS-patienten mit einer linksventrikulären auswurffraktion ≤30% zu studienbeginn

Research paper thumbnail of Open-Label Follow-Up of the PEPITES Study (PEOPLE) to Evaluate the Long-Term Efficacy and Safety of Epicutaneous Peanut Immunotherapy in Peanut-Allergic Children

Journal of Allergy and Clinical Immunology, 2020

Carolina at Chapel H. RATIONALE: Though peanut sublingual immunotherapy (SLIT) is a potentially e... more Carolina at Chapel H. RATIONALE: Though peanut sublingual immunotherapy (SLIT) is a potentially efficacious treatment for patients with peanut allergy, its use is limited by adverse events, which are understudied. METHODS: We conducted a retrospective pooled cohort analysis from two peanut SLIT trials to determine characteristics and rates of AEs. We abstracted in-home AEs from daily symptom diaries. We characterized events that were at least possibly related to SLIT dosing. Bivariate analyses were performed to determine differences in rates of AEs by season and other patient characteristics. RESULTS: Of 101 participants (mean age 6.9 years) enrolled in 2 SLIT trials (mean duration 4.6 years), 86% experienced a total of 6377 possiblyor likely-related AEs associated with SLIT dosing; 14 participants (14%) accounted for 75% of all AEs. Ninety-six percent of AEs were mild; 2 reactions (0.03%) were severe. Systemic reactions accounted for 3.7% of AEs in 34% of participants. Most AEs involved transient oropharyngeal symptoms (84%), which occurred in 69% of participants. Those with AR had more frequent AEs, with increased AEs in June, July, and August (1247 in those with AR vs. 772 in those without AR, p<0.001). No epinephrine was administered. Antihistamines were used in 4% of AEs by 43% of participants. CONCLUSIONS: While peanut SLIT is associated with frequent AEs, nearly all are graded mild and most symptoms are limited to the oropharynx. Those with allergic rhinitis are at increased risk for AEs, particularly during the summer months and possibly implicates crossreactive pollen sensitization as one mechanism for AEs in peanut SLIT.

Research paper thumbnail of Results of the REALISE (Real-life Use and Safety of EPIT) Study: A Multicenter Blinded Randomized Controlled Trial Investigating the Safety of Epicutaneous Immunotherapy for Peanut Allergy in Peanut-Allergic Children

Journal of Allergy and Clinical Immunology, 2020

Indoor air quality (IAQ) is a major risk factor for the development and aggravation of asthma. Pr... more Indoor air quality (IAQ) is a major risk factor for the development and aggravation of asthma. Preschool children in developed countries spend most of their time indoors and often in child care centers where IAQ is unregulated. METHODS: 18 small and 18 large Milwaukee County, Wisconsin child care centers were recruited and randomized in a stepped-wedge protocol to an early or delayed provision of a Greener Cleaning educational program. Nursing students, community health workers or asthma coalition members taught the curriculum and administered a survey regarding acceptance of the programming and also to administrators regarding cleaning behaviors. An internet-enabled consumer-grade multi-variable IAQ monitor was installed in the centers to establish baseline and post-intervention IAQ. RESULTS: 31 childcare centers completed the study. Baseline weekday mean PM2.5 during occupancy was 11.7 and 24.5, tVOC 354 and 259 ppb, CO2 was ;1280 and ;938 ppm, and humidity was 44.5% and 46.5% in family and group licensed facilities respectively, with wide variance. Observed smoke, mold, perfume, spray air-freshener and bleach use were common. Rodent infestation, ammonia use and carpet cleaning were rare. Non-HEPA vacuuming was common. The educational program was well accepted by staff. Negligible improvements of IAQ followed the educational intervention overall. Time (family) and administrator support (group) were primary reported obstacles to cleaning behavior change. CONCLUSIONS: Exceedences of threshold tVOC and CO2 concentrations were common, particularly in residential centers. A brief educational intervention did not appear sufficient to alter cleaning behaviors. Opportunities for improved ventilation and VOC reduction were noted.

Research paper thumbnail of 55 Eplerenone benefit in patients with elevated baseline heart rate in the EPHESUS trial

European Journal of Heart Failure Supplements, 2005

Research paper thumbnail of 353 Eplerenone benefit at 30 days in high-risk subgroups in the EPHESUS trial

European Journal of Heart Failure Supplements, 2005

Background: Hyponatremia (HYPO) is a known predictor of mortality in pts hospitalized for worseni... more Background: Hyponatremia (HYPO) is a known predictor of mortality in pts hospitalized for worsening heart failure. However, it is not known whether ITYPO is only a marker of disease severity or whether improving sodium levels in hyponatremic patients would lead to improved outcomes. We studied the relationship between changes in serum sodium during hospitalization and mortality in hyponatremic patients admitted for decompensated heart failure (HI:) in a post-hoc analysis of the ACTIV in CHF trial. Methods: The ACTIV in CIIF trial randomized 319 pts with systolic dysfunction hospitalized for worsening HI: to receive placebo or 30, 60, or 90 mg tolvaptan, a novel vasopressin V2 receptor antagonist. Cox proportional hazards regression-analysis was used to explore the relationship between ITYPO (Na+<136 mEq/L) at baseline and improvements >2 mEq/L in serum sodium by hospital discharge, and mortality within sixty days. Results: Mild to moderate HYPO was observed in 69 patients (21.6%), with median (IR) levels of 133 (131, 134) mEq/L at baseline. After adjustment for other covariates, HYPO was a highly statistically significant predictor of mortality at 60 days post hospital discharge (p<0.005). At hospital discharge, 45 out of 69 pts (65.2%) had improvements in serum sodium levels >2 mEq/L. These pts had a median (IR) baseline sodium of 133 (131, 134) mEq/L, as compared with 133 (132, 135) mEq/L in those who did not improve by hospital discharge. Pts with a serum sodium improvement at discharge had a mortality rate of 15.6% at 60 days post discharge, as compared with a 30.4% mortality rate in those showing no improvement (p=0.0842, log-rank). After adjustment for other covariates, change in serum sodium within the hospitalization period was a statistically significant predictor of mortality at 60 days post hospital discharge (p<0.0269). Conclusions: Hyponatremia appears to be a modifiable therapeutic target and not purely a marker of disease severity. Improvements in serum sodium levels during hospitalization were associated with improved mortality at 60 days. Prospective studies are necessary in this population to assess if therapies aimed at increasing serum sodium will result in improved outcome.

Research paper thumbnail of 56 The impact of statin therapy on the efficacy of eplerenone

European Journal of Heart Failure Supplements, 2005

Research paper thumbnail of Similar effect of losartan/hydrochlorothiazide therapy for black and non-black patients with severe hypertension

American Journal of Hypertension, 2004

morning DBP evaluated by ABPM, in connection with the resting/ inactivity period: Group A: Ͼ5% MD... more morning DBP evaluated by ABPM, in connection with the resting/ inactivity period: Group A: Ͼ5% MDBPD (Ͼ 5% morning diastolic blood pressure decrease); Group B: Ͼ5% morning DBP increase. Group C: NON-A, NON-B. Cardiovascular risk (CVR): FRAMINGHAM and PROCAM. PAI-1(ng/ml): MENARINI ELISA. Glycemia, creatinin, HDL-cholesterol, LDL-cholesterol, total cholesterol, and triglycerides, by Hitachi autoanalyzer. Statistical analysis: t-student, chi-square, ANOVA and Multivariate Analysis. Results: 1. The prevalence of MDBPD was of nϭ21 (11.1%). 2. The group with MDBPD was of younger age and showed lower CVR. 3-The average SBP was lower in Group A (p Ͻ 0.01). 4-PAI-1 levels were lower in a significant and independent way in the multivariate analysis (31,91 ϩϪ5,4 in group A vs 46,12 ϩϪ 3,79 in group B and 46,18 ϩϪ 1,81 in group C) Conclusions: 1-The MDBPD is a phenomenon present in the younger population, with lower CVR, but its protective effect on the endothelium seems to be an independent factor. 2-The above-mentioned suggests the introduction of this new concept, as a prognostic marker, in ABPM analysis.

Research paper thumbnail of MP388RESOLUTION and Recurrence of Hyperkalemia in Adults in the Uk

Nephrology Dialysis Transplantation, 2017

Research paper thumbnail of MP380CLINICAL Outcomes Associated with Hyperkalemia in Adults in the Uk

Nephrology Dialysis Transplantation, 2017

Patients with chronic kidney disease (CKD) have increased risk of urinary tract infections (UTIs)... more Patients with chronic kidney disease (CKD) have increased risk of urinary tract infections (UTIs). The recent emergence of multidrugresistant (MDR) uropathogens is an alarming public health issue which complicates therapeutic strategies for UTIs. The present study aimed to determine the asssociation between CKD and MDR among inpatients with UTI. METHODS: We prospectively assessed the urine samples obtained from all inpatients suspected of having a UTI, admited in County Hospital Timisoara, between January 2012 and January 2013. Demographic variables of these patients, uropathogens and their antimicrobial susceptibilities were evaluated. Isolated bacteria were identified by standard tests, and antibiotic susceptibility was determined by disk diffusion method. An MDR UTI was defined as an infection caused by an uropathogen resistant to three or more classes of drugs. CKD was defined acording to the KDIGO guideline. RESULTS: During the follow-up period, from the 4328 samples analyzed, 1135 (26.22%) were cultures-positive for bacterial infection. The most frequently isolated microorganisms were Escherichia coli (61.32%), Klebsiella spp. (22.02%), Proteus mirabillis (8.01%), Pseudomonas aeruginosa (4.41%). Three hundred forty nine (30.74%) isolates were MDR. Pseudomonas aeruginosa presented the highest percentage of MDR isolates (60%). Univariate analysis showed an increased risk of MDR in males (odds ratio [OR]=3.16, p<0.001), in patients with diabetes mellitus (OR=1.65, p=0.0002), in chronic obstructive pulmonary disease (OR=5.09, p<0.001), in patients with urinary catheter before admission (OR=2.76, p<0.001), in patients with previous UTIs (OR=2.20, p<0.001) and in patients with CKD (OR=2.75, p<0.001). In multivariable analysis, CKD remained an independent predictor for MDR (OR=3.04, 95%CI:2.23 to 4.13, p<0.001). CONCLUSIONS: A high prevalence of MDR in bacterial uropathogens was observed. Particularly, resistance patterns were alarmingly higher for Pseudomonas. CKD turned out to be an independent predictor for UTI with MDR bacteria.

Research paper thumbnail of SP321HEALTH Care Resource Utilization Following Hyperkalemia in Adults in the Uk

Nephrology Dialysis Transplantation, 2017

disease (ESRD), there are scarce data on the impact of pre-ESRD serum calcium levels on post-ESRD... more disease (ESRD), there are scarce data on the impact of pre-ESRD serum calcium levels on post-ESRD mortality. METHODS: Among 21,826 US veterans who transitioned to dialysis between April 2009 and March 2014, we examined the association of albumin-corrected serum calcium (cSCa) levels averaged over the last 6 months before dialysis initiation (i.e., pre-ESRD or 'prelude' period) with post-ESRD all-cause mortality using Cox regression with adjustment for demographics, comorbidities, medications, BMI, eGFR, and serum albumin. We also calculated the rate of cSCa decline using mixed-effects model among 16,349 patients with 2 measurements during their prelude 1 year, where the last measurement had to be in the prelude 6-month period and at least 90 days apart from the first one, and then examined its mortality risk stratified by baseline cSCa values. RESULTS: Mean concentrations and median rate of decline of cSCa were 9.3 6 0.7 mg/ dL and-0.15 (interquartile range,-0.39 to 0.07) mg/dL/year, respectively. A total of 9,596 patients died during follow up with an incidence rate of 23.1 per 100 patient-years. There was an independent linear association between higher cSCa with higher mortality (P trend <0.001). This association was modified by active vitamin D (AVD) use (P interaction <0.001), but not by calcium supplements. A trend towards higher mortality across higher cSCa was observed among both AVD users and non-users (P trend =0.024 and <0.001, respectively), but AVD use substantially attenuated the mortality risk associated with cSCa 9.0 mg/dL (Figure 1).The relationship between the rate of cSCa decline and mortality was not significant, irrespective of baseline cSCa levels (Figure 2). CONCLUSIONS: Lower pre-ESRD cSCa levels were linearly associated with better post-ESRD survival among US veterans, and AVD use attenuated the mortality risk associated with higher cSCa. Further studies are needed to determine if correcting hypocalcemia is beneficial or harmful and which intervention is preferred when indicated among patients with late-stage CKD.

Research paper thumbnail of MP370INCIDENCE and Risk Factors for Hyperkalemia in Adults in the Uk

Nephrology Dialysis Transplantation, 2017

Research paper thumbnail of Hyzaar as a first line agent in the treatment of severe hypertensive patients

American Journal of Hypertension, 2002

sive drug) with weekly observations. During the checkup visits, blood pressure was measured with ... more sive drug) with weekly observations. During the checkup visits, blood pressure was measured with Dinamap R , and blood samples were obtained to measured serum levels of Hcys and the folate according to the Fluorescence Polarizing Immunoassay (FPIA) technique (first week), and 1 mg of folic acid was administered oral during eight week and at the end, serum levels of Hcys were determined. Results: There were a statistical difference between Hcys and intake of fortificated folic acid in patients with High Blood Pressure. A value of pϭ0,000 was obtained (tϭ8,327). Conclusions: Fortified Folic Acid reduces serum levels of Homocysteine in Hypertensive Patients. Table 1 SBP ϭ Sistolic Blood Pressure, DBP ϭ Diastolic Blood Pressure. SD ϭ Standard Deviation. Hcys ϭ Homocysteine

Research paper thumbnail of Randomized, double-blind, multicenter, placebo-controlled study evaluating the effect of aldosterone antagonism with eplerenone on ventricular remodeling in patients with mild-to-moderate heart failure and left ventricular systolic dysfunction

Circulation. Heart failure, 2010

Aldosterone antagonism has been studied in patients with advanced heart failure (HF) and also in ... more Aldosterone antagonism has been studied in patients with advanced heart failure (HF) and also in patients with post-myocardial infarction and left ventricular (LV) dysfunction with HF symptoms. Few data are available on effects of aldosterone antagonism in patients with mild-to-moderate HF. In a multicenter, randomized, double-blind, placebo-controlled study in patients with mild-to-moderate HF and LV systolic dysfunction, patients with New York Heart Association class II/III HF and LV ejection fraction (EF) < or =35% were randomly assigned to receive eplerenone 50 mg/d versus placebo in addition to contemporary background therapy. Quantitative radionuclide ventriculograms to assess LV volumes and ejection fraction were performed at baseline and again after 9 months of double-blind treatment and were analyzed in a central core laboratory, blinded to treatment. The primary efficacy analysis was the between-group comparison of the change in LV end-diastolic volume index. Secondary ...

Research paper thumbnail of LV and myocyte structure and function after early recovery from tachycardia-induced cardiomyopathy

The American journal of physiology, 1995

Left ventricular (LV) function and mass were measured in six conscious dogs at weekly intervals d... more Left ventricular (LV) function and mass were measured in six conscious dogs at weekly intervals during the progression of tachycardia-induced dilated cardiomyopathy (DCM) and during a 1-mo recovery period from DCM (post-DCM). LV end-diastolic volume and LV wall stress increased and LV ejection fraction decreased with each week of pacing. Despite the increased LV wall stress, LV mass did not change during the progression of tachycardia DCM. One week post-DCM resulted in an improved LV ejection fraction and normalization of neurohormonal profiles. However, 1 wk post-DCM was accompanied by a 26% increase in LV mass and persistent LV chamber dilation. Isolated myocyte function was examined and compared with that in six normal control dogs. Myocyte percent and myocyte velocity of shortening were 19 and 32% lower, respectively, in the post-DCM group compared with controls. Thus termination of the tachycardia subsequent to the development of DCM resulted in persistent LV chamber dilation a...

Research paper thumbnail of Eplerenone Reduces Mortality 30 Days After Randomization Following Acute Myocardial Infarction in Patients With Left Ventricular Systolic Dysfunction and Heart Failure

Journal of the American College of Cardiology, 2005

OBJECTIVES This study sought to assess the impact of the selective aldosterone blocker eplerenone... more OBJECTIVES This study sought to assess the impact of the selective aldosterone blocker eplerenone on mortality 30 days after randomization in patients after acute myocardial infarction (AMI) with a left ventricular ejection fraction (LVEF) Յ40% and clinical signs of heart failure. BACKGROUND In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone reduced all-cause mortality by 15% (p ϭ 0.008) over a mean follow-up of 16 months when used with standard therapy in patients after AMI with an LVEF Յ40% and clinical signs of heart failure. METHODS We analyzed the effect of eplerenone 25 mg/day initiated 3 to 14 days after AMI (mean, 7.3 days) on the co-primary end points of time to death from any cause and the composite end point of time to death from cardiovascular (CV) causes or hospitalization for CV events, and the secondary end points of CV mortality, sudden cardiac death, and fatal/nonfatal hospitalization for heart failure, after 30 days of therapy in the EPHESUS trial. RESULTS At 30 days after randomization, eplerenone reduced the risk of all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone and placebo-treated patients, respectively; p ϭ 0.004) and reduced the risk of CV mortality/CV hospitalization by 13% (8.6% vs. 9.9% in eplerenone and placebo-treated patients, respectively; p ϭ 0.074). Eplerenone also reduced the risk of CV mortality by 32% (p ϭ 0.003) and the risk of sudden cardiac death by 37% (p ϭ 0.051). CONCLUSIONS Eplerenone 25 mg/day significantly reduced all-cause mortality 30 days after randomization (when initiated at a mean of 7.3 days after AMI) in addition to conventional therapy in patients with an LVEF Յ40% and signs of heart failure. Based on its early survival benefit, eplerenone should be administered in the hospital after AMI.

Research paper thumbnail of Combination Angiotensin Receptor Blocker/Hydrochlorothiazide as Initial Therapy in the Treatment of Patients With Severe Hypertension

The Journal of Clinical Hypertension, 2004

Research paper thumbnail of Effect of Neurohormones, Cytokines, and Collagen Markers on the Risk of All-Cause Mortality: Results from the EPHESUS Trial

Journal of Cardiac Failure, 2005

Research paper thumbnail of Early Intensive vs a Delayed Conservative Simvastatin Strategy in Patients With Acute Coronary Syndromes

JAMA, 2004

ONG-TERM THERAPY WITH STATIN drugs has been shown to reduce the risk for death, myocardial infarc... more ONG-TERM THERAPY WITH STATIN drugs has been shown to reduce the risk for death, myocardial infarction (MI), and stroke among patients with established coronary artery disease, even when low-density lipoprotein (LDL) cholesterol levels are not elevated. 1-4 Most of the landmark clinical trials evaluating statins for secondary prevention enrolled patients who were stable for at least several months after an index acute coronary syndrome (ACS) event. 1-3 More recently, 2 ran-domized controlled trials have evaluated earlier initiation of statin therapy following an ACS event and have noted a corresponding early reduction in major cardiovascular events. 5,6

Research paper thumbnail of Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction ≤30%

European Journal of Heart Failure, 2006

Aims: Because of the prognostic importance of LV dysfunction following an AMI and the increasing ... more Aims: Because of the prognostic importance of LV dysfunction following an AMI and the increasing use of electrical and/or mechanical interventions in patients with LV systolic dysfunction, this retrospective analysis of EPHESUS patients with LVEF 30% at baseline was conducted to determine the value of eplerenone in this setting. Methods and results: In EPHESUS, 6632 patients with LVEF 40% and clinical heart failure (HF) post-AMI who were receiving standard therapy were randomized to eplerenone 25 mg/day titrated to 50 mg/day or placebo for a mean follow-up of 16 months. Treatment with eplerenone in the subgroup of patients with LVEF 30% (N = 2106) resulted in relative risk reductions of 21% versus placebo in both allcause mortality (P = 0.012) and cardiovascular (CV) mortality/CV hospitalization (P = 0.001), and 23% for CV mortality (P = 0.008). The relative risk of sudden cardiac death (SCD) was reduced 33% (P = 0.01) and HF mortality/HF hospitalization was reduced 25% (P = 0.005) with eplerenone compared with placebo. Within 30 days of randomization, eplerenone resulted in relative risk reductions of 43% for all-cause mortality (P = 0.002), 29% for CV mortality/CV hospitalization (P = 0.006), and 58% for SCD (P = 0.008). Conclusions: Treatment with eplerenone plus standard therapy in patients with post-AMI HF and LVEF 30% provided significant incremental benefits in reducing both early and late mortality and morbidity.

Research paper thumbnail of Selective Aldosterone Blockade with Eplerenone Reduces Albuminuria in Patients with Type 2 Diabetes

Clinical Journal of the American Society of Nephrology, 2006

Previous studies have shown that the selective aldosterone blocker eplerenone, in doses of up to ... more Previous studies have shown that the selective aldosterone blocker eplerenone, in doses of up to 200 mg/d, reduces albuminuria in patients with type 2 diabetes. This study was conducted to ascertain whether lower doses of eplerenone (50 or 100 mg/d) co-administered with the angiotensin-converting enzyme (ACE) inhibitor enalapril would produce a similar antialbuminuric effect while obviating the hyperkalemia observed previously. After open-label run-in with enalapril 20 mg/d, patients with diabetes and a urinary albumin:creatinine ratio (UACR) >50 mg/g were randomly assigned to receive enalapril plus one of three double-blind daily treatments for 12 wk: placebo, eplerenone 50 mg (EPL50), or eplerenone 100 mg (EPL100). After week 4, amlodipine 2.5 to 10 mg/d was allowed for BP control (systolic/diastolic BP < 130/80 mmHg). The primary study end points were the percentage change from baseline at week 12 in UACR and the incidence of hyperkalemia. Secondary end points included percentage changes from baseline in UACR at weeks 4 and 8 and changes from baseline in systolic and diastolic BP. Treatment with EPL50 or EPL100 but not placebo significantly reduced albuminuria from baseline. By week 12, UACR was reduced by 7.4% in the placebo group, by 41.0% in the EPL50 group, and by 48.4% in the EPL100 group (both eplerenone groups, P < 0.001 versus placebo). The incidences of sustained and severe hyperkalemia were not significantly different in any of the three treatment arms and did not differ on the basis of quartile of estimated GFR (all NS). For the secondary end points, both eplerenone treatment groups significantly reduced albuminuria from baseline as early as week 4 (P < 0.001), whereas placebo treatment (including enalapril) did not result in any significant decreases in UACR. Systolic BP decreased significantly in all treatment groups at all time points, but, generally, all treatment groups experienced similar decreases in BP. Co-administration of EPL50 or EPL100 with an ACE inhibitor as compared with an ACE inhibitor alone significantly reduces albuminuria in patients with diabetes without producing significant increases in hyperkalemia.

Research paper thumbnail of Beurteilung der wirkung von eplerenon in der subgruppe der EPHESUS-patienten mit einer linksventrikulären auswurffraktion ≤30% zu studienbeginn

Research paper thumbnail of Open-Label Follow-Up of the PEPITES Study (PEOPLE) to Evaluate the Long-Term Efficacy and Safety of Epicutaneous Peanut Immunotherapy in Peanut-Allergic Children

Journal of Allergy and Clinical Immunology, 2020

Carolina at Chapel H. RATIONALE: Though peanut sublingual immunotherapy (SLIT) is a potentially e... more Carolina at Chapel H. RATIONALE: Though peanut sublingual immunotherapy (SLIT) is a potentially efficacious treatment for patients with peanut allergy, its use is limited by adverse events, which are understudied. METHODS: We conducted a retrospective pooled cohort analysis from two peanut SLIT trials to determine characteristics and rates of AEs. We abstracted in-home AEs from daily symptom diaries. We characterized events that were at least possibly related to SLIT dosing. Bivariate analyses were performed to determine differences in rates of AEs by season and other patient characteristics. RESULTS: Of 101 participants (mean age 6.9 years) enrolled in 2 SLIT trials (mean duration 4.6 years), 86% experienced a total of 6377 possiblyor likely-related AEs associated with SLIT dosing; 14 participants (14%) accounted for 75% of all AEs. Ninety-six percent of AEs were mild; 2 reactions (0.03%) were severe. Systemic reactions accounted for 3.7% of AEs in 34% of participants. Most AEs involved transient oropharyngeal symptoms (84%), which occurred in 69% of participants. Those with AR had more frequent AEs, with increased AEs in June, July, and August (1247 in those with AR vs. 772 in those without AR, p<0.001). No epinephrine was administered. Antihistamines were used in 4% of AEs by 43% of participants. CONCLUSIONS: While peanut SLIT is associated with frequent AEs, nearly all are graded mild and most symptoms are limited to the oropharynx. Those with allergic rhinitis are at increased risk for AEs, particularly during the summer months and possibly implicates crossreactive pollen sensitization as one mechanism for AEs in peanut SLIT.

Research paper thumbnail of Results of the REALISE (Real-life Use and Safety of EPIT) Study: A Multicenter Blinded Randomized Controlled Trial Investigating the Safety of Epicutaneous Immunotherapy for Peanut Allergy in Peanut-Allergic Children

Journal of Allergy and Clinical Immunology, 2020

Indoor air quality (IAQ) is a major risk factor for the development and aggravation of asthma. Pr... more Indoor air quality (IAQ) is a major risk factor for the development and aggravation of asthma. Preschool children in developed countries spend most of their time indoors and often in child care centers where IAQ is unregulated. METHODS: 18 small and 18 large Milwaukee County, Wisconsin child care centers were recruited and randomized in a stepped-wedge protocol to an early or delayed provision of a Greener Cleaning educational program. Nursing students, community health workers or asthma coalition members taught the curriculum and administered a survey regarding acceptance of the programming and also to administrators regarding cleaning behaviors. An internet-enabled consumer-grade multi-variable IAQ monitor was installed in the centers to establish baseline and post-intervention IAQ. RESULTS: 31 childcare centers completed the study. Baseline weekday mean PM2.5 during occupancy was 11.7 and 24.5, tVOC 354 and 259 ppb, CO2 was ;1280 and ;938 ppm, and humidity was 44.5% and 46.5% in family and group licensed facilities respectively, with wide variance. Observed smoke, mold, perfume, spray air-freshener and bleach use were common. Rodent infestation, ammonia use and carpet cleaning were rare. Non-HEPA vacuuming was common. The educational program was well accepted by staff. Negligible improvements of IAQ followed the educational intervention overall. Time (family) and administrator support (group) were primary reported obstacles to cleaning behavior change. CONCLUSIONS: Exceedences of threshold tVOC and CO2 concentrations were common, particularly in residential centers. A brief educational intervention did not appear sufficient to alter cleaning behaviors. Opportunities for improved ventilation and VOC reduction were noted.

Research paper thumbnail of 55 Eplerenone benefit in patients with elevated baseline heart rate in the EPHESUS trial

European Journal of Heart Failure Supplements, 2005

Research paper thumbnail of 353 Eplerenone benefit at 30 days in high-risk subgroups in the EPHESUS trial

European Journal of Heart Failure Supplements, 2005

Background: Hyponatremia (HYPO) is a known predictor of mortality in pts hospitalized for worseni... more Background: Hyponatremia (HYPO) is a known predictor of mortality in pts hospitalized for worsening heart failure. However, it is not known whether ITYPO is only a marker of disease severity or whether improving sodium levels in hyponatremic patients would lead to improved outcomes. We studied the relationship between changes in serum sodium during hospitalization and mortality in hyponatremic patients admitted for decompensated heart failure (HI:) in a post-hoc analysis of the ACTIV in CHF trial. Methods: The ACTIV in CIIF trial randomized 319 pts with systolic dysfunction hospitalized for worsening HI: to receive placebo or 30, 60, or 90 mg tolvaptan, a novel vasopressin V2 receptor antagonist. Cox proportional hazards regression-analysis was used to explore the relationship between ITYPO (Na+<136 mEq/L) at baseline and improvements >2 mEq/L in serum sodium by hospital discharge, and mortality within sixty days. Results: Mild to moderate HYPO was observed in 69 patients (21.6%), with median (IR) levels of 133 (131, 134) mEq/L at baseline. After adjustment for other covariates, HYPO was a highly statistically significant predictor of mortality at 60 days post hospital discharge (p<0.005). At hospital discharge, 45 out of 69 pts (65.2%) had improvements in serum sodium levels >2 mEq/L. These pts had a median (IR) baseline sodium of 133 (131, 134) mEq/L, as compared with 133 (132, 135) mEq/L in those who did not improve by hospital discharge. Pts with a serum sodium improvement at discharge had a mortality rate of 15.6% at 60 days post discharge, as compared with a 30.4% mortality rate in those showing no improvement (p=0.0842, log-rank). After adjustment for other covariates, change in serum sodium within the hospitalization period was a statistically significant predictor of mortality at 60 days post hospital discharge (p<0.0269). Conclusions: Hyponatremia appears to be a modifiable therapeutic target and not purely a marker of disease severity. Improvements in serum sodium levels during hospitalization were associated with improved mortality at 60 days. Prospective studies are necessary in this population to assess if therapies aimed at increasing serum sodium will result in improved outcome.

Research paper thumbnail of 56 The impact of statin therapy on the efficacy of eplerenone

European Journal of Heart Failure Supplements, 2005

Research paper thumbnail of Similar effect of losartan/hydrochlorothiazide therapy for black and non-black patients with severe hypertension

American Journal of Hypertension, 2004

morning DBP evaluated by ABPM, in connection with the resting/ inactivity period: Group A: Ͼ5% MD... more morning DBP evaluated by ABPM, in connection with the resting/ inactivity period: Group A: Ͼ5% MDBPD (Ͼ 5% morning diastolic blood pressure decrease); Group B: Ͼ5% morning DBP increase. Group C: NON-A, NON-B. Cardiovascular risk (CVR): FRAMINGHAM and PROCAM. PAI-1(ng/ml): MENARINI ELISA. Glycemia, creatinin, HDL-cholesterol, LDL-cholesterol, total cholesterol, and triglycerides, by Hitachi autoanalyzer. Statistical analysis: t-student, chi-square, ANOVA and Multivariate Analysis. Results: 1. The prevalence of MDBPD was of nϭ21 (11.1%). 2. The group with MDBPD was of younger age and showed lower CVR. 3-The average SBP was lower in Group A (p Ͻ 0.01). 4-PAI-1 levels were lower in a significant and independent way in the multivariate analysis (31,91 ϩϪ5,4 in group A vs 46,12 ϩϪ 3,79 in group B and 46,18 ϩϪ 1,81 in group C) Conclusions: 1-The MDBPD is a phenomenon present in the younger population, with lower CVR, but its protective effect on the endothelium seems to be an independent factor. 2-The above-mentioned suggests the introduction of this new concept, as a prognostic marker, in ABPM analysis.

Research paper thumbnail of MP388RESOLUTION and Recurrence of Hyperkalemia in Adults in the Uk

Nephrology Dialysis Transplantation, 2017

Research paper thumbnail of MP380CLINICAL Outcomes Associated with Hyperkalemia in Adults in the Uk

Nephrology Dialysis Transplantation, 2017

Patients with chronic kidney disease (CKD) have increased risk of urinary tract infections (UTIs)... more Patients with chronic kidney disease (CKD) have increased risk of urinary tract infections (UTIs). The recent emergence of multidrugresistant (MDR) uropathogens is an alarming public health issue which complicates therapeutic strategies for UTIs. The present study aimed to determine the asssociation between CKD and MDR among inpatients with UTI. METHODS: We prospectively assessed the urine samples obtained from all inpatients suspected of having a UTI, admited in County Hospital Timisoara, between January 2012 and January 2013. Demographic variables of these patients, uropathogens and their antimicrobial susceptibilities were evaluated. Isolated bacteria were identified by standard tests, and antibiotic susceptibility was determined by disk diffusion method. An MDR UTI was defined as an infection caused by an uropathogen resistant to three or more classes of drugs. CKD was defined acording to the KDIGO guideline. RESULTS: During the follow-up period, from the 4328 samples analyzed, 1135 (26.22%) were cultures-positive for bacterial infection. The most frequently isolated microorganisms were Escherichia coli (61.32%), Klebsiella spp. (22.02%), Proteus mirabillis (8.01%), Pseudomonas aeruginosa (4.41%). Three hundred forty nine (30.74%) isolates were MDR. Pseudomonas aeruginosa presented the highest percentage of MDR isolates (60%). Univariate analysis showed an increased risk of MDR in males (odds ratio [OR]=3.16, p<0.001), in patients with diabetes mellitus (OR=1.65, p=0.0002), in chronic obstructive pulmonary disease (OR=5.09, p<0.001), in patients with urinary catheter before admission (OR=2.76, p<0.001), in patients with previous UTIs (OR=2.20, p<0.001) and in patients with CKD (OR=2.75, p<0.001). In multivariable analysis, CKD remained an independent predictor for MDR (OR=3.04, 95%CI:2.23 to 4.13, p<0.001). CONCLUSIONS: A high prevalence of MDR in bacterial uropathogens was observed. Particularly, resistance patterns were alarmingly higher for Pseudomonas. CKD turned out to be an independent predictor for UTI with MDR bacteria.

Research paper thumbnail of SP321HEALTH Care Resource Utilization Following Hyperkalemia in Adults in the Uk

Nephrology Dialysis Transplantation, 2017

disease (ESRD), there are scarce data on the impact of pre-ESRD serum calcium levels on post-ESRD... more disease (ESRD), there are scarce data on the impact of pre-ESRD serum calcium levels on post-ESRD mortality. METHODS: Among 21,826 US veterans who transitioned to dialysis between April 2009 and March 2014, we examined the association of albumin-corrected serum calcium (cSCa) levels averaged over the last 6 months before dialysis initiation (i.e., pre-ESRD or 'prelude' period) with post-ESRD all-cause mortality using Cox regression with adjustment for demographics, comorbidities, medications, BMI, eGFR, and serum albumin. We also calculated the rate of cSCa decline using mixed-effects model among 16,349 patients with 2 measurements during their prelude 1 year, where the last measurement had to be in the prelude 6-month period and at least 90 days apart from the first one, and then examined its mortality risk stratified by baseline cSCa values. RESULTS: Mean concentrations and median rate of decline of cSCa were 9.3 6 0.7 mg/ dL and-0.15 (interquartile range,-0.39 to 0.07) mg/dL/year, respectively. A total of 9,596 patients died during follow up with an incidence rate of 23.1 per 100 patient-years. There was an independent linear association between higher cSCa with higher mortality (P trend <0.001). This association was modified by active vitamin D (AVD) use (P interaction <0.001), but not by calcium supplements. A trend towards higher mortality across higher cSCa was observed among both AVD users and non-users (P trend =0.024 and <0.001, respectively), but AVD use substantially attenuated the mortality risk associated with cSCa 9.0 mg/dL (Figure 1).The relationship between the rate of cSCa decline and mortality was not significant, irrespective of baseline cSCa levels (Figure 2). CONCLUSIONS: Lower pre-ESRD cSCa levels were linearly associated with better post-ESRD survival among US veterans, and AVD use attenuated the mortality risk associated with higher cSCa. Further studies are needed to determine if correcting hypocalcemia is beneficial or harmful and which intervention is preferred when indicated among patients with late-stage CKD.

Research paper thumbnail of MP370INCIDENCE and Risk Factors for Hyperkalemia in Adults in the Uk

Nephrology Dialysis Transplantation, 2017

Research paper thumbnail of Hyzaar as a first line agent in the treatment of severe hypertensive patients

American Journal of Hypertension, 2002

sive drug) with weekly observations. During the checkup visits, blood pressure was measured with ... more sive drug) with weekly observations. During the checkup visits, blood pressure was measured with Dinamap R , and blood samples were obtained to measured serum levels of Hcys and the folate according to the Fluorescence Polarizing Immunoassay (FPIA) technique (first week), and 1 mg of folic acid was administered oral during eight week and at the end, serum levels of Hcys were determined. Results: There were a statistical difference between Hcys and intake of fortificated folic acid in patients with High Blood Pressure. A value of pϭ0,000 was obtained (tϭ8,327). Conclusions: Fortified Folic Acid reduces serum levels of Homocysteine in Hypertensive Patients. Table 1 SBP ϭ Sistolic Blood Pressure, DBP ϭ Diastolic Blood Pressure. SD ϭ Standard Deviation. Hcys ϭ Homocysteine

Research paper thumbnail of Randomized, double-blind, multicenter, placebo-controlled study evaluating the effect of aldosterone antagonism with eplerenone on ventricular remodeling in patients with mild-to-moderate heart failure and left ventricular systolic dysfunction

Circulation. Heart failure, 2010

Aldosterone antagonism has been studied in patients with advanced heart failure (HF) and also in ... more Aldosterone antagonism has been studied in patients with advanced heart failure (HF) and also in patients with post-myocardial infarction and left ventricular (LV) dysfunction with HF symptoms. Few data are available on effects of aldosterone antagonism in patients with mild-to-moderate HF. In a multicenter, randomized, double-blind, placebo-controlled study in patients with mild-to-moderate HF and LV systolic dysfunction, patients with New York Heart Association class II/III HF and LV ejection fraction (EF) < or =35% were randomly assigned to receive eplerenone 50 mg/d versus placebo in addition to contemporary background therapy. Quantitative radionuclide ventriculograms to assess LV volumes and ejection fraction were performed at baseline and again after 9 months of double-blind treatment and were analyzed in a central core laboratory, blinded to treatment. The primary efficacy analysis was the between-group comparison of the change in LV end-diastolic volume index. Secondary ...

Research paper thumbnail of LV and myocyte structure and function after early recovery from tachycardia-induced cardiomyopathy

The American journal of physiology, 1995

Left ventricular (LV) function and mass were measured in six conscious dogs at weekly intervals d... more Left ventricular (LV) function and mass were measured in six conscious dogs at weekly intervals during the progression of tachycardia-induced dilated cardiomyopathy (DCM) and during a 1-mo recovery period from DCM (post-DCM). LV end-diastolic volume and LV wall stress increased and LV ejection fraction decreased with each week of pacing. Despite the increased LV wall stress, LV mass did not change during the progression of tachycardia DCM. One week post-DCM resulted in an improved LV ejection fraction and normalization of neurohormonal profiles. However, 1 wk post-DCM was accompanied by a 26% increase in LV mass and persistent LV chamber dilation. Isolated myocyte function was examined and compared with that in six normal control dogs. Myocyte percent and myocyte velocity of shortening were 19 and 32% lower, respectively, in the post-DCM group compared with controls. Thus termination of the tachycardia subsequent to the development of DCM resulted in persistent LV chamber dilation a...

Research paper thumbnail of Eplerenone Reduces Mortality 30 Days After Randomization Following Acute Myocardial Infarction in Patients With Left Ventricular Systolic Dysfunction and Heart Failure

Journal of the American College of Cardiology, 2005

OBJECTIVES This study sought to assess the impact of the selective aldosterone blocker eplerenone... more OBJECTIVES This study sought to assess the impact of the selective aldosterone blocker eplerenone on mortality 30 days after randomization in patients after acute myocardial infarction (AMI) with a left ventricular ejection fraction (LVEF) Յ40% and clinical signs of heart failure. BACKGROUND In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone reduced all-cause mortality by 15% (p ϭ 0.008) over a mean follow-up of 16 months when used with standard therapy in patients after AMI with an LVEF Յ40% and clinical signs of heart failure. METHODS We analyzed the effect of eplerenone 25 mg/day initiated 3 to 14 days after AMI (mean, 7.3 days) on the co-primary end points of time to death from any cause and the composite end point of time to death from cardiovascular (CV) causes or hospitalization for CV events, and the secondary end points of CV mortality, sudden cardiac death, and fatal/nonfatal hospitalization for heart failure, after 30 days of therapy in the EPHESUS trial. RESULTS At 30 days after randomization, eplerenone reduced the risk of all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone and placebo-treated patients, respectively; p ϭ 0.004) and reduced the risk of CV mortality/CV hospitalization by 13% (8.6% vs. 9.9% in eplerenone and placebo-treated patients, respectively; p ϭ 0.074). Eplerenone also reduced the risk of CV mortality by 32% (p ϭ 0.003) and the risk of sudden cardiac death by 37% (p ϭ 0.051). CONCLUSIONS Eplerenone 25 mg/day significantly reduced all-cause mortality 30 days after randomization (when initiated at a mean of 7.3 days after AMI) in addition to conventional therapy in patients with an LVEF Յ40% and signs of heart failure. Based on its early survival benefit, eplerenone should be administered in the hospital after AMI.

Research paper thumbnail of Combination Angiotensin Receptor Blocker/Hydrochlorothiazide as Initial Therapy in the Treatment of Patients With Severe Hypertension

The Journal of Clinical Hypertension, 2004

Research paper thumbnail of Effect of Neurohormones, Cytokines, and Collagen Markers on the Risk of All-Cause Mortality: Results from the EPHESUS Trial

Journal of Cardiac Failure, 2005

Research paper thumbnail of Early Intensive vs a Delayed Conservative Simvastatin Strategy in Patients With Acute Coronary Syndromes

JAMA, 2004

ONG-TERM THERAPY WITH STATIN drugs has been shown to reduce the risk for death, myocardial infarc... more ONG-TERM THERAPY WITH STATIN drugs has been shown to reduce the risk for death, myocardial infarction (MI), and stroke among patients with established coronary artery disease, even when low-density lipoprotein (LDL) cholesterol levels are not elevated. 1-4 Most of the landmark clinical trials evaluating statins for secondary prevention enrolled patients who were stable for at least several months after an index acute coronary syndrome (ACS) event. 1-3 More recently, 2 ran-domized controlled trials have evaluated earlier initiation of statin therapy following an ACS event and have noted a corresponding early reduction in major cardiovascular events. 5,6

Research paper thumbnail of Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction ≤30%

European Journal of Heart Failure, 2006

Aims: Because of the prognostic importance of LV dysfunction following an AMI and the increasing ... more Aims: Because of the prognostic importance of LV dysfunction following an AMI and the increasing use of electrical and/or mechanical interventions in patients with LV systolic dysfunction, this retrospective analysis of EPHESUS patients with LVEF 30% at baseline was conducted to determine the value of eplerenone in this setting. Methods and results: In EPHESUS, 6632 patients with LVEF 40% and clinical heart failure (HF) post-AMI who were receiving standard therapy were randomized to eplerenone 25 mg/day titrated to 50 mg/day or placebo for a mean follow-up of 16 months. Treatment with eplerenone in the subgroup of patients with LVEF 30% (N = 2106) resulted in relative risk reductions of 21% versus placebo in both allcause mortality (P = 0.012) and cardiovascular (CV) mortality/CV hospitalization (P = 0.001), and 23% for CV mortality (P = 0.008). The relative risk of sudden cardiac death (SCD) was reduced 33% (P = 0.01) and HF mortality/HF hospitalization was reduced 25% (P = 0.005) with eplerenone compared with placebo. Within 30 days of randomization, eplerenone resulted in relative risk reductions of 43% for all-cause mortality (P = 0.002), 29% for CV mortality/CV hospitalization (P = 0.006), and 58% for SCD (P = 0.008). Conclusions: Treatment with eplerenone plus standard therapy in patients with post-AMI HF and LVEF 30% provided significant incremental benefits in reducing both early and late mortality and morbidity.

Research paper thumbnail of Selective Aldosterone Blockade with Eplerenone Reduces Albuminuria in Patients with Type 2 Diabetes

Clinical Journal of the American Society of Nephrology, 2006

Previous studies have shown that the selective aldosterone blocker eplerenone, in doses of up to ... more Previous studies have shown that the selective aldosterone blocker eplerenone, in doses of up to 200 mg/d, reduces albuminuria in patients with type 2 diabetes. This study was conducted to ascertain whether lower doses of eplerenone (50 or 100 mg/d) co-administered with the angiotensin-converting enzyme (ACE) inhibitor enalapril would produce a similar antialbuminuric effect while obviating the hyperkalemia observed previously. After open-label run-in with enalapril 20 mg/d, patients with diabetes and a urinary albumin:creatinine ratio (UACR) >50 mg/g were randomly assigned to receive enalapril plus one of three double-blind daily treatments for 12 wk: placebo, eplerenone 50 mg (EPL50), or eplerenone 100 mg (EPL100). After week 4, amlodipine 2.5 to 10 mg/d was allowed for BP control (systolic/diastolic BP < 130/80 mmHg). The primary study end points were the percentage change from baseline at week 12 in UACR and the incidence of hyperkalemia. Secondary end points included percentage changes from baseline in UACR at weeks 4 and 8 and changes from baseline in systolic and diastolic BP. Treatment with EPL50 or EPL100 but not placebo significantly reduced albuminuria from baseline. By week 12, UACR was reduced by 7.4% in the placebo group, by 41.0% in the EPL50 group, and by 48.4% in the EPL100 group (both eplerenone groups, P < 0.001 versus placebo). The incidences of sustained and severe hyperkalemia were not significantly different in any of the three treatment arms and did not differ on the basis of quartile of estimated GFR (all NS). For the secondary end points, both eplerenone treatment groups significantly reduced albuminuria from baseline as early as week 4 (P < 0.001), whereas placebo treatment (including enalapril) did not result in any significant decreases in UACR. Systolic BP decreased significantly in all treatment groups at all time points, but, generally, all treatment groups experienced similar decreases in BP. Co-administration of EPL50 or EPL100 with an ACE inhibitor as compared with an ACE inhibitor alone significantly reduces albuminuria in patients with diabetes without producing significant increases in hyperkalemia.