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Prospective, randomized, controlled, open-label study to compare efficacy of a mineral-rich solution vs normal saline after complete ethmoidectomy.
de Gabory, L, Escabasse, V, Boudard, P, de Bonnecaze, G, Rumeau, C, Jankowski, R, Debry, C, Morinière, S, Merino, B, Mortuaire, G, et al
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2019;(2):447-457
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Abstract
PURPOSES The purpose of this study was to compare the efficacy of a mineral-rich solution vs normal saline solution (0.9% NaCl) following endoscopic complete bilateral ethmoidectomy. METHODS This was a prospective, multicenter, randomized, controlled, open-label trial in subjects suffering from steroid-resistant sinonasal polyposis. Adults performed 4 nasal irrigations of mineral or saline solutions daily for 28 days. Evaluations included subject-reported RHINO quality of life (QoL) and NOSE scores, tolerability, and satisfaction, the Lund-Kennedy endoscopic score and assessments of crusting, secretions and mucociliary clearance (rhinoscintigraphy). RESULTS A total of 189 subjects were randomized. Clinically relevant improvements (> 20 points) in RhinoQOL and NOSE scores were measured in both groups without any significant inter-group difference. Among the subjects with impaired RhinoQOL at pre-inclusion, the change in Impact-RhinoQOL score was significantly superior in mineral-rich vs saline solution at day 21 (p = 0.028) and day 28 (p = 0.027). The Lund-Kennedy score continuously improved in both groups earlier with the mineral-rich solution. Crusts were significantly fewer in number and less severe/obstructive in patients receiving mineral-rich vs saline solution at day 7 (p = 0.026) and day 14 (p = 0.016). Furthermore, secretions disappeared significantly more quickly and were less thick/purulent with mineral-rich solution at day 14 (p = 0.002) and day 21 (p = 0.043). Less epistaxis was reported in the mineral vs saline solution (p = 0.008 at day 21). CONCLUSIONS Our findings indicate that the composition of a nasal irrigation solution influences endoscopic scores and QoL after sinus surgery for patients over 60, those with an initially poor QoL and higher symptom score, and smokers.
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Perturbations in serum chloride homeostasis in heart failure with preserved ejection fraction: insights from TOPCAT.
Grodin, JL, Testani, JM, Pandey, A, Sambandam, K, Drazner, MH, Fang, JC, Tang, WHW
European journal of heart failure. 2018;(10):1436-1443
Abstract
AIMS: Prior cohorts demonstrating the importance of serum chloride levels in heart failure either excluded or had partial representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between serum chloride concentration and outcomes in HFpEF. METHODS AND RESULTS We included participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) who met the following criteria: met inclusion by the natriuretic peptide stratum, had recorded serum chloride levels, and were from the Americas (n = 942). Multivariable Cox proportional hazards models tested the association of serum chloride with clinical outcomes, and mixed effects modelling tested the association of spironolactone or loop diuretic on serial serum chloride levels. The median serum chloride level was 102 [25th-75th percentile 100-105 mmol/L (range 84-114 mmol/L)]. After multivariable adjustment, every standard deviation decrease in serum chloride (4.05 mmol/L) was associated with ∼50% increased risk for cardiovascular death [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.11-2.06, P = 0.008] and ∼30% increased risk for all-cause death (HR 1.29, 95% CI 1.02-1.62, P = 0.04), but not with the primary composite endpoint or heart failure hospitalization (P > 0.3 for both). There were no significant interactions between spironolactone use and the serum chloride-risk relationship (P > 0.1) for each endpoint. Spironolactone was not (P = 0.33) but loop diuretic use was associated with lower serial serum chloride levels (P < 0.001). CONCLUSION Lower serum chloride was independently associated with increased risk of cardiovascular and all-cause death in HFpEF. Loop diuretic use, but not spironolactone, lead to a decrease in serum chloride levels over time.
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Novel effects of phytoestrogenic soy isoflavones on serum calcium and chloride in premenopausal women: A 2-year double-blind, randomized, placebo-controlled study.
Lu, LW, Chen, NW, Nayeem, F, Ramanujam, VS, Kuo, YF, Brunder, DG, Nagamani, M, Anderson, KE
Clinical nutrition (Edinburgh, Scotland). 2018;(6 Pt A):1862-1870
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BACKGROUND Soy phytoestrogens are potential alternatives to postmenopausal hormone replacement therapy (HRT). Adverse effects of HRT such as myocardial infarction, stroke, and pulmonary embolism are mediated by calcium-induced signaling. OBJECTIVE To determine whether soy isoflavones affect serum calcium in healthy female subjects. DESIGN In a double-blind trial, 197 premenopausal women were randomly assigned to either isoflavone (N = 99) or placebo pills (N = 98) 5 days per week for up to 2 years, plus prenatal vitamins. Isoflavone pills contained 60 mg genistein, 60 mg daidzein and 16.6 mg glycitein (expressed as aglycone equivalents). All pills contained 15 mg riboflavin as an adherence marker. Blood chemistries and urinary daidzein, genistein and riboflavin were measured multiple times during the luteal phase before and during treatment. RESULTS Analysis of the adherent population (N = 83 per group), revealed significantly strong associations between urinary levels of isoflavones and serum concentrations of calcium (regression coefficients 0.082 for daidzein and 0.229 for genistein, all P < 0.01) and chloride (regression coefficient, -1.537 for genistein, P < 0.0001), mediated in part by albumin. The effects amounted to mean changes of +0.24 mg/dL for calcium and -1.45 mEq/L for chloride, with each visit for subjects excreting the most vs. the least amounts of isoflavones. These associations were not evident in the intention-to-treat analysis (N = 197) that did not assess expected variations in isoflavone levels within and between subjects from metabolism and adherence. CONCLUSIONS These novel and strong effects of soy isoflavones on calcium homeostasis have important implications for long term effects of these natural substances on cardiovascular diseases.
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Implications of Serum Chloride Homeostasis in Acute Heart Failure (from ROSE-AHF).
Grodin, JL, Sun, JL, Anstrom, KJ, Chen, HH, Starling, RC, Testani, JM, Tang, WH
The American journal of cardiology. 2017;(1):78-83
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Lower serum chloride (Cl) levels are strongly associated with increased long-term mortality after admission for acute heart failure (AHF). However, the therapeutic implications of serum Cl levels during AHF are unknown. We sought to determine the short-term clinical response and postdischarge outcomes associated with serum Cl levels in AHF. Serum Cl was measured at randomization (n = 358) and during hospitalization from patients with AHF in the Renal Optimization Strategies Evaluation in Acute Heart Failure trial. Outcomes included diuretic response and renal function at 72 hours and death and rehospitalization at 60 and 180 days. Baseline Cl tertiles were 84 to 98; 99 to 102; and 103 to 117 meq/l. Baseline Cl level was associated with diuretic efficiency (p <0.001) but not change in cystatin C (p = 0.30) at 72 hours and was associated with 60-day death (hazard ratio [HR] 0.86, p = 0.029), 60-day death and rehospitalization (HR 0.90, p = 0.01), and 180-day death (HR 0.91, p = 0.049). These associations were attenuated with additional adjustment for loop diuretic dose (p >0.05). Chloride change correlated with weight change (ρ 0.18, p = 0.001), cystatin C change (ρ -0.35, p <0.001), and cumulative sodium excretion (ρ -0.21, p <0.001) but was not associated with any clinical outcomes (p >0.05 for all). In conclusion, serum Cl levels in AHF were inversely associated with loop diuretic response and were prognostic. However, changes in Cl levels were associated with parameters of decongestion but not with clinical outcomes.
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Lumacaftor/Ivacaftor Treatment of Patients with Cystic Fibrosis Heterozygous for F508del-CFTR.
Rowe, SM, McColley, SA, Rietschel, E, Li, X, Bell, SC, Konstan, MW, Marigowda, G, Waltz, D, Boyle, MP, ,
Annals of the American Thoracic Society. 2017;(2):213-219
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Abstract
RATIONALE In a prior study, lumacaftor/ivacaftor treatment (≤28 d) in patients with cystic fibrosis (CF) heterozygous for F508del-CFTR did not improve lung function. OBJECTIVES To evaluate an optimized lumacaftor/ivacaftor dosing regimen with a longer duration in a cohort of patients heterozygous for F508del-CFTR. METHODS Patients aged 18 years or older with a confirmed CF diagnosis and percent predicted FEV1 (ppFEV1) of 40 to 90 were randomized to lumacaftor/ivacaftor (400 mg/250 mg every 12 h) or placebo daily for 56 days. Primary outcomes were change in ppFEV1 at Day 56 and safety. Other disease markers were evaluated. MEASUREMENTS AND MAIN RESULTS Of 126 patients, 119 (94.4%) completed the study. Lumacaftor/ivacaftor was well tolerated, although chest tightness and dyspnea occurred more frequently with active treatment than with placebo (27.4% vs. 14.3% and 14.5% vs. 6.3%, respectively). Mean (SD) ppFEV1 values at baseline were 62.9 (14.3) in the active treatment group and 60.1 (14.0) in the placebo group. Absolute changes in ppFEV1 (least squares mean [SE]) at Day 56 were -0.6 (0.8) percentage points in the active treatment group and -1.2 (0.8) percentage points in the placebo group (P = 0.60). CF respiratory symptom scores in the active treatment group improved by a mean of 5.7 points versus a decrease of -0.8 in the placebo group (P < 0.01). No changes in body mass index occurred. Changes from baseline in sweat chloride (least squares mean [SE]) at Day 56 were -11.8 (1.3) mmol/L in the active treatment group and -0.8 (1.2) mmol/L in the placebo group (P < 0.0001). CONCLUSIONS Sweat chloride and respiratory symptom scores improved with lumacaftor/ivacaftor, though no meaningful benefit was seen in ppFEV1 or body mass index in patients heterozygous for F508del-CFTR. Clinical trial registered with www.clinicaltrials.gov (NCT01225211).
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Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations.
Vermeulen, F, Le Camus, C, Davies, JC, Bilton, D, Milenković, D, De Boeck, K
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2017;(1):36-40
Abstract
INTRODUCTION Sweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although there is consensus on a cut-off value to diagnose CF, we have only limited information on the within subject variability of sweat chloride over time. Such information would be useful for sample size calculations in clinical trials. Therefore, we retrospectively analyzed repeated sweat chloride values obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial. METHODS In subjects with G551D at least 12years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48weeks. We explored 1062 pilocarpine sweat test values obtained in 78 placebo patients of the VX08-770-102 trial. RESULTS Mean overall sweat chloride value (all patients, all tests, n=1062) was 100.8mmol/L (SD 12.7mmol/L). Using a multilevel mixed model, the between-subject standard deviation (SD) for sweat chloride was 8.9mmol/L (95% CI 7.4-10.6) and within-subject SD was 8.1mmol/L (95% CI 7.5-8.7). Limits of repeatability for repeat measurements were -19.7 to +21.6mmol/L using values from one arm, and -13.3 to 11.8mmol/L using mean of values obtained at 4 test occasions. Sample size calculations showed that the minimal treatment effect on sweat chloride concentration that can be demonstrated for a group of 5 patients is around 15mmol/L, using a cross-over design and combinations of 4 tests for each phase of the trial. CONCLUSION Although the sweat test is considered a robust measure, sweat chloride measurements in patients with CF and a G551D mutation had an inherent biological variability that is higher than commonly considered. Further analyses of placebo group data are crucial to learn more about the natural variability of this outcome parameter.
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Hypochloremia, Diuretic Resistance, and Outcome in Patients With Acute Heart Failure.
Ter Maaten, JM, Damman, K, Hanberg, JS, Givertz, MM, Metra, M, O'Connor, CM, Teerlink, JR, Ponikowski, P, Cotter, G, Davison, B, et al
Circulation. Heart failure. 2016;(8)
Abstract
BACKGROUND Chloride plays a role in renal salt sensing, neurohormonal activation, and regulation of diuretic targets, and hypochloremia predicts mortality in acute heart failure (AHF). AHF therapies, such as diuretics, alter chloride homeostasis. We studied the association between (changes in) chloride levels and diuretic responsiveness, decongestion, and mortality in patients with AHF. METHODS AND RESULTS Patients hospitalized for AHF in the PROTECT trial (n=2033) with serum chloride levels within 24 hours of admission and 14 days later were studied (n=1960). Hypochloremia was defined as serum chloride <96 mEq/L. Mean baseline chloride was 100.8±5.0 mEq/L. Low baseline chloride was associated with high bicarbonate, poor diuretic response, less hemoconcentration, and worsening heart failure (all P<0.01). Newly developed hypochloremia at day 14 was common and associated with a decline in renal function and an increase in blood urea nitrogen (P<0.01). In multivariable analyses, chloride measured at day 14, but not baseline chloride, was strongly and independently associated with mortality through 180 days (hazard ratio per unit decrease: 1.07 [1.03-1.10]; P<0.001). In comparison, sodium was not significantly associated with mortality after multivariable adjustment at any time point. Hypochloremia at baseline that resolved was not associated with mortality (P=0.55), but new or persistent hypochloremia at day 14 was associated with increased mortality (hazard ratio: 3.11 [2.17-4.46]; P<0.001). CONCLUSIONS Low serum chloride at AHF hospital admission was strongly associated with impaired decongestion. New or persistent hypochloremia 14 days later was independently associated with reduced survival, whereas hypochloremia that resolved by day 14 was not. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354458.
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Moderate intensity exercise mediates comparable increases in exhaled chloride as albuterol in individuals with cystic fibrosis.
Wheatley, CM, Baker, SE, Morgan, MA, Martinez, MG, Liu, B, Rowe, SM, Morgan, WJ, Wong, EC, Karpen, SR, Snyder, EM
Respiratory medicine. 2015;(8):1001-11
Abstract
RATIONALE Despite the demonstrated advantageous systemic changes in response to regular exercise for individuals with cystic fibrosis (CF), exercise is still viewed as an elective rather than a vital component of therapy, and it is likely that these benefits extend to and are partially mediated by exercise-induced changes in ion regulation. OBJECTIVE We sought to determine if exercise could provide comparable improvements in ion regulation in the CF lung as albuterol, measured using exhaled breath condensate (EBC) collection and nasal potential difference (NPD). METHODS Fourteen CF (13-42 yrs.) and sixteen healthy (18-42 yrs.) subjects completed a randomized crossover study of albuterol and submaximal exercise. EBC was collected at baseline, 30- and 60-min post-albuterol administration, and at baseline and during three separate 15 min cycling exercise bouts at low, moderate, and vigorous intensity (25, 50 and 65% of the maximum workload, respectively). NPD was performed at 30- and 80-min post albuterol or following moderate and vigorous intensity exercise. RESULTS CF subjects had lower EBC Cl(-), but no difference in EBC Na(+) at baseline when compared to healthy subjects. EBC Cl(-) increased four-fold with moderate exercise which was similar to that seen 60-min post albuterol administration for CF subjects. Neither exercise nor albuterol altered EBC Na(+). The change in NPD voltage with amiloride (ΔAmil) was greater and there was minimal Cl(-) secretion (ΔTCC) seen at baseline in the CF compared to the healthy subjects. ΔAmil was greater with both albuterol and exercise when compared to baseline within both CF and healthy groups, but there was no significant difference in the ΔTCC response with either treatment. CONCLUSION Both exercise and albuterol can alter ion regulation increasing Cl(-) secretion to a significant and similar degree in individuals with CF.
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Effect of three different contamination removal methods on bond strength of a self-etching adhesive to dentin contaminated with an aluminum chloride hemostatic agent.
Ajami, AA, Kahnamoii, MA, Kimyai, S, Oskoee, SS, Pournaghi-Azar, F, Bahari, M, Firouzmandi, M
The journal of contemporary dental practice. 2013;(1):26-33
Abstract
AIM: This study evaluated the effect of three different contamination removal methods on bond strength of one-step self-etching adhesive to dentin contaminated with an aluminum chloride hemostatic agent. MATERIALS AND METHODS One hundred noncarious adult molars were used in this study; 2-mm-thick dentin disks were prepared and randomly assigned to 5 groups (n = 20). Group I: control; group II: hemostatic agent-contaminated; group III: hemostatic agent-contaminated and rinsing with water; group IV: hemostatic agent-contaminated and ethylene diamine tetraacetic acid (EDTA) application; and group V: hemostatic agent-contaminated and phosphoric acid application. Clearfil S3 Bond was used to bond composite to dentin surfaces. Subsequent to adding composite cylinders the shear bond strength test was performed. Data were analyzed by one-way ANOVA and Tukey test. Two additional specimens from each group were prepared and evaluated under scanning electron microscope (SEM). RESULTS There were statistically significant differences in bond strength among the groups (p < 0.001). In two-by-two comparisons statistically significant differences were observed in bond strength values between all the groups (p < 0.001) except for groups I and IV (p = 0.933). CONCLUSION Aluminum chloride hemostatic agent adversely affected the bond strength of self-etch adhesive to dentin. However, application of EDTA increased the bond strength to the level of normal dentin. CLINICAL SIGNIFICANCE EDTA and phosphoric acid removed aluminum chloride hemostatic agent contamination of dentin surfaces. However, unlike EDTA phosphoric acid failed to increase the bond strength of self-etch adhesive to dentin to the level of the control group.
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Long term effects of denufosol tetrasodium in patients with cystic fibrosis.
Ratjen, F, Durham, T, Navratil, T, Schaberg, A, Accurso, FJ, Wainwright, C, Barnes, M, Moss, RB, ,
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2012;(6):539-49
Abstract
RATIONALE Denufosol stimulates chloride secretion independent of the chloride channel which is dysfunctional in cystic fibrosis (CF) and therefore has the potential to benefit CF patients regardless of genotype. OBJECTIVES To assess the efficacy of denufosol in CF patients with mild lung function impairment age 5 years and older. METHODS This multicenter, randomized, parallel group double-blind placebo-controlled trial was conducted at 102 CF care centers in Australia, Canada and the United States (NCT00625612) The active group (n=233) received 60 mg denufosol via inhalation three times daily The primary efficacy endpoint was change in FEV(1) in liters from Day 0 to week 48. MEASUREMENTS AND MAIN RESULTS 685 patients were screened for the study and 466 patients (233 in each group) were randomized to study treatment. The adjusted mean change in FEV(1)was 40 mL for denufosol and 32 mL for placebo with a resulting treatment effect of 8 mL (95% CI -0.040, 0.056). The average rate of change in FEV(1) percent of predicted over 0 to 48 weeks was -3.04% for placebo vs. -2.30 for denufosol (a difference of 24% relative to placebo) among all patients. The incidence of pulmonary exacerbation was 26% vs. 21% for the placebo and denufosol groups with no differences in the time to first event. The study treatments were well tolerated and there was no evidence of systemic effects in any safety parameter assessed. CONCLUSIONS In patients with CF treatment with denufosol for 48 weeks did not improve pulmonary function or reduce the incidence of pulmonary exacerbations.