Effectiveness and Safety of A Nutraceutical Formulation for the Treatment of Functional Dyspepsia in Primary Care.

BACKGROUND: Although FD may affect up to 10% of the general population, the therapy for FD is not standard. Recently, ginger-based food supplements have been proposed in order to restore FD symptoms. Our aim was to assess the efficacy of a new nutraceutical formulation containing extract of gingerol and thymus as a possible natural treatment in managing the symptoms of functional dyspepsia (FD). METHODS: We retrospectively analyzed the efficacy and safety profiles of a nutraceutical formulation containing Zingiber officinalis root extract and a standardized Thymus extract. It was administered as 1 ml/day twice a day for 90 days. Patients were assessed at baseline and after 1, 2 and 3 months of treatment, following a month of pharmacological washout by completing a questionnaire reporting the trend of the following symptoms: epigastric pain, epigastric heaviness, early satiety, belching, and regurgitation. Every symptom was assessed by a Visual Analogic Scale (VAS), ranging from 0= absence to 10= maximal severity. RESULTS: We enrolled 272 patients (99 males and 173 females; median IQR age 49.5, 36-64 yrs). Obesity (BMI>30) was present in 28 (12.5%) patients; smokers were 83 (30.5%); and comorbidities were present in 107 (39.3%) patients. Improvement of symptom scores during treatment and one month after its suspension was extremely significant (p<0.000). CONCLUSION: This large study found that nutraceutical formulation could be one of the tools for an empirical approach to treat patients with FD, especially when a non-conventional drug treatment is preferable for the patient and considered suitable by the physician.

Long-term effects of high-efficiency on-line haemodiafiltration on uraemic toxicity. A multicentre prospective randomized study.

BACKGROUND: Haemodiafiltration (HDF) may improve survival of chronic dialysis patients. This prospective, multicentre randomized cross-over study evaluated the effects of long-term on-line HDF on the levels of solutes of different molecular weight markers or causative agents of the most common metabolic derangements in uraemia. METHODS: Sixty-nine patients from eight Italian centres were randomly assigned to two 6-month treatment sequences: A-B and B-A [A, low-flux haemodialysis (HD) and B, on-line HDF]. Comparative evaluation of basal levels of small, medium-sized and protein-bound solutes at the end of the two treatment periods and analysis of parameters dependence during the interventions were performed. RESULTS: On-line HDF showed greater efficiency than low-flux HD in removing small solutes (eKt/Vurea 1.60 ± 0.31 versus 1.44 ± 0.26, P < 0.0001) and in reducing basal levels of beta2-microglobulin (22.2 ± 7.8 versus 33.5 ± 11.8 mg/L, P < 0.0001), total homocysteine (15.4 ± 5.0 versus 18.7 ± 8.2 µmol/L, P = 0 .003), phosphate (4.6 ± 1.3 versus 5.0 ± 1.4 mg/dL, P = 0.008) and, remarkably, of intact parathyroid hormone (202 ± 154 versus 228 ± 176 pg/mL, P = 0.03). Moreover, in on-line HDF, lower levels of C-reactive protein (5.5 ± 5.5 versus 6.7 ± 6.1 mg/L, P = 0.03) and triglycerides (148 ± 77 versus 167 ± 87 mg/dL, P = 0.008) and increased HDL cholesterol (49.2 ± 12.7 versus 44.7 ± 12.4 mg/dL, P = <0.0001) were observed. The asymmetric dimethylarginine level was not significantly affected (0.97 ± 0.4 versus 0.84 ± 0.37 µmol/L). Erythropoietin and phosphate binders' doses could be reduced. CONCLUSIONS: On-line high-efficiency HDF resulted in enhanced removal and lower basal levels of small, medium-sized and protein-bound solutes, which are markers or causative agents of uraemic pathologies, mainly inflammation, secondary hyperparathyroidism and dyslipidaemia. This may contribute to reducing uraemic complications and possibly to improving patient survival.

Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy.

The optimal treatment for IgA nephropathy (IgAN) remains unknown. Some patients respond to corticosteroids, suggesting that more aggressive treatment may provide additional benefit. We performed a randomized, multicenter, controlled trial to determine whether adding azathioprine to steroids improves renal outcome. We randomly assigned 207 IgAN patients with creatinine ≤2.0 mg/dl and proteinuria ≥1.0 g/d to either (1) a 3-day pulse of methylprednisolone in months 1, 3, and 5 in addition to both oral prednisone 0.5 mg/kg every other day and azathioprine 1.5 mg/kg per day for 6 months (n = 101, group 1) or (2) steroids alone on the same schedule (n = 106, group 2). The primary outcome was renal survival (time to 50% increase in plasma creatinine from baseline); secondary outcomes were changes in proteinuria over time and safety. After a median follow-up of 4.9 years, the primary endpoint occurred in 13 patients in group 1 (12.9%, 95% CI 7.5 to 20.9%) and 12 patients in group 2 (11.3%, CI 6.5 to 18.9%) (P = 0.83). Five-year cumulative renal survival was similar between groups (88 versus 89%; P = 0.83). Multivariate Cox regression analysis revealed that female gender, systolic BP, number of antihypertensive drugs, ACE inhibitor use, and proteinuria during follow-up predicted the risk of reaching the primary endpoint. Treatment significantly decreased proteinuria from 2.00 to 1.07 g/d during follow-up (P < 0.001) on average, with no difference between groups. Treatment-related adverse events were more frequent among those receiving azathioprine. In summary, adding low-dose azathioprine to corticosteroids for 6 months does not provide additional benefit to patients with IgAN and may increase the risk for adverse events.

A simple approach for assessing equilibrated Kt/V beta 2-M on a routine basis.

BACKGROUND: Large observational studies have shown a reduction in morbidity and mortality in patients on high-flux haemodialysis (HD) or convective techniques, compared with low-flux HD. An index to evaluate treatment efficiency in middle molecule (MM) removal would be recommended. Since beta-2-microglobulin (beta2-M) is a recognized MM marker, we evaluated an easy approach for Kt/V(beta2-M) assessment on a routine basis, avoiding other complex methods. METHODS: An equation that estimates single-pool (sp) Kt/V(beta2-M) was derived from Leypoldt's formula, which calculates beta2-M dialyser clearance (K(beta2-M)) from the post/pre-dialysis beta2-M concentration (C(t)/C(0)) ratio and the weight loss/end-dialysis weight (Delta W/W) ratio. Our equation, spKt/V(beta2-M) = 6.12 Delta W/W [1 - ln(C(t)/C(0))/ln(1 + 6.12 Delta W/W)], was derived by assuming urea distribution volume (V(u)) as 49% of W and beta2-M volume (V(beta2-M)) as V(u)/3, in agreement with the average patient values in the HEMO Study. The spKt/V(beta2-M) values calculated with our equation (F) in 129 patients on 407 sessions of different high-flux treatments were compared with those calculated with the method applied in the HEMO Study (HM). Equilibrated beta2-M concentration (C(eq)) of the same sessions was also estimated with the equation for C(eq) by Tattersall, and equilibrated Kt/V (eKt/V(beta2-M)) was calculated by introducing Tattersall's equation into our simplified spKt/V(beta2-M) formula. RESULTS: Mean results of our spKt/V(beta2-M) equation (F) were very close to those of the HM method (1.48 +/- 0.38 vs 1.47 +/- 0.37). The difference was less than +/-0.1 in 95% of cases. A mean end-session beta2-M rebound of 44 +/- 14% was predicted, which caused a mean reduction in actual Kt/V(beta2-M) of ~27% (eKt/V(beta2-M) = 1.08 +/- 0.26). CONCLUSIONS: The method proposed to estimate spKt/V(beta2-M) and eKt/V(beta2-M) could become a simple tool to monitor the efficiency of high-flux HD and convective techniques and to evaluate the adequacy of treatments in terms of MM removal. Moreover, it might help to better understand the effects of different dialysis schedules. Validation on a larger dialysis population is required.

Sudden death and associated factors in a historical cohort of chronic haemodialysis patients.

BACKGROUND: In haemodialysis patients, deaths due to cardiovascular causes constitute a large proportion of total mortality and sudden cardiac deaths account for approximately 22% of all deaths. The aim of this study was to evaluate the incidence of sudden cardiac death and associated risk factors in a cohort of haemodialysis patients. METHODS AND RESULTS: The 3-year cumulative incidence of death in a cohort of 476 patients on chronic haemodialysis treatment was 34.3% (SE 2.3). Sudden death had a 6.9% (SE 1.2) cumulative incidence, with 32 events representing 19.2% of all deaths, while cardiovascular not sudden death and noncardiovascular death accounted for a 3-year cumulative incidence of 7.3% (SE 1.2) and 20.1% (SE 1.9), respectively. According to Cox multivariate analysis, significant risk factors for sudden death were the presence of atrial fibrillation, diabetes mellitus, predialytic hyperkalaemia, haemodialysis mode and C-reactive protein level, which were associated with a 2.9 (CI(95%) 1.3-6.4), 3.0 (CI(95%) 1.3-7.2), 2.7 (CI(95%) 1.3-5.8), 4.5 (CI(95%) 1.3-15.5) and 3.3 (CI(95%) 1.2-8.8)-fold increase in the risk of sudden death, respectively. Sudden death was significantly more frequent during the first 24 h of the first short interdialytic interval and during the last 24 h of the long interval, i.e. immediately before and immediately after the first weekly haemodialysis session (P = 0.02). CONCLUSIONS: Our data show that the incidence of sudden death in haemodialysis patients is high and that atrial fibrillation, diabetes, hyperkalaemia, haemodialysis mode and C-reactive protein play an important role in developing fatal arrhythmia. Further studies will be necessary to define which interventions could be helpful in reducing this cause of mortality.

On-line mixed hemodiafiltration with a feedback for ultrafiltration control: effect on middle-molecule removal.

BACKGROUND: Increased middle-molecular uremic toxin removal seems to favorably influence survival in dialysis patients. The aim of this study was to verify if, in on-line mixed hemodiafiltration, solute removal by convection may be enhanced by forcing the ultrafiltration rate (QUF) and optimizing the infusion technique in order to achieve the highest possible filtration fraction (FF). METHODS: Removal of beta2-microglobulin (beta2-m), urea, creatinine, and phosphate were compared in 20 patients randomly submitted to one dialysis session (A), one postdilution hemodiafiltration session (B), and three sessions of mixed hemodiafiltration (C, D, and E) at different infusion rates (QS). In mixed hemodiafiltration, a newly developed feedback system automatically maintained the transmembrane pressure (TMP) within its highest range of safety (250 to 300 mm Hg) at constant QUF, while ensuring the maximum FF by splitting infusion between pre- and postdilution. RESULTS: A mean QS of 134 +/- 20 mL/min (mean FF = 0.65) was attained in post-HDF, and up to 307 +/- 41 mL/min (mean FF = 0.69) in mixed hemodiafiltration. The mean dialysate clearances (KDQ) for all tested solutes and urea eKt/V were significantly higher in all hemodiafiltration sessions than in dialysis. Only in the case of urea did the infusion mode have no significant effect. KDQ for beta2-m was maximal in session D and significantly higher than in session B (90.2 +/- 11 mL/min vs. 77.5 +/- 11 mL/min; P = 0.02). KDQ for beta2-m significantly correlated with QS and the plasma water flow rate (QPW). The highest KDQ for beta2-m was found at values of QS approximately QPW. Beyond this value KDQ decreased. CONCLUSION: The mixed infusion mode in hemodiafiltration, controlled by the TMP-ultrafiltration feedback, seems to improve the efficiency of hemodiafiltration by fully exploiting the convective mechanism of solute removal. The feedback automatically adjusted the infusion rate and site to the maximum FF taking into account flow conditions, internal pressures, and hydraulic permeability of the dialyzer and their complex interactions.