Urinary urgency outcomes after propiverine treatment for an overactive bladder: the ‘Propiverine study on overactive bladder including urgency data’

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To investigate the effects of a daily regimen of propiverine 20 mg in patients with an overactive bladder (OAB), focused on improving urgency, as the clinical efficacy of treatment for OAB should be measured in terms of urgency, the cornerstone symptom of OAB.

PATIENTS AND METHODS

Eligible patients aged ≥18 years with symptoms of OAB were enrolled in this multicentre, prospective, parallel, double‐blind, placebo‐controlled trial. Of 264 patients (mean age 52.2 years), 221 who had efficacy data available from baseline and at least one on‐treatment visit with >75% compliance with medication were analysed (142 in the propiverine group and 79 in the placebo group). All patients were randomized to receive a placebo or 20 mg propiverine once daily in a 12‐week study. They completed a 3‐day voiding diary before visits during the study period, including the severity of urgency associated with every voiding, using the Indevus Urgency Severity Scale and the Urgency Perception Score. The patients’ overall self‐evaluation of treatment benefits at the end of the study, and safety data, were also collected.

RESULTS

The daily urgency episodes reduced significantly from baseline to 12 weeks on propiverine treatment, compared with placebo (?46.0% vs ?31.3%, P = 0.005). Secondary endpoints, including sum of urgency severity per 24 h, urgency severity per void, and daytime voiding frequency, were also improved significantly in the propiverine group. Overall, of those patients treated with propiverine, 38.7% rated their treatment as providing ‘much benefit’, compared with 15.2% of the placebo group (P = 0.025). Adverse events reported by 32 (22.5%) and 10 (12.7%) patients in the propiverine and placebo group were all tolerable. However, this is a short‐term study using only one fixed regimen.

CONCLUSIONS

Propiverine 20 mg once‐daily could be an effective treatment for patients with OAB, by improving urgency.     

Effects of cinacalcet on gastrointestinal hormone release in patients with secondary hyperparathyroidism undergoing dialysis.

Objective. Our aim has been evaluating the influence of an acute dose of cinacalcet on the gastrointestinal hormonal responses to a test meal in uraemic patients with secondary hyperparathyroidism undergoing peritoneal dialysis (PD) or haemodialysis (HD). METHODS: Twenty patients (11 PD, 9 HD) on cinacalcet treatment (30-120 mg/day) were studied. Twelve patients (1 PD, 11 HD) who never received cinacalcet were studied as control group. Each patient received a test meal with blood samples at 0, 2 and 4 h. At 0 time, patients in the cinacalcet group received their usual oral dose of this calcimimetic. Plasma concentrations of intact parathyroid hormone (PTH), vasoactive intestinal peptide (VIP), ghrelin, substance P, serotonin, cholecystokinin (CCK) and gastrin were quantified at 0, 2 and 4 h. RESULTS: No significant differences in baseline concentrations of serum VIP, ghrelin, substance P, serotonine, CCK and gastrin were found between controls and cinacalcet-treated patients. In comparison with the control group, cinacalcet administration was followed by a significant decrease in VIP concentration at 4 h and a significant increase in substance P at 4 h. However, the areas under the curves of all studied gut hormones were similar in both groups. CONCLUSION: An acute dose of cinacalcet exerts minimal influence on gut hormone responses to a mixed meal in dialysis patients on chronic therapy with this drug. The small but significant differences between control subjects and patients on cinacalcet in VIP and substance P levels at 4 h should be investigated in symptomatic patients.     

Appetite disorders in uremia.

Patients with chronic kidney disease frequently experience loss of appetite (anorexia), which increases in severity during the progression of the disease and may lead to protein-energy wasting, morbidity, and mortality. Anorexia represents a multiple, complex, and multifactorial disorder that may have its origin in renal failure (contemplating not only retention of uremic toxins but also peptides and cytokines) but that later on also involves metabolic abnormalities not yet corrected by dialysis therapy. This paper reviews current knowledge about the clinical signs of uremic anorexia as well as mechanisms involved. Based on megestrol acetate interventions and the recent observation that sex may modulate uremic appetite behavior, the potential role of sex hormones in treating chronic kidney disease anorexia needs to be further explored.     

Avoiding Axillary Treatment in Sentinel Lymph Node Micrometastases of Breast Cancer: A Prospective Analysis of Axillary or Distant Recurrence

Background

The need for axillary lymph node dissection (ALND) in breast cancer patients with sentinel lymph node (SLN) micrometastases remains controversial. The aims of the study were to evaluate the locoregional failure and outcome of breast cancer patients with sentinel node micrometastases who did not undergo completion ALND.

Methods

Between November 2000 and December 2006, SLN biopsy was successfully performed in 1178 patients with invasive breast carcinoma. Only patients with macrometastasis (>2 mm) underwent ALND, while patients with negative SLN or micrometastases did not undergo further treatment of the axilla, by either surgery or radiotherapy. Regarding adjuvant therapy decision, patients with SLN-micrometastases (pN1_mi) were considered as node-positive patients.

Results

Of 1,178 patients, 59 (5%) had micrometastases. Of those with micrometastases, 14 (24%) underwent ALND because the intraoperative study of the SLN yielded a positive result. With a median follow-up of 60 (range, 8–94) months, none of the patients with SLN micrometastases in whom ALND was omitted developed an axillary recurrence, while one patient in whom ALND was performed developed infraclavicular lymph node recurrence. One patient, who declined postoperative breast irradiation, developed breast recurrence and distant metastasis.

Conclusions

Breast cancer patients with SLN micrometastases in whom ALND was omitted had a very low locoregional failure rate. This study supports the theory that ALND might be avoided in these patients, providing that adjuvant systemic treatment equal to treatment provided to treat node-positive disease is administered. However, longer follow-up and results of additional prospective studies are needed.     

Increased Serum Amyloid A Concentrations in Morbid Obesity Decrease after Gastric Bypass

Background: Obesity is considered a state of low-grade chronic inflammation, which may favor the development of cardiovascular diseases. Serum amyloid A (SAA) is an acute phase protein synthesized in response to infection, inflammation, injury, and stress. The aim of the present study was to compare the circulating concentrations of SAA and the mRNA expression in omental adipose tissue between lean and obese individuals and to analyze the effect of weight loss after gastric bypass. Methods: 16 lean volunteers (BMI 20.5 ± 0.6 kg/m²) and 24 obese patients (BMI 47.0 ± 1.2 kg/m²) were included in the study. Serum concentrations of SAA were measured by ELISA. In addition, the concentrations of SAA in 18 morbidly obese patients (7 male/11 female; BMI 44.6 ± 1.9 kg/m²) were measured before and after weight loss following Roux-en-Y gastric bypass (RYGBP). SAA expression in omental adipose tissue was quantified by RT-PCR in biopsies from obese patients undergoing RYGBP and from age-matched lean individuals subjected to Nissen fundoplication. Results: Obese patients exhibited significantly increased circulating SAA concentrations (6.6 ± 0.5 vs 39.3 ± 9.1 μg/ml; P<0.01) compared to lean subjects. A significant positive correlation was found between logSAA and body fat (r=0.631, P<0.0001). Obese patients showed significantly increased (P<0.05) mRNA expression of SAA in omental adipose tissue compared to lean subjects. Weight loss significantly decreased SAA concentrations after RYGBP (final BMI 28.5 ± 0.9 kg/m², P<0.0001 vs initial) from 47.5 ± 14.5 to 15.7 ± 2.9 μg/ml (P<0.05). Conclusion: It can be concluded that serum SAA and mRNA expression of SAA in omental adipose tissue are increased in obese patients contributing to the obesity-associated cardiovascular disease risk. Moreover, weight loss reduces SAA concentrations, which may contribute to the beneficial effects accompanying weight reduction.     

Robot-assisted epicardial ablation of the pulmonary veins: is a completed isolation necessary?

AIMS: To study the feasibility and electrophysiological efficacy of minimally invasive beating heart ablation of the pulmonary veins (PVs) via a robot-assisted single-sided approach. BACKGROUND: PV isolation by minimally invasive epicardial ablation may offer a new treatment for patients with lone atrial fibrillation (AF). However, complete PV isolation has been shown to be difficult to obtain. METHODS AND RESULTS: In 14 mongrel dogs, robot-assisted epicardial microwave ablation was performed on the beating heart by a single-sided right chest approach. Isolation of all PVs was performed in two steps to study the effect of an incomplete and a complete isolation on AF. AF was studied by random and burst pacing. Incremental pacing was performed to study conduction characteristics across the lesions. Opening of the pericardial reflections, introduction of the catheter and ablation were robotically feasible by a single-sided approach in 11 dogs. The AF duration decreased from 6.6+/-4.1 to 1.3+/-0.8 s (P=0.03) and 1.6+/-1.6 s (P=0.04 compared with control) after incomplete and completed isolation of the PVs. The AF cycle length increased from 134+/-5 to 141+/-5 and 145+/-8 ms (P=0.03) after incomplete and complete isolation, respectively. Several incomplete lesions showed 2:1 exit and/or entrance block during incremental pacing. After complete isolation, AF was no longer inducible from the PVs. CONCLUSION: Epicardial PV isolation can be successfully performed by a single-sided robot-assisted approach. The effect of PV ablation on AF is not an all or none phenomenon. Incomplete isolation already decreases AF duration and lengthens the AF cycle length. However, complete isolation is necessary to prevent AF induction by triggering from the isolated area.