Does the Number of Previous Vaginal Deliveries Affect Overactive Bladder Symptoms and their Response to Treatment?

Objectives: To explore associations between the number of vaginal deliveries (primary aim) or gender (secon‐ dary aim) and overactive bladder (OAB) symptoms as well as their response to treatment with a muscarinic antagonist. Methods: Preplanned secondary analysis of an observational study of solifenacin in OAB patients. Episode frequencies of OAB symptoms, pad use and scores on OAB rating scales were documented in 4450 patients before and after a 12–14 week treatment period with solifenacin 5 or 10 mg. Results: Women without, and with one, two or more than two vaginal deliveries and men were similar in their baseline characteristics. All groups also exhibited rather similar reductions in symptoms and improvements in rating scales upon treatment. Conclusion: These data indicate that solifenacin, and perhaps other muscarinic receptor antagonists, are similarly suitable for the treatment of OAB symptoms in both genders, irrespective of previous vaginal deliveries.     

Are Bladder Diaries Helpful in Management of Overactive Bladder?

Bladder diaries have long been used in both research and clinical practice to measure lower urinary tract symptoms in overactive bladder, yet their practical role in clinical practice remains questioned. In this review, we evaluate current literature to assess the usefulness of bladder diaries in the management of overactive bladder. A MEDLINE search was performed to identify literature regarding bladder diaries. Seven hundred sixty were returned of which 52 were considered relevant and reviewed. The review was limited to papers published in peer reviewed journals. Studies were selected based on their use of formal bladder diaries rather than short-form questionnaires in evaluating overactive bladder symptoms. Studies were excluded that focused primarily on bladder diaries for prostate and lower urinary tract symptoms (LUTS) rather than overactive bladder symptoms. Bladder diaries provide accurate data and are more reliable than patients’ recollections of symptoms. In addition to being inexpensive and low risk, patients view diaries as easy to complete and helpful for their care. Bladder diaries assist providers in differentiating between urge incontinence caused by overactive bladder and stress incontinence of separate etiology, allowing for correct tailoring of treatment regimens. The level of scientific rigor surrounding the development of bladder diaries continues to increase, and there are now several validated diaries available for clinical use. The 3- to 7-day bladder diary is a useful tool for both clinicians and patients in the management of overactive bladder. For patients, recording their voiding habits in a bladder diary provides insight into their urinary habits and symptom triggers. It allows them to contribute in the treatment decision process in a meaningful way and also empowers them to identify ways in which to control their symptoms. For providers, the bladder diary serves as an objective, prospective tool to assess the severity of patients’ symptoms as well as the effectiveness of various interventions.     

History of the Term “Overactive Bladder”

The history of the term overactive bladder touches many of the favorite controversies in urology; standardization of often subjective symptoms, the distinction between normal and disease, the role of industry, and the significance of a finding on urodynamic studies versus a patient’s chief complaint. This review explores the evolution of the term overactive bladder, from its popularization by Drs. Abrams and Wein in 1997 to the formalization by the ICS in 2002. We discuss the rationale for the use of the term over others, particularly the transition from multiple urodynamics based definitions to a symptoms-based definition and the arguments supporting as well as criticizing the shift. Lastly, we explore the history of pharmaceutical involvement surrounding the use of this term. The term overactive bladder is only 15 years old, but its invention and history drastically changed the way we discuss and treat voiding dysfunction, and its definition or perhaps, inevitable successor, could very well do the same in years to come.     

Is There a Role for Stem Cell Therapy for Overactive Bladder?

The traditional approach to the treatment of overactive bladder (OAB) consists of behavioral therapies and pharmacologic interventions, both of which are effective in the short term but have failed to demonstrate durability over time. Patients who fail these interventions for OAB have other more invasive surgical options available that carry their own attendant risks. Herein we provide an up-to-date overview of contemporary research being performed in the treatment of OAB. Namely, we discuss the risks and benefits of pharmacogenomic medicine, whereby we can study the genetic differences in metabolic pathways that affect an individual’s response to certain drugs. We also look at molecular medicine and the use of viral vectors to deliver gene therapy to target cells. Finally, we provide an overview of stem cells and the purported therapeutic benefits as well as the challenges faced by researchers in the use of these emerging treatment modalities.     

Objective Evaluation of Overactive Bladder: Which Surveys Should I Use?

Overactive bladder (OAB) is a common condition that affects many adults, and prevalence increases with age in both men and women. It is characterized by symptoms of urinary frequency and urgency with or without urge incontinence in the absence of another proven etiology. As a diagnosis based solely on urinary symptoms, proper evaluation of OAB often depends on the use of psychometrically validated questionnaires to assess symptom severity and degree of bother. General urinary assessment forms can evaluate many urinary symptoms while modular questionnaires can focus on the most bothersome complaints. Many questionnaires have been formulated and validated to achieve these goals. Currently, the ideal questionnaire does not exist. This review attempts to outline the range of questionnaires available to the clinician to assist in evaluating symptoms as well as degree of impact on quality of life.     

What Is the Cause of Toxicity of Silicone Oil?

Purpose: To investigate the toxicity of the low-molecular-weight components (LMWCs) in ophthalmic silicone oils (SilOils) on retinal cell lines. Methods: The toxicity of six types of LMWCs were studied and compared with conventional SilOil 1000 cSt. In vitro cytotoxic tests of LMWCs, in both liquid and emulsified forms, on three retinal cell lines (Müller cells (rMC-1), photoreceptor cells (661W) and retinal pigment epithelial cells (ARPE-19)) were conducted using a transwell cell culturing system. The morphology and viability of cells were assessed by light microscopy and Cell Counting Kit-8 (CCK-8) assay at different time points (6, 24 and 72 h). The ARPE-19 apoptotic pathway was investigated by Mitochondrial Membrane Potential/Annexin V Apoptosis Kit at different time points (6, 24 and 72 h). Results: Apart from dodecamethylpentasiloxane (L5), all liquid LMWCs showed varying degrees of acute cytotoxicity on retinal cell lines within 72 h. Emulsified LMWCs showed comparable cytotoxicity with liquid LMWCs on retinal cell lines. Cyclic LMWCs, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) had significantly higher cytotoxicity when compared with their linear counterparts decamethyltetrasiloxane (L4) and L5 with similar molecular formula. Using ARPE-19 cells as an example, we showed that LMWCs induce the apoptosis of retinal cells. Conclusions: Most LMWCs, in both liquid and emulsified forms, can induce acute cytotoxicity. In addition, cyclic LMWCs are suspected to have higher cytotoxicity than their linear counterparts. Therefore, LMWCs are suspected to be the main cause of the long-term toxicity of ophthalmic SilOil, due to their toxicity and propensity to cause ophthalmic SilOil to emulsify. The amount of LMWCs should be considered as the paramount parameter when referring to the quality of SilOil.     

What Is the Clinical Utility of Intravascular Ultrasound?

Purpose of Review

This article reviews the contemporary evidence base for use of coronary intravascular ultrasound (IVUS).

Recent Findings

Recent studies have strongly associated IVUS guidance during percutaneous coronary angioplasty (PCI) with lower major adverse cardiac events (MACE), stent thrombosis, and in selected groups, mortality. The PROSPECT study found in acute coronary syndromes patients, IVUS-determined minimal luminal area?≤?4.0 mm² and the presence of thin-cap fibroatheromas were independent predictors of future MACE in non-culprit lesions. A sub-analysis of the ADAPT-DES trial demonstrated significant reductions in stent thrombosis, myocardial infarction, and composite MACE in patients with IVUS-guided PCI versus angiography alone. In patients with cardiac allograft vasculopathy, IVUS measurements of intimal thickening and attenuated-signal plaque are associated with increased mortality.

Summary

IVUS has become a ubiquitous and versatile adjunct to conventional angiography. It is a powerful tool for identification and assessment of atherosclerotic disease, guidance of percutaneous coronary intervention, and detection of cardiac allograft vasculopathy.

     

What Is the Source of Serum Allergen-Specific IgE?

Immunoglobulin E (IgE), the key effector element in the induction and propagation of allergic diseases, is the least abundant antibody class. In allergic patients, class switch recombination to IgE in B cells is induced by allergen contact in conjunction with T cell interaction and a Th2 cytokine environment. With regard to future therapeutic approaches, the sites of IgE production in human subjects and the nature and characteristics of IgE-producing cells are of great interest. In this context, it has been shown that allergen-specific IgE levels can be boosted by contact with allergens via the respiratory mucosa of the nose. Also, it has been proposed that allergy effector organs (e.g., the nasal mucosa and the lung) may be important sites of IgE production in allergic patients. IgE-producing cells have also been found in the blood, but their numbers are extremely low. Transfer of specific sensitization during bone marrow transplantation indicates the presence of IgE-producing B memory cells or plasma cells also in the bone marrow. This review summarizes data on the induction of IgE production, IgE memory and the sites of IgE production in human allergic patients.     

Heart Rate Variability in Peritoneal Dialysis Patients: What Is the Role of Residual Renal Function?

Background: The relationship between heart rate variability (HRV) and residual renal function (RRF) has not been elucidated previously. Methods: In this cross-sectional study, HRV was evaluated in 71 peritoneal dialysis patients. Patients were divided into RRF decline group, RRF stable group and anuric group. Results: RRF was negatively correlated with SDNN (r = -0.284, p = 0.017), TP (r = -0.247, p = 0.039), and HF (r = -0.238, p = 0.047). Significant sympathetic nerve activation was found in the RRF decline group (significantly lower SDNN, SDSD, RMSSD, pNN50, LF, HF, TP and higher LF/HF ratio) as compared to the RRF stable and anuric groups. Besides, significantly parasympathetic activation was found in the anuric group (the lowest LF/HF ratio as compared to the other groups (both p < 0.05). Multivariate stepwise regression analysis showed that the status of RRF was an independent factor associated with HRV parameters. Conclusion: This study showed autonomic nervous function in peritoneal dialysis patients was associated with a different status of RRF.     

Impact of Sitagliptin on Markers of β-cell Function: A Meta-Analysis

BackgroundProgressive β-cell dysfunction and β-cell failure are fundamental pathogenic consequences of type 2 diabetes. Dipeptidyl peptidase-IV inhibitors may exhibit improvement on preclinical measures of both β-cell function, homeostasis model assessment of β-cell (HOMA-β) index, and β-cell dysfunction, proinsulin/insulin ratio (PI/IR), correlating to β-cell survival.Research Design and MethodsA systematic literature search through July 2008 was conducted to extract a consensus of randomized, controlled trials of sitagliptin therapy on measures of β-cell function. A random-effects model meta-analysis evaluated effects on HOMA-β and PI/IR versus placebo. Several subgroup analyses, including active control, were conducted. Studies were included if they met the following criteria: (1) randomized trials on sitagliptin; (2) placebo or active control; and (3) data reported on HOMA-β or PI/IR.ResultsA total of 11 trials (n = 3039) reported effects on HOMA-β and 8 trials (n = 2325) on PI/IR versus placebo. Four trials (n = 1425) were included in the active control subgroup analysis. Sitagliptin significantly improved HOMA-β index by 12.03% [95% confidence interval (CI), 9.45-14.60] versus placebo. Sitagliptin also significantly decreased PI/IR ?0.06 (95% CI, ?0.08 to ?0.04). Sitagliptin was inferior to active control for HOMA-β index [5.64% (95% CI, 0.38-10.90)], but not different in terms of PI/IR [0.01 (95% CI, ?0.04 to 0.06)].ConclusionsDespite significant improvement in HOMA-β index and PI/IR from placebo, there does not seem to be a benefit of dipeptidyl peptidase-IV inhibitors over other agents with respect to β-cell function/activity. Long-term prevention of β-cell dysfunction cannot be ruled out.