Clinical and morphological effects of hyperbaric oxygen therapy in patients with interstitial cystitis associated with fibromyalgia.

BACKGROUND: Interstitial Cystitis (IC) is a debilitating disorder of the bladder, with a multifactorial and poorly understood origin dealing with microcirculation repeated damages. Also Fibromyalgia (FM) is a persistent disorder whose etiology is not completely explained, and its theorized alteration of pain processing can compromise the quality of life. Both these conditions have a high incidence of conventional therapeutic failure, but recent literature suggests a significant beneficial response to Hyperbaric Oxygen Therapy (HBOT). With this study, this study we evaluated the effects of HBOT on quality of life, symptoms, urodynamic parameters, and cystoscopic examination of patients suffering from both IC and FM. METHODS: We structured an observational clinical trial design with repeated measures (questionnaires, urodynamic test, and cystoscopy) conducted before and 6 months after a therapeutic protocol with hyperbaric oxygen for the treatment of patients suffering from both IC and FM. Patients were exposed to breathing 100% oxygen at 2 atm absolute (ATA) in a multiplace pressure chamber for 90 min using an oro-nasal mask. Patients undertook a cycle of 20 sessions for 5 days per week, and a second cycle of 20 sessions after 1 week of suspension. RESULTS: Twelve patients completed the protocol. Changes after HBOT were not significant, except for hydrodistension tolerance (mean pre-treatment: 409.2 ml; mean post-treatment: 489.2 ml; p < 0.05). A regression of petechiae and Hunner's ulcers was also noted 6 months after the completion of HBOT. CONCLUSIONS: Our study showed no improvement of symptoms, quality of life, and urodynamic parameters, except for hydrodistension, and a slight improvement in cystoscopic pattern. However, to date, we could not demonstrate the significance of overall results to justify the use of HBOT alone in patients with IC and FM. This observation suggests that additional studies are needed to better understand if HBOT could treat this subset of patients. TRIAL REGISTRATION: NCT03693001 ; October 2, 2018. Retrospectively registered.

Adelmidrol + sodium hyaluronate in IC/BPS or conditions associated to chronic urothelial inflammation. A translational study.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by frequent urination, bladder inflammation and pain. It is a particular challenging disease and a clear unmet medical need in terms of identifying new therapeutic strategies. The aim of study was to evaluate the anti-inflammatory effects of intravesical Vessilen® (a new formulation of 2% adelmidrol (the diethanolamide derivative of azelaic acid) + 0.1% sodium hyaluronate) administration in rodent models of IC/BPS and in IC/BPS patients or other bladder disorders. Acute and chronic animal models of cystitis were induced by a single or repetitive intraperitoneal injections of cyclophosphamide (CYP); patients with IC/BPS or with bladder pain syndrome associated with symptoms of the lower urinary tract treated once weekly by bladder instillation of Vessilen® for 8 weeks. CYP instillation caused macroscopic and histological bladder alterations, inflammatory infiltrates, increased mast cell numbers, bladder pain, increased expression of nitrotyrosine, decreased expression of endothelial tight junction zonula occludens-1. Intravesical Vessilen® treatment was able to ameliorate CYP induced bladder inflammation and pain by inhibiting nuclear factor-κB pathway and inflammatory mediator levels as well as reduced mechanical allodynia and nerve growth factor levels. A significant improvement in quality of life and symptom intensity were evident in patients with IC/BPS or other bladder disorders treated with Vessilen®. Vessilen® could be a new therapeutic approach for human cystitis.

A randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome/interstitial cystitis.

AIMS: Intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS) in women with bladder pain syndrome/interstitial cystitis (BPS/IC) has shown promising results. This study compared the efficacy, safety, and costs of intravesical HA/CS (Ialuril® , IBSA) to dimethyl sulfoxide (DMSO). METHODS: Randomized, open-label, multicenter study involving 110 women with BPS/IC. The allocation ratio (HA/CS:DMSO) was 2:1. Thirteen weekly instillations of HA (1.6%)/CS (2.0%) or 50% DMSO were given. Patients were evaluated at 3 (end-of-treatment) and 6 months. Primary endpoint was reduction in pain intensity at 6 months by visual analogue scale (VAS) versus baseline. Secondary efficacy measurements were quality of life and economic analyses. RESULTS: A significant reduction in pain intensity was observed at 6 months in both treatment groups versus baseline (P < 0.0001) in the intention-to-treat population. Treatment with HA/CS resulted in a greater reduction in pain intensity at 6 months compared with DMSO for the per-protocol population (mean VAS reduction 44.77 ± 25.07 vs. 28.89 ± 31.14, respectively; P = 0.0186). There were no significant differences between treatment groups in secondary outcomes. At least one adverse event was reported in 14.86% and 30.56% of patients in the HA/CS and DMSO groups, respectively. There were significantly fewer treatment-related adverse events for HA/CS versus DMSO (1.35% vs. 22.22%; P = 0.001). Considering direct healthcare costs, the incremental cost-effectiveness ratio of HA/CS versus DMSO fell between 3735€/quality-adjusted life years (QALY) and 8003€/QALY. CONCLUSIONS: Treatment with HA/CS appears to be as effective as DMSO with a potentially more favorable safety profile. Both treatments increased health-related quality of life, while HA/CS showed a more acceptable cost-effectiveness profile.

Sacral neuromodulation and Botulinum toxin A for refractory idiopathic overactive bladder: a cost-utility analysis in the perspective of Italian Healthcare System.

OBJECTIVES: To assess the relative cost-effectiveness of two therapeutic strategies: one starting with sacral neuromodulation (SNM) versus one starting with Botulinum toxin A (BTX-A) for the management of refractory incontinent idiopathic overactive bladder (OAB) patients, from the perspective of the Italian National Health Service (INHS). METHODS: Direct medical costs (2011) and benefits (quality-adjusted life years-QALYs) were assessed over a ten-year time frame adapting to the Italian practice a published Markov model. Clinical inputs were based on the published literature and on the expert opinion. Resource consumption rates were provided by clinical experts; unit costs were collected from a single hospital accounting and from standard tariff lists and public prices. Interventional procedures and management of adverse events were costed through a micro-costing approach. The primary outcome was incremental costs per QALYs gained (i.e. differential costs divided by differential benefits). Deterministic (DSA) and probabilistic (PSA) sensitivity analyses were conducted to assess the robustness of the model. RESULTS: Starting with SNM appears to be cost effective (i.e. under 40.000/QALY) from year three (21,259/QALY) onwards and becomes dominant (i.e. more effective and less costly) at year ten: cumulative costs were 32,975 for early SNM and 33,309 for early BTX-A, while cumulative QALYs were 7.52 and 6.93, respectively. At year ten, DSA suggests the results robustness and 99.8 % of the PSA iterations fell within the cost-effectiveness threshold. CONCLUSIONS: A therapeutic strategy starting with SNM may be considered cost effective in the midterm and cost saving in the long-term treatment of idiopathic OAB from the INHS perspective.

Usefulness of sacral nerve modulation in a series of multiple sclerosis patients with bladder dysfunction.

OBJECTIVE: Bladder dysfunctions are common in multiple sclerosis (MS) often causing the most distressing symptoms. The aim of this paper was to evaluate the effectiveness of sacral nerve modulation (SNM) in this disease. METHODS: We conducted an observational retrospective survey in 17 patients treated with SNM in the north-east of Italy, all complaining of bladder symptoms (storage in 41%, voiding in 24%, mixed in 35%) unresponsive to conventional therapies, with a mean follow-up of 52 ± 26 months and mean Expanded Disability Status Scale score of 5.8 ± 1.8. RESULTS: 75% of patients reported significant and lasting improvement in bladder symptoms and in quality of life. We observed a statistically significant improvement in frequency, urgency, number of pads, residual volumes, number of catheterizations and in the voided volumes. In 5 out of 6 cases with mixed symptoms the stimulation was discontinued (device totally explanted or turned off) after a mean time of 66 months (range 10-84 months) after the implant, for disease progression or loss of efficacy. CONCLUSION: SNM could be an option in very selected cases of storage and voiding symptoms refractory to conservative treatments caused by a stable or slowly progressive MS considering its minimal invasiveness and reversibility. The poor results observed suggest avoiding this therapy in mixed symptoms and in cases of advanced disability.

Efficacy of sacral neuromodulation on urological diseases: a multicentric research project.

INTRODUCTION AND AIM OF THE STUDY: Sacral neuromodulation has been used as a safe, effective treatment option for patients with lower urinary tract dysfunction (LUTD). Several clinical studies demonstrated its positive effects on refractory urge incontinence, non-osbstructive urinary retention, urgency frequency syndrome, as well as on other non- urological disorders, such as fecal incontinence and chronic constipation. The aim of this research project was to evaluate the efficacy and safety of sacral neuromodulation on the management of LUTD refractory to the standardized first line treatment options. MATERIALS AND METHODS: We retrospectively collected and evaluated data from patients undergoing sacral neuromodulations between September 2001 and November 2010 in 4 Urological Centres of North-East Italy. The patients were affected by Overactive Bladder Syndrome (OAB), Urinary Retention (UR), Fecal Incontinence (FI), Constipation (CO), Chronic Pelvic Pain (CPP). All the patients were evaluated with voiding diaries, before and after implantation.Patients included in the present evaluation were followed up in a network of 4 Italian urological centres, which participate to in the Italian Clinical Service project - a national urological database and medical care project aiming at describing and improving the use of implantable urological devices in the Italian clinical practice. Continuous normally distributed variables were reported as the mean value ± standard deviation (SD). Continuous non-normally distributed variables were presented as the median values and an interquartile range (IQR). The t-test and Wilcoxon test were used to compare continuous variables, as appropriate. A two-sided p <0.05 was considered statistically significant. RESULTS: Overall, 157 patients underwent implantation of sacral neuromodulator during the period under review. Eighty-three out of 157 (53%) patients complained of OAB; 52 (33%) of UR; 5 (3%) of faecal incontinence; 4 (2%) of chronic constipation; 12 (8%) of CPP. The median follow- up was 11 months (IQR 1 - 91 months). In patients treated for OAB, we documented a statistically significant reduction in the mean number of: incontinence episodes/die, pads/die, daily micturitions, nocturnal micturitions and global micturitions. In patients treated for UR, we observed a statistically significant reduction in the mean post- voiding residual volume and in the number of self catheterization. Interpretation of results: It is difficult to translate into quantifiable data the subjective perception of improvement of the symptoms expressed by the patients, as they are frequently subjective perceptions, not always numeric data. This subjective perception makes it difficult to the clinician to evaluate the real outcomes of this procedure, and makes it difficult to achieve a complete follow-up. CONCLUSIONS: This multicenter research project confirmed the midterm safety and effectiveness of sacral neuromodulation in the treatment of refractory overactive bladder syndrome and urinary retention, showing high cure rates and low complication rates.

New tined lead electrode in sacral neuromodulation: experience from a multicentre European study.

The use of a new tined lead electrode for sacral neuromodulation (SNS) was evaluated in a European study including 127 patients with chronic voiding dysfunction. The tined lead can be implanted during the first stage of the SNS procedure, which makes a longer test period possible before implanting the pulse generator in a second stage. Implantation of the tined lead was performed under local anaesthesia in 89% of patients. Screening lasted on average 30 days. Screening with the tined lead was considered successful by the physicians in 77% of patients (n=72). In 74% of first stage patients (n=70), at least 50% improvement in the main symptoms versus baseline was obtained. This was sustained for up to 6 weeks. All of these patients received the pulse generator in a second stage. The outcome of this study supports the use of the tined lead electrode as a screening tool in SNS therapy.