OBJECTIVES:

To compare the different endovesical therapeutic regimes in terms of clinical effectiveness based on glycosaminoglycan replenishment agents (RA-GAG) available on the market in Spain.

MATERIAL AND METHODS:

A bibliographic analysis was made of the studies published in Medline from 1996 to 2012 on RA-GAG of application in the bladder, placing emphasis on the clinical results. A post-hoc comparison was made of the efficacy of this treatment in the studies conducted in patients with interstitial cystitis in different conditions by calculating the effect sizes to analyze improvement on the pain visual analogue scale (VAS) and clinical response rate. The number of patients needed to treat (NNT) for the different agents was calculated based on the odds ratio and associated economic implications.

RESULTS:

The globally available evidence is scarce. There are 38 articles about RA-GAGs in different indications, 71 of them in interstitial cystitis and only 8 may assist in establishing a comparison between the results presented. The treatments used were placebo, 0.8% high molecular weight hyaluronic acid (Cystistat(®)), 2% chondroitin sulfate sodium (Uracyst(®)) and a combination of 1.6% low molecular weight hyaluronic acid plus 2% chondroitin sulfate (Ialuril(®)), between 6 and 12 instillations. Another low molecular weight hyaluronic acid preparation (Uromac(®)) lacks any scientific evidence. All the therapeutic elements studied show a mean score decrease on the pain VAS and increase in the rate of post-treatment response. The NNT for the treatments that are statistically more beneficial over placebo ranges from 1.6 and 4.1. The post-hoc comparison of the response rates has established that Cystistat(®) 12 instillations (OR 18.8; 95% CI 6.4-57.2; P=.001) or 10 instillations (OR 19.2; 95% CI 5.3-75.3; P=.001) are the treatment regimes that obtain maximum effectiveness. In both cases, the NNT was 1.6.

CONCLUSIONS:

This study has multiple limitations inherent to the nature of the design. However, although the available literature is scarce, it shows that there are differences regarding the clinical effectiveness of the different agents and regimes used for endovesical treatment of interstitial cystitis. These differences also entail economic type implications.

AIMS:

The purpose of this review is to update the current understanding of dimethyl sulfoxide (DMSO) and its role in the treatment of interstitial cystitis (IC).

METHODS:

A systematic review was conducted using the PRIMSA checklist to identify published articles involving intravesical DMSO for the treatment of IC.

RESULTS:

Thirteen cohort studies and three randomized-controlled trials were identified. Response rates relying on subjective measurement scores range from 61 to 95%. No increased efficacy was found with "cocktail" DMSO therapy. Great variation existed in diagnostic criteria, DMSO instillation protocols and response measurements.

CONCLUSIONS:

The current evidence backing DMSO is a constellation of cohort studies and a single randomized-controlled trial versus placebo. The optimal dose, dwell time, type of IC most likely to respond to DMSO, definitions of success/failure and the number of treatments are not universally agreed upon. Improvements in study design, phenotyping patients based on symptoms, as well as the emergence of reliable biomarkers of the disease may better guide the use of DMSO in the future.

Objetivos: Comparación de los diferentes regímenes terapéuticos endovesicales a base de agentes restituidores de glucosaminoglicanos (AR-GAG) comercialmente disponibles en España en términos de efectividad clínica. Material y método: Análisis bibliográfico de los estudios publicados en Medline entre 1996 y 2012 sobre AR-GAG de aplicación vesical con énfasis en los resultados clínicos. Comparación post-hoc de la eficacia de dicho tratamiento en los estudios realizados en pacientes con cistitis intersticial en diferentes condiciones, mediante el cálculo de los tamaños de efecto para el análisis de mejora en la escala analógica visual (EAV) de dolor y la tasa de respuesta clínica. Cálculo del número necesario de pacientes a tratar (NNT) para los distintos agentes a partir de la odds ratio (OR) e implicaciones económicas asociadas. Resultados: La evidencia disponible es globalmente escasa. Un total de 38 artículos tratan de AR-GAG en diferentes indicaciones, 17 de ellos en cistitis intersticial y solamente 8 son subsidiarios de establecer comparación entre los resultados presentados. Los tratamientos empleados fueron placebo, ácido hialurónico de alto peso molecular al 0,8% (Cystistat®), condroitín sulfato sódico al 2% (Uracyst®) y una combinación de ácido hialurónico de bajo peso molecular al 1,6% más condroitín sulfato al 2% (Ialuril®), entre 6 y 12 instilaciones. Otro preparado de ácido hialurónico de bajo peso molecular (Uromac®) carece de evidencia científica alguna. Todos los elementos terapéuticos estudiados muestran disminución de la puntuación media de la EAV de dolor y aumento de la tasa de respuesta postratamiento. El NNT para los tratamientos estadísticamente ventajosos sobre placebo oscila entre 1,6 y 4,1. La comparación post-hoc de las tasas de respuesta establece que Cystistat® 12 instilaciones (OR: 18,8; IC 95%: 6,4-57,2; p=0,001) o 10 instilaciones (OR: 19,2; IC 95%: 5,3-75,3; p=0,001) son las pautas de tratamiento que obtienen máxima efectividad. En ambos casos el NNT fue 1,6. Conclusiones: Este estudio está sujeto a múltiples limitaciones inherentes a la naturaleza de su diseño; no obstante, muestra que, a pesar de que la literatura disponible es escasa, existen diferencias en cuanto a la efectividad clínica de los diferentes agentes y regímenes aplicados para el tratamiento endovesical de la cistitis intersticial. Estas diferencias conllevan también implicaciones de índole económica (AU)

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic disease characterised by persistent irritating micturition symptoms and pain. The objective was to compare the clinical efficacy of currently available products for intravesical therapy of BPS/IC and to assess their pharmacoeconomic impact. A Pubmed/Medline database search was performed for articles on intravesical therapy for BPS/IC. A total of 345 publications were identified, from which 326 were excluded. Statistical evaluation was performed with effect size (ES) assessment of symptom reduction and response rates. The final set of 19 articles on intravesical BPS/IC therapy included 5 prospective controlled trials (CTs), the remaining were classified as uncontrolled clinical studies. The total number of patients included was 801, 228 of whom had been evaluated in a CT. For CTs, the largest ES for symptom reduction as well as response rate was observed for high molecular weight hyaluronic acid (HMW-HA), with similar findings in two uncontrolled studies with HMW-HA. The number needed to treat to achieve a response to intravesical therapy was 2.67 for intravesical pentosan polysulphate and 1.31 for HMW-HA which were superior to all other instillates. HMW-HA was significantly superior in cost effectiveness and cost efficacy to all other instillation regimes. The present meta-analysis combined medical and pharmacoeconomic aspects and demonstrated an advantage of HMW-HA over other instillation agents; however, direct comparisons between the different products have not been performed to date in properly designed controlled studies.

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Pivmecillinam was compared with cotrimoxazole in the treatment of uncomplicated bacterial cystitis in general practice. Similar bacteriological cure rates were obtained with the two treatments. Although micrococci were judged resistant to pivmecillinam by the disc sensitivity method used, cystitis attributed to these organisms and to resistant strains of Proteus mirabilis responded as readily as those due to apparently sensitive Gram-negative bacteria. Pivmecillinam was well tolerated.

BACKGROUND:

There is a paucity of data on the efficacy of nitrofurantoin for the treatment of acute uncomplicated cystitis in regimens shorter than 7 days. Evidence-based use of this drug is increasingly important as trimethoprim-sulfamethoxazole resistance among uropathogens increases.

METHODS:

To assess the efficacy of nitrofurantoin vs trimethoprim-sulfamethoxazole, 338 women aged 18 to 45 years with acute uncomplicated cystitis were randomized to open-label treatment with either trimethoprim-sulfamethoxazole, 1 double-strength tablet twice daily for 3 days, or nitrofurantoin, 100 mg twice daily for 5 days. Clinical cure 30 days after therapy was the main outcome measure. Secondary outcomes included clinical and microbiological cure rates 5 to 9 days after therapy and, for trimethoprim-sulfamethoxazole-treated women, clinical cure stratified by the trimethoprim-sulfamethoxazole susceptibility of the uropathogen.

RESULTS:

Clinical cure was achieved in 79% of the trimethoprim-sulfamethoxazole group and in 84% of the nitrofurantoin group, for a difference of -5% (95% confidence interval, -13% to 4%). Clinical and microbiological cure rates at the first follow-up visit were also equivalent between the 2 groups. In the trimethoprim-sulfamethoxazole arm, 7 of 17 women (41%) with a trimethoprim-sulfamethoxazole-nonsusceptible isolate had a clinical cure compared with 84% of women with a trimethoprim-sulfamethoxazole-susceptible isolate (P < .001).

CONCLUSION:

A 5-day course of nitrofurantoin is equivalent clinically and microbiologically to a 3-day course of trimethoprim-sulfamethoxazole and should be considered an effective fluoroquinolone-sparing alternative for the treatment of acute cystitis in women.

Female patients with interstitial cystitis (IC) unresponsive to standard oral and intravesical therapy were enrolled at three clinical sites for percutaneous sacral nerve root stimulation (PNS) in a prospective, observational pilot study. Evaluation was in the form of a 3-day voiding diary completed both prior to and following the commencement of sacral nerve root stimulation. Symptoms were also assessed by the O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices (ICSI and ICPI). Baseline and test stimulation values for voiding diary parameters and O'Leary-Sant scores were compared to determine treatment efficacy. A total of 33 patients were enrolled. Statistically significant improvements were seen in frequency, pain, average voided volume and maximum voided volume. Significant improvements were also seen in ICSI and ICPI scores. Subacute PNS appears to be effective in reducing symptom severity and increasing voided volumes in patients with IC previously unresponsive to standard therapy.

STUDY OBJECTIVE:

The prevalence of interstitial cystitis (IC) in young women, especially in those 18 years old or younger, is not well defined. This case series was performed to investigate IC as a cause of chronic pelvic pain (CPP) in young women.

DESIGN:

Case series.

SETTING:

University medical center.

PARTICIPANTS:

Twenty-eight women with CPP, ages 13 to 25, who underwent concomitant laparoscopy and cystoscopy.

INTERVENTIONS:

All subjects underwent concomitant diagnostic laparoscopy and cystoscopy with hydrodistension for evaluation of CPP. Charts were reviewed to discern preoperative symptoms, operative findings, and postoperative diagnoses.

MAIN OUTCOME MEASURE:

Diagnosis of IC based on symptoms and cystoscopic findings.

RESULTS:

All 28 women had CPP, 23 (82%) had dysmenorrhea, and 12 of 25 (48%) sexually active subjects had dyspareunia. Twenty-six subjects (93%) had urinary symptoms including frequency (75%), nocturia (32%), urgency (25%), and dysuria (18%). Eleven (39%) subjects were diagnosed with IC and 18 (64%) with endometriosis, including 7 (25%) subjects with both IC and endometriosis. Laparoscopic findings were normal in 6 (21%) subjects. Of the 26 subjects with urinary symptoms, 21 (81%) had findings on laparoscopy or cystoscopy. In this cohort of young women with chronic pelvic pain, urinary frequency and dyspareunia were significantly associated with the diagnosis of IC.

CONCLUSIONS:

The results of this study suggest that interstitial cystitis is an etiology of CPP in young women. Evaluation of the bladder as an origin of pelvic pain is warranted in young women with CPP and urinary frequency or dyspareunia.

CRD COMMENTARY:

This was a clearly presented review with well-defined methods and inclusion criteria. The authors performed an adequate search of the literature and although they did not specifically search for unpublished data they did contact the manufacturer. The authors also stated that publication bias was a possibility but unlikely considering that interstitial cystitis is not common disease and calculations suggest that 12-81 unpublished studies would be required to overturn the findings. They may however have missed relevant data by only including English language publications. A quality assessment and an assessment of study heterogeneity were performed before the studies were combined and the statistical methods used to combine the data appear to be reasonable. It would however have been interesting to know, in the interests of completeness, the drug dose regimens for each individual study. However, it would appear that the evidence presented supports the authors' conclusions.