nach oben

Erschienen in:

06.05.2019 | Review Article

Adverse Events Associated with Nonsurgical Treatments for Urinary Incontinence in Women: a Systematic Review

verfasst von: Ethan M. Balk, MD, MPH, Gaelen P. Adam, MLIS, Katherine Corsi, PharmD, Amanda Mogul, PharmD, Thomas A. Trikalinos, MD, PhD, Peter C. Jeppson, MD

Erschienen in: Journal of General Internal Medicine | Ausgabe 8/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Urinary incontinence (UI) is a common malady in women. Numerous nonsurgical treatments are available, each associated with risk of adverse events (AEs).

Methods

We systematically reviewed nonsurgical interventions for urgency, stress, or mixed UI in women, focusing on AEs. We searched MEDLINE®, Cochrane Central Trials Registry, Cochrane Database of Systematic Reviews, and Embase® through December 4, 2017. We included comparative studies and single-group studies with at least 50 women. Abstracts were screened independently in duplicate. One researcher extracted study characteristics and results with verification by another independent researcher. When at least four studies of a given intervention reported the same AE, we conducted random effects model meta-analyses of proportions. We also assessed the strength of evidence.

Results

There is low strength of evidence that AEs are rare with behavioral therapies and neuromodulation, and that periurethral bulking agents may result in erosion and increase the risk of voiding dysfunction. High strength of evidence finds that anticholinergics and alpha agonists are associated with high rates of dry mouth and constitutional effects such as fatigue and gastrointestinal complaints. Onabotulinum toxin A (BTX) is also associated with increased risk of urinary tract infections (UTIs) and voiding dysfunction (moderate strength of evidence).

Discussion

Behavioral therapies and neuromodulation have low risk of AEs. Anticholinergics and alpha agonists have high rates of dry mouth and constitutional effects. BTX is associated with UTIs and voiding dysfunction. Periurethral bulking agents are associated with erosion and voiding dysfunction. These AEs should be considered when selecting appropriate UI treatment options. AE reporting is inconsistent and AE rates across studies tended to vary widely. Trials should report AEs more consistently.

Nur mit Berechtigung zugänglich

Balk EM, Rofeberg V, Adam GP, et al. Pharmacological and Non-Pharmacological Treatments for Urinary Incontinence in Women: A Systematic Review and Network Meta-Analysis of Clinical Outcomes. Ann Intern Med. 2019; 170(7):465-479. https://doi.org/10.7326/M18-3227.

Heisen M, Baeten SA, Verheggen BG, et al. Patient and physician preferences for oral pharmacotherapy for overactive bladder: two discrete choice experiments. Curr Med Res Opin 2016;32:787–96. https://doi.org/10.1185/03007995.2016.1142959.CrossRefPubMed

Cardozo L, Hall T, Ryan J, et al. Safety and efficacy of flexible-dose fesoterodine in British subjects with overactive bladder: insights into factors associated with dose escalation. Int Urogynecol J 2012;23:1581–90. https://doi.org/10.1007/s00192-012-1804-1.CrossRefPubMed

Lee KS, Lee YS, Kim JC, et al. Patient-reported goal achievement after antimuscarinic treatment in patients with overactive bladder symptoms. Int J Clin Pract 2012;66:663–70. https://doi.org/10.1111/j.1742-1241.2012.02951.x.CrossRefPubMed

Cartwright R, Srikrishna S, Cardozo L, et al. Validity and reliability of patient selected goals as an outcome measure in overactive bladder. Int Urogynecol J 2011;22:841–7. https://doi.org/10.1007/s00192-011-1360-0.CrossRefPubMed

Coyne KS, Sexton CC, Kopp Z, et al. Assessing patients’ descriptions of lower urinary tract symptoms (LUTS) and perspectives on treatment outcomes: results of qualitative research. Int J Clin Pract 2010;64:1260–78. https://doi.org/10.1111/j.1742-1241.2010.02450.x.CrossRefPubMed

Balk E, Adam GP, Kimmel H, et al. Nonsurgical Treatments for Urinary Incontinence in Women: A Systematic Review Update. (Prepared by the Brown Evidence-based Practice Center under Contract No. 290–2015-00002-I for AHRQ and PCORI.) AHRQ Publication No. 18-EHC016-EF. PCORI Publication No. 2018-SR-03. Rockville, MD: Agency for Healthcare Research and Quality; August 2018. Available at: https://doi.org/10.23970/AHRQEPCCER212. Accessed 5 March 2019.

Methods Guide for Effectiveness and Comparative Effectiveness Reviews. AHRQ Publication No. 10(14)-EHC063-EF. Rockville, MD: Agency for Healthcare Research and Quality. January 2014. Chapters available at: https://effectivehealthcare.ahrq.gov/research-methods. Accessed 5 March 2019.

Shamliyan T, Wyman J, Kane RL. Nonsurgical Treatments for Urinary Incontinence in Adult Women: Diagnosis and Comparative Effectiveness. Comparative Effectiveness Review No. 36. (Prepared by the University of Minnesota Evidence-based Practice Center under Contract No. HHSA 290–2007-10064-I.) AHRQ Publication No. 11(12)-EHC074- EF. Rockville, MD. Agency for Healthcare Research and Quality; April 2012. Available at: https://effectivehealthcare.ahrq.gov/topics/urinary-incontinence-treatment/research. Accessed March 5, 2019.

10.

Trikalinos TA, Hoaglin DC, Schmid CH. Empirical and Simulation-Based Comparison of Univariate and Multivariate Meta-Analysis for Binary Outcomes. Methods Research Report. (Prepared by the Tufts Evidence-based Practice Center under Contract No. 290–2007-10055-I.) AHRQ Publication No. 13-EHC066-EF. Rockville, MD: Agency for Healthcare Research and Quality; March 2013. Available at: https://effectivehealthcare.ahrq.gov/topics/methods-binary-outcomes-evaluation/research. Accessed 5 March 2019.

11.

Berkman ND, Lohr KN, Ansari M, et al. Grading the Strength of a Body of Evidence When Assessing Health Care Interventions for the Effective Health Care Program of the Agency for Healthcare Research and Quality: An Update. Methods Guide for Comparative Effectiveness Reviews (Prepared by the RTI-UNC Evidence-based Practice Center under Contract No. 290–2007-10056-I). AHRQ Publication No. 13(14)-EHC130-EF. Rockville, MD: Agency for Healthcare Research and Quality. November 2013. Available at: https://effectivehealthcare.ahrq.gov/topics/methods-guidance-grading-evidence/methods. Accessed 5 March 2019.

12.

Abdelbary AM, El-Dessoukey AA, Massoud AM, et al. Combined Vaginal Pelvic Floor Electrical Stimulation (PFS) and Local Vaginal Estrogen for Treatment of Overactive Bladder (OAB) in Perimenopausal Females. Randomized Controlled Trial (RCT). Urology. 2015;86:482–6. https://doi.org/10.1016/j.urology.2015.06.007.CrossRefPubMed

13.

Alves PG, Nunes FR, Guirro EC. Comparison between two different neuromuscular electrical stimulation protocols for the treatment of female stress urinary incontinence: a randomized controlled trial. Rev Bras Fis 2011;15:393–8.CrossRef

14.

Baker J, Costa D, Guarino JM, et al. Comparison of mindfulness-based stress reduction versus yoga on urinary urge incontinence: a randomized pilot study. with 6-month and 1-year follow-up visits. Female Pelvic Med Reconstr Surg. 2014;20:141–6. https://doi.org/10.1097/spv.0000000000000061.CrossRefPubMed

15.

Beer GM, Gurule MM, Komesu YM, et al. Cycling Versus Continuous Mode In Neuromodulator Programming: A Crossover, Randomized, Controlled Trial. Urol Nurs 2016;36:123–32.CrossRef

16.

Betschart C, Mol SE, Lutolf-Keller B, et al. Pelvic floor muscle training for urinary incontinence: a comparison of outcomes in premenopausal versus postmenopausal women. Female Pelvic Med Reconstr Surg. 2013;19:219–24. https://doi.org/10.1097/SPV.0b013e31829950e5.CrossRefPubMed

17.

Castellani D, Saldutto P, Galica V, et al. Low-Dose Intravaginal Estriol and Pelvic Floor Rehabilitation in Post-Menopausal Stress Urinary Incontinence. Urol Int 2015;95:417–21. https://doi.org/10.1159/000381989.CrossRefPubMed

18.

de Souza Abreu N, de Castro Villas Boas B, Netto JM, et al. Dynamic lumbopelvic stabilization for treatment of stress urinary incontinence in women: Controlled and randomized clinical trial. Neurourol Urodyn. 2017;36:2160–2168. https://doi.org/10.1002/nau.23261.CrossRef

19.

Ferreira M, Santos PC. Impact of exercise programs in woman's quality of life with stress urinary incontinence. Rev Port Saúde Pública 2012;30:3–10.CrossRef

20.

Fitz FF, Stupp L, da Costa TF, et al. Outpatient biofeedback in addition to home pelvic floor muscle training for stress urinary incontinence: a randomized controlled trial. Neurourol Urodyn 2017; 36:2034–43. https://doi.org/10.1002/nau.23226.CrossRefPubMed

21.

Galea MP, Tisseverasinghe S, Sherburn M. A randomised controlled trial of transabdominal ultrasound biofeedback for pelvic floor muscle training in older women with urinary incontinence. Aust N Z Continence J 2013;19:38-44.

22.

Gozukara YM, Akalan G, Tok EC, et al. The improvement in pelvic floor symptoms with weight loss in obese women does not correlate with the changes in pelvic anatomy. Int Urogynecol J 2014;25:1219–25. https://doi.org/10.1007/s00192-014-2368-z.CrossRefPubMed

23.

Hirakawa T, Suzuki S, Kato K, et al. Randomized controlled trial of pelvic floor muscle training with or without biofeedback for urinary incontinence. Int Urogynecol J 2013;24:1347–54. https://doi.org/10.1007/s00192-012-2012-8.CrossRefPubMed

24.

Huebner M, Riegel K, Hinninghofen H, et al. Pelvic floor muscle training for stress urinary incontinence: a randomized, controlled trial comparing different conservative therapies. Physiother Res Int 2011;16:133–40. https://doi.org/10.1002/pri.489.CrossRefPubMed

25.

Jha S, Walters SJ, Bortolami O, et al. Impact of pelvic floor muscle training on sexual function of women with urinary incontinence and a comparison of electrical stimulation versus standard treatment (IPSU trial): a randomised controlled trial. Physiotherapy. 2017; 104:91–7. https://doi.org/10.1016/j.physio.2017.06.003.CrossRefPubMed

26.

Kaya S, Akbayrak T, Beksac S. Comparison of different treatment protocols in the treatment of idiopathic detrusor overactivity: a randomized controlled trial. Clin Rehabil 2011;25:327–38. https://doi.org/10.1177/0269215510385481.CrossRefPubMed

27.

Kaya S, Akbayrak T, Gursen C, et al. Short-term effect of adding pelvic floor muscle training to bladder training for female urinary incontinence: a randomized controlled trial. Int Urogynecol J 2015;26:285–93. https://doi.org/10.1007/s00192-014-2517-4.CrossRefPubMed

28.

Labrie J, Berghmans BL, Fischer K, et al. Surgery versus physiotherapy for stress urinary incontinence. N Engl J Med 2013;369:1124–33. https://doi.org/10.1056/NEJMoa1210627.CrossRefPubMed

29.

Leong BS, Mok NW. Effectiveness of a new standardised Urinary Continence Physiotherapy Programme for community-dwelling older women in Hong Kong. Hong Kong Med J. 2015;21:30–7. https://doi.org/10.12809/hkmj134185.CrossRefPubMed

30.

Manonai J, Kamthaworn S, Petsarb K, et al. Development of a pelvic floor muscle strength evaluation device. J Med Assoc Thail 2015;98:219–25.

31.

McLean L, Varette K, Gentilcore-Saulnier E, et al. Pelvic floor muscle training in women with stress urinary incontinence causes hypertrophy of the urethral sphincters and reduces bladder neck mobility during coughing. Neurourol Urodyn 2013;32:1096–102. https://doi.org/10.1002/nau.22343.CrossRefPubMedPubMedCentral

32.

Oldham J, Herbert J, McBride K. Evaluation of a new disposable “tampon like” electrostimulation technology (Pelviva(R)) for the treatment of urinary incontinence in women: a 12-week single blind randomized controlled trial. Neurourol Urodyn 2013;32:460–6. https://doi.org/10.1002/nau.22326.CrossRefPubMed

33.

Olmo Carmona MV, González Molleja ÁM, Luque Ríos I, et al. Neuroestimulación percutánea del nervio tibial posterior frente a neuroestimulación de B 6 (Sanyinjiao) en incontinencia urinaria de urgencia. Rev Int Acupuntura 2013;7:124–30.

34.

Pereira VS, de Melo MV, Correia GN, et al. Long-term effects of pelvic floor muscle training with vaginal cone in post-menopausal women with urinary incontinence: a randomized controlled trial. Neurourol Urodyn 2013;32:48–52. https://doi.org/10.1002/nau.22271.CrossRefPubMed

35.

Peters KM, Shen L, McGuire M. Effect of Sacral Neuromodulation Rate on Overactive Bladder Symptoms: A Randomized Crossover Feasibility Study. Low Urin Tract Symptoms. 2013;5:129–33. https://doi.org/10.1111/luts.12000.CrossRefPubMed

36.

Porta-Roda O, Vara-Paniagua J, Diaz-Lopez MA, et al. Effect of vaginal spheres and pelvic floor muscle training in women with urinary incontinence: a randomized, controlled trial. Neurourol Urodyn 2015;34:533–8. https://doi.org/10.1002/nau.22640.CrossRefPubMed

37.

Resnick NM, Perera S, Tadic S, et al. What predicts and what mediates the response of urge urinary incontinence to biofeedback? Neurourol Urodyn 2013;32:408–15. https://doi.org/10.1002/nau.22347.CrossRefPubMed

38.

Segal S, Morse A, Sangal P, et al. Efficacy of FemiScan Pelvic Floor Therapy for the Treatment of Urinary Incontinence. Female Pelvic Med Reconstr Surg 2016;22:433–7. https://doi.org/10.1097/spv.0000000000000307.CrossRefPubMed

39.

Sherburn M, Bird M, Carey M, et al. Incontinence improves in older women after intensive pelvic floor muscle training: an assessor-blinded randomized controlled trial. Neurourol Urodyn 2011;30:317–24. https://doi.org/10.1002/nau.20968.CrossRefPubMed

40.

Siegel S, Noblett K, Mangel J, et al. Three-year Follow-up Results of a Prospective, Multicenter Study in Overactive Bladder Subjects Treated With Sacral Neuromodulation. Urology. 2016;94:57–63. https://doi.org/10.1016/j.urology.2016.04.024.CrossRefPubMed

41.

Sjostrom M, Umefjord G, Stenlund H, et al. Internet-based treatment of stress urinary incontinence: a randomised controlled study with focus on pelvic floor muscle training. BJU Int 2013;112:362–72. https://doi.org/10.1111/j.1464-410X.2012.11713.x.CrossRefPubMedPubMedCentral

42.

Sran M, Mercier J, Wilson P, et al. Physical therapy for urinary incontinence in postmenopausal women with osteoporosis or low bone density: a randomized controlled trial. Menopause. 2016;23:286–93. https://doi.org/10.1097/gme.0000000000000594.CrossRefPubMed

43.

Wang S, Lv J, Feng X, et al. Efficacy of Electrical Pudendal Nerve Stimulation versus Transvaginal Electrical Stimulation in Treating Female Idiopathic Urgency Urinary Incontinence. J Urol 2017;197:1496–501. https://doi.org/10.1016/j.juro.2017.01.065.CrossRefPubMed

44.

Yamanishi T, Suzuki T, Sato R, et al. Effects of magnetic stimulation on urodynamic stress incontinence refractory to pelvic floor muscle training in a randomized sham-controlled study. Low Urin Tract Symptoms 2017;11:61–5. https://doi.org/10.1111/luts.12197.CrossRefPubMed

45.

Kafri R, Deutscher D, Shames J, et al. Randomized trial of a comparison of rehabilitation or drug therapy for urgency urinary incontinence: 1-year follow-up. Int Urogynecol J 2013;24:1181–9. https://doi.org/10.1007/s00192-012-1992-8.CrossRefPubMed

46.

Ozdedeli S, Karapolat H, Akkoc Y. Comparison of intravaginal electrical stimulation and trospium hydrochloride in women with overactive bladder syndrome: a randomized controlled study. Clin Rehabil 2010;24:342–51. https://doi.org/10.1177/0269215509346092.CrossRefPubMed

47.

Peters KM, Macdiarmid SA, Wooldridge LS, et al. Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial. J Urol 2009;182:1055–61. https://doi.org/10.1016/j.juro.2009.05.045.CrossRefPubMed

48.

Burgio KL, Locher JL, Goode PS, et al. Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial. JAMA. 1998;280:1995–2000.CrossRef

49.

Ahlund S, Nordgren B, Wilander EL, et al. Is home-based pelvic floor muscle training effective in treatment of urinary incontinence after birth in primiparous women? A randomized controlled trial. Acta Obstet Gynecol Scand 2013;92:909–15. https://doi.org/10.1111/aogs.12173.CrossRefPubMed

50.

Amundsen CL, Richter HE, Menefee SA, et al. OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial. JAMA. 2016;316:1366–74. https://doi.org/10.1001/jama.2016.14617.CrossRefPubMedPubMedCentral

51.

Kim H, Yoshida H, Suzuki T. Effects of exercise treatment with or without heat and steam generating sheet on urine loss in community-dwelling Japanese elderly women with urinary incontinence. Geriatr Gerontol Int 2011;11:452–9. https://doi.org/10.1111/j.1447-0594.2011.00705.x.CrossRefPubMed

52.

Lim R, Liong ML, Leong WS, et al. Pulsed Magnetic Stimulation for Stress Urinary Incontinence: 1-Year Followup Results. J Urol 2017;197:1302–8. https://doi.org/10.1016/j.juro.2016.11.091.CrossRefPubMed

53.

Liu Z, Liu Y, Xu H, et al. Effect of Electroacupuncture on Urinary Leakage Among Women With Stress Urinary Incontinence: A Randomized Clinical Trial. JAMA. 2017;317:2493–501. https://doi.org/10.1001/jama.2017.7220.CrossRefPubMedPubMedCentral

54.

Lovatsis D, Best C, Diamond P. Short-term Uresta efficacy (SURE) study: a randomized controlled trial of the Uresta continence device. Int Urogynecol J 2017;28:147–50. https://doi.org/10.1007/s00192-016-3090-9.CrossRefPubMed

55.

Pereira VS, Bonioti L, Correia GN, et al. [Effects of surface electrical stimulation in older women with stress urinary incontinence: a randomized controlled pilot study]. Actas Urol Esp 2012;36:491–6. https://doi.org/10.1016/j.acuro.2011.11.016.CrossRefPubMed

56.

Samuelsson E. Treatment of Stress Urinary Incontinence Via Smartphone; 2017. https://clinicaltrials.gov/ct2/show/NCT01848938. Accessed 5 March 2019.

57.

Solberg M, Alraek T, Mdala I, et al. A pilot study on the use of acupuncture or pelvic floor muscle training for mixed urinary incontinence. Acupunct Med 2016;34:7–13. https://doi.org/10.1136/acupmed-2015-010828.CrossRefPubMed

58.

Terlikowski R, Dobrzycka B, Kinalski M, et al. Transvaginal electrical stimulation with surface-EMG biofeedback in managing stress urinary incontinence in women of premenopausal age: a double-blind, placebo-controlled, randomized clinical trial. Int Urogynecol J 2013;24:1631–8. https://doi.org/10.1007/s00192-013-2071-5.CrossRefPubMedPubMedCentral

59.

Wallis MC, Davies EA, Thalib L, et al. Pelvic static magnetic stimulation to control urinary incontinence in older women: a randomized controlled trial. Clin Med Res 2012;10:7–14. https://doi.org/10.3121/cmr.2011.1008.CrossRefPubMedPubMedCentral

60.

Wiegersma M, Panman CM, Kollen BJ, et al. Effect of pelvic floor muscle training compared with watchful waiting in older women with symptomatic mild pelvic organ prolapse: randomised controlled trial in primary care. BMJ. 2014;349:g7378. https://doi.org/10.1136/bmj.g7378.CrossRefPubMedPubMedCentral

61.

Abdulaziz K, Hasan T. Role of pelvic floor muscle therapy in obese perimenopausal females with stress incontinence: A randomized control trial. Int J Gynecol Obstet 2012;16:34–42.

62.

Cornu JN, Mouly S, Amarenco G, et al. 75NC007 device for noninvasive stress urinary incontinence management in women: a randomized controlled trial. Int Urogynecol J 2012;23:1727–34. https://doi.org/10.1007/s00192-012-1814-z.CrossRefPubMed

63.

Xu H, Liu B, Wu J, et al. A Pilot Randomized Placebo Controlled Trial of Electroacupuncture for Women with Pure Stress Urinary Incontinence. PLoS One 2016;11:e0150821. https://doi.org/10.1371/journal.pone.0150821.CrossRefPubMedPubMedCentral

64.

Bray R, Cartwright R, Cardozo L, et al. Tolterodine ER reduced increased bladder wall thickness in women with overactive bladder. A randomized, placebo-controlled, double-blind, parallel group study. Neurourol Urodyn 2017; 37:237–43. https://doi.org/10.1002/nau.23281.CrossRefPubMed

65.

Dmochowski RR, Davila GW, Zinner NR, et al. Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence. J Urol 2002;168:580–6.CrossRef

66.

Dmochowski RR, Staskin DR, Duchin K, et al. Clinical safety, tolerability and efficacy of combination tolterodine/pilocarpine in patients with overactive bladder. Int J Clin Pract 2014;68:986–94. https://doi.org/10.1111/ijcp.12409.CrossRefPubMed

67.

DuBeau CE, Khullar V, Versi E. “Unblinding” in randomized controlled drug trials for urinary incontinence: Implications for assessing outcomes when adverse effects are evident. Neurourol Urodyn 2005;24:13–20. https://doi.org/10.1002/nau.20083.CrossRefPubMed

68.

Frenkl T, Railkar R, Shore N, et al. Evaluation of an experimental urodynamic platform to identify treatment effects: a randomized, placebo-controlled, crossover study in patients with overactive bladder. Neurourol Urodyn 2012;31:69–74. https://doi.org/10.1002/nau.21094.CrossRefPubMed

69.

Gittelman M, Weiss H, Seidman L. A phase 2, randomized, double-blind, efficacy and safety study of oxybutynin vaginal ring for alleviation of overactive bladder symptoms in women. J Urol 2014;191:1014–21. https://doi.org/10.1016/j.juro.2013.11.019.CrossRefPubMed

70.

Homma Y, Paick JS, Lee JG, et al. Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial. BJU Int 2003;92:741–7.CrossRef

71.

Khullar V, Hill S, Laval KU, et al. Treatment of urge-predominant mixed urinary incontinence with tolterodine extended release: a randomized, placebo-controlled trial. Urology. 2004;64:269–74. https://doi.org/10.1016/j.urology.2004.02.029.CrossRefPubMed

72.

Klarskov N, Darekar A, Scholfield D, et al. Effect of fesoterodine on urethral closure function in women with stress urinary incontinence assessed by urethral pressure reflectometry. Int Urogynecol J 2014;25:755–60. https://doi.org/10.1007/s00192-013-2269-6.CrossRefPubMed

73.

McMichael J. Safety and Efficacy Study of a New Treatment for Symptoms of Urinary Incontinence; 2013. https://clinicaltrials.gov/ct2/show/NCT01340066. Accessed 5 March 2019.

74.

Moore KH, Hay DM, Imrie AE, et al. Oxybutynin hydrochloride (3 mg) in the treatment of women with idiopathic detrusor instability. Br J Urol 1990;66:479–85.CrossRef

75.

Nelken RS, Ozel BZ, Leegant AR, et al. Randomized trial of estradiol vaginal ring versus oral oxybutynin for the treatment of overactive bladder. Menopause. 2011;18:962–6. https://doi.org/10.1097/gme.0b013e3182104977.CrossRefPubMed

76.

Orri M, Lipset CH, Jacobs BP, et al. Web-based trial to evaluate the efficacy and safety of tolterodine ER 4 mg in participants with overactive bladder: REMOTE trial. Contemp Clin Trials 2014;38:190–7. https://doi.org/10.1016/j.cct.2014.04.009.CrossRefPubMed

77.

Rogers R, Bachmann G, Jumadilova Z, et al. Efficacy of tolterodine on overactive bladder symptoms and sexual and emotional quality of life in sexually active women. Int Urogynecol J Pelvic Floor Dysfunct 2008;19:1551–7. https://doi.org/10.1007/s00192-008-0688-6.CrossRefPubMed

78.

Sand PK, Dmochowski RR, Zinner NR, et al. Trospium chloride extended release is effective and well tolerated in women with overactive bladder syndrome. Int Urogynecol J Pelvic Floor Dysfunct 2009;20:1431–8. https://doi.org/10.1007/s00192-009-0969-8.CrossRefPubMed

79.

Swift S, Garely A, Dimpfl T, et al. A new once-daily formulation of tolterodine provides superior efficacy and is well tolerated in women with overactive bladder. Int Urogynecol J Pelvic Floor Dysfunct 2003;14:50–4. https://doi.org/10.1007/s00192-002-1009-0.CrossRefPubMed

80.

Szonyi G, Collas DM, Ding YY, et al. Oxybutynin with bladder retraining for detrusor instability in elderly people: a randomized controlled trial. Age Ageing 1995;24:287–91.CrossRef

81.

Tapp AJ, Cardozo LD, Versi E, et al. The treatment of detrusor instability in post-menopausal women with oxybutynin chloride: a double blind placebo controlled study. Br J Obstet Gynaecol 1990;97:521–6.CrossRef

82.

Thuroff JW, Bunke B, Ebner A, et al. Randomized, double-blind, multicenter trial on treatment of frequency, urgency and incontinence related to detrusor hyperactivity: oxybutynin versus propantheline versus placebo. J Urol 1991;145:813–6.CrossRef

83.

Zinner N, Tuttle J, Marks L. Efficacy and tolerability of darifenacin, a muscarinic M3 selective receptor antagonist (M3 SRA), compared with oxybutynin in the treatment of patients with overactive bladder. World J Urol 2005;23:248–52. https://doi.org/10.1007/s00345-005-0507-3.CrossRefPubMed

84.

Anderson RU, Mobley D, Blank B, et al. Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. OROS Oxybutynin Study Group. J Urol. 1999;161:1809–12.CrossRef

85.

Anderson RU, MacDiarmid S, Kell S, et al. Effectiveness and tolerability of extended-release oxybutynin vs extended-release tolterodine in women with or without prior anticholinergic treatment for overactive bladder. Int Urogynecol J Pelvic Floor Dysfunct 2006;17:502–11. https://doi.org/10.1007/s00192-005-0057-7.CrossRefPubMed

86.

Appell RA. Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis. Urology. 1997;50(6A Suppl):S90–6.CrossRef

87.

Armstrong RB, Luber KM, Peters KM. Comparison of dry mouth in women treated with extended-release formulations of oxybutynin or tolterodine for overactive bladder. Int Urol Nephrol 2005;37:247–52. https://doi.org/10.1007/s11255-004-4703-7.CrossRefPubMed

88.

Aziminekoo E, Ghanbari Z, Hashemi S, et al. Oxybutynin and tolterodine in a trial for treatment of overactive bladder in Iranian women. J Family Reprod Health 2014;8:73–6.PubMedPubMedCentral

89.

Bodeker RH, Madersbacher H, Neumeister C, et al. Dose escalation improves therapeutic outcome: post hoc analysis of data from a 12-week, multicentre, double-blind, parallel-group trial of trospium chloride in patients with urinary urge incontinence. BMC Urol 2010;10:15. https://doi.org/10.1186/1471-2490-10-15.CrossRefPubMedPubMedCentral

90.

But I, Goldstajn MS, Oreskovic S. Comparison of two selective muscarinic receptor antagonists (solifenacin and darifenacin) in women with overactive bladder--the SOLIDAR study. Coll Antropol 2012;3:1347–53.

91.

Butt F, Badar N, Rana M. Comparison of Side Effects of Solifenacin Vs Tolteridine in Patients with Urinary Incontinence. Pakistan J Med Health Sci 2016;10:590–3.

92.

Chapple C, van Kerrebroeck P, Tubaro A, et al. Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder. Eur Urol 2007;52:1204–12. https://doi.org/10.1016/j.eururo.2007.07.009.CrossRefPubMed

93.

Chu FM, Dmochowski RR, Lama DJ, et al. Extended-release formulations of oxybutynin and tolterodine exhibit similar central nervous system tolerability profiles: a subanalysis of data from the OPERA trial. Am J Obstet Gynecol 2005;192:1849–54. https://doi.org/10.1016/j.ajog.2005.03.036.CrossRefPubMed

94.

Chughtai B, Forde JC, Buck J, et al. The concomitant use of fesoterodine and topical vaginal estrogen in the management of overactive bladder and sexual dysfunction in postmenopausal women. Post Reprod Health 2016;22:34–40. https://doi.org/10.1177/2053369116633017.CrossRefPubMed

95.

Davila GW, Daugherty CA, Sanders SW. A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol 2001;166:140–5.CrossRef

96.

Dede H, Dolen I, Dede FS, et al. What is the success of drug treatment in urge urinary incontinence? What should be measured? Arch Gynecol Obstet 2013;287:511–8. https://doi.org/10.1007/s00404-012-2596-8.CrossRefPubMed

97.

Gameiro MO, Moreira EH, Gameiro FO, et al. Vaginal weight cone versus assisted pelvic floor muscle training in the treatment of female urinary incontinence. A prospective, single-blind, randomized trial. Int Urogynecol J 2010;21:395–9. https://doi.org/10.1007/s00192-009-1059-7.CrossRefPubMed

98.

Gupta SK, Sathyan G, Lindemulder EA, et al. Quantitative characterization of therapeutic index: application of mixed-effects modeling to evaluate oxybutynin dose-efficacy and dose-side effect relationships. Clin Pharmacol Ther 1999;65:672–84. https://doi.org/10.1016/s0009-9236(99)90089-9.CrossRefPubMed

99.

Gupta SK, Sathyan G. Pharmacokinetics of an oral once-a-day controlled-release oxybutynin formulation compared with immediate-release oxybutynin. J Clin Pharmacol 1999;39:289–96.PubMed

100.

Hess R, Huang AJ, Richter HE, et al. Long-term efficacy and safety of questionnaire-based initiation of urgency urinary incontinence treatment. Am J Obstet Gynecol. 2013;209:244.e1–9. https://doi.org/10.1016/j.ajog.2013.05.008.CrossRef

101.

Jafarabadi M, Jafarabadi L, Shariat M, et al. Considering the prominent complaint as a guide in medical therapy for overactive bladder syndrome in women over 45 years. J Obstet Gynaecol Res 2015;41:120–6. https://doi.org/10.1111/jog.12483.CrossRefPubMed

102.

Kinjo M, Sekiguchi Y, Yoshimura Y, et al. Long-term Persistence with Mirabegron versus Solifenacin in Women with Overactive Bladder: Prospective, Randomized Trial. Low Urin Tract Symptoms. 2016; 10:148–52. https://doi.org/10.1111/luts.12151.CrossRefPubMed

103.

Lackner TE, Wyman JF, McCarthy TC, et al. Randomized, placebo-controlled trial of the cognitive effect, safety, and tolerability of oral extended-release oxybutynin in cognitively impaired nursing home residents with urge urinary incontinence. J Am Geriatr Soc 2008;56:862–70. https://doi.org/10.1111/j.1532-5415.2008.01680.x.CrossRefPubMed

104.

Madersbacher H, Halaska M, Voigt R, et al. A placebo-controlled, multicentre study comparing the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence. BJU Int 1999;84:646–51.CrossRef

105.

Milani R, Scalambrino S, Milia R, et al. Double-Blind Crossover Comparison of Flavoxate and Oxybutynin in Women Affected by Urinary Urge Syndrome. Int Urogynecol J 1993;4:3–8.CrossRef

106.

Preik M, Albrecht D, O'Connell M, et al. Effect of controlled-release delivery on the pharmacokinetics of oxybutynin at different dosages: severity-dependent treatment of the overactive bladder. BJU Int 2004;94:821–7. https://doi.org/10.1111/j.1464-410X.2004.05040.x.CrossRefPubMed

107.

Rogers RG, Bachmann G, Scarpero H, et al. Effects of tolterodine ER on patient-reported outcomes in sexually active women with overactive bladder and urgency urinary incontinence. Curr Med Res Opin 2009;25:2159–65. https://doi.org/10.1185/03007990903103279.CrossRefPubMed

108.

Saks EK, Wiebe DJ, Cory LA, et al. Beliefs about medications as a predictor of treatment adherence in women with urinary incontinence. J Women's Health (Larchmt) 2012;21:440–6. https://doi.org/10.1089/jwh.2011.2952.CrossRef

109.

Salvatore S, Khullar V, Cardozo L, et al. Long-term prospective randomized study comparing two different regimens of oxybutynin as a treatment for detrusor overactivity. Eur J Obstet Gynecol Reprod Biol 2005;119:237–41. https://doi.org/10.1016/j.ejogrb.2004.07.042.CrossRefPubMed

110.

Sand PK, Miklos J, Ritter H, et al. A comparison of extended-release oxybutynin and tolterodine for treatment of overactive bladder in women. Int Urogynecol J Pelvic Floor Dysfunct 2004;15:243–8.PubMed

111.

Sand PK, Morrow JD, Bavendam T, et al. Efficacy and tolerability of fesoterodine in women with overactive bladder. Int Urogynecol J Pelvic Floor Dysfunct 2009;20:827–35. https://doi.org/10.1007/s00192-009-0857-2.CrossRefPubMed

112.

Zellner M, Madersbacher H, Palmtag H, et al. Trospium chloride and oxybutynin hydrochloride in a german study of adults with urinary urge incontinence: results of a 12-week, multicenter, randomized, double-blind, parallel-group, flexible-dose noninferiority trial. Clin Ther 2009;31:2519–39. https://doi.org/10.1016/j.clinthera.2009.11.005.CrossRefPubMed

113.

Zimmern P, Litman HJ, Mueller E, et al. Effect of fluid management on fluid intake and urge incontinence in a trial for overactive bladder in women. BJU Int 2010;105:1680–5. https://doi.org/10.1111/j.1464-410X.2009.09055.x.CrossRefPubMed

114.

Visco AG, Brubaker L, Richter HE, et al. Anticholinergic therapy vs. onabotulinumtoxina for urgency urinary incontinence. N Engl J Med 2012;367:1803–13. https://doi.org/10.1056/NEJMoa1208872.CrossRefPubMedPubMedCentral

115.

Dmochowski RR, Sand PK, Zinner NR, et al. Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence. Urology. 2003;62:237–42.CrossRef

116.

Drutz HP, Appell RA, Gleason D, et al. Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder. Int Urogynecol J Pelvic Floor Dysfunct 1999;10:283–9.CrossRef

117.

Huang AJ, Hess R, Arya LA, et al. Pharmacologic treatment for urgency-predominant urinary incontinence in women diagnosed using a simplified algorithm: a randomized trial. Am J Obstet Gynecol. 2012;206:444.e1–11. https://doi.org/10.1016/j.ajog.2012.03.002.CrossRef

118.

Marencak J, Cossons NH, Darekar A, et al. Investigation of the clinical efficacy and safety of pregabalin alone or combined with tolterodine in female subjects with idiopathic overactive bladder. Neurourol Urodyn 2011;30:75–82. https://doi.org/10.1002/nau.20928.CrossRefPubMed

119.

Sung HH, Han DH, Kim TH, et al. Interventions do not enhance medication persistence and compliance in patients with overactive bladder: a 24 weeks, randomised, open-label, multi-center trial. Int J Clin Pract 2015;69:1309–15. https://doi.org/10.1111/ijcp.12705.CrossRefPubMed

120.

van Kerrebroeck P, Abrams P, Lange R, et al. Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence. BJOG. 2004;111:249–57.CrossRef

121.

Balachandran A, Duckett J. The efficacy and tolerability of mirabegron in a non-trial clinical setting. Eur J Obstet Gynecol Reprod Biol 2016;200:63–7. https://doi.org/10.1016/j.ejogrb.2016.02.030.CrossRefPubMed

122.

Bent AE, Gousse AE, Hendrix SL, et al. Duloxetine compared with placebo for the treatment of women with mixed urinary incontinence. Neurourol Urodyn 2008;27:212–21. https://doi.org/10.1002/nau.20471.CrossRefPubMed

123.

Capobianco G, Donolo E, Borghero G, et al. Effects of intravaginal estriol and pelvic floor rehabilitation on urogenital aging in postmenopausal women. Arch Gynecol Obstet 2012;285:397–403. https://doi.org/10.1007/s00404-011-1955-1.CrossRefPubMed

124.

Cardozo L, Drutz HP, Baygani SK, et al. Pharmacological treatment of women awaiting surgery for stress urinary incontinence. Obstet Gynecol 2004;104:511–9. https://doi.org/10.1097/01.AOG.0000134525.86480.0f.CrossRefPubMed

125.

Castro-Diaz D, Palma PC, Bouchard C, et al. Effect of dose escalation on the tolerability and efficacy of duloxetine in the treatment of women with stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2007;18:919–29. https://doi.org/10.1007/s00192-006-0256-x.CrossRefPubMed

126.

Dmochowski RR, Miklos JR, Norton PA, et al. Duloxetine versus placebo for the treatment of North American women with stress urinary incontinence. J Urol 2003;170:1259–63. https://doi.org/10.1097/01.ju.0000080708.87092.cc.CrossRefPubMed

127.

Ghoniem GM, Van Leeuwen JS, Elser DM, et al. A randomized controlled trial of duloxetine alone, pelvic floor muscle training alone, combined treatment and no active treatment in women with stress urinary incontinence. J Urol 2005;173:1647–53. https://doi.org/10.1097/01.ju.0000154167.90600.c6.CrossRefPubMed

128.

Hurley DJ, Turner CL, Yalcin I, et al. Duloxetine for the treatment of stress urinary incontinence in women: an integrated analysis of safety. Eur J Obstet Gynecol Reprod Biol 2006;125:120–8. https://doi.org/10.1016/j.ejogrb.2005.08.006.CrossRefPubMed

129.

Kinchen KS, Obenchain R, Swindle R. Impact of duloxetine on quality of life for women with symptoms of urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2005;16:337–44. https://doi.org/10.1007/s00192-004-1270-5.CrossRefPubMed

130.

Lin AT, Sun MJ, Tai HL, et al. Duloxetine versus placebo for the treatment of women with stress predominant urinary incontinence in Taiwan: a double-blind, randomized, placebo-controlled trial. BMC Urol 2008;8:2. https://doi.org/10.1186/1471-2490-8-2.CrossRefPubMedPubMedCentral

131.

Michel MC, Minarzyk A, Schwerdtner I, et al. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice. Br J Clin Pharmacol 2013;75:1098–108. https://doi.org/10.1111/j.1365-2125.2012.04389.x.CrossRefPubMed

132.

Millard RJ, Moore K, Rencken R, et al. Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial. BJU Int 2004;93:311–8.CrossRef

133.

Norton PA, Zinner NR, Yalcin I, et al. Duloxetine versus placebo in the treatment of stress urinary incontinence. Am J Obstet Gynecol 2002;187:40–8.CrossRef

134.

Schagen van Leeuwen JH, Lange RR, Jonasson AF, et al. Efficacy and safety of duloxetine in elderly women with stress urinary incontinence or stress-predominant mixed urinary incontinence. Maturitas. 2008;60:138–47. https://doi.org/10.1016/j.maturitas.2008.04.012.CrossRefPubMed

135.

Steers WD, Herschorn S, Kreder KJ, et al. Duloxetine compared with placebo for treating women with symptoms of overactive bladder. BJU Int 2007;100:337–45. https://doi.org/10.1111/j.1464-410X.2007.06980.x.CrossRefPubMed

136.

Cardozo L, Lange R, Voss S, et al. Short- and long-term efficacy and safety of duloxetine in women with predominant stress urinary incontinence. Curr Med Res Opin 2010;26:253–61. https://doi.org/10.1185/03007990903438295.CrossRefPubMed

137.

Ghoniem G, Corcos J, Comiter C, et al. Cross-linked polydimethylsiloxane injection for female stress urinary incontinence: results of a multicenter, randomized, controlled, single-blind study. J Urol 2009;181:204–10. https://doi.org/10.1016/j.juro.2008.09.032.CrossRefPubMed

138.

Robinson D, Abrams P, Cardozo L, et al. The efficacy and safety of PSD503 (phenylephrine 20%, w/w) for topical application in women with stress urinary incontinence. A phase II, multicentre, double-blind, placebo controlled, 2-way cross over study. Eur J Obstet Gynecol Reprod Biol 2011;159:457–60. https://doi.org/10.1016/j.ejogrb.2011.07.030.CrossRefPubMed

139.

Brubaker L, Richter HE, Visco A, et al. Refractory idiopathic urge urinary incontinence and botulinum A injection. J Urol 2008;180:217–22. https://doi.org/10.1016/j.juro.2008.03.028.CrossRefPubMedPubMedCentral

140.

Dmochowski R, Chapple C, Nitti VW, et al. Efficacy and safety of onabotulinumtoxinA for idiopathic overactive bladder: a double-blind, placebo controlled, randomized, dose ranging trial. J Urol 2010;184:2416–22. https://doi.org/10.1016/j.juro.2010.08.021.CrossRefPubMed

141.

Jabs C, Carleton E. Efficacy of botulinum toxin a intradetrusor injections for non-neurogenic urinary urge incontinence: a randomized double-blind controlled trial. J Obstet Gynaecol Can 2013;35:53–60.CrossRef

142.

Nitti VW, Ginsberg D, Sievert KD, et al. Durable Efficacy and Safety of Long-Term OnabotulinumtoxinA Treatment in Patients with Overactive Bladder Syndrome: Final Results of a 3.5-Year Study. J Urol 2016;196:791–800. https://doi.org/10.1016/j.juro.2016.03.146.CrossRefPubMed

143.

Lightner D, Rovner E, Corcos J, et al. Randomized controlled multisite trial of injected bulking agents for women with intrinsic sphincter deficiency: mid-urethral injection of Zuidex via the Implacer versus proximal urethral injection of Contigen cystoscopically. Urology. 2009;74:771–5. https://doi.org/10.1016/j.urology.2009.05.034.CrossRefPubMed

144.

Mohr S, Siegenthaler M, Mueller MD, et al. Bulking agents: an analysis of 500 cases and review of the literature. Int Urogynecol J 2013;24:241–7. https://doi.org/10.1007/s00192-012-1834-8.CrossRefPubMed

145.

Mohr S, Marthaler C, Imboden S, et al. Bulkamid (PAHG) in mixed urinary incontinence: What is the outcome? Int Urogynecol J 2017;28:1657–61. https://doi.org/10.1007/s00192-017-3332-5.CrossRefPubMed

146.

Sokol ER, Karram MM, Dmochowski R. Efficacy and safety of polyacrylamide hydrogel for the treatment of female stress incontinence: a randomized, prospective, multicenter North American study. J Urol 2014;192:843–9. https://doi.org/10.1016/j.juro.2014.03.109.CrossRefPubMed

147.

Futyma K, Miotla P, Galczynski K, et al. An Open Multicenter Study of Clinical Efficacy and Safety of Urolastic, an Injectable Implant for the Treatment of Stress Urinary Incontinence: One-Year Observation. Biomed Res Int 2015;2015:851823. https://doi.org/10.1155/2015/851823.CrossRefPubMedPubMedCentral

148.

Pai A, Al-Singary W. Durability, safety and efficacy of polyacrylamide hydrogel (Bulkamid((R))) in the management of stress and mixed urinary incontinence: three year follow up outcomes. Cent European J Urol 2015;68:428–33. https://doi.org/10.5173/ceju.2015.647.CrossRefPubMedPubMedCentral

149.

Toozs-Hobson P, Al-Singary W, Fynes M, et al. Two-year follow-up of an open-label multicenter study of polyacrylamide hydrogel (Bulkamid®) for female stress and stress-predominant mixed incontinence. Int Urogynecol J 2012;23:1373–8. https://doi.org/10.1007/s00192-012-1761-8.CrossRefPubMedPubMedCentral

150.

Syan R, Brucker BM. Guideline of guidelines: urinary incontinence. BJU Int 2016;117:20–33. https://doi.org/10.1111/bju.13187.CrossRefPubMed

151.

Lineberry N, Berlin JA, Mansi B, et al. Recommendations to improve adverse event reporting in clinical trial publications: a joint pharmaceutical industry/journal editor perspective. BMJ. 2016;355:i5078. https://doi.org/10.1136/bmj.i5078.CrossRefPubMed

152.

Zarin DA, Tse T, Williams RJ, et al. Trial Reporting in ClinicalTrials.gov - The Final Rule. N Engl J Med. 2016;375:1998–2004. https://doi.org/10.1056/NEJMsr1611785.

Titel: Adverse Events Associated with Nonsurgical Treatments for Urinary Incontinence in Women: a Systematic Review
verfasst von: Ethan M. Balk, MD, MPH
Gaelen P. Adam, MLIS
Katherine Corsi, PharmD
Amanda Mogul, PharmD
Thomas A. Trikalinos, MD, PhD
Peter C. Jeppson, MD
Publikationsdatum: 06.05.2019
Verlag: Springer US
Erschienen in: Journal of General Internal Medicine / Ausgabe 8/2019
Print ISSN: 0884-8734
Elektronische ISSN: 1525-1497
DOI: https://doi.org/10.1007/s11606-019-05028-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

24.04.2024 | DGIM 2024 | Kongressbericht | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Adverse Events Associated with Nonsurgical Treatments for Urinary Incontinence in Women: a Systematic Review

Abstract

Background

Methods

Results

Discussion

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Thrombophiliescreening – Wenn, dann richtig und nur bei therapeutischer Konsequenz

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Update Innere Medizin

Springer Medizin

Abstract

Background

Methods

Results

Discussion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2019

Secular Trends in Long-Term Oral Bisphosphonate Use

Ten Ways Artificial Intelligence Will Transform Primary Care

How Often Do Systematic Reviews Exclude Articles Not Published in English?

Pneumococcal Bacteremia Complicated by Hemophagocytic Lymphohistiocytosis

Physicians’ Perspectives About Burnout: a Systematic Review and Metasynthesis

Characterizing the Role of the Primary Care Provider in Preventive Health Exams: NAMCS 2011–2014

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Thrombophiliescreening – Wenn, dann richtig und nur bei therapeutischer Konsequenz

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Update Innere Medizin