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Inal-Gültekin G, Çetin Z, Mangır N. Exploring Drug Repurposing for Interstitial Cystitis/Bladder Pain Syndrome: Defining Novel Therapeutic Targets. Neurourol Urodyn 2025; 44:496-503. [PMID: 39723619 DOI: 10.1002/nau.25651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 12/04/2024] [Indexed: 12/28/2024]
Abstract
INTRODUCTION Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating pain condition of unknown etiology. Effective therapies for this condition could not have been developed in the last century. Drug repurposing is a practical strategy for enhancing patient access to successful therapies. It is an approach for discovering novel applications for licensed or investigational pharmaceuticals that extend beyond the initial medical indication. This work aims to identify repurposable medications through bioinformatics to discover potential drugs or compounds that can reverse the IC/BPS disease signature. METHODS AND MATERIAL The analysis involved examining the differentially expressed genes in IC/BPS patients with two distinct disease phenotypes (Hunner's lesion disease, non-Hunner's lesion disease) and controls using the datasets GSE11783, GSE28242, and GSE57560. The goal was to assess the reversal of the disease signature on the L1000CDS2 and cMAP platforms. RESULTS Twenty-one compounds were repurposed, consisting of 11 small molecules, 10 chemical compounds, 3 natural products, and 6 FDA-approved drugs, currently used for clinical indications such as cancer, myelofibrosis, and diabetes. DISCUSSION Bioinformatics can be useful for identifying therapeutic agents for IC/BPS by accessing and processing big data on molecular and cellular levels. Prospective in vivo experiments must validate repurposed drugs. The expansion of large-scale genome sequencing, gene expression studies, and clinical data for IC/BPS will improve successful drug selection.
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Affiliation(s)
- Güldal Inal-Gültekin
- Department of Physiology, Faculty of Medicine, Istanbul Okan University, Istanbul, Türkiye
| | - Zeliha Çetin
- Department of Bioinformatics, Bingen University of Applied Sciences, Bingen am Rhein, Germany
| | - Naşide Mangır
- Faculty of Medicine, Department of Urology, Hacettepe University, Ankara, Türkiye
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Mazza M, Margoni S, Mandracchia G, Donofrio G, Fischetti A, Kotzalidis GD, Marano G, Simonetti A, Janiri D, Moccia L, Marcelli I, Sfratta G, De Berardis D, Ferrara O, Bernardi E, Restaino A, Lisci FM, D'Onofrio AM, Brisi C, Grisoni F, Calderoni C, Ciliberto M, Brugnami A, Rossi S, Spera MC, De Masi V, Marzo EM, Abate F, Boggio G, Anesini MB, Falsini C, Quintano A, Torresi A, Milintenda M, Bartolucci G, Biscosi M, Ruggiero S, Lo Giudice L, Mastroeni G, Benini E, Di Benedetto L, Caso R, Pesaresi F, Traccis F, Onori L, Chisari L, Monacelli L, Acanfora M, Gaetani E, Marturano M, Barbonetti S, Specogna E, Bardi F, De Chiara E, Stella G, Zanzarri A, Tavoletta F, Crupi A, Battisti G, Monti L, Camardese G, Chieffo D, Gasbarrini A, Scambia G, Sani G. This pain drives me crazy: Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome. World J Psychiatry 2024; 14:954-984. [PMID: 38984334 PMCID: PMC11230088 DOI: 10.5498/wjp.v14.i6.954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 04/22/2024] [Accepted: 05/07/2024] [Indexed: 06/19/2024] Open
Abstract
BACKGROUND Interstitial cystitis/bladder pain syndrome (IC/BPS) is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic, abdominal, and/or pelvic pain. Although the term cystitis suggests an inflammatory or infectious origin, no definite cause has been identified. It occurs in both sexes, but women are twice as much affected. AIM To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS. METHODS Hypothesizing that particular psychological characteristics could underpin IC/BPS, we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy: ("interstitial cystitis" OR "bladder pain syndrome") AND ("mood disorder" OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk). RESULTS On September 27, 2023, the PubMed search produced 223 articles, CINAHL 62, and the combined PsycLIT/ PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36. Search on ClinicalTrials.gov produced 14 studies, of which none had available data. Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS, i.e. 63 articles spanning from 2000 to October 2023. These studies identified depression and anxiety problems in the IC/BPS population, along with sleep problems and the tendency to catastrophizing. CONCLUSION Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS. Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.
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Affiliation(s)
- Marianna Mazza
- Department of Neurosciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Stella Margoni
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Giuseppe Mandracchia
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Guglielmo Donofrio
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Alessia Fischetti
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | | | - Giuseppe Marano
- Department of Neurosciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Alessio Simonetti
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Delfina Janiri
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Lorenzo Moccia
- Department of Neurosciences, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Ilaria Marcelli
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Greta Sfratta
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | | | - Ottavia Ferrara
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Evelina Bernardi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Restaino
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | | | | | - Caterina Brisi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Flavia Grisoni
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Claudia Calderoni
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Michele Ciliberto
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Andrea Brugnami
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Sara Rossi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Maria Chiara Spera
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Valeria De Masi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Ester Maria Marzo
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Abate
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Gianluca Boggio
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | | | - Cecilia Falsini
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Anna Quintano
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Alberto Torresi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Miriam Milintenda
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Giovanni Bartolucci
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Marco Biscosi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Sara Ruggiero
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Lo Giudice
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Giulia Mastroeni
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Elisabetta Benini
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Di Benedetto
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Romina Caso
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesco Pesaresi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesco Traccis
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Onori
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Chisari
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Leonardo Monacelli
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Mariateresa Acanfora
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Eleonora Gaetani
- Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Monia Marturano
- Division of Gynecologic Oncology, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Sara Barbonetti
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Elettra Specogna
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Bardi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Emanuela De Chiara
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Gianmarco Stella
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Andrea Zanzarri
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Flavio Tavoletta
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Arianna Crupi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Giulia Battisti
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Laura Monti
- UOS Psicologia Clinica, Governo Clinico, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Giovanni Camardese
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Daniela Chieffo
- UOS Psicologia Clinica, Governo Clinico, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome 00168, Italy
| | - Giovanni Scambia
- Department of Woman and Child Health, Catholic University, Rome 00168, Italy
| | - Gabriele Sani
- UOC Psichiatria Clinica e d’Urgenza, Dipartimento di Scienze Dell’Invecchiamento, Neurologiche, Ortopediche e Della Testa-collo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
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Porru D, Anselmo D, Magliano A, Scalmati S, DE Silvestri A, Ilardi M, Gardella B, Spinillo A, Politi P, Naspro R. Quality of life analysis in bladder pain syndrome/interstitial cystitis: implications for a multimodal integrated treatment. Minerva Urol Nephrol 2023; 75:634-641. [PMID: 37728498 DOI: 10.23736/s2724-6051.23.05292-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/21/2023]
Abstract
BACKGROUND The aim of this study was to evaluate whether there is a higher prevalence of anxiety-depressive disorders in women with BPS/IC (bladder pain syndrome/interstitial cystitis) than in women with chronic non-neoplastic pain with or without fibromyalgia, to examine possible correlations between urological and psychiatric symptoms. METHODS The patients included in the study were divided into two groups: 1) group 0: patients with an existing diagnosis of BPS/IC. BPS/IC was confirmed by reviewing medical record; group 1+2: patients with chronic non-neoplastic pain, suffering from fibromyalgia or other types of chronic pain (chronic arthralgia or lower back pain). Three questionnaires were administered: PHQ-9 to investigate psychological symptoms, O'Leary Saint (ICSI-ICPI) to investigate urological symptoms in women with BPS/IC and BPI to investigate specifically pain. RESULTS The survey included 69 patients, 42 patients had a diagnosis of BPS/IC while 27 of them had chronic non-neoplastic pain. The average PHQ-9 Score was 10.3 in BPS/IC group, considered as major depression (score between 10 and 14); the average score of PHQ-9 was 6.9 in group 1+2, as in sub-threshold depression (between 5-9). CONCLUSIONS The chronic pain of BPS/IC can affect mood more than in other painful conditions, as more than half of this population has a score that identifies depression with the PHQ-9 questionnaire, confirming the hypothesis that the syndrome is associated with a higher prevalence of an anxious-depressive condition.
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Affiliation(s)
- Daniele Porru
- Unit of Urology, San Matteo Polyclinic Foundation, Pavia, Italy -
| | - Daniela Anselmo
- Unit of Urology, San Matteo Polyclinic Foundation, Pavia, Italy
| | | | | | - Annalisa DE Silvestri
- Unit of Clinical and Biostatistic Epidemiology, San Matteo Polyclinic Foundation, Pavia, Italy
| | - Marcella Ilardi
- Unit of Pain Therapy Service, IRCCS San Matteo Polyclinic Foundation, Pavia, Italy
| | - Barbara Gardella
- Obstetrics and Gynecological Clinic, IRCCS San Matteo Polyclinic Foundation, Pavia, Italy
| | - Arsenio Spinillo
- Obstetrics and Gynecological Clinic, IRCCS San Matteo Polyclinic Foundation, Pavia, Italy
| | | | - Richard Naspro
- Unit of Urology, San Matteo Polyclinic Foundation, Pavia, Italy
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Şahin MF, Özcan R, Malak A, Doğan Ç, Yazıcı CM, Özcan M, Akgül M. The effect of the pandemic period on Bladder Pain Syndrome patients under amitriptyline treatment. Neurourol Urodyn 2023. [PMID: 37155258 DOI: 10.1002/nau.25199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 04/19/2023] [Accepted: 05/01/2023] [Indexed: 05/10/2023]
Abstract
INTRODUCTION COVID-19 is a disease that may cause anxiety, depression, and stress. Bladder pain syndrome (BPS) is a disease in which stress and psychological factors might negatively affect its course. In this study, we aimed to examine the possible clinical aggregation of the pandemic period on BPS patients. MATERIALS AND METHODS A total of 35 BPS patients diagnosed between 2010 and 2018 were included. All patients were using medical treatment, and the follow-up period was at least 6 months. According to our clinical follow-up protocol, the BPS patients were given the King's Health Questionnaire (KHQ), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Overactive Bladder Form V8 (OAB-V8), and Visual Analog Score (VAS) in every visit. In the sixth month of the pandemic, the clinical course of the patients was questioned by telephone or video interview, and their treatment continuities were questioned. Information was received about the delays in their follow-up and the difficulties in accessing healthcare opportunities. The same questionnaires were filled out and compared with pre-pandemic scores. RESULTS The mean age of the patients included in the study was 50.2 ± 13.32 (min:20, max:74), 11 were males and 24 were females. The mean follow-up periods were 71.8 ± 35.6 months. All questionnaire scores showed an increase compared to the pre-pandemic period. A statistically significant increase was detected during the pandemic in all sub-units of the KHQ. The VAS and OAB-V8 scores of 16 patients who requested hospital admission were significantly higher than before the pandemic. However, there was no statistically significant difference in the increase in VAS and OAB-V8 scores of the 19 patients who refused to come to the hospital. CONCLUSION BPS patients have been negatively affected by the emotional effects of the COVID-19 pandemic. Due to the fear, stress, anxiety, and depression, the symptoms of BPS patients exacerbated, and the patients could not receive the necessary support due to a lack of regular follow-ups.
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Affiliation(s)
| | - Rıdvan Özcan
- Department of Urology, Bursa City Hospital, Bursa, Nilüfer, Turkey
| | - Arzu Malak
- School of Health Nursing Department, Tekirdag Namık Kemal University, Süleymanpaşa, Tekirdağ, Turkey
| | - Çağrı Doğan
- Department of Urology, Tekirdag Namık Kemal University Medical School, Süleymanpaşa, Tekirdağ, Turkey
| | - Cenk Murat Yazıcı
- Department of Urology, Tekirdag Namık Kemal University Medical School, Süleymanpaşa, Tekirdağ, Turkey
| | - Müge Özcan
- Department of Urology, Tekirdag Namık Kemal University Medical School, Süleymanpaşa, Tekirdağ, Turkey
| | - Murat Akgül
- Department of Urology, Tekirdag Namık Kemal University Medical School, Süleymanpaşa, Tekirdağ, Turkey
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Topcuoglu M, Karaburun MC, İbiş A, Gokce Mİ, Süer E, Gülpinar O. Sexual dysfunction in women with interstitial cystitis/bladder pain syndrome: Do onabotulinum toxin-A injections improve sexual function? Neurourol Urodyn 2023; 42:607-614. [PMID: 36708358 DOI: 10.1002/nau.25139] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 12/21/2022] [Accepted: 01/16/2023] [Indexed: 01/29/2023]
Abstract
INTRODUCTION Interstitial cystitis/bladder pain syndrome (IC/BPS) has a negative impact on female sexual function. We aimed to evaluate the effect of intravesical botulinum toxin-A (BTX-A) injection on the improvement of sexual dysfunction and urinary symptoms using the multi-domain female sexual function Index (FSFI), interstitial cystitis symptom index (ICSI), and interstitial cystitis problem index (ICPI). MATERIAL AND METHOD The data of the 23 patients (study group) who received intravesical BTX-A with the diagnosis of IC/BPS were reviewed. Twenty-three age-matched healthy, sexually active women were determined as the control group. Patients received 100 U BTX-A submucosally injections, including the trigone. One hundred units of BTX-A were diluted to 20 cc 0.9% saline, and 1 cc was then applied submucosally on 20 different points of the bladder wall (5 U/1 mL per site). The study group was asked to fill out FSFI, ICSI, and ICPI, as well as the visual analog scale (VAS) and bladder diary before and 3 months after the treatment. Patients in the control group completed the same questionnaires once. The pre- and post-treatment questionnaire scores were compared in the study group. The study group's data were also compared to the control group. RESULTS Compared to the pretreatment period, the study group showed statistically significant improvement in the total FSFI score and each domain of the FSFI after BTX-A injection. The mean total FSFI score and three domains of FSFI (desire, lubrication, pain) reached to the score of the control group following BTX-A injection. Statistically significant improvements were also shown in scores of ICSI, ICPI, and VAS. (p < 0.05). CONCLUSION IC/BPS is associated with a very high incidence of sexual dysfunction. Intravesical BTX-A injection may provide significant improvement in sexual dysfunction in women with IC/BPS.
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Affiliation(s)
- Murat Topcuoglu
- Department of Urology, Alaaddin Keykubat University Education and Research Hospital, Denizli, Turkey
| | | | - Arif İbiş
- Department of Urology, Ankara University School of Medicine, Ankara, Turkey
| | - Mehmet İlker Gokce
- Department of Urology, Ankara University School of Medicine, Ankara, Turkey
| | - Evren Süer
- Department of Urology, Ankara University School of Medicine, Ankara, Turkey
| | - Omer Gülpinar
- Department of Urology, Ankara University School of Medicine, Ankara, Turkey
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Jhang JF, Jiang YH, Kuo HC. Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome. Biomedicines 2022; 10:biomedicines10102380. [PMID: 36289642 PMCID: PMC9598807 DOI: 10.3390/biomedicines10102380] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 09/08/2022] [Accepted: 09/17/2022] [Indexed: 12/19/2022] Open
Abstract
The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is multifactorial. Identifying the clinical characteristics and cystoscopic findings of bladder-centered IC/BPS facilitates optimal treatment strategies targeting the diseased urinary bladder. Patients with Hunner’s lesion (HIC) and without Hunner’s lesion (NHIC) should be treated differently. Based on the histopathological findings, NHIC can be treated with intravesical instillation of urothelial protective agents, such as hyaluronic acid, to cover the urothelial defects. In non-responders, chronic inflammation and higher urothelial dysfunction can be treated with intravesical botulinum toxin A injection, platelet-rich plasma injection, or low-energy shock wave treatment to reduce inflammation, increase tissue regeneration, and improve the urothelial barrier. Patients with HIC should be treated with electrocauterization first; augmentation enterocystoplasty should only be used in end-stage HIC when the contracted bladder is refractory to other treatments. The antiviral agent, valacyclovir, can be used in patients with HIC, small bladder capacity, and high-grade glomerulations. In addition, behavioral modification is always recommended from the beginning of treatment. Treatment with cognitive behavioral therapy interventions in combination with bladder therapy can reduce anxiety and improve treatment outcomes. Herein, recent advances in the pathophysiology and novel treatments for IC/BPS are reviewed.
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Affiliation(s)
| | | | - Hann-Chorng Kuo
- Correspondence: ; Tel.: +886-3-8561825 (ext. 2117); Fax: +886-3-8560794
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Fischer-Grote L, Fössing V, Aigner M, Boeckle M, Fehrmann E. Comorbidities of bladder pain syndrome in the context of the HITOP distress category: a systematic review and meta-analysis. Int Urogynecol J 2022; 33:2335-2356. [PMID: 35262767 PMCID: PMC9427913 DOI: 10.1007/s00192-022-05129-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 02/09/2022] [Indexed: 11/16/2022]
Abstract
INTRODUCTION AND HYPOTHESIS The aim of this systematic review and meta-analysis is, looking at different care settings, to examine prevalence rates of psychological distress-level comorbidities in female interstitial cystitis/bladder pain syndrome (IC/BPS) patients, their impact on Quality of Life (QoL), and the correlation between such comorbidities and symptom severity. METHODS A systematic literature search according to PRISMA guidelines was conducted in PubMed, PsycInfo, Web of Science, Science Direct, and Google Scholar. RESULTS Twenty-nine studies were found that met inclusion criteria. Prevalence rates of depression and anxiety are higher in IC/BPS patients compared to the general population; however, due to a wide array of measurements, statistical comparisons between care settings were only possible in two cases showing mixed results. No studies meeting inclusion criteria exist that examine PTSD and borderline personality disorder, though rates of past traumatic experiences seem to be higher in patients than in healthy controls. Psychological comorbidities of the distress category, especially depression, are found in most studies to be related to symptom severity, also yielding statistically significant associations. CONCLUSIONS While there is still need for studies focused on some of the comorbidities as well as on different care settings, the data already show that psychological comorbidities of the distress category play an important role in IC/BPS patients regarding suffering, QoL, and symptom severity, thus emphasizing the need for highly specialized interdisciplinary treatment.
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Affiliation(s)
- Linda Fischer-Grote
- Karl Landsteiner Institute for Outpatient Rehabilitation Research, Vienna, Austria
| | - Vera Fössing
- Karl Landsteiner Institute for Outpatient Rehabilitation Research, Vienna, Austria
| | - Martin Aigner
- Department of Psychiatry for Adults, University Hospital Tulln, Tulln, Austria
| | - Markus Boeckle
- Scientific Working Group, DOT-Die offene Tür (the open door), Karl Landsteiner University of Health Sciences, Dr.-Karl-Dorrek-Straße 30, 3500, Krems, an der Donau, Austria.
- Department of Psychiatry for Adults, University Hospital Tulln, Tulln, Austria.
| | - Elisabeth Fehrmann
- Karl Landsteiner Institute for Outpatient Rehabilitation Research, Vienna, Austria
- Scientific Working Group, DOT-Die offene Tür (the open door), Karl Landsteiner University of Health Sciences, Dr.-Karl-Dorrek-Straße 30, 3500, Krems, an der Donau, Austria
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Rahman-Enyart A, Yaggie RE, Bollinger JL, Arvanitis C, Winter DR, Schaeffer AJ, Klumpp DJ. Acyloxyacyl hydrolase regulates microglia-mediated pelvic pain. PLoS One 2022; 17:e0269140. [PMID: 35980963 PMCID: PMC9387837 DOI: 10.1371/journal.pone.0269140] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 05/15/2022] [Indexed: 12/04/2022] Open
Abstract
Chronic pelvic pain conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) remain clinical and mechanistic enigmas. Microglia are resident immune cells of the central nervous system (CNS) that respond to changes in the gut microbiome, and studies have linked microglial activation to acute and chronic pain in a variety of models, including pelvic pain. We have previously reported that mice deficient for the lipase acyloxyacyl hydrolase (AOAH) develop pelvic allodynia and exhibit symptoms, comorbidities, and gut dysbiosis mimicking IC/BPS. Here, we assessed the role of AOAH in microglial activation and pelvic pain. RNAseq analyses using the ARCHS4 database and confocal microscopy revealed that AOAH is highly expressed in wild type microglia but at low levels in astrocytes, suggesting a functional role for AOAH in microglia. Pharmacologic ablation of CNS microglia with PLX5622 resulted in decreased pelvic allodynia in AOAH-deficient mice and resurgence of pelvic pain upon drug washout. Skeletal analyses revealed that AOAH-deficient mice have an activated microglia morphology in the medial prefrontal cortex and paraventricular nucleus, brain regions associated with pain modulation. Because microglia express Toll-like receptors and respond to microbial components, we also examine the potential role of dysbiosis in microglial activation. Consistent with our hypothesis of microglia activation by leakage of gut microbes, we observed increased serum endotoxins in AOAH-deficient mice and increased activation of cultured BV2 microglial cells by stool of AOAH-deficient mice. Together, these findings demonstrate a role for AOAH in microglial modulation of pelvic pain and thus identify a novel therapeutic target for IC/BPS.
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Affiliation(s)
- Afrida Rahman-Enyart
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
- Currently Proteintech Group Incorporated, Rosemont, Illinois, United States of America
| | - Ryan E. Yaggie
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
| | - Justin L. Bollinger
- Department of Pharmacology & Systems Physiology, College of Medicine University of Cincinnati, Cincinnati, Ohio, United States of America
| | - Constadina Arvanitis
- Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
- Center for Advanced Microscopy & Nikon Imaging Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
| | - Deborah R. Winter
- Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
| | - Anthony J. Schaeffer
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
| | - David J. Klumpp
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
- Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
- * E-mail:
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9
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Ko KJ, Lim J, Yu J, Kang D, Cho J, Lee KS. The impact of Hunner lesion-type interstitial cystitis/bladder pain syndrome on health-related quality of life and the effects of transurethral ablation. Qual Life Res 2022; 31:3221-3228. [DOI: 10.1007/s11136-022-03183-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2022] [Indexed: 12/01/2022]
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10
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Laden BF, Bresee C, De Hoedt A, Dallas KB, Scharfenberg A, Saxena R, Senechal JF, Barbour KE, Kim J, Freedland SJ, Anger JT. Comorbidities in a Nationwide, Heterogenous Population of Veterans with Interstitial Cystitis/Bladder Pain Syndrome. Urology 2021; 156:37-43. [PMID: 33901534 PMCID: PMC8536792 DOI: 10.1016/j.urology.2021.04.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 04/05/2021] [Accepted: 04/12/2021] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To examine the prevalence of comorbid conditions in a nationwide population of men and women with IC/BPS utilizing a more heterogeneous sample than most studies to date. METHODS Using the Veterans Affairs Informatics and Computing Infrastructure, we identified random samples of male and female patients with and without an ICD-9/ICD-10 diagnosis of IC/BPS. Presence of comorbidities (NUAS [chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, migraines], back pain, diabetes, and smoking) and psychosocial factors (alcohol abuse, post-traumatic stress disorder, sexual trauma, and history of depression) were determined using ICD-9 and ICD-10 codes. Associations between these variables and IC/BPS status were evaluated while adjusting for the potential confounding impact of race/ethnicity, age, and gender. RESULTS Data was analyzed from 872 IC/BPS patients (355 [41%] men, 517 [59%] women) and 558 non-IC/BPS patients (291 [52%] men, 267 [48%] women). IC/BPS patients were more likely than non-IC/BPS patients to have a greater number of comorbidities (2.72+/-1.77 vs 1.73+/-1.30, P < 0.001), experience one or more NUAS (chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and migraines) (45% [388/872] vs. 18% [101/558]; P < 0.001) and had a higher prevalence of at least one psychosocial factor (61% [529/872] v. 46% [256/558]; P < 0.001). Differences in the frequencies of comorbidities between patients with and without IC/BPS were more pronounced in female patients. CONCLUSION These findings validate the findings of previous comorbidity studies of IC/BPS in a more diverse population.
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Affiliation(s)
- Bethany F Laden
- Urology Section, Department of Surgery, Veterans Affairs Health Care System, Durham, NC
| | - Catherine Bresee
- Department of Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Amanda De Hoedt
- Urology Section, Department of Surgery, Veterans Affairs Health Care System, Durham, NC
| | - Kai B Dallas
- Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA
| | - April Scharfenberg
- Urology Section, Department of Surgery, Veterans Affairs Health Care System, Durham, NC
| | - Roopali Saxena
- Urology Section, Department of Surgery, Veterans Affairs Health Care System, Durham, NC
| | - Justin F Senechal
- Urology Section, Department of Surgery, Veterans Affairs Health Care System, Durham, NC
| | - Kamil E Barbour
- National Center for Chronic Disease Prevention and Health Promotion, CDC, Atlanta, GA
| | - Jayoung Kim
- Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Stephen J Freedland
- Urology Section, Department of Surgery, Veterans Affairs Health Care System, Durham, NC; Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Jennifer T Anger
- Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA.
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11
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Ruggeri M, Pavan M, Soato M, Panfilo S, Barbera C, Galesso D, Miele D, Rossi S, Di Lucia A, Ferrari F, Sandri G. Synergy of Hydeal-D ® and Hyaluronic Acid for Protecting and Restoring Urothelium: In Vitro Characterization. Pharmaceutics 2021; 13:1450. [PMID: 34575526 PMCID: PMC8465558 DOI: 10.3390/pharmaceutics13091450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/06/2021] [Accepted: 09/08/2021] [Indexed: 11/29/2022] Open
Abstract
Interstitial cystitis (IC) or painful bladder syndrome is a chronic dysfunction due to an inflammatory condition, characterized by bladder pain and urinary frequency. Currently, no gold standard therapy is available since IC does not respond to conventional ones. Given these premises, the aim of this work was the in vitro characterization of biological properties (mucoadhesion and anti-inflammatory activity) of a commercial product (HydealCyst-HydC) based on hyaluronic acid (HA) and the benzyl ester of HA (Hydeal-D®) intended for bladder instillation to restore and/or protect the urothelial layer of glycosamino glycans (GAGs). The in vitro characterization demonstrated that an interaction product is formed between HA and Hydeal-D® that has a role in the rheological behavior and mucoadhesive properties. HA was identified as a key component to form the mucoadhesive joint, while the interaction of HA with Hydeal-D® improved polysaccharide stability and prolonged the activity ex vivo. Moreover, HydC is cytocompatible with urothelial cells (HTB-4) and possesses an anti-inflammatory effect towards these cells by decreasing the secretion of IL-6 and IL-8, which were both increased in patients with IC, and by increasing the secretion of sulfated GAGs. These two findings, along with the resilience properties of the formulation due to mucoadhesion, suggest the active role of HydC in protecting and restoring urothelium homeostasis.
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Affiliation(s)
- Marco Ruggeri
- Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; (M.R.); (D.M.); (S.R.); (F.F.)
| | - Mauro Pavan
- Fidia Farmaceutici S.p.A., Via Ponte Della Fabbrica 3/A, 35031 Abano Terme, Italy; (M.P.); (M.S.); (S.P.); (C.B.); (D.G.)
| | - Matteo Soato
- Fidia Farmaceutici S.p.A., Via Ponte Della Fabbrica 3/A, 35031 Abano Terme, Italy; (M.P.); (M.S.); (S.P.); (C.B.); (D.G.)
| | - Susi Panfilo
- Fidia Farmaceutici S.p.A., Via Ponte Della Fabbrica 3/A, 35031 Abano Terme, Italy; (M.P.); (M.S.); (S.P.); (C.B.); (D.G.)
| | - Carlo Barbera
- Fidia Farmaceutici S.p.A., Via Ponte Della Fabbrica 3/A, 35031 Abano Terme, Italy; (M.P.); (M.S.); (S.P.); (C.B.); (D.G.)
| | - Devis Galesso
- Fidia Farmaceutici S.p.A., Via Ponte Della Fabbrica 3/A, 35031 Abano Terme, Italy; (M.P.); (M.S.); (S.P.); (C.B.); (D.G.)
| | - Dalila Miele
- Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; (M.R.); (D.M.); (S.R.); (F.F.)
| | - Silvia Rossi
- Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; (M.R.); (D.M.); (S.R.); (F.F.)
| | - Alba Di Lucia
- Fidia Farmaceutici S.p.A., Via Ponte Della Fabbrica 3/A, 35031 Abano Terme, Italy; (M.P.); (M.S.); (S.P.); (C.B.); (D.G.)
| | - Franca Ferrari
- Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; (M.R.); (D.M.); (S.R.); (F.F.)
| | - Giuseppina Sandri
- Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; (M.R.); (D.M.); (S.R.); (F.F.)
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12
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Hsieh KL, Chin HY, Lo TS, Long CY, Ho CH, Huang SKH, Chuang YC, Wu MP. Interstitial cystitis/bladder pain syndrome patient is associated with subsequent increased risks of outpatient visits and hospitalizations: A population-based study. PLoS One 2021; 16:e0256800. [PMID: 34492065 PMCID: PMC8423233 DOI: 10.1371/journal.pone.0256800] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 08/17/2021] [Indexed: 12/30/2022] Open
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) is not only a chronic urinary bladder pain syndrome but is also associated with multifactorial etiology. Our study aimed to test the hypothesis that IC/BPS is associated with subsequent increased risks of outpatient visits and hospitalizations. Using nationwide database, the diagnoses were based on the International Classification Codes (ICD-9-CM) (595.1) of at least three outpatient services during 2002-2008, (n = 27,990) and cystoscopic finding Hunner type and/or glomerulation with pre-audit criteria. All recruited cases monitored for subsequent outpatient visits and hospitalizations for 2 years, including all-cause and specialty-specific departments, were classified according to medical specialty and age group (<40, 40-60, ≥60 years of age). IC/BPS patients have more overall outpatient department (OPD) visits and an overall adjusted incidence rate ratio (IRR) of 1.64. As for specialty, IRRs were higher in psychiatry (2.75), Chinese medicine (2.01), and emergency medicine (2.00), besides urology and gynecology. The IRRs decreased as age advanced (2.01, 1.71, and 1.44, respectively), except for gynecology (2.42, 2.52, and 2.81). A similar phenomenon happens in hospitalization with IRR of 1.69. Due to claim data characteristics, whether ulcer type IC/BPS findings can be deductive to non-ulcer type remains inclusive. Current results indicate the impacts of healthcare burden in broad spectrum about IC/PBS patients. IC/BPS has been suggested to be associated with lower threshold of healthcare visits and some coexisting disease and is comprised of systemic dysregulation, and is beyond the scope of local bladder-urethra disease. Adequate recognition of associated or comorbid factors and possible recommendation or referral for IC/BPS patients can help provide better healthcare quality.
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Affiliation(s)
- Kun-Lin Hsieh
- Division of Urology, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Yen Chin
- Department of Obstetrics and Gynecology, Taipei Medical University Hospital, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Tsia-Shu Lo
- Division of Urogynecology, Department of Obstetrics and Gynecology, Linkou, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, Republic of China
- School of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China
| | - Cheng-Yu Long
- Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Obstetrics and Gynecology, Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Han Ho
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | | | - Yao-Chi Chuang
- Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Ping Wu
- Division of Urogynecology, Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan
- Department of Obstetrics and Gynecology, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan
- * E-mail:
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13
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Rahman-Enyart A, Yang W, Yaggie RE, White BA, Welge M, Auvil L, Berry M, Bushell C, Rosen JM, Rudick CN, Schaeffer AJ, Klumpp DJ. Acyloxyacyl hydrolase is a host determinant of gut microbiome-mediated pelvic pain. Am J Physiol Regul Integr Comp Physiol 2021; 321:R396-R412. [PMID: 34318715 PMCID: PMC8530758 DOI: 10.1152/ajpregu.00106.2021] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/24/2021] [Accepted: 07/16/2021] [Indexed: 12/30/2022]
Abstract
Dysbiosis of gut microbiota is associated with many pathologies, yet host factors modulating microbiota remain unclear. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition of chronic pelvic pain often with comorbid urinary dysfunction and anxiety/depression, and recent studies find fecal dysbiosis in patients with IC/BPS. We identified the locus encoding acyloxyacyl hydrolase, Aoah, as a modulator of pelvic pain severity in a murine IC/BPS model. AOAH-deficient mice spontaneously develop rodent correlates of pelvic pain, increased responses to induced pelvic pain models, voiding dysfunction, and anxious/depressive behaviors. Here, we report that AOAH-deficient mice exhibit dysbiosis of gastrointestinal (GI) microbiota. AOAH-deficient mice exhibit an enlarged cecum, a phenotype long associated with germ-free rodents, and a "leaky gut" phenotype. AOAH-deficient ceca showed altered gene expression consistent with inflammation, Wnt signaling, and urologic disease. 16S sequencing of stool revealed altered microbiota in AOAH-deficient mice, and GC-MS identified altered metabolomes. Cohousing AOAH-deficient mice with wild-type mice resulted in converged microbiota and altered predicted metagenomes. Cohousing also abrogated the pelvic pain phenotype of AOAH-deficient mice, which was corroborated by oral gavage of AOAH-deficient mice with stool slurry of wild-type mice. Converged microbiota also alleviated comorbid anxiety-like behavior in AOAH-deficient mice. Oral gavage of AOAH-deficient mice with anaerobes cultured from IC/BPS stool resulted in exacerbation of pelvic allodynia. Together, these data indicate that AOAH is a host determinant of normal gut microbiota, and dysbiosis associated with AOAH deficiency contributes to pelvic pain. These findings suggest that the gut microbiome is a potential therapeutic target for IC/BPS.
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Affiliation(s)
- Afrida Rahman-Enyart
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Wenbin Yang
- Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Ryan E Yaggie
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Bryan A White
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois
- National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - Michael Welge
- National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - Loretta Auvil
- National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - Matthew Berry
- National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - Colleen Bushell
- National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, Illinois
| | - John M Rosen
- Department of Gastroenterology, Children's Mercy, Kansas City, Missouri
- Department of Pediatrics, University of Missouri, Kansas City, Missouri
| | - Charles N Rudick
- Clinical Pharmacology and Toxicology, Indiana University School of Medicine, Bloomington, Indiana
| | - Anthony J Schaeffer
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - David J Klumpp
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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14
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Mahjani B, Koskela LR, Batuure A, Gustavsson Mahjani C, Janecka M, Hultman CM, Reichenberg A, Buxbaum JD, Akre O, Grice DE. Systematic review and meta-analysis identify significant relationships between clinical anxiety and lower urinary tract symptoms. Brain Behav 2021; 11:e2268. [PMID: 34402598 PMCID: PMC8442597 DOI: 10.1002/brb3.2268] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 06/10/2021] [Accepted: 06/13/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lower urinary tract symptoms (LUTS), such as voiding symptoms, overactive bladder, and interstitial cystitis, and anxiety disorders are often comorbid conditions in patients. However, the existing evidence regarding the rates and nature of the co-occurrence of these conditions has not been systematically evaluated. The aim of this study was to examine these relationships. METHODS We conducted a systematic review and meta-analysis to examine the relationship between LUTS and anxiety. We searched for articles published from January 1990 to July 2019 in PubMed, CENTRAL, PsycINFO, and Google Scholar. Outcomes were anxiety-related disorders and symptoms (clinically significant anxiety) and LUTS. We performed random-effects meta-analyses, inspected funnel plots, and applied the Egger's test to evaluate publication bias. We followed PRISMA guidelines and recorded our protocol on PROSPERO (ID = CRD42019118607). RESULTS We identified 814 articles, of which 94 fulfilled inclusion criteria, and 23 had sufficient data for meta-analysis. The odds ratio (OR) for clinically significant anxiety among individuals with LUTS was 2.87 (95% CI: 2.38,3.46, p < .001). The OR for LUTS among individuals with clinically significant anxiety was 2.87 (95% CI: 1.07,7.74, p < .001), although very few studies examined this relationship. A large value of I2 index suggests high heterogeneity between studies. CONCLUSION The results demonstrate a significant association between clinically significant anxiety and LUTS in both females and males. There were limited studies on younger individuals and on individuals ascertained for clinically significant anxiety, which should motivate further study in these areas. Understanding the co-occurrence of these conditions will lead to better prevention and interventions to ameliorate the progression of the symptoms and improve the quality of life. A thorough assessment of anxiety may provide more optimal care for LUTS patients.
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Affiliation(s)
- Behrang Mahjani
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.,Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, USA.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Division of Tics, OCD, and Related Disorders, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Lotta Renström Koskela
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Anita Batuure
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.,Division of Tics, OCD, and Related Disorders, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Christina Gustavsson Mahjani
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.,Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, USA.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Magdalena Janecka
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.,Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Christina M Hultman
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Abraham Reichenberg
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.,Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Joseph D Buxbaum
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.,Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, USA.,Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.,Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA.,The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, USA.,Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Olof Akre
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Department of Pelvic Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Dorothy E Grice
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.,The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, USA.,Division of Tics, OCD, and Related Disorders, Icahn School of Medicine at Mount Sinai, New York, USA.,Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, USA
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15
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Kawasaki S, Soga M, Sakurai Y, Nanchi I, Yamamoto M, Imai S, Takahashi T, Tsuno N, Asaki T, Morioka Y, Fujita M. Selective blockade of transient receptor potential vanilloid 4 reduces cyclophosphamide-induced bladder pain in mice. Eur J Pharmacol 2021; 899:174040. [PMID: 33737012 DOI: 10.1016/j.ejphar.2021.174040] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 03/11/2021] [Accepted: 03/12/2021] [Indexed: 12/30/2022]
Abstract
Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel activated by various physical stimuli such as cell swelling and shear stress. TRPV4 is expressed in bladder sensory nerves and epithelium, and its activation produces urinary dysfunction in rodents. However, there have been few reports regarding its involvement in bladder pain. Therefore, we investigated whether TRPV4 is involved in bladder pain in mouse cystitis model. Intraperitoneal injection of cyclophosphamide (CYP; 300 mg/kg) produced mechanical hypersensitivity in the lower abdomen associated with a severe inflammatory bladder in mice. The mechanical threshold was reversed significantly in Trpv4-knockout (KO) mice. Repeated injections of CYP (150 mg/kg) daily for 4 days provoked mild bladder inflammation and persistent mechanical hypersensitivity in mice. Trpv4-KO mice prevented a reduction of the mechanical threshold without an alteration in bladder inflammation. A selective TRPV4 antagonist also reversed the mechanical threshold in chronic cystitis mice. Although expression of Trpv4 was unchanged in the bladders of chronic cystitis mice, the level of phosphorylated TRPV4 was increased significantly. These results suggest involvement of TRPV4 in bladder pain of cystitis mice. A TRPV4 antagonist might be useful for patients with irritable bladder pain such as those with interstitial cystitis/painful bladder syndrome.
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MESH Headings
- Analgesics/pharmacology
- Animals
- Behavior, Animal/drug effects
- Cells, Cultured
- Cyclophosphamide
- Cystitis, Interstitial/chemically induced
- Cystitis, Interstitial/metabolism
- Cystitis, Interstitial/physiopathology
- Cystitis, Interstitial/prevention & control
- Disease Models, Animal
- Ganglia, Spinal/drug effects
- Ganglia, Spinal/metabolism
- Ganglia, Spinal/physiopathology
- Male
- Mice, Inbred C57BL
- Mice, Knockout
- Nociceptive Pain/chemically induced
- Nociceptive Pain/metabolism
- Nociceptive Pain/physiopathology
- Nociceptive Pain/prevention & control
- Pain Threshold/drug effects
- Phosphorylation
- TRPV Cation Channels/antagonists & inhibitors
- TRPV Cation Channels/genetics
- TRPV Cation Channels/metabolism
- Urinary Bladder/drug effects
- Urinary Bladder/metabolism
- Urinary Bladder/physiopathology
- Mice
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Affiliation(s)
- Shiori Kawasaki
- Laboratory for Drug Discovery & Disease Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan
| | - Masahiko Soga
- Animal Production Technology for Animal Models, Shionogi Techno Advance Research Co. Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan
| | - Yusuke Sakurai
- Laboratory for Drug Discovery & Disease Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan
| | - Isamu Nanchi
- Laboratory for Innovative Therapy Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan
| | - Miyuki Yamamoto
- Laboratory for Drug Discovery & Disease Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan
| | - Sunao Imai
- Laboratory for Advanced Medicine Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan
| | - Tatsuya Takahashi
- Laboratory for Advanced Medicine Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan
| | - Naoki Tsuno
- API R&D Laboratory, CMC R&D Division, Shionogi & Co., Ltd., 1-3, Kuise terajima 2-chome, Amagasaki, Hyogo, 660-0813, Japan
| | - Toshiyuki Asaki
- Laboratory for Drug Discovery & Disease Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan
| | - Yasuhide Morioka
- Laboratory for Drug Discovery & Disease Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan
| | - Masahide Fujita
- Laboratory for Drug Discovery & Disease Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan.
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Relationship of Pain Catastrophizing With Urinary Biomarkers in Women With Bladder Pain Syndrome. Female Pelvic Med Reconstr Surg 2021; 27:746-752. [PMID: 33787562 DOI: 10.1097/spv.0000000000001041] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Brain-derived neurotrophic factor (BDNF) has been implicated in central neurological processes. We hypothesize that greater pain catastrophizing is associated with higher urinary BDNF levels in women with bladder pain syndrome. METHODS A secondary analysis of a database of women with urinary urgency was conducted. We identified women who met AUA criteria of bladder pain syndrome. Urinary symptoms, pain catastrophizing, and neuropathic pain were measured using the Female Genitourinary Pain Index, Pain Catastrophizing Scale and painDETECT questionnaires respectively. The relationship of the catastrophizing score with urinary BDNF (primary outcome) and other urinary biomarkers, including nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and osteopontin, was evaluated using univariable and multivariable analyses. RESULTS In 62 women with bladder pain syndrome, 15 (24%) reported pain catastrophizing symptoms (Pain Catastrophizing Scale score >30). Higher catastrophizing scores were associated with worse urinary symptoms, greater pelvic pain, greater neuropathic pain, and worse quality of life scores (all P < 0.01). On multivariable analysis, after controlling for age, body mass index and urinary symptoms, a higher pain catastrophizing score was associated with lower BDNF (P = 0.04) and lower VEGF levels (P = 0.03). Urinary urgency was associated with a higher NGF level (P = 0.04) while bladder pain was associated with higher levels of NGF (P = 0.03) and VEGF (P = 0.01). CONCLUSIONS Neuroinflammatory mechanisms contribute to the central processing of pain in women with bladder pain syndrome. Worse urinary symptoms are associated with higher NGF and VEGF levels, but worse pain catastrophizing is associated with lower BDNF and VEGF levels. Urinary BDNF levels may be useful in phenotyping women who have central augmentation of pain processing.
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Lifestyle and behavioral modifications made by patients with interstitial cystitis. Sci Rep 2021; 11:3055. [PMID: 33542405 PMCID: PMC7862395 DOI: 10.1038/s41598-021-82676-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 01/22/2021] [Indexed: 11/08/2022] Open
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) negatively affects the quality of life. In this study, we investigated the lifestyle behavioral changes patients with IC/BPS make to cope with their symptoms. This prospective study was conducted between August 2018 and June 2019. All patients had a primary symptom of suprapubic pain with a full bladder and other lower urinary tract symptoms for more than 6 weeks as well as cystoscopic findings. All participants completed our self-developed questionnaire, which included informations about their living and work environment, occupational garments, dietary habits, and personal habits. Continuous variables were compared using an independent sample t test, and categorical variables were compared using a chi-square test. We recruited 86 patients with IC/BPS and age-matched 86 controls without IC/BPS. In our study, patients with IC/BPS had more cranberry intake (45.34% vs. 5.81%, P < 0.05) than non-IC/BPS controls; the IC/BPS group had decreased consumption of coffee and spicy food; and wore less makeup or special work garments. In conclusion, patients with IC/BPS tend to make several lifestyle behavioral changes to cope with their symptoms.
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18
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Himle JA, Weaver A, Zhang A, Xiang X. Digital Mental Health Interventions for Depression. COGNITIVE AND BEHAVIORAL PRACTICE 2021. [DOI: 10.1016/j.cbpra.2020.12.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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19
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McKernan LC, Crofford LJ, Kim A, Vandekar SN, Reynolds WS, Hansen KA, Clauw DJ, Williams DA. Electronic Delivery of Pain Education for Chronic Overlapping Pain Conditions: A Prospective Cohort Study. PAIN MEDICINE 2021; 22:2252-2262. [PMID: 33871025 DOI: 10.1093/pm/pnab018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVE To examine the impact of educational materials for chronic overlapping pain conditions (COPCs), the feasibility of delivering materials online, and to explore its impact on self-reported self-management applications at 3-month follow-up. DESIGN Prospective cohort study. SETTING Online. SUBJECTS Individuals from a university-wide active research repository with ≥1 coded diagnostic COPC by ICD-9/10 in the medical record. METHODS We determined the number of COPCs per participant as indicated by diagnostic codes in the medical record. Consenting participants completed self-report questionnaires and read educational materials. We assessed content awareness and knowledge pre- and post-exposure to education. Comprehension was assessed via embedded questions in reading materials in real time. Participants then completed assessments regarding concept retention, self-management engagement, and pain-related symptoms at 3-months. RESULTS N = 216 individuals enrolled, with 181 (84%) completing both timepoints. Results indicated that participants understood materials. Knowledge and understanding of COPCs increased significantly after education and was retained at 3-months. Patient characteristics suggested the number of diagnosed COPCs was inversely related to age. Symptoms or self-management application did not change significantly over the 3-month period. CONCLUSIONS The educational materials facilitated teaching of key pain concepts in self-management programs, which translated easily into an electronic format. Education alone may not elicit self-management engagement or symptom reduction in this population; however, conclusions are limited by the study's uncontrolled design. Education is likely an important and meaningful first step in comprehensive COPC self-management.
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Affiliation(s)
- Lindsey C McKernan
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.,Department of Physical Medicine & Rehabilitation, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.,Osher Center for Integrative Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Leslie J Crofford
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Ahra Kim
- Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Simon N Vandekar
- Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - William S Reynolds
- Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Kathryn A Hansen
- Department of Physical Medicine & Rehabilitation, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.,Osher Center for Integrative Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Daniel J Clauw
- Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan, USA
| | - David A Williams
- Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan, USA
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20
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Metabolic syndrome in women with and without interstitial cystitis/bladder pain syndrome. Int Urogynecol J 2020; 32:1299-1306. [PMID: 33215272 DOI: 10.1007/s00192-020-04605-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 11/10/2020] [Indexed: 02/05/2023]
Abstract
INTRODUCTION AND HYPOTHESIS The aim of this study was to compare the frequency of metabolic syndrome (MetS) in patients with and without interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS This case-control study evaluated the indicators of MetS in 287 females with IC/BPS and in 287 females without IC/BPS in West China Hospital between January 2010 and January 2020. Then, the number of voids per day, frequency of night urination, O'Leary-Sant Interstitial Cystitis Symptom/Problem Index, and visual analog scale were examined in the two groups. RESULTS Based on both the National Cholesterol Education Program Adult Treatment Panel III recommendations and the International Diabetes Federation criteria, the distribution of MetS was statistically higher in patients with IC/BPS than in the control group, with 34.8% vs 17.8% (P < 0.0001) and 34.2% vs 20.9% (P = 0.0005), respectively. Regarding symptom scores, the IC/BPS group demonstrated significantly higher scores than the control group in all aspects (P < 0.0001). More patients with anxiety (P < 0.0001), insomnia (P < 0.0001), hypertension (P = 0.0001), and diabetes mellitus (P = 0.017) were observed in the IC/BPS group. Moreover, the findings indicated that patients with IC/BPS had a higher BMI (P = 0.0001) and larger waist circumference (P = 0.0001). Blood tests presented a significantly higher level of fasting glycemia, serum cystatin-C, and triglycerides in patients with IC/BPS. Furthermore, higher ORs for the occurrence of MetS among cases were observed, although this was not statistically significant. CONCLUSIONS MetS frequency was relatively high in patients with IC/BPS. Further research is needed to understand the common pathophysiologic mechanism of IC/BPS and MetS.
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21
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McKernan LC, Bonnet KR, Finn MTM, Williams DA, Bruehl S, Reynolds WS, Clauw D, Dmochowski RR, Schlundt DG, Crofford LJ. Qualitative Analysis of Treatment Needs in Interstitial Cystitis/Bladder Pain Syndrome: Implications for Intervention. Can J Pain 2020; 4:181-198. [PMID: 33367196 PMCID: PMC7751614 DOI: 10.1080/24740527.2020.1785854] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 05/26/2020] [Accepted: 06/18/2020] [Indexed: 11/06/2022]
Abstract
BACKGROUND Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition carrying substantial psychosocial burden. Psychological treatment for IC/BPS is little studied, and there are barriers to its use in clinical management. Whether psychological treatments benefit patients with IC/BPS is unclear and we do not know if such treatments would meet patient needs. AIMS Incorporating patient-reported needs and acknowledging diversity in pain experiences can inform patient-centered interventions for IC/BPS. This project characterized the experience of living with IC/BPS and patient perceptions of needs in its treatment, with the goal of informing patient-centered treatment for IC/BPS. METHODS Using both quantitative and qualitative methods, 27 females with IC/BPS participated in a focus group and completed validated self-report assessments evaluating urinary symptoms, pain, and emotional functioning. Focus groups were audio recorded and transcribed, then coded and analyzed using an iterative inductive/deductive approach. Linear regression models evaluated the relationship between psychological functioning and symptom severity. RESULTS We conducted six focus groups between 8/2017-12/2017. Five major themes emerged from qualitative analysis: managing physical symptoms, emotional symptoms, impact on daily life and socio-contextual factors, responding to illness, and addressing needs in treatment. The physiological and emotional consequences of IC/BPS were reported, highlighting their impact on interpersonal relationships and challenges obtaining appropriate treatment for IC/BPS. Quantitative analysis showed depression levels were significantly associated with worsened IC/BPS symptomology, after controlling for known confounding factors. CONCLUSION Individuals with IC/BPS could benefit from tailored psychological interventions focusing on pain management, emotion regulation, communications skills, along with sexual dysfunction and intimacy fears.
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Affiliation(s)
- Lindsey C. McKernan
- Department of Psychiatry & Behavioral Sciences, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Physical Medicine & Rehabilitation, Vanderbilt University School of Medicine, Nashville, TN, USA
| | | | - Michael T. M. Finn
- Department of Psychiatry & Behavioral Sciences, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - David A. Williams
- Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA
| | - Stephen Bruehl
- Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - W. Stuart Reynolds
- Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Daniel Clauw
- Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA
| | - Roger R. Dmochowski
- Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - David G. Schlundt
- Department of Psychology, Vanderbilt University, Nashville, Tennessee, USA
| | - Leslie J Crofford
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
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22
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Hung HH, Chen WC, Chen YH, Chiu LT, Chen HY. Evaluation of the efficacy of Chinese herbal medicine and acupuncture for the prevention of mental disorders in interstitial cystitis patients: A nationwide population-based study. Medicine (Baltimore) 2020; 99:e21422. [PMID: 32791761 PMCID: PMC7386994 DOI: 10.1097/md.0000000000021422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Traditional Chinese medicine (TCM) is commonly used for urinary symptoms in Eastern countries. Since there are few effective treatments available for patients with interstitial cystitis/bladder pain syndrome (IC/BPS), the psychological burden leads to increased healthcare-seeking behavior. Some patients may therefore seek TCM treatment for related urinary symptoms. Due to limited clinical research evaluating the effects of TCM on IC/BPS, we conducted a nationwide population-based cohort study to investigate the relationship between TCM and mental disorders among these patients. The IC/BPS cohort and its matched non-IC/BPS comparison cohort were recruited from the National Health Insurance (NHI) Research Database between 2000 and 2011. Patients with the use of Chinese herbal medicine (CHM) granules or acupuncture over 90 days per year were enrolled as the TCM users. Multivariable Cox proportional hazards models were used to evaluate the hazard ratio (HR) of mental disorders related to interstitial cystitis. The incidence of mental disorders in the 2 cohorts was assessed with Kaplan-Meier curves. A total of 1123 patients with IC/BPS and 4492 matched non-IC/BPS subjects were included in this study. The IC/BPS cohort demonstrated higher incidence rate of mental disorders than the cohort without IC/BPS (adjusted HR: 2.21, 95% confidence interval [CI]: 1.73-2.81). There was no statistically significant difference in the risk of mental disorders between IC/BPS patients with and without CHM granules or acupuncture treatment (adjusted HR: 0.99, 95% CI: 0.58-1.68). Our results indicated that CHM and acupuncture showed insignificant efficacy in the prevention of mental disorders in IC/BPS patients.
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Affiliation(s)
| | - Wen-Chi Chen
- Graduate Institute of Integrated Medicine, College of Chinese Medicine
- Departments of Obstetrics and Gynecology, Urology, and Medical Research
| | - Yung-Hsiang Chen
- Graduate Institute of Integrated Medicine, College of Chinese Medicine
- Departments of Obstetrics and Gynecology, Urology, and Medical Research
- Department of Psychology, College of Medical and Health Science, Asia University
| | - Lu-Ting Chiu
- Management office for Health Data, China Medical University Hospital
- College of Medicine, China Medical University, Taichung, Taiwan
| | - Huey-Yi Chen
- Graduate Institute of Integrated Medicine, College of Chinese Medicine
- Departments of Obstetrics and Gynecology, Urology, and Medical Research
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Chen JL, Zhou X, Liu BL, Wei XH, Ding HL, Lin ZJ, Zhan HL, Yang F, Li WB, Xie JC, Su MZ, Liu XG, Zhou XF. Normalization of magnesium deficiency attenuated mechanical allodynia, depressive-like behaviors, and memory deficits associated with cyclophosphamide-induced cystitis by inhibiting TNF-α/NF-κB signaling in female rats. J Neuroinflammation 2020; 17:99. [PMID: 32241292 PMCID: PMC7118907 DOI: 10.1186/s12974-020-01786-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 03/25/2020] [Indexed: 01/01/2023] Open
Abstract
Background Bladder-related pain symptoms in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) are often accompanied by depression and memory deficits. Magnesium deficiency contributes to neuroinflammation and is associated with pain, depression, and memory deficits. Neuroinflammation is involved in the mechanical allodynia of cyclophosphamide (CYP)-induced cystitis. Magnesium-L-Threonate (L-TAMS) supplementation can attenuate neuroinflammation. This study aimed to determine whether and how L-TAMS influences mechanical allodynia and accompanying depressive symptoms and memory deficits in CYP-induced cystitis. Methods Injection of CYP (50 mg/kg, intraperitoneally, every 3 days for 3 doses) was used to establish a rat model of BPS/IC. L-TAMS was administered in drinking water (604 mg·kg−1·day−1). Mechanical allodynia in the lower abdomen was assessed with von Frey filaments using the up-down method. Forced swim test (FST) and sucrose preference test (SPT) were used to measure depressive-like behaviors. Novel object recognition test (NORT) was used to detect short-term memory function. Concentrations of Mg2+ in serum and cerebrospinal fluid (CSF) were measured by calmagite chronometry. Western blot and immunofluorescence staining measured the expression of tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), interleukin-1β (IL-1β), and N-methyl-d-aspartate receptor type 2B subunit (NR2B) of the N-methyl-d-aspartate receptor in the L6–S1 spinal dorsal horn (SDH) and hippocampus. Results Free Mg2+ was reduced in the serum and CSF of the CYP-induced cystitis rats on days 8, 12, and 20 after the first CYP injection. Magnesium deficiency in the serum and CSF correlated with the mechanical withdrawal threshold, depressive-like behaviors, and short-term memory deficits (STMD). Oral application of L-TAMS prevented magnesium deficiency and attenuated mechanical allodynia (n = 14) and normalized depressive-like behaviors (n = 10) and STMD (n = 10). The upregulation of TNF-α/NF-κB signaling and IL-1β in the L6–S1 SDH or hippocampus was reversed by L-TAMS. The change in NR2B expression in the SDH and hippocampus in the cystitis model was normalized by L-TAMS. Conclusions Normalization of magnesium deficiency by L-TAMS attenuated mechanical allodynia, depressive-like behaviors, and STMD in the CYP-induced cystitis model via inhibition of TNF-α/NF-κВ signaling and normalization of NR2B expression. Our study provides evidence that L-TAMS may have therapeutic value for treating pain and comorbid depression or memory deficits in BPS/IC patients.
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Affiliation(s)
- Jia-Liang Chen
- Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600 W Tianhe Rd, Guangzhou, 510630, China
| | - Xin Zhou
- Pain Research Center and Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Rd. 2, Guangzhou, 510080, China
| | - Bo-Long Liu
- Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600 W Tianhe Rd, Guangzhou, 510630, China
| | - Xu-Hong Wei
- Pain Research Center and Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Rd. 2, Guangzhou, 510080, China
| | - Hong-Lu Ding
- Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600 W Tianhe Rd, Guangzhou, 510630, China
| | - Zhi-Jun Lin
- Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600 W Tianhe Rd, Guangzhou, 510630, China
| | - Hai-Lun Zhan
- Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600 W Tianhe Rd, Guangzhou, 510630, China
| | - Fei Yang
- Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600 W Tianhe Rd, Guangzhou, 510630, China
| | - Wen-Biao Li
- Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600 W Tianhe Rd, Guangzhou, 510630, China
| | - Jun-Cong Xie
- Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600 W Tianhe Rd, Guangzhou, 510630, China
| | - Min-Zhi Su
- Department of Rehabilitation, The Third Affiliated Hospital and Lingnan Hospital of the Sun Yat-sen University, 2693 Kaichuang Rd, Guangzhou, 510700, China
| | - Xian-Guo Liu
- Pain Research Center and Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Rd. 2, Guangzhou, 510080, China. .,Guangdong Provincial Key Laboratory of Brain Function and Disease, 74 Zhongshan Rd. 2, Guangzhou, 510080, China.
| | - Xiang-Fu Zhou
- Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, 600 W Tianhe Rd, Guangzhou, 510630, China.
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Hsu CY, Lin CL, Kao CH. Association between Chronic Interstitial Cystitis and Herpes Zoster. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17072228. [PMID: 32224999 PMCID: PMC7177600 DOI: 10.3390/ijerph17072228] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 01/14/2023]
Abstract
Objectives: Herpes zoster (HZ) infection has been associated with disease burdens such as infection and depression. However, the relationship between chronic interstitial cystitis (CIC) and HZ is unknown. This study investigated HZ risk in patients with CIC. Patients and Methods: The Longitudinal Health Insurance Database, which is a subset of the Taiwan National Health Insurance Research Database, was used in the study. The case cohort consisted of patients with newly diagnosed CIC between 2000 and 2012. Each patient with CIC was matched to four controls by age and index year. All participants were traced from the index date to HZ diagnosis, and loss to follow-up or death, or to the end of the study (31 December 2013). Results: A total of 1096 patients with CIC and 4384 controls were enrolled. The incidence rate of HZ in patients with CIC was 10.8 per 1000 person-years, whereas that for controls was 7.25 per 1000 person-years. HZ risk for the case cohort was 1.48 times that for the control cohort. Among participants aged ≤49 years, patients with CIC had a 1.91-fold-increased HZ risk compared to those without CIC. Conclusion: Patients with CIC had a higher risk of HZ than those without CIC. CIC should not be ignored, particularly in young adults.
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Affiliation(s)
- Chao-Yu Hsu
- Department of Medical Education and Research, Puli Christian Hospital, Puli 545, Taiwan;
- Department of Family Medicine, Puli Christian Hospital, Puli 545, Taiwan
- Department of Optometry, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan
- Center for General Education, National Taichung University of Science and Technology, Taichung 404, Taiwan
- The General Education Center, Chaoyang University of Technology, Taichung 413, Taiwan
- Department of General Education, National Chin-Yi University of Technology, Taichung 41170, Taiwan
- Center for General Education, National Chi Nan University, Puli 54561, Taiwan
- Rural Generalist Program Japan, genepro, Asahi Shi 289-2505, Japan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung 40447, Taiwan;
- School of Medicine, College of Medicine, China Medical University, Taichung 40447, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40447, Taiwan
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung 40447, Taiwan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung 40447, Taiwan
- Center of Augmented Intelligence in Healthcare, China Medical University Hospital, Taichung 40447, Taiwan
- Correspondence: ; Tel.: +886-4-22052121
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25
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Lin CE, Chun CH, Chen LF, Chien WC. Increased Risk of Pain after Electroconvulsive Therapy among Depressed Patients: a Nationwide Study in Taiwan. Psychiatr Q 2020; 91:237-250. [PMID: 31823195 DOI: 10.1007/s11126-019-09682-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
The risk of pain after electroconvulsive therapy (ECT) among depressed patients is still controversial. We aimed to investigate the risk of pain post-ECT among patients with depression. We investigated patients with depression, based on the data in the National Health Insurance Research Database. A comparison cohort comprising depressed non-ECT patients with at least three psychiatric admissions were matched. A Cox proportional regression model was used to investigate the risk of pain between the ECT and comparison cohorts. The ECT and comparison cohorts consisted of 1246 and 4984 patients, respectively. Compared to the control group patients, the ECT group patients had a significantly increased risk of developing overall pain (aHR = 5.753; 95% CI: 2.405-11.760; P < 0.001). Specifically, the risk of developing headache (aHR = 7.270; 95% CI: 1.226-47.731; P = 0.026) and musculoskeletal pain (MSP; aHR = 5.330; 95% CI: 2.937-11.663; P = 0.001) was significantly higher than in the control group. The sensitivity analysis, which involved checking pain events for each week to the end of the study, also provided significant findings in overall pain (aHR = 13.013, 95% CI: 2.121-94.258, P < 0.001), headache (aHR = 10.995; 95% CI: 1.099-122.601; P = 0.042) and MSP (aHR = 14.210, 95% CI: 2.436-82.898, P = 0.003) within 3 weeks of follow-up. This study suggests that depressed patients who undergo ECT may have an increased risk of developing subsequent pain. Further research is warranted to elucidate whether pain is associated with ECT because several potential confounders existed.
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Affiliation(s)
- Ching-En Lin
- Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan, Republic of China.,School of Medicine, Tzu Chi University, Hualien, Taiwan, Republic of China
| | - Chi-Hsiang Chun
- Department of Medical Research, Tri-Service General Hospital, Number 325, Section 2, Chenggong Road, Neihu District, Taipei City, 11490, Taiwan, Republic of China.,School of Public Health, National Defense Medical Centre, Taipei, Taiwan, Republic of China
| | - Li-Fen Chen
- National Defense Medical Centre, Taipei, Taiwan, Republic of China.,Department of Psychiatry, Hualien Armed Forces General Hospital, Hualien, Taiwan, Republic of China
| | - Wu-Chien Chien
- Department of Medical Research, Tri-Service General Hospital, Number 325, Section 2, Chenggong Road, Neihu District, Taipei City, 11490, Taiwan, Republic of China. .,School of Public Health, National Defense Medical Centre, Taipei, Taiwan, Republic of China.
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Aguiniga LM, Searl TJ, Rahman-Enyart A, Yaggie RE, Yang W, Schaeffer AJ, Klumpp DJ. Acyloxyacyl hydrolase regulates voiding activity. Am J Physiol Renal Physiol 2020; 318:F1006-F1016. [PMID: 32003596 DOI: 10.1152/ajprenal.00442.2019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Corticotropin-releasing factor (CRF) regulates diverse physiological functions, including bladder control. We recently reported that Crf expression is under genetic control of Aoah, the locus encoding acyloxyacyl hydrolase (AOAH), suggesting that AOAH may also modulate voiding. Here, we examined the role of AOAH in bladder function. AOAH-deficient mice exhibited enlarged bladders relative to wild-type mice and had decreased voiding frequency and increased void volumes. AOAH-deficient mice had increased nonvoiding contractions and increased peak voiding pressure in awake cystometry. AOAH-deficient mice also exhibited increased bladder permeability and higher neuronal firing rates of bladder afferents in response to stretch. In wild-type mice, AOAH was expressed in bladder projecting neurons and colocalized in CRF-expressing neurons in Barrington's nucleus, an important brain area for voiding behavior, and Crf was elevated in Barrington's nucleus of AOAH-deficient mice. We had previously identified aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor-γ as transcriptional regulators of Crf, and conditional knockout of AhR or peroxisome proliferator-activated receptor-γ in Crf-expressing cells restored normal voiding in AOAH-deficient mice. Finally, an AhR antagonist improved voiding in AOAH-deficient mice. Together, these data demonstrate that AOAH regulates bladder function and that the AOAH-Crf axis is a therapeutic target for treating voiding dysfunction.
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Affiliation(s)
- Lizath M Aguiniga
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Timothy J Searl
- Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Afrida Rahman-Enyart
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Ryan E Yaggie
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Wenbin Yang
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Anthony J Schaeffer
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - David J Klumpp
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.,Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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Chen HC, Liu CY, Liao CH, Tsao LI. Self-perception of symptoms, medical help seeking, and self-help strategies of women with interstitial cystitis/painful bladder syndrome. Low Urin Tract Symptoms 2020; 12:183-189. [PMID: 31970901 DOI: 10.1111/luts.12300] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 12/20/2019] [Accepted: 01/03/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study aims to investigate the self-perception of symptoms, medical help seeking, and self-help strategies of women with interstitial cystitis (IC). METHODS A mixed method of qualitative and quantitative approaches was employed. The qualitative approach used in-depth interviews about the subjective experience of symptoms, medical help seeking, and self-help strategies for their IC. The quantitative inquiry was conducted by a yes or no response to the question "Did self-perceived severe symptoms of IC interfere with your daily life?" A loglinear model was applied to investigate the associations between possible factors. RESULTS This study recruited 68 women aged 20 to 69 years, of whom 22 were interviewed for qualitative data. About 72.1% of the women responded that self-perceived severe IC symptoms interfered with their daily life. A significant negative association between employment and self-perceived severe IC symptoms (P < .05) was observed. Qualitative results revealed three important themes: (1) bothersome symptoms-all-day bladder pain and lower urinary tract symptoms and deteriorated quality of life, (2) medical help seeking-exhaustion and frustration, (3) self-help strategies-coexisting with IC or feeling helpless. CONCLUSIONS IC women feel exhausted and frustrated by seeking medical attention for this incurable disease for a long time. IC women have troubled and uneasy daily lives. Being employed or engaging in activities can divert attention to alleviate symptoms. IC patient support groups allow patients to share their self-help experiences with interdisciplinary medical teams to provide physical and psychological treatment.
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Affiliation(s)
- Hui-Chun Chen
- Department of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
| | - Chieh-Yu Liu
- Department of Speech Language Pathology and Audiology, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
| | - Chun-Hou Liao
- Department of Urology, Cardinal Tien Hospital and Fu-Jen Catholic University, New Taipei, Taiwan
| | - Lee-Ing Tsao
- College of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
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Scarneciu I, Bungau S, Lupu AM, Scarneciu CC, Bratu OG, Martha O, Tit DM, Aleya L, Lupu S. Efficacy of instillation treatment with hyaluronic acid in relieving symptoms in patients with BPS/IC and uncomplicated recurrent urinary tract infections - Long-term results of a multicenter study. Eur J Pharm Sci 2019; 139:105067. [DOI: 10.1016/j.ejps.2019.105067] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 09/05/2019] [Accepted: 09/05/2019] [Indexed: 12/27/2022]
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Yeh HL, Jhang JF, Kuo YC, Kuo HC. Long-term outcome and symptom improvement in patients with interstitial cystitis/bladder pain syndrome with or without regular follow-up and treatment. Neurourol Urodyn 2019; 38:1985-1993. [PMID: 31310370 DOI: 10.1002/nau.24104] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 06/25/2019] [Indexed: 11/09/2022]
Abstract
AIMS Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease, which is difficult to treat. Patients usually seek for new therapies and might not follow-up regularly. This study investigated long-term symptom changes in patients with IC/BPS, especially in those who were lost to follow-up. METHODS We enrolled patients with IC/BPS with a history of >5 years and having comprehensive medical records, baseline IC symptom index and IC problem index, O'Leary-Sant symptom score, and visual analog scale (VAS). A telephone interview was conducted to assess current symptoms with the same questionnaires. A 5-point scale (from -1 to 3) was used to grade current treatment outcomes. RESULTS A total of 198 patients with IC/BPS with a mean age of 57.4 ± 12.2 years were included. At a mean follow-up duration of 16.6 ± 9.75 years, 12% of the patients were free of symptoms and 47% exhibited symptom improvement of more than 50%. Totally, 47 (23.7%) patients were lost to follow-up for >5 years, and 151 (76.3%) had a regular follow-up. The patients with IC/BPS who were not regularly followed up had no Hunner's lesion, and had a higher bladder volume (P = .023), higher urine flow (P = .019), and fewer comorbidities (P = .014) than those who had a regular follow-up. The number of treatment modalities was significantly less in the patients who were lost to follow-up (P = .037). CONCLUSIONS About half of the patients with IC/BPS exhibited symptom improvement with time, with or without regular follow-up and receiving a new treatment.
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Affiliation(s)
- Hui-Ling Yeh
- Department of Nursing, Hualien Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Jia-Fong Jhang
- Department of Urology, Hualien Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Yuh-Chen Kuo
- Department of Urology, Yang Ming Hospital, Taipei, Taiwan
| | - Hann-Chorng Kuo
- Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
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30
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Wen JY, Lo TS, Chuang YC, Ho CH, Long CY, Law KS, Tong YC, Wu MP. Risks of interstitial cystitis among patients with systemic lupus erythematosus: A population-based cohort study. Int J Urol 2019; 26:897-902. [PMID: 31311067 DOI: 10.1111/iju.14065] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 06/18/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To investigate whether the risk of interstitial cystitis increases among the patients with systemic lupus erythematosus. METHODS This was a nationwide population-based cohort study. Data were obtained from the National Health Insurance Research Database in Taiwan. Women aged >18 years newly diagnosed as systemic lupus erythematosus during 2001-2008 were identified as the control group. The comparison included individuals randomly selected from the National Health Insurance Research Database in the year of 2000, by matching one systemic lupus erythematosus participant with eight non-systemic lupus erythematosus participants with sex and age. These participants were followed up until being diagnosed as interstitial cystitis, or the end of 2011. Women diagnosed with lupus cystitis were excluded from this study. RESULTS This study included 7240 women with systemic lupus erythematosus and 57 920 women without systemic lupus erythematosus as controls. The incidence rate of interstitial cystitis was significantly higher in the systemic lupus erythematosus group, with an incidence rate ratio of 2.26 (95% confidence interval 1.57-3.27, P < 0.0001). After adjustment, the risk increased by 2.45-fold (adjusted hazard ratio 2.45, 95% confidence interval 1.57-3.27, P < 0.05). Age as a factor increases incidence rate ratios among all age groups, 2.12-, 3.32- and 4.65-fold. Age ≥45 years had an increased adjusted hazard ratio (2.07, 95% confidence interval 1.37-3.13, P < 0.05). Comorbidities, for example, hypertension, diabetes mellitus, dyslipidemia and renal disease, were insignificant. CONCLUSIONS This is the first population-based cohort study showing a higher incidence of interstitial cystitis among patients with systemic lupus erythematosus. These findings support the concordance of interstitial cystitis with autoimmune diseases, and the temporal relationship to develop interstitial cystitis in patients with systemic lupus erythematosus.
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Affiliation(s)
- Jen-Yu Wen
- Division of Urogynecology, Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan
| | - Tsia-Shu Lo
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Keelung Medical Center, Keelung, Taiwan.,School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yao-Chi Chuang
- Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Han Ho
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.,Department of Hospital and Health Care Administration, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Cheng-Yu Long
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Obstetrics and Gynecology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kim-Seng Law
- Department of Obstetrics and Gynecology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan
| | - Yat-Ching Tong
- Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Ping Wu
- Division of Urogynecology, Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan.,Department of Obstetrics and Gynecology, College of Medicine, Fu-Jen University, Taipei, Taiwan
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Pape J, Falconi G, De Mattos Lourenco TR, Doumouchtsis SK, Betschart C. Variations in bladder pain syndrome/interstitial cystitis (IC) definitions, pathogenesis, diagnostics and treatment: a systematic review and evaluation of national and international guidelines. Int Urogynecol J 2019; 30:1795-1805. [PMID: 31073635 DOI: 10.1007/s00192-019-03970-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 04/22/2019] [Indexed: 12/30/2022]
Abstract
INTRODUCTION AND HYPOTHESIS Interstitial cystitis (IC) and bladder pain syndrome (BPS) are challenging and encompassing hypersensitivity disorders of the lower urinary tract. A variety of national and international guidelines have been published including guidance on nomenclature, definitions, etiopathology, diagnostics and treatment. A lack of universally established clinical guidance is apparent. The aim of this review is to evaluate key guidelines on this area of practice, identify variations, compare their recommendations and grade them using AGREE II. METHODS Literature searches were performed using the PUBMED and CINAHL database from January 1, 1983, to December 1, 2018, referring to the search strategy of AUA. Ten national and international guidelines were included into the analysis. We assessed the guidelines with the updated AGREE II. RESULTS Symptoms congruent in all guidelines are: pain, pressure, discomfort and frequency, urgency and nocturia. Urinalysis is a prerequisite for diagnostics, cystoscopy for most and urodynamics not part of the routine assessment. Treatment options are recommended stepwise. The highest level of evidence and consensus was identified for oral therapies. Nine guidelines had an overall quality score ≥ 50% and three scored ≥ 70% (AUA, GG, RCOG). CONCLUSIONS The guidelines are congruent in symptom reporting, quite congruent in diagnostics and vary to a high degree on treatment recommendations. The complexity of BPS and emerging evidence indicate the need for regular updating of the guidelines and a wider consensus.
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Affiliation(s)
- Janna Pape
- Department of Gynecology, University Hospital of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland
| | - Gabriele Falconi
- Department of Obstetrics and Gynecology, "San Bortolo" Hospital, Vicenza, Italy
| | | | - Stergios K Doumouchtsis
- Department of Obstetrics and Gynaecology, Epsom and St Helier University Hospitals NHS Trust, London, UK.,St George's University of London, London, UK
| | - Cornelia Betschart
- Department of Gynecology, University Hospital of Zurich, Frauenklinikstrasse 10, 8091, Zurich, Switzerland.
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Yu WR, Peng TC, Yeh HL, Kuo HC. Anxiety severity does not influence treatment outcomes in patients with interstitial cystitis/bladder pain syndrome. Neurourol Urodyn 2019; 38:1602-1610. [PMID: 31059599 DOI: 10.1002/nau.24019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 04/11/2019] [Accepted: 04/11/2019] [Indexed: 11/09/2022]
Abstract
AIMS Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) typically experience anxiety mood status, which is closely connected with physical and psychological status and treatment outcome. This study aimed to evaluate the impact of anxiety severity on therapeutic results in IC/BPS patients. METHODS We prospectively enrolled IC/BPS patients who had previously undergone any kind of treatment for their disease. The primary endpoint was a change in Beck Anxiety Inventory (BAI) scores at 3 months after treatment. Secondary endpoints included changes in the Global Response Assessment (GRA), O'Leary-Sant symptom score (OSS), and Numerical Rating Scale (NRS) at 3 months after treatment. Urodynamic studies were also compared with the clinical symptom scores. RESULTS Overall, 85 IC/BPS patients (mean age, 53.1 ± 12.4 years) were included in the study. At 3 months, changes in the GRA were not significantly different among the different anxiety severity groups. At baseline, 55 (64.7%) patients had moderate or severe anxiety. We observed a significant positive correlation between the change in BAI and the change in OSS after treatment and a significantly negative correlation with GRA at 3 months. Moreover, improvements in OSS and NRS were associated with the change in GRA. Changes in IC symptoms, but not physiological outcomes, were associated with improved anxiety status after treatment. In addition, the change in BAI was significantly associated with age, baseline BAI, and changes in OSS and GRA after treatment. CONCLUSIONS Baseline anxiety severity does not influence treatment outcomes of IC/BPS. Patients should receive active treatment regardless of their baseline anxiety status.
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Affiliation(s)
- Wan Ru Yu
- Hualien Tzu Chi Hospital, Nursing, Hualien, Taiwan
| | - Tai Chu Peng
- Tzu Chi University College of Medicine, Nursing, Hualien, Taiwan
| | - Hui Ling Yeh
- Hualien Tzu Chi Hospital, Nursing, Hualien, Taiwan
| | - Hann-Chorng Kuo
- Department of Urology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
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Long-term follow-up after cystectomy for bladder pain syndrome: pain status, sexual function and quality of life. World J Urol 2018; 37:1597-1603. [DOI: 10.1007/s00345-018-2554-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 10/29/2018] [Indexed: 10/27/2022] Open
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Risk of Urinary Tract Carcinoma among Subjects with Bladder Pain Syndrome/Interstitial Cystitis: A Nationwide Population-Based Study. BIOMED RESEARCH INTERNATIONAL 2018; 2018:7495081. [PMID: 30050942 PMCID: PMC6046152 DOI: 10.1155/2018/7495081] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 04/10/2018] [Accepted: 06/05/2018] [Indexed: 12/24/2022]
Abstract
Objective To investigate the subsequent risks of urinary tract cancers among individuals with bladder pain syndrome/interstitial cystitis (BPS/IC), and gender differences, as well as the effect of associated comorbidity using a population-based administrative database in Taiwan. Patients and Methods BPS/IC subjects (10192) and their age- and sex-matched non-BPS/IC control subjects (30576), who had no previous upper urinary tract cancer (UUC), bladder cancer (BC), and prostate cancer (PC), subsequently developed these disorders from the recruited date between 2002 and 2008 and the end of follow-up 2011. A Cox proportional hazards regression model was constructed to estimate the risk of subsequent UUC, BC, and PC following a diagnosis of IC/BPS. The effect of associated comorbidities was measured by Charlson Comorbidity Index (CCI). The risk of outcomes was assessed with Kaplan-Meier curves. Results In the BPS/IC subjects, 37 (0.36%) received a diagnosis of BC, and 22 (0.22%) received a diagnosis of UUC; both were significantly higher than the control group, 19 (0.06%) for BC and 30 (0.10%) for UUC. Cox proportional analysis revealed that the adjusted HR for BC and UUC during the follow-up period for patients with IC/BPS was 5.44 (95% CI: 3.10-9.54) and 1.97 (95% CI: 1.13-3.45) than that of comparison subjects. The HRs went up to 5.66 (95% CI: 3.21-9.99) and 2.01 (95% CI: 1.14-3.55) after adjusted by Comorbidity Index (CCI). The male BPS/IC patients have a higher adjusted HR for BC; however, female patients have a higher adjusted HR for both BC and UUC. The adjusted HR for PC has no difference between BPS/IC and control group. Conclusion Patients with BPS/IC are at risk of developing BC in both males and females, and UUC in females. This result reminds physicians to evaluate the potential risk of subsequent development of BC and UUC among individuals with BPS/IC.
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Liang CC, Lin YH, Hsieh WC, Huang L. Urinary and psychological outcomes in women with interstitial cystitis/bladder pain syndrome following hyaluronic acid treatment. Taiwan J Obstet Gynecol 2018; 57:360-363. [DOI: 10.1016/j.tjog.2018.04.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/15/2018] [Indexed: 11/28/2022] Open
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36
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Giron SE, Bjurstrom MF, Griffis CA, Ferrante FM, Wu II, Nicol AL, Grogan TR, Burkard JF, Irwin MR, Breen EC. Increased Central Nervous System Interleukin-8 in a Majority Postlaminectomy Syndrome Chronic Pain Population. PAIN MEDICINE (MALDEN, MASS.) 2018; 19:1033-1043. [PMID: 29016958 PMCID: PMC6659015 DOI: 10.1093/pm/pnx126] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Background and Objectives Multiple processes have been identified as potential contributors to chronic pain, with increasing evidence illustrating an association with aberrant levels of neuroimmune mediators. The primary objectives of the present study were to examine central nervous system cytokines, chemokines, and growth factors present in a chronic pain population and to explore patterns of the same mediator molecules over time. Secondary objectives explored the relationship of central and peripheral neuroimmune mediators while examining the levels of anxiety, depression, sleep quality, and perception of pain associated with the chronic pain patient experience. Methods Cerebrospinal fluid (CSF) from a population of majority postlaminectomy syndrome patients (N = 8) was compared with control CSF samples (N = 30) to assess for significant differences in 10 cytokines, chemokines, and growth factors. The patient population was then followed over time, analyzing CSF, plasma, and psychobehavioral measures. Results The present observational study is the first to demonstrate increased mean CSF levels of interleukin-8 (IL-8; P < 0.001) in a small population of majority postlaminectomy syndrome patients, as compared with a control population. Over time in pain patients, CSF levels of IL-8 increased significantly (P < 0.001). Conclusions These data indicate that IL-8 should be further investigated and psychobehavioral components considered in the overall chronic pain paradigm. Future studies examining the interactions between these factors and IL-8 may identify novel targets for treatment of persistent pain states.
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Affiliation(s)
- Sarah E Giron
- Department of Anesthesiology, University of Southern California, Los Angeles, California
| | | | | | | | | | - Andrea L Nicol
- Department of Anesthesiology, University of Kansas School of Medicine, Kansas City, Kansas
| | | | - Joseph F Burkard
- Hahn School of Nursing and Health Science, University of San Diego, San Diego, California
- Department of Anesthesiology, University of California, San Diego, San Diego, California, USA
| | - Michael R Irwin
- Cousins Center for Psychoneuroimmunology
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California
| | - Elizabeth Crabb Breen
- Cousins Center for Psychoneuroimmunology
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California
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Rhon DI, Clewley D, Young JL, Sissel CD, Cook CE. Leveraging healthcare utilization to explore outcomes from musculoskeletal disorders: methodology for defining relevant variables from a health services data repository. BMC Med Inform Decis Mak 2018; 18:10. [PMID: 29386010 PMCID: PMC5793373 DOI: 10.1186/s12911-018-0588-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 01/17/2018] [Indexed: 12/29/2022] Open
Abstract
Background Large healthcare databases, with their ability to collect many variables from daily medical practice, greatly enable health services research. These longitudinal databases provide large cohorts and longitudinal time frames, allowing for highly pragmatic assessment of healthcare delivery. The purpose of this paper is to discuss the methodology related to the use of the United States Military Health System Data Repository (MDR) for longitudinal assessment of musculoskeletal clinical outcomes, as well as address challenges of using this data for outcomes research. Methods The Military Health System manages care for approximately 10 million beneficiaries worldwide. Multiple data sources pour into the MDR from multiple levels of care (inpatient, outpatient, military or civilian facility, combat theater, etc.) at the individual patient level. To provide meaningful and descriptive coding for longitudinal analysis, specific coding for timing and type of care, procedures, medications, and provider type must be performed. Assumptions often made in clinical trials do not apply to these cohorts, requiring additional steps in data preparation to reduce risk of bias. The MDR has a robust system in place to validate the quality and accuracy of its data, reducing risk of analytic error. Details for making this data suitable for analysis of longitudinal orthopaedic outcomes are provided. Results Although some limitations exist, proper preparation and understanding of the data can limit bias, and allow for robust and meaningful analyses. There is the potential for strong precision, as well as the ability to collect a wide range of variables in very large groups of patients otherwise not captured in traditional clinical trials. This approach contributes to the improved understanding of the accessibility, quality, and cost of care for those with orthopaedic conditions. Conclusion The MDR provides a robust pool of longitudinal healthcare data at the person-level. The benefits of using the MDR database appear to outweigh the limitations.
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Affiliation(s)
- Daniel I Rhon
- Center for the Intrepid, Brooke Army Medical Center, 3551 Roger Brooke Drive, San Antonio, TX, 78234, USA.
| | - Derek Clewley
- Baylor University, 3630 Stanley Road, Bldg 2841, Suite 1301; Joint Base San Antonio - Fort Sam Houston, San Antonio, TX, 78234, USA
| | - Jodi L Young
- Division of Physical Therapy, Department of Orthopedics, Duke University, 2200 W. Main Street, Durham, NC, 27701, USA
| | - Charles D Sissel
- Department of Physical Therapy, Arizona School of Health Sciences, 5850 E. Still Circle, Mesa, AZ, 85206, USA
| | - Chad E Cook
- Headquarters, U.S. Army Medical Command, Analysis & Evaluation Division, 3630 Stanley Road; Joint Base San Antonio - Fort Sam Houston, San Antonio, TX, 78234, USA
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Lin YC, Lai CC, Chien CC, Chen CM, Chiang SR, Ho CH, Weng SF, Cheng KC. Is insomnia a risk factor for new-onset asthma? A population-based study in Taiwan. BMJ Open 2017; 7:e018714. [PMID: 29187415 PMCID: PMC5719310 DOI: 10.1136/bmjopen-2017-018714] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
OBJECTIVES To determine whether insomnia at baseline is a risk factor for new-onset asthma. METHODS We recruited 48 871 patients with insomnia (insomnia group) newly diagnosed between 2002 and 2007, and 97 742 matched controls without insomnia (control group) from Taiwan's Longitudinal Health Insurance Database 2000. All of the patients were followed up for 4 years to see whether new-onset asthma developed. Patients with previous asthma or insomnia were excluded. The Poisson regression was used to estimate the incidence rate ratios (IRRs) and 95% CIs of asthma. Cox proportional hazard regression was used to calculate the risk of asthma between the two groups. RESULTS After a 4-year follow-up, 424 patients in the insomnia group and 409 in the control group developed asthma. The incidence rate of asthma was significantly higher in the insomnia group (22.01vs10.57 per 10 000 person-years). Patients with insomnia have a higher risk of developing new-onset asthma during the 4-year follow-up (HR: 2.08, 95% CI 1.82 to 2.39). The difference remained significant after adjustment (adjusted HR: 1.89, 95% CI 1.64 to 2.17). CONCLUSIONS This large population-based study suggests that insomnia at baseline is a risk factor for developing asthma.
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Affiliation(s)
- Yu-Chieh Lin
- Department of Family Medicine, Jiannren Hospital, Kaohsiung, Taiwan
| | - Chih-Cheng Lai
- Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan
| | - Chih-Chiang Chien
- Department of Internal Medicine, Chi Mei Medical Center, Yung Kang, Tainan, Taiwan
| | - Chin-Ming Chen
- Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Shyh-Ren Chiang
- Department of Internal Medicine, Chi Mei Medical Center, Yung Kang, Tainan, Taiwan
- Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Chung-Han Ho
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
- Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Shih-Feng Weng
- Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuo-Chen Cheng
- Department of Internal Medicine, Chi Mei Medical Center, Yung Kang, Tainan, Taiwan
- Department of Safety, Health, and Environmental Engineering, Chung Hwa University of Medical Technology, Tainan, Taiwan
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McKernan LC, Walsh CG, Reynolds WS, Crofford LJ, Dmochowski RR, Williams DA. Psychosocial co-morbidities in Interstitial Cystitis/Bladder Pain syndrome (IC/BPS): A systematic review. Neurourol Urodyn 2017; 37:926-941. [PMID: 28990698 DOI: 10.1002/nau.23421] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 08/28/2017] [Indexed: 01/26/2023]
Abstract
AIMS Psychosocial factors amplify symptoms of Interstitial Cystitis (IC/BPS). While psychosocial self-management is efficacious in other pain conditions, its impact on an IC/BPS population has rarely been studied. The objective of this review is to learn the prevalence and impact of psychosocial factors on IC/BPS, assess baseline psychosocial characteristics, and offer recommendations for assessment and treatment. METHOD Following PRISMA guidelines, primary information sources were PubMed including MEDLINE, Embase, CINAHL, and GoogleScholar. Inclusion criteria included: (i) a clearly defined cohort with IC/BPS or with Chronic Pelvic Pain Syndrome provided the IC/BPS cohort was delineated with quantitative results from the main cohort; (ii) all genders and regions; (iii) studies written in English from 1995 to April 14, 2017; (iv) quantitative report of psychosocial factors as outcome measures or at minimum as baseline characteristics. RESULTS Thirty-four of an initial 642 articles were reviewed. Quantitative analyses demonstrate the magnitude of psychosocial difficulties in IC/BPS, which are worse than average on all measures, and fall into areas of clinical concern for 7 out of 10 measures. Meta-analyses shows mean Mental Component Score of the Short-Form 12 Health Survey (MCS) of 40.80 (SD 6.25, N = 2912), where <36 is consistent with severe psychological impairment. Averaged across studies, the population scored in the range seen in clinical depression (CES-D 19.89, SD 13.12, N = 564) and generalized anxiety disorder (HADS-A 8.15, SD 4.85, N = 465). CONCLUSION The psychological impact of IC/BPS is pervasive and severe. Existing evidence of treatment is lacking and suggests self-management intervention may be helpful.
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Affiliation(s)
- Lindsey C McKernan
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee
- Department of Physical Medicine and Rehabilitation, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Colin G Walsh
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
- Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - William S Reynolds
- Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Leslie J Crofford
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Roger R Dmochowski
- Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - David A Williams
- Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan
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Naliboff BD, Stephens AJ, Lai HH, Griffith JW, Clemens JQ, Lutgendorf S, Rodriguez LV, Newcomb C, Sutcliffe S, Guo W, Kusek JW, Landis JR. Clinical and Psychosocial Predictors of Urological Chronic Pelvic Pain Symptom Change in 1 Year: A Prospective Study from the MAPP Research Network. J Urol 2017; 198:848-857. [PMID: 28528930 PMCID: PMC5720154 DOI: 10.1016/j.juro.2017.05.065] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2017] [Indexed: 12/30/2022]
Abstract
PURPOSE We examined baseline clinical and psychosocial characteristics that predict 12-month symptom change in men and women with urological chronic pelvic pain syndromes. MATERIALS AND METHODS A total of 221 female and 176 male patients with urological chronic pelvic pain syndromes were recruited from 6 academic medical centers in the United States and evaluated at baseline with a comprehensive battery of symptom, psychosocial and illness-impact measures. Based on biweekly symptom reports, a functional clustering procedure classified participant outcome as worse, stable or improved on pain and urinary symptom severity. Cumulative logistic modeling was used to examine individual predictors associated with symptom change as well as multiple predictor combinations and interactions. RESULTS About 60% of participants had stable symptoms with smaller numbers (13% to 22%) showing clear symptom worsening or improvement. For pain and urinary outcomes the extent of widespread pain, amount of nonurological symptoms and poorer overall health were predictive of worsening outcomes. Anxiety, depression and general mental health were not significant predictors of outcomes but pain catastrophizing and self-reported stress were associated with pain outcome. Prediction models did not differ between men and women and for the most part they were independent of symptom duration and age. CONCLUSIONS These results demonstrate for the first time in a large multisite prospective study that presence of widespread pain, nonurological symptoms and poorer general health are risk factors for poorer pain and urinary outcomes in men and women. The results point to the importance of broad based assessment for urological chronic pelvic pain syndromes and future studies of the mechanisms that underlie these findings.
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Affiliation(s)
- Bruce D Naliboff
- Departments of Medicine and Psychiatry and Biobehavioral Sciences, University of California-Los Angeles, Los Angeles, California.
| | - Alisa J Stephens
- Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - H Henry Lai
- Division of Urologic Surgery, Department of Surgery and Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri
| | - James W Griffith
- Department of Medical Social Sciences, Northwestern University, Evanston, Illinois
| | - J Quentin Clemens
- Department of Urology, University of Michigan School of Medicine, Ann Arbor, Michigan
| | - Susan Lutgendorf
- Department of Psychological and Brain Sciences and Urology, University of Iowa, Iowa City, Iowa
| | - Larissa V Rodriguez
- Departments of Urology and Obstetrics and Gynecology, University of Southern California, Los Angeles, California
| | - Craig Newcomb
- Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Siobhan Sutcliffe
- Division of Public Health Sciences and Alvin J. Siteman Cancer Center, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Wensheng Guo
- Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - John W Kusek
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
| | - J Richard Landis
- Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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Alexithymia and anesthetic bladder capacity in interstitial cystitis/bladder pain syndrome. J Psychosom Res 2017; 100:15-21. [PMID: 28789788 DOI: 10.1016/j.jpsychores.2017.06.019] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 06/28/2017] [Accepted: 06/29/2017] [Indexed: 12/30/2022]
Abstract
OBJECTIVE In contrast to the inconsistent results of organic causes, it has been found that psychological risk factors are reliably related to functional somatic syndromes (FSSs), including interstitial cystitis/bladder pain syndrome (IC/BPS). Compared to patients with acute cystitis, a subgroup of IC/BPS patients with a history of childhood relational trauma reported intensified unregulated affective states (i.e., anxiety and depression) and trauma-related psychopathology (i.e., dissociation). Nevertheless, it remains unknown whether psychosocial risk factors can be separated from bladder-centric factors. This study aimed to verify whether psychosocial factors such as alexithymia, which is a key psychological factor of FSSs, are less likely to be linked to a low bladder capacity in patients with IC/BPS. METHODS Ninety-four female IC/BPS patients were recruited from the outpatient departments of urology, obstetrics, and gynecology. Anxiety, depression, dissociation, childhood relational trauma, and alexithymia were assessed using standardized scales, and anesthetic bladder capacity was examined by cystoscopic hydrodistention. RESULTS Positive correlations were found between anesthetic bladder capacity and the psychosocial variables, including alexithymia. An increased bladder capacity was associated with anxiety, dissociation, and childhood relational trauma, and a combination of high cognitive and low affective alexithymia mediated the correlations between bladder capacity and the psychosocial variables. CONCLUSIONS Psychosocial variables that are associated with an aversive childhood relational environment and affect dysregulation may constitute a pathogenic trajectory that differs from bladder-centric defects such as a lower bladder capacity. The findings of this study support the notion that IC/BPS in some patients may be due to an FSS.
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Chen PJ, Huang CLC, Weng SF, Wu MP, Ho CH, Wang JJ, Tsai WC, Hsu YW. Relapse insomnia increases greater risk of anxiety and depression: evidence from a population-based 4-year cohort study. Sleep Med 2017; 38:122-129. [PMID: 29031746 DOI: 10.1016/j.sleep.2017.07.016] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 06/23/2017] [Accepted: 07/03/2017] [Indexed: 02/06/2023]
Abstract
OBJECTIVE We investigated the longitudinal impacts of insomnia on the subsequent developments of anxiety and depression during a four-year follow-up. We further categorized individuals with insomnia into different insomnia subgroups to examine whether the risk of anxiety and depression varies by subtype. METHODS Participants were identified from National Health Insurance enrollees in Taiwan during 2002-2009. The study included 19,273 subjects with insomnia and 38,546 matched subjects without insomnia. All subjects did not have previous diagnosis of insomnia, sleep apnea, anxiety, or depression. RESULTS Compared with non-insomniacs, insomniacs had a higher risk of developing anxiety only [adjusted hazard ratio (HR) = 8.83, 95% CI = 7.59-10.27], depression only (adjusted HR = 8.48, 95% CI = 6.92-10.39), and both anxiety and depression (adjusted HR = 17.98, 95% CI = 12.65-25.56). When breaking down the insomnia subgroups, individuals with a relapse of insomnia (adjusted HR = 10.42-26.80) had the highest risk of anxiety only, depression only, and both anxiety and depression, followed by persistent insomnia (adjusted HR = 9.82-18.98), then remitted insomnia (adjusted HR = 4.50-8.27). All three insomnia subgroups had a greater four-year cumulative incidence rate than the non-insomnia group for anxiety only, depression only, and both anxiety and depression (p < 0.0001). CONCLUSION Our findings reinforce the clinical predictor role of insomnia in the future onset of anxiety or/and depression. Awareness of insomnia and treatment of insomnia should be recommended at clinics, and patterns of insomnia should be monitored to help treatment and control of subsequent psychiatric disorders. Future research with comprehensive data collection is needed to identify factors that contribute to different insomnia subtypes.
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Affiliation(s)
- Ping-Jen Chen
- Department of Geriatrics and Gerontology, Chi-Mei Medical Center, Tainan, Taiwan; Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Charles Lung-Cheng Huang
- Department of Psychiatry, Chi-Mei Medical Center, Tainan, Taiwan; Department of Social Work, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Shih-Feng Weng
- Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Ping Wu
- Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan, Taiwan; Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; Center of General Education, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Chung-Han Ho
- Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Jhi-Joung Wang
- Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan
| | - Wan-Chi Tsai
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ya-Wen Hsu
- Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan; Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
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Chen IC, Lee MH, Lin HH, Wu SL, Chang KM, Lin HY. Somatoform disorder as a predictor of interstitial cystitis/bladder pain syndrome: Evidence from a nested case-control study and a retrospective cohort study. Medicine (Baltimore) 2017; 96:e6304. [PMID: 28471951 PMCID: PMC5419897 DOI: 10.1097/md.0000000000006304] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) has several well-known comorbid psychiatric manifestations, including insomnia, anxiety, and depression. We hypothesized that somatoform disorder, which is a psychosomatic disease, can be used as a sensitive psychiatric phenotype of IC/BPS. We investigated whether somatoform disorder increases the risk of IC/BPS.A nested case-control study and a retrospective cohort study were followed up over a 12-year period (2002-2013) in the Taiwan Health Insurance Reimbursement Database. In the nested case-control study, 1612 patients with IC/BPS were matched in a 1:2 ratio to 3224 controls based on propensity scores. The odds ratio for somatoform disorder was calculated using conditional logistic regression analysis. In the retrospective cohort study, 1436 patients with somatoform disorder were matched in a 1:2 ratio to 2872 patients with nonsomatoform disorder based on propensity scores. Cox regression analysis was used to estimate the hazard ratio associated with the development of IC/BPS in patients with somatoform disorder, and the cumulative survival probability was tested using the Kaplan-Meier analysis.We found that the odds ratio for somatoform disorder was 2.46 (95% confidence interval [CI], 1.05-5.76). Although the average time until IC/BPS development in the control subjects was 11.5 ± 1.3 years, this interval was shorter in patients with somatoform disorder (6.3 ± 3.6 years). The hazard ratio for developing IC/BPS was 2.50 (95% CI 1.23-5.58); the adjusted hazard ratio was 2.26 (95% CI 1.002-5.007). The patients and controls also differed significantly in their cumulative survival probability for IC/BPS (log rank P < .05).Evidence from the nested case-control study and retrospective cohort study consistently indicated that somatoform disorder increases the risk for IC/BPS. Our study suggests that somatoform disorder can be used as a sensitive psychiatric phenotype to predict IC/BPS. Any past history of somatoform disorder should be documented while examining patients with IC/BPS.
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Affiliation(s)
- I-Chun Chen
- Department of Psychiatry, Taichung Veterans General Hospital
| | - Ming-Huei Lee
- Department of Urology, Feng-Yuan Hospital, Ministry of Health and Welfare, Fengyuan District
| | - Hsuan-Hung Lin
- Central Taiwan University of Science and Technology, Beitun District, Taichung City, Taiwan
| | - Shang-Liang Wu
- Centre for Environment and Population Health, Griffith University
- Nathan Campus, Griffith University, Nathan QLD, Australia
| | | | - Hsiu-Ying Lin
- Department of Anaesthesiology, Feng-Yuan Hospital, Ministry of Health and Welfare, Fengyuan Dist., Taichung City, Taiwan
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Bladder Capacity is a Biomarker for a Bladder Centric versus Systemic Manifestation in Interstitial Cystitis/Bladder Pain Syndrome. J Urol 2017; 198:369-375. [PMID: 28202356 DOI: 10.1016/j.juro.2017.02.022] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/08/2017] [Indexed: 12/30/2022]
Abstract
PURPOSE Interstitial cystitis/bladder pain syndrome presents a significant clinical challenge due to symptom heterogeneity and the myriad associated comorbid medical conditions. We recently reported that diminished bladder capacity may represent a specific interstitial cystitis/bladder pain syndrome subphenotype. The objective of this study was to investigate the relationship between anesthetic bladder capacity, and urological and nonurological clinical findings in a cohort of patients with interstitial cystitis/bladder pain syndrome who had undergone therapeutic urinary bladder hydrodistention. MATERIALS AND METHODS This is a retrospective chart review of prospectively collected data on women diagnosed with interstitial cystitis/bladder pain syndrome between 2011 and 2015 who underwent bladder hydrodistention. Assessments in each patient included a detailed history and physical examination, ICPI (Interstitial Cystitis Problem Index), ICSI (Interstitial Cystitis Symptom Index) and PUF (Pelvic Pain and Urgency/Frequency Patient Symptom Scale). Bladder capacity was determined during bladder hydrodistention with the patient under general anesthesia. RESULTS Mean age was 45.8 years and mean bladder capacity was 857 ml in the 110 enrolled patients. We found a significant inverse correlation between bladder capacity and scores on 3 gold standard interstitial cystitis/bladder pain syndrome metrics, including ICPI (p = 0.0014), ICSI (p = 0.0022) and PUF (p = 0.0009) as well as urination frequency (p = 0.0025). Women with higher bladder capacity were significantly more likely to report depression (p = 0.0059) and irritable bowel syndrome (p = 0.022). CONCLUSIONS Low bladder capacity while under anesthesia was significantly associated with high symptom scores on 3 validated interstitial cystitis/bladder pain syndrome questionnaires as well as with urinary frequency. However, it was not associated with depression or other common systemic pain problems. These results suggest that low bladder capacity is a marker for a bladder centric manifestation of interstitial cystitis/bladder pain syndrome.
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Chiu CD, Lee MH, Chen WC, Ho HL, Wu HC. Childhood trauma perpetrated by close others, psychiatric dysfunction, and urological symptoms in patients with interstitial cystitis/bladder pain syndrome. J Psychosom Res 2017; 93:90-95. [PMID: 28107899 DOI: 10.1016/j.jpsychores.2016.12.014] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Revised: 12/20/2016] [Accepted: 12/23/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND A psychosocial phenotype of interstitial cystitis/bladder pain syndrome (IC/BPS), a urogenital condition without known organic causes, was proposed. While psychosocial variables, including interpersonal maltreatment and negative affect, were studied in association with IC/BPS, the specificities of the relationships between childhood trauma by close others, psychiatric dysfunctions (negative affect and post-traumatic psychopathology), and urogenital symptoms have not been established. METHODS 94 IC/BPS patients were recruited together with 47 patients with acute cystitis who served as clinical controls. Standardized scales were used to assess various potentially traumatizing events in childhood and adulthood as well as psychiatric (dissociation and negative affect) and urogenital symptoms. RESULTS Among the potentially traumatizing events, those perpetrated by close others during childhood were found to be the most salient features discriminating the IC/BPS group from the control group. When divided into 2 subgroups according to their history of childhood trauma by close others, only IC/BPS patients with childhood trauma by close others had more dissociative and anxiety symptoms compared with the control group. These two subgroups did not differ in urogenital symptom severity. CONCLUSIONS Childhood trauma by close others, rather than other types of interpersonal trauma, was a differentiating characteristic in IC/BPS patients, and a childhood trauma related psychosocial phenotype with a distinct clinical profile of dissociation and anxiety proneness was identified. Future studies should investigate whether a distinct set of pathogenic factors exists in IC/BPS patients with a history of childhood trauma by close others, even if this subgroup is not readily differentiated by urogenital symptoms.
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Affiliation(s)
- Chui-De Chiu
- Department of Psychology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
| | - Ming-Huei Lee
- Department of Urology, Feng Yuan Hospital, Taichung, Taiwan
| | - Wei-Chih Chen
- Department of Urology, Feng Yuan Hospital, Taichung, Taiwan.
| | - Hoi Lam Ho
- Department of Psychology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Huei-Ching Wu
- Department of Urology, Feng Yuan Hospital, Taichung, Taiwan
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Chen IC, Lee M, Wu SL, Lin HH, Chang KM, Lin H. Somatic symptoms are sensitive in predicting interstitial cystitis/bladder pain syndrome. Int J Psychiatry Med 2017; 52:48-61. [PMID: 28486876 DOI: 10.1177/0091217417703286] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Objectives Somatic symptoms are somatic complaints accompanied by disproportionate thoughts, feelings, and behaviors related to such symptoms. The study investigated five International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses hallmarked by somatic symptoms. The study hypothesized an increased risk of interstitial cystitis/bladder pain syndrome in patients with somatic symptoms. Methods The raw data were obtained from a nationwide health insurance reimbursement database over a 12-year period from 2002 to 2013. The study followed a somatic symptoms cohort ( n = 34,393) and non-somatic symptoms cohort ( n = 637,999) for interstitial cystitis/bladder pain syndrome. Both cohorts were stratified into three subgroups based on propensity scores calculated by sex, age, and 17 comorbidities of interstitial cystitis/bladder pain syndrome. Results The incidence density of interstitial cystitis/bladder pain syndrome between the somatic symptoms cohort and non-somatic symptoms cohort was significantly different in the three subgroups (relative ratio [95% confidence interval], 2.14 [1.01, 4.53], 1.52 [1.47, 1.57], and 1.59 [1.28, 1.98], respectively). The adjusted hazard ratio for interstitial cystitis/bladder pain syndrome was significantly greater in the female-dominant and older age subgroups-subgroup 2 and subgroup 3 (adjusted hazard ratios, 1.47 [1.07, 2.01] and 1.72 [1.38, 2.16], respectively). Conclusion The longitudinal investigation identified a subsequent risk of interstitial cystitis/bladder pain syndrome in patients with somatic symptoms. Somatic symptoms might be linked to biological pathways that might increase the risk of interstitial cystitis/bladder pain syndrome, much like more traditional psychosocial factors.
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Affiliation(s)
- I-Chun Chen
- 1 Department of Psychiatry, Taichung Veterans General Hospital, Taiwan
| | - MingHuei Lee
- 2 Department of Urology, Feng-Yuan Hospital, Ministry of Health and Welfare, Taiwan.,3 Central Taiwan University of Science and Technology, Taichung, Taiwan
| | - Shang-Liang Wu
- 4 Centre for Environment and Population Health, Griffith University, Queensland, Australia
| | - Hsuan-Hung Lin
- 3 Central Taiwan University of Science and Technology, Taichung, Taiwan
| | - Kun-Min Chang
- 5 Department of Obstetrics and Gynecology, Feng-Yuan Hospital, Ministry of Health and Welfare, Taiwan
| | - HsiuYing Lin
- 6 Department of Anesthesiology, Feng-Yuan Hospital, Ministry of Health and Welfare, Taiwan
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Kanter G, Volpe KA, Dunivan GC, Cichowski SB, Jeppson PC, Rogers RG, Komesu YM. Important role of physicians in addressing psychological aspects of interstitial cystitis/bladder pain syndrome (IC/BPS): a qualitative analysis. Int Urogynecol J 2016; 28:249-256. [PMID: 27581769 DOI: 10.1007/s00192-016-3109-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 07/26/2016] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Interstitial cystitis/bladder pain syndrome (IC/BPS) is a poorly understood source of chronic pain causing significant morbidity, with variable treatment success. Despite the need to understand patient perspectives in chronic pain, there is a paucity of qualitative data for IC/BPS. We aimed to acquire information regarding patient experience with IC/BPS symptoms and with their medical care to elicit suggestions to improve patient satisfaction with that care. METHODS Fifteen women with IC/PBS participated in a total of four focus groups. Sessions were recorded and transcribed and information deidentified. Focus groups were conducted until thematic saturation was reached. All transcripts were coded and analyzed by a minimum of three independent physician reviewers. Investigators identified emergent themes and concepts using grounded-theory methodology. RESULTS Participant's mean age was 52.6 years, with an average IC/BPS duration of 6.3 years. Thematic saturation was reached after four focus groups. We identified three emergent patient experience concepts: IC/PBS is debilitating, the disease course is unpredictable and unrelenting, and patients experience significant isolation. Importantly, suicidal ideation was expressed in each group. Patients voiced strong preference for physicians who provided education regarding the condition, an array of treatment options, organized treatment plans, and optimism and hope regarding treatment outcomes. CONCLUSIONS Our study presents novel findings of the importance of patient-physician interaction in IC/BPS and reinforces the tremendous disability and burden of this disease, which frequently manifests in suicidal ideation. Patients preferred organized treatment plans with diverse choices and providers who offered hope in dealing with their condition.
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Affiliation(s)
- Gregory Kanter
- Department of Obstetrics and Gynecology, MSC 10-5580, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA
| | - Katherine A Volpe
- Department of Obstetrics and Gynecology, MSC 10-5580, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA
| | - Gena C Dunivan
- Department of Obstetrics and Gynecology, MSC 10-5580, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA
| | - Sara B Cichowski
- Department of Obstetrics and Gynecology, MSC 10-5580, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA
| | - Peter C Jeppson
- Department of Obstetrics and Gynecology, MSC 10-5580, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA
| | - Rebecca G Rogers
- Department of Obstetrics and Gynecology, MSC 10-5580, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA
| | - Yuko M Komesu
- Department of Obstetrics and Gynecology, MSC 10-5580, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA.
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Chuang YC, Chermansky C, Kashyap M, Tyagi P. Investigational drugs for bladder pain syndrome (BPS) / interstitial cystitis (IC). Expert Opin Investig Drugs 2016; 25:521-9. [PMID: 26940379 DOI: 10.1517/13543784.2016.1162290] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Bladder pain syndrome (BPS)/interstitial cystitis (IC) is associated with sensory lower urinary tract symptoms. Unfortunately, many of the existing oral treatments are ineffective in most patients of BPS/IC, which is the motivation for developing new drugs and therapeutic approaches. This review covers the latest drugs that have been investigated in BPS/IC patients. Intravesical treatments offer the opportunity to directly target the painful bladder with less systemic side effects. AREAS COVERED In this review, the authors analyze the existing literature supporting the treatment of BPS/IC with conventional drugs including heparin, hyaluronic acid, chondroitin sulfate, and dimethylsulfoxide (DMSO). Furthermore, investigational drugs such as tanezumab and adalimumab, capable of sequestering nerve growth factor (NGF), and Tumor necrosis factor-α (TNF- α) are discussed. Investigational treatments such as liposomes, botulinum toxin (BTX), liposomal BTX, PD-0299685 (a Ca(2+) channel ɑ2δ ligand), continuous intravesical lidocaine, and AQX-1125 (a novel SHIP1 activating compound) are also covered. EXPERT OPINION New investigational drugs offer promising improvements in clinical outcomes for BPS/IC patients; however, BPS/IC is a chronic pain disorder that is very vulnerable to a strong placebo effect. In addition, BPS/IC is a heterogeneous disorder that can be classified into several phenotypes. Since different phenotypes of BPS/IC respond differently to systemic and intravesical treatments, the authors believe that new drugs developed for BPS/IC are more likely to meet their predetermined clinical endpoints if the inclusion/exclusion criterion is tailored to specific phenotype of BPS/IC patients.
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Affiliation(s)
- Yao-Chi Chuang
- a Department of Urology, Kaohsiung Chang Gung Memorial Hospital , Chang Gung University College of Medicine , Kaohsiung , Taiwan.,b Institute of Medicine , Chung Shan Medical University , Taichung , Taiwan
| | - Christopher Chermansky
- c Department of Urology , University of Pittsburgh School of Medicine , Pittsburgh , PA , USA
| | - Mahendra Kashyap
- c Department of Urology , University of Pittsburgh School of Medicine , Pittsburgh , PA , USA
| | - Pradeep Tyagi
- c Department of Urology , University of Pittsburgh School of Medicine , Pittsburgh , PA , USA
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Shah N, Ginzburg N, Morrissey D, Whitmore K. Update in Diagnosis and Treatment of Chronic Pelvic Pain Syndromes. CURRENT BLADDER DYSFUNCTION REPORTS 2015. [DOI: 10.1007/s11884-015-0302-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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