[Conservative treatment of atraumatic femoral head necrosis]. / Konservative Therapie der atraumatischen Hüftkopfnekrose.

BACKGROUND: Femoral head necrosis is a progressive disease that can progress within a relatively short time. Therefore, an early and clear diagnosis including stage classification and treatment is necessary to prevent or delay the onset of the femoral head and joint destruction. TREATMENT: In addition to the identification of possible risk factors and treatment, the question of the available treatment options arises. The present article deals with conservative treatment options and presents the published results in the sense of the currently available evidence and against the background of the S3 guideline on atraumatic femoral head necrosis. The results of physical therapy, drug therapy (iloprost and bisphosphonates ), electrotherapy, shockwave therapy, etc. are presented. In the early stages of femoral head necrosis with low expansion, alendronate gives positive results. Iloprost is also a successful conservative treatment option in the early stages of atraumatic femoral head necrosis (ARCO I and II). In stages ARCO III and IV, Ilomedin is no longer indicated. Anticoagulants, such as enoxaparin, have demonstrated an arthroprotective effect.

Effects of ovarian fluid and genetic differences on sperm performance and fertilization success of alternative reproductive tactics in Chinook salmon.

In many species, sperm velocity affects variation in the outcome of male competitive fertilization success. In fishes, ovarian fluid (OF) released with the eggs can increase male sperm velocity and potentially facilitate cryptic female choice for males of specific phenotypes and/or genotypes. Therefore, to investigate the effect of OF on fertilization success, we measured sperm velocity and conducted in vitro competitive fertilizations with paired Chinook salmon (Oncorhynchus tshawytscha) males representing two alternative reproductive tactics, jacks (small sneaker males) and hooknoses (large guarding males), in the presence of river water alone and OF mixed with river water. To determine the effect of genetic differences on fertilization success, we genotyped fish at neutral (microsatellites) and functional [major histocompatibility complex (MHC) II ß1] markers. We found that when sperm were competed in river water, jacks sired significantly more offspring than hooknoses; however, in OF, there was no difference in paternity between the tactics. Sperm velocity was significantly correlated with paternity success in river water, but not in ovarian fluid. Paternity success in OF, but not in river water alone, was correlated with genetic relatedness between male and female, where males that were less related to the female attained greater paternity. We found no relationship between MHC II ß1 divergence between mates and paternity success in water or OF. Our results indicate that OF can influence the outcome of sperm competition in Chinook salmon, where OF provides both male tactics with fertilization opportunities, which may in part explain what maintains both tactics in nature.

[Compliance of osteoporosis patients with additional specific osteoporosis-training course]. / Compliance der medikamentösen Behandlung der Osteoporosepatienten nach Patientenschulung.

BACKGROUND: In the present study patients with an osteoporotic fracture were examined in order to determine how many patients decided to continue their therapy as outpatients having taken part in osteoporosis training at the Dr. Becker Rhein-Sieg Clinic. PATIENTS AND METHODS: Patients who had previously suffered an osteoporotic fracture and thereafter received inpatient rehabilitation were selected for the study. Patients (n = 95) who had taken part in inpatient rehabilitation after an osteoporotic fracture were approached either via telephone or mail and were then followed up after 6 and 12 months with regard to their adherence to the treatment. RESULTS: From a total of 95 patients, after 6 months 82 % (n = 78) were contacted successfully and included in the study. 68 out of 78 patients (72 %) had continued their medication. After 1 year 76 % of patients (n = 72) were successfully contacted once. Here, 62 % of patients (n = 59) had continued their medication under medical supervision. In the 1­year follow-up period there were eight cases of falls, and one of these resulted in a peripheral fracture, which was treated conservatively. CONCLUSION: Osteoporosis-specific information and osteoporosis training of patients after osteoporotic fracture are important tools to improve the motivation and compliance of patients. One possibility to realize this is osteoporosis-specific training with video presentations and individual care and education of the patients within outpatient or inpatient rehabilitation.

S3-Guideline non-traumatic adult femoral head necrosis.

INTRODUCTION: The treatment of adult non-traumatic avascular necrosis of the femoral head (AVN; N-ANFH) within an estimated incidence of 5000-7000 cases per annum in Germany remains a challenge. Risk factors include steroids, alcohol abuse, chemotherapy and immunosuppressive medication, but a genetic predisposition has been suggested. Early diagnosis of this often bilateral disease process is essential for successful conservative or joint preserving surgical management. In this review, we present the update German consensus S3 guideline "diagnosis and management for N-ANFH" as a concise summary. MATERIALS AND METHODS: This systematic review is based on the published literature from January 1, 1970 to April 31, 2013 (German and English language). Inclusion criteria were systematic reviews, meta-analyses and relevant peer review publications. We identified a total of 3715 related publications, of which 422 were suitable according to the SIGN criteria, but only 159 fulfilled our inclusion criteria. RESULTS AND CONCLUSIONS: Clinical suspicion of N-ANFH mandates radiographic evaluation. If radiographs are normal MRI scans are recommended, which should be evaluated according to the ARCO-classification. Differential diagnoses include transient osteoporosis, bone bruise, insufficiency fracture and destructive arthropathy. Untreated, subchondral fractures commonly occur within 2 years, during which the risk for contralateral involvement is high-thereafter unlikely. Conservative management with Ilomedin and Alendronat can be tried, but other pharmacological or physical treatments are inappropriate. No specific joint preserving procedure can be recommended, but core decompression should be considered in early stages if necrosis is <30 %. In ARCO stages IIIc or IV total hip arthroplasty (THA) should be contemplated, which offers similar outcome compared to osteoarthritis. Young age is the main risk factor for higher revision rates after THA for N-ANFH.

[Use of osteoanabolics in fracture nonunion]. / Anwendung von Osteologika bei gestörter Frakturheilung.

BACKGROUND: The treatment of fracture nonunion (pseudarthrosis) is often lengthy and debilitating for the patient. There are operative and conservative therapies available. RESEARCH QUESTION: Does the systemic use of osteoanabolic acting substances (osteoanabolics) lead to an acceleration of the delayed fracture healing and/or strengthening of the fracture? Which types of pseudarthrosis are suitable for this treatment option? MATERIALS AND METHODS: A literature review was carried out focusing on the systemic anabolic therapy options for the treatment of delayed healing of fractures or pseudarthrosis. Additionally, our own case studies are presented. RESULTS: Teriparatide and strontium ranelate have a positive effect on the healing of fractures in animal studies and in humans. There are also case studies on the use of both substances in delayed fracture healing or pseudarthrosis. The scientific knowledge regarding teriparatide is significantly more comprehensive. However, prospective randomized trials are lacking so far. CONCLUSION: The systemic use of anabolics can be a therapeutic option, especially for biological reactive pseudarthrosis. However, these are off-label treatments and contraindications should be especially well heeded. Because of the numerous positive results, from the point of view of teriparatide treatment, a multicentric, prospective randomized study on the treatment of aseptic pseudarthrosis should be initiated.

[Flexible rehabilitation times after total hip and knee replacement]. / Flexibilisierte Rehabilitationsdauer nach alloplastischem Hüft- und Kniegelenkersatz.

BACKGROUND: In the literature, many studies have focussed on the efficacy of individual rehabilitative treatments and therapies, whereas the duration of the rehabilitation after uncomplicated total alloarthoplastic hip and knee replacement in a previously known Cox and gonarthrosis is rarely mentioned. Therefore, the purpose of the present study was to analyze the duration of inpatient medical follow-up treatment. PATIENTS AND METHODS: In the present prospective study, 127 patients with uncomplicated total hip replacement (THR) and 110 patients with total knee replacement (TKR) implantation caused by advanced Cox or gonarthrosis were postoperatively examined. In this study only patients with the health insurance AOK Rheinland/Hamburg were included. To detect the degree of mobility of the patients, the Staffelstein score was used. It was measured at admission of the patient (T1) and afterwards at the weekly follow-ups (T2-T4), and on the day of discharge (T5). For a better assessment of the necessary individual period of rehabilitation, a target number of points was specified in the Staffelstein score whose achievement was defined as a rehabilitation aim. On the day of admission and in the following weeks of rehabilitation, the degree of mobility was recorded and evaluated in order to adapt the rehabilitation period to the individual situation of each patient. RESULTS: The study showed that the highest rehabilitation progress associated with a significant improvement of mobility degree has been achieved in both THR and TKR patients at the end of the second week of rehabilitation (T2-T3). In the Staffelstein score, 45 % of THR patients and 44 % of TKR patients had reached their rehabilitation aim between T2 and T3. The level of mobility could be significantly improved at the end of rehabilitation (t-test: p < 0.001) in both the THR (n = 127) and TKR patients (n = 110). THR patients required an average of 19.1 ± 4.0 days (range 8-33 days) and the TKR patients on average 19.8 ± 3.4 days (range 12-29 days). Thus, 58 % (n = 74) of THR patients and 51 % (n = 56) of TKR patients had achieved their rehabilitation goal within 21 days. By adapting the rehabilitation period we had achieved the following economic effects: a saving of 28,469 euros could be achieved for THR patients and 15,574 euros for TKR patients. CONCLUSION: Based on the score-driven detection of degree of mobility at the beginning of inpatient rehabilitation, an individual adaptation of the rehabilitation period based on the progress of the patient is possible. Thus, patients who had achieved their rehabilitation goal within the 21 days could be discharged sooner. As a result, in times of limited financial resources, the saved resources can be used for other rehabilitation groups.

Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

Urinary incontinence after radical retropubic prostatectomy is not related to patient body mass index.

To determine if a relationship exists between patient body habitus and urinary incontinence after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. A questionnaire developed by combining parts of lower urinary tract symptom questionnaires concerning voiding symptoms after RRP was mailed to 268 consecutive patients who underwent RRP over a 2-year period. The interval between surgery and questionnaire administration was greater than 24 months for each patient. No interval was greater than 54 months. The questionnaire attempted to overcome the subjectivity of patient documented urinary incontinence by probing different aspects of each patient's voiding symptoms. Body mass index (BMI), obtained from preoperative anesthesia records, was used as the measurement for body habitus. Pearson correlations were used to determine relationships between BMI and responses and the independent t-test was used to determine differences between grouped responses and BMI. One hundred and eighty-two of 268 (68%) questionnaires were returned. No relationship was detected between BMI and patient estimates of urinary control, QOL relating to urinary symptoms, severity of stress incontinence, or use of protection (pad use). As well, no statistically significant relationship was found between BMI and a patient's willingness to undergo RRP again, based on his voiding symptoms, if given the choice. In conclusion, although patient body habitus may be related to other clinical outcomes following RRP, there does not appear to be a relationship of BMI to post-RRP urinary incontinence.

Strain- and host species-specific inflammasome activation, IL-1ß release, and cell death in macrophages infected with uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1ß (IL-1ß) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin α-hemolysin mediated a substantial proportion of CFT073-triggered IL-1ß secretion in mouse but not human macrophages. There was also a more substantial α-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1ß secretion pathway in human macrophages. This has important implications for understanding UTI in humans.

[Score-controlled duration of follow-up treatment after alloplastic hip and knee replacement]. / Scoregesteuerte Dauer der Anschlussheilbehandlung nach alloplastischem Hüft- und Kniegelenkersatz.

BACKGROUND: In the literature many studies can be found addressing the effectiveness of individual measures and therapies within the medical rehabilitation. The duration of the rehabilitation itself is rarely taken into account. Consequently the duration of postoperative inpatient medical rehabilitation after initial implantation of alloarthroplastic hip and knee replacements in osteoarthritis of the hip or knee was the object of our analysis. PATIENTS AND METHODS: In the present prospective study 100 patients each with osteoarthritis of the hip or knee were presented at a follow-up treatment postoperatively after primary implantation of alloarthroplastic hip and knee replacements. Two different scores were used (Staffelstein score, Lequesne score), which were collected at a weekly follow-up (T1-T4) to determine the degree of mobility in the initial examination of the patient and after three weeks. By setting a target score at admission of the patient to the CSO, which stood for achieving the rehabilitation objective, the rehabilitation period could be changed individually. RESULTS: Our study showed that the highest rehabilitation progress has been achieved in both the total hip replacement and total knee replacement in patients at the end of the second week of rehabilitation (T2-T3). Thus, in the Staffelstein score 74 % (n = 74) of hip replacement patients and 46 % (n = 46) of knee replacement patients had already reached their rehabilitation aim between T2 and T3. From the third week on there was a marked flattening of the rehabilitation progress. Also the Lequesne scores obtained confirmed these results. CONCLUSION: Based on the score-driven detection of mobility degree of rehabilitation at the beginning of the follow-up treatment, the individual design of the rehabilitation process with the active participation of the patient is possible. In a large number of cases a reduction of the rehabilitation period can be achieved to less than 21 days. This finding is particularly important in times of limited financial resources, because the saved resources can be used for other rehabilitation groups. Therefore, in a greater number of patients, a shortening of the duration of the rehabilitation is possible.

[S3 Guideline. Part 1: Diagnosis and Differential Diagnosis of Non-Traumatic Adult Femoral Head Necrosis]. / S3-Leitline. Teil 1: Diagnostik und Differenzialdiagnostik der atraumatischen Femurkopfnekrose (aFKN) des Erwachsenen.

Non-traumatic femoral head necrosis (FHN) is primarily a disease of the middle-aged adult. Early diagnosis, at a time with lacking or minimal clinical symptoms, is mandatory to consider conservative therapy or joint preserving operations as a therapeutic option. The new German S3 guideline about diagnosis and therapy of FHN is a cooperative effort of five professional medical societies, overall headed by the Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie (DGOOC). This review (part I/III) cites and explains the statements of the S3 guideline as agreed on the use of imaging methods for diagnosis of FHN. A diagnostic algorithm is presented. FHN clinically has to be considered in case of equivocal pain of a hip joint with a minimum of 6 weeks duration, when risk factors can be revealed, groin pain at clinical investigation, limping, pain or limitation of movement in case of load, and no obvious differential diagnoses. Is an FHN clinically suspected, primarily radiographs of the pelvis ap and a Lauenstein projection of the hip involved should be carried out. When the radiographs are normal, an MRI of the hips should follow routinely. MRI allows the diagnosis of FNH with high accuracy. Furthermore, MRI reveals the site and the size of the necrotic area involved and evaluates the integrity of the joint surface and subchondral fractures. When ARCO stage II (ARCO: Association Research Circulation Osseous) is diagnosed and MRI does not allow one to determine the joint surface with certainty, a CT of the hip joints should be performed. The S3 guideline explains and recommends the use of the ARCO classification. Although, this classification of 1993 is still largely based on radiographs, the pragmatic use of an "extended" version seems reasonable. Today, classical radiographic criteria like impression of the joint surface and subchondral fractures ("crescent sign") are better to be evaluated by MRI, in cases of subtle findings MRI is even surpassed by CT. The extent of the necrosis in the femoral head as well as the size of the surface area involved is best revealed with MRI. Additionally, in the era of cross sectional imaging a stage "0" seems obsolete. The guideline also addresses practically important considerations about the differential diagnosis of misleading MRI findings. This especially holds true for bone marrow oedema in the femoral head which may be misinterpreted. The differentiating features between FHN, transient bone marrow oedema and destructive arthropathy are discussed.

[S3 guideline. Part 2: Non-Traumatic Avascular Femoral Head Necrosis in Adults - Untreated Course and Conservative Treatment]. / S3-Leitlinie. Teil 2: Atraumatische Femurkopfnekrose des Erwachsenen - unbehandelter Verlauf und konservative Behandlung.

BACKGROUND: In Germany there are 5000 to 7000 new cases of atraumatic avascular necrosis of the femoral head in adults per year. It occurs mostly in middle age. An increased frequency of idiopathic cases can be observed. Chemotherapy, corticoids and kidney transplants are frequently associated with the disease. In most cases the disease occurs on both sides. Early diagnosis is of particular importance, since in early stages it is most likely to avoid late damage with joint destruction. Whereas previously the temporary operational joint preservation and subsequent joint replacement were often the only option of treatment, conservative and joint-preserving measures today play an increasing role. MATERIAL AND METHODS: After the AWMF guidelines for S3 guideline clinical questions were formulated. Over the period from 01/01/1970 to 31/05/2013 a literature search was conducted. Systematic reviews, metaanalyses, original papers and clinical trials of all designs were evaluated. There were a total of 3715 references, of which 422 for the assessment regarding SIGN were eligible and finally 180 were in accord with the defined inclusion and exclusion criteria. For the untreated course and the assessment of conservative measures, a total of 42 references was suitable. In formulating the recommendations the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system was used, which distinguishes A "shall", B "should" and 0 "can". RESULTS AND CONCLUSION: If left untreated, the aFKN within 2 years leads to a subchondral fracture and subsequent collapse. After the diagnosis of femoral head necrosis, the risk of a disease of the opposite side is high within the next 2 years, then unlikely. The sole conservative treatment brings no benefit for the treatment of atraumatic avascular necrosis in the adult. Although it improves function, less pain can be obtained, and surgical intervention can be delayed, the progression is not stopped. Conservative treatment must therefore always be part of the overall treatment. In ARCO stage I to II Iloprost may be considered as a pharmacological approach to reduce the pain and the bone marrow oedema. This also applies to alendronate. Since this is an off-label use, and thus a therapeutic trial, an appropriate patient education must take place. For the use of anticoagulants and statins, there is no recommendation. Also the hyperbaric oxygen therapy, shock waves and pulsating electromagnetic fields or electrical stimulation cannot be recommended.

[Immune competence of human tissue lymphocytes in contact with loosened hip joint prostheses. On the topic of cellular or humoral rejection reaction as the mechanism of loosening]. / Immunkompetenz menschlicher Lymphocyten im Kontaktgewebe gelockerter Hüftgelenkendoprothesen. Zur Frage der cellulären oder humoralen Abstossungsreaktionen als Mechanismus der Auslockerung.

In several investigations rejections were accused of being a possible cause for the loosening of hip endoprostheses. Using immunocytochemical techniques we studied the number and type of lymphocytes in the tissue adjacent to loosened hip endoprostheses. Tissue samples were taken from 18 patients being reoperated for a loosened endoprostheses. Impressive lymphocyte infiltrates were found in 4 of 18 patients (22%). These infiltrates only consisted of T-cells. In the other samples only few lymphocytes were detected belonging to T- and B-lymphocyte population, respectively. In our patients T-cell mediated rejections were of minor importance for the loosening of total hip replacement. B-cell accumulations were detected in none of the samples.

[Neopterin as a marker of aspecific immunostimulation with Propionibacterium avidum KP-40 in patients with gastrointestinal tumors. A prospective randomized study]. / Neopterin als Marker einer unspezifischen Immunstimulation mittels Propionibacterium avidum KP-40 bei Patienten mit gastrointestinalen Tumoren. Eine prospektiv randomisierte Studie.

This prospective randomized study demonstrated that a preoperative intravenous infusion of 10 mg of the bacterial preparation Propionibacterium avidum KP-40 to patients with gastrointestinal tumors significantly (P less than 0.001) enhanced the secretion of neopterin, measurable as long-lasting (greater than 16 days) elevated urine excretion. Postoperative re-infusion of P. avidum KP-40 caused (statistically significant (p less than 0.001] re-enhancement of neopterin urine levels.

The diagnosis and treatment of interstitial cystitis.

Interstitial cystitis is a severe bladder disease of unknown etiology with no cure. The diagnosis and treatment of this difficult disease has frustrated both patients and clinicians alike. Multimodality therapy is the most effective treatment for interstitial cystitis.

[Treatment of osteomyelitis and reconstructive measures in patients with war injuries]. / Osteomyelitisbehandlung und rekonstruktive Massnahmen bei kriegsverletzten Patienten.

54 wartime trauma patients injured by bombs, shell splinters or rockets were treated between 1985 and 1989 in the Orthopaedic Clinic of RWTH Aachen. Lesions of the lower limbs were dominating (78%). Treatment was often tedious, and up to 12 operations had to be performed. In 81% one extremity was injured, in 17% two extremities were involved. 78% of the patients were already primarily treated at home, mostly by amputations. 33% of the patients suffered from bone infections at admission. Infections were mostly caused by Staphylococcus aureus or Pseudomonas aeruginosa. In 41% of all patients operative treatment for osteomyelitis was necessary (37% sequesterectomies, 44% stabilisations with fixateur externe). In advanced bone infection amputations were indispensable in 28%. In 27% of our wartime trauma patients reconstructive surgery was performed (spongiosa transplantations in 91%, stabilisation with fixateur externe in 44%). In none of our patients treated with reconstructive surgery an amputation was necessary later on.

[Non-infective inflammations of the vertebral spine]. / Nicht infektiöse Entzündungen der Wirbelsäule.

Non-infective inflammations of the vertebral spine can be caused by seronegative spondylarthropathies or rheumatoid arthritis, respectively. Seronegative spondylarthropathies include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel diseases and undifferentiated arthritis. This review discusses etiology and pathogenesis, epidemiology, clinical features, diagnosis and differential diagnoses of these chronic inflammatory diseases with a special focus on vertebral involvement.

Responsiveness of symptom scales for interstitial cystitis.

OBJECTIVES: To evaluate the responsiveness of composite scales to change over time in a clinical trial of patients with interstitial cystitis (IC). The measurement of symptoms in IC includes the O'Leary-Sant Symptom and Problem Indexes and the University of Wisconsin Interstitial Cystitis Inventory and scales that measure the individual symptom domains of pain/discomfort, urgency, and voiding frequency. METHODS: The data were derived from a randomized clinical trial conducted by the Interstitial Cystitis Clinical Trials Group. Participants met the National Institutes of Health-National Institute for Diabetes, and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency. The primary endpoint was a patient-reported global response assessment (GRA) at 24 weeks. Secondary endpoints included the three composite indexes, pain/discomfort and urgency, and 24-hour frequency. Responsiveness was assessed by comparing symptom score changes against response categories defined by the GRA. RESULTS: Of the 121 subjects in the original trial, 94 with complete data were included. All three composite indexes were sensitive to subject improvement over time as measured by the GRA. A 1.2-point change in the O'Leary-Sant indexes and a 3.1-point change in the Wisconsin IC inventory corresponded to a one-category change in the GRA. Individual symptoms were also responsive. The correlation was high among the changes in the six outcome measures. CONCLUSIONS: The three composite symptom scales are responsive to change over time in patients with IC. These indexes provide important insight into symptom changes and are recommended as secondary endpoints in future clinical trials of IC. Additional endpoints addressing individual symptom domains should also be considered to aid in the evaluation of effect mechanisms.