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.

The long-term outcome of hip replacement in adults with juvenile idiopathic arthritis: the influence of steroids and methotrexate.

Juvenile idiopathic arthritis (JIA) is a chronic disease of childhood; it causes joint damage which may require surgical intervention, often in the young adult. The aim of this study was to describe the long-term outcome and survival of hip replacement in a group of adult patients with JIA and to determine predictors of survival for the prosthesis. In this retrospective comparative study patients were identified from the database of a regional specialist adult JIA clinic. This documented a series of 47 hip replacements performed in 25 adult patients with JIA. Surgery was performed at a mean age of 27 years (11 to 47), with a mean follow-up of 19 years (2 to 36). The mean Western Ontario and McMaster Universities osteoarthritis index questionnaire (WOMAC) score at the last follow-up was 53 (19 to 96) and the mean Health Assessment Questionnaire score was 2.25 (0 to 3). The mean pain component of the WOMAC score (60 (20 to 100)) was significantly higher than the mean functional component score (46 (0 to 97)) (p = 0.02). Kaplan-Meier survival analysis revealed a survival probability of 46.6% (95% confidence interval 37.5 to 55.7) at 19 years, with a trend towards enhanced survival with the use of a cemented acetabular component and a cementless femoral component. This was not, however, statistically significant (acetabular component, p = 0.76, femoral component, p = 0.45). Cox's proportional hazards regression analysis showed an implant survival rate of 54.9% at 19 years at the mean of covariates. Survival of the prosthesis was significantly poorer (p = 0.001) in patients who had been taking long-term corticosteroids and significantly better (p = 0.02) in patients on methotrexate.

Thymic function in juvenile idiopathic arthritis.

OBJECTIVE: Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined. METHODS: Thymic function was measured in 70 children and young adults with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the alphaTREC/SigmabetaTREC ratio. Lastly, regulatory T cells (T(Reg)) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset. RESULTS: Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)(+) polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD. CONCLUSIONS: It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term "JIA" suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.

Delay in access to appropriate care for children presenting with musculoskeletal symptoms and ultimately diagnosed with juvenile idiopathic arthritis.

OBJECTIVE: To document pathways of care, management, and interval from onset of symptoms to first pediatric rheumatology multidisciplinary team (PRhMDT) assessment for children with incident juvenile idiopathic arthritis (JIA). METHODS: We conducted a retrospective observational study of children with incident JIA over a 3-year period. RESULTS: The study included 152 patients with JIA (87 females). The median interval from symptom onset to first PRhMDT assessment was 20 weeks (range 0-416), with significant variation between JIA subtypes (P = 0.0097); children with extended oligoarticular JIA had the longest interval (median 60 weeks, range 12-320). Prior to pediatric rheumatology assessment, many children had referrals to multiple secondary care specialties and had been subjected to multiple and often invasive procedures including arthroscopy/synovial biopsy (18 [11.8%] of 152), but none were referred for ophthalmologic screening, physical therapy, or nursing input and a diagnosis of JIA was rarely made (98%). At first PRhMDT assessment, most patients had untreated active disease with active joint count >or=1 (135 [89%] of 152), restricted joint count >or=1 (135 [89%] of 152), and functional disability by Child Health Assessment Questionnaire score >0 (53 [68%] of 118); 1 child had undetected uveitis. Following PRhMDT assessment, interventions were invariably indicated, including joint injections (69 [45%] of 152), methotrexate (49 [32%] of 152), and physical therapy programs (all patients). CONCLUSION: Delay in access to pediatric rheumatology assessment is common with complex pathways of referral. Many children were subjected to inappropriate invasive investigations and many had prolonged untreated active disease at the initial PRhMDT assessment. This delay is likely to affect long-term outcome and warrants further exploration.

Musculoskeletal screening examination (pGALS) for school-age children based on the adult GALS screen.

OBJECTIVE: To develop and validate a musculoskeletal screening examination applicable to school-age children based on the adult Gait, Arms, Legs, Spine (GALS) screen. METHODS: Adult GALS was tested in consecutive school-age children attending pediatric rheumatology clinics and was compared with an examination conducted, on the same day, by a pediatric rheumatologist who classified children as having abnormal or normal joints. Adult GALS was tested for validity compared with the pediatric rheumatologist's assessment and deficiencies in adult GALS were identified. Experts proposed amendments to adult GALS, achieving consensus by modified Delphi techniques. The resultant pediatric screening tool (pGALS) was tested (methodology identical to the testing of adult GALS) in an additional group of children. RESULTS: Adult GALS was tested in 50 children (median age 11 years, range 4-16), of whom 37 (74%) had juvenile idiopathic arthritis. Adult GALS missed important abnormalities in 18% of children, mostly at the ankle, foot, and temporomandibular joints. The pGALS was tested in 65 children (median age 13 years, range 5-17 years) and demonstrated excellent sensitivity (97-100%) and specificity (98-100%) at all joints, with high acceptability scored by child and parent/guardian. The median time to perform pGALS was 2 minutes (range 1.5-3 minutes). CONCLUSION: The pGALS musculoskeletal screening tool has excellent validity, is quick to perform, and is acceptable to school-age children and parents/guardians. We propose that pGALS be incorporated into undergraduate and postgraduate medical training to improve pediatric musculoskeletal clinical skills and facilitate diagnosis and referral to specialists.

Interleukin-6 signalling in juvenile idiopathic arthritis is limited by proteolytically cleaved soluble interleukin-6 receptor.

OBJECTIVES: Interleukin-6 (IL-6) exerts multiple effects on chondrocytes and fibroblasts within the joint and is associated with disease activity in juvenile idiopathic arthritis (JIA). Although these cells express the ubiquitous signalling receptor for all IL-6-related cytokines, gp130, they do not express a cognate IL-6 receptor. Consequently, IL-6 responses within these cells occur via IL-6 trans-signalling relying on the presence of a soluble receptor (sIL-6R). Levels of sIL-6R in vivo are governed by either proteolytic cleavage (PC) of cognate receptor or by differential sIL-6R mRNA splicing (DS). The aim of this study was to evaluate the contribution of both isoforms to clinical parameters associated with IL-6 signalling in JIA. METHODS: IL-6, sIL-6R and DS-sIL-6R were measured by ELISA in serum and synovial fluid (SF) samples from 86 JIA patients. These data were related to indicators of inflammation-erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and compared between patients stratified by subtype, age and disease duration. RESULTS: SF IL-6 significantly correlated with general indicators of activity (ESR and CRP) and SF PC-sIL-6R to a lesser degree with CRP. When the IL-6:sIL-6R ratio was calculated as an indicator of the potential for IL-6 signalling within the joint, 33% of SF samples showed a ratio >1 indicating saturation of sIL-6R by IL-6. Mean DS-sIL-6R levels were 0.71 ng/ml, whereas PC-sIL-6R levels constituted the majority of sIL-6R at 20.89 ng/ml. CONCLUSIONS: IL-6 trans-signalling within the joints of JIA patients is predominantly governed by the presence of PC-sIL-6R, and the data provided suggest that synovial levels of IL-6 and sIL-6R would be sufficient to drive IL-6 responses in chondrocytes and synovial fibroblasts.

Assessment of the clinical significance of gelatinase activity in patients with juvenile idiopathic arthritis using quantitative protein substrate zymography.

OBJECTIVE: To measure gelatinase activities in paired synovial fluid (SF) and serum of patients with juvenile idiopathic arthritis (JIA), and to assess how these activities relate to clinical and laboratory measures of disease activity. METHODS: A quantitative protein substrate zymography method was adapted and validated for use with serum and SF. Bands of activity were measured by densitometry and correlated with standard laboratory indicators of inflammation: erythrocyte sedimentation rate and platelet count. RESULTS: Gelatinase activity was found consistently in patients with JIA, with reproducible, quantified bands of activity corresponding to pro-matrix metalloproteinase-9 (pro-MMP-9), including the neutrophil associated lipocalin complex, and pro- and active forms of MMP-2. Both active MMP-2 and pro-MMP-9 were higher in JIA serum than in controls, though no differences were seen between patients grouped according to age, disease duration, or JIA subtype. However, SF MMP-9 correlated significantly with the laboratory indicators of inflammation, as did the relative level of active MMP-2. CONCLUSIONS: Both MMP-2 and MMP-9 gelatinolytic activities are raised during active JIA and associated with inflammatory activity regardless of age and disease duration, supporting a role for MMPs in the breakdown of joint components from early in disease. These MMPs may be specific markers of active joint destruction linked to inflammatory JIA, MMP-9 as a product of infiltrating cells, and the activation of MMP-2 produced within the joint.

Levels of matrix metalloproteinase (MMP)-1 in paired sera and synovial fluids of juvenile idiopathic arthritis patients: relationship to inflammatory activity, MMP-3 and tissue inhibitor of metalloproteinases-1 in a longitudinal study.

OBJECTIVES: To measure levels of the collagenases matrix metalloproteinase (MMP)-1 and -13 in the synovial fluid (SF) and serum of patients with juvenile idiopathic arthritis (JIA), and to correlate these measurements with inflammatory activity, levels of the collagenase activator MMP-3 and the tissue inhibitor of metalloproteinases-1 (TIMP-1). METHODS: Levels of MMP-1, -3, -13 and TIMP-1 were measured in paired SF and serum from 82 JIA patients using enzyme-linked immunsorbent assay and compared between subtypes and patients of different ages and disease durations. These levels were also correlated to the active joint count (AJC) and standard measures of inflammatory activity and therapeutic response, including erythrocyte sedimentation rate (ESR) and platelet count (PLT). RESULTS: MMP-1 was detected in JIA SF and correlated with PLT. MMP-3 levels were high in SF and detectable in serum where they correlated with PLT, ESR and AJC. MMP-13, however, was not detected in SF or serum. No differences were observed between patients grouped by subtype, age or disease duration. MMP-3 contributed the majority of total MMP in SF samples resulting in excess MMP levels over TIMP-1. CONCLUSIONS: MMP-1 is up-regulated in SF concordant with inflammatory activity in JIA. This was true for patients in all JIA subtypes and age groups, suggesting that the capability for degradation of type II collagen is present in early disease, and throughout the disease course. MMP-3 may be important in the activation of collagenases and the saturation of exogenous inhibitors. Serum MMP-3 may therefore be a useful, measurable and specific marker of active disease in JIA.

The dental attitudes, knowledge and health practices of patients with Juvenile Idiopathic Arthritis.

AIM: To investigate the dental attitudes, knowledge and dental health practices of children and adults with a previous diagnosis of Juvenile Idiopathic Arthritis (JIA). STUDY DESIGN: A self-completion questionnaire. METHODS: Ninety-one children and 82 adults with JIA were age and gender matched with 152 healthy controls. For those below the age of 16 years, the parents' attitude, knowledge and dental health practices were investigated by the questionnaire. The adult subjects and controls completed an identical questionnaire assessing their own attitude, knowledge and dental health practices. RESULTS: Response rates of 84% and 75% were achieved for the subject and controls respectively. Both groups responded similarly to questions assessing perception of different medical conditions. The majority of respondents thought leukaemia was a very serious condition. Twenty-seven percent of subjects and 34% of controls felt dental decay was "slightly or not serious". Ninety percent of subjects and 93% of controls knew having sweet snacks during the day would harm teeth, but fewer were sure that eating sweet foods at mealtimes only would help reduce decay. The majority of respondents (63% and 56% respectively) did not know whether children should receive fluoride tablets but the majority of subjects in both groups had attended a dentist within the last year. STATISTICS: Descriptive analyses and chi-squared analysis were undertaken. A p-value of < or =0.01 was taken as strong evidence of a difference between groups. CONCLUSION: The perception of health and illness by both groups was appropriate. The questions investigating dental knowledge revealed understanding of the basic messages of prevention of dental disease, but finer detail appeared less well understood. Responses concerning dental health confirmed positive attitudes towards good dental health habits. The benefits of brushing with fluoride toothpaste were known, and the majority toothbrushed daily and received dental care within the previous year.

Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity.

OBJECTIVE: To evaluate the safety and efficacy of autologous stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA). DESIGN: Retrospective analysis of follow up data on 34 children with JIA who were treated with ASCT in nine different European transplant centres. Rheumatological evaluation employed a modified set of core criteria. Immunological reconstitution and infectious complications were monitored at three month intervals after transplantation. RESULTS: Clinical follow up ranged from 12 to 60 months. Eighteen of the 34 patients (53%) with a follow up of 12 to 60 months achieved complete drug-free remission. Seven of these patients had previously failed treatment with anti-TNF. Six of the 34 patients (18%) showed a partial response (ranging from 30% to 70% improvement) and seven (21%) were resistant to ASCT. Infectious complications were common. There were three cases of transplant related mortality (9%) and two of disease related mortality (6%). CONCLUSIONS: ASCT in severely ill patients with JIA induces a drug-free remission of the disease and a profound increase in general wellbeing in a substantial proportion of patients, but the procedure carries a significant mortality risk. The following adjustments are proposed for future protocols: (1) elimination of total body irradiation from the conditioning regimen; (2) prophylactic administration of antiviral drugs and intravenous immunoglobulins until there is a normal CD4+ T cell count.

More 'cries from the joints': assessment of the musculoskeletal system is poorly documented in routine paediatric clerking.

OBJECTIVES: The aim of this study was to describe the assessment of the musculoskeletal (MSK) system in comparison with other systems in routine paediatric medical clerking. Furthermore, to survey trainee paediatricians (SPRs, specialist registrars) about their self-rated confidence in assessing the MSK system. METHODS: Case notes of consecutive general paediatric medical patients admitted to three UK hospitals over a 4-week period were assessed using a standard pro forma. All patients had been assessed by a consultant paediatrician during their admission. A postal questionnaire was sent to all SPRs in training in each of the hospitals, regarding their confidence in assessing the MSK system compared with other systems and their exposure to MSK teaching. RESULTS: Case notes of 257 patients [117 females, median age 3 yr (range 1-18 yr)] were reviewed. The most common reason for admission was acute infection, although the spectrum of other recorded diagnoses varied between hospitals. Thirteen children (5%) had an acute problem (e.g. infection) against a background of chronic disease. The case note documentation showed that cardiovascular (CVS), respiratory (RS) and gastrointestinal (GI) systems were assessed in the vast majority (>90%) of patients, irrespective of the underlying diagnosis. However, other systems were less well recorded; the trend being the same in each hospital and in descending order, the neurological system (38%), skin (32%), eyes (10%) and musculoskeletal system (4%). Only 2.7% (7/257) patients were documented to have been asked about MSK symptoms, and only 1.6% (4/257) had any documentation of joint examination--in all cases this was limited (e.g. range of movement of the knee only), and no patients had documentation of gait being examined, even in those children presenting with 'limp'. The response rate to the postal questionnaire was 60% (67/112). The self-rated confidence in MSK assessment was markedly low in comparison with other systems, even though 61/67 recalled some teaching of the MSK system as an undergraduate (61/67) or postgraduate (50/67). Of note none could recall teaching as an undergraduate in paediatric MSK assessment and where there had been postgraduate rheumatology MSK teaching this had been delivered by paediatric rheumatologists in many cases (34/50), reflecting the centres participating in the study. CONCLUSIONS: In routine general paediatric medical in-patient clerking and throughout the admission, MSK assessment was rarely documented, and even where present was limited. This contrasts markedly with other systems which were examined in most children irrespective of the presenting complaint. Self-rated confidence in MSK assessment is low amongst SPRs compared with other systems, despite most recalling some teaching. This discrepancy between teaching and clinical practice needs to be addressed in undergraduate and postgraduate training.

Increased prevalence of dental caries and poor oral hygiene in juvenile idiopathic arthritis.

OBJECTIVES: Recent decades have seen a trend to treat juvenile idiopathic arthritis (JIA) with increasing immunosuppression to improve the long-term outcome. Poor oral hygiene and dental decay cause significant morbidity, and patients with chronic disease (who may be further immunocompromised by treatment) are at greater risk. This study investigated patients with JIA using standard measures of oral health. METHODS: One hundred and forty-nine patients with JIA were included. The children were attending a regional paediatric rheumatology service and the adults were attending an adult rheumatology clinic. Random age- and sex-matched healthy controls were recruited from a dental teaching hospital. The structured dental examination included standard epidemiological indices of oral hygiene (gingival index, plaque index, oral cleanliness index) and dental decay [DMFT (decayed, missing or filled teeth) index]. RESULTS: JIA patients, at all ages, had increased levels of dental decay and poor oral hygiene. This increased level of decay was statistically significant in the patients aged 0-11 yr. Significant levels of untreated caries and increased levels of missing teeth were found in JIA, suggesting that patients with JIA had less restorative dental treatment, with tooth extraction often the chosen option for the treatment of dental decay. CONCLUSIONS: This is the largest study of oral health in JIA and is cross-sectional with non-diseased controls. It shows significantly increased levels of poor oral hygiene and dental decay in patients with JIA. The high levels of untreated dental decay suggest barriers to dental care. These results emphasize the role of regular dental care in the multidisciplinary management of JIA.

Sialochemistry in juvenile idiopathic arthritis.

OBJECTIVES: To investigate whether there are any differences in salivary flow rates and saliva composition that may contribute to the reported increase in caries prevalence in patients with juvenile idiopathic arthritis (JIA). DESIGN: Randomized controlled trial. SETTING: The sialochemistry of children with JIA has rarely been investigated. METHODS: Unstimulated and stimulated whole saliva was collected from 17 randomly selected JIA patients and 17 age and sex matched controls. Both samples were analysed for salivary flow rate, pH, calcium and phosphate. RESULTS: Unstimulated and stimulated JIA saliva flow rates, and the flow rate change from unstimulated to stimulated in JIA saliva were all significantly lower than the controls. There were no significant differences in the pH of unstimulated and stimulated JIA saliva compared with the controls, however, the change in pH (from unstimulated to stimulated) in the study group was significantly greater. The JIA patients had non-significantly lower levels of both calcium and phosphate ions in the unstimulated and stimulated samples. CONCLUSIONS: This data would suggest that there is both a reduced resting salivary flow and a reduced response to stimulation in JIA patients, which may contribute to a previously reported higher caries prevalence.

Type and extent of enamel defects in juvenile idiopathic arthritis (JIA).

AIM: To establish whether there is an increased prevalence and extent of enamel defects associated with Juvenile Idiopathic Arthritis (JIA) in patients in the North of England. STUDY DESIGN: clinical examination of subjects and age and sex matched controls. METHODS: The labial surfaces of all erupted permanent teeth in subjects, as well as age and sex matched controls, were examined. They were classified for type and extent of defects according to the Modified DDE index. The records of 146 subjects and 142 controls were available for analysis. STATISTICS: defects were expressed as the percentage of subjects or controls with or without any defects or specific types of defect. Fisher's exact test was used to compare the prevalence of disease in the two groups with significance being accepted at the 5% level. In addition, 95% confidence intervals for the relative risk of disease in the two groups were derived. RESULTS: There was no significant difference between subjects and controls for the presence of any type of defect (p=0.48), demarcated opacities (p=0.39), diffuse opacities (p=0.71), or hypoplasias (p=0.19). There was no significant increase in severity of defects in subjects compared with controls. There was also no significant difference when comparing the group diagnosed before the age of 4 (0-3) and the group diagnosed after the age of 4 (>4) years. CONCLUSION: There was no greater overall prevalence of enamel defects or specific type of defects and no greater extent of them in subjects with JIA compared with age and sex matched controls.