Transurethral prostatic resection or laser therapy for men with acute urinary retention: the ClasP randomized trial.

PURPOSE: Transurethral resection of the prostate is the standard operation for acute urinary retention, although laser prostatectomy is reportedly effective and safe. The ClasP (conservative management, laser, transurethral resection of the prostate) study compared transurethral prostatic resection and noncontact neodymium (Nd):YAG visual laser assisted prostatectomy for treatment of acute urinary retention. MATERIALS AND METHODS: This study was a multicenter randomized controlled trial, analyses were by intention to treat and followup was at 7.5 months after randomization. Primary outcomes were treatment failure, and included International Prostate Symptom Score, International Prostate Symptom Score quality of life score, residual urine and flow rate. Secondary outcomes included complications, and duration of catheterization and hospitalization. RESULTS: A total of 148 men were randomized to transurethral prostatic resection (74) and laser (74). There were fewer treatment failures after prostatic resection (p = 0.008) and fewer men after resection required secondary surgery for poor results (1 versus 7, p = 0.029). Maximum flow rates after transurethral prostatic resection were better than after laser (mean difference 4.4 ml. per second). Comparison of symptom and quality of life scores demonstrated that any clinically significant advantage for laser could be ruled out. Patients stayed a mean of 2 extra days in the hospital after resection. The duration of catheterization was greater after laser but significantly fewer major treatment complications were found with laser therapy. CONCLUSIONS: Transurethral prostatic resection was more effective, resulted in fewer failures than laser treatment and remains the procedure of choice for men with acute urinary retention.

A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: The CLasP study.

PURPOSE: We evaluated the effectiveness of a new technology (noncontact laser therapy) versus that of standard surgery (transurethral prostatic resection) and conservative management for lower urinary tract symptoms associated with benign prostatic enlargement. MATERIALS AND METHODS: Men with uncomplicated lower urinary tract symptoms, that is no acute or chronic urinary retention, were randomized to receive laser therapy with a noncontact, side firing neodymium:YAG probe, standard transurethral prostatic resection or conservative management, including monitoring without active intervention, in a large multicenter pragmatic randomized controlled trial called the CLasP study. Primary outcomes were International Prostate Symptom Score (I-PSS), maximum urinary flow rate, a composite measure of success based on I-PSS and maximum urinary flow rate categories, I-PSS quality of life score and post-void residual urine volume. Secondary outcomes included treatment failure, hospital stay and major complications. Followup was 7.5 months after randomization. Intent to treat analysis was done using analysis of covariance, proportional odds models and the Newman-Keuls multiple comparisons procedure. RESULTS: Of symptomatic patients 117, 117 and 106 were randomized to receive laser therapy, transurethral prostatic resection and conservative management, respectively. Baseline characteristics were similar. All primary outcomes indicated that transurethral prostatic resection and laser therapy were superior to conservative management, and resection was superior to laser therapy. As measured by combined improved symptoms and maximum urinary flow, a successful outcome was achieved in 81%, 67% and 15% of men who underwent transurethral prostatic resection, laser therapy and conservative management, respectively. Hospital stay was significantly shorter and complications fewer for laser therapy than for resection but catheters were in place significantly longer. Men treated conservatively did not have deterioration or treatment failure. CONCLUSIONS: Laser therapy and transurethral prostatic resection are effective for decreasing lower urinary tract symptoms and post-void residual urine volume as well as improving quality of life and maximum urinary flow in the short term in men presenting with moderate to severe symptoms. Transurethral prostatic resection is superior to laser therapy in terms of effectiveness but some patients may elect laser therapy due to the shorter hospital stay and lower risk of complications. Conservative management may be acceptable and safe in men with lower urinary tract symptoms since we observed no marked deterioration in the short term.

The role of germline polymorphisms in the T-cell receptor in susceptibility to ankylosing spondylitis.

The role of germline polymorphisms of the T-cell receptor A/D and B loci in susceptibility to ankylosing spondylitis was investigated by linkage studies using microsatellite markers in 215 affected sibling pairs. The presence of a significant susceptibility gene (lambda > or = 1.6) at the TCRA/D locus was excluded (LOD score < -2.0). At the TCRB locus, there was weak evidence of the presence of a susceptibility gene (P = 0.01, LOD score 1.1). Further family studies will be required to determine whether this is a true or false-positive finding. It is unlikely that either the TCRA/D or TCRB loci contain genes responsible for more than a moderate proportion of the non-MHC genetic susceptibility to ankylosing spondylitis.

A genome-wide screen for susceptibility loci in ankylosing spondylitis.

OBJECTIVE: To localize the regions containing genes that determine susceptibility to ankylosing spondylitis (AS). METHODS: One hundred five white British families with 121 affected sibling pairs with AS were recruited, largely from the Royal National Hospital for Rheumatic Diseases AS database. A genome-wide linkage screen was undertaken using 254 highly polymorphic microsatellite markers from the Medical Research Council (UK) (MRC) set. The major histocompatibility complex (MHC) region was studied more intensively using 5 microsatellites lying within the HLA class III region and HLA-DRB1 typing. The Analyze package was used for 2-point analysis, and GeneHunter for multipoint analysis. RESULTS: When only the MRC set was considered, 11 markers in 7 regions achieved a P value of < or =0.01. The maximum logarithm of odds score obtained was 3.8 (P = 1.4 x 10(-5)) using marker D6S273, which lies in the HLA class III region. A further marker used in mapping of the MHC class III region achieved a LOD score of 8.1 (P = 1 x 10(-9)). Nine of 118 affected sibling pairs (7.6%) did not share parental haplotypes identical by descent across the MHC, suggesting that only 31% of the susceptibility to AS is coded by genes linked to the MHC. The maximum non-MHC LOD score obtained was 2.6 (P = 0.0003) for marker D16S422. CONCLUSION: The results of this study confirm the strong linkage of the MHC with AS, and provide suggestive evidence regarding the presence and location of non-MHC genes influencing susceptibility to the disease.

The effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis.

OBJECTIVE: To analyze the effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis (AS). METHODS: Three hundred sixty-three white British AS patients were studied; 149 were carefully assessed for a range of clinical manifestations, and disease severity was assessed using a structured questionnaire. Limited HLA class I typing and complete HLA-DR typing were performed using DNA-based methods. HLA data from 13,634 healthy white British bone marrow donors were used for comparison. RESULTS: A significant association between DR1 and AS was found, independent of HLA-B27 (overall odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8, P = 0.02; relative risk [RR] 2.7, 95% CI 1.5-4.8, P = 6 x 10(-4) among homozygotes; RR 2.1, 95% CI 1.5-2.8, P = 5 x 10(-6) among heterozygotes). A large but weakly significant association between DR8 and AS was noted, particularly among DR8 homozygotes (RR 6.8, 95% CI 1.6-29.2, P = 0.01 among homozygotes; RR 1.6, 95% CI 1.0-2.7, P = 0.07 among heterozygotes). A negative association with DR12 (OR 0.22, 95% CI 0.09-0.5, P = 0.001) was noted. HLA-DR7 was associated with younger age at onset of disease (mean age at onset 18 years for DR7-positive patients and 23 years for DR7-negative patients; Z score 3.21, P = 0.001). No other HLA class I or class II associations with disease severity or with different clinical manifestations of AS were found. CONCLUSION: The results of this study suggest that HLA-DR genes may have a weak effect on susceptibility to AS independent of HLA-B27, but do not support suggestions that they affect disease severity or different clinical manifestations.

Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment.

OBJECTIVE: To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS). METHODS: Twins with AS were identified from the Royal National Hospital for Rheumatic Diseases database. Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed using a combination of validated scoring systems. HLA typing for HLA-B27, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction with sequence-specific primers, and zygosity was assessed using microsatellite markers. Genetic and environmental variance components were assessed with the program Mx, using data from this and previous studies of twins with AS. RESULTS: Six of 8 monozygotic (MZ) twin pairs were disease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twin pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignificant increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concordant MZ twins compared with concordant DZ twins. HLA-B27 and B60 were associated with the disease in probands, and the rate of disease concordance was significantly increased among DZ twin pairs in which the co-twin was positive for both B27 and DR1. Additive genetic effects were estimated to contribute 97% of the population variance. CONCLUSION: Susceptibility to AS is largely genetically determined, and the environmental trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.

Socioeconomic status in ankylosing spondylitis: relationship between occupation and disease activity.

OBJECTIVE: To identify the socioeconomic status through occupation of a large cohort of patients with ankylosing spondylitis (AS) and to determine possible relationships between occupation and clinical variables. METHODS: We analyzed the employment status of 1,044 patients with AS. RESULTS: 85% of patients (890 of 1,044) were in full employment at the time of the assessment compared to 15% who were unemployed. When 50 employed patients were compared to 50 unemployed cases, the latter had increased disease activity and lower psychosocial well being. CONCLUSION: Employed patients from the higher occupational group (I), had less disease activity, and lower pain and depression than patients from the lowest occupational group (IV).

Juvenile onset ankylosing spondylitis--more girls than we thought?

OBJECTIVE: To define the sex ratio of juvenile onset ankylosing spondylitis (AS) among a large population. METHODS: Using a standard questionnaire, data were collected from 3362 subjects, members of the National Ankylosing Spondylitis Society and patients at a tertiary referral center. RESULTS: Of 3362 patients, 2461 (73%) were male; male:female sex ratio was 2.7:1. Of the total, 379 (11%) had disease onset between the ages of 5 and 16 years. Of these, 278 were boys and 101 girls, giving an overall male:female ratio, in juvenile AS, of 2.6:1. For those with onset ages 5-13 years there was a ratio of 2.1:1, while for those aged over 14 years at onset, the ratio was 3.2:1. CONCLUSION: Older published ratios, ranging from 4.5:1 to 6:1, used smaller samples, focusing only on subjects who were juveniles at the time of the study. Our data collection method, which recruits from 2 sources and includes adults with juvenile onset, attempts to avoid these methodological problems. The data suggest a higher incidence of juvenile AS among females than previously described.

Which patients with ankylosing spondylitis derive most benefit from an inpatient management program?

OBJECTIVE: To evaluate the benefit achieved from an inpatient management program by testing the hypothesis that more mobile, younger patients on their first course show the most improvement. METHODS: We assessed 236 patients over an 18 month period. Patients were assessed at the beginning and end of the course by 4 indices, 3 of which were self-administered (disease activity, functional ability, and global well being) and one administered by a trained physiotherapist (metrology). Paired t tests and ordinary least squares regression analysis were used to compare pre and postcourse results for each index. RESULTS: The wide range of disease duration (0-53 years) and disease severity [0.69-9.39 (on a 0-10 scale)] reveal that patients are from a wide spectrum of disease. Results revealed a mean improvement of 18-27% over baseline in the 4 indices. Significant predictors of greater improvement over the 2 week course were found for each index. CONCLUSION: Our results confirm the benefit of an intensive regime of inpatient physiotherapy. Although the original hypothesis cannot be accepted or rejected as the results were different for the 4 indices, the following general conclusions may be drawn: (1) there is a trend for females to improve more than males; (2) patients who have attended fewer courses tend to achieve more improvement; (3) younger patients do better than older patients; and (4) age of disease onset has little effect.

HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.

OBJECTIVE: To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. METHODS: HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. RESULTS: The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p < 10(-99)). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10(-5)), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p < 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HLA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. CONCLUSION: HLA-B27 and -B60 are associated with susceptibility to AS, but differences in HLA-B27 subtype do not affect susceptibility to AS in this white population.

Ankylosing spondylitis: the correlation between a new metrology score and radiology.

The objective was to compare the Bath Ankylosing Spondylitis Metrology Index (BASMI) with radiology as a measure of disease outcome. Fifty-three patients, covering the entire spectrum of disease severity, were blindly and independently assessed using the BASMI (total of five standardized measurements, scoring range 0-10) and a radiology score of the four main spinal areas affected by ankylosing spondylitis (AS). BASMI correlates positively with the total radiology score (r = 0.74), while the individual BASMI scores for cervical rotation (r = 0.59), wall to tragus (r = 0.61), lumbar side flexion (r = 0.56), lumbar flexion (r = 0.68) and intermalleolar distance (r = 0.50) correlate positively with their respective radiology scores. BASMI and radiology do not relate well to each other as BASMI takes account of normal physical limitation and soft tissue involvement. In addition, although radiology scores are termed a 'gold standard', they are unreliable. Therefore, BASMI may be judged to be more important in assessing AS and become a 'gold standard' itself.

A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index.

OBJECTIVE: Disease status, in terms of disease activity, disease progression and prognosis is difficult to define in ankylosing spondylitis (AS). No gold standard exists. Therefore, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a self-administered instrument, has been developed as a new approach to defining disease activity in patients with AS. METHODS: The index, designed by a multidisciplinary team with input from patients, consists of six 10 cm horizontal visual analog scales to measure severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness (both qualitative and quantitative). The final BASDAI score has a range of 0 to 10. The index was distributed to a cross section of patients, including inpatients receiving 3 weeks of intensive physiotherapy treatment and hospital outpatients. BASDAI was completed by a total of 154 patients. Validation of the new instrument was achieved through analysis of user friendliness, reliability (consistency), score distribution and sensitivity to change. Comparisons were made with a previous Bath disease activity index (DAI) and the Newcastle Enthesis Index. RESULTS: The BASDAI was found by patients to be quick and simple to complete (mean: 67 s). Test-retest reliability was good (r = 0.93; p < 0.001), as was the distribution of scores across the scale (score range: 0.5-10; mean: 4.31). BASDAI was sensitive to change, reflecting a 16% (mean) improvement in inpatient scores after 3 weeks of treatment. It is superior to the DAI in terms of construct and content validity and to the Enthesis Index in all aspects. CONCLUSION: In summary, BASDAI is user friendly, reliability, sensitive to change and reflects the entire spectrum of disease. It is a comprehensive self-administered instrument for assessing disease activity in AS.

A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index.

OBJECTIVE: After pain and stiffness, one of the most important complaints of patients with ankylosing spondylitis (AS) is disability. The main aims of treatment are to control pain but also to improve function. Various methods of assessing function exist but are either not specific for the disease or have not been adequately validated. As a result of this deficiency we developed the Bath Ankylosing Spondylitis Functional Index (BASFI) as a new approach to defining and monitoring functional ability in patients with AS. METHODS: This self-assessment instrument was designed by a team of medical professionals in conjunction with patients, and consists of 8 specific questions regarding function in AS and 2 questions reflecting the patient's ability to cope with everyday life. Each question is answered on a 10 cm horizontal visual analog scale, the mean of which gives the BASFI score (0-10). The questionnaire was completed 257 times in total: once by 116 outpatients and by 47 inpatients on 3 occasions over a 3-week intensive physiotherapy course. In addition, the instrument was compared with the Dougados functional index. RESULTS: Patients scores covered 95% of the BASFI range, giving a normal distribution of results. In contrast only 65% of the Dougados functional index scale was used. Furthermore, over the 3 week period of inpatient treatment, the BASFI revealed a significant improvement in function (20%, p = 0.004) while there was a less impressive change in the Dougados functional index (6%, p = 0.03). This demonstrates the superior sensitivity of the BASFI: Consistency was good for both indices (p < 0.001), as was the relationship between patient perception of function and function as assessed by an external observer (p < 0.001). CONCLUSION: The BASFI satisfies the criteria required of a functional index: it is quick and easy to complete, is reliable and is sensitive to change across the whole spectrum of disease.

Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index.

OBJECTIVE: To determine the most appropriate clinical measurements for the assessment of ankylosing spondylitis (AS) to develop the new metrology index. METHODS: One hundred and ninety-three individuals with AS were studied. The patients reflected the entire spectrum of cases of AS. Metrology was performed on 327 occasions. First the metrology (20 measurements) of 43 patients was analyzed. From this, 5 simple clinical measurements were defined which most accurately reflect axial status: cervical rotation, tragus to wall distance, lateral flexion, modified Schober's, and intermalleolar distance. These measurements were assessed for reliability, speed and both inter and intraobserver variability in another 40 patients. RESULTS: Analysis of the first group of 43 patients and a subsequent group of 54 patients, using the 5 measurements that constitute this new Bath AS Metrology Index (BASMI), demonstrated that they accurately and reliably mirror the 20 clinical measurements assessed previously (r = 0.92, p < 0.001). In a new group of 40 patients the measurements were demonstrated to be accurate and reproducible for both intraobserver variability (r = 0.99, p < 0.001) and interobserver variability (r = 0.97, p < 0.001). In a further 56 patients, admitted for inpatient therapy, an improvement in the BASMI from 3.34 (SD 2.71) to 2.16 (SD 2.42) was noted over a period of 3 weeks (regardless of disease severity) which indicates a sensitivity to change (chi 2 = 6.55, p < 0.01). The mean improvement over baseline was about 30%. CONCLUSION: Five clinical measurements provide a composite index (BASMI) and define disease status in AS. The BASMI is quick (7 min), reproducible and sensitive to change across the disease spectrum.