Assessment of Response to Treatment, Remission, and Minimal Disease Activity in Axial Psoriatic Arthritis Treated with Tumor Necrosis Factor Inhibitors.

OBJECTIVE: To assess the response to treatment, remission, and minimal disease activity (MDA) in a group of patients with predominant axial psoriatic arthritis (axPsA). Predictors of response were also evaluated. METHODS: Patients fulfilling the ClASsification of Psoriatic ARthritis (CASPAR) criteria and treated with anti-tumor necrosis factor (anti-TNF) agents adalimumab, etanercept, and golimumab were enrolled and prospectively followed every 4 months for 1 year in a clinical practice setting. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 was assessed as a set of response criteria to treatment; Composite Psoriatic Disease Activity Index (CPDAI) < 4, Disease Activity Index for Psoriatic Arthritis (DAPSA) score ≤ 3.3, and partial remission (PR) were also evaluated as remission criteria. Patients were considered in MDA when they met at least 5/7 of the criteria previously defined. Patients achieving BASDAI 50, PR, and MDA were compared to identify outcome predictor factors. Concordance between the outcome measures was also performed. RESULTS: Of the 58 patients treated with anti-TNF, at baseline no patients were in PR or MDA. No patients had a CPDAI < 4 or a DAPSA score ≤ 3.3. After 12 months, BASDAI 50 was achieved in 15/48 patients (31.2%). CPDAI < 4, DAPSA score ≤ 3.3, PR, and MDA were achieved, respectively, in 17/48 (35.4%), 11/48 (22.9%), 11/48 (22.9%), and 24/48 (50%) patients. No difference was found among the 3 anti-TNF. Predictors for MDA were male sex, young age, low disease duration, low Health Assessment Questionnaire score, and absence of enthesitis. CONCLUSION: This longitudinal observational study, based on a clinical practice setting, showed that remission and MDA are achievable targets in axPsA treated with anti-TNF. Predictors of remission and MDA were also identified.

Patient's Global Assessment as an Outcome Measure for Psoriatic Arthritis in Clinical Practice: A Surrogate for Measuring Low Disease Activity?

OBJECTIVE: To assess the low disease activity (LDA) in a group of patients with psoriatic arthritis (PsA) receiving antitumor necrosis factor-α (TNF-α) by using the patient's global assessment (PtGA) in clinical practice, and to compare PtGA with minimal disease activity (MDA) and other outcome measures. METHODS: Patients with PsA classified by the ClASsification for Psoriatic ARthritis (CASPAR) criteria and consecutively admitted to an outpatient clinic dedicated to biologic therapy were assessed during their routine followup. The primary outcome measure was the proportion of patients achieving a PtGA ≤ 20 at 4-, 8-, and 12-month followups. Secondary outcome measures included the proportion of patients achieving MDA and other outcome measures. Correlation of PtGA with MDA and other process and outcome measures were also performed. RESULTS: During the period of observation, 124 patients were evaluated. PtGA ≤ 20 was achieved in 25.7% at 4 months, 48.9% at 8 months, and 65.3% at 12 months of followup. The percentage of PtGA ≤ 20 statistically improved throughout the 3 timepoint assessments and it was statistically correlated to MDA. A significant correlation with the Disease Activity index for PSoriatic Arthritis (DAPSA), Bath Ankylosing Spondylitis Disease Activity Index, and Health Assessment Questionnaire was also observed. MDA, DAPSA, and Disease Activity Score at 28 joints with C-reactive protein remission were achieved at 12 months in 64%, 36%, and 71% of patients, respectively. CONCLUSION: PtGA can estimate the LDA status and could be considered as a surrogate of outcome measures for the assessment of global disease activity in patients with PsA receiving anti-TNF therapy during routine clinical practice. These data suggest that PtGA might be used in outpatient settings, being a simple, reliable, and not time-consuming instrument.

The Definition and Measurement of Axial Psoriatic Arthritis.

This review seeks to update the state of the art of axial psoriatic arthritis (axPsA). The definition and assessment of axPsA can be problematic because no agreement and no definitive data on this topic have been published, resulting in uncertainty as to the best approach to deal with these patients. A few recent scientific reports show new data on the possible coincidence of diffuse idiopathic skeletal hyperostosis and axPsA, as well as on the radiological assessment as measured with the validated instruments for axPsA. Moreover, the role of magnetic resonance imaging has also been evaluated for this intriguing subset. All data confirmed that radiological assessment is a useful tool to detect typical findings of axPsA, while other imaging techniques remain to be validated. Finally, there is no evidence to support treatment of axPsA with traditional disease-modifying antirheumatic drugs, while a "leap" to biologic agents is the only treatment after failure with nonsteroidal antiinflammatory drugs.

Evaluating school wellness policy in curbing childhood obesity in Anchorage, Alaska.

In 2006, the Anchorage School District implemented a school wellness policy to address the problem of obesity among its elementary-aged students. We assessed whether the addition of this policy is effective in protecting or preventing students from becoming overweight/obese over time. The methods involved following two cohorts of students for 5 years, a cohort not exposed and a cohort exposed to the policy. The results show that exposure to the policy does not significantly protect or prevent students from becoming overweight/obese. However, we found that regardless of being exposed to the policy, boys (odds ratio [OR] = 1.12), ethnic minorities, (OR = 1.18), and students from low socioeconomic backgrounds (OR = 1.44) were more likely to remain or become overweight/obese. Our findings suggest that factors outside the school may be impacting students' overweight/obese status. Efforts to curb the problem of childhood obesity should extend to the children's communities and homes.

The radiological assessment of axial involvement in psoriatic arthritis.

This article summarizes the state of radiological assessment of axial involvement in psoriatic arthritis (PsA). The definition and measurement of axial disease in PsA remain problematic and this situation in turn could affect the choice of approach to evaluate radiological findings of the spine. At present, the radiological assessment has been evaluated by using scoring systems borrowed from ankylosing spondylitis (AS). In particular, the Bath AS Radiology Index (BASRI) and the modified Stoke AS Spine Score (m-SASSS) have been validated for axial PsA. A recent study showed that BASRI and m-SASSS were valid instruments; however, neither score encompassed all radiological features of PsA. Therefore, a new index for assessing radiological axial involvement in PsA was developed--the PsA Spondylitis Radiology Index (PASRI). This new index encompassed a greater range of the spinal radiological features of PsA, providing a greater score range, and it correlated well with anthropometric and patient-reported outcomes. Recently, a study assessed the sensitivity to change of BASRI, m-SASSS, and PASRI, and showed that these 3 instruments provided a moderate sensitivity to change but high specificity to detect the true changes.

Patient global assessment in psoriatic arthritis: a multicenter GRAPPA and OMERACT study.

OBJECTIVE: During OMERACT 8, delegates selected patient global assessment (PGA) of disease as a domain to be evaluated in randomized controlled trials in psoriatic arthritis (PsA). This study assessed the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional utility of separate VAS scales for joints (PJA) and skin (PSA). METHODS: In total, 319 consecutive patients with PsA (186 men, 133 women, mean age 51 ± 13 yrs) were enrolled. PGA, PJA, and PSA were administered at enrolment (W0) and after 1 week (W1). Detailed clinical data, including ACR joint count, Psoriasis Area and Severity Index (PASI), and Hospital Anxiety and Depression Scale, were recorded. RESULTS: Comparison of W0 and W1 scores showed no significant variations (intraclass correlation coefficients for PGA 0.87, PJA 0.86, PSA 0.78), demonstrating the reliability of the instrument. PGA scores were not influenced by patient anxiety or depression, but were dependent on PJA and PSA (p = 0.00001). PJA was dependent on the number of swollen and tender joints (p < 0.00001). PSA scores were influenced by the extent of skin psoriasis and by hand skin involvement (p = 0.00001). Joint and skin disease were found not to correlate in terms of disease activity as evidenced by the swollen joint count compared to PASI (r = 0.11) and by the PJA compared to PSA (r = 0.38). CONCLUSION: PGA assessed by means of VAS is a reliable tool related to joint and skin disease activity. Because joint and skin disease often diverge it is suggested that in some circumstances both PJA and PSA are also assessed.

Rehabilitation in psoriatic arthritis.

This article summarizes the state of the art of rehabilitation in psoriatic arthritis (PsA). Very little evidence was available to assess the efficacy of rehabilitation. Some data were borrowed from studies on ankylosing spondylitis. Covering certain aspects of the disease by the standard measure of functioning was difficult. However, rehabilitation was considered by the GRAPPA Group (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), as part of treatment of axial PsA.

Psoriatic arthritis spondylitis radiology index: a modified index for radiologic assessment of axial involvement in psoriatic arthritis.

OBJECTIVE: To develop and validate a modified index for assessing the radiologic axial involvement in psoriatic arthritis (PsA) in a group of patients with established disease. METHODS: Patients were included on clinical and/or radiologic criteria. The modified index combined features of existing radiologic indices for ankylosing spondylitis (AS) with the addition of scores for the facet joints of the cervical and lumbar regions. Scores for the BathAS Radiology Index (BASRI), the modified Stoke AS Scoring System (mSASSS), and the new index were obtained from current radiographs. The construct validity of the new index was assessed by examining the correlation with patient reported outcomes, such as the Revised Leeds Disability Questionnaire (RLDQ) and BathAS Functional Index (BASFI), and anthropometric measures. RESULTS: Radiographs were available for 73 patients (54 men, 19 women, mean age 49.4 +/- 11.0 yrs, mean disease duration 14.0 +/- 7.9 yrs). Due to difficulty in visualizing and interpreting the lumbar facet joints, only the cervical facet joints were included in the new score, called the PsA Spondylitis Radiology Index (PASRI). Overall, the PASRI resulted in less missing data than the mSASSS, but had less complete data than the BASRI. The PASRI also had fewer zero scores than the mSASSS and the score range for the PASRI exceeded that of the mSASSS and the BASRI. Correlation with anthropometric and patient reported outcomes was good for both the PASRI and BASRI, with both these measures outscoring the mSASSS. CONCLUSION: The PASRI encompasses a greater range of the spinal radiologic features of PsA, provides a greater score range and fewer zero scores, and correlates well with anthropometric and patient reported measures.

Effects of a combination treatment of an intensive rehabilitation program and etanercept in patients with ankylosing spondylitis: a pilot study.

OBJECTIVE: To determine the effects of a combination treatment including rehabilitation and etanercept versus rehabilitation only, on function, disability, and quality of life in a group of patients with active ankylosing spondylitis (AS). METHODS: Nineteen patients with AS consecutively admitted to a rehabilitation inpatient clinic were enrolled. Patients first participated in an intensive rehabilitation program and after a 6-month interval started etanercept therapy. After 3 weeks, they started a combination of rehabilitation and etanercept. The primary outcome measure was an improvement of the Bath Ankylosing Spondylitis Functional Index (BASFI) defined as the difference (Delta) between the 2 measurements (beginning and end). The difference between the 2 measurements for the first rehabilitation program was expressed as Delta1 and for the second as Delta2; the comparison between Delta1 and Delta2 for each outcome measure was taken into account. Secondary outcome measures included an improvement in the Revised Leeds Disability Questionnaire (LDQ), anthropometric measures, EuroQol (EQ-5Dvas), and the 6 minute walking test (6-MWT). RESULTS: A statistically significant improvement was observed both for BASFI (Delta1 = -0.71 +/- 0.23; Delta2 = -1.19 +/- 0.36, p < 0.001) and for LDQ (Delta1 = -0.28 +/- 0.08; Delta2 = -0.46 +/- 0.17, p = 0.001). All anthropometric measures as well as 6-MWT were statistically improved. Finally, EQ5Dvas showed a statistically significant difference (Delta1 = 6.63 +/- 2.81; Delta2 = 20.26 +/- 4.89, p < 0.001). No adverse effects were seen during treatment with etanercept. CONCLUSION: This combination treatment seems to improve function, disability, and quality of life in patients with active AS.

The modern abdominoperineal excision: the next challenge after total mesorectal excision.

OBJECTIVES: Examine the cause of local recurrence (LR) and patient survival (S) following abdominoperineal resection (APR) and anterior resection (AR) for rectal carcinoma and the effect of introduction of total mesorectal excision (TME) on APR. METHODS: A total of 608 patients underwent surgery for rectal cancer in Leeds from 1986 to 1997. CRM status and follow-up data of local recurrence and patient survival were available for 561 patients, of whom 190 underwent APR (32.4%) and 371 AR (63.3%). Also, a retrospective study of pathologic images of 93 specimens of rectal carcinoma. RESULTS: Patients undergoing APR had a higher LR and lower survival (LR, 22.3% versus 13.5%, P = 0.002; S, 52.3% versus 65.8%, P = 0.003) than AR. LR free rates were lower in the APR group and cancer specific survival was lowered (LR, 66% versus 77%, log rank P = 0.03; S, 48% versus 59%, log rank P = 0.02). Morphometry: total area of surgically removed tissue outside the muscularis propria was smaller in APR specimens (n = 27) than AR specimens (n = 66) (P < 0.0001). Linear dimensions of transverse slices of tissue containing tumor, median posterior, and lateral measurements were smaller (P < 0.05) in the APR than the AR group. APR specimens with histologically positive CRM (n = 11) had a smaller area of tissue outside the muscularis propria (P = 0.04) compared with the CRM-negative APR specimens (n = 16). Incidence of CRM involvement in the APR group (41%) was higher than in the AR group (12%) (P = 0.006) in the 1997 to 2000 cohort. Similar results (36% and 22%) were found in the 1986 to 1997 cohort (P = 0.002). CONCLUSIONS: Patients treated by APR have a higher rate of CRM involvement, a higher LR, and poorer prognosis than AR. The frequency of CRM involvement for APR has not diminished with TME. CRM involvement in the APR specimens is related to the removal of less tissue at the level of the tumor in an APR. Where possible, a more radical operation should be considered for all low rectal cancer tumors.

Thrombotic risk factors in primary antiphospholipid syndrome: a 5-year prospective study.

BACKGROUND AND PURPOSE: Because thromboembolic events are frequently observed in primary antiphospholipid syndrome (PAPS), we assessed the risk factors for new thrombotic episodes. METHODS: Fifty-six PAPS patients (mean age, 37+/-10 years) were prospectively studied for 5 years. The preliminary Sapporo classification criteria for antiphospholipid syndrome (APS; a medium-high anticardiolipin antibody [aCL] titer and/or a positive lupus anticoagulant [LA] test in the presence of vascular thrombosis and/or pregnancy morbidity) were used to confirm the diagnosis. Thrombotic episodes or pregnancy losses before a diagnosis of PAPS were considered events, and any new disease manifestation other than thrombocytopenia was considered a recurrent event. Only patients with objectively verified thrombotic events were included in the study. RESULTS: Twenty-one new thrombotic events were observed in 15 subjects (26.8%), including 3 (5.4%) who died during the follow-up. The patients with IgG aCL levels of >40 IgG phospholipid unit (GPL-U) showed a higher incidence of new thrombotic events (43.3%) than those with levels of < or =40 GPL-U (7.7%). Univariate analysis identified a history of recurrent clinical events (P=0.004), a highly positive aCL titer (P=0.007), and the presence of cardiac abnormalities (P=0.036) as significant risk factors for new thrombotic events. A multivariate regression model confirmed that an IgG aCL titer of >40 GPL-U was an independent risk factor for thrombosis (odds ratio, 9.17; 95% confidence interval, 1.83 to 46.05). CONCLUSIONS: A high IgG aCL titer is the strongest predictor of new thrombotic events in PAPS patients.

Expression of BUB1 protein in gastric cancer correlates with the histological subtype, but not with DNA ploidy or microsatellite instability.

During mitosis, the spindle checkpoint delays the onset of anaphase until all chromosomes have attached properly to the mitotic spindle, preventing chromosome missegregation. BUB (budding uninhibited by benzimidazole) 1 is one of the key components of this checkpoint. BUB1 mutations are rare in cancer tissues and no mutations have been identified in gastric cancer. In mice, immunodepletion of BUB1 abolished the spindle checkpoint. Thus, aberrant expression of BUB1 protein could impair mitotic checkpoint function, resulting in aneuploidy, a common phenomenon in gastric cancer. In the present study, an antibody was generated against BUB1 and its expression was studied in gastric cancer tissue sections (n = 80) by immunohistochemistry. Nuclear BUB1 expression was found in all gastric cancer cases. The proportion of tumour cells expressing BUB1 was significantly greater in diffuse-type than in intestinal-type gastric carcinoma (p < 0.001). No correlation was found between BUB1 expression and deoxyribonucleic acid (DNA) ploidy, microsatellite instability or any other histopathological parameters investigated. To the authors' knowledge, this is the first study of BUB1 protein expression in gastric cancer tissues. Different BUB1 protein expression levels in intestinal- and diffuse-type gastric cancer may provide further evidence of a potential link between different genetic pathways and morphological phenotype in gastric carcinogenesis. However, further studies are needed to establish whether there is an association between BUB1 protein expression level and mitotic spindle checkpoint function in gastric cancer.

Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer--association with tumour cell proliferation.

The mitotic spindle assembly checkpoint modulates the timing of anaphase initiation in response to improper alignment of chromosomes at the metaphase plate. The BUB gene family encodes proteins which are part of a large multi-protein kinetochore complex and which are believed to be key components of the checkpoint regulatory pathway. Failure of this surveillance system can lead to genomic instability and could be responsible for the increased incidence of aneuploidy in gastric cancer. Since mutations of BUB genes have not been identified in gastric cancer to date, altered BUB expression levels may significantly impair mitotic checkpoint function. To explore this possibility, the expression levels of BUB1, BUBR1, and BUB3 were determined in 43 gastric carcinomas and corresponding normal gastric mucosa by reverse transcription-polymerase chain reaction (RT-PCR). Gene expression levels were compared with histopathological parameters and DNA ploidy, as well as with proliferative activity, measured by Ki-67 mRNA expression. To the authors' knowledge, this is the first study to investigate the expression levels of mitotic checkpoint genes together with DNA ploidy in gastric cancer. BUB1 was overexpressed in 84%, BUBR1 in 68%, and BUB3 in 79% of gastric cancers. This study also revealed that all three genes were simultaneously overexpressed in 61% of the tumours and that there was a statistically significant positive correlation between overexpression of BUB1, BUBR1 or BUB3 and Ki-67 expression (p < 0.001). Eighty-one per cent of the tumours were classified as aneuploid. However, no correlation was found between ploidy and BUB transcript expression levels. These results suggest that inactivation of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 by epigenetic silencing does not seem to play a role in gastric carcinogenesis. The strong correlation of BUB expression level and tumour cell proliferation suggests that BUB overexpression is a proliferation-dependent phenomenon in gastric cancer. However, overexpression due to lack of normal BUB protein function or due to a yet unknown additional BUB function has to be considered.

Skin colonization by Malassezia in neonates and infants.

OBJECTIVE: To identify the timing, pattern, and determinants of colonization of neonates by Malassezia. DESIGN: Prospective observational study. SETTING: A neonatal medical and surgical unit consisting of 10 special care, 10 high-dependency, 10 intensive care, and 10 surgical cots. PARTICIPANTS: All neonates (< or = 28 days of age) or infants (> 28 days of age) admitted to the unit during the 20-week period from October 1995 to March 1996. METHODS: All infants or neonates were swabbed on the day of admission and every third day thereafter and risk factors were collected for every day on the unit. RESULTS: During the study period, 245 neonates and 42 infants were sampled for their entire duration of stay on the unit. Of these, 41 infants (97.6%) were colonized with Malassezia on admission to the unit and thereafter, as assessed by subsequent samples. Within the neonate population, 78 (31.8%) became colonized, but none were colonized immediately after birth. Univariate analysis showed that many factors appeared to be significantly associated with colonization in the neonates, including use of ventilation, presence of central venous catheters, use of parenteral nutrition, and use of antibacterial or antifungal drugs. However, when the data were analyzed by multivariate logistic regression to control for confounding variables, only gestational age and length of stay on the unit were found to be significantly associated with colonization. CONCLUSION: Colonization of infants is not as unusual as previously thought and many infants have established a cutaneous Malassezia commensal flora by the age of 3 to 6 months. Factors that predispose to colonization in neonates may not be the same as those that predispose to infection.

Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery.

OBJECTIVE: To analyze the potential variability in rates of circumferential resection margin (CRM) involvement between different surgeons and time periods and to determine the suitability of using CRM status as an immediate predictor of outcome after rectal cancer surgery. SUMMARY BACKGROUND DATA: After disease stage has been taken into account, survival in rectal cancer has been shown to be very variable between surgeons and institutions. One of the major factors influencing survival is local recurrence, and this in turn is strongly related to inadequate tumor excision, particularly at the CRM. METHODS: In a study involving 608 patients who underwent surgery for rectal cancer in Leeds during the 12-year period 1986 to 1997, the authors examined the role of CRM status as an immediate predictor of likely outcome, paying particular attention to its relationships with different surgeons and time periods. RESULTS: Of 586 patients on whom full clinical follow-up was obtained, 165 (28.2%) had CRM involvement by carcinoma on pathologic examination. Up to the end of 1998, 105 (17.9%) patients had developed local recurrence. A significantly higher proportion (38.2%) of CRM-positive patients developed local recurrence than CRM-negative ones (10.0%). Kaplan-Meier survival analysis showed significant improvements in survival for CRM-negative patients over CRM-positive patients. Survival analysis in relation to two gastrointestinal surgeons and a group of other surgeons showed survival improvements that paralleled a reduction in the rates of CRM involvement for the two gastrointestinal surgeons during the period of the study. No improvement in survival or reduction in rates of CRM involvement was seen in the group of other surgeons. CONCLUSIONS: These results show that CRM status may be used as an immediate predictor of survival after rectal cancer surgery and serves as a useful indicator of the quality of surgery. The frequency of CRM involvement can be used both for overall surgical audit and for monitoring the value of training programs in improving rectal surgery by individual surgeons. Its use in the current MRC CR07 study is valid and the best indicator of a requirement for further local therapy.