Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients - control survival is much better than previously assumed.

AIM: Lung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5-year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial. METHOD: Multidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two-arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention-to-treat analysis. RESULTS: From 2010 to 2016, 93 participants were randomized. These patients were 35-86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1-6.6) years compared with 3.8 (95% CI: 3.1-4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56-1.56). Use of chemotherapy or local ablation was infrequent and similar in each group. CONCLUSION: Patients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single-arm follow-up studies. The groups were well matched with features similar to those reported in case series.

Do drugs offering only PFS maintain quality of life sufficiently from a patient's perspective? Results from AVALPROFS (Assessing the 'VALue' to patients of PROgression Free Survival) study.

PURPOSE: Trials of novel drugs used in advanced disease often show only progression-free survival or modest overall survival benefits. Hypothetical studies suggest that stabilisation of metastatic disease and/or symptom burden are worth treatment-related side effects. We examined this premise contemporaneously using qualitative and quantitative methods. METHODS: Patients with metastatic cancers expected to live > 6 months and prescribed drugs aimed at cancer control were interviewed: at baseline, at 6 weeks, at progression, and if treatment was stopped for toxicity. They also completed Functional Assessment of Cancer Therapy (FACT-G) plus Anti-Angiogenesis (AA) subscale questionnaires at baseline then monthly for 6 months. RESULTS: Ninety out of 120 (75%) eligible patients participated: 41 (45%) remained on study for 6 months, 36 progressed or died, 4 had treatment breaks, and 9 withdrew due to toxicity. By 6 weeks, 66/69 (96%) patients were experiencing side effects which impacted their activities. Low QoL scores at baseline did not predict a higher risk of death or dropout. At 6-week interviews, as the side effect severity increased, patients were significantly less inclined to view the benefit of cancer control as worthwhile (X2 = 50.7, P < 0.001). Emotional well-being initially improved from baseline by 10 weeks, then gradually returned to baseline levels. CONCLUSION: Maintaining QoL is vital to most patients with advanced cancer so minimising treatment-related side effects is essential. As side effect severity increased, drugs that controlled cancer for short periods were not viewed as worthwhile. Patients need to have the therapeutic aims of further anti-cancer treatment explained honestly and sensitively.

Meta-analysis of colorectal cancer follow-up after potentially curative resection.

BACKGROUND: After potentially curative resection of primary colorectal cancer, patients may be monitored by measurement of carcinoembryonic antigen and/or CT to detect asymptomatic metastatic disease earlier. METHODS: A systematic review and meta-analysis was conducted to find evidence for the clinical effectiveness of monitoring in advancing the diagnosis of recurrence and its effect on survival. MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science and other databases were searched for randomized comparisons of increased intensity monitoring compared with a contemporary standard policy after resection of primary colorectal cancer. RESULTS: There were 16 randomized comparisons, 11 with published survival data. More intensive monitoring advanced the diagnosis of recurrence by a median of 10 (i.q.r. 5-24) months. In ten of 11 studies the authors reported no demonstrable difference in overall survival. Seven RCTs, published from 1995 to 2016, randomly assigned 3325 patients to a monitoring protocol made more intensive by introducing new methods or increasing the frequency of existing follow-up protocols versus less invasive monitoring. No detectable difference in overall survival was associated with more intensive monitoring protocols (hazard ratio 0·98, 95 per cent c.i. 0·87 to 1·11). CONCLUSION: Based on pooled data from randomized trials published from 1995 to 2016, the anticipated survival benefit from surgical treatment resulting from earlier detection of metastases has not been achieved.

Psychological morbidity associated with ovarian cancer screening: results from more than 23,000 women in the randomised trial of ovarian cancer screening (UKCTOCS).

OBJECTIVE: To examine the psychological sequelae associated with abnormal screening in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). DESIGN: Prospective, longitudinal randomised control trial. SETTING: Sixteen UKCTOCS centres. SAMPLE: Women aged 50-70 years randomised to annual multimodal screening, ultrasound screening or control groups. METHODS: Two groups were followed for 7 years: (1) a random sample (n = 1339), taken from all three study groups; and (2) an events sample (n = 22,035) of women with abnormal screens resulting in the need for repeat testing of either low or higher level intensity. MAIN OUTCOME MEASURES: Patient-reported measures of anxiety (scores ranging from 20 to 80) and psychological morbidity. RESULTS: In the random sample the mean difference between anxiety scores after a repeat screening and those following an annual screening was 0.4 (95% CI -0.46, 1.27), and in the events sample it was 0.37 (95% CI 0.23, 0.51). The risk of psychological morbidity was only increased in the event sample for women requiring higher level repeat screening (OR 1.28; 95% CI 1.18, 1.39). The risk of psychological morbidity in women with ovarian cancer was higher at both 6 weeks (OR 16.2; 95% CI 9.19, 28.54) and 6 months (OR 3.32; 95% CI 1.91, 5.77) following surgery. CONCLUSIONS: Screening does not appear to raise anxiety but psychological morbidity is elevated by more intense repeat testing following abnormal annual screens, and in women after surgical treatment for ovarian cancer.

The functional MICA-129 polymorphism is associated with skin but not joint manifestations of psoriatic disease independently of HLA-B and HLA-C.

A methionine/valine polymorphism at amino acid 129 of the major histocompatibility complex class I chain-related gene A (MICA-129) categorizes alleles into strong and weak binders of the natural killer (NK) and T-cell receptor NKG2D. We investigated whether MICA-129 is differentially associated with skin and joint manifestations of psoriatic disease (PsD) independently of human leukocyte antigen (HLA)-C and HLA-B in patients and controls from Toronto and St. John's. The MICA-129 methionine (Met) allele, particularly Met/Met homozygosity, was strongly associated with both cutaneous psoriasis (PsC) and psoriatic arthritis (PsA) independently of HLA-B and HLA-C in Toronto patients, and was also associated with PsA in St. John's patients, but with no additional effect of Met/Met homozygosity. No association remained after adjustment for HLA alleles in St. John's patients. MICA-129 was not associated with PsA when compared with PsC. We conclude that MICA-129 is a marker of skin manifestations of PsD that is independent of HLA class I in Toronto patients.

Drivers and barriers to patient participation in RCTs.

BACKGROUND: Recruitment of patients into randomised clinical trials (RCTs) is essential for treatment evaluation. Appreciation of the barriers and drivers towards participation is important for trial design, communication and information provision. METHOD: As part of an intervention to facilitate effective multidisciplinary team communication about RCTs, cancer patients completed two study-specific questionnaires following trial discussions. One questionnaire examined reasons why patients accepted or declined trial entry, the other perceptions about their health-care professionals' (HCPs) information giving. RESULTS: Questionnaires were completed by 74% (358/486) of patients approached; of these 81% (291/358) had joined an RCT, 16% (56/358) had declined and 3% (11/358) were undecided. Trial participation status of the 128 patients not returning questionnaires is unknown. Trial acceptance was not dependent on disease stage, tumour type, sex or age. Satisfaction with trial information and HCPs' communication was generally very good, irrespective of participation decisions. The primary reason given for trial acceptance was altruism (40%; 110/275), and for declining, trust in the doctor (28%; 12/43). Decliners preferred doctors to choose their treatment rather than be randomised (54% vs 39%; P<0.027). Acceptors were more likely to perceive doctors as wanting them to join trials (54% vs 30%; P<0.001). Trial type, that is, standard treatment vs novel or different durations of treatment, also influenced acceptance rates. CONCLUSION: The drivers and barriers to trial participation are partly related to trial design. Unease about randomisation and impact of duration on treatment efficacy are barriers for some. Altruism and HCPs' perceived attitudes are powerful influencing factors.

Teams Talking Trials: results of an RCT to improve the communication of cancer teams about treatment trials.

BACKGROUND: Previous research has shown that communication between members of multidisciplinary teams (MDTs) is often suboptimal and communication about trials between MDTs and their patients is difficult. Educational interventions can help dyadic exchanges with different aspects of trial recruitment but less work has focussed on team interventions. METHODS: 22 multidisciplinary cancer teams in the UK participated in an RCT of a novel Teams Talking Trials (TTT) Workshop aimed at improving the following: awareness, involvement, communication and recruitment to cancer trials. MDTs were randomised following either 6 or 12 months of audits, which were repeated after the intervention. Audits included numbers approached about trials, team members' attitudes, involvement and awareness of their teams' trial portfolios. RESULTS: There was no significant difference in the rate of approaching patients about trials post workshop (estimated improvement 22% higher regression coefficient of 0.2, exp. (0.2)=1.22). There was improvement in team members' involvement in trials in 4 areas (p≤0.04): the pressure to enter patients into RCTs, the likelihood of a start-up meeting to discuss a newly accepted trial, the informational role played by individuals and recognition of this HCP's role by other team members. Also, confidence in communication about RCTS increased and awareness of different aspects of trial management improved on all 14 aspects (p=0.001). CONCLUSION: Attendance by teams at focussed workshops designed to enhance communication and trial recruitment improved several aspects of team functioning, but a significant impact on the number of patients approached could not be demonstrated.

Differential major histocompatibility complex class I chain-related A allele associations with skin and joint manifestations of psoriatic disease.

About 30% of patients with psoriasis have psoriatic arthritis (PsA), an inflammatory arthritis that can affect both axial and peripheral joints. Major histocompatibility complex class I chain-related A (MICA) alleles have previously been shown to be associated with PsA; however it is unclear whether there is a differential association of MICA alleles with skin and joint manifestations of PsA. Here, we describe a case-control study that aims to validate previously reported MICA allele associations with PsA and determine whether MICA alleles differentiate patients with PsA from those with psoriasis without PsA. Two hundred forty-nine unrelated Caucasian PsA patients, 243 psoriasis patients without arthritis, and 248 healthy controls were genotyped for 55 MICA alleles using PCR-SSP, and for human leucocyte antigen (HLA)-B and HLA-C alleles by PCR-SSO reverse line blot. Allele frequencies were calculated and logistic regressions were performed, adjusting for HLA-B and HLA-C alleles previously shown to be associated with psoriasis and/or PsA. Several MICA alleles were associated with psoriatic disease, PsA, and psoriasis compared with controls, and PsA compared with psoriasis in univariate analyses. Haplotype analysis showed evidence of strong linkage disequilibrium (LD) between PsA and psoriasis risk alleles of HLA-C, HLA-B, and MICA. After adjusting for significant HLA-B and HLA-C alleles in multivariate analyses, MICA*016 remained significantly associated with psoriasis [odds ratio (OR) = 5.5, P = 0.008]. MICA*00801 homozygosity was associated with susceptibility to PsA when compared with patients with psoriasis alone (OR = 2.26, P = 0.009). We conclude that most MICA allele associations with psoriasis and PsA are dependent on LD with HLA-B and HLA-C risk alleles. Independent of HLA, only MICA*016 influences the risk of developing psoriasis without arthritis, and homozygosity for MICA*00801 increases the risk of developing PsA in patients with psoriasis.

Clinicians' attitudes towards clinical trials of cancer therapy.

BACKGROUND: Patient accrual into cancer clinical trials remains at low levels. This survey elicited attitudes and practices of cancer clinicians towards clinical trials. METHOD: The 43-item Clinicians Attitudes to Clinical Trials Questionnaire was completed by participants in an intervention study aimed at improving multi-disciplinary involvement in randomised trials. Responses from 13 items were summed to form a research-orientation score. RESULTS: Eighty-seven clinicians (78%) returned questionnaires. Physicians, more often than surgeons, chose to prioritise prolonging a patient's life, recruited ≥50% of patients into trials and attended more research-focussed conferences. Clinicians at specialist centres were more positive about trials with no-treatment arms than those at district general hospitals, more likely to believe clinician, rather than patient reluctance to participate was the greater obstacle to trial accrual, and preferred national and international to local recognition. Clinicians belonging to breast and colorectal teams were less disappointed about not enrolling patients in trials and more accepting of no-treatment arm trials. Research orientation was higher in physicians than surgeons and higher in specialist centres than district hospitals. CONCLUSIONS: This study provides greater understanding of clinicians' attitudes to trials. Results have been used to inform training interventions for clinicians targeting the problem of low and selective accrual.

The attitudes of 1066 patients with cancer towards participation in randomised clinical trials.

BACKGROUND: barriers to randomised clinical trial (RCT) recruitment include failure to identify eligible patients, reluctance of staff to approach them and attitudes of some health-care professionals and patients. As part of a larger UK prospective study examining the communication and involvement in RCTs of 22 multidisciplinary teams in Wales, we also assessed the attitudes of patients they treat towards trials. METHODS: out of 1146 patients attending outpatient departments who were approached, 1146 (93%) completed the seven-item Attitudes to Randomised Trials Questionnaire (ARTQ), probing their general attitudes towards medical research and likely participation in a hypothetical two-arm RCT. RESULTS: randomisation initially deterred many patients from endorsing a willingness to participate. However, if information about the trial logic, voluntary nature and rights to withdraw were provided, together with further treatment details, 83% (886 out of 1066) would potentially participate. Other variables associated with a positive inclination towards participation included previous trial experience (P<0.01), male gender (P<0.01) and younger age, with patients > or =70 years less likely to consider trial entry (P<0.01). CONCLUSION: the majority of patients were receptive to RCT participation. Many of those initially disinclined because of randomisation would consider joining if given further details that form part of standard GCP consent guidelines. These data show the importance and need for clear communication and information to encourage RCT participation. Evidence-based training courses are available to assist with this.

One-stage parametric meta-analysis of time-to-event outcomes.

Methodology for the meta-analysis of individual patient data with survival end-points is proposed. Motivated by questions about the reliance on hazard ratios as summary measures of treatment effects, a parametric approach is considered and percentile ratios are introduced as an alternative to hazard ratios. The generalized log-gamma model, which includes many common time-to-event distributions as special cases, is discussed in detail. Likelihood inference for percentile ratios is outlined. The proposed methodology is used for a meta-analysis of glioma data that was one of the studies which motivated this work. A simulation study exploring the validity of the proposed methodology is available electronically.

Awareness of ovarian cancer risk factors, beliefs and attitudes towards screening: baseline survey of 21,715 women participating in the UK Collaborative Trial of Ovarian Cancer Screening.

BACKGROUND: Women's awareness of ovarian cancer (OC) risks, their attitudes towards and beliefs about screening, together with misunderstandings or gaps in knowledge, may influence screening uptake. METHODS: In total, 21 715 post-menopausal women completed questionnaires before randomisation into the UK Collaborative Trial of Ovarian Cancer Screening. RESULTS: In all, 42.3% correctly identified their lifetime risk of OC; 87.1% knew that a family history of OC increased risk, but only 26.7% appreciated the association with a family history of breast cancer. Although 38.2% acknowledged increased risk post-menopause, only 8.8% were aware that OC diagnoses are highest in women over 65 years. Few (13.7%) recognised the association between pregnancy and reduced OC risk or protective effects of breastfeeding (6.2%). There were common misconceptions; 37.2% thought that an abnormal cervical smear and 26.4% that oral contraception increased the likelihood of OC. Although 84.4% recognised that most ovarian masses are benign, 20.2% thought having had a benign cyst increased OC risk. Most (99.4%) believed that a high uptake of OC screening would reduce mortality and (96.2%) that screen-detected cancers would have an improved prognosis. CONCLUSIONS: The results show a need for improved public understanding about OC risks and provide important information for GPs and health educationalists about initiatives needed for future awareness, prevention and screening programmes.

Pulmonary metastasectomy in colorectal cancer: time for a trial.

Pulmonary metastasectomy is undertaken for a range of cancers. The questions we raise here are specifically related to colorectal cancer, the commonest tumour for which pulmonary metastasectomy is undertaken. The primary objective of metastasectomy is to increase survival. There are no randomised trials in support of this practice nor are there any other forms of controlled studies. We present a critical look at the assumption of efficacy for this surgery and propose that a trial is needed and suggest a trial design.

Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS).

OBJECTIVE: To develop and validate a psoriatic arthritis (PsA) screening questionnaire: the Toronto Psoriatic Arthritis Screen (ToPAS). METHODS: The ToPAS was developed through review of items seen in patients with PsA and evaluation by patients with PsA and patients with other rheumatological conditions, and was administered to consecutive consenting patients attending five clinics: PsA, psoriasis, general dermatology, general rheumatology (excluding PsA patients) and family medicine. All patients were assessed by a rheumatologist according to a standard protocol. A three-step analysis strategy was adopted: a stepwise logistic regression to identify the questions most important in discriminating between those with and without PsA; a logistic model was fitted to three clinically relevant domains for PsA: skin, joints and nails; and a simpler weighting of each of the domains used in step 2. Receiver operating characteristic (ROC) curves were obtained based on these various models. RESULTS: In all, there were 134 patients from the PsA clinic, 123 with psoriasis, 118 from dermatology, 135 from rheumatology and 178 from family medicine. A simplified discriminatory score based on the skin, joint and nail domains gave results comparable to other methods with an observed overall sensitivity and specificity, based on a single cut point, of 86.8% and 93.1%. When the patients with PsA were compared with each of the other four patient groups individually, the sensitivity and specificity of the ToPAS were: psoriasis 89.1%, 86.3%; dermatology 91.9%, 95.2%; rheumatology 92.6%, 85.7%; and family medicine 90.4%, 100%. CONCLUSION: Our simplified index is very good at classifying those who are not diagnosed with PsA and those who are diagnosed with PsA.

Cardiovascular morbidity in psoriatic arthritis.

BACKGROUND: Increasing evidence for cardiovascular mortality among patients with psoriasis and psoriatic arthritis (PsA) has accumulated, together with evidence for increased prevalence of risk factors for cardiovascular disease (CVD). OBJECTIVES: To describe cardiovascular morbidity in PsA, determine its prevalence and identify risk factors for its development. METHODS: At the University of Toronto, patients were followed up prospectively according to a standard protocol, including disease-related features and comorbidities. Patients with CVD, including myocardial infarction (MI), angina, hypertension and cerebrovascular accident (CVA), were identified. The prevalence of CVD morbidities in these patients was compared with data from the Canadian Community Health Survey through standardised prevalence ratios (SPRs). Cox relative risk regression analysis was used to analyse risk factors. RESULTS: At the time of analysis, 648 patients were registered in the database. After clinic entry, 122 developed hypertension, 38 had an MI and 5, 21 and 11 had CVA, angina and congestive heart failure (CHF), respectively. 155 patients had at least one of these conditions. The SPRs for MI (2.57; 95% CI 1.73 to 3.80), angina (1.97; 95% CI 1.24 to 3.12) and hypertension (1.90; 95% CI 1.59 to 2.27) were statistically significant, whereas the SPRs for CHF (1.19; 95% CI 0.50 to 2.86) and CVA (0.91; 95% CI 0.34 to 2.43) were not. Factors associated with CVD included diabetes, hyperlipidaemia and high Psoriasis Area and Severity Index scores. CONCLUSION: Patients with PsA are at increased risk of cardiovascular morbidities compared with the general population. In addition to known risk factors for CVD, severe psoriasis is an important predictor in patients with PsA.

Occurrence and correlates of fatigue in psoriatic arthritis.

OBJECTIVE: To determine the relationship between fatigue and disease-related and psychosocial variables in psoriatic arthritis (PsA). METHOD: 499 patients attending the University of Toronto PsA Clinic were administered the modified fatigue severity scale (mFSS). At the time of mFSS administration, clinical and laboratory measures of disease activity and damage were recorded. Linear regression models were used to examine the cross-sectional relationship between disease-related and psychosocial variables and mFSS scores. RESULTS: At least moderate fatigue occurred in 49.5% of patients and severe fatigue in 28.7%. Univariately the vast majority of variables were significantly associated with mFSS scores. The final multivariate model was composed of female sex, the medical outcome survey short form 36 (SF-36) pain and mental health scales, the number of fibromyalgia tender points, the health assessment questionnaire (HAQ) and "ever used" methotrexate, and explained 54.5% of the variation in mFSS scores. The SF-36 mental health scale played the largest role in the multivariate model, uniquely accounting for 6.6% of the variation in the fatigue severity scale. The disease-related factors significant at the univariate level did not achieve statistical significance in the context of HAQ and pain measures. CONCLUSION: Fatigue is a common symptom in PsA, and is associated, in a multivariate model, with pain, female sex, physical functional disability, medication status and psychological distress. Fatigue appears to provide some information that does not overlap with the core set of outcome domains in PsA.

Dynamic modelling in a study of surgical error management.

We demonstrate the use of dynamic longitudinal models to investigate error management in cardiac surgery. Case study data were collected from a multicentre study of the neonatal arterial switch operation (ASO). Information on two types of negative events, or 'errors', observed during surgery, major and minor events, was extracted from case studies. Each event was judged to be recovered from (compensated) or not (uncompensated). The aim of the study was to model compensation given the occurrence of past events within a case. Two models were developed, one for the probability of compensating for a major event and a second model for the probability of compensating for a minor event. Analyses based on dynamic logistic regression models suggest that the total number of preceding minor events, irrespective of compensation status, is negatively related with the ability to compensate for major events. The alternative use of random effects models is investigated for comparison purposes.

Clinical and radiological damage in psoriatic arthritis.

BACKGROUND: Psoriatic arthritis may progress to joint damage. Joint damage may be assessed clinically, by identifying deformed, fused, or flail joints, or radiologically, by recording erosions, joint space narrowing, ankylosis, lysis, or surgery. The relation between clinical and radiological damage is unclear. OBJECTIVE: To study the ordering of clinical and radiological damage detection, and the clinical features associated with the type of damage detected first. METHODS: The University of Toronto psoriatic arthritis database was used to relate clinical and radiological damage in the hand joints in 655 patients followed prospectively between 1978 and 2003. Generalised estimating equations were used to fit logistic regression models to identify factors that predict classification of damage by radiographic assessment first. RESULTS: The majority of the joints were not informative, as they either had evidence of damage by both methods at entry, or remained undamaged. Of the remainder, 81% of the joints showed radiological damage first and 19% had clinical damage first. Development of radiological damage first was related to previous detection of swollen joints, and was inversely related to duration of arthritis. CONCLUSIONS: Radiological damage is often detected before clinical damage is observed. Clinical inflammation often precedes the detection of radiological damage.

TNFalpha polymorphisms and risk of psoriatic arthritis.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a cytokine of critical importance in psoriatic arthritis. OBJECTIVES: (1) To examine the association between TNFalpha promoter gene polymorphisms and psoriatic arthritis in two well characterised Canadian populations with the disease; (2) to carry out a meta-analysis of all TNFalpha association studies in white psoriatic arthritis populations. METHODS: DNA samples were genotyped for five TNF variants by time of flight mass spectrometry using the Sequenom platform. All five single nucleotide polymorphisms were in the 5' flanking region of TNFalpha gene at the following positions: -1031 (T-->C), -863 (C-->A), -857 (C-->T), -308 (G-->A), and -238 (G-->A). Primary analyses were based on logistic regression. Summary estimates of disease/genotype relations from several studies were derived from random effects meta-analyses. RESULTS: 237 psoriatic arthritis subjects and 103 controls from Newfoundland and 203 psoriatic arthritis subjects and 101 controls from Toronto were studied. A combined analysis of data from both populations, showed a significant association between disease status and the -238(A) variant (p=0.01). The meta-analysis estimate for the -238(A) TNFalpha variant in eight psoriatic arthritis populations was also significant (odds ratio=2.29 (95% confidence interval, 1.48 to 3.55)). CONCLUSIONS: Analysis of TNFalpha variants in psoriatic arthritis populations shows that the -238 (A) variant is a significant risk factor for this disease.