Modifiable risk factors and the development of psoriatic arthritis in people with psoriasis.

BACKGROUND: Psoriatic arthritis (PsA) is a progressive and often destructive joint disease affecting approximately 20% of people with psoriasis. OBJECTIVES: To investigate associations between obesity, changes in body mass index (BMI), alcohol intake and smoking status and the development of PsA in people with psoriasis. METHODS: We undertook a cohort study involving incident cases of psoriasis identified from the U.K. Clinical Practice Research Datalink between 1998 and 2014. The associations between smoking, alcohol and BMI and development of PsA were assessed using generalized additive models. Additionally, the risks associated with a change in BMI during follow-up were investigated using distributed lag nonlinear models. RESULTS: We identified 90 189 incident cases of psoriasis (42% male, mean age 51 years), of whom 1409 had a subsequent record of PsA diagnosis. BMIs of 25·0-29·9, 30·0-34·9 and ≥ 35·0 kg m-2 were significantly associated with an increased risk of developing PsA compared with BMIs < 25·0 kg m-2 : adjusted odds ratios (95% confidence intervals) 1·79 (1·46-2·19), 2·10 (1·67-2·63) and 2·68 (2·09-3·43), respectively. Reducing BMI over a 10-year period (linearly) was associated with a reduction in the risk of developing PsA compared with BMI remaining constant over the same period. Increased risks of developing PsA were associated with moderate drinking but not with former or heavy drinking or with current or past smoking status. CONCLUSIONS: In this incident psoriasis cohort, increased BMI and moderate drinking, but not heavy drinking or smoking status, were associated with an increased risk of PsA in people with psoriasis. Importantly, we have shown that reducing weight may result in a reduction in the risk of developing PsA. What's already known about this topic? There is some evidence that increased body mass index is associated with an increased risk of developing psoriatic arthritis. There are conflicting results surrounding the relationship between smoking and the development of psoriatic arthritis among patients with psoriasis. What does this study add? Using a nonlinear and lagged effect of body mass index measured over time we have shown that reducing body mass index may be associated with a reduction in the risk of developing psoriatic arthritis. We have found no evidence that smoking alters the risk of developing psoriatic arthritis in patients with psoriasis.

Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients.

OBJECTIVES: To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. METHODS: Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. RESULTS: MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2-7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p < 0.001) with cutaneous involvement. Anti-TIF1 and anti-Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti-SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti-tRNA synthetases, anti-MDA5, and anti-U1RNP/Sm. Overlap disease was strongly associated with anti-PMScl, anti-Ku, anti-U1RNP/Sm and anti-Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations. CONCLUSIONS: Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers.

Feasibility, reliability, and sensitivity to change of four radiographic scoring methods in patients with psoriatic arthritis.

OBJECTIVE: We set out to assess the feasibility, reliability, and sensitivity to change of 4 radiographic scoring methods in psoriatic arthritis (PsA). METHODS: Hand and feet radiographs from 50 patients with PsA were scored at 2 time points by 2 assessors with each of the following methods: modified Steinbrocker score, modified Sharp score (MSS), modified Sharp/van der Heijde score (SHS), and the Ratingen score for PsA. The radiographs of 10 patients were scored by both assessors to assess reliability using intraclass correlation coefficients (ICCs). Sensitivity to change was estimated using a standardized response mean (SRM) and smallest detectable change (SDC). RESULTS: The patients' mean ± SD age at baseline was 50 ± 12.1 years, the mean ± SD disease duration was 10 ± 8.4 years, and the mean ± SD followup period was 25 ± 9.6 months. Intrarater reliability was excellent for all methods (ICC >0.97). Interrater reliability was highest for the SHS (ICC 0.95-0.99). The percentage SDC for the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 2.9%, 2.1%, 1.4%, and 1.2%, respectively, and the SRMs were 0.46, 0.44, 0.77, and 0.79, respectively. The mean time to score each of the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 6.2, 10.5, 14.6, and 14.4 minutes, respectively. CONCLUSION: The SHS method was the most reliable and sensitive to change but took longer to perform. The Steinbrocker method is the most feasible but lacks the sensitivity of the SHS. The SDC of the Ratingen method is close to that of the SHS and MSS, but is quicker to perform.

Cancer incidence near municipal solid waste incinerators in Great Britain. Part 2: histopathological and case-note review of primary liver cancer cases.

We reported previously a 37% excess risk of liver cancer within 1 km of municipal incinerators. Of 119/235 (51%) cases reviewed, primary liver cancer was confirmed in 66 (55%) with 21 (18%) definite secondary cancers. The proportions of true primaries ranging between 55% and 82% (i.e. excluding secondary cancers) give revised estimates of between 0.53 and 0.78 excess cases per 10(5) per year within 1 km.

Cancer incidence and mortality around the Pan Britannica Industries pesticide factory, Waltham Abbey.

OBJECTIVES: To examine the incidence and mortality of cancer near the Pan Britannica Industries factory, Waltham Abbey, after reports of a possible cluster of all cancers and brain cancer in the vicinity. METHOD: Small area study of cancer incidence 1977-89, and mortality 1981-92, within a 7.5 km radius of the factory site. Postcoded cancer registrations and deaths in the study area were extracted from national data sets held by the Small Area Health Statistics Unit and compared with expected numbers computed by applying national rates stratified for age, sex, and deprivation to the local population (1981 and 1991 censuses). Observed/ expected (O/E) ratios were examined from 0-1 km and 0-7.5 km of the plant, and tests applied for a decline in relative risk with distance up to 7.5 km. RESULTS: There were 12,859 incidence cancers (1977-89) from 0-7.5 km (O/E ratio 1.04; 95% confidence interval (95% CI) 1.02 to 1.06) and 385 from 0-1 km (O/E 1.10; 1.00 to 1.22). There was an excess of skin melanoma from 0-1 km based on 11 cases (O/E 2.13; 1.06 to 3.80), and an excess from 0-7.5 km of cancer of the lung, stomach and pancreas combined, and prostate (O/Es ranged from 1.09 to 1.13). Only the findings from lung cancer were suggestive of a decline in risk with distance, especially in the later period (1982-9). There were 9196 cancer deaths (1981-92) from 0-7.5 km (O/E 1.04; 95% CI 1.02 to 1.06) and 308 from 0-1 km (O/E 1.24; 1.11 to 1.39); and 25507 non-cancer deaths (O/E 1.02; 1.01 to 1.04) from 0-7.5 km and 745 (O/E 1.14; 1.06 to 1.22) from 0-1 km. There was evidence of a decline in mortality with distance for all cancers combined, lung cancer (P = 0.001 for each), and colorectal cancer (P < 0.05), and also for non-cancers (P = 0.001). Proportional mortality analyses suggested a decline in risk with distance for lung cancer (P = 0.003) but not for all cancers or the site specific cancers examined. There was no evidence of an excess in the incidence or mortality from brain cancer. For cancer mortality in the inner-most wards, the findings were, for the most part, well within the range of variation across the region as a whole. CONCLUSIONS: The study provides limited and inconsistent evidence for a localised excess of cancer in the vicinity of the PBI plant. At present, further investigation does not seem warranted other than continued surveillance of mortality and cancer incidence in the locality.

Cancer incidence near radio and television transmitters in Great Britain. II. All high power transmitters.

A small area study of cancer incidence, 1974-1986, near 20 high power television (TV) and frequency modulation (FM) radio transmitters in Great Britain was carried out to place in context the findings of an earlier study around the Sutton Coldfield transmitter. The national database of postcoded cancer registrations was used with population and socioeconomic data from the 1981 census. Cancers examined were adult leukemias, skin melanoma, and bladder cancer, following the findings in the earlier study of significant declines in risk of these cancers with distance from the Sutton Coldfield transmitter. Childhood leukemia and brain cancer were also examined. Statistical analysis was performed for all transmitters combined, four overlapping groups of transmitters defined by their transmission characteristics, and for all transmitters separately. There were 3,305 adult leukemia cases from 0-10 km (observed/expected (O/E) ratio = 1.03, 95% confidence interval (CI) 1.00-1.07). A decline in risk of adult leukemia was found for all transmitters combined (p = 0.05), two of the transmitter groups, and three of the single transmitters; for all transmitters combined, observed excess risk was no more than 15% at any distance up to 10 km, and there was no observed excess within 2 km of transmitters (O/E ratio = 0.97, 95% CI 0.78-1.21). For childhood leukemia and brain cancer, and adult skin melanoma and bladder cancer, results were not indicative of a decline in risk with distance from transmitters. The magnitude and pattern of risk found in the Sutton Coldfield study did not appear to be replicated. The authors conclude that the results at most give no more than very weak support to the Sutton Coldfield findings.

Cancer incidence near radio and television transmitters in Great Britain. I. Sutton Coldfield transmitter.

A small area study of cancer incidence in 1974-1986 was carried out to investigate an unconfirmed report of a "cluster" of leukemias and lymphomas near the Sutton Coldfield television (TV) and frequency modulation (FM) radio transmitter in the West Midlands, England. The study used a national database of postcoded cancer registrations, and population and socioeconomic data from the 1981 census. Selected cancers were hematopoietic and lymphatic, brain, skin, eye, male breast, female breast, lung, colorectal, stomach, prostate, and bladder. Expected numbers of cancers in small areas were calculated by indirect standardization, with stratification for a small area socioeconomic index. The study area was defined as a 10 km radius circle around the transmitter, within which 10 bands of increasing distance from the transmitter were defined as a basis for testing for a decline in risk with distance, and an inner area was arbitrarily defined for descriptive purposes as a 2 km radius circle. The risk of adult leukemia within 2 km was 1.83 (95% confidence interval 1.22-2.74), and there was a significant decline in risk with distance from the transmitter (p = 0.001). These findings appeared to be consistent over the periods 1974-1980, 1981-1986, and were probably largely independent of the initially reported cluster, which appeared to concern mainly a later period. In the context of variability of leukemia risk across census wards in the West Midlands as a whole, the Sutton Coldfield findings were unusual. A significant decline in risk with distance was also found for skin cancer, possibly related to residual socioeconomic confounding, and for bladder cancer. Study of other radio and TV transmitters in Great Britain is required to put the present results in wider context. No causal implications can be made from a single cluster investigation of this kind.

Small-area study of the incidence of neoplasms of the brain and central nervous system among adults in the West Midlands region, 1974-86. Small Area Health Statistics Unit.

This small-area study of incidence of cancers of the brain and central nervous system found evidence of trend (P = 0.02) of cancer risk with deprivation (8% higher risk in affluent areas), but no significant association with urban-rural status. Results were not indicative of a strong geographically determined risk at small-area level.

Use of Stone's method in studies of disease risk around point sources of environmental pollution.

The Small Area Health Statistics Unit is a national facility funded by the U.K. government for the analysis of disease risk around sources of environmental pollution. It holds cancer incidence (from 1974) and mortality data (from 1981) for Great Britain. Data retrieval is based on the postcode of residence, relating on average to 14 households. Population data for the calculation of disease rates and small area measures of socioeconomic deprivation are from census small area statistics for 1981 and 1991. Isotonic regression methods first described by Stone are used to test for declines in disease risk with distance from point sources of environmental pollution. This paper describes modifications of the method to include adjustments for socioeconomic confounding, a conditional approach to allow for generally elevated risks near the source, and methods to deal with pooling of data around a number of point sources. Examples from recent studies are given.

Cancer incidence near municipal solid waste incinerators in Great Britain.

By use of the postcoded database held by the Small Area Health Statistic Unit, cancer incidence of over 14 million people living near 72 municipal solid waste incinerators in Great Britain was examined from 1974-86 (England), 1974-84 (Wales) and 1975-87 (Scotland). Numbers of observed cases were compared with expected numbers calculated from national rates (regionally adjusted) after stratification by a deprivation index based on 1981 census small area statistics. Observed-expected ratios were tested for decline in risk with distance up to 7.5 km. The study was conducted in two stages: the first involved a stratified random sample of 20 incinerators; the second the remaining 52 incinerators. Over the two stages of the study was a statistically significant (P<0.05) decline in risk with distance from incinerators for all cancers combined, stomach, colorectal, liver and lung cancer. Among these cancers in the second stage, the excess from 0 to 1 km ranged from 37% for liver cancer (0.95) excess cases 10(-5) per year to 5% for colorectal cancer. There was evidence of residual confounding near the incinerators, which seems to be a likely explanation of the finding for all cancers, stomach and lung, and also to explain at least part of the excess of liver cancer. For this reason and because of a substantial level of misdiagnosis (mainly secondary tumours) found among registrations and death certificates for liver cancer, further investigation, including histological review of the cases, is to be done to help determine whether or not there is an increase in primary liver cancer in the vicinity of incinerators.

A standardisation approach to the control of socioeconomic confounding in small area studies of environment and health.

OBJECTIVE: To assess how effectively a routine adjustment can be made for socio-economic confounding in small area studies of environment and health using indirect standardisation and small area deprivation indices, including analysis of the appropriate size of population unit on which to base the deprivation index and the importance of region and urban/rural status as axes of stratification. METHODS: Standardised morbidity ratios were calculated for cancers in Great Britain for 1981 and standardised mortality ratios for all cause mortality in Great Britain between 1982 and 1985. Deprivation indices were calculated for enumeration districts and wards from 1981 small area census statistics. Cancers and deaths were allocated to enumeration districts via their postcode. Standardised morbidity and mortality ratios were calculated by quintile of enumeration district according to the deprivation index. Standardised mortality ratios were further analysed by deprivation of ward, region, and urban/rural status. RESULTS: Strong relationships were found between all cause mortality and the incidence of selected cancers and deprivation quintile-there was up to a twofold difference in lung cancer incidence between the highest and lowest quintile. The deprivation index can be used to measure gradients of deprivation according to the distance from industrial sites. The deprivation index for enumeration districts showed similar discrimination of mortality as the index forwards. There is some interaction between deprivation and region in their effect on the standardised mortality ratios, leading to a small bias in the estimation of expected numbers if this is not taken into account. The relationship between deprivation, urban/rural status, and mortality is complex and confounded by region, but mortality tends to be higher in urban than in rural areas within quintiles of deprivation. DISCUSSION: Whether calculated for enumeration districts or wards, the main problems in the interpretation of the deprivation index may be its limited correlation with the risk factors of interest and its concentration on present rather than past socioeconomic status. Indirect standardisation based on stratification for deprivation and other variable involves a trade off between bias and precision in determining the fineness and the number of axes of stratification. Some bias may occur due to interaction between region and deprivation and the effects of urban/rural status. Complementary approaches including modeling and proportional mortality or morbidity analyses may be needed and the possibility of residual socioeconomic confounding must always be considered. CONCLUSION: There is potential for important socioeconomic confounding in small area studies of environmental pollution and health where the health outcome under examination has a strong relationship to socioeconomic status and where the putative excess risk due to pollution may be small. One method of controlling for confounding is to use an ecological measurement of deprivation in small areas, and to adjust for deprivation by indirect standardisation. However, residual socioeconomic confounding can be expected, which may seriously complicate the interpretation of small area studies.

Cancer incidence and mortality near the Baglan Bay petrochemical works, South Wales.

OBJECTIVES: To study incidence and mortality of leukaemias, cancer of the larynx, and other cancers near the petrochemical plant at Baglan Bay, in response to local concerns of an alleged cluster of cancers in the vicinity. METHODS: This is a small area study of cancer incidence, 1974-84 and of mortality, 1981-91 based on the national postcoded data held by the Small Area Health Statistics Unit and with population and socioeconomic data from the 1981 census. The study is centred on BP Chemicals Ltd, Baglan Bay, Port Talbot, West Glamorgan, South Wales and includes a general population sample of 115,721 people (1981 census) living within 7.5 km of the plant. Cancer incidence and mortality for all cancers, leukaemias, and cancer of the larynx were examined within 7.5 km and 3 km of the plant, and tests for decline in risk of these cancers with distance from the plant were carried out. Mortality from several other cancers possibly associated with the petrochemical industry was also studied. RESULTS: There were 5417 incident cancer cases and 2458 cancer deaths within 7.5 km of the plant during the periods of study. There was an 8% excess incidence of all cancers within 7.5 km, and a 24% excess of cancer of the larynx, consistent with a general excess of these cancers in West Glamorgan, but no apparent decline in incidence with distance from the plant, nor excess mortality. There was also no evidence of decline in leukaemia incidence or mortality with distance, at all ages or in children. Among the other causes included in the mortality study, there was an excess of multiple myeloma within 7.5 km, especially among women, and a significant decline in mortality from non-Hodgkin's lymphomas although there was no excess overall within 7.5 km. CONCLUSIONS: The apparent excess incidence of all cancers and cancer of the larynx within 7.5 km of the BP Chemical Ltd works was consistent with an excess more generally in West Glamorgan, possibly related, at least to some extent, to cancer registration in Wales. There was no excess mortality from these cancers. The results for multiple myeloma and especially non-Hodgkin's lymphomas may have been chance findings in view of the multiple tests of significance carried out in the study. A study of lymphatic and haematopoietic cancers near oil refineries in Great Britain is to be undertaken that will help put the findings of the present study in wider context.