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1.  Hepatitis C and Non-Hodgkin Lymphoma Among 4784 Cases and 6269 Controls From the International Lymphoma Epidemiology Consortium 
Background & Aims
Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkin’s lymphoma (NHL) subtypes after HCV infection.
Methods
The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded.
Results
HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40–2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44–4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68–2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14–5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65–1.60).
Conclusions
These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma).
doi:10.1016/j.cgh.2008.02.011
PMCID: PMC3962672  PMID: 18387498
2.  Are the special educational needs of children in their first year in primary school in Ireland being identified: a cross-sectional study 
BMC Pediatrics  2014;14:52.
Background
If the window of opportunity presented by the early years is missed, it becomes increasingly difficult to create a successful life-course. A biopsychosocial model of special educational need with an emphasis on participation and functioning moves the frame of reference from the clinic to the school and the focus from specific conditions to creating supportive environments cognisant of the needs of all children. However, evidence suggests that an emphasis on diagnosed conditions persists and that the needs of children who do not meet these criteria are not identified.
The Early Development Instrument (EDI) is a well-validated, teacher-completed population-level measure of five domains of child development. It is uniquely placed, at the interface between health and education, to explore the developmental status of children with additional challenges within a typically developing population. The aim of this study was to examine the extent to which the special educational needs of children in their first year of formal education have been identified.
Methods
This cross-sectional study was conducted in Ireland in 2011. EDI (teacher completed) scores were calculated for 1344 children. Data were also collected on special needs and on children identified by the teacher as needing assessment. Mean developmental scores were compared using one-way ANOVA.
Results
Eighty-three children in the sample population (6.2%) had identified special educational needs. A further 132 children were judged by the teacher as needing assessment. Children with special needs had lower mean scores than typically developing children, in all five developmental domains. Children considered by the teacher as needing assessment also had lower scores, which were not significantly different from those of children with special needs. Speech, emotional or behavioural difficulties were the most commonly reported problems among children needing further assessment. There was also a social gradient among this group.
Conclusions
A small but significant number of children have not had their needs adequately assessed. Teacher observation is an effective means of identifying children with a level of impairment which prevents them from fully participating in their educational environment and could be integrated into a multi-disciplinary approach to meeting the needs of all children.
doi:10.1186/1471-2431-14-52
PMCID: PMC3936996  PMID: 24552187
Child development; Special educational needs; Population-health; Social determinants of health; Educational needs assessment
3.  Non-Hodgkin lymphoma and Obesity: a pooled analysis from the InterLymph consortium 
Nutritional status is known to alter immune function, a suspected risk factor for non-Hodgkin lymphoma (NHL). To investigate whether long-term over, or under, nutrition is associated with NHL self-reported anthropometric data on weight and height from over 10000 cases of NHL and 16000 controls were pooled across 18 case-control studies identified through the International Lymphoma Epidemiology Consortium. Study-specific odds ratios (OR) were estimated using logistic regression and combined using a random-effects model. Severe obesity, defined as BMI of 40 kg m−2 or more, was not associated with NHL overall (pooled OR=1.00, 95% confidence interval (CI) 0.70–1.41) or the majority of NHL subtypes. An excess was however observed for diffuse large B-cell lymphoma (pooled OR=1.80, 95% CI 1.24–2.62), although not all study-specific ORs were raised. Among the overweight (BMI 25–29.9 kg m−2) and obese (BMI 30–39.9 kg m−2), associations were elevated in some studies and decreased in others, while no association was observed among the underweight (BMI<18.5 kg m−2). There was little suggestion of increasing ORs for NHL or its subtypes with every 5 kg m−2 rise in BMI above 18.5 kg m−2. BMI components height and weight were also examined, and the tallest men, but not women, were at marginally increased risk (pooled OR=1.19, 95% CI 1.06–1.34). In summary, whilst we conclude that there is no evidence to support the hypothesis that obesity is a determinant of all types of NHL combined, the association between severe obesity and diffuse large B-cell lymphoma may warrant further investigation.
doi:10.1002/ijc.23344
PMCID: PMC3928289  PMID: 18167059
non-Hodgkin lymphoma; lymphoma; body mass index; weight; height; epidemiology
4.  A functional TNFRSF5 polymorphism and risk of non-Hodgkin lymphoma, a pooled analysis 
Interaction between CD40 and its ligand, CD154, has a key function in immune regulation. Recent experimental data support a role of deregulated CD40 signalling in lymphomagenesis. Data from earlier studies that are part of this pooling study implicate a functional polymorphism (−1C>T, rs1883832) in the TNFRSF5 gene encoding CD40 in the etiology of follicular lymphoma. Here, the association of this variant with non-Hodgkin lymphoma (NHL) risk was replicated in a European multicenter study of 855 NHL cases and 1,206 controls. In the combined analysis of 2,617 cases and 3,605 controls, carrying the TT genotype was associated with an increased risk for all NHL (OR = 1.4; p for linear trend = 0.00009), diffuse large B-cell lymphoma (OR = 1.6; p for linear trend = 0.002) and follicular lymphoma (OR = 1.6; p for linear trend = 0.001). These data suggest a possible role of this functional polymorphism in lymphomas originating within the germinal center.
doi:10.1002/ijc.25420
PMCID: PMC3876741  PMID: 20473910
lymphoma; TNFRSF5; CD40; polymorphism; epidemiology
5.  Self-reported history of infections and the risk of non-Hodgkin lymphoma: an InterLymph pooled analysis 
We performed a pooled analysis of data on self-reported history of infections in relation to the risk of non-Hodgkin lymphoma (NHL) from 17 case-control studies that included 12,585 cases and 15,416 controls aged 16–96 years at recruitment. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were estimated in two-stage random-effect or joint fixed-effect models, adjusting for age, sex and study centre. Data from the two years prior to diagnosis (or date of interview for controls) were excluded. A self-reported history of infectious mononucleosis (IM) was associated with an excess risk of NHL (OR=1.26, 95% CI=1.01–1.57 based on data from 16 studies); study-specific results indicate significant (I2=51%, p=0.01) heterogeneity. A self-reported history of measles or whooping cough was associated with an approximate 15% reduction in risk. History of other infection was not associated with NHL. We find little clear evidence of an association between NHL risk and infection although the limitations of data based on self-reported medical history (particularly of childhood illness reported by older people) are well recognised.
doi:10.1002/ijc.27438
PMCID: PMC3406230  PMID: 22266776
6.  Survival Analysis of Irish Amyotrophic Lateral Sclerosis Patients Diagnosed from 1995–2010 
PLoS ONE  2013;8(9):e74733.
Introduction
The Irish ALS register is a valuable resource for examining survival factors in Irish ALS patients. Cox regression has become the default tool for survival analysis, but recently new classes of flexible parametric survival analysis tools known as Royston-Parmar models have become available.
Methods
We employed Cox proportional hazards and Royston-Parmar flexible parametric modeling to examine factors affecting survival in Irish ALS patients. We further examined the effect of choice of timescale on Cox models and the proportional hazards assumption, and extended both Cox and Royston-Parmar models with time varying components.
Results
On comparison of models we chose a Royston-Parmar proportional hazards model without time varying covariates as the best fit. Using this model we confirmed the association of known survival markers in ALS including age at diagnosis (Hazard Ratio (HR) 1.34 per 10 year increase; 95% CI 1.26–1.42), diagnostic delay (HR 0.96 per 12 weeks delay; 95% CI 0.94–0.97), Definite ALS (HR 1.47 95% CI 1.17–1.84), bulbar onset disease (HR 1.58 95% CI 1.33–1.87), riluzole use (HR 0.72 95% CI 0.61–0.85) and attendance at an ALS clinic (HR 0.74 95% CI 0.64–0.86).
Discussion
Our analysis explored the strengths and weaknesses of Cox proportional hazard and Royston-Parmar flexible parametric methods. By including time varying components we were able to gain deeper understanding of the dataset. Variation in survival between time periods appears to be due to missing data in the first time period. The use of age as timescale to account for confounding by age resolved breaches of the proportional hazards assumption, but in doing so may have obscured deficiencies in the data. Our study demonstrates the need to test for, and fully explore, breaches of the Cox proportional hazards assumption. Royston-Parmar flexible parametric modeling proved a powerful method for achieving this.
doi:10.1371/journal.pone.0074733
PMCID: PMC3786977  PMID: 24098664
7.  A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2 genes and lymphoma risk 
Owing to their role in controlling the efflux of toxic compounds, transporters are central players in the process of detoxification and elimination of xenobiotics, which in turn is related to cancer risk. Among these transporters, ATP-binding cassette B1/multidrug resistance 1 (ABCB1/MDR1), ABCC2/multidrug resistance protein 2 (MRP2), and ABCG2/breast cancer resistance protein (BCRP) affect susceptibility to many hematopoietic malignancies. The maintenance of regulated expression of these transporters is governed through the activation of intracellular “xenosensors” like the nuclear receptor 1I2/pregnane X receptor (NR1I2/PXR). SNPs in genes encoding these regulators have also been implicated in the risk of several cancers. Using a tagging approach, we tested the hypothesis that common polymorphisms in the transporter genes ABCB1, ABCC2, ABCG2, and the regulator gene NR1I2 could be implicated in lymphoma risk. We selected 68 SNPs in the 4 genes, and we genotyped them in 1,481 lymphoma cases and 1,491 controls of the European cases-control study (EpiLymph) using the Illumina™ GoldenGate assay technology.Carriers of the SNP rs6857600 minor allele in ABCG2, was associated with a decrease in risk of B-cell lymphoma (B-NHL) overall (p<0.001). Furthermore, a decreased risk of chronic lymphocytic leukemia (CLL) was associated with the ABCG2 rs2231142 variant (p=0.0004), which could be replicated in an independent population. These results suggest a role for this gene in B-NHL susceptibility, especially for CLL.
doi:10.1002/ijc.26436
PMCID: PMC3432449  PMID: 21918980
Lymphoma; multidrug resistance 1 (MDR1); multidrug resistance protein 2 (MRP2); breast cancer resistance protein (BCRP); pregnane X receptor (PXR)
8.  Determinants of vulnerability in early childhood development in Ireland: a cross-sectional study 
BMJ Open  2013;3(5):e002387.
Objectives
Early childhood development strongly influences lifelong health. The Early Development Instrument (EDI) is a well-validated population-level measure of five developmental domains (physical health and well-being, social competence, emotional maturity, language and cognitive skills, and communication skills and general knowledge) at school entry age. The aim of this study was to explore the potential of EDI as an indicator of early development in Ireland.
Design
A cross-sectional design was used.
Setting
The study was conducted in 42 of 47 primary schools in a major Irish urban centre.
Participants
EDI (teacher completed) scores were calculated for 1243 children in their first year of full-time education. Contextual data from a subset of 865 children were collected using a parental questionnaire.
Primary and secondary outcome measures
Children scoring in the lowest 10% of the population in one or more domains were deemed ‘developmentally vulnerable’. Scores were correlated with contextual data from the parental questionnaire.
Results
In the sample population, 29% of children were not developmentally ready to engage in school. Factors associated with increased risk of vulnerability were being male OR 2.1 (CI 1.6 to 2.7); under 5 years OR 1.5 (CI 1.1 to 2.1) and having English as a second language OR 3.7 (CI 2.6 to 5.2). Adjusted for these demographics, low birth weight, poor parent/child interaction and mother's lower level of education showed the most significant ORs for developmental vulnerability. Calculating population attributable fractions, the greatest population-level risk factors were being male (35%), mother's education (27%) and having English as a second language (12%).
Conclusions
The EDI and linked parental questionnaires are promising indicators of the extent, distribution and determinants of developmental vulnerability among children in their first year of primary school in Ireland.
doi:10.1136/bmjopen-2012-002387
PMCID: PMC3657679  PMID: 23674442
9.  Genome-Wide Association Study of Classical Hodgkin Lymphoma and Epstein–Barr Virus Status–Defined Subgroups 
Background
Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein–Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification.
Methods
We conducted a genome-wide association study of 1200 cHL patients and 6417 control subjects, with validation in an independent replication series, to identify common genetic variants associated with total cHL and subtypes defined by tumor EBV status. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) assuming a log-additive genetic model for the variants. All statistical tests were two-sided.
Results
Two novel loci associated with total cHL irrespective of EBV status were identified in the major histocompatibility complex region; one resides adjacent to MICB (rs2248462: OR = 0.61, 95% CI = 0.53 to 0.69, P = 1.3 × 10−13) and the other at HLA-DRA (rs2395185: OR = 0.56, 95% CI = 0.50 to 0.62, P = 8.3 × 10−25) with both results confirmed in an independent replication series. Consistent with previous reports, associations were found between EBV-positive cHL and genetic variants within the class I region (rs2734986, HLA-A: OR = 2.45, 95% CI = 2.00 to 3.00, P = 1.2 × 10−15; rs6904029, HCG9: OR = 0.46, 95% CI = 0.36 to 0.59, P = 5.5 × 10−10) and between EBV-negative cHL and rs6903608 within the class II region (rs6903608, HLA-DRA: OR = 2.08, 95% CI = 1.84 to 2.35, P = 6.1 × 10−31). The association between rs6903608 and EBV-negative cHL was confined to the nodular sclerosis histological subtype. Evidence for an association between EBV-negative cHL and rs20541 (5q31, IL13: OR = 1.53, 95% CI = 1.32 to 1.76, P = 5.4 x 10−9), a variant previously linked to psoriasis and asthma, was observed; however, the evidence for replication was less clear. Notably, one additional psoriasis-associated variant, rs27524 (5q15, ERAP1), showed evidence of an association with cHL in the genome-wide association study (OR = 1.21, 95% CI = 1.10 to 1.33, P = 1.5 × 10−4) and replication series (P = .03).
Conclusion
Overall, these results provide strong evidence that EBV status is an etiologically important classification of cHL and also suggest that some components of the pathological process are common to both EBV-positive and EBV-negative patients.
doi:10.1093/jnci/djr516
PMCID: PMC3274508  PMID: 22286212
10.  Disparities in fatal and non-fatal injuries between Irish travellers and the Irish general population are similar to those of other indigenous minorities: a cross-sectional population-based comparative study 
BMJ Open  2013;3(1):e002296.
Objectives
To assess recent disparities in fatal and non-fatal injury between travellers and the general population in Ireland.
Design
A cross-sectional population-based comparative study.
Setting
Republic of Ireland.
Participants
Population census and retrospective mortality data were collected from 7042 traveller families, travellers being those identified by themselves and others as members of the traveller community. Retrospective injury incidence was estimated from a survey of a random sample of travellers in private households, aged 15 years or over (702 men and 961 women). Comparable general population data were obtained from official statistical reports, while retrospective incidence was estimated from the Survey of Lifestyle, Attitude and Nutrition 2002, a random sample of 5992 adults in private households aged 18 years or over.
Outcome measures
Potential Years of Life Lost (PYLL), Standardised Mortality Ratios (SMR), Standardised Incidence Ratios (SIR) and Case Fatality Ratios (CFR).
Results
Injury accounted for 36% of PYLL among travellers, compared with 13% in the general population. travellers were more likely to die of unintentional injury than the general population (SMR=454 (95% CI 279 to 690) in men and 460 (95% CI 177 to 905) in women), with a similar pattern for intentional injury (SMR=637 (95% CI 367 to 993) in men and 464 (95% CI 107 to 1204 in women). They had a lower incidence of unintentional injury but those aged 65 years or over were about twice as likely to report an injury. Travellers had a higher incidence of intentional injuries (SIR=181 (95% CI 116 to 269) in men and 268 (95% CI 187 to 373) in women). Injury CFR were consistently higher among travellers.
Conclusions
Irish travellers continue to bear a disproportionate burden of injury, which calls for scaling up injury prevention efforts in this group. Prevention and further research should focus on suicide, alcohol misuse and elderly injury among Irish travellers.
doi:10.1136/bmjopen-2012-002296
PMCID: PMC3563128  PMID: 23358563
Health and safety; Health Status; Epidemiology; Public Health
11.  Multiple Myeloma and lifetime occupation: results from the EPILYMPH study 
Background
The EPILYMPH study applied a detailed occupational exposure assessment approach to a large multi-centre case–control study conducted in six European countries. This paper analysed multiple myeloma (MM) risk associated with level of education, and lifetime occupational history and occupational exposures, based on the EPILYMPH data set.
Methods
277 MM cases and four matched controls per each case were included. Controls were randomly selected, matching for age (+/− 5 years), centre and gender. Lifetime occupations and lifetime exposure to specific workplace agents was obtained through a detailed questionnaire. Local industrial hygienists assessed likelihood and intensity for specific exposures. The odds ratio and 95% confidence intervals (OR, 95% CI) were calculated for level of education, individual occupations and specific exposures. Unconditional logistic regression models were run for individual occupations and exposures.
Results
A low level of education was associated with MM OR=1.68 (95% CI 1.02-2.76). An increased risk was observed for general farmers (OR=1.77; 95% CI 1.05-2.99) and cleaning workers (OR=1.69; 95% CI 1.04-2.72) adjusting for level of education. Risk was also elevated, although not significant, for printers (OR=2.06; 95% CI 0.97-4.34). Pesticide exposure over a period of ten years or more increased MM risk (OR=1.62; 95% CI 1.01-2.58).
Conclusion
These results confirm an association of MM with farm work, and indicate its association with printing and cleaning. While prolonged exposure to pesticides seems to be a risk factor for MM, an excess risk associated with exposure to organic solvents could not be confirmed.
doi:10.1186/1745-6673-7-25
PMCID: PMC3557218  PMID: 23241100
Multiple Myeloma; Occupation; Pesticide; Epidemiology; Case–control study; EPILYMPH study
12.  Birth Order and Risk of Non-Hodgkin Lymphoma—True Association or Bias? 
American Journal of Epidemiology  2010;172(6):621-630.
There is inconsistent evidence that increasing birth order may be associated with risk of non-Hodgkin lymphoma (NHL). The authors examined the association between birth order and related variables and NHL risk in a pooled analysis (1983–2005) of 13,535 cases and 16,427 controls from 18 case-control studies within the International Lymphoma Epidemiology Consortium (InterLymph). Overall, the authors found no significant association between increasing birth order and risk of NHL (P-trend = 0.082) and significant heterogeneity. However, a significant association was present for a number of B- and T-cell NHL subtypes. There was considerable variation in the study-specific risks which was partly explained by study design and participant characteristics. In particular, a significant positive association was present in population-based studies, which had lower response rates in cases and controls, but not in hospital-based studies. A significant positive association was present in higher-socioeconomic-status (SES) participants only. Results were very similar for the related variable of sibship size. The known correlation of high birth order with low SES suggests that selection bias related to SES may be responsible for the association between birth order and NHL.
doi:10.1093/aje/kwq167
PMCID: PMC2950815  PMID: 20720098
birth order; case-control studies; lymphoma, non-Hodgkin; selection bias; social class
13.  The reliability of clinical judgments and criteria associated with mechanisms-based classifications of pain in patients with low back pain disorders: a preliminary reliability study 
Mechanisms-based classifications of pain have been advocated for their potential to aid understanding of clinical presentations of pain and improve clinical outcomes. However, the reliability of mechanisms-based classifications of pain and the clinical criteria upon which such classifications are based are not known. The purpose of this investigation was to assess the inter- and intra-examiner reliability of clinical judgments associated with: (i) mechanisms-based classifications of pain; and (ii) the identification and interpretation of individual symptoms and signs from a Delphi-derived expert consensus list of clinical criteria associated with mechanisms-based classifications of pain in patients with low back (±leg) pain disorders. The inter- and intra-examiner reliability of an examination protocol performed by two physiotherapists on two separate cohorts of 40 patients was assessed. Data were analysed using kappa and percentage of agreement values. Inter- and intra-examiner agreement associated with clinicians’ mechanisms-based classifications of low back (±leg) pain was ‘substantial’ (kappa  = 0.77; 95% confidence interval (CI): 0.57–0.96; % agreement  = 87.5) and ‘almost perfect’ (kappa  = 0.96; 95% CI: 0.92–1.00; % agreement = 92.5), respectively. Sixty-eight and 95% of items on the clinical criteria checklist demonstrated clinically acceptable (kappa ⩾ 0.61 or % agreement ⩾ 80%) inter- and intra-examiner reliability, respectively. The results of this study provide preliminary evidence supporting the reliability of clinical judgments associated with mechanisms-based classifications of pain in patients with low back (±leg) pain disorders. The reliability of mechanisms-based classifications of pain should be investigated using larger samples of patients and multiple independent examiners.
doi:10.1179/106698110X12640740712897
PMCID: PMC3101074  PMID: 21655393
Classification; Low back pain; Pain mechanisms; Reliability
14.  Tumor Necrosis Factor (TNF) and Lymphotoxin-α (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium 
American Journal of Epidemiology  2010;171(3):267-276.
In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF –308G>A (rs1800629), lymphotoxin-α (LTA) 252A>G (rs909253), IL10 –3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for “new” participant TNF –308A carriers (NHL: per-allele odds ratio (ORallelic) = 1.10, Ptrend = 0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic = 1.23, Ptrend = 0.004). In the combined population, odds ratios were increased for TNF –308A carriers (NHL: ORallelic = 1.13, Ptrend = 0.0001; DLBCL: ORallelic = 1.25, Ptrend = 3.7 × 10−6; marginal zone lymphoma: ORallelic = 1.35, Ptrend = 0.004) and LTA 252G carriers (DLBCL: ORallelic = 1.12, Ptrend = 0.006; mycosis fungoides: ORallelic = 1.44, Ptrend = 0.015). The LTA 252A>G/TNF –308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 × 10−8). Results suggested associations between IL10 –3575T>A and DLBCL (Ptrend = 0.02) and IL10 –1082A>G and mantle cell lymphoma (Ptrend = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF –308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.
doi:10.1093/aje/kwp383
PMCID: PMC2842204  PMID: 20047977
lymphoma; lymphoma, non-Hodgkin; lymphotoxin-alpha; meta-analysis; polymorphism, genetic; polymorphism, single nucleotide; tumor necrosis factor-alpha
15.  Atopic disease and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis 
Cancer research  2009;69(16):6482-6489.
We performed a pooled analysis of data on atopic disease and risk of non-Hodgkin lymphoma (NHL) from 13 case-control studies, including13,535 NHL cases and 16,388 controls. Self-reported atopic diseases diagnosed two or more years before NHL diagnosis (cases) or interview (controls) were analyzed. Pooled odds ratios (OR) and 95% confidence intervals were computed in two-stage random-effects or joint fixed-effects models, adjusted for age, sex, and study center. When modeled individually, lifetime history of asthma, hay fever, a specific allergy (excluding hay fever, asthma and eczema), and food allergy were associated with a significant reduction in NHL risk, and there was no association for eczema. When each atopic condition was included in the same model, reduced NHL risk was only associated with history of allergy (OR 0.80, 95% CI 0.68–0.94), and reduced B-cell NHL risk was associated with history of hay fever (OR 0.85, 95% CI 0.77–0.95) and allergy (OR 0.84, 95% CI 0.76–0.93). Significant reductions in B-cell NHL risk were also observed in individuals who were likely to be truly or highly atopic - those with hay fever, allergy or asthma and at least one other atopic condition over their lifetime. The inverse associations were consistent for the diffuse large B-cell and follicular subtypes. Eczema was positively associated with lymphomas of the skin; misdiagnosis of lymphoma as eczema is likely, but progression of eczema to cutaneous lymphoma cannot be excluded. This pooled study demonstrates evidence of a modest but consistent reduction in the risk of B-cell NHL associated with atopy.
doi:10.1158/0008-5472.CAN-08-4372
PMCID: PMC2758272  PMID: 19654312
non-Hodgkin lymphoma; atopy; case-control; pooled analysis; risk
16.  Persistent circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification? 
BMC Public Health  2009;9:295.
Background
Ireland is an example of a country that has extensive voluntary fortification with folic acid. After a public consultation process, in 2006, the Food Safety Authority in Ireland FSAI [1] recommended mandatory fortification. However due to safety considerations this decision is now on hold. Before mandatory fortification goes ahead, existing levels of unmetabolised folic acid and their anticipated increase after fortification needs investigation because of the potential of folic acid to mask pernicious anaemia and possibly accelerate the growth of existing cancers. The aim of this study was to examine the levels of circulatory unmetabolised folic acid in Irish adults (both fasted and un-fasted) and new-born infants (fasted) before the proposed implementation of mandatory folic acid fortification. A secondary aim was to predict the increase in circulatory unmetabolised folic acid levels after fortification.
Methods
Study 1. Setting: Irish Blood Transfusion Service (IBTS). Whole blood samples were collected from blood donors (n = 50) attending for routine blood donation sessions (representing the general population). Subjects were not fasted prior to sampling. Study 2. Setting: Coombe Women's and Infant's University Hospital, Dublin. Whole blood samples were collected by venipuncture from mothers (n = 20), and from their infant's umbilical-cords (n = 20) immediately after caesarean section. All women had been fasted for at least 8 hours prior to the surgery. A questionnaire on habitual and recent dietary intakes of folic acid was administered by an interviewer to all subjects. The data collection period was February to April 2006. Serum samples were analysed for plasma folate, plasma folic acid and red cell folate.
Results
Blood Donor Group: Circulatory unmetabolised folic acid was present in 18 out of 20 mothers (fasted) (CI: 68.3%–99.8%) comprising 1.31% of total plasma folate, 17 out of 20 babies (fasted) (CI: 62.1%–96.8%), and 49 out of 50 blood donors (unfasted) (CI: 88.0%–99.9%), comprising 2.25% of total plasma folate,
Conclusion
While the levels of circulatory unmetabolised folic acid reported are low, it is persistently present in women immediately after caesarean section who were fasting indicating that there would be a constant/habitual exposure of existing tumours to folic acid, with the potential for accelerated growth. Mandatory fortification might exacerbate this. This has implications for those with responsibility for drafting legislating in this area.
doi:10.1186/1471-2458-9-295
PMCID: PMC2734856  PMID: 19689788
17.  Multiple myeloma and farming. A systematic review of 30 years of research. Where next? 
Background
Multiple myeloma has been linked to farming for over thirty years. However, there is little clarity about the magnitude of the risk, nor about the specific agricultural exposures which contribute to the risk.
Methods
We have carried out a systematic review of case-control studies of multiple myeloma published from 1970 to October 2007. Studies were identified through database searches and from references in the literature.
Studies reporting risk estimates from farming, agricultural exposures, and exposure to animals were identified, and details abstracted. The impact of study heterogeneity, publication bias, variation in methods of case identification and exposure ascertainment between studies were considered in analysis.
Results
Case control studies showed a pooled odds ratio (OR) for working as a farmer of 1.39 95% CI 1.18 to 1.65. There was no graphic evidence of publication bias, for pesticide exposure 1.47; 95% 1.11 to 1.94, for DDT 2.19; CI 95% 1.30 to 2.95; for exposed to herbicides 1.69; 95 %CI 1.01 to 1.83. For working on a farm for more than ten years OR was 1.87; 95% CI 1.15 to 3.16.
Conclusion
Farmers seem to have increase risk for MM. However, a major limitation of this analysis is the presence of significant heterogeneity across the studies and the evidence of publication bias in some models.
A pooled analysis using individual level data could provide more power and permit the harmonization of occupational and exposure coding data.
doi:10.1186/1745-6673-3-27
PMCID: PMC2628921  PMID: 19014617
18.  Hepatitis C infection among injecting drug users in general practice: a cluster randomised controlled trial of clinical guidelines' implementation 
Background
Hepatitis C is a common infection among injecting drug users and has important implications for general practice. Although several clinical guidelines concerning the infection have been published, their effectiveness has yet to be tested.
Aim
To assess the effectiveness of a general practice-based complex intervention to support the implementation of clinical guidelines for hepatitis C management among current or former drug users attending general practice.
Design of study
Cluster randomised controlled trial.
Setting
General practices in the Eastern Regional Health Authority area of Ireland.
Method
Twenty-six practices were randomly allocated within strata to receive the intervention under study or to provide care as usual for a period of 6 months. There was screening for patients attending general practice for methadone maintenance treatment for hepatitis C and referral of anti-HCV antibody positive patients to a specialist hepatology department for assessment.
Results
At study completion, patients in the intervention group were significantly more likely to have been screened for hepatitis C than those in the control group, odds ratio adjusted for clustering 3.76 (95% confidence interval [CI] = 1.3 to 11.3) and this association remained significant after adjusting for other potentially confounding variables, using multiple logistic regression, with the odds ratio adjusted for clustering 4.53 (95% CI = 1.39 to 14.78). Although anti-HCV antibody positive patients in the intervention group were more likely to have been referred to a hepatology clinic, this was not statistically significant (P = 0.06).
Conclusion
General practice has an important role in the care of people at risk of hepatitis C and when appropriately supported can effectively implement current best practice.
PMCID: PMC1927093  PMID: 17132352
clinical trial; cluster analysis; family practice; guidelines; hepatitis C; randomised controlled trial; screening

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