Charlene McShane

Family-based associations in measures of psychological distress and quality of life in a cardiac screening clinic for inheritable cardiac diseases: a cross-sectional study

BackgroundFamily-based cardiac screening programmes for persons at risk for genetic cardiac diseases are now recommended. However, the psychological wellbeing and health related quality of life (QoL) of such screened patients is poorly understood, especially in younger patients. We sought to examine wellbeing and QoL in a representative group of adults aged 16 and over in a dedicated family cardiac screening clinic.MethodsProspective survey of consecutive consenting patients attending a cardiac screening clinic, over a 12 month period. Data were collected using two health measurement tools: the Short Form 12 (version 2) and the Hospital Anxiety and Depression Scale (HADS), along with baseline demographic and screening visit-related data. The HADS and SF-12v.2 outcomes were compared by age group. Associations with a higher HADS score were examined using logistic regression, with multi-level modelling used to account for the family-based structure of the data.ResultsThere was a study response rate of 86.6%, with n=334 patients providing valid HADS data (valid response rate 79.5%), and data on n=316 retained for analysis. One-fifth of patients were aged under 25 (n=61). Younger patients were less likely than older to describe significant depression on their HADS scale (p<0.0001), although there were overall no difference between the prevalence of a significant HADS score between the younger and older age groups (18.0% vs 20.0%, p=0.73). Significant positive associates of a higher HADS score were having lower educational attainment, being single or separated, and being closely related to the family proband. Between-family variance in anxiety and depression scores was greater than within-family variance.ConclusionsHigh levels of anxiety were seen amongst patients attending a family-based cardiac screening clinic.Younger patients also had high rates of clinically significant anxiety. Higher levels of anxiety and depression tends to run in families, and this has implications for family screening and intervention programmes.

Prior Autoimmune Disease and Risk of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma: A Systematic Review

Background: Several observational studies have investigated autoimmune disease and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Findings have been largely inconsistent and hindered by the rarity and heterogeneity of the autoimmune disorders investigated. A systematic review of the literature was undertaken to evaluate the strength of the evidence linking prior autoimmune disease and risk of MGUS/multiple myeloma. Methods: A broad search strategy using key terms for MGUS, multiple myeloma, and 50 autoimmune diseases was used to search four electronic databases (PubMed, Medline, Embase, and Web of Science) from inception through November 2011. Results: A total of 52 studies met the inclusion criteria, of which 32 were suitably comparable to perform a meta-analysis. “Any autoimmune disorder” was associated with an increased risk of both MGUS [n = 760 patients; pooled relative risk (RR) 1.42; 95% confidence interval (CI), 1.14–1.75] and multiple myeloma (n>2,530 patients; RR 1.13, 95% CI, 1.04–1.22). This risk was disease dependent with only pernicious anemia showing an increased risk of both MGUS (RR 1.67; 95% CI, 1.21–2.31) and multiple myeloma (RR 1.50; 95% CI, 1.25–1.80). Conclusions: Our findings, based on the largest number of autoimmune disorders and patients with MGUS/multiple myeloma reported to date, suggest that autoimmune diseases and/or their treatment may be important in the etiology of MGUS/multiple myeloma. The strong associations observed for pernicious anemia suggest that anemia seen in plasma cell dyscrasias may be of autoimmune origin. Impact: Underlying mechanisms of autoimmune diseases, general immune dysfunction, and/or treatment of autoimmune diseases may be important in the pathogenesis of MGUS/multiple myeloma. Cancer Epidemiol Biomarkers Prev; 23(2); 332–42. ©2014 AACR.

PTGS2 (Cyclooxygenase-2) Expression and Survival among Colorectal Cancer Patients: A Systematic Review

Background: Studies have examined whether tumor expression of PTGS2 (also known as COX-2), an enzyme inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, is associated with prognosis in patients with colorectal cancer. However, results to date have been mixed. Methods: Using terms for PTGS2 and colorectal cancer, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until December 2011. Random effects meta-analyses were used to calculate pooled HRs [95% confidence intervals (CI)] for the association between PTGS2 expression and tumor recurrence, colorectal cancer–specific survival, and overall survival. Results: In total, 29 studies, which had prognostic data on 5,648 patients, met the inclusion criteria. PTGS2-positive patients were at an increased risk of tumor recurrence (n = 9 studies; HR, 2.79; 95% CI, 1.76–4.41; P < 0.001) and had poorer colorectal cancer–specific survival (n = 7; HR, 1.36; 95% CI, 1.02–1.82; P = 0.04). However, there was funnel plot asymmetry, possibly due to publication bias, for the association with cancer-specific survival but less so for recurrence. PTGS2 expression was not associated with overall survival [(n = 16; pooled unadjusted HR, 1.30; 95% CI, 0.94–1.79; P = 0.11) and (n = 9; pooled adjusted HR, 1.02; 95% CI, 0.72–1.45; P = 0.91)]. Conclusions: PTGS2 expression was associated with an increased risk of tumor recurrence and poorer colorectal cancer–specific survival but not overall survival among patients with colorectal cancer. However, confounding by tumor characteristics such as tumor stage seems likely. Impact: There is insufficient evidence to recommend PTGS2 expression as a prognostic marker in patients with colorectal cancer. Furthermore, studies providing adjusted results are required. Cancer Epidemiol Biomarkers Prev; 22(9); 1490–7. ©2013 AACR.

Common infection-related conditions and risk of lymphoid malignancies in older individuals

Background:Chronic antigenic stimulation may initiate non-Hodgkin (NHL) and Hodgkin lymphoma (HL) development. Antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited.Methods:From the US SEER-Medicare database, 44 191 NHL, 1832 HL and 200 000 population-based controls, frequency-matched to all SEER cancer cases, were selected. Logistic regression models, adjusted for potential confounders, compared infection-related conditions in controls with HL and NHL patients and by the NHL subtypes diffuse large B-cell, T-cell, follicular and marginal zone lymphoma (MZL). Stratification by race was undertaken.Results:Respiratory tract infections were broadly associated with NHL, particularly MZL. Skin infections were associated with a 15–28% increased risk of NHL and with most NHL subtypes, particularly cellulitis with T-cell lymphoma (OR 1.36, 95%CI 1.24–1.49). Only herpes zoster remained associated with HL following Bonferroni correction (OR 1.55, 95% CI 1.28–1.87). Gastrointestinal and urinary tract infections were not strongly associated with NHL or HL. In stratified analyses by race, sinusitis, pharyngitis, bronchitis and cellulitis showed stronger associations with total NHL in blacks than whites (P<0.001).Conclusions:Infections may contribute to the aetiologic pathway and/or be markers of underlying immune modulation. Precise elucidation of these mechanisms may provide important clues for understanding how immune disturbance contributes to lymphoma.

Community-acquired infections and their association with myeloid malignancies

INTRODUCTION Antigenic stimulation is a proposed aetiologic mechanism for many haematological malignancies. Limited evidence suggests that community-acquired infections may increase the risk of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). However, associations with other myeloid malignancies including chronic myeloid leukaemia (CML) and myeloproliferative neoplasms (MPNs) are unknown. MATERIALS AND METHODS Using the Surveillance, Epidemiology and End Result (SEER)-Medicare database, fourteen community-acquired infections were compared between myeloid malignancy patients [AML (n=8489), CML (n=3626) diagnosed 1992-2005; MDS (n=3072) and MPNs (n=2001) diagnosed 2001-2005; and controls (200,000 for AML/CML and 97,681 for MDS/MPN]. Odds ratios (ORs) and 95% confidence intervals were adjusted for gender, age and year of selection excluding infections diagnosed in the 13-month period prior to selection to reduce reverse causality. RESULTS Risk of AML and MDS respectively, were significantly associated with respiratory tract infections, bronchitis (ORs 1.20 [95% CI: 1.14-1.26], 1.25 [95% CI: 1.16-1.36]), influenza (ORs 1.16 [95% CI: 1.07-1.25], 1.29 [95% CI: 1.16-1.44]), pharyngitis (ORs 1.13 [95% CI: 1.06-1.21], 1.22 [95% CI: 1.11-1.35]), pneumonia (ORs 1.28 [95% CI: 1.21-1.36], 1.52 [95% CI: 1.40-1.66]), sinusitis (ORs 1.23 [95% CI: 1.16-1.30], 1.25 [95% CI: 1.15-1.36]) as was cystitis (ORs 1.13 [95% CI: 1.07-1.18], 1.26 [95% CI: 1.17-1.36]). Cellulitis (OR 1.51 [95% CI: 1.39-1.64]), herpes zoster (OR 1.31 [95% CI: 1.14-1.50]) and gastroenteritis (OR 1.38 [95% CI: 1.17-1.64]) were more common in MDS patients than controls. For CML, associations were limited to bronchitis (OR 1.21 [95% CI: 1.12-1.31]), pneumonia (OR 1.49 [95% CI: 1.37-1.62]), sinusitis (OR 1.19 [95% CI: 1.09-1.29]) and cellulitis (OR 1.43 [95% CI: 1.32-1.55]) following Bonferroni correction. Only cellulitis (OR 1.34 [95% CI: 1.21-1.49]) remained significant in MPN patients. Many infections remained elevated when more than 6 years of preceding claims data were excluded. DISCUSSION Common community-acquired infections may be important in the malignant transformation of the myeloid lineage. Differences in the aetiology of classic MPNs and other myeloid malignancies require further exploration.

Common community‐acquired infections and subsequent risk of multiple myeloma: A population‐based study

The role of bacteria and viruses as aetiological agents in the pathogenesis of cancer has been well established for several sites, including a number of haematological malignancies. Less clear is the impact of such exposures on the subsequent development of multiple myeloma (MM). Using the population‐based U.S. Surveillance Epidemiology and End Results‐Medicare dataset, 15,318 elderly MM and 200,000 controls were identified to investigate the impact of 14 common community‐acquired infections and risk of MM. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were adjusted for sex, age and calendar year of selection. The 13‐month period prior to diagnosis/selection was excluded. Risk of MM was increased by 5–39% following Medicare claims for eight of the investigated infections. Positive associations were observed for several infections including bronchitis (adjusted OR 1.14, 95% CI 1.09–1.18), sinusitis (OR 1.15, 95% CI 1.10–1.20) pneumonia (OR 1.27, 95% CI 1.21–1.33), herpes zoster (OR 1.39, 95% CI 1.29–1.49) and cystitis (OR 1.09, 95% CI 1.05–1.14). Each of these infections remained significantly elevated following the exclusion of more than 6 years of claims data. Exposure to infectious antigens may therefore play a role in the development of MM. Alternatively, the observed associations may be a manifestation of an underlying immune disturbance present several years prior to MM diagnosis and thereby part of the natural history of disease progression.

The prevalence of viral agents in esophageal adenocarcinoma and Barrett’s esophagus: A systematic review

Background and aims Human papilloma virus (HPV), which may reach the esophagus through orogenital transmission, has been postulated to be associated with esophageal adenocarcinoma (EAC). A systematic review of the literature investigating the prevalence of infectious agents in EAC and Barrett’s esophagus (BE) was carried out. Methods Using terms for viruses and EAC, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until June 2016 that assessed the prevalence of viral agents in EAC or BE. Random-effects meta-analyses of proportions were carried out to calculate the pooled prevalence and 95% confidence intervals (CIs) of infections in EAC and BE. Results A total of 30 studies were included. The pooled prevalence of HPV in EAC tumor samples was 13% (n=19 studies, 95% CI: 2–29%) and 26% (n=6 studies, 95% CI: 3–59%) in BE samples. HPV prevalence was higher in EAC tissue than in esophageal tissue from healthy controls (n=5 studies, pooled odds ratio=3.31, 95% CI: 1.15–9.50). The prevalence of Epstein–Barr virus (EBV) in EAC was 6% (n=5, 95% CI: 0–27%). Few studies have assessed other infectious agents. For each of the analyses, considerable between-study variation was observed (I2=84–96%); however, sensitivity analyses did not show any major sources of heterogeneity. Conclusion The prevalence of HPV and EBV in EAC is low compared with other viral-associated cancers, but may have been hampered by small sample sizes and detection methods susceptible to fixation processes. Additional research with adequate sample sizes and high-quality detection methods is required.

Community-acquired infections associated with increased risk of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinaemia.

Emerging evidence supports the role of immune stimulation in the development of lymphoplasmacytic lymphoma/Waldenström Macroglobulinaemia (LPL/WM). Using the population‐based Surveillance, Epidemiology End Results‐Medicare database we investigated the exposure to 14 common community‐acquired infections and subsequent risk of LPL/WM in 693 LPL/WM cases and 200 000 controls. Respiratory tract infections, bronchitis [odds ratio (OR) 1·56], pharyngitis (OR 1·43), pneumonia (OR 1·42) and sinusitis (OR 1·33) and skin infection, herpes zoster (OR 1·51) were all significantly associated with subsequent increased risk of LPL/WM. For each of these infections, the findings remained significantly elevated following the exclusion of more than 6 years of Medicare claims data prior to LPL/WM diagnosis. Our findings may support a role for infections in the development of LPL/WM or could reflect an underlying immune disturbance that is present several years prior to diagnosis and thereby part of the natural history of disease progression.

Monoclonal gammopathy of undetermined significance (MGUS) as viewed by haematology healthcare professionals

To investigate the words and descriptions used by haematology healthcare professionals (HCPs) to describe monoclonal gammopathy of undetermined significance (MGUS) to their patients.

Risk factors for Burkitt lymphoma: a nested case-control study in the UK Clinical Practice Research Datalink

Burkitt lymphoma (BL) occurs as three subtypes: endemic BL, immunosuppression‐related BL and sporadic BL. Descriptive studies of BL age‐specific incidence patterns have suggested multimodal peaks near 10, 40 and 70 years of age, but the risk factors for BL at different ages are unknown. We investigated risk factors for BL in the United Kingdom among 156 BL cases and 608 matched BL‐free controls identified in the Clinical Practice Research Datalink (CPRD) between 1992 and 2016. Associations with pre‐diagnostic body mass index, cigarette smoking, alcohol consumption, hepatitis, Epstein–Barr virus (EBV), human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), malaria, allergic and autoimmune conditions, and prednisone use were evaluated. Overall, we identified inverse associations between smoking and BL risk, and positive associations between prior EBV infection, HIV/AIDS and prescription or use of prednisone with BL risk. In age‐group stratified analyses, BL was associated with malaria exposure (vs. no exposure, odds ratio [OR] 8·00, 95% confidence interval [CI] 1·46–43·7) among those aged 20–59 years old and with hepatitis infection (vs. no infection, OR 3·41, 95% CI 1·01–11·5) among those aged 60+ years old. The effects of EBV, malaria, HIV/AIDS, prednisone and hepatitis on BL remained significant in mutually‐adjusted age‐group‐specific analyses. No risk factors were associated with childhood BL. We report novel associations for BL in non‐endemic settings.