Residential Environmental Exposures and other Characteristics Associated with Detectable PAH-DNA Adducts in Peripheral Mononuclear Cells in a Population-Based Sample of Adult Females

The detection of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human lymphocytes may be useful as a surrogate end point for individual cancer risk prediction. In this study, we examined the relationship between environmental sources of residential PAH, as well as other potential factors that may confound their association with cancer risk, and the detection of PAH-DNA adducts in a large population-based sample of adult women. Adult female residents of Long Island, New York, aged at least 20 years were identified from the general population between August 1996 and July 1997. Among 1556 women who completed a structured questionnaire, 941 donated sufficient blood (25+ ml) to allow use of a competitive ELISA for measurement of PAH-DNA adducts in peripheral blood mononuclear cells. Ambient PAH exposure at the current residence was estimated using geographic modeling (n=796). Environmental home samples of dust (n=356) and soil (n=360) were collected on a random subset of long-term residents (15+ years). Multivariable regression was conducted to obtain the best-fitting predictive models. Three separate models were constructed based on data from : (A) the questionnaire, including a dietary history; (B) environmental home samples; and (C) geographic modeling. Women who donated blood in summer and fall had increased odds of detectable PAH-DNA adducts (OR=2.65, 95% confidence interval (CI)=1.69, 4.17; OR=1.59, 95% CI=1.08, 2.32, respectively), as did current and past smokers (OR=1.50, 95% CI=1.00, 2.24; OR=1.46, 95% CI=1.05, 2.02, respectively). There were inconsistent associations between detectable PAH-DNA adducts and other known sources of residential PAH, such as grilled and smoked foods, or a summary measure of total dietary benzo-[a]-pyrene (BaP) intake during the year prior to the interview. Detectable PAH-DNA adducts were inversely associated with increased BaP levels in dust in the home, but positively associated with BaP levels in soil outside of the home, although CIs were wide. Ambient BaP estimates from the geographic model were not associated with detectable PAH-DNA adducts. These data suggest that PAH-DNA adducts detected in a population-based sample of adult women with ambient exposure levels reflect some key residential PAH exposure sources assessed in this study, such as cigarette smoking

Patient engagement in designing, conducting, and disseminating clinical pain research : IMMPACT recommended considerations

The consensus recommendations are based on the views of IMMPACT meeting participants and do not necessarily represent the views of the organizations with which the authors are affiliated. The following individuals made important contributions to the IMMPACT meeting but were not able to participate in the preparation of this article: David Atkins, MD (Department of Veterans Affairs), Rebecca Baker, PhD (National Institutes of Health), Allan Basbaum, PhD (University of California San Francisco), Robyn Bent, RN, MS (Food and Drug Administration), Nathalie Bere, MPH (European Medicines Agency), Alysha Croker, PhD (Health Canada), Stephen Bruehl, PhD (Vanderbilt University), Michael Cobas Meyer, MD, MBS (Eli Lilly), Scott Evans, PhD (George Washington University), Gail Graham (University of Maryland), Jennifer Haythornthwaite, PhD (Johns Hopkins University), Sharon Hertz, MD (Hertz and Fields Consulting), Jonathan Jackson, PhD (Harvard Medical School), Mark Jensen, PhD (University of Washington), Francis Keefe, PhD (Duke University), Karim Khan, MD, PhD, MBA (Canadian Institutes of Health Research), Lynn Laidlaw (University of Aberdeen), Steven Lane (Patient-Centered Outcomes Research Institute), Karen Morales, BS (University of Maryland), David Leventhal, MBA (Pfizer), Jeremy Taylor, OBE (National Institute for Health Research), and Lena Sun, MD (Columbia University). The manuscript has not been submitted, presented, or published elsewhere. Parts of the manuscript have been presented in a topical workshop at IASP World Congress on Pain in Toronto, in 2022.Peer reviewedPublisher PD

A simple measure with complex determinants: investigation of the correlates of self-rated health in older men and women from three continents

Self-rated health is commonly employed in research studies that seek to assess the health status of older individuals. Perceptions of health are, however, influenced by individual and societal level factors that may differ within and between countries. This study investigates levels of self-rated health (SRH) and correlates of SRH among older adults in Australia, United States of America (USA), Japan and South Korea. We conclude that when examining correlates of SRH, the similarities are greater than the differences between countries. There are however differences in levels of SRH which are not fully accounted for by the health correlates. Broad generalizations about styles of responding are not helpful for understanding these differences, which appear to be country- and possibly cohort-specific. When using SRH to characterize the health status of older people, it is important to consider earlier life experiences of cohorts as well as national and individual factors in later life. Further research is required to understand the complex societal influences on perceptions of health.The Australian data on which this research is based were drawn from several Australian longitudinal studies including: the Australian Longitudinal Study of Ageing (ALSA), the Australian Longitudinal Study of Women’s Health (ALSWH) and the Personality And Total Health Through Life Study (PATH). These studies were pooled and harmonized for the Dynamic Analyses to Optimize Ageing (DYNOPTA) project. DYNOPTA was funded by a National Health and Medical Research Council (NHMRC) grant (# 410215)

Selenium and Lung Cancer: A Systematic Review and Meta Analysis

Selenium is a natural health product widely used in the treatment and prevention of lung cancers, but large chemoprevention trials have yielded conflicting results. We conducted a systematic review of selenium for lung cancers, and assessed potential interactions with conventional therapies.Two independent reviewers searched six databases from inception to March 2009 for evidence pertaining to the safety and efficacy of selenium for lung cancers. Pubmed and EMBASE were searched to October 2009 for evidence on interactions with chemo- or radiation-therapy. In the efficacy analysis there were nine reports of five RCTs and two biomarker-based studies, 29 reports of 26 observational studies, and 41 preclinical studies. Fifteen human studies, one case report, and 36 preclinical studies were included in the interactions analysis. Based on available evidence, there appears to be a different chemopreventive effect dependent on baseline selenium status, such that selenium supplementation may reduce risk of lung cancers in populations with lower baseline selenium status (serum<106 ng/mL), but increase risk of lung cancers in those with higher selenium (≥ 121.6 ng/mL). Pooling data from two trials yielded no impact to odds of lung cancer, OR 0.93 (95% confidence interval 0.61-1.43); other cancers that were the primary endpoints of these trials, OR 1.51 (95%CI 0.70-3.24); and all-cause-death, OR 0.93 (95%CI 0.79-1.10). In the treatment of lung cancers, selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy.Selenium may be effective for lung cancer prevention among individuals with lower selenium status, but at present should not be used as a general strategy for lung cancer prevention. Although promising, more evidence on the ability of selenium to reduce cisplatin and radiation therapy toxicity is required to ensure that therapeutic efficacy is maintained before any broad clinical recommendations can be made in this context

A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>The relationship between <it>Helicobacter pylori </it>infection and pancreatic cancer has been investigated in three previous studies with contradictory results. The aim of the present study was to investigate the association between <it>H. pylori </it>seropositivity and the risk for pancreatic cancer in a nested case-control study within a population based cohort.</p> <p>Methods</p> <p>Selected birth-year cohorts (born 1921–1949) of residents in Malmö, Sweden, were invited to a health screening investigation. A total of 33 346 subjects participated. Cases with pancreatic cancer (n = 87) were matched to controls (n = 263) using age, sex and time for baseline investigation as matching variables. <it>H. pylori </it>serology was analysed in stored serum samples using an enzyme-linked immunosorbent assay. Odds ratios (OR) for pancreatic cancer were calculated with 95% confidence intervals (CI) using logistic regression.</p> <p>Results</p> <p><it>H. pylori </it>seropositivity was not associated with pancreatic cancer in the total cohort (adjusted OR 1.25 (0.75–2.09)). However, a statistically significant association was found in never smokers (OR 3.81 (1.06–13.63) adjusted for alcohol consumption) and a borderline statistically significant association was found in subjects with low alcohol consumption (OR 2.13 (0.97–4.69) adjusted for smoking).</p> <p>Conclusion</p> <p>We conclude that no association between <it>H. pylori </it>infection and the risk for pancreatic cancer was found in the total cohort. However, in never smokers and in subjects with low risk alcohol consumption, a positive <it>H. pylori </it>serology was associated with an increased risk for pancreatic cancer. These findings should be interpreted cautiously due to the limited number of cases in these subgroups.</p

Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement

Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care. This article summarizes methodological considerations for pragmatic trials, mainly concerning methods of fundamental importance to the internal validity of trials. The relationship between these methods and common pragmatic trials methods and goals is considered, recognizing that the resulting trial designs are highly dependent on the specific research question under investigation. The basis of this statement was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) systematic review of methods and a consensus meeting. The meeting was organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership. The consensus process was informed by expert presentations, panel and consensus discussions, and a preparatory systematic review. In the context of pragmatic trials of pain treatments, we present fundamental considerations for the planning phase of pragmatic trials, including the specification of trial objectives, the selection of adequate designs, and methods to enhance internal validity while maintaining the ability to answer pragmatic research questions

The prevalence of psychiatric and chronic pain comorbidities in fibromyalgia: An acttion systematic review

Fibromyalgia (FM) is a chronic widespread pain condition that overlaps with multiple comorbid health conditions and contributes to considerable patient distress. The aim of this review was to provide a systematic overview of psychiatric and chronic pain comorbidities among patients diagnosed with FM and to inform the development of recommendations for the design of clinical trials. Thirty-one, cross-sectional, clinical epidemiology studies that evaluated patients diagnosed with FM were included for review. None of the reviewed studies reported on the incidence of these comorbidities. Sample size-weighted prevalence estimates were calculated when prevalence data were reported in 2 or more studies for the same comorbid condition. The most prevalent comorbidity across all studies reviewed was depression/major depressive disorder (MDD) with over half of the patients included having this diagnosis in their lifetime (weighted prevalence up to 63%). In addition, nearly one-third of FM patients examined had current or lifetime bipolar disorder, panic disorder, or post-traumatic stress disorder. Less common psychiatric disorders reported included generalized anxiety disorder, obsessive compulsive disorder, and specific phobias (agoraphobia, social phobia). There were fewer studies that examined chronic pain comorbidities among FM patients, but when evaluated, prevalence was also high ranging from 39% to 76% (i.e., chronic tension-type or migraine headache, irritable bowel syndrome, myofascial pain syndrome, and temporomandibular disorders). The results of the review suggest that depression and chronic pain conditions involving head/jaw pain and IBS were elevated among FM patients compared to other conditions in the clinic-based studies. In contrast, anxiety-related disorders were much less common. Addressing the presence of these comorbid health conditions in clinical trials of treatments for FM would increase the generalizability and real-world applicability of FM research