Citations

Objectives To summarise and synthesise published qualitative studies to characterise factors that shape patient and caregiver experiences of chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). Design Meta-review of qualitative systematic reviews and metasyntheses. Papers analysed using content analysis. Data sources CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus and Web of Science were searched from January 2000 to April 2015. Eligibility criteria for selecting studies Systematic reviews and qualitative metasyntheses where the participants were patients, caregivers and which described experiences of care for CHF, COPD and CKD in primary and secondary care who were aged ≥18 years. Results Searches identified 5420 articles, 53 of which met inclusion criteria. Reviews showed that patients' and caregivers' help seeking and decision-making were shaped by their degree of structural advantage (socioeconomic status, spatial location, health service quality); their degree of interactional advantage (cognitive advantage, affective state and interaction quality) and their degree of structural resilience (adaptation to adversity, competence in managing care and caregiver response to demands). Conclusions To the best of our knowledge, this is the first synthesis of qualitative systematic reviews in the field. An important outcome of this overview is an emphasis on what patients and caregivers value and on attributes of healthcare systems, relationships and practices that affect the distressing effects and consequences of pathophysiological deterioration in CHF, COPD and CKD. Interventions that seek to empower individual patients may have limited effectiveness for those who are most affected by the combined weight of structural, relational and practical disadvantage identified in this overview. We identify potential targets for interventions that could address these disadvantages. Systematic review registration number PROSPERO CRD42014014547.

Abstract Gene expression profiling has identified molecular subtypes that classify invasive breast cancers into distinct categories that vary in their clinical behavior and response to treatment. These subtypes highlight the many possible biologically and clinically distinct types of breast cancer. Immunohistochemical (IHC) staining of tumor sections using antibody panels has been used as a surrogate for the molecular subtypes identified through gene expression profiling, resulting in a set of intrinsic molecular subtypes. Given the heterogeneity within breast cancer, one might expect that different risk factors influence specific subtypes of breast cancer through various etiologic pathways. We evaluated whether percent mammographic density (MD), the proportion of fibroglandular or white tissue on a mammogram and one of the strongest and most consistent risk factors for breast cancer, is associated equally with all intrinsic molecular subtypes. Data were pooled from six cohort or case-control studies including 3389 women with invasive breast cancer and 9860 without, who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms (for cases, at a median 4 years prior to diagnosis) using a computer-assisted threshold technique, and categorized as 0-10%, 11-25%, 26-50% and 51%+. Receptor status was abstracted from clinical pathology records and supplemented by IHC staining of tumor sections or microarrays. With estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) information, we classified tumors into the intrinsic molecular subtypes: Luminal A ( ER+ and/or PR+ and HER2- and grade 1 or 2), Luminal B (ER+ and/or PR+ and HER2+ or Luminal A and grade 3), HER2 expressing (HER2+/ER-/PR-) and triple negative (ER-/PR-/HER2-). For cancers found to be triple negative (TN), we also stained for epidermal growth factor receptor (EGFR) and cytokeratins (CK) 5/6 to differentiate basal-like tumors (positive for EGFR and/or CK 5/6) from the unclassifieds (negative on both EGFR and CK 5/6). We used polytomous logistic regression to calculate the odds (OR) of each of the intrinsic subtypes of breast cancer by categories of percent MD, adjusting for age, BMI and study. Contrasts were constructed and tested within the polytomous model framework to investigate differences in the strength of association of percent MD across subtypes. On average, cases were slightly older (56.4 years [SD=11.3]) than controls (55.8 [10.9]). Of the 3389 invasive breast cancer cases, 2146 (63%) were classified as Luminal A, 709 (21%) as Luminal B, 169 (5%) as HER-2 expressing, and 365(11%) as triple negative (TN). Of the TN tumors, 203 had tumor tissue available and were evaluated for CK 5/6 and EGFR, with 167 (82%) classified as basal-like and 36 (18%) as unclassified. Percent (%) MD was associated with breast cancer risk across all intrinsic subtypes. For Luminal A, compared to women with 11-25% MD (reference), women with 0-10% MD had a reduced risk of breast cancer (OR=0.64 [95% confidence interval (CI): 0.55, 0.74]) while women with 26-50% MD had an OR=1.5 (1.3,1.7) and women with 51%+ MD had the highest risk, OR=2.4 (2.0, 2.8). Similar associations were seen for Luminal B, HER2 expressing, and TN across percent MD categories. The small differences among the percent MD-breast cancer associations observed for the different subtypes were not statistically significant, either when comparing the four (Luminal A, Luminal B, HER-2 expressing and TN; p=0.61) or five categories of subtypes (Luminal A, Luminal B, HER-2 expressing, basal-like, unclassified; p=0.66). Our results suggest percent MD is a risk factor for all intrinsic molecular subtypes. Additional study is needed to examine whether these results hold for younger and older aged women. Understanding the importance of mammographic density measures for subtypes of breast cancer has significance for development of subtype-specific risk models. Citation Format: Celine Vachon, Rulla Tamimi, Yunn-Yi Chen, Christopher Scott, Kimberly Bertrand, Matthew Jensen, Daniel Visscher, Aaron Norman, Fergus Couch, John Shepherd, Bo Fan, Fang-Fang Wu, Lin Ma, Andrew Beck, Steve Cummings, V. Shane Pankratz, Karla Kerlikowske. Mammographic density: A risk factor for all breast cancers or only specific subtypes? [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA22.

Abstract During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this “silent” stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

SUMMARYThis comprehensive review outlines the impact of military-relevant respiratory infections, with special attention to recruit training environments, influenza pandemics in 1918 to 1919 and 2009 to 2010, and peacetime operations and conflicts in the past 25 years. Outbreaks and epidemiologic investigations of viral and bacterial infections among high-risk groups are presented, including (i) experience by recruits at training centers, (ii) impact on advanced trainees in special settings, (iii) morbidity sustained by shipboard personnel at sea, and (iv) experience of deployed personnel. Utilizing a pathogen-by-pathogen approach, we examine (i) epidemiology, (ii) impact in terms of morbidity and operational readiness, (iii) clinical presentation and outbreak potential, (iv) diagnostic modalities, (v) treatment approaches, and (vi) vaccine and other control measures. We also outline military-specific initiatives in (i) surveillance, (ii) vaccine development and policy, (iii) novel influenza and coronavirus diagnostic test development and surveillance methods, (iv) influenza virus transmission and severity prediction modeling efforts, and (v) evaluation and implementation of nonvaccine, nonpharmacologic interventions.

Carriers of germline mutations in DNA mismatch repair (MMR) genes are at increased risk of several cancers including colorectal and gynecologic cancers (Lynch syndrome). There is no substantial evidence that these mutations are associated with an increased risk of cervical cancer. A total of 369 families with at least one carrier of a mutation in a MMR gene (133 MLH1, 174 MSH2, 35 MSH6 and 27 PMS2) were ascertained via population cancer registries or via family cancer clinics in Australia, New Zealand, Canada, and USA. Personal and family histories of cancer were obtained from participant interviews. Modified segregation analysis was used to estimate the hazard ratio (incidence rates for carriers relative to those for the general population), and age‐specific cumulative risks of cervical cancer for carriers. A total of 65 cases of cervical cancer were reported (including 10 verified by pathology reports). The estimated incidence was 5.6 fold (95% CI: 2.3–13.8; p = 0.001) higher for carriers than for the general population with a corresponding cumulative risk to 80 years of 4.5% (95% CI: 1.9–10.7%) compared with 0.8% for the general population. The mean age at diagnosis was 43.1 years (95% CI: 40.0–46.2), 3.9 years younger than the reported USA population mean of 47.0 years (p = 0.02). Women with MMR gene mutations were found to have an increased risk of cervical cancer. Due to limited pathology verification we cannot be certain that a proportion of these cases were not lower uterine segment endometrial cancers involving the endocervix, a recognized cancer of Lynch syndrome.

Abstract Purpose: The purpose of this study was to evaluate oncologists' preferences for methods to increase delivery of tobacco cessation support to cancer patients. Methods: An email list of 6844 physicians at NCI Designated Cancer Centers was generated using publically available online resources. An online survey was conducted in the fall of 2013 to assess tobacco assessment and cessation practices by physicians, barriers to providing cessation support, and methods to improve access to cessation services for cancer patients. Results of this survey are compared to similar survey findings by the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLC). Results: Of 6844 electronically delivered survey invitations, we received 887 responses (13%). Consistent with previously published ASCO and IASLC surveys, 90% of physicians agreed that tobacco use by patients affects cancer treatment outcomes (vs. 87-92% in ASCO/IASLC), 90% of respondents reported that they ask patients about their tobacco use (vs. 90% in ASCO/IASLC), and 83% routinely advise tobacco users to quit (vs. 80-82% in ASCO/IASLC). However, only 37% of respondents regularly discussed medications, and 35% actively treated patients (vs. 39-44% in ASCO/IASLC). Most (71%) responding oncologists preferred cessation support be provided at the initial patient consult, and few (11%) were concerned about the use of tobacco cessation medications. Lack of time and lack of available resources were the dominant barriers to the administration of tobacco cessation support to cancer patients by oncologists. Only 10% of oncologists believed they were adequately trained to counsel patients on smoking cessation, but 55% reported that training for someone else in their clinic would increase tobacco cessation support. When asked what provider they prefer to administer cessation support to cancer patients, 16% reported a primary care physician, 18% reported a mid-level (nurse practitioner or physician assistant), 50% reported any other clinical staff, and only 1% preferred to personally provide cessation support. Whereas most (58%) oncologists preferred to have dedicated cessation services within their institution, 38% reported they would use dedicated services either within, or outside their institution. Conclusions: Most oncologists at NCI Designated Cancer Centers recognize the importance of tobacco cessation, but prefer to have tobacco cessation support for cancer patients provided by another trained professional. Citation Format: Alix Pommerenke, Anthony Alberg, Thomas H. Brandon, Ivana Croghan, Michael K. Cummings, Carolyn Dresler, Ellen R. Gritz, Roy Herbst, Scott Leischow, James R. Marshall, Benjamin Toll, Graham Warren. Physician preferences in tobacco cessation support for cancer patients: A survey of physicians at National Cancer Institute Designated Cancer Centers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5049. doi:10.1158/1538-7445.AM2014-5049