Implementing universal Lynch syndrome screening (IMPULSS): protocol for a multi-site study to identify strategies to implement, adapt, and sustain genomic medicine programs in different organizational contexts

BACKGROUND: Systematic screening of all colorectal tumors for Lynch Syndrome (LS) has been recommended since 2009. Currently, implementation of LS screening in healthcare systems remains variable, likely because LS screening involves the complex coordination of multiple departments and individuals across the healthcare system. Our specific aims are to (1) describe variation in LS screening implementation across multiple healthcare systems; (2) identify conditions associated with both practice variation and optimal implementation; (3) determine the relative effectiveness, efficiency, and costs of different LS screening protocols by healthcare system; and (4) develop and test in a real-world setting an organizational toolkit for LS screening program implementation and improvement. This toolkit will promote effective implementation of LS screening in various complex health systems. METHODS: This study includes eight healthcare systems with 22 clinical sites at varied stages of implementing LS screening programs. Guided by the Consolidated Framework for Implementation Research (CFIR), we will conduct in-depth semi-structured interviews with patients and organizational stakeholders and perform economic evaluation of site-specific implementation costs. These processes will result in a comprehensive cross-case analysis of different organizational contexts. We will utilize qualitative data analysis and configurational comparative methodology to identify facilitators and barriers at the organizational level that are minimally sufficient and necessary for optimal LS screening implementation. DISCUSSION: The overarching goal of this project is to combine our data with theories and tools from implementation science to create an organizational toolkit to facilitate implementation of LS screening in various real-world settings. Our organizational toolkit will account for issues of complex coordination of care involving multiple stakeholders to enhance implementation, sustainability, and ongoing improvement of evidence-based LS screening programs. Successful implementation of such programs will ultimately reduce suffering of patients and their family members from preventable cancers, decrease waste in healthcare system costs, and inform strategies to facilitate the promise of precision medicine. TRIAL REGISTRATION: N/A

Clinical Molecular Marker Testing Data Capture to Promote Precision Medicine Research Within the Cancer Research Network

PURPOSE: To evaluate health care systems for the availability of population-level data on the frequency of use and results of clinical molecular marker tests to inform precision cancer care. METHODS: We assessed cancer-related molecular marker test data availability across 12 US health care systems in the Cancer Research Network. Overall, these systems provide care to a diverse population of more than 12 million people in the United States. We performed qualitative analyses of test data availability for five blood-based protein, nine germline, and 14 tissue-based tumor marker tests in each health care system\u27s electronic health record and tumor registry using key informants, test code lists, and manual review of data types and output. We then performed quantitative analyses to estimate the proportion of patients with cancer with test utilization data and results for specific molecular marker tests. RESULTS: Health systems were able to systematically capture population-level data on all five blood protein markers, six of 14 tissue-based tumor markers, and none of the nine germline markers. Successful, systematic data capture was achievable for tests with electronic data feeds for test results (blood protein markers) or through prior manual abstraction by tumor registrars (select tumor-based markers). For test results stored in scanned image files (particularly germline and tumor marker tests), information on which test was performed and test results was not readily accessible in an electronic format. CONCLUSION: Even in health care systems with sophisticated electronic health records, there were few codified data elements available for evaluating precision cancer medicine test use and results at the population level. Health care organizations should establish standards for electronic reporting of precision medicine tests to expedite cancer research and facilitate the implementation of precision medicine approaches

Trends in Cause of Death among Puerto Rican and United States Multiple Myeloma Patients

Background/Objective: Multiple myeloma (MM) is an incurable, yet treatable, cancer of plasma cells. Due to recent improvements in treatment, people diagnosed with MM have been living longer, and other co-morbid conditions may be of increasing importance. This study examines temporal trends in specific causes of death among MM patients in Puerto Rico (PR) and United States (US). Methods: We analyzed primary cause of death among all incident MM cancer cases recorded in the Puerto Rico Central Cancer Registry (PRCCR) (n=3,018) and the US Surveillance, Epidemiology, and End Results Program (SEER) (n=67,733) between 1987-2013, overall and by follow-up time, age, and sex. We calculated the cumulative incidence of death due to seven selected causes and analyzed age-adjusted mortality trends by MM and other causes using joinpoint regression. Results: MM accounted for 71.7% and 71.3% of all reported deaths in PR and US, respectively, among people diagnosed with MM. In PR, the proportion of patients that died from MM decreased with increasing follow-up time since diagnosis (72.3% of deaths with ≤2 years vs 65.6% with \u3e5 years of follow-up) and the proportion of patients who died from circulatory (4.6% vs 9.0%) and respiratory system (3.7% vs 5.0%) diseases increased slightly. A similar trend of decreasing MM deaths with follow-up time was observed in the US (73.2% of deaths with ≤2 years vs 66.5% with \u3e5 years of follow-up). Joinpoint regression showed a decreasing trend in MM mortality in the US (APC1987-2007=-2.8%, and APC2007-2013=-18.4%) and a similar, though somewhat weaker, trend in PR (APC1987-2013=-2.73). Conclusion: In both PR and the US, people diagnosed with MM are still more likely to die from MM than from another cause. However, a decrease in MM mortality is evident, particularly in more recent years, but this decrease is lower in Puerto Rico

The impact of changing guidelines on prostate cancer screening in a population-based setting, 2000-2014

Introduction: This study evaluates the potential impact of the publication of conflicting prostate cancer (PCa) screening trial results in 2009 and changes to the US Preventive Services Task Force (USPSTF) guidelines to recommend against screening in 2012 on temporal trends in PSA testing at two participating sites in the NCI-funded Cancer Research Network. Methods: Study participants were men aged 40-80 without a history of PCa who sought care at Fallon Health (Worcester, MA) or Henry Ford Health System (Detroit, MI) between 2000-2014. We used health claims and electronic health record data to identify men who underwent PSA testing per calendar year. We also examined trends in PSA testing among high-risk men (African-American, family history of PCa). Testing rates were compared between 2000-2008, 2009-2012, and 2013-2014. Results: From a population of 279,350 eligible men, 133,038 (48%) had at least one PSA test during the study period. Mean age at PSA test was 57 years, which increased over time at both sites. Overall, PSA testing rates rose between 2000-2008 (27-32% of eligible men per year), but declined between 2009-2012 (25% of eligible men). Testing rates declined further in 2013-2014 (23% of eligible men). We observed similar rates of decline in testing for men aged 55-69 and those aged ≥70. High-risk men were less likely to be screened across all time periods, although data was limited. Conclusions: This analysis of two population-based electronic health datasets provides evidence of a recent decrease in PSA testing, following an increase in the early 2000s. Although we are unable to determine causality, it is plausible that results of recent screening trials and/or changes to the USPSTF guidelines have impacted PSA testing practices over the past 14 years

The All of Us Research Program: Engaging the Community for the Future of Health

The All of Us Research Program (AoURP), funded by the National Institutes of Health, is an ambitious ten-year effort to enroll over one million participants across the country. The AoURP is a key part of the Precision Medicine Initiative and seeks to build a national cohort collecting self-reported health data, medical record data, biospecimen samples and physical measurements to accelerate precision medicine. Precision Medicine is an emerging approach for healthcare treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Researchers at the Meyers Primary Care Institute and the University of Massachusetts Medical School have partnered with Reliant Medical Group to enroll over 10,000 participants in 5 years. The Meyers/Reliant team is actively working to engage the local community, educational institutions, and community organizations to increase awareness of the program and encourage participation. Our efforts have focused specifically on populations previously underrepresented in biomedical research, including older adults, racial and ethnic minority group members, and others. We are hoping to grow new relationships and build strong community partnerships to help us achieve our enrollment goals and communicate the great potential of the AoU Research Program to change the future of medical research with a focus on precision medicine

Predicting the 10-year risk of death from other causes in men with localized prostate cancer using patient-reported factors: Development of a tool

OBJECTIVE: To develop a tool for estimating the 10-year risk of death from other causes in men with localized prostate cancer. SUBJECTS AND METHODS: We identified 2,425 patients from the Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey database, age \u3c 80, newly diagnosed with clinical stage T1-T3a prostate cancer from 1/1/1998-12/31/2009, with follow-up through 2/28/2013. We developed a Fine and Gray competing-risks model for 10-year other cause mortality considering age, patient-reported comorbid medical conditions, component scores and items of the SF-36 Health Survey, activities of daily living, and sociodemographic characteristics. Model discrimination and calibration were compared to predictions from Social Security life table mortality risk estimates. RESULTS: Over a median follow-up of 7.7 years, 76 men died of prostate-specific causes and 465 died of other causes. The strongest predictors of 10-year other cause mortality risk included increasing age at diagnosis, higher approximated Charlson Comorbidity Index score, worse patient-reported general health (fair or poor vs. excellent-good), smoking at diagnosis, and marital status (all other vs. married) (all p \u3c 0.05). Model discrimination improved over Social Security life tables (c-index of 0.70 vs. 0.59, respectively). Predictions were more accurate than predictions from the Social Security life tables, which overestimated risk in our population. CONCLUSIONS: We provide a tool for estimating the 10-year risk of dying from other causes when making decisions about treating prostate cancer using pre-treatment patient-reported characteristics

A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non-Hodgkin lymphoma

Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses\u27 Health Study (NHS) and Health Professionals Follow-up Study (HPFS). RBC membrane fatty acid levels were measured using gas chromatography. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL and major NHL subtypes including T cell NHL (T-NHL), B cell NHL (B-NHL) and three individual B-NHLs: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. RBC SFA and MUFA levels were not associated with NHL risk overall. However, RBC very long chain SFA levels (VLCSFA; 20:0, 22:0, 23:0) were inversely associated with B-NHLs other than CLL/SLL; ORs (95% CIs) per standard deviation (SD) increase in level were 0.81 (0.70, 0.95) for 20:0, 0.82 (0.70, 0.95) for 22:0, and 0.82 (0.70, 0.96) for 23:0 VLCSFA. Also, both VLCSFA and MUFA levels were inversely associated with T-NHL [ORs (95% CIs) per SD: VLCSFA, 0.63 (0.40, 0.99); MUFA, 0.63 (0.40, 0.99)]. The findings of inverse associations for VLCSFAs with B-NHLs other than CLL/SLL and for VLCSFA and MUFA with T-NHL suggest an influence of fatty acid metabolism on lymphomagenesis

Pre-diagnosis plasma immune markers and risk of non-Hodgkin lymphoma in two prospective cohort studies

Inflammation and B-cell hyperactivation have been associated with non-Hodgkin lymphoma development. This prospective analysis aimed to further elucidate pre-diagnosis plasma immune marker profiles associated with non-Hodgkin lymphoma risk. We identified 598 incident lymphoma cases and 601 matched controls in Nurses\u27 Health Study and Health Professionals Follow-up Study participants with archived pre-diagnosis plasma samples and measured 13 immune marker levels with multiplexed immunoassays. Using multivariable logistic regression we calculated odds ratios and 95% confidence intervals per standard deviation unit increase in biomarker concentration for risk of non-Hodgkin lymphoma and major histologic subtype, stratifying additional models by years ( \u3c 5, 5 to \u3c 10, \u3e /=10) after blood draw. Soluble interleukin-2 receptor-alpha, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lymphoma and one or more subtypes. The biomarker combinations associated independently with lymphoma varied somewhat by subtype and years after blood draw. Of note, the unexpected inverse association between B-cell activating factor and chronic lymphocytic leukemia/small lymphocytic lymphoma risk (odds ratio: 95% confidence interval: 0.51, 0.43-0.62) persisted more than 10 years after blood draw (odds ratio: 0.70; 95% confidence interval: 0.52-0.93). In conclusion, immune activation precedes non-Hodgkin lymphoma diagnosis by several years. Decreased B-cell activating factor levels may denote nascent chronic lymphocytic leukemia many years pre-diagnosis

The Democratic Biopolitics of PrEP

PrEP (Pre-Exposure Prophylaxis) is a relatively new drug-based HIV prevention technique and an important means to lower the HIV risk of gay men who are especially vulnerable to HIV. From the perspective of biopolitics, PrEP inscribes itself in a larger trend of medicalization and the rise of pharmapower. This article reconstructs and evaluates contemporary literature on biopolitical theory as it applies to PrEP, by bringing it in a dialogue with a mapping of the political debate on PrEP. As PrEP changes sexual norms and subjectification, for example condom use and its meaning for gay subjectivity, it is highly contested. The article shows that the debate on PrEP can be best described with the concepts ‘sexual-somatic ethics’ and ‘democratic biopolitics’, which I develop based on the biopolitical approach of Nikolas Rose and Paul Rabinow. In contrast, interpretations of PrEP which are following governmentality studies or Italian Theory amount to either farfetched or trivial positions on PrEP, when seen in light of the political debate. Furthermore, the article is a contribution to the scholarship on gay subjectivity, highlighting how homophobia and homonormativity haunts gay sex even in liberal environments, and how PrEP can serve as an entry point for the destigmatization of gay sexuality and transformation of gay subjectivity. ‘Biopolitical democratization’ entails making explicit how medical technology and health care relates to sexual subjectification and ethics, to strengthen the voice of (potential) PrEP users in health politics, and to renegotiate the profit and power of Big Pharma

Development of a new version of the Liverpool Malaria Model. II. Calibration and validation for West Africa

<p>Abstract</p> <p>Background</p> <p>In the first part of this study, an extensive literature survey led to the construction of a new version of the <it>Liverpool Malaria Model </it>(LMM). A new set of parameter settings was provided and a new development of the mathematical formulation of important processes related to the vector population was performed within the LMM. In this part of the study, so far undetermined model parameters are calibrated through the use of data from field studies. The latter are also used to validate the new LMM version, which is furthermore compared against the original LMM version.</p> <p>Methods</p> <p>For the calibration and validation of the LMM, numerous entomological and parasitological field observations were gathered for West Africa. Continuous and quality-controlled temperature and precipitation time series were constructed using intermittent raw data from 34 weather stations across West Africa. The meteorological time series served as the LMM data input. The skill of LMM simulations was tested for 830 different sets of parameter settings of the undetermined LMM parameters. The model version with the highest skill score in terms of entomological malaria variables was taken as the final setting of the new LMM version.</p> <p>Results</p> <p>Validation of the new LMM version in West Africa revealed that the simulations compare well with entomological field observations. The new version reproduces realistic transmission rates and simulated malaria seasons are comparable to field observations. Overall the new model version performs much better than the original model. The new model version enables the detection of the epidemic malaria potential at fringes of endemic areas and, more importantly, it is now applicable to the vast area of malaria endemicity in the humid African tropics.</p> <p>Conclusions</p> <p>A review of entomological and parasitological data from West Africa enabled the construction of a new LMM version. This model version represents a significant step forward in the modelling of a weather-driven malaria transmission cycle. The LMM is now more suitable for the use in malaria early warning systems as well as for malaria projections based on climate change scenarios, both in epidemic and endemic malaria areas.</p