Precision health approaches: ethical considerations for health data processing

This thesis provides insights and recommendations on some of the most crucial elements necessary for an effective, legally and ethically sound implementation of precision health approaches in the Swiss context (and beyond), specifically for precision medicine and precision public health. In this regard, this thesis recognizes the centrality of data in these two abovementioned domains, and the ethical and scientific imperative of ensuring the widespread and responsible sharing of high quality health data between the numerous stakeholders involved in healthcare, public health and associated research domains. It also recognizes the need to protect not only the interests of data subjects but also those of data processors. Indeed, it is only through a comprehensive assessment of the needs and expectations of each and every one regarding data sharing activities that sustainable solutions to known ethical and scientific conundrums can be devised and implemented. In addition, the included chapters in this thesis emphasize recommending solutions that could be convincingly applied to real world problems, with the ultimate objective of having a concrete impact on clinical and public health practice and policies, including research activities. Indeed, the strengths of this thesis reside in a careful and in-depth interdisciplinary assessment of the different issues at stake in precision health approaches, with the elaboration of the least disruptive solutions (as far as possible) and recommendations for an easy evaluation and subsequent adoption by relevant stakeholders active in these two domains. This thesis has three main objectives, namely (i) to investigate and identify factors influencing the processing of health data in the Swiss context and suggest some potential solutions and recommendations. A better understanding of these factors is paramount for an effective implementation of precision health approaches given their strong dependence on high quality and easily accessible health datasets; (ii) to identify and explore the ethical, legal and social issues (ELSI) of innovative participatory disease surveillance systems – also falling under precision health approaches – and how research ethics are coping within this field. In addition, this thesis aims to strengthen the ethical approaches currently used to cater for these ELSIs by providing a robust ethical framework; and lastly, (iii) to investigate how precision health approaches might not be able to achieve their social justice and health equity goals, if the impact of structural racism on these initiatives is not given due consideration. After a careful assessment, this thesis provides recommendations and potential actions that could help these precision health approaches adhere to their social justice and health equity goals. This thesis has investigated these three main objectives using both empirical and theoretical research methods. The empirical branch consists of systematic and scoping reviews, both adhering to the PRISMA guidelines, and two interview-based studies carried out with Swiss expert stakeholders. The theoretical branch consists of three chapters, each addressing important aspects concerning precision health approaches

Micronutrient Status and Telomere Length in Adult Men and Women.

Background: Telomeres are the noncoding nucleotide sequences at the end of eukaryotic chromosomes, serving to protect DNA during mitotic division. Given their guanine-rich structure, telomeres are highly susceptible to oxidative damage often mediated by inflammation. Recently, telomere attrition and dysfunction have been associated with age-related diseases, including cardiovascular disease, type 2 diabetes, Alzheimer’s disease, and certain cancers. Several modifiable risk factors have also been associated with shortened telomere length, including physical inactivity, obesity, stress, smoking, and poor diet. Objective: We examined the relations between vitamin B12 status, folate status, and iron status, relative to telomere length in eligible participants in the 1999-2002 US National Health and Nutrition Examination Survey. Design: Eligible participants had no evidence of kidney or liver disease, or pregnancy, and had complete data on outcome, exposure and covariates (n = 5,941). Low B12 status was defined as serum B12 ≤148 pmol/L or serum methylmalonic acid concentration ≥210 nmol/L. Folate status was defined as serum folate ≤13.4 nmol/L (suboptimal), and ≥45.3 nmol/L (elevated). Iron (Fe) status was defined as meeting ≥2 of the following criteria: serum ferritin ≤15 µg/L, erythrocyte protoporphyrin \u3e80 µg/dL, transferrin saturation (TS)50%, serum Fe ≥155 µg/L (women) or ≥160 µg/L (men), or serum ferritin ≥150 µg/L (women) or ≥200 µg/L (men) with no signs of inflammation. Results: After controlling for covariates including, age, race/ethnicity, sex, BMI, education level, smoking, alcohol intake, and blood glucose level, low B12 status in the presence of elevated folate status was significantly associated with a shorter mean telomere length in middle-aged adults. Elevated iron status was associated with a shorter mean telomere length in adult men and women. Conclusion: In middle-aged adults, low vitamin B12 in the presence of elevated folate status was associated with significant telomeric attrition equivalent to 27 years of additional biological aging. The shorter mean telomere length associated with an elevated iron status was equivalent to 2.6 years of additional biological aging in adult men and women. Thus, poor micronutrient status is associated with shorter mean telomere lengths in adult men and women

Alcohol Use, HIV Infection, and Antiretroviral Adherence

Alcohol use appears to negatively impact antiretroviral (ART) adherence, though conclusions about its effects are inconsistent, and the mechanisms of these effects are unclear. Accurate assessment of alcohol use is important for adherence counseling in HIV/AIDS. This secondary data analysis aimed to 1) determine if positive alcohol screening tests can predict ART adherence; 2) compare the effects of two ART adherence interventions with usual care across alcohol screening status; 3) explore mediation by self-efficacy in the relationship between adherence and several psychosocial variables; and 4) evaluate the psychometric properties and factor structure of the Alcohol Use Disorders Identification Test—Consumption (AUDIT-C). The sample included 310 HIV+ adults on ART. Over 25% of the sample was AUDIT-C positive. Through sequential multiple linear regression analyses, AUDIT-C status (but not AUDIT-3 status) significantly added to the prediction of dose adherence (p=.005) and days under-dosing (p=.021) after controlling for confounders and covariates. In repeated measures analysis to determine if alcohol use impacts the effect of the interventions on dose adherence over time, only main effects for time and alcohol screening status were significant. Adherence was significantly lower at Time 2 than at baseline, F (1, 236.287) = 25.595, p = .000, and significantly lower for AUDIT-C positive individuals than for AUDIT-C negative individuals, F (1, 340.338) = 12.304, p = .001. In path analysis, near-significant results suggest partial mediation of the relationship between adherence and conscientiousness by self-efficacy. The internal consistency and test-retest reliability of the AUDIT-C were high. Multi-sample confirmatory factor analysis revealed factor invariance for sex, but the best-fitting model for race allowed partial invariance where AUDIT-C item 3 (episodic heavy drinking) was free to vary across whites/nonwhites, X2 (3, 310) = 1.818, p = .6111. Inconsistent AUDIT-C data and missing Time 2 adherence data were significantly related to baseline opioid use. In conclusion, positive AUDIT-C status may serve as an indirect indicator for ART nonadherence. The AUDIT-C appears to reliably assess alcohol use in PWHIV, but common modifications may risk compromising validity, particularly in drug users. Further attention to the cultural equivalence of the AUDIT-C across racial groups may be warranted

Socio-economics of Personalized Medicine in Asia

The second decade of the twenty-first century has witnessed a surging interest in personalized medicine with the concomitant promise to enable more precise diagnosis and treatment of disease and illness, based upon an individual’s unique genetic makeup. In this book, my goal is to contribute to a growing body of literature on personalized medicine by tracing and analyzing how this field has blossomed in Asia. In so doing, I aim to illustrate how various social and economic forces shape the co-production of science and social order in global contexts. This book shows that there are inextricable transnational linkages between developing and developed countries and also provides a theoretically guided and empirically grounded understanding of the formation and usage of particular racial and ethnic human taxonomies in local, national and transnational settings

Identifying Clinical Phenotypes of Type 1 Diabetes for the Co-Optimization of Weight and Glycemic Control

Obesity is an increasing concern in the clinical care of youth with type 1 diabetes (T1D). Standard approaches to co-optimize weight and glycemic control are challenged by profound population-level heterogeneity. Therefore, the goal of the dissertation was to apply novel analytic methods to understand heterogeneity in the co-occurrence of weight, glycemia, and underlying patterns of minute-to-minute dysglycemia among youth with T1D. Data from the SEARCH for Diabetes in Youth study were used to characterize subgroups of youth with T1D showing similar weight status and level of glycemic control as distinct ‘weight-glycemia phenotypes’ of T1D. Cross-sectional weight-glycemia phenotypes were identified at the 5+ year follow-up visit (n=1,817) using hierarchical clustering on five measures summarizing the joint distribution of body mass index z-score (BMIz) and hemoglobin A1c (HbA1c), generated by reinforcement learning tree predictions. Longitudinal weight-glycemia phenotypes spanning eight years were identified with longitudinal k-means clustering using baseline and follow-up BMIz and HbA1c measures (n=570). Logistic regression modeling tested for differences in the emergence of early/subclinical diabetes complications across subgroups. Seven-day blinded continuous glucose monitoring (CGM) data from baseline of the Flexible Lifestyles Empowering Change randomized trial (n=234, 13-16 years, HbA1c 8-13%) was clustered with a neural network approach to identify subgroups of adolescents with T1D and elevated HbA1c sharing patterns in their CGM data as ‘dysglycemia phenotypes.’ We identified six cross-sectional weight-glycemia phenotypes, including four normal-weight, one overweight, and one subgroup with obesity. Subgroups showed striking differences in other sociodemographic and clinical characteristics suggesting underlying health inequity. We identified four longitudinal weight-glycemia phenotypes associated with different patterns of early/subclinical complications, providing evidence that exposure to co-occurring obesity and worsening glycemic control may accelerate the development and increase the burden of co-morbid complications. We identified three dysglycemia phenotypes with significantly different patterns in hypoglycemia, hyperglycemia, glycemic variability, and 18-month changes in HbA1c. Patient-level drivers of the dysglycemia phenotypes appear to be different from risk factors for poor glycemic control as measured by HbA1c. These studies provide pragmatic, clinically-relevant examples of how novel statistics may be applied to data from T1D to derive patient subgroups for tailored interventions to improve weight alongside glycemic control.Doctor of Philosoph

Infected Judgment: Legal Responses to Physician Bias

Substantial evidence indicates that clinically irrelevant patient characteristics, including race and gender, may at times influence a physician\u27s choice of treatment. Less clear, however, is whether a patient who is the victim of a biased medical decision has any effective legal recourse. Heedful of the difficulties of designing research to establish conclusively the role of physician bias, this article surveys published evidence suggesting the operation of physician bias in clinical decision making. The article then examines potential legal responses to biased medical judgments. A patient who is the subject of a biased decision may sue her doctor for violating his professional duties, including his fiduciary obligation to the patient. Courts may be unwilling, however, to expand the scope of physicians\u27 professional liability beyond existing medical malpractice law. While federal anti-discrimination laws may prohibit some instances of biased medical decisions, those laws leave many instances of physician bias unaddressed. Moreover, those laws typically would require a patient to prove that her doctor acted intentionally in discriminating, a daunting task if the physician\u27s bias is unconscious, as is probably often the case. Finally, under either a professional liability action or a civil rights suit, the patient faces the fundamental problem of proving that bias in fact infected her physician\u27s judgment. Because of these difficulties, the article concludes that existing law does not provide a ready remedy for a patient who is the victim of a biased medical decision

Patient–Provider Language Concordance and Health Outcomes: A Systematic Review, Evidence Map, and Research Agenda

Although patient–provider language concordance has the potential to reduce health disparities for people with limited English proficiency, no previous work has synthesized this literature. Our systematic review sought to describe the characteristics of studies examining relationships between language concordance and health outcomes, summarize the nature of observed associations, and propose an evidence map and research agenda. A comprehensive search of published articles identified 38 quantitative studies for inclusion. Most studies were cross-sectional, conducted in primary care, concentrated in Western states, and focused on Spanish speakers and physician providers. Results were split between supporting a positive association versus no association of language concordance with patient behaviors, provider behaviors, interpersonal processes of care, and clinical outcomes. Several methodological limitations were identified. Based on these results, we developed an evidence map, identified knowledge gaps, and proposed a research agenda. There is a particular need for quasi-experimental longitudinal studies with well-characterized samples