resident Obama's Precision Medicine Initiative has refocused national attention on the ability of genomics and other emerging technologies to provide a better understanding of the relationship between genetics, environment, lifestyles, and the development of disease 1. This initiative was heralded as a "bold new research effort to revolutionize how to improve health and treat disease" 2. Yet, in 2000 the sequencing of the human genome was also anticipated to lead to new ways to personalize medicine and to prevent, diagnose, and cure disease. While there have been major advances in diagnosing and treating disease, the goals for personalized medicine to improve health and prevent disease have not yet been achieved 3-5. Despite the benefits of more targeted disease treatments, the real promise of personalized/precision medicine lies in its ability to prevent disease and improve health as, in addition to the human cost, our nation spends almost 80% of its unaffordable health care expenses on treating complex, chronic diseases which are preventable. Research in precision medicine will certainly provide new capabilities to improve health and minimize disease, but to actually do so, the approach to the practice of medicine must change so it is prepared to use them. The Limitations of Reductionism in Medicine Medical care today is derivative of concepts developed over a century ago when science began to be applied to the practice of medicine and identified the causes of many, particularly infectious, diseases. The logical assumption arose that diseases have a root cause and the role of the physician became to "find it and fix it." This concept led to a paradigm of care based on the capability of the physician to identify the disease underlying the patient's chief clinical complaint and, when possible, eliminate the cause. With improving technologies and clinical experience, this reductionist approach to care has improved and resulted in wondrous cures and treatments for many diseases. However, the concept of treating disease by removing its root cause is overly simplistic in dealing with the increasingly common chronic multifactorial diseases that develop over long periods of time. Complex chronic diseases such as obesity, type II diabetes, and cardiovascular disease are but a few examples of many conditions which account for a vast proportion of our nation's health and medical expenses. As medical practice continues to be reactive to the patient's chief complaint rather than also being proactive, care is not designed to effectively adopt new technologies to improve health or predict and prevent disease. To do this, a new approach to care is needed; one that utilizes the best of what works in the current system but is based on what we know about the evolution of disease.
recurrence (HR, 3.53 for recurrent lobar ICH vs 4.23 for recurrent nonlobar ICH).Vidale et al mention systemic diseases (including chronic kidney disease) as relevant contributors to ICH incidence and recurrence. We found no association between medical history of chronic kidney disease and ICH recurrence after adjusting for BP measurements (HR for lobar ICH, 1.35 [95% CI,; HR for nonlobar ICH, 1.29 [95% CI,). These findings may indicate lack of an independent effect of renal function abnormality on risk of ICH recurrence, once systemic pressure elevation is accounted for. We do agree, however, that chronic kidney disease and other comorbidities remain important factors to be incorporated in clinical decision making for individual patients.We agree with Vidale et al that the potential role of BP variability and circadian rhythms in determining risk of ICH recurrence is of great interest, but definitive evidence on this topic is lacking. Although additional investigation is warranted, widespread use of continuous BP monitoring to investigate the adequacy and temporal dynamics of BP control is currently not part of ICH secondary prevention guidelines, given unclear benefits in reducing risk of ICH recurrence. 4,5 Furthermore, continuous BP monitoring for all survivors of ICH (outside of dedicated randomized trials) would currently be unfeasible in all but the highest-resource settings.
In Reply Dr Karayiannis and colleagues raise 3 important points regarding our results. Adjusting for baseline aspirin use does not change the estimated treatment effect for the primary outcome (HR, 0.64; 95% CI, 0.49-0.83), nor do we observe any evidence of an interaction with intensive blood pressure control (P = .98). In terms of serious adverse events, regardless of frailty status, there were no differences in overall serious adverse events when ascertained using protocol-based standard interviews at specified intervals. However, for specific events assigned by clinicians as being possibly or definitely related to the intervention, the result in participants aged 75 years or older parallels the result from the primary SPRINT publication. In the intensive treatment group, 89 (6.8%) experienced such an event compared with 47 (3.6%) in the standard treatment group (HR, 1.93; 95% CI, 1.34-2.76). However, because treatment assignment was not blinded to clinicians and participants were also specifically warned about the possible occurrence of these conditions, intervention-related serious adverse events may have been overreported in the intensive group. Karayiannis and colleagues are also correct that this same observation is true for the frail subgroup.We agree with Dr Kim that frailty indices are currently better suited to relative comparisons within a cohort. Even though frailty indices are somewhat robust to variability in the precise composition of deficits, difficulties still arise in comparing absolute values across cohorts owing to this variability. An additional consideration is calendar time variation in the association between frailty and mortality because the National Long-Term Care Survey data cited by Kim predates SPRINT by as much as 28 years. Recent data have suggested a weakening of the association over time between frailty measured via a frailty index and mortality. 1 Although frail older participants in SPRINT certainly do not generalize to the entire population of frail older adults, the primary message remains that intensive blood pressure control provided benefit for a large segment of older adults, and the frailty index in SPRINT identified a more vulnerable subgroup likely to require more careful clinical management.Dr Dimitri and colleagues raise important questions about the potential effect of multimorbidity on our results and the effect of intensive therapy on quality of life. We acknowledge that SPRINT was not designed to be representative of the entire population of adults aged 75 years or older, and we encourage clinicians to consider the exclusion criteria in applying the results to their own patient population. Although a full presentation is not possible here, comorbidity was captured at baseline in SPRINT via self-report 2 and so can be investigated in future analyses. Several analyses are also in progress that will address the effect of intensive blood pressure control and quality of life, sexual function, and mobility.We acknowledge the interesting mechanistic hypotheses proposed...
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