What Will Healthcare Look Like in 20 Years?

Transcription

1 What Will Healthcare Look Like in 20 Years? Laurie Scudder, DNP, NP; Lauri R. Graham December 20, 2015 Image from Dreamstime

2 Looking Into Our Collective Crystal Ball As we conclude our celebration and examination of the first 20 years at Medscape, we wondered what we'd be talking about in another 20 years. So we asked our readers and our panel of experts and advisors to tell us the realistic, coming-to-a-patient-near-you advances that they predict will be an everyday part of our armamentarium in Here is what you and they told us. The Microbiome: Beyond the Gut Understanding of the world beneath the seething, teeming microbial world that inhabits every orifice and surface of the body has led to a whole new paradigm in the prevention and treatment of a range of diseases. Studies examining the gut microbiome led to an explosion of research that linked disruptions in the microbiota to conditions from atopy to cardiovascular disease. David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, predicts that over the next 20 years, the "gut microbiome effect on health and disease will become clearer. Identification of microbial dysbiosis and directed efforts to restore more normative equilibrium in microflora will transform our current approach to disease management for gastrointestinal disease and beyond." The Microbiome/Inflammation/Infection Link Back in the day pre-2000 a patient with a cough was categorized as having an infectious process or an inflammatory (ie, allergic) process. No longer. Disruptions in the microbiome are now recognized to play a pivotal role in the development of acute and chronic processes. The "microbiota hypothesis"[1] proposes that alterations in the microbiome disrupt host homeostasis and, therefore, affect disease risk in myriad ways, with manifestations ranging from alterations in immunity to changes in metabolism. Recognizing, and learning to minimize, the many factors that can disrupt the microbiome will continue to be a focus of research. Antibiotics may be the best known of these disruptors, but numerous other environmental factors, including changes in population density, proximity to animals, pollution, and diet, are all now known to effect the transmission and maintenance of indigenous microbiota.

3 A Medscape reader predicted that the next two decades would bring a better "understanding of how and why microbes cause chronic inflammatory disease." Hand in hand with this improved understanding of the microbiome and its important role in maintaining health will be increased therapeutic use of bacteriophages, already widely used in agriculture,[1] that only minimally disrupt normal flora[2] in order to treat infections caused by resistant organisms. The Microbiome/Chronic Disease Link It is recognized that microbiota composition is altered in patients with various chronic inflammatory conditions. In addition to gastrointestinal conditions, such as Crohn disease,[3] ulcerative colitis,[4] and irritable bowel syndrome,[5] dysbiosis, or microbial imbalance, has been associated with psoriasis,[6] both type 1[7] and type 2[8] diabetes, and cardiovascular disease.[9] Dr Johnson commented that the emerging evidence strongly suggests that changes in the gut microbiota play a pivotal role in the regulation of energy homeostasis and the development and progression of obesity and its associated metabolic disorders. Myron Genel, MD, professor emeritus of pediatrics and senior research scientist at Yale Child Health Research Center, speculated that potential therapeutic interventions would be developed "on the basis of a better understanding of the pathophysiologic implications of microflora in body cavities." Dr Johnson added that although it appears that manipulation of the gut flora may be an avenue for potential new targeted therapies, further studies are necessary before introducing them into standard clinical practice. The hope is that this enhanced understanding will finally begin to yield results that will improve the management of chronic disorders, autoimmune disease, allergy, and even dental disease in the decades to come. The Microbiome/Environment Link It is now well-known that microbial equilibrium can be disrupted by antibiotics, probiotics, dietary factors, environmental contaminants, and even stress. Will the next 20 years bring therapies that intentionally alter microbiota to produce a desired effect, similar to today's use of fecal transplantation in the treatment of recurrent Clostridium difficile infection? Will knowledge of an individual's microbiota profile become essential in tailoring therapy? The American Gut Project, by encouraging the general

4 public to participate, seeks to create a robust and comprehensive reference set of microbiome samples and metadata available for unrestricted use by researchers. The goal of the project is to improve understanding of population-wide variances and enable stringent hypothesis testing and evaluation of effect sizes.[10] Although none of our experts were willing to hazard a guess about specific therapies or developments that will result from this widening investigation of the microbiome, all were certain that it would result in insights that will definitively alter the way we prevent and treat a wide spectrum of disease. Genomics: The Revolution We've All Been Waiting For On April 14, 2003, the International Human Genome Sequencing Consortium announced the successful completion of the Human Genome Project.[11] Predictions of its impact on health and amelioration of disease proliferated and in many cases fizzled. Yet slowly but surely, one painstaking study after another, the collective science community added new insights to our understanding of the human genome and the potential for gene therapy to revolutionize the care of patients across a wide spectrum of disease as well as prevent disease in successive generations. What are some of the specific ways in which advances in understanding of genomics might change medicine? Understanding Disease Exome and genome sequencing have allowed identification of the genetic causes of neurologic disease and potentially the ability to prevent or mitigate these disorders, but the hope in the future is that these will also extend to a wide array of diseases. Maurie Markman, MD, a clinical professor at Drexel University College of Medicine and president, Medical & Science, at the Cancer Treatment Centers of America in Philadelphia, notes that an improved knowledge of germline data is already an important area of cancer risk (eg, BRCA mutations). Eric Topol, MD, Medscape's editor-in-chief, enthuses that "we are indeed in the midst of a genomic revolution, with CRISPR genome editing moving into clinical trials for the detection and treatment of cancer and infectious disease, fetal screening for chromosomal abnormalities, and molecular diagnosis of unknown diseases. This will accelerate: Whereas 1 million humans have had genome sequencing in 2015, the projection is that more than 1 billion

5 people will have been sequenced by 2025." William F. Balistreri, MD, professor at Cincinnati Children's Hospital Medical Center, looks forward to the potential of whole-exome sequencing to assist in accurately diagnosing diseases and in structuring personalized medicine. "Whole-exome sequencing offers a high yield of relevant predictive and diagnostic information, which will be used in the evaluation of patients with suspected genetic disorders. The diagnostic success resulting from exome sequencing will lead to the development of novel, targeted treatment strategies." Along these same lines, John G. Bartlett, MD, professor emeritus in the Department of Medicine at Johns Hopkins Hospital in Baltimore, Maryland, predicts that gene sequencing will become routine and serve as the "standard for infection control, epidemic control, and food safety." William T. Basco, MD, MS, professor of pediatrics and director, Division of General Pediatrics at the Medical University of South Carolina, is enthused about the potential for the increased availability of genomic data to help predict individual response to therapeutics, including in autoimmune conditions, but perhaps also for other prevalent conditions, such as asthma, attentiondeficit/hyperactivity disorder, and seizure disorders. "Wouldn't it be nice to know which drug a patient is more likely to respond to rather than just taking a guess?" Pharmacogenomics Drugs are currently "one size fits all" but pharmacogenomics is changing that, by looking at how our genes affect our response to drugs. Experts such as the Clinical Pharmacogenetics Implementation Consortium anticipate that a growing knowledge and understanding of germline genomic data will be translated into actionable guidelines for use of an array of drugs that will lead to widespread use of pre-prescription genotyping. Although still in its infancy, the hope moving forward is that pharmacogenomics will allow patient-tailored therapy for a wide range of diseases. Of course, the barriers to its use will include cost, because these therapies can be anticipated to be monumentally expensive. Pharmacogenomics in Cancer

6 Nearly every aspect of cancer research has benefited from The Cancer Genome Atlas[12], according to Bert Vogelstein, MD, Clayton Professor of Oncology and Pathology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. Begun in 2006 and completed in 2015, the Atlas is a compilation of the genomic changes in all cancers and is a "source book" informing the practice of individualized cancer therapy. Gene sequencing of specific tumors has allowed identification of precision therapies to treat cancers, regardless of where in the body they may occur. In 20 years, the division of cancers into brain or breast or prostate will be eliminated. The improved understanding of the normal germline as well as genetic mutations in individual tumors will allow specialists in tumor type to aggregate information and develop strategies to treat patients with specifically targeted therapies. In addition to better knowledge of cancer genomes, advances in the understanding of the normal human germline and its variations will allow clinicians to predict differences in the ability of an individual to metabolize a chemotherapeutic agent (or other drugs). Gene Editing, Gene Therapy, and Stem Cells Gene editing, which involves eliminating or replacing an existing, specific DNA sequence, has the potential to treat conditions with an identified molecular pathology. Experts predict that clinical trials that use gene editing to treat single-gene disorders will expand in the near future, with therapies that edit more than one gene genome editing rapidly following. Gene therapy, which in contrast to gene editing adds a gene copy, is still new and largely experimental. However, both our readers and our experts predicted that its use in preventing and treating disease, and also in restoring organ function, would become more commonplace in the decades to come. Using genetically modified stem cells for gene therapy is a natural partnership, though one that is still fraught with unanswered questions at this time. The next 20 years could very well bring gene therapies for the treatment of hereditary disorders, such as cystic fibrosis[13] and primary immunodeficiencies[14]; a range of cancers[15]; cardiovascular disease[16]; and other serious and often fatal illnesses into the mainstream. Charles C. Wykoff, MD, PhD, director of clinical research, Retina Consultants of Houston and deputy chair for ophthalmology at the Blanton Eye Institute at the Houston Methodist Hospital in Texas, commented that "the eye is ideally suited for gene therapy. Many pathologies that cause vision loss are

7 in theory treatable or even curable by gene transfer technology, and the next 20-year horizon will bring many of them to fruition." On the flip side, the ethics of both gene editing and gene therapy could also pose dilemmas for future clinicians. Already a concern voiced by some experts in sports medicine, genetic enhancement so-called "gene doping" to enhance performance is impossible to detect. Gene therapies utilizing direct injection of viruses or other DNA delivery agents might be used to regulate energy metabolism, alter blood flow to muscles, modify pain perception, or increase endurance, creating cyber-athletes and posing risks that currently cannot be predicted.[17] One can only wonder what the ramifications might be if or when this becomes widely used across all areas of medicine. A statement issued by the Organizing Committee for the International Summit on Human Gene Editing after their December 2015 meeting concluded that it would be "irresponsible" to move ahead with any clinical use of germline editing unless and until relevant safety and efficacy issues are resolved. Epigenetics Epigenetics, information transmitted during cell division via a means other than the DNA sequence, links genetics and environment through modification of gene expression. External factors, such as diet; viral exposure; and environmental insults, including smoking, all have the potential to alter the normal genome functions of DNA methylation, histone post-translation modifications, and nucleosome remodeling, thus modifying the epigenome. Epigenetic modifications are now recognized to play a key role in the development of disease, and epigenetic marks on the genome have shown promise as biomarkers of environmental exposure, thus providing data that allow improved risk prediction and insights into disease etiology.[18] Changes to the epigenome can be long-lasting and even inheritable, although in some cases damaging epigenetic marks may be reversible, leading to the possibility of novel epigenetic drugs and other nonpharmacologic lifestyle therapies.[19] Current trials are examining the potential for pretreatment of cancer progenitor cells with epigenetic therapies to eliminate resistance to chemotherapeutic agents.[20] The next few decades are likely to bring multiple new inhibiting agents targeting various epigenetic processes to treat a range of diseases from cancer to cardiovascular disease. Promising early work examining the leptin gene in mice with diet-induced obesity even

8 holds the potential for the development of an epigenetic treatment of obesity, though Joel Dudley, PhD, assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York, cautions that epigenetic therapies are likely to be only one of many tools needed to tackle complex diseases, such as obesity, where the pathogenesis is attributable to genetics, epigenetics, lifestyle, and even the microbiome (eg, gut bacteria). Immunotherapy The progress over the past year in the development of a significant number of new immunotherapies for the treatment of cancer has been unprecedented. From new data supporting use of atezolizumab for the treatment of non-small cell lung cancer to the US Food and Drug Administration's approval of nivolumab for treatment of renal cell carcinoma, cancer experts have cheered the mounting evidence of longterm efficacy and clinical benefit in rare cancers. A dramatic example of the potential for this group of therapies came in December 2015 with the announcement by former president Jimmy Carter that he no longer has evidence of active cancer in his brain after treatment with a recently approved immunotherapy for melanoma that had metastasized to his brain. Dr Markman predicts that this is just the start and that over the next two decades, "the single most important goal/innovation will be the development of a complete understanding of how to establish a highly effective anticancer immune response in individual patients that will successfully control the growth and spread of their cancer. This will include activation or reversal of suppression of the response, as well as prevention of an excessive response that results in unacceptable toxicity." Although immunotherapy has been most investigated as a cancer therapy, research can be expected in other disease states, such as autoimmune disorders. As with genomic therapies, however, potential barriers, such as huge cost, will have to be overcome before treatment will be widely implemented. Business of Medicine The whole paradigm of healthcare is shifting, and will continue to shift from technological advances (finally, an electronic health record that works!) to changes in the historic doctor/patient relationship (patient

9 empowerment) and changes in the way in which healthcare is financed (with creation of ever-larger healthcare conglomerates). These changes will go well beyond the upheaval begun with the Affordable Care Act's passage in Medicine Goes Mobile Robert Glatter, MD, editor-at-large for Medscape Emergency Medicine, assistant professor at Hofstra North Shore-LIJ School of Medicine, and an attending physician in emergency medicine at Lenox Hill Hospital in New York, predicts that one of the "most significant breakthroughs in the practice of emergency medicine will be the routine use of the smartphone for gathering patient data and integrating it into triage and assessment" and also for making laboratory and imaging data available at the point of care. Handheld point-of-care ultrasound (in a smartphone or tablet) will likely replace the stethoscope and other routine aspects of the physical examination of patients. Emerging 3D and 4D ultrasound technology will become a cornerstone of medical education and a requisite aspect in the care of patients. The smartphone will be part of not only patient assessment but also the diagnostic process, through the use of mobile algorithms, and management, including the ever-widening use of e-prescribing. Medicine Goes Global Many aspects of telehealth for example, teleradiology with sophisticated imaging studies routinely interpreted not just out of the hospital, but increasingly out of the state or even out of the country have become routine. But will the virtual environment eventually replace the familiar doctor's office? Kendra L. Campbell, MD, a clinical assistant instructor at the State University of New York Downstate Medical Center in Brooklyn, predicts that telemedicine will become more ubiquitous and extend even into the area of telepsychiatry. "The importance of telepsychiatry is extremely evident; there is a national shortage of psychiatrists, and it's predicted to only get worse." Medscape readers agreed, predicting the increasing use of tele-technology to deliver care and remote diagnostics. Citing corporations, such as Mercy Virtual, that provide 24/7 consultation services and access to a broad range of specialists using virtual technology, Dr Topol predicts that "regular hospital rooms will be history."

10 The Rise of the Patient Dr Topol has long advocated for the empowered patient, most notably in his book The Patient Will See You Now, which anticipates smartphonebased apps that will allow patients to view their own lab results, monitor vital signs, and apply artificially intelligent algorithms to diagnose themselves. Desiree Lie, MD, a clinical professor in the Department of Family Medicine at the Keck School of Medicine at the University of Southern California in Los Angeles, envisions online electronic portals that will provide access to the individual's current health status, suggest behavior changes, calculate current and ideal body mass index, set blood pressure targets, offer needed advice about lifestyle changes, and notify patients when preventive care is needed. These resources will calculate a "health report card" that will coach users on how to attain the best health outcomes. "It would be like having a bank statement of one's health or a financial retirement projection to help the consumer achieve the best longterm outcome." Valerie Gilchrist, MD, professor and chair of the Department of Family Medicine at the University of Wisconsin in Madison, likens it to a personal electronic medical record. Greater patient control will translate to more emphasis on wellness and patient accountability for their health, predicts Renee S. Holleran, RN, PhD, a nurse at Intermountain Medical Center in Salt Lake City, Utah. The Rise of the Corporation Large medical conglomerates are here and are likely to only get bigger creating, in the words of Robert Morrow, MD, a clinical associate professor in the Department of Family and Social Medicine at Albert Einstein College of Medicine in Bronx, New York, institutions that are "too big to fail." Skeptics voice concern about a corporate healthcare mentality that values profit over outcome. Optimists point to the potential for savings through economy of scale and improved interoperability, particularly in electronic health records. Having access on a large, national scale to medical information would completely alter the way in which we can practice medicine. Daniel J. Egan, MD, an assistant professor of emergency medicine at the Icahn School of Medicine at Mount Sinai, counts himself in that latter group. "Imagine a world where you could log into a portal and obtain an old electrocardiogram on a patient without having to try and track down another primary care physician, or even a hospital in another state.

11 Imagine if you were able to get results of a recent culture to guide antibiotic therapy in real time." Medscape readers and experts predicted that the next 20 years will bring numerous other advances in disease understanding, prevention, diagnosis, and treatment, as well as major changes in the ways these services are delivered. Roger F. Steinert, MD, Irving H. Leopold Professor; Chair, Department of Ophthalmology; and Director, Gavin Herbert Eye Institute, University of California, Irvine, said it best: "The next 20 years of breakthroughs and innovation are those we can't imagine yet!"