Source: Institute for Systems Biology

Leroy Hood, president of the Institute for Systems Biology (ISB) in Seattle, Washington, likes to talk about what he calls P4 medicine: health care that is predictive, preventive, personalized and participatory. Medicine today is a string of infrequent interventions prompted mainly by symptoms of illness. Hood argues instead for continuous management of health, making full use of whole-genome sequencing and biomarkers to correct disease before it gains a foothold.

In March, Hood will embark on the first big test of his ideas: a nine-month pilot study, dubbed the Hundred Person Wellness Project, in which 100 healthy individuals will be intensively monitored (see An examined life), offered regular feedback and counselled on lifestyle changes such as shifts in their dietary or sleep habits. The effects of these behavioural changes on their health will, in turn, be tracked using a battery of diagnostic tests.

The study violates many rules of trial design: it dispenses with blinding and randomization, and will not even have a control group. But Hood is confident in its power to disrupt the conventional practice of medicine. We hope to develop a whole series of stories about how actionable opportunities have changed the wellness of individuals, or have made them aware of how they can avoid disease, he says.

If the pilot study works as hoped, it will expand in several phases until it encompasses 100,000 subjects monitored over 25 years. The ISB is paying for the first hundred people through private donations and has budgeted around US$10,000 per person. Hood expects those costs to drop drastically in a larger study, thanks to economies of scale and rapidly evolving diagnostic technologies. But he acknowledges the challenge of securing the hundreds of millions of dollars that a generation-long trial would require.

Even in its pilot phase, the project is unusually thorough. The ISB will sequence the whole genome of each participant at the outset. And in later phases, Hood says, the study team will also examine epigenetics: methylation and other modifications to DNA that can reflect environmental exposures. But that is just the tip of the data-collection iceberg.

Institute for Systems Biology

Leroy Hood: We hope to develop a whole series of stories about how actionable opportunities have changed the wellness of individuals.

Participants will be asked to wear digital devices that will continuously record their physical activity, heart rate and sleep patterns; subjects will periodically upload those data to the institutes systems. Every three months, researchers will gather samples of participants blood, urine, saliva and stool. They will measure five biochemicals in saliva and urine, and sequence the stool samples to track the ecology of major microbial species in the gut. Blood-chemistry screens will extend well beyond the usual tests for cholesterol and glucose to include 20less-commonly monitored variables, such as C-reactive protein which signals inflammation at high levels. Hoods teams will also monitor about 100 organ-specific proteins that, he says, are sensitive markers for transitions from health to disease in mouse and cell models.

The point of the study and of P4 medicine in general is to detect those transitions and respond to them before symptoms appear. To that end, participants (mostly residents of the Seattle area, invited through social media) will have full access to their personal cloud of data points. Some will have enough scientific training to dive into the literature and interpret their data themselves. But Hood expects most to rely on ISB-provided wellness coaches and their own physicians to interpret the results and recommend medical treatment or changes in diet or behaviour.

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Medicine gets up close and personal

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Newswise PHILADELPHIAPenn Medicine today announced a collaboration with software and analytics company Teqqa, LLC that could revolutionize the way antibiotics are tracked and prescribed in clinical settings. The two will work together to develop a new software platform and mobile app that aims to encourage appropriate antibiotic use by providing real-time data to clinicians, and minimize the risk of dangerous pathogens developing resistance to life-saving antibiotics.

The resistance of bacteria to commonly-used antibiotics has been increasing at an alarming rate, and resistance patterns vary internationally, nationally, regionally, and locally. These differences matter a drug that is effective against a life-threatening bacterial infection at one hospital may be much less effective at another, and appropriate stewardship of antibiotic drugs is essential to slowing the growing resistance.

Understanding these patterns, particularly within a given hospital, is essential to determine the best methods to track, prevent, and treat these infections. Without a clear, real-time and accurate understanding of drug sensitivity and resistance patterns within individual hospitals and the community, however, physicians typically choose antibiotics empirically, potentially contributing to resistance and poor patient outcomes.

The appropriate use of antibiotics to treat infections depends on knowing what antibiotics kill which bacteria, said Keith Hamilton, MD, associate director of Healthcare Epidemiology, Infection Prevention and Control and director of Antimicrobial Stewardship at the Hospital of the University of Pennsylvania. Predicting and understanding the trends and patterns of resistance allows clinicians to choose appropriate medications to treat a patients infection, and provides the health system real, actionable data to make broad recommendations for use of these life-saving drugs.

As part of the collaboration, Penn Medicine and Teqqa will jointly develop the software to allow for real-time microbiology data analysis, as well as a mobile app giving the userprimarily prescribing physiciansimmediate access to this critical information, allowing them to choose the best antibiotics for their patients. This will replace the current practice of providing data to clinicians every 9 to 12 months, where data is nearly obsolete as soon as it is made available.

The project with Teqqa builds upon Penns successful Antimicrobial Stewardship Program, which since its inception in 1993 has been shown to improve appropriateness of antibiotic use and cure rates, decrease failure rates, and reduce healthcare-related costs with its multifaceted approach.

This innovative software has the potential to improve patient outcomes and resistance patterns in hospitals across the country by allowing practitioners to understand the behavior of infections locally, regionally and most importantly, within their healthcare facilities, said Patrick J. Brennan, MD, chief medical officer for the University of Pennsylvania Health System. This is an important step in more effectively designing interventions to control and treat these infections.

We are thrilled to be working together with Penn Medicine, a leader in antibiotic stewardship and innovation in health care delivery, to develop this novel solution to the growing problem of antibiotic resistance, said Dan Peterson, MD, CEO of Teqqa. "Penn Medicine's equity position in Teqqa demonstrates both their strong commitment to improving patient outcomes and novel approaches to care delivery, and their desire to benefit from Teqqa's expertise in data analytics and software development to achieve those goals. Its a great opportunity to work with Penn to develop applications for Penn Medicine and for use more broadly with other health systems."

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Penn Medicine, Teqqa LLC Developing New Software and App to Track Antibiotic Resistance

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Newswise PHILADELPHIA -- Penn Medicine researchers have developed a better way to assess and diagnose psychosis in young children. By growth charting cognitive development alongside the presentation of psychotic symptoms, they have demonstrated that the most significant lags in cognitive development correlate with the most severe cases of psychosis. Their findings are published online this month in JAMA Psychiatry.

We know that disorders such as schizophrenia come with a functional decline as well as a concurrent cognitive decline, says Ruben Gur, PhD, director of the Brain Behavior Laboratory and professor of Neuropsychology at the Perelman School of Medicine of the University of Pennsylvania. Most physicians have a clinical basis from which to assess psychosis, but less idea as to how to best assess and measure a decline in cognitive function. To make this easier and to aid in early diagnosis and treatment, we created growth charts of cognitive development to integrate brain behavior into the diagnostic process.

Psychosis is a severe mental illness, characterized by hallucinations, delusions, social withdrawal and a loss of contact with reality. Genetics and environment, including emotional or physical trauma, can both play a role in its development.

The Penn researchers assessed the brain behavior of a cohort of about 10,000 patients between the ages of eight and 21 at Childrens Hospital of Philadelphia from November 2009 to November 2011, including 2,321 who reported psychotic symptoms. Of those, 1,423 reported significant psychotic symptoms, 898 had limited psychotic symptoms, and 1,963 were typically developing children with no psychotic, mental or any medical disorders.

Researchers administered a structured psychiatric evaluation, looking for symptoms of psychosis, anxiety, mood, attention-deficit, disruptive behavior and eating disorders; for the younger children, independent interviews with their caregivers were also conducted. The team also administered 12 computerized neurocognitive tests to evaluate each childs brain development across five domains: executive function, testing abstraction and mental flexibility, attention and working memory; episodic memory, testing knowledge of words, faces and shapes; complex cognition, evaluating verbal and nonverbal reasoning and spatial processing; social cognition, looking at emotion identification, intensity differentiation and age estimation; and sensorimotor speed, to understand the workings of their motor and sensorimotor skills.

The results were analyzed to predict chronological age for each child.

They showed that those with the most extreme psychotic symptoms had a lower chronological than predicted age, compared with the typically-developing group and the group with other psychiatric symptoms. They also had a greater developmental lag than the psychosis-limited group, with the lags most pronounced for complex cognition and social cognition and smallest for sensorimotor speed.

Broken down further, we found that boys on the psychosis spectrum showed an early decline in memory, complex and social understanding, compared with typically developing children, while girls showed minimal lag in memory across all ages groups, with a lag in complex cognition appearing later in development, explains Gur. This seems to follow the differences in how disorders such as schizophrenia manifest themselves across the sexes.

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Study Suggests "Growth Charts" for Cognitive Development May Lead to Earlier Diagnosis and Treatment for Children with ...