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Real-Time Ebola And HIV Dx
Tomorrow's Results Today: Real-Time Ebola And HIV Dx
Nicole Fisher | Contributor
In a world where nearly 4 billion people lack access to basic healthcare, the need for mobile testing using simple methods such as a single drop of blood could have momentous impacts on care. The level of individualized, near real-time care could become a reality in the developing world, as well as in many remote areas of the industrialized world. Anita Goel, M.D., Ph.D., a Harvard-MIT-trained physicist and physician, claims, “technologies like our Gene-RADAR® are emerging from the new field of nanobiophysics which will mobilize, personalize, and decentralize the next generation of health infrastructure, exponentially increasing access on a global scale.”
Although there are significant gaps in health care around the world, there is no lack of technology in the health sector. But how do we prepare the ecosystem – especially the deeply entrenched, regulated system in the US – to adopt next-generation technologies like Gene-RADAR® – the first product coming out of Nanobiosym. Gene-RADAR® is an iPad-sized mobile diagnostic platform that works off of a drop of blood or saliva to deliver a real-time diagnosis at a price point makers claim are 10 to 100 times cheaper than conventional tests.
Decentralizing Health Care
When Google was launched in 1998 it revolutionized the world and our access to knowledge about the world, by taking books, manuscripts, music, general history and information out of libraries, and into homes, information began to decentralize immediately. Like that ground-breaking endeavor, Gene-RADAR® has the ability to be the
for diabetes, tuberculosis, AIDS, HIV, Ebola, E.Coli and even certain types of cancer in under an hour. The ability, domestically and abroad, for individuals and providers to know this information without the US-based four-walled hospital could fundamentally transform the way we understand and practice medicine.
In the United States however, this means that we must prepare the ecosystem for the kinds of shocks that could result from unleashing this kind of technology. Further, it means understanding and harnessing the power of such technology that intersects physics, nanotechnology and information technology. When there are critical gaps and limitations to what can be done in silos, the need for combining these kinds of technologies and innovations is paramount. Gene-RADAR® integration means that potentially the unmet need for diagnosis is not only in the hands of those who need it, but that the costs also plummet. With Gene-RADAR®, Nanobiosym aims to deliver the same test in a mobile device for at least 10 times cheaper and with real time results.
Unmet Need Meets Customization
Empowering individuals to take responsibility for their own health care begins with access. By bringing Gene-RADAR® to individuals, Dr. Goel believes that consumers will be more empowered to take ownership over their own health. Further, both industrialized nations and developing countries can benefit from increased access and quality of care.
Currently, Gene-RADAR® is custom building “apps” for customers in both the developed and developing worlds and have already designed two pilot studies to run simultaneously in a large US hospital system and in Rwanda.
The aim in Rwanda, where 3% of the population is HIV+, is to improve basic testing and efficiency. In collaboration with the country’s Ministry of Health, USAID, and other global health agencies, Nanobiosym hopes to eventually provide a low cost solution to an estimated 200,000 people in Rwanda in urgent need of HIV viral load tests today – a demand that their current traditional centralized lab infrastructure is not able to fulfill.
In the United States, Nanobiosym’s goal is to use Gene-RADAR® to demonstrate a mobile cost-effective and real-time solution to cut costs while delivering better patient care. This also enables the next generation of pharma, and how these changes will impact the way Americans are diagnosed and treated. What makes Gene-RADAR® special, says Dr. Goel, is that the applications behind the platform are extremely flexible, and therefore can be customized for each partners’ needs, accommodating their nuances such as the user group who will be tested, the disease targets and even the site location.
Policy Change Must Happen For The Entire Ecosystem
Health care is a multibillion-dollar industry in the US with significant supply chain issues. This says nothing of the trillions of dollars spent globally each year on health care. For the world to embrace and realize the proposed impact of a disruptive technology like Gene-RADAR® many changes and partnerships will have to be forged.
Due to the potential disruption in diagnostics, access to care, treatment planning, monitoring, medical reimbursements and compensation, pharma and medical device industries, Nanobiosym has the potential to revolutionize what we consider personalized health care. This, however, will not come without difficulty, as none of those changes can exist in a vacuum. Policy, regulatory and pricing changes will have to occur across the ecosystem.
Dr. Anita Goel
At present, Dr. Goel and NBS have earned prestigious funding awards from many US-based government sponsors including, but not limited to, the Department of Defense,Department of Energy, US Air Force Office of Scientific Research, USAID and National Science Foundation. Nanobiosym also has an Advisory Board comprised of some of the world’s foremost science and technology experts such as MIT Professor Bob Langerand Cloud Computing Pioneer Paul Maritz, as well as business leaders like Ratan Tataof India’s Tata Group, Ambassador John Palmer, John Abele from Boston Scientific BSX 0% and Alfred Ford of the Ford Motor F -0.36% Company.
On September 27th and 28th, Nanobiosym convened on Harvard’s campus to host a Global Summit to “democratize health care.” In line with Dr. Goel’s vision, the Summit was created to focus on personalization and decentralization of the next generation of health care practices and the early adopters and change agents across various siloes within our ecosystem that are driving this transformation on a global scale.
Real-time Health Monitoring Will Revolutionize Patient Home Care in 2015
Real-time Health Monitoring Will Revolutionize Patient Home Care in 2015
Real-time health monitoring including the patient’s home continues to gain importance as pressures come from a variety of sources to reduce risks and costs of readmissions and hospitalizations. The Centers for the Medicare and Medicaid Services (CMS), enforcing the 2012 Medicare Readmission Reduction Program, the States and managed care organizations have to deal with tighter budgets, rising costs of service, and stricter capitation rates.
Until recently, home care reporting was archaic at best. The home was a “black box” where no information was generated when a home aide entered the residence and closed the door. Well-intentioned aides and nurses visited a patient’s home, administered care, and documented their visit in piles of paperwork that were often not reviewed or actionable.
Robert Herzog | CEO of eCaring
Data input was first “modernized” to record home aide hours and minimal
data about care by telephone. Such systems are used primarily for time and attendance. Aides visit the patient’s homes and use the patient’s home phone to document that their work shift has started. When the shift ends (and only when the shift is over), the home aide dials the phone to report the end of their shift, and with all the limitations inherent in pressing numbers on a dial pad, report that they had administered a few elements of care. Since they cannot see the output of what they entered, such data entry is error prone and of limited value.
To move home health care forward and to reduce costs requires a new approach. Forward thinking home aide agencies, health care providers, managed care organizations and hospitals are looking for innovative solutions that leverage the proliferation of tablets, smartphones and the ubiquitous Cloud to improve care at home, where patients spend most of their lives and where so many significant health events occur.
Thanks to technology, the “black box” of healthcare monitoring can be transformed into a sea of data where home health aides can gather 500-1,000 data points per month. The real-time collection and utilization of data from the home will offer these ten key benefits for specific patient populations, their families and every member of the patient’s care team in 2015:
1. Bringing the Internet into the home sheds light on the “black box.”
Often overlooked in a country where 58% of Americans have smartphones is that the neediest and often costliest health care users often fall below the poverty line and have no Internet access in their homes.
Bringing the Internet to the homes of America’s costliest users, who are often low-income seniors that qualify for both Medicare and Medicaid assistance (“dual eligible”) quickly transforms the home into a rich sea of meaningful data. With Internet access, seniors and their caregivers can transmit important patient data to care managers and doctors, as well as open the world of the Internet to the homes of the many that the “Information Super Highway” still passes by.
2. Using icons promotes simplicity of use.
Just as important as the establishment of the Web in the home is functional access to technology by creating systems that can be quickly understood by the home aide and patient, who have various levels of computer skills and English literacy limitations. Traditional text-based systems have much more limited utility.
Using icon-based systems dramatically increases the ability of aide and patients to enter significant and actionable data. Caregiving shouldn’t be about spelling and grammar — icons easily communicate information, overcome language barriers and technophobia, as well as are enjoyable to use.
New York’s Beth Israel Medical Center, as one example, saw the value of an icon-rich software system for reporting real-time results of patients with congestive heart failure (CHF). As one of the nation’s leading cardiovascular care providers, Beth Israel enrolled a group of its patients with CHF in a real-time monitoring post-discharge program to assess the impact on reducing readmission within 30 days. Beth Israel requested CHF-specific easy-to-understand icons, care management tools, and a tracking component for each patient participating in the trial.
Beth Israel learned that the system’s new icons eliminated any language barrier, while ensuring quick input of key data on the patient’s weight, medication regimen, behavioral patterns and vital signs.
3. Improving communication and sharing of information means constant dialogue among patient’s home, care managers and doctors that focuses on generating the best results for the patient. The virtuous cycle of communication provides the best means to engage the patient, who is more likely to provide data input if doctor, nurse or care manager respond in timely way. Knowing that “someone was there” and “I am not alone” helps patients to cope and better manage their plan of care.
Remote patient monitoring can serve as the communications hub of a continuum of care. As part of the post-discharge process, remote monitoring care managers can quickly:
4. Monitoring can be modified to the critical needs of a particular patient population, as was shown in the Beth Israel study. One of the leading causes of readmissions is heart failure, followed by pneumonia, chronic obstructive pulmonary disease (COPD), urinary tract infection, and diabetes. Heart failure can often lead to comorbidities, including dementia, renal failure, and hypertension.
Heart failure affects nearly 6 million Americans annually, with 550,000 new patients diagnosed each year. Four of five cases of heart failure occur in older adults. Each year, congestive heart failure (CHF) is associated with 1 million hospitalizations. The majority are readmissions or re-hospitalizations. CHF is in part responsible for close to $35 billion that is spent on heart failure each year. To reduce the risks associated with CHF, real-time monitoring can be utilized to track sudden weight gain, swelling of ankles, shortness of breath, chest pain, severe fatigue, loss of appetite, frequent nighttime urination, rapid heartbeat and other critical factors.
5. Tracking critical activities, vital signs, medications, mental and physical state, on a daily basis from the home, ensures continuity of care and the best possible outcomes for patients.
Using real time data, members of the care team can quickly spot changes or new trends that require immediate attention, keeping small problems in the home from leading to visits to the ER.
In the case of Beth Israel, data inputted by the home aide or the patient was quickly uploaded to the Cloud where information was evaluated by a care manager. The program showed significant, quantifiable reductions. Beth Israel saw its average rate of 29% CHF patient readmissions drop by 60% to 10.5% for this trial population.
6. Customizing alerts with tailored thresholds that require prompt attention, which are communicated to the care manager, family member, physician or other members of the care management team via text message or e-mail, enables overburdened care managers to focus their time and resources where they will have the greatest positive impact. Serious problems, like a rapid change in a vital sign, sudden weakness, slurring of speech, depression, excessive fatigue, failure to take medications, loss of vision, or sudden shortness of breath can be quickly addressed.
7. Configuring data into customizable care reports can be sorted by fields, such as mental and physical state, vital signs, sleep, eating, etc., enables better care management review and oversight. Longitudinal data can be evaluated on an hourly, daily, weekly or monthly basis to determine anomalies and trends requiring further analysis, leading to changes in long-term plans of care.
Data points can be tracked by time entry of the event and by the home aide to assess care quality and to ensure best practices. Having a historical timeline of the patient’s data points can show key inflection points or events that are outliers and indicative of preventable future problems.
8. Sharing information, through 24/7 Web access, can lead to lower stress for patients, caregivers, and families, who can have greater peace of mind by getting control over the situation and measuring progress. Patients not maintained in a stable condition cause stress, which can lead to rapid heartbeat, immune system compromise, fatigue, and time off from work. Longer stays at home increase comfort and lower stress as well as costs for patients, families, and caregivers
9. Using analytics by patient populations can improve risk stratification and assessment.
Most risk stratification programs are based on prior history and in-hospital experience, with generalized risk factors. Real time post-discharge and care data can substantially enhance assessments for determining readmissions and utilization risk. Analytics can also help predict outcomes of recovery while pointing to outliers that may need further attention. Harnessing analytics can also determine best next steps in a particular patient population.
10. Improving Time Management of Activities and Expenses is essential for proper distribution of limited resources. Tracking of actual vs. budgeted or reimbursable time is demanded by today’s payors. Using technology rather than telephone or, even worse, paper time sheets, can lessen time associated with time entry and increase accuracy. Resources can be better managed, which is essential under capitated rate and value and performance payment systems.
The success of real-time monitoring in reducing readmissions for patients with CHF at Beth Israel has led to the development of different modules for the needs of other special patient populations. Among the patient populations being considered for real-time data monitoring modules are patients with developmental disabilities, chronic obstructive pulmonary disease (COPD), diabetes, acute myocardial infarction, and other likely causes of readmission.
One module showing particular promise is the day-to-day work being performed by a home for people with developmental disabilities. Have a Heart, a home for people with developmental disabilities in Wisconsin, is using real-time monitoring to report on therapy progress, physical activities, medication adherence and eating habits.
As evidenced by Have a Heart, Beth Israel Medical Center, select managed care companies, and patients with CHF, real-time monitoring is at the dawn of a new technological revolution with profound implications for the millions of patients and caregivers coping each day. Technology has revolutionized real-time monitoring and reporting to the point where it can generate big data from the home to deliver on its potential for CMS, state governments, hospitals, home health aide agencies, managed care organizations, providers, accountable care organizations, medical and health homes and even families providing care. Utilizing real time actionable health care data from the home can enhance the quality of care while reducing costs and risks, thus improving health outcomes for potentially millions of elderly and chronically ill patients.
Robert Herzog is the founder and CEO of eCaring, a web-based home health care management and monitoring system that brings the benefits of digital record keeping and communications to the millions of Americans receiving home health care.
Robert’s interest and involvement in home-based healthcare emerged several years ago when he was deeply involved in the home and extended care of his mother Grace. The issues both she and he encountered ensuring that she received proper treatment gave him the initial understanding of the problems eCaring was subsequently designed to solve.
Reduce Healthcare Supply Chain Costs for Providers
10 Ways to Reduce Healthcare Supply Chain Costs for Providers
GHX outlines a list of documented opportunities to reduce supply costs healthcare supply chain costs for providers.
The healthcare supply chain is the second highest and fastest-growing operating expense for healthcare providers. Faced with significant medical supply costs and evaporating reimbursements, healthcare are increasingly seeking ways to reduce their supply chain expenses. GHX, provider of healthcare supply chain solutions has provided the following ten ways healthcare providers can reduce healthcare supply chain costs:
10 Ways to Reduce Healthcare Supply Chain Costs for Providers by Jasmine Pennic
Rehumanize the Doctor-Patient Interaction
Google Glass Startup Augmedix Nabs $3.2M to Rehumanize the Doctor-Patient Interaction
Google Glass startup Augmedix announced today it has raised $3.5 million in venture funding from DCM and Emergence Capital Partners to rehumanize healthcare through Google Glass. With 36 employees, the startup announced that it will be moving into their own 7,000-square-foot office in San Francisco’s Mid-Market neighborhood.
Founded by Stanford grads CEO Ian Shakil and Chief Product Officer Pelu Tran in 2012, Augmedix – a service powered by Google Glass — reclaims the hours physicians spend on the computer entering or retrieving data from electronic health records and refocuses them on what matters most: patient care.
Augmedix plans to utilize the capital to expand its growing team and scale up its efforts to reach outpatient doctors across the nation. After completing several successful pilot studies, the startup is already generating revenue with a select number of healthcare providers.
Ian Shakil, Augmedix CEO
“Doctors spend more than 1/3 of their day on the computer, inputting or retrieving data from electronic health records. The amount of data and documentation is overwhelming. Powered by Google Glass, Augmedix rehumanizes the doctor-patient interaction by delivering patient satisfaction, doctor efficiency, doctor satisfaction and health record quality. Augmedix reclaims the majority of the time that would otherwise be spent feeding the beast,” said Shakil, referring to the time that doctors spend on the EHR.
The startup is a graduate of Rock Health, a San Francisco-based digital health seed fund. Augmedix has established a host of other service partners, including Cooper, Fenwick & West LLP, PLC, Schox, Stanford Venture Studio, and others.
Google Glass Startup Augmedix Nabs $3.2M to Rehumanize the Doctor-Patient Interaction by Fred Pennic
Remote Patient Monitoring Lets Doctors Spot Trouble Early
Remote Patient Monitoring Lets Doctors Spot Trouble Early
For patients with chronic conditions, tracking of vital signs allows quick adjustments in care
The router was sent by the University of Pittsburgh Medical Center to track how Mr. Setzenfand’s diseased heart was doing. The device wirelessly collects the measurements taken in the patient’s home by a scale, blood-pressure cuff and fingertip blood-oxygen meter, and sends them to the medical center.
Based on those transmissions, Mr. Setzenfand’s doctor adjusted the doses of two blood-pressure drugs without the patient needing to visit the doctor or ending up in the emergency room. “I don’t have to do anything other than use the equipment,” says Mr. Setzenfand, a 78-year-old retired accountant.
Such a merging of wireless technology and medical care is still in its infancy, but health systems that began pilot programs with the technology in recent years say they see signs that it is keeping patients healthier. By enabling doctors to continuously monitor patients, they say, the systems can detect problems well before they grow serious.
“We’ve been able to show significant reduction” in hospital admissions, says Mark Rumans, chief medical officer at Vidant Health, which operates hospitals and other health-care facilities in eastern North Carolina.
Cost, Care Concerns
Vidant, which started its program in February 2012, has 600 to 700 patients with congestive heart failure, diabetes and high blood pressure participating in its remote-monitoring program at any one time. Each receives various devices to measure blood pressure and other vital signs, along with a transmitting device to send the data via cellular service to Vidant.
Hospital admissions for these patients fell 74% in 2013 and dropped 54% during the first eight months of last year from the same period a year earlier, to 192, according to Dr. Rumans.
Remote-monitoring programs tend to focus on serious, chronic conditions like congestive heart failure, which typically have resulted in repeat hospitalizations. Readmissions for these conditions are a major health-care expense, and Medicare has begun penalizing hospital systems with high readmission rates.
“We are under considerable pressure all around to deliver better outcomes and keep costs down,” says Ravi Ramani, director of the Integrated Heart Failure Program at the University of Pittsburgh Medical Center, or UPMC. “What we’re trying to do is use technology” to further those efforts.
About 250 heart-failure, diabetes and other patients participate at any one time in the UPMC remote-monitoring program, says Andrew Watson, medical director of the program.
For instance, UPMC patients recovering from severe wounds take photos, which doctors and nurses then look at remotely to see if the wounds are healing well or require antibiotics or other treatment. Diabetics transmit their blood-sugar levels, while the weight, blood-oxygen levels and blood pressure of patients with congestive heart failure are monitored.
Last year, 12.9% of the patients with congestive heart failure in the program were readmitted to a hospital within 30 days of their initial hospitalization, compared with 20% of patients with the condition who didn’t participate, Dr. Ramani says.
Working Out the Kinks
Leading manufacturers of remote-monitoring equipment include Medtronic Inc., PhilipsNV and St. Jude Medical Inc. Sales are expected to total about $32 billion this year, with a compound annual growth rate of 9.2% between 2014 and 2019, according to Kalorama Information, a medical-market division of Market Research Group LLC.
Still, adoption of the technology hasn’t always been smooth.
One persistent obstacle to running the programs, industry officials say, is a general lack of reimbursement from insurers for the costs of equipment and monitoring, which leaves providers to absorb those expenses.
Health systems also say they experienced growing pains as they began trying to keep tabs on patients from a distance. The volume of incoming data was overwhelming, requiring fine-tuning of algorithms to help sort out what should come to nurses’ immediate attention. And some health systems decided it was better to hire a telecommunications company to install the equipment, rather than do it themselves.
In addition, some doctors complained that the information arrived in an unwieldy format that didn’t relate the readings to each patient’s overall health. So, UPMC tweaked its software to allow doctors to tailor the target levels for each patient’s vital signs, so that they would only get clinically meaningful data, and developed an easy-to-use format, Dr. Ramani says.
At Mercy health system in Missouri and neighboring states, chronic-condition nurse Penny Lee watches the daily data stream on two computer screens at a Springfield, Mo., office and makes calls to patients if a red alert appears.
Ms. Lee says she makes about 20 calls a day prompted by the red warnings. For instance, if a patient with congestive heart failure is reported to have gained 3 pounds overnight, Ms. Lee asks questions designed to determine whether the patient’s condition is worsening, there is a medication problem or the weight gain is simply a false alarm, maybe caused by a family member stepping on the scale.
Sometimes the problem is caused by the patient eating salt-heavy food or drinking too much fluid, in which case Ms. Lee will review proper diet. She reports her actions to the patient’s doctor.
Allen England, 65, of Wheaton, Mo., had his blood-pressure medicines and their doses adjusted some 20 times remotely by Mercy after he was diagnosed with congestive heart failure and another heart condition called myocardiopathy in 2013 and a home blood-pressure monitor reported dangerously low levels, says Jan England, his wife.
“It saved many trips to the emergency room,” Ms. England says. Eventually, doctors and nurses decided Mr. England needed a defibrillator pacemaker, which was implanted in April 2014.
Mercy, based in Chesterfield, Mo., has anywhere from 270 to 500 patients with congestive heart failure and chronic obstructive pulmonary disease in its remote-monitoring program. Hospital readmission rates for the heart-failure patients fell to 15.7% last year from 18% in 2009. Mercy says it doesn’t have data yet on COPD patients because the program won’t be fully implemented for them until April.
A big component of the programs is teaching patients about their conditions and medicines, and helping them to manage both correctly. That usually starts when nurses talk with patients about joining the program and continues as feedback from the monitoring provides teaching moments.
“We see patients for only 15, 20 minutes at a time, but there is so much more that goes on in patients’ lives, so we are trying to be out there with patients, at their homes, at their workplaces and in their communities” through remote monitoring, says Parag Agnihotri, who directs the Continuum of Care programs at Sharp HealthCare’s Sharp Rees-Stealy Medical Group in San Diego.
Sharp Rees-Stealy puts a sensor on asthma inhalers to make sure patients are using them appropriately. The sensors record when asthmatics like David Hogben press down on the button triggering their inhalers, then sends a signal to Mr. Hogben’s cellphone, which transmits the information to Sharp Rees-Stealy.
Sharp Rees-Stealy nurses monitoring the data can see if Mr. Hogben is using his emergency inhaler, a possible sign that he isn’t regularly using his controller inhaler as he should and could be heading toward the kind of troubled breathing that leads to an emergency-room visit.
Mr. Hogben, a 44-year-old San Diego resident, says he also gets text messages and emails from Sharp Rees-Stealy every day reminding him to use his regular inhaler and when to recharge the sensors.
After joining the program last year, Mr. Hogben says he experiences just one breathing episode a month, down from three a week. “This system has made such a big change in my asthma,” he says.
Mr. Rockoff is a Wall Street Journal reporter in New York. He can be reached at email@example.com.
MORE IN UNLEASHING INNOVATION: HEALTH CARE
If one out of three people develops cancer, that means two others don’t. Understanding why could lead to insights relevant to prevention and treatment.
Pathologists have shown that virtually all men age 60 or older have microscopic prostate cancer when examined at autopsy. Most of these microtumors never develop into cancer, however. It is also known that disseminated cancer cells are present throughout the body in most cancer patients, but only a small minority of these cells develop into secondary tumors. The rest are kept under control by the body.
Indeed, metazoan evolution has led to many adaptations that protect species across the animal kingdom from outlaw cells. Immune surveillance plays a major role in the defense against virus-associated tumors, where the virally encoded transforming proteins provide readily recognizable foreign targets. But nonviral tumors, which are composed of aberrant host cells, do not provide such targets, and the immune response is suppressed by defenses against autoimmune reactions. Rather, we now know that the main safeguards against cancer are not immunological at all.
Metazoan evolution has led to many adaptations that protect species across the animal kingdom from outlaw cells.
Several cancer-resistance mechanisms appear to have evolved to maintain cellular or genomic integrity. For example, normal stroma, the connective material that supports the cells of a tissue, appears to inhibit cancer growth. Other resistance mechanisms include DNA repair, suppression of oncogene activation, tumor-suppressor genes, epigenetic stabilization of chromatin structure, and apoptosis. These mechanisms are well-studied, and each provides a potential road map for prevention and treatment.
Abnormal cell division is a hallmark of tumor cells. The mutated genes responsible for this proliferation are called cancer genes, or oncogenes, but this is a misnomer. Their normal function is not to cause cancer but to participate in the regulation of normal cell division. Meanwhile, more-appropriately named tumor suppressor genes recognize the illegitimate activation of proliferation-driving genes and hit the brakes. Once again, mutations that disrupt this function can lead to cancer.
Tumor risk can also be influenced by mutations in genes that control the fidelity of DNA replication, the efficacy of DNA repair, and the checkpoint controls involved in DNA synthesis and chromosomal mechanics. Xeroderma pigmentosum, for example, stems from a specific DNA repair deficiency. The predominant form of this condition is caused by a recessive mutation in one of the essential components of the nucleotide excision repair (NER) system, whose main function is to snip out molecular DNA lesions caused by exposure of skin epithelium to ultraviolet light. Patients with xeroderma pigmentosum must protect themselves from sunlight all their lives, but they nevertheless develop multiple skin carcinomas, and in about one-third of cases, also progressive neurological abnormalities. This highlights the paramount importance of DNA repair as a frontline surveillance mechanism.
Yet another group of genes associated with cancer formation regulates programmed cell death, or apoptosis. The normal function of the proteins expressed by these genes is to recognize superfluous, damaged, aged, or aberrant cells that must be eliminated. The importance of apoptosis is exemplified by the vertebrate adaptive immune system, in which B lymphocytes, as they differentiate from their precursor cells, rearrange the DNA of immunoglobulin genes to generate a vast number of potential antibodies. If an antibody happens to recognize an antigen in the body, the B cell producing it will be stimulated to expand clonally. But those B lymphocytes whose product does not bind a corresponding antigen must die to avoid clogging the system. Potential cancer cells that upset tissue integrity also elicit signals that initiate apoptosis. Cancers cannot develop unless the apoptotic mechanism is functionally impaired.
The genes that contribute to cancer development by mutation, illegitimate activation, or—conversely—inactivation or loss are practically identical in all mammals.
The genes that contribute to cancer development by mutation, illegitimate activation, or—conversely—inactivation or loss are practically identical in all mammals. Many of them are even conserved among distant groups, such as Drosophila, C. elegans, and yeast. Moreover, these cancer-associated genes mutate at similar frequencies across species. Therefore, it might have been expected that the blue whale, which has 1017 cells, would develop cancer more often than the mouse, with 109 cells, or humans, with 1013. This, however, is not so. In fact, blue whales rarely get cancer, and when they do, they seem able to live a full life span with it. The fact that the frequency of tumors does not increase with the total number of cells that make up an animal suggests that some sort of systemic control is preventing cancer development. Even typical laboratory animals vary in their cancer-proneness. Mice, rats, and hamsters are relatively cancer-prone, whereas rabbits and guinea pigs are relatively resistant. At the far end of the spectrum, two species of mole rat have been found to be completely cancer free, despite living relatively long lives. (See “Cancer-Free for Life.”)
Is there any genetic variation among humans with regard to cancer resistance? There is no proof of this, but it is highly likely that it occurs. In genealogically well-mapped Icelandic families, there are several cases of six or more long-lived siblings with no cancer incidence and whose parents did not die of the disease. It is not possible, however, to distinguish between the existence of genetically resistant families and the occurrence of cancer-free families purely by chance.
Interestingly, the sharp increase in human tumor incidence with age is followed by a decrease around 80 to 85 years. Centenarians rarely develop new cancers. The most probable reason is that cancer-susceptible individuals in the population have already died off. Freedom from cancer may be a necessary, but in itself insufficient, precondition to reach very old age.
People with a type of dwarfism called Laron syndrome represent another documented example of cancer-resistant humans. Found in an Ecuadorian population with frequent cousin marriages, Laron patients have no problem with skeleton, cartilage, or joint development and, in contrast to other dwarfs, have very high levels of growth hormone. However, their cells lack a receptor required for the functional activity of the hormone.1 An unusual mutation in the growth hormone receptor gene appears to be responsible for cancer resistance in this case.
There thus appear to be diverse mechanisms that protect against cancer. In addition to driving the proliferation of cancer cells, mutations or epigenetic changes may influence the ability of the cells to invade bordering tissues, to give rise to systemic metastasis, or to resist treatment. Notably, metastasis-favoring mutations may occur at a very early stage of tumor development, long before there are sufficient numbers of tumor cells to allow the manifestation of this property.
© MOLLY MENDOZA
In the 1960s, British cancer biologist Michael Stoker made an unexpected observation: when he explanted a certain number of tumor cells into a dish with appropriate nutrients, he obtained about 100 small, growing tumor-cell colonies. But when he mixed the same number of tumor cells with normal fibroblasts, the number of growing colonies was reduced by 99 percent. It seemed as though normal neighbor cells had suppressed the ability of the tumor cells to make colonies, a phenomenon later termed contact inhibition or neighbor suppression. (See illustration.)
Adherens junctions, protein complexes that occur at cell-cell points of contact in epithelial and endothelial tissues, appear to play an important role in this phenomenon. E-cadherin, an essential mediator of adhesion in these junctions, is downregulated in most epithelial tumors, usually by methylation of the gene’s promoter region. Reexpression of E-cadherin appears to suppress the transformed phenotype in isolated cancer cells, whereas blocking E-cadherin function enhances invasion.2
Other structural components of the cell membrane may be similarly involved in microenvironmental inhibition of tumor growth. β-integrins, subunits of transmembrane receptors that link cells to the extracellular matrix and to each other, and that also play key signaling roles in tissue organization, are often abnormally expressed by tumor cells. Targeting tumor-associated β-integrins with antibodies inhibits tumor growth.3 Components of the Notch signaling pathway, which regulates cell differentiation and proliferation, are another example. Deletion of Notch receptors or their ligands from the basal layer of mouse epidermis can lead to epidermal hyperplasia and skin tumors.4
Interestingly, the sharp increase in human tumor incidence with age is followed by a decrease around 80 to 85 years. Centenarians rarely develop new cancers.
A few years ago, we reexamined the role of neighbor suppression in cancer resistance by labeling human prostatic carcinoma cells with green florescent protein and plating the cells alongside normal fibroblasts from different tissues. Fibroblasts from skin strongly inhibited tumor growth. While the tumor cells were not killed, and continued to grow in size and make proteins, they could not divide. Fibroblasts taken from cancerous prostates, on the other hand, hardly inhibited cell proliferation at all.5 In fact, these so-called cancer-associated fibroblasts (CAFs) may even support the growth and survival of adjacent tumor cells. Looking more closely at gene expression in these fibroblasts, we identified genes activated by inflammation or wound healing, a finding in line with the established fact that inflammation can favor the growth of cancer cells that have been inactive, often for long periods of time.
Another defense against cancer was discovered in the 1970s by American biologist Beatrice Mintz. Working with a highly malignant line of teratoma cells, Mintz found that adult mice subcutaneously inoculated with the cells all succumbed to teratomas. When the teratoma cells were introduced into very early embryos, however, no malignancies developed. The introduced cells simply became part of the organism, participating in the normal development of the mouse and contributing to many tissues of the embryo. The normalized tumor cells even contributed to the production of sperm in the recipient mouse.6
This normalization of embryonic tumor cells in the early developmental environment is the most extreme example of the differentiation of malignant into normal cells. There are many other, less spectacular examples in the later literature. Highly malignant murine leukemia cells can be induced to differentiate into nonmalignant cells by natural or artificial substances. One form of human leukemia, acute promyelocytic leukemia, is routinely cured in this way: the combination of a naturally occurring signal receptor and an empirically identified chemical compound, genistein, induces the cancerous cells to differentiate from a granulocyte precursor into a mature myelocyte that can no longer divide.7 Although similar examples are still relatively few, they suggest that most and perhaps all tumors could be induced to differentiate and stop growing if one could find the right combination of inducing substances.
Evolution has provided us and other animals with multiple mechanisms that stop normal cells from escaping into uncontrolled division. If they nevertheless escape, the cell mobilizes multiple mechanisms to stop the outlaw cell and preserve the normal organization of tissues. These mechanisms can nip life-threatening malignant growths in the bud. Only after the normal tissue neighborhood has been corrupted by the tumor cells so that it no longer inhibits, but rather stimulates, malignant growth can the cancer sail forth uninhibited.
Two species of mole rat serve as exceptional examples of cancer resistance. The blind mole rat (BMR) and the naked mole rat (NMR), which live up to 20 and 30 years, respectively, never develop the disease. Understanding the molecular mechanisms that afford these animals such powerful protection against cancer could inform the fight against human cancers.
The NMR, a eusocial species that lives in highly organized matriarchal societies, has to force its way through narrow and often sinuous underground tunnels. The connective tissue in its skin contains a high-molecular-weight form of hyaluronic acid (HA) that makes the animal’s skin malleable like model clay. The corresponding HA in mice and humans has less than one-fifth the molecular weight. The heavy form of HA that occurs in the NMR prevents the transformation of normal cells into cancer cells; only after it has been removed can the NMR’s cells be transformed into cancer cells (Nature, 499:346-49, 2013).
© JOEL SARTORE/GETTY IMAGES
Moreover, NMR fibroblasts exhibit an unusual form of contact inhibition. Mouse and human fibroblasts inhibit their own continued proliferation when they bump up against other cells. NMR fibroblasts do this much earlier, when cells barely touch one another. When the cells come into contact, p16, a protein involved in causing growth arrest, is upregulated. This is not seen in the late contact inhibition of human and mouse fibroblasts, where another growth-arrest protein, p27, is upregulated.
In contrast to the NMR, the BMR is a solitary, nonsocial, and aggressive species. And its cancer resistance mechanisms differ from the NMR’s. The BMR does not have heavy HA or early contact inhibition, but when its fibroblasts grow to confluence they commit collective suicide by releasing a type of interferon (PNAS, 109:9392-96, 2012). Once again, evolution appears to have devised diverse solutions to keep rogue cells in line, and in these two cancer-free species, those mechanisms may be key to their remarkable longevity.
Resolving Conflict among Medical Practice Staff
Resolving Conflict among Medical Practice Staff
By Keith L. Martin
Consultant and coach Charlie Hauck of Growth Dynamics provides five key components every practice should implement to reduce conflict and provide prescriptions for resolution when conflict does occur.
For more on settling staff disputes at your medical practice, see the October 2014 Cover Story.
Revenue Cycle Management for 2015 ICD-10 Go-Live
Revenue Cycle Management for 2015 ICD-10 Go-Live
In July 2014, the U.S. Department of Health and Human Services (HHS) issued a rule finalizing Oct. 1, 2015 as the new go-live date for healthcare providers, health plans, and healthcare clearinghouses to transition to ICD-10.
Will your organization be ready on October 1, 2015?
Download this latest Healthcare Informatics eBook, sponsored by Greenway Health, to shine some light on your organization’s journey to ICD-10’s October go-live.
Readers will debunk and investigate crucial ICD-10 topics, including:
October is coming, don’t be left behind. Read this Healthcare Informatics eBook, and discover the nuances, processes, and best practices to tackle ICD -10.
Please read the attached eBook
Riesgos tecnológicos en salud digital
Riesgos tecnológicos en salud digital
Publicado por José Miguel Cacho
Top 10 Health Technology Hazards for 2015
Desde que las TICs comenzaron a utilizarse en el cuidado de la salud de forma masiva, hay una consciencia clara que su uso redunda en beneficios para la seguridad del paciente y en la gestión de los riesgos de la atención médica, pero evidentemente eso no exime de que se tenga que prestar atención especial a ciertos usos.
Hace unos meses se publicó el informe ‘Top 10 Health Technology Hazards for 2015’ elaborado por el InstitutoECRI de Estados Unidos donde se recogían los diez riesgos más importantes en tecnología sanitaria.
Y del que se hizo eco la Sociedad Española de Electromedicina e Ingeniería Clínica (SEEIC).
Aunque el informe se refiere a tecnología en general, algunos de estos peligros pertenecen al ámbito TIC y otros, debido a la imbricación de las tecnologías de información en el sector sanitario, ya están o estarán relacionados en un futuro muy cercano con las tecnologías de la información y la comunicación.
Los riesgos incluidos en la lista de ámbito TIC son: La integridad de datos y la ciberseguridad, sobre ambos trata ampliamente el informe.
Respecto a los datos el informe hace referencia a aquellos datos incorrectos, por errores en su introducción o por el tratamiento que de ellos realizan los usuarios. En este punto la imprescindible interoperabilidad entre los sistemashace más importante los esfuerzos en el diseño y desarrollo de programas e integraciones para evitar estos errores que puedan derivar en daños o perjuicios para la salud y el tratamiento de los pacientes.
La ciberseguridad o la insuficiente protección de los sistemas y dispositivos médicos, es uno de los temas que más preocupa a los CIO sanitarios, y con razón. 2014 fue el año de mayor crecimiento en infracciones de seguridad (hasta el punto de que en las organizaciones sanitarias se cometieron el 42% de todas las infracciones de seguridad) y en documentos robados en USA, pese a que existe una clara conciencia de la necesidad de seguridad entre los actores sanitarios (PDF). El robo de información sanitaria tiene todo un mercado negro detrás que saca beneficio de las identidades de los pacientes y de su información médica o aseguradora.
Los expertos afirman que la seguridad no es tanto un problema tecnológico como un problema de personas y procesos y que la responsabilidad debe ser recogida por la dirección TI.
No hay que olvidar que la ciberseguridad también va a afectar de forma ineludible a la telemedicina y a los dispositivos usados ahora o conectados un futuro cercano (wearables, medical devices, apps, IoT, etc) para evitar vulnerabilidades de malware o ataques maliciosos.
Pero además hay otro punto que en el informe de ECRI no es asociado a las TICs, pero al que sí se debe tener en cuenta por parte de las empresas de tecnología de la información, las inadecuadas políticas y prácticas de configuración de alarmas. Este riesgo referenciado en principio para instrumental y aparatos clínicos se centra en los avisos perdidos o no reconocidos por los profesionales debido a una mala configuración de las alarmas.
El informe aconseja establecer rangos de prioridad según las necesidades de cada área terapéutica y gravedad de los pacientes, evitando la llamada “fatiga de alarma”.
Esa misma confianza que los médicos tienen en las alarmas de los dispositivos para informar sobre los cambios en el estado de los pacientes, deben seguir teniendo cuando sea un sistema o una aplicación TIC la que le informe de los datos recogidos a un paciente monitorizado en el hogar, o a un enfermo crónico cuando realice elautoseguimiento de su patología.
En estos casos, los sistemas de información se apoyarían en herramientas como los gestores de procesos (BPM) o los gestores de reglas (BRM) que son los que ayudan a los técnicos informáticos a establecer las políticas, en función de los objetivos, y a poner en marcha los procesos que las garanticen. De una forma sencilla se consigue que se basen en parámetros medidos aquellas alarmas que consideramos tienen que desencadenar la actuación de un profesional médico.
Imaginemos que un sistema de información se ocupa de gestionar los datos de unos pacientes crónicos que utilizan dispositivos para monitorizar sus patologías (EPOC, diabetes e hipertensión), tendríamos que definir las reglas que nos asegurarían que cualquier medida o conjunto de medidas activarían las alarmas necesarias para comenzar elproceso de atención asistencial adecuado.
El uso de estos sistemas informáticos permite cambiar de forma automática y para todo el rango de pacientes deseados tanto los avisos como los procedimientos de actuación, por supuesto estas políticas deberán estaraprobadas y mantenerse documentadas, para cumplir con las obligadas auditorías informáticas.
Por favor lea el PDF adjunto.