Five Drugs in the Polypill

Technology and the pressure of cost containment and improving patient compliance are resulting in an interest in developing a pill with 3,4, or even 5 drug combinations.  There are however some obstacles for this advance in poly-pharmacology.


Patients often are not compliant with treatment recommendations, even for one medication.  As more medications are prescribed compliance deteriorates further.

If a safe, inexpensive, once-a-day pill could substantially reduce the risk of myocardial infarction (MI) or stroke, would people want it? Most would probably say yes because MI and stroke are the first and third leading causes of death, respectively, in the United States.1 It is likely that many employers, health plans, and payers would also say yes because MI and stroke cost the US economy more than $300 billion annually in health care expenditures and lost productivity.2

Improving adherence by simplifying drug regimens and reducing their cost could have far-reaching consequences. In 2003, Wald and Law3 proposed to combine 3 half-dose antihypertensive agents, an intermediate-dose statin, low-dose aspirin, and folic acid into a once per day polypill for primary and secondary prevention of cardiovascular disease. Based on epidemiological models, they estimated that daily use by individuals aged 55 years or older could reduce the incidence of MI and stroke by more than 80%.3

The 4 drugs in the current version of the polypill have long histories of safe use. Although all 4 are frequently prescribed in the United States, the US Food and Drug Administration (FDA) has not approved combining them in a single pill. It has, however, authorized approximately 50 two-drug pills for hypertension.4 Recently, an FDA advisory committee expressed cautious support for using the polypill for secondary prevention of MI and stroke in patients who are unlikely to be closely monitored by a physician. It did not address the larger question of primary prevention.5

Although the polypill could produce substantial public health benefits, people in the United States are unlikely to find out anytime soon. This is because the pill’s price is so low (≤$1 per tablet) and the cost of the large clinical trials required for FDA approval is so high, it is unattractive to investors. The inventor’s dilemma is that creating a product that improves health is not enough; the product must also be able to generate a healthy return on investment. In the United States, the surest way to generate a healthy return on investment is to increase health care spending, not reduce it.

In reality advances in drug delivery systems will be very important for pubic health reasons, compliance and cost reduction.  It will require some creative and innovative for financing drug development costs.  The technology is ready, can we afford it ?  We need innovative venture capitalists.  It is doubtful whether the Affordable Care Act will nourish this embryonic technology.  What can be done?

First, to inspire innovators, federal agencies and philanthropies should commit a larger share of their research budgets to high-risk, high-reward science. Second, to entice inventors to address challenging problems, there could be greater use of prizes (eg, cash for the first inventor who creates a drug or device that meets a specific need).

Third, to ensure that low-cost, high-value discoveries reach the market, patent buyouts could be offered. This could increase the likelihood that these products are commercialized and offered at prices sufficiently low to encourage widespread adoption.

Fourth, to give inventors access to the capital required to bring a cost-lowering technology to market, a public-interest investment fund could be established. The public-interest investment fund would seek out promising products that are not attractive to conventional investors, and replenish its coffers with shared savings from successful inventions.

Fifth, to streamline the regulatory approval process, the FDA could be authorized to use existing mechanisms, such as fast-track or breakthrough therapy authority, to expedite review of cost-lowering technologies. This would require expanding the FDA’s mission beyond safety and efficacy to address costs.

What is the actual cost to develop a new medication ? The California Biomedical Research Association outlines the process

Surveys from different sources reveal estimates between $800 M and 5.0 B. That is a substantial range as reported by Tuft's

The studies are spread out from 2010 to 2015 and the increases have been substantial during this period. Keep in mind that reports from pharma are used to justify the high costs of drugs.

In addition the costs vary greatly among disease categories and the category of the drug.  Some drugs are a variation of one already approved, while others are in new classes such as oncology drugs designed as antibodies to cancer cells.  Variations in cost estimates suggest that policymakers should not use a single number to characterize drug costs. It is important to also be aware that different drug types might have substantially different actual costs of clinical trials. Therefore, the estimated variation in drug costs could be higher or lower, depending on whether the correlation between actual costs, success probabilities, and durations is positive or negative. As discussed below, recent work suggests that HIV/AIDS drugs have high clinical costs.


Poly drug combinations are made of already approved drugs for single use, and development costs may be far less. 





JAMA Network | JAMA | Effects of a Fixed-Dose Combination Strategy on Adherence and Risk Factors in Patients With or at High Risk of CVD:  The UMPIRE Randomized Clinical Trial

Meaningful Use....What the AMA has to say about Meaningful Use

October 1, 2015 is fast approaching. That is the deadline for providers to adopt ICD-10.  In addition to that requirement Meaningful Use continues to be a bane on providers.  Physicians perceive meaningful use as less than meaningful when resources could be better used to improve EHR usability rather than  some bureaucratic bloat/.

Meaningful Use (MU) isn't working, and now the government wants to move forward with Stage 3 implementation. But if it's not fixed, that could lead to less time with patients, less innovation and costly penalties if physicians are unable to comply. Currently physician participation in MU Stage 2 sits at less than 10 percent, compared to the 80 percent adoption of EHRs.

Recently Rep. Renee Ellmers, R-N.C., introduced H.R. 3309, the "Flex IT 2 Act." This legislation would provide much needed flexibility in the MU program and enhance electronic health records (EHRs) to improve patient care and access to health information. The bill also addresses key interoperability challenges by ensuring certified EHR systems are capable of sending, receiving and seamlessly incorporating patient data.

At a recent AMA town hall meeting on EHRs and MU, the response from physicians was overwhelming: MU is not working, and physicians cannot move to a learning health system unless they have the tools to do so. They need state-of-the-art technology that can interoperate with other systems and providers.

In Washington, D.C., August means one thing—congressional recess. 

Some of the reflections spoken about at the AMA meeting:

     80% of physicians are using EHR

     Rather than improving efficient patient care, the current state of EHR design interferes with the

     goal of improving patient relationships. 

     The current administration continues to push forward with more meaningful use requirements instead

     of correcting what does not contribute to patient care.

     The proposals to change from procedural based reimbursement to value will require EHR modification

     to integrate with the proposed changes of health reform.

     The AMA's goals are to have physicians play a key role in improving patient care, improve                            interoperability, and eliminate the digital silos that have replaced paper silos.

     

     Please take advantage of this time when your members of Congress are back at home: Email or call (888) 434-6200 to be connected with their district offices, and urge them to cosponsor H.R. 3309 today!

To learn more about MU and to share your story, please visit: breaktheredtape.org

https://www.votervoice.net/Shares/BUyuPAqYACVOKAjpVYN7FAA

Oliver Sacks: My Periodic Table - The New York Times

I received an email from Oliver Sacks this morning (or rather from his staff at the Oliver Sack's Foundation.)

So what does this post have to do with health care ?  Nothing, or everything. Oliver  is a neurologist who has terminal cancer. He was diagnosed with ocular melanoma  He has had a rich productive life, not just as a physician but as an accomplished writer, admired by all.  And when he was young this man loved motorcycles, weight lifting and swimming,  several of which he still pursued.

The news was that Dr. Sack's has terminal cancer at age 82. He explains it in his genius and quirky sense of humor that those who know him will recognize by his commentary about dying.

"Bismuth is element 83. I do not think I will see my 83rd birthday, but I feel there is something hopeful, something encouraging, about having “83” around. Moreover, I have a soft spot for bismuth, a modest gray metal, often unregarded, ignored, even by metal lovers. My feeling as a doctor for the mistreated or marginalized extends into the inorganic world and finds a parallel in my feeling for bismuth.  I almost certainly will not see my polonium (84th) birthday, nor would I want any polonium around, with its intense, murderous radioactivity. But then, at the other end of my table — my periodic table — I have a beautifully machined piece of beryllium (element 4) to remind me of my childhood, and of how long ago my soon-to-end life began."

Sack's early years were not easy, as he describes his diversions from emotional pain with numbers and equations, as he eloquently states,

"I have tended since early boyhood to deal with loss — losing people dear to me — by turning to the nonhuman. When I was sent away to a boarding school as a child of 6, at the outset of the Second World War, numbers became my friends; when I returned to London at 10, the elements and the periodic table became my companions. Times of stress throughout my life have led me to turn, or return, to the physical sciences, a world where there is no life, but also no death."

Oliver Sacks Books










Oliver Sacks: My Periodic Table - The New York Times

Euthanasia: Has it's time come ? Do you have an Advanced Directive?

Health Reform has led to more openness and transparency. Along with preparing financially for death, how many plan how to die ?  Will you have choices ? Who should decide ?  Should relatives or children  be a part of the decision? What if you are unable to make a decision toward the end?

Physicians and patients struggle watching loved ones dwindle, suffer pain and lose any quality of life.Whether it is from incurable cancer Alzheimer's disease or chronic wasting disease,  it presents enormous conflict for loved ones.

Humans like answers that are black and white rather than shades of grey.  Our society is firmly in the grip of the ten commandments, "thou shalt not murder'.

Should we let life run it's course without interference?  Religious people would hypothesize that the process of dying is much like the act of childbirth, with gradual change leading up to the pain and ecstasy of birth.  Could it be dying is the same ?  Does the process of dying prepare us to enter a new realm, or does it all just end and go blank ?  Is suffering an important process of dying.  One might ask about people who are suddenly killed by accident, or intent?

Some would argue that with rapidly growing population and decreasing resources, and more expensive medical treatment that euthanasia is justified for some.

In Belgium and the Netherlands Euthanasia has been legalized beginning in 2007.

Comparison of the Expression and Granting of Requests for Euthanasia in Belgium in 2007 vs 2013

A Study of the First Year of the End-of-Life Clinic for Physician-Assisted Dying in the Netherlands

             Legalization of the right to die   ("Termination of Life on Request and Assisted Suicide (Review Procedures) Act" from 2002.)  (Netherlands)

            Legalization of the right to die   The Belgian parliament legalised euthanasia on 28 May 2002.^[4][5]

As of June 2015, human euthanasia is legal only in the Netherlands,Belgium, Colombia^[1] and Luxembourg. Assisted suicide is legal in Switzerland, Germany, Japan, Albania and in the US states ofWashington, Oregon, Vermont, New Mexico and Montana.


W A R N I N G   The following videos of euthanasia may  be very disturbing to some. The videos present real instances of euthanasia

The author offers no opinion on right or wrong regarding euthanasia, but states that death with dignity should outweigh other considerations and should be protected by law without penalty and only to be performed with the consent of a patient.  The patient's desires should be incorporated in an Advanced Directive.

And for those with hope, there is Dr. Steven Eisenberg

On a Slippery Slope?  Euthanasia in Belgium and the Netherlands

JAMA Network | JAMA Internal Medicine | Euthanasia in Belgium and the Netherlands:  On a Slippery Slope?

Legionairres Disease Outbreak in NYC...

A sign hangs outside Lincoln Medical Center where a cooling tower has been tested and disinfected following a deadly outbreak of Legionnaires' disease in the South Bronx region, New York August 7, 2015.
REUTERS/LUCAS JACKSON

The New York City Council voted unanimously on Thursday to pass legislation that mandates strict regulations of cooling towers, a move that comes in response to the current outbreak of Legionnaires’ disease in the South Bronx. The Council voted 42-0 in favor of new regulations that will require all cooling towers be registered, tested and then disinfected if they’re found to contain Legionellabacteria. Cooling towers are used to regulate temperatures indoors and are part of ventilation systems in many modern residential buildings. Failure to comply with the law could cost a property owner as much as $25,000 in fines and a year in jail.

The current outbreak of the potentially fatal bacterial pneumonia has killed 12 people and sickened more than 100 in the South Bronx. The victims contracted the illness after breathing in contaminated water vaporized through cooling systems.

“We must do everything we can to proactively prevent outbreaks of Legionnaires’ disease, which is why legislation requiring regular inspections and testing of cooling towers is extremely important,” Jumaane Williams, city council member and chair of the committee on housing and buildings, said in statement. “Without proper maintenance, cooling towers can accrue an overgrowth of Legionella,causing what has proven to be a fatal outcome for far too many New Yorkers.”

What is Legionnaires Disease?

The illness was originally called " Pontiac Disease",  named after an outbreak in Michigan. It was associated with steam cleaning of water turbines.

Microscopic view of Legionela pneumophila

The bacteria are the long cylindrical figures. The cells are leucocytes, macrophages (single nucleus) polymorphonucleophages (multilobed nucleus) The nucleus is the darkly stained structure near the center of each cell. It takes up the stain more intensely since the nucleus contains DNA.

Startups Vie to Build an Uber for Health Care -

The uberization of health care access in the United States is a real  possibility.

Given the enormous change in the business of health, and it's rapid adoption of new technologies the trend may bein place for this to occur.  Insurers are desperate to control costs,and providers seem to have become pawns in the chess game of health care management.

There has already been a reduction in hospital admissions and penalties for readmissions. Outpatent care reigns, and that too will come under scrutiny.  The house call may return with the assistance of wearables, remote monitoring of cardiac EKG, thermal imaging and technician ultrasound, (technicians already perform these tests in office). Results can be electronically transmitted and analyzed remotely by a provider and other  certified mobile devices that measure blood chemistry, urine analysis. external photography, including diabetic eye screening for diabetic retinopathy.

Most of these procedures can be reimbursed for the service and provider interpretation. Insurers may w ish to contract directly with mobile health services for efficiency and to reduce administrative burden on  provider facilities.
Many rapid micro-analytic devices are in the FDA approval pipeline.

In the coming decade medicine and health care routines may become unrecognizable compared to today's practice patterns.

Eve Rorison, a nurse who works for Pager, conducts a wellness check for Facebook executive Kunal Merchant at his New York offices. Services like Pager are putting a high-tech spin on old-fashioned house calls. PHOTO: MELINDA BECK/THE WALL STREET JOURNAL

Can providers and regulatory bodies survive the change as providers and patients demand patient centered medicine.  Perhaps forward looking boards and licensing organizations will become leaders.

But don't hold your breath.  Current and past behavior runs counter to this change..  The synergy of HIT,increasing utilization, and the mandates of the Affordable Care Act will conspire to accelerate the process of change.





tartups Vie to Build an Uber for Health Care - WSJ

We're overdosing on medicine – it's time to embrace life's uncertainty

The more we learn about the problem of too much medicine and what’s driving it, the harder it seems to imagine effective solutions. Winding back unnecessary tests and treatments will require a raft of reforms across medical research, education and regulation.

But to enable those reforms to take root, we may need to cultivate a fundamental shift in our thinking about the limits of medicine. It’s time to free ourselves from the dangerous fantasy that medical technology can deliver us from the realities of uncertainty, ageing and death.

We’re all ill now

A growing body of evidence shows that when it comes to health care, we may simply be getting too much of a good thing. In the United States, it’s estimated that more than US$200 billion a year is squandered on unnecessary tests and treatments. In the United Kingdom, senior medical groups are calling on doctors to reduce all the wasteful things they do. And in Australia, the Choosing Wisely campaign recently kicked off with lists of unnecessary and harmful health care.

Not only are we overusing pills and procedures, we’re creating even more problems with “overdiagnosis” by labelling more and more healthy people with diseases that will never harm them.

Screening programs targeting the healthy can detect potentially deadly cancers and extend lives. But they can also find many early abnormalities that are then treated as cancers, even though they would never have caused anyone any symptoms if left undetected.

The common ups and downs of our sex lives are often re-labelled as medical dysfunctions. Older people who are simply at risk of future illness – those with high cholesterol, for instance, or reduced kidney function, or low bone mineral density – are portrayed as if they were diseased.  Have we set the threshold for illness and/or disease too low?

•   

The more we learn about the problem of too much medicine and what’s driving it, the harder it seems to imagine effective solutions. Winding back unnecessary tests and treatments will require a raft of reforms across medical research, education and regulation.

But to enable those reforms to take root, we may need to cultivate a fundamental shift in our thinking about the limits of medicine. It’s time to free ourselves from the dangerous fantasy that medical technology can deliver us from the realities of uncertainty, ageing and death.

We’re all ill now

A growing body of evidence shows that when it comes to health care, we may simply be getting too much of a good thing. In the United States, it’s estimated that more than US$200 billion a year is squandered on unnecessary tests and treatments. In the United Kingdom, senior medical groups are calling on doctors to reduce all the wasteful things they do. And in Australia, the Choosing Wisely campaign recently kicked off with lists of unnecessary and harmful health care.

Not only are we overusing pills and procedures, we’re creating even more problems with “overdiagnosis” by labelling more and more healthy people with diseases that will never harm them.

Screening programs targeting the healthy can detect potentially deadly cancers and extend lives. But they can also find many early abnormalities that are then treated as cancers, even though they would never have caused anyone any symptoms if left undetected.

The common ups and downs of our sex lives are often re-labelled as medical dysfunctions. Older people who are simply at risk of future illness – those with high cholesterol, for instance, or reduced kidney function, or low bone mineral density – are portrayed as if they were diseased.

The doctors expanding disease definitions and lowering the thresholds at which diagnoses are made are often being paid directly by the companies that stand to benefit from turning millions more people into patients.

Fundamental shifts in thinking

Indeed, intolerance of uncertainty has been suggested as among the most important drivers of medical excess. Doctors order ever more tests to try, often in vain, to be sure about what they’re seeing – to be more certain. But disease and the benefits and harms of treating it are inevitably fraught with uncertainty because we’re trying to apply knowledge derived from populations to unique individuals.

More broadly, uncertainty is the basis of all scientific creativity, intellectual freedom and political resistance. We should nurture uncertainty, treasure it and teach its value, rather than be afraid of it.

No matter how much the marketers of medicines try to make us feel broken by the

mere passing of time, ageing is not a disease. Disease definitions that equate “normal” with being young are fundamentally flawed and require urgent review.

Everyone must die and everyone, patients and doctors alike, is more or less fearful of dying. So, it’s perhaps not surprising that we so often turn to biotechnical approaches rather than paying real attention to the care of the dying – a core purpose of medicine.

But, there are many positive signs of change within medicine. The Choosing Wisely campaign mentioned above is a partnership between doctors and wider civil society. And it’s now an international movement to wind back excess medicine.

A new approach called shared decision making is promoting much more honest conversations between doctors and the people they care for, embracing uncertainty about benefits and harms, rather than peddling false hopes. Another new approach among GPs called quaternary prevention is urging doctors to protect people from unnecessary medical labels and unwarranted tests and treatments.

Quaternary prevention is a group of measures taken to prevent, decrease and/or alleviate the harm caused by health activities. Health activities not only generally produce benefits, but also harm. That is to say, although medical intervention is mainly favourable, there is a dynamic balance that requires continuous assessment of the clinical situation as naturally only those health activities that achieve more benefit than harm at the end are justified. Quaternary prevention is the avoidance of unnecessary medical activity, such as "check-ups". In another example, quaternary prevention is the recommendation of preventive measures of proven efficacy. As regards diagnosis, quaternary prevention is, for example, the avoidance of screening without foundation, such as in prostate cancer. The appropriate use of antibiotics in upper respiratory tract infections serves as an example of quaternary prevention in the field of treatment. Another example is the application of the correct rehabilitation techniques in non-specific low back pain, such as swimming and maintaining an active life as much as possible. Not to forget other important "non-classic" aspects in the elderly, such as to limit the harm that can be caused by physical movement restriction devices. These and other examples in daily practice are considered in this article to encourage the continual assessment of quaternary prevention, the classic primum non nocere "first, do no harm".



We're overdosing on medicine – it's time to embrace life's uncertainty

Small Businesses Face New Obamacare Threat - Forbes

Small Businesses Face New Obamacare Threat - Forbes

Health IT Cyber Thieves have their own "ENIGMA"` machines

Veterans of World War II will remember the efforts to crack the Japanese encryption used for military communication during WWII.

Enigma was invented by the German engineer Arthur Scherbius at the end of World War I.^[1] Early models were used commercially from the early 1920s, and adopted by military and government services of several countries, most notably Nazi Germany before and during World War II.^[2] Several different Enigma models were produced, but the German military models are the most commonly recognised.

The mechanical/electrical components of the device were easily duplicated. The secret sauce was in the encryption method. 

German military messages enciphered on the Enigma machine were first broken by the Polish Cipher Bureau, beginning in December 1932. This success was a result of efforts by three Polish cryptologists, Marian Rejewski, Jerzy Różycki and Henryk Zygalski, working for Polish military intelligence. Rejewski reverse-engineered the device, using theoretical mathematics and material supplied by French military intelligence. Subsequently the three mathematicians designed mechanical devices for breaking Enigma ciphers, including the cryptologic bomb. From 1938 onwards, additional complexity was repeatedly added to the Enigma machines, making decryption more difficult and requiring further equipment and personnel—more than the Poles could readily produce.

On 25 July 1939, in Warsaw, the Poles initiated French and British military intelligence representatives into their Enigma-decryption techniques and equipment, including Zygalski sheets and the cryptologic bomb, and promised each delegation a Polish-reconstructed Enigma. The demonstration represented a vital basis for the later British continuation and effort.^[3] During the war, British cryptologists decrypted a vast number of messages enciphered on Enigma. The intelligence gleaned from this source, codenamed "Ultra" by the British, was a substantial aid to the Allied war effort.^[4]

What does this have to do with health information technology and mobile health in particular?

Ask Google, since they are planning regular weekly updates to the android operating system.

Google's comment regarding the 'stagefright' hack, 

"This vulnerability was identified in a laboratory setting on older Android devices, and as far as we know, no one has been affected. As soon as we were made aware of the vulnerability we took immediate action and sent a fix to our partners to protect users...As part of a regularly scheduled security update, we plan to push further safeguards to Nexus devices starting next week. And, we'll be releasing it in open source when the details are made public by the researcher at BlackHat."  How to see if your Android Device is vulnerable to the Stagefright hack ?

Google's Android Blog  "Nexus devices will continue to receive major updates for at least two years and security patches for the longer of three years from initial availability or 18 months from last sale of the device via the Google Store."

In recent months many breaches have been reported by health insurers. In most instances medical records were not accessed other than an attempt to gather consumer identification and credit information. Identity theft is a major concern.

The moral of the story is that security breaches will be present for a long time. Thieves are inventive.

Catch and Release - Finding Life in Death: Michael Fratkin at TEDxEureka

Dying is not a medical Condition



The Boundaries of Living and Dying, is discussed by Michael Fratkin describing his first experience with death as a six year old, and his anger with  adults keeping a secret about dying from a child.

A palliative physician manages his fear that he would fail a family.   Story telling and laughing replace the handwringing at death. The family reconnects in a way never possible before.

He reviews the stages of dying, as set to stages by  Elizabeth Kubler-Ross. Anger, Bargaining  Depression, Denial, & Acceptance








"We prepare for birth, but rarely prepare for death."  .
Manage yourself to be present at death.

Dr Michael Fratkin practices in Humbholdt community, Eureka, California.  Listening to a SoundCloud Presentation audio file, Dr Fratkin discusses one of his major goals to help people dying where there is no hospice and few trained cancer specialists (oncologist)

Dr. Fratkin developed a Crowdfunding Campaign to support these services, for patients who could not afford these types of services.

Closing Music on Dying (Alex Fox) Soundcloud audio file