DIA 2012


We would like to welcome our new readers from the annual DIA meeting, held in Philadelphia last week. ON TARGET now goes out directly to over 4,300 readers each week.


Brain Power in the lounge section of the Target Health Inc. booth at DIA, this past week.  From left to right: Joonhyuk Choi,  Neil Lassalle, Warren Pearlson, Yong Joong Kim.


It was a productive meeting for all and good to meet our friends and colleagues. The presentations at the Forum of Risk-Based and Centralized Monitoring were well-received, and the topic has a lot of buzz for sure. We spent quality time with Dr. Jack Lee, CEO of LSK, our Korean partner, who is running full speed ahead building EDC applications with Target e*Studio™.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com




Head and Neck


Alimentary system


Reproductive system


Calcium Regulation






The endocrine system is the system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the 1) ___. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words “endo” meaning inside, within, and “crinis” for secrete. The endocrine system is an information signal system like the nervous system, yet its effects and mechanism are classifiably different. The endocrine system’s effects are slow to initiate, and prolonged in their response, lasting from a few hours up to weeks. The nervous system sends information very 2) ___, and responses are generally short lived. Hormones are substances (chemical mediators) released from endocrine tissue into the bloodstream where they travel to target tissue and generate a response. Hormones 3) ___ various human functions, including metabolism, growth and development, tissue function, and mood. The field of study dealing with the endocrine system and its disorders is endocrinology, a branch of internal medicine.


Features of endocrine glands are, in general, their ductless nature, their vascularity, and usually the presence of intracellular vacuoles or granules storing their hormones. In contrast, 4) ___ glands, such as salivary glands, sweat glands, and glands within the gastrointestinal tract, tend to be much less vascular and have ducts or a hollow lumen. In addition to the specialized endocrine organs mentioned above, many other organs that are part of other body systems, such as the kidney, liver, heart and gonads, have secondary endocrine functions. For example the kidney secretes endocrine hormones such as erythropoietin and renin.


The endocrine system is made of a series of 5) ___ that produce chemicals called hormones. A number of glands that signal each other in sequence are usually referred to as an axis, for example, the hypothalamic-pituitary-adrenal axis.


Endocrinology is a branch of 6) ___ and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation (including histogenesis and organogenesis) and the coordination of metabolism, respiration, excretion, movement, reproduction, and sensory perception depend on chemical cues, substances synthesized and secreted by specialized cells. 7) ___ is concerned with the study of the biosynthesis, storage, chemistry, and physiological function of hormones and with the cells of the endocrine glands and tissues that secrete them.


The endocrine system consists of several glands, all and in different parts of the body, that secrete hormones directly into the blood rather than into a duct system. Hormones have many different functions and modes of action; one hormone may have several effects on different target organs, and, conversely, one target organ may be affected by more than one 8) ___.


In the original 1902 definition by Bayliss and Starling, they specified that, to be classified as a hormone, a chemical must be produced by an organ, be released (in small amounts) into the blood, and be transported by the blood to a distant organ to exert its specific function. This definition holds for most “classical” hormones, but there are also paracrine mechanisms (chemical communication between cells within a tissue or organ), autocrine signals (a chemical that acts on the same cell), and intracrine signals (a chemical that acts within the same cell). A neuroendocrine signal is a “classical” hormone that is released into the 9) ___ by a neurosecretory neuron.


Hormones act by binding to specific receptors in the target organ. As Baulieu notes, a receptor has at least two basic constituents: a recognition site, to which the hormone binds and an effector site, which precipitates the modification of cellular function. Between these is a “transduction mechanism” in which hormone binding induces allosteric modification that, in turn, produces the appropriate response.


Diseases of the endocrine system are common, including conditions such as 10) ___ mellitus, thyroid disease, and obesity. Endocrine disease is characterized by disregulated hormone release (a productive pituitary adenoma), inappropriate response to signaling (hypothyroidism), lack of a gland (diabetes mellitus type 1, diminished erythropoiesis in chronic renal failure), or structural enlargement in a critical site such as the thyroid (toxic multinodular goitre). Hypofunction of endocrine glands can occur as a result of loss of reserve, hyposecretion, agenesis, atrophy, or active destruction. Hyperfunction can occur as a result of hypersecretion, loss of suppression, hyperplastic or neoplastic change, or hyperstimulation.


Endocrinopathies are classified as primary, secondary, or tertiary. Primary endocrine disease inhibits the action of downstream glands. Secondary endocrine 11) ___ is indicative of a problem with the pituitary gland. Tertiary endocrine disease is associated with dysfunction of the hypothalamus and its releasing hormones. As the thyroid, and hormones have been implicated in signaling distant tissues to proliferate, for example, the estrogen receptor has been shown to be involved in certain breast cancers. Endocrine, paracrine, and autocrine signaling have all been implicated in proliferation, one of the required steps of oncogenesis. Oncogenesis or tumorigenesis is literally the creation of 12) ___. It is a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes on the cellular and genetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.


ANSWERS: 1) body; 2) quickly; 3) regulate; 4) exocrine; 5) glands; 6) biology; 7) Endocrinology; 8) hormone; 9) blood; 10) diabetes; 11) disease; 12) cancer

History and Key Discoveries of Endocrinology


Arnold Adolph Berthold 1803-1861


Arnold Berthold, known as a pioneer in endocrinology, was a German physiologist and zoologist. He studied medicine in Gottingen in 1819 and wrote his thesis under the direction of Johann Friedrich Blumenbach (1752-1840). Berthold became a private lecturer in 1825 and began to teach physiology at the University of Gottingen where he spent the rest of his career. He is known as a pioneer in endocrinology due to his experiments on the role of the gonads in the development of secondary sexual characteristics. He published important works on reptiles and amphibians as well as on avian physiology. In the field of entomology, he authored Naturliche Familien des Thierreichs (1827). Berthold is particularly famous for his work on endocrinology. In 1849, Berthold performed ground breaking experiments with chicken castration.


According to Robert K. G. Temple, the study of endocrinology began in China. The Chinese were isolating reproduction and pituitary hormones from human urine and using them for medicinal purposes by 200 BCE. They used many complex methods, such as saponification. Chinese medical texts, some dating no later than 1110 CE, specified a method with the use of gypsum (containing calcium sulfate) as well as saponin from the beans of Gleditschia sinensis to extract hormones. Eventually, in 1849, when Arnold Berthold noted that castrated cockerels did not develop combs and wattles or exhibit overtly male behavior, modern endocrinology began. He found that replacement of testes back into the abdominal cavity of the same bird or another castrated bird resulted in normal behavioral and morphological development, and he concluded (erroneously) that the testes secreted a substance that “conditioned” the blood that, in turn, acted on the body of the cockerel. In fact, one of two other things could have been true: that the testes modified or activated a constituent of the blood or that the testes removed an inhibitory factor from the blood. It was not proven that the testes released a substance that engenders male characteristics until it was shown that the extract of testes could replace their function in castrated animals. Pure, crystalline testosterone was isolated in 1938.


Although most of the relevant tissues and endocrine glands had been identified by early anatomists, a more humoral approach to understanding biological function and disease was favored by the ancient Greek and Roman thinkers such as Aristotle, Hippocrates, Lucretius, Celsus, and Galen, according to Freeman et al., and these theories held sway until the advent of germ theory, physiology, and organ basis of pathology in the 19th century.


According to Iranian author Nabipour I., in medieval Persia, Avicenna (980-1037) provided a detailed account on diabetes mellitus in The Canon of Medicine (c. 1025), “describing the abnormal appetite and the collapse of sexual functions and he documented the sweet taste of diabetic urine.” Like Aretaeus of Cappadocia before him, Avicenna recognized a primary and secondary diabetes. He also described diabetic gangrene, and treated diabetes using a mixture of lupine, trigonella (fenugreek), and zedoary seed, which produces a considerable reduction in the excretion of sugar, a treatment which is still prescribed in modern times. Avicenna also “described diabetes insipidus very precisely for the first time”, though it was later Johann Peter Frank (1745-1821) who first differentiated between diabetes mellitus and diabetes insipidus.


According to Jan-Gustaf Ljunggren, in an article in the Swedish journal Lakartidningen (1983; No 32-33), in the 12th century, Zayn al-Din al-Jurjani, another Muslim physician, provided the first description of Graves’ disease after noting the association of goitre and exophthalmos in his Thesaurus of the Shah of Khwarazm, the major medical dictionary of its time. Al-Jurjani also established an association between goiter and palpitation. Graves’ disease was named after Irish doctor Robert James Graves, who described a case of goiter with exophthalmos in 1835. The German Karl Adolph von Basedow also independently reported the same constellation of symptoms in 1840, while earlier reports of the disease were also published by the Italians Giuseppe Flajani and Antonio Giuseppe Testa, in 1802 and 1810 respectively, and by the English physician Caleb Hillier Parry (a friend of Edward Jenner) in the late 18th century. Thomas Addison was first to describe Addison’s disease in 1849.


Thomas Addison (1793 – 1860) was a renowned 19th-century English physician and scientist. He is traditionally regarded as one of the “great men” of Guy’s Hospital in London. Among other pathologies he discovered Addison’s disease (a degenerative disease of the adrenal glands) and Addisonian anemia (pernicious anemia), a hematological disorder later found to be caused by failure to absorb vitamin B12.


Thomas Addison MD 1793-1860


In 1902 William Bayliss and Ernest Starling performed an experiment in which they observed that acid instilled into the duodenum caused the pancreas to begin secretion, even after they had removed all nervous connections between the two. The same response could be produced by injecting extract of jejunum mucosa into the jugular vein, showing that some factor in the mucosa was responsible. They named this substance “secretin” and coined the term hormone for chemicals that act in this way.


Joseph von Mering and Oskar Minkowski made the observation in 1889 that removing the pancreas surgically led to an increase in blood sugar, followed by a coma and eventual death – symptoms of diabetes mellitus. In 1922, Banting and Best realized that homogenizing the pancreas and injecting the derived extract reversed this condition. The hormone responsible, insulin, was not discovered until Frederick Sanger sequenced it in 1953.


Neurohormones were first identified by Otto Loewi in 1921. He incubated a frog’s heart (innervated with its vagus nerve attached) in a saline bath, and left in the solution for some time. The solution was then used to bathe a non-innervated second heart. If the vagus nerve on the first heart was stimulated, negative inotropic (beat amplitude) and chronotropic (beat rate) activity were seen in both hearts. This did not occur in either heart if the vagus nerve was not stimulated. The vagus nerve was adding something to the saline solution. The effect could be blocked using atropine, a known inhibitor to heart vagal nerve stimulation. Clearly, something was being secreted by the vagus nerve and affecting the heart. The “vagusstuff” (as Loewi called it) causing the myotropic (muscle enhancing) effects was later identified to be acetylcholine and norepinephrine. Loewi won the Nobel Prize for his discovery.


Recent work in endocrinology focuses on the molecular mechanisms responsible for triggering the effects of hormones. The first example of such work being done was in 1962 by Earl Sutherland. Sutherland investigated whether hormones enter cells to evoke action, or stayed outside of cells. He studied norepinephrine, which acts on the liver to convert glycogen into glucose via the activation of the phosphorylase enzyme. He homogenized the liver into a membrane fraction and soluble fraction (phosphorylase is soluble), added norepinephrine to the membrane fraction, extracted its soluble products, and added them to the first soluble fraction. Phosphorylase activated, indicating that norepinephrine’s target receptor was on the cell membrane, not located intracellularly. He later identified the compound as cyclic AMP (cAMP) and with his discovery created the concept of second-messenger-mediated pathways. He, like Loewi, won the Nobel Prize for his groundbreaking work in endocrinology.

NIH Provides Heat-Related Illness Advice for Older People


Hyperthermia is an abnormally high body temperature caused by a failure of the heat-regulating mechanisms of the body to deal with the heat coming from the environment. Heat fatigue, heat syncope (sudden dizziness after prolonged exposure to the heat), heat cramps, heat exhaustion and heat stroke are commonly known forms of hyperthermia. Risk for these conditions can increase with the combination of outside temperature, general health and individual lifestyle.


Lifestyle factors can include not drinking enough fluids, living in housing without air conditioning, lack of mobility and access to transportation, overdressing, visiting overcrowded places and not understanding how to respond to hot weather conditions. Hot summer weather can pose special health risks to older adults. The National Institute on Aging (NIA), part of the National Institutes of Health, has some advice for helping older people avoid heat-related illnesses.


Older people, particularly those with chronic medical conditions, should stay indoors on hot and humid days, especially when an air pollution alert is in effect. People without air conditioners should go to places that do have air conditioning, such as senior centers, shopping malls, movie theaters and libraries. Cooling centers, which may be set up by local public health agencies, religious groups and social service organizations in many communities, are another option.


Health-related factors, some especially common among older people, that may increase risk of hyperthermia include:


  • Being dehydrated.
  • Age-related changes to the skin such as impaired blood circulation and inefficient sweat glands.
  • Heart, lung and kidney diseases, as well as any illness that causes general weakness or fever.
  • High blood pressure or other conditions that require changes in diet. For example, people on salt-restricted diets may be at increased risk. However, salt pills should not be used without first consulting a doctor.
  • Reduced sweating, caused by medications such as diuretics, sedatives, tranquilizers and certain heart and blood pressure drugs.
  • Taking several drugs for various conditions. It is important, however, to continue to take prescribed medication and discuss possible problems with a physician.
  • Being substantially overweight or underweight.
  • Drinking alcoholic beverages.


Heat stroke is a life-threatening form of hyperthermia. It occurs when the body is overwhelmed by heat and unable to control its temperature. Heat stroke occurs when someone’s body temperature increases significantly (generally above 104 degrees Fahrenheit) and has symptoms such as mental status changes (like confusion or combativeness), strong rapid pulse, lack of sweating, dry flushed skin, faintness, staggering, or coma. Seek immediate emergency medical attention for a person with any of these symptoms, especially an older adult.


If you suspect that someone is suffering from a heat-related illness:


  • Get the person out of the heat and into a shady, air-conditioned or other cool place. Urge them to lie down.
  • If you suspect heat stroke, call 911.
  • Encourage the individual to shower, bathe or sponge off with cool water.
  • Apply a cold, wet cloth to the wrists, neck, armpits, and/or groin. These are places where blood passes close to the surface of the skin, and the cold cloths can help cool the blood.
  • If the person can swallow safely, offer fluids such as water, fruit and vegetable juices, but avoid alcohol and caffeine.


The Low Income Home Energy Assistance Program (LIHEAP) within the Administration for Children and Families in the U.S. Department of Health and Human Services helps eligible households pay for home cooling and heating costs. People interested in applying for assistance should contact their local or state LIHEAP agency.


You can get a free copy of the NIA’s AgePage on hyperthermia.


Cumulative Birth Rates with Linked Assisted Reproductive Technology Cycles


Live-birth rates after treatment with assisted reproductive technology (AKA “test-tube babies”) have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure. As a result, in order to estimate cumulative live-birth rates in individual women, a study published in the New England Journal of Medicine (2012; 366:2483-2491) linked data from cycles of assisted reproductive technology from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009.


For the study, conservative estimates assumed that women who did not return for treatment would not have a live birth. In contrast, optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment.


Results were from summarized from 246,740 women, with 471,208 cycles and 140,859 live births. The data showed that live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age, and to 6.6% and 11.3% for those 43 years of age or older.


When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used.


According to the authors, the results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used.

Effectiveness of the H1N1 Vaccine for the Prevention of Pandemic Influenza in Scotland


It is all about evolution and good science.


A targeted vaccination program for pandemic H1N1 2009 influenza was introduced in Scotland, UK, in October, 2009. A study, published in The Lancet Infectious Diseases, Early Online Publication (26 June 2012), assessed the effectiveness of this vaccine in a sample of the Scottish population during the 2009-10 pandemic using a retrospective cohort design.


The authors linked data of patient-level primary care, hospital records, death certification, and virological swabs to construct the cohort. Vaccine effectiveness was estimated in a nationally representative sample of the Scottish population by establishing the risk of hospital admission and death (adjusted for potential confounders) resulting from influenza-related morbidity in vaccinated and unvaccinated patients and laboratory-confirmed cases of influenza H1N1 2009 in a subset of patients.


The Pandemic H1N1 2009 influenza vaccination began in week 43 of 2009 (Oct 21, 2009) and was given to 38,296 (15.5%) of 247,178 people by the end of the study period (Jan 31, 2010). As a result, 208,882 (85%) were unvaccinated. During the study there were 5,207 emergency hospital admissions and 579 deaths in the unvaccinated population and 924 hospital admissions and 71 deaths in the vaccinated population during 23,893,359 person-days of observation.


The effectiveness of H1N1 vaccination for prevention of emergency hospital admissions from influenza-related disorders was 19.5% and the vaccine’s effectiveness in preventing laboratory-confirmed influenza was 77.0%.


According to the authors, Pandemic H1N1 2009 influenza vaccination was associated with protection against pandemic influenza and a reduction in hospital admissions from influenza-related disorders in Scotland during the 2009-10 pandemic.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area


FDA Approves Belviq to Treat Some Overweight or Obese Adults


Body mass index (BMI), which measures body fat based on an individual’s weight and height, is used to define the obesity and overweight categories. According to the Centers for Disease Control and Prevention, more than one-third of adults in the United States are obese.


The FDA has approved Belviq (lorcaserin hydrochloride), as an addition to a reduced-calorie diet and exercise, for chronic weight management. The drug is approved for use in adults with a BMI of 30 or greater (obese), or adults with a BMI of 27 or greater (overweight) and who have at least one weight-related condition such as high blood pressure (hypertension), type 2 diabetes, or high cholesterol (dyslipidemia). Belviq works by activating the serotonin 2C receptor in the brain. Activation of this receptor may help a person eat less and feel full after eating smaller amounts of food.


The safety and efficacy of Belviq were evaluated in three randomized, placebo-controlled trials that included nearly 8,000 obese and overweight patients, with and without type 2 diabetes, treated for 52 to 104 weeks. All participants received lifestyle modification that consisted of a reduced calorie diet and exercise counseling. Compared with placebo, treatment with Belviq for up to one year was associated with average weight loss ranging from 3% to 3.7%.


About 47% of patients without type 2 diabetes lost at least 5% of their body weight compared with about 23% of patients treated with placebo. In people with type 2 diabetes, about 38% of patients treated with Belviq and 16% treated with placebo lost at least 5% of their body weight. Belviq treatment was associated with favorable changes in glycemic control in those with type 2 diabetes. The approved labeling for Belviq recommends that the drug be discontinued in patients who fail to lose 5% of their body weight after 12 weeks of treatment, as these patients are unlikely to achieve clinically meaningful weight loss with continued treatment.


Belviq should not be used during pregnancy.


Treatment with Belviq may cause serious side effects, including serotonin syndrome, particularly when taken with certain medicines that increase serotonin levels or activate serotonin receptors. These include, but are not limited to, drugs commonly used to treat depression and migraine. Belviq may also cause disturbances in attention or memory.


In 1997, the weight-loss drugs fenfluramine and dexfenfluramine were withdrawn from the market after evidence emerged that they caused heart valve damage. This effect is assumed to be related to activation of the serotonin 2B receptor on heart tissue. When used at the approved dose of 10 milligrams twice a day, Belviq does not appear to activate the serotonin 2B receptor.


Heart valve function was assessed by echocardiography in nearly 8,000 patients in the Belviq development program. There was no statistically significant difference in the development of FDA-defined valve abnormalities between Belviq and placebo-treated patients. Because preliminary data suggest that the number of serotonin 2B receptors may be increased in patients with congestive heart failure, Belviq should be used with caution in patients with this condition. Belviq has not been studied in patients with serious valvular heart disease.


The drug’s manufacturer will be required to conduct six postmarketing studies, including a long-term cardiovascular outcomes trial to assess the effect of Belviq on the risk for major adverse cardiac events such as heart attack and stroke.


The most common side effects of Belviq in non-diabetic patients are headache, dizziness, fatigue, nausea, dry mouth, and constipation, and in diabetic patients are low blood sugar (hypoglycemia), headache, back pain, cough, and fatigue.


Belviq is manufactured by Arena Pharmaceuticals GmbH of Zofingen, Switzerland, and distributed by Eisai Inc. of Woodcliff Lake, N.J.

Rooftop Gardens in New York City


Brooklyn Grange Urban Rooftop Farming



Brooklyn Grange is a commercial organic farm located on New York City rooftops. They grow vegetables in the city and sell them to local people and businesses. The goal is to improve access to very good food, to connect city people more closely to farms and food production, and to make urban farming a viable enterprise and livelihood.


Although the Brooklyn Grange functions as a privately owned and operated enterprise, it is is community oriented and open to the public. School groups, families and volunteers are welcome to visit, participate and learn. This is a green space that contributes to the overall health and quality of life of the community, bringing people together through green business and around good food.


The first farm is located at 37-18 Northern Boulevard, in Long Island City Queens. Our goal is to put more farms on roofs throughout New York and beyond, and grow more food, train and employ more farmers, and improve overall quality of life in the city.


Brooklyn Grange is a small business now, but they plan to expand so that they can build more farms on roofs throughout New York and beyond. If you are interested in getting involved with the farm, please contact brooklyngrangefarm@gmail.com.

Affordable Care – Where Do We Go From Here?


By Mark L. Horn, MD, MPH, Chief Medical Officer, Target Health Inc.



The complex Supreme Court decision on the Affordable Care Act (hereafter the ‘ACA) has managed to surprise virtually everyone. As one of my colleagues noted just after it was issued, the decision was destined to be controversial and guaranteed to infuriate a significant segment of the body politic. Given that inevitable certainty, at least the Court made it interesting.


It is beyond the scope of this brief commentary and certainly beyond the expertise of this writer to venture into the complexities of constitutional law or the merits of Chief Justice Robert’s surprising and clearly unexpected opinion. What can be addressed is its salutary impact upon widespread (and realistic) individual anxieties about health care as a consequence of the (at this point almost certainly permanent) policy changes embedded in the ACA.


Specifically, significant numbers of our fellow citizens, among them those with pre-existing conditions unable to secure insurance and threatened by catastrophic health expenses, and those living in poverty, unable to afford insurance or pay ‘out of pocket’ for care and consequently unable or unwilling to access the system absent an emergency, will now have options. In addition, citizens lacking employer based coverage will be eligible for income based subsidies to help purchase insurance through insurance exchanges, income levels for Medicaid eligibility will be adjusted, and the reimbursement for primary care providers to this cohort, currently so low it impedes care, will be  increased.


The reason these changes are likely permanent is that they are both logical and humane; on multiple levels they are good for patients, physicians, and society. Sadly, our current system assures that individuals who have ‘played by the rules’ their entire lives, worked hard and contributed to the economy (and through payroll withholding into our social welfare system), can suddenly find themselves unemployed, uninsured, ill and facing financial ruin.


It is virtually impossible to envision any political solution that would ‘undo’ these fixes in the ACA and be acceptable to the public. Therefore, it is highly likely that initiatives to repeal the ACA, to have any hope of success, will necessarily need to propose replacement legislation that addresses these key deficiencies in our current system. If the coming debate now focuses on designing potentially improved and more cost effective solutions to these same problems, that is a good outcome. However, and happily, proposals overturning the solution now in place while offering no viable alternative seem implausible, political ‘non-starters’.


Therefore, those opposed to the ACA are now working from a different, and for society more constructive set of premises; they must now propose solutions that offer either higher quality and/or lower cost solutions to these critical health system challenges.


Given all the angst of the past months, that is not a bad place to be. Congress, Silicon Valley, and software developers everywhere, this is an interesting challenge for all.