We Welcome CRO Partners to Use Our Software

 

Target Health Inc. (THI) is pleased to announce that we are now also a CRO to CRO’s, as software developed by THI is now being used under direct contracts with 4 CROs in regions as far away as China, Korea, Israel and Argentina. We are cost effective and our eSource software has been used or is being used in 17 studies, including 2 pivotal studies with FDA submissions planned for this year. The first FDA submission will occur in January 2015. Additional highlights include an ongoing 400 patient, 40-center study in neurology and a 25 center study with 300 patients in autism, which will start in February 2015.

 

All of our software is web-based and can be used on any device that has an Internet connection, even on the iPhone, iPad and any android device.

 

There is NO CHARGE for training and no up-front costs for those CROs who want to in-license Target e*Studio® to build EDC applications. With the new graphic user interface (GUI), for a recent study, we were able to build 99% of forms and edit checks with staff with NO programming experience. Our software is ideal for large and small CROs/companies and we have a track record of regulatory approvals.  Note that the EDC application comes with built in features such as:

 

1. Target e*CTR® (eClinical Trial Record eSource solution)

2. Target Randomization (online randomization/allocation)

3. Encoder® (Coding with MedDRA and WHODrug)

4. Target SAE Management™ (generates For, FDA 3500A and CIOMS 1 and 2)

5. Target Monitoring Reports™ (Qualification, Initiation, Onsite, Central and Closeout)

6. Target IMP Management (Drug supply tracking)

7. Target RBM™ (fully integrated reports supporting risk-based monitoring)

8. Target Informed Consent™ (online eSignature of study subjects and caregivers)

9. Target ePRO™ (Online data entry by study subjects and caregivers)

 

We also have a very sophisticated document system ideal for the eTrial Master File (eTMF)

 

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Freedom Tower, New York City at Dusk – ©Target Health 2015

 

ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.

 

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.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

QUIZ

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A 100-Year Study of Artificial Intelligence

20150112-8

MICROSOFT RESEARCH – Eric Horvitz

 

Eric Horvitz, managing director of the Microsoft Research lab in Redmond, Washington, is launching a project he wants to last a century. The One Hundred Year Study on Artificial Intelligence (AI100), based at Stanford University in Palo Alto, California, and funded by Horvitz and his wife, aims to track the impact of artificial intelligence (AI) on all aspects of 1) ___, from national security to public psychology and privacy. Horvitz recently helped create a standing committee of interdisciplinary researchers who serve rotating terms, to convene study panels that will produce a major report every 5 years. The first report is expected at the end of this year.

 

According to Horvitz, machine intelligence will have deep effects on people and society, and the influences will be changing over time. In addition, it would be nice to have a platform where there’s a long vision to the future as well as a sharp connected memory through sets of studies. For example, when it comes to understanding the relationship of machine 2) ___ and privacy, we are already seeing science that uses innocuous data like search logs and tweets to make predictions about the likelihood of somebody being at higher risks for certain illnesses. These kinds of things need to be studied. The goal is to set up a system with an initial standing committee that will do a great job at self-sustaining and continuing a chain of these standing committees and study panels over 3) ___ years. Imagine how certain topics might become strong forerunners in different decades. For example, ethical issues with the automation of key high-stakes decisions might come to the fore sometime in the next decade, when we might have more autonomous cars on the roads and automated systems being used in warfare. Horvitz thinks that it will be interesting for these panels to look back at what [earlier panels] addressed and had forecast, what guidance [they] provided, and how it all went. One hundred years can seem like a long time, but a lot can happen in 100 years of 4) ___. Imagine we were planning on tracking how the rise of electricity might change the world from 1900 on.

 

Horvitz thinks that the studies will be ahead of the wave. It’s not just studying and writing about phenomena, but also about playing the role of soothsayer and providing guidance to government agencies, funding agencies, and researchers – on both the costs and opportunities of AI. For example, in 5) ___ care, we’ve built systems than can be very valuable for enhancing the delivery of health care while reducing costs. Yet there’s been such sluggish translation of these advances into the real world. You can imagine a focused study on these challenges of translation that could provide recommendations and guidance to the NIH (6) ___ ___ of ___ ) and the National Science Foundation. You can also imagine that government committees might call and say: “Hey, we need urgent research on X because of what we see with A, B, and C.“ It’s a chance to, on a clock, have a reflection about a set of important issues when it comes to machine intelligence.

 

It’s not clear what public attitudes are on machine intelligence. Horvitz thinks that many people really enjoy the fruits of systems like search engines without even thinking that they are AI. We’ve also seen, in the last year, luminaries like Stephen Hawking and Elon Musk talking in the press about how AI will 7) ___ humanity someday. To many researchers, these kinds of scares are unfounded. Others are uncertain, and some share concerns. Either way, we need to address them and make sure that people understand that there are practical things that can be done to make sure that things go well as we build and deploy these intelligences. As scientists, we do need to work on making sure that concerns are addressed about the safety and autonomy of AI systems and understand how to avoid or disprove some of these dystopian visions of the future by asking the questions scientifically: Are these outcomes that some people fear possible? And, if possible, how can we make sure they don’t happen by being proactive?

 

Horvitz’s view is that AI will be incredibly empowering to humanity. It will help solve problems, it will help us do better science, it promises to really help with challenges in education, healthcare and hunger. He think there are lots of opportunities there on the upside. In many ways, some of the concerns that he’s had over the years have been more about what he calls the rough edges that can be addressed. Horvitz is very optimistic about 8) ___ intelligence, and sees a need for studying and guiding its influences on people and society, and for continuing dialogue with the public.

 

ANSWERS: 1) life; 2) intelligence; 3) one hundred; 4) technology; 5) health; 6) National Institutes of Health; 7) threaten; 8) machine

 

Computers, Algorithms and Leibniz

 

Gottfried Wilhelm Leibniz (1646-1716)

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Gottfried Wilhelm von Leibniz, a German mathematician and philosopher, occupies a prominent place in the history of mathematics, the history of philosophy and the creator of the first binary number system, the foundation of all digital computers. Most scholars believe Leibniz developed calculus independently of Isaac Newton, and Leibniz’s mathematical notation has been widely used ever since it was published. It was only in the 20th century that his Law of Continuity and Transcendental Law of Homogeneity found mathematical implementation (by means of non-standard analysis). He became one of the most prolific inventors in the field of mechanical calculators. While working on adding automatic multiplication and division to Pascal’s calculator, he was the first to describe a pinwheel calculator in 1685. He also invented the Leibniz wheel, used in the arithmometer, the first mass-produced mechanical calculator. He also refined the binary number system, which is the foundation of virtually all digital computers.

 

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The Staffelwalze, or Stepped Reckoner, a digital calculating machine invented by Gottfried Wilhelm Leibniz around 1672 and built around 1700, on display in the Technische Sammlungen museum in Dresden, Germany.

 

The Staffelwalze was the first known calculator that could perform all four arithmetic operations; addition, subtraction, multiplication and division. The cover plate of the rear section is off to show the wheels of the 16 digit accumulator. Only two machines were made. The single surviving prototype, 67 cm (26 inches) long, is in the National Library of Lower Saxony(Niedersachsische Landesbibliothek) in Hannover.

 

In philosophy, Leibniz is most noted for his optimism, i.e., his conclusion that our Universe is, in a restricted sense, the best possible one that God could have created. Leibniz, along with Rene Descartes and Baruch Spinoza, was one of the three great 17th century advocates of rationalism. The work of Leibniz anticipated modern logic and analytic philosophy, but his philosophy also looks back to the scholastic tradition, in which conclusions are produced by applying reason to first principles or prior definitions rather than to empirical evidence.

 

Leibniz made major contributions to physics and technology, and anticipated notions that surfaced much later in philosophy, probability theory, biology, medicine, geology, psychology, linguistics, and computer science. He wrote works on philosophy, politics, law, ethics, theology, history, and philology. Leibniz’s contributions to this vast array of subjects were scattered in various learned journals, in tens of thousands of letters, and in unpublished manuscripts. He wrote in several languages, but primarily in Latin, French, and German. There is no complete gathering of the writings of Leibniz.

 

Gottfried Leibniz was born on July 1, 1646, toward the end of the Thirty Years’ War, in Leipzig, Saxony, to Friedrich Leibniz and Catharina Schmuck. Friedrich noted in his family journal: “On Sunday 21 June 1646, my son Gottfried Wilhelm is born into the world a quarter after seven in the evening, in Aquarius.“ His father died when Leibniz was six years old, and from that point on he was raised by his mother. Her teachings influenced Leibniz’s philosophical thoughts in his later life. Leibniz’s father had been a Professor of Moral Philosophy at the University of Leipzig, and the boy inherited his father’s personal library. He was given free access to it from the age of seven. While Leibniz’s schoolwork was largely confined to the study of a small canon of authorities, his father’s library enabled him to study a wide variety of advanced philosophical and theological works – ones that he would not have otherwise been able to read until his college years. Access to his father’s library, largely written in Latin, also led to his proficiency in the Latin language, which he achieved by the age of 12. He also composed 300 hexameters of Latin verse, in a single morning, for a special event at school at the age of 13. Leibniz enrolled in his father’s former university at age 15, and completed his Bachelor’s degree in Philosophy in December 1662. He defended his Disputatio Metaphysica de Principio Individui, in which addressed the principle of individuation, on June 9, 1663. Leibniz earned his Master’s degree in Philosophy on February 7, 1664. He published and defended a dissertation Specimen Quaestionum Philosophicarum ex Jure collectarum, arguing for both a theoretical and a pedagogical relationship between philosophy and law, in December 1664. After one year of legal studies, he was awarded his Bachelor’s degree in Law on September 28, 1665.

 

In 1666, at age 20, Leibniz wrote his first book, On the Art of Combinations, the first part of which was also his habilitation thesis in Philosophy. His next goal was to earn his license and Doctorate in Law, which normally required three years of study. In 1666, the University of Leipzig turned down Leibniz’s doctoral application and refused to grant him a Doctorate in Law, most likely due to his relative youth. Leibniz subsequently left Leipzig. Leibniz then enrolled in the University of Altdorf and quickly submitted a thesis, which he had probably been working on earlier in Leipzig. The title of his thesis was Disputatio Inauguralis De Casibus Perplexis In Jure. Leibniz earned his license to practice law and his Doctorate in Law in November 1666. He next declined the offer of an academic appointment at Altdorf, saying that “my thoughts were turned in an entirely different direction.“ As an adult, Leibniz often introduced himself as “Gottfried von Leibniz“. Many posthumously published editions of his writings presented his name on the title page as “Freiherr G. W. von Leibniz.“ However, no document has ever been found from any contemporary government that stated his appointment to any form of nobility.

 

1666-1674

Leibniz’s first position was as a salaried secretary to an alchemical society in Nuremberg. He knew fairly little about the subject at that time but presented himself as deeply learned. He soon met Johann Christian von Boyneburg (1622-1672), the dismissed chief minister of the Elector of Mainz, Johann Philipp von Schonborn. Von Boyneburg hired Leibniz as an assistant, and shortly thereafter reconciled with the Elector and introduced Leibniz to him. Leibniz then dedicated an essay on law to the Elector in the hope of obtaining employment. The stratagem worked; the Elector asked Leibniz to assist with the redrafting of the legal code for his Electorate. In 1669, Leibniz was appointed Assessor in the Court of Appeal. Although von Boyneburg died late in 1672, Leibniz remained under the employment of his widow until she dismissed him in 1674. Von Boyneburg did much to promote Leibniz’s reputation, and the latter’s memoranda and letters began to attract favorable notice. Leibniz’s service to the Elector soon followed a diplomatic role. He published an essay, under the pseudonym of a fictitious Polish nobleman, arguing (unsuccessfully) for the German candidate for the Polish crown. The main force in European geopolitics during Leibniz’s adult life was the ambition of Louis XIV of France, backed by French military and economic might.

 

Meanwhile, the Thirty Years’ War had left German-speaking Europe exhausted, fragmented, and economically backward. Leibniz proposed to protect German-speaking Europe by distracting Louis as follows. France would be invited to take Egypt as a stepping stone towards an eventual conquest of the Dutch East Indies. In return, France would agree to leave Germany and the Netherlands undisturbed. This plan obtained the Elector’s cautious support. In 1672, the French government invited Leibniz to Paris for discussion, but the plan was soon overtaken by the outbreak of the Franco-Dutch War and became irrelevant. Napoleon’s failed invasion of Egypt in 1798 can be seen as an unwitting, late implementation of Leibniz’s plan, after the Eastern hemisphere colonial supremacy in Europe had already passed from the Dutch to the British. Thus Leibniz began several years in Paris. Soon after arriving, he met Dutch physicist and mathematician Christiaan Huygens and realized that his own knowledge of mathematics and physics was patchy. With Huygens as mentor, he began a program of self-study that soon pushed him to making major contributions to both subjects, including discovering his version of the differential and integral calculus. He met Nicolas Malebranche and Antoine Arnauld, the leading French philosophers of the day, and studied the writings of Descartes and Pascal, unpublished as well as published. He befriended a German mathematician, Ehrenfried Walther von Tschirnhaus; they corresponded for the rest of their lives. In 1675 he was admitted by the French Academy of Sciences as a foreign honorary member, despite his lack of attention to the academy. When it became clear that France would not implement its part of Leibniz’s Egyptian plan, the Elector sent his nephew, escorted by Leibniz, on a related mission to the English government in London, early in 1673. There Leibniz came into acquaintance of Henry Oldenburg and John Collins. He met with the Royal Society where he demonstrated a calculating machine that he had designed and had been building since 1670. The machine was able to execute all four basic operations (adding, subtracting, multiplying, and dividing), and the Society quickly made him an external member. The mission ended abruptly when news reached it of the Elector’s death, whereupon Leibniz promptly returned to Paris and not, as had been planned, to Mainz. The sudden deaths of his two patrons in the same winter meant that Leibniz had to find a new basis for his career. In this regard, a 1669 invitation from the Duke of Brunswick to visit Hanover proved fateful. Leibniz declined the invitation, but began corresponding with the Duke in 1671. In 1673, the Duke offered him the post of Counselor which Leibniz very reluctantly accepted two years later, only after it became clear that no employment in Paris, whose intellectual stimulation he relished, or with the Habsburg imperial court was forthcoming.

 

House of Hanover, 1676-1716

Leibniz managed to delay his arrival in Hanover until the end of 1676 after making one more short journey to London, where he was later accused by Newton of being shown some of Newton’s unpublished work on the calculus. This was alleged to be evidence supporting the accusation, made decades later, that he had stolen the calculus from Newton. On the journey from London to Hanover, Leibniz stopped in The Hague where he met Leeuwenhoek, the discoverer of microorganisms. He also spent several days in intense discussion with Spinoza, who had just completed his masterwork, the Ethics. In 1677, he was promoted, at his request, to Privy Counselor of Justice, a post he held for the rest of his life. Leibniz served three consecutive rulers of the House of Brunswick as historian, political adviser, and most consequentially, as librarian of the ducal library. He thenceforth employed his pen on all the various political, historical, and theological matters involving the House of Brunswick; the resulting documents form a valuable part of the historical record for the period. Among the few people in north Germany to accept Leibniz were the Electress Sophia of Hanover (1630-1714), her daughter Sophia Charlotte of Hanover (1668-1705), the Queen of Prussia and his avowed disciple, and Caroline of Ansbach, the consort of her grandson, the future George II. To each of these women he was correspondent, adviser, and friend. In turn, they all approved of Leibniz more than did their spouses and the future king George I of Great Britain.

 

The population of Hanover was only about 10,000, and its provinciality eventually grated on Leibniz. Nevertheless, to be a major courtier to the House of Brunswick was quite an honor, especially in light of the meteoric rise in the prestige of that House during Leibniz’s association with it. In 1692, the Duke of Brunswick became a hereditary Elector of the Holy Roman Empire. The British Act of Settlement 1701, designated the Electress Sophia and her descent as the royal family of England, once both King William III and his sister-in-law and successor, Queen Anne, were dead. Leibniz played a role in the initiatives and negotiations leading up to that Act, but not always an effective one. For example, something he published anonymously in England, thinking to promote the Brunswick cause, was formally censured by the British Parliament. The Brunswicks tolerated the enormous effort Leibniz devoted to intellectual pursuits unrelated to his duties as a courtier, pursuits such as perfecting the calculus, writing about other mathematics, logic, physics, and philosophy, and keeping up a vast correspondence. He began working on the calculus in 1674; the earliest evidence of its use in his surviving notebooks is 1675. By 1677 he had a coherent system in hand, but did not publish it until 1684. Leibniz’s most important mathematical papers were published between 1682 and 1692, usually in a journal which he and Otto Mencke founded in 1682, the Acta Eruditorum. That journal played a key role in advancing his mathematical and scientific reputation, which in turn enhanced his eminence in diplomacy, history, theology, and philosophy. The Elector Ernest Augustus commissioned Leibniz to write a history of the House of Brunswick, going back to the time of Charlemagne or earlier, hoping that the resulting book would advance his dynastic ambitions. From 1687 to 1690, Leibniz traveled extensively in Germany, Austria, and Italy, seeking and finding archival materials bearing on this project. Decades went by but no history appeared; the next Elector became quite annoyed at Leibniz’s apparent dilatoriness. Leibniz never finished the project, in part because of his huge output on many other fronts, but also because he insisted on writing a meticulously researched and erudite book based on archival sources, when his patrons would have been quite happy with a short popular book, one perhaps little more than a genealogy with commentary, to be completed in three years or less. They never knew that he had in fact carried out a fair part of his assigned task: when the material Leibniz had written and collected for his history of the House of Brunswick was finally published in the 19th century, it filled three volumes.

 

In 1708, John Keill, writing in the journal of the Royal Society and with Newton’s presumed blessing, accused Leibniz of having plagiarized Newton’s calculus. Thus began the calculus priority dispute which darkened the remainder of Leibniz’s life. A formal investigation by the Royal Society (in which Newton was an unacknowledged participant), undertaken in response to Leibniz’s demand for a retraction, upheld Keill’s charge. Historians of mathematics writing since 1900 or so have tended to acquit Leibniz, pointing to important differences between Leibniz’s and Newton’s versions of the calculus. In 1711, while traveling in northern Europe, the Russian Tsar Peter the Great stopped in Hanover and met Leibniz, who then took some interest in Russian matters for the rest of his life. In 1712, Leibniz began a two-year residence in Vienna, where he was appointed Imperial Court Councilor to the Habsburgs. On the death of Queen Anne in 1714, Elector George Louis became King George I of Great Britain, under the terms of the 1701 Act of Settlement. Even though Leibniz had done much to bring about this happy event, it was not to be his hour of glory. Despite the intercession of the Princess of Wales, Caroline of Ansbach, George I forbade Leibniz to join him in London until he completed at least one volume of the history of the Brunswick family his father had commissioned nearly 30 years earlier. Moreover, for George I to include Leibniz in his London court would have been deemed insulting to Newton, who was seen as having won the calculus priority dispute and whose standing in British official circles could not have been higher. Finally, his dear friend and defender, the Dowager Electress Sophia, died in 1714.

 

Leibniz never married. He complained on occasion about money, but he willed a fair amount to his sole heir, his sister’s stepson. Leibniz died in Hanover in 1716: at the time, he was so out of favor that neither George I (who happened to be near Hanover at that time) nor any fellow courtier other than his personal secretary attended the funeral. Even though Leibniz was a life member of the Royal Society and the Berlin Academy of Sciences, neither organization saw fit to honor his passing. His grave went unmarked for more than 50 years. Leibniz was eulogized by Fontenelle, before the Academie des Sciences in Paris, which had admitted him as a foreign member in 1700. The eulogy was composed at the behest of the Duchess of Orleans, a niece of the Electress Sophia.

 

Niemann-Pick Type C Disease – NIH Collaborates with Industry

 

Lysosomal storage diseases, also known as lipid storage diseases, comprise about 50 rare inherited disorders that usually affect children. Fatty materials accumulate in the cells and tissues of the body. These diseases can result in damage to the brain, peripheral nervous system, liver, and other organs and tissues; they are often fatal. The National Institutes of Health (NIH) has entered into an agreement with biotechnology company Vtesse, Inc., of Gaithersburg, Maryland, to develop treatments for Niemann-Pick disease type C (NPC) and other lysosomal storage disorders. Clinical investigators at the National Center for Advancing Translational Sciences (NCATS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both parts of NIH, will conduct studies on NPC and other lysosomal storage disorders with funding provided by Vtesse.

 

Vtesse will support the ongoing phase I clinical trial for NPC at the NIH Clinical Center, where researchers have been evaluating the safety of the drug cyclodextrin. Vtesse also plans to collaborate with NICHD to launch a second clinical study of cyclodextrin for the treatment of NPC in the United States and Europe, anticipated to begin in 2015. The use of cyclodextrin for NPC has been granted orphan drug designation in the United States and Europe, providing development incentives for products that demonstrate promise for the diagnosis and treatment of rare diseases or conditions.

 

Patients with NPC typically develop impaired coordination and movement (ataxia) and other neurological problems as a result of cholesterol buildup in their brain cells. Researchers in NCATS’ Therapeutics for Rare and Neglected Diseases (TRND) program developed cyclodextrin as part of a project focused on finding treatments for NPC. The goal of TRND projects is to develop therapeutic candidates through a strategy known as de-risking, which involves the pre-clinical development of therapeutics to the stage where they attract biotechnology and pharmaceutical companies such as Vtesse to invest in their further clinical development.

 

The NPC project is a collaboration among government, academic and industry researchers, who worked with patient groups and the NPC community to advance knowledge about the disease. Before the TRND project, it was found that cyclodextrin showed promise as a treatment for NPC in studies of animal models for the disease. Additional NCATS efforts provided further evidence that cyclodextrin demonstrated potential as a treatment for NPC.

 

Through this agreement, Vtesse will also fund pre-clinical studies to develop various types of the compound delta-tocopherol, a form of vitamin E, to target lysosomal storage disorders. The NCATS team will optimize the delta-tocopherol compounds for further testing as potential single treatments or as a combination therapy with cyclodextrin. Vtesse has exclusively licensed several NCATS patent applications specifically for their use in the treatment of lysosomal storage disorders.

 

Rather than focusing on specific diseases and attempting to address them one at a time, NCATS researchers look for commonalities among multiple diseases. In the case of lysosomal storage disorders, NCATS researchers found in studies using patient skin cells as disease models that cyclodextrin and delta-tocopherol, each given alone or combined, showed promise for NPC and other lysosomal storage disorders, including Batten, Farber, Fabry, Tay-Sachs and Niemann-Pick type A diseases and mucopolysaccharidosis type 1. Cyclodextrin and delta-tocopherol reduced the accumulation of lipids and other macromolecules though lysosome exocytosis, a process by which materials are transported out of a cell. The results suggest that lysosome exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases.

 

NCATS is a distinctly different entity in the research ecosystem. Rather than targeting a particular disease or fundamental science, NCATS focuses on what is common across diseases and the translational process. The Center emphasizes innovation and deliverables, relying on the power of data and new technologies to develop, demonstrate and disseminate improvements in translational science that bring about tangible improvements in human health.

 

Despite Risks, Benzodiazepine Use Highest in Older People

 

Benzodiazepines are among the most commonly prescribed medications in developed countries, and include drug products such as alprazolam (Xanax), diazepam (Valium), and lorazepam (Ativan). The most common uses of benzodiazepines are to treat anxiety and sleep problems. While effective for both conditions, the medications have risks, especially when used over long periods. Long-term use can lead to dependence and withdrawal symptoms when discontinued. In older people, research has shown that benzodiazepines can impair cognition, mobility, and driving skills, and they increase the risk of falls. Practice guidelines recommend as first-line treatment, non-pharmacologic approaches such as psychotherapy, as well as antidepressants, rather than benzodiazepines. While rates of insomnia increase with age, practice guidelines also recommend that health care providers consider behavioral interventions as first-line treatment over medication.

 

According to a comprehensive analysis of benzodiazepine prescribing in the United States, published online in JAMA Psychiatry (18 December 2014), prescription use of benzodiazepines increases steadily with age, despite the known risks for older people. Given existing guidelines cautioning health providers about benzodiazepine use among older adults, findings from the National Institutes of Health-funded study raises questions about why so many prescriptions — many for long-term use — are being written for this age group. The study found that among all adults 18 to 80 years old, about 1 in 20 received a benzodiazepine prescription in 2008, the period covered by the study. But this fraction rose substantially with age, from 2.6% among those 18 to 35, to 8.7% in those 65 to 80, the oldest group studied. Long-term use — a supply of the medication for more than 120 days — also increased markedly with age. Of people 65 to 80 who used benzodiazepines, 31.4% received prescriptions for long-term use, vs. 14.7% of users 18 to 35. In all age groups, women were about twice as likely as men to receive benzodiazepines. Among women 65 to 80 years old, 1 in 10 was prescribed one of these medications, with almost a third of those receiving long-term prescriptions.

 

Despite the large number of prescriptions in the United States — 85 million in 2007 — relatively little was known prior to this study about the specifics of benzodiazepine prescribing in the United States relative to other countries. To examine prescription patterns from 2008, the authors used data from a national prescription database (IMS LifeLink LRx Longitudinal Prescription database) and a national database on medical expenditures collected by the Agency for Healthcare Research and Quality.

 

Among the findings:

 

Use of benzodiazepines increased steadily with age: 5.2% of adults 18 to 80 years old received one or more benzodiazepine prescriptions in 2008; 2.6% of those 18 to 35, 5.4% of those 36 to 50, 7.4% of those 51 to 64, and 8.4% of those 65 to 80.

 

Overall, about one quarter of prescriptions involve long-acting formulations of benzodiazepines.

 

Most prescriptions for benzodiazepines are written by non-psychiatrists. For adults 18 to 80 years old, about two thirds of prescriptions for long-term use are written by non-psychiatrists; for adults 65 to 80, the figure is 9 out of 10.

 

Adding to concerns about the possible health consequences of benzodiazepine use, a recently reported study found an association between benzodiazepine use in older people and increased risk of Alzheimer’s disease. The association was stronger with increasing length of use; the risk was nearly doubled for those using benzodiazepines for more than 180 days.

 

REGULATORY AFFAIRS – 2014 Drug Approvals

 

2014 Drug Approvals

 

Each year, FDA approves a wide range of new drugs and biological products. Some of these products are innovative new products that never before have been used in clinical practice. Others are the same as, or related to, previously approved products, and they will compete with those products in the marketplace. This year, FDA approved 41 new molecular entities (NMEs), submitted to the Centers for Drug Evaluation and Research (CDER) in New Drug Applications (NDAs) and new therapeutic biologics submitted to CDER in Biologics License Applications (BLAs). The list of CDER’s New Molecular Entities and New Therapeutic Biological Products for 2015 can be found at the FDA website.

 

Certain drugs are classified as new molecular entities (“NMEs“) for purposes of FDA review. Many of these products contain active moieties that have not been approved by FDA previously, either as a single ingredient drug or as part of a combination product; these products frequently provide important new therapies for patients. Some drugs are characterized as NMEs for administrative purposes, but nonetheless contain active moieties that are closely related to active moieties in products that have previously been approved by FDA. For example, CDER classifies biological products submitted in an application under section 351(a) of the Public Health Service Act as NMEs for purposes of FDA review, regardless of whether the Agency previously has approved a related active moiety in a different product. FDA’s classification of a drug as an “NME“ for review purposes is distinct from FDA’s determination of whether a drug product is a “new chemical entity“ or “NCE“ within the meaning of the Federal Food, Drug, and Cosmetic Act.

 

According to FDA’s Blog, the numbers don’t tell the full story. What really matters is that many of these new products offer significant clinical value to the care of thousands of patients with serious and life-threatening diseases. For example, in 2014, FDA reached a milestone with a record 15 approvals for rare diseases. The previous high was 13 drugs in 2012 where one of the drugs for Gaucher disease was championed by Target Health on behalf of Protalix Biotherapeutics (Israel). These results are all the more significant because patients with rare diseases often have few or no drugs available to treat their conditions. And here’s another point of interest, 15 of the approvals have been first in their class drugs, another indicator of their potentially strong clinical impact.

 

To ensure that 2014’s novel drugs get to patients as quickly as possible, CDER effectively employed a variety of regulatory tools including FDA’s expedited development and review programs – fast track, priority review, accelerated approval and our new breakthrough therapy designation. Early and repeated communications with sponsors have also been helpful in speeding these products to market. For Blincyto, approved to treat Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia, CDER employed all of its expedited review programs to help get this drug to market as early as possible, five months ahead of its review goal date. The sponsor also benefited from incentives for drugs that treat rare diseases. Another example is Harvoni, the first combination pill approved to treat chronic hepatitis C virus genotype 1 infection and the first approved regimen that does not require administration with interferon or ribavirin. With this and other recent approvals, FDA is helping to change the treatment paradigm for patients living with hepatitis C. Harvoni received breakthrough therapy designation and was assigned priority review.

 

One of the more challenging areas of drug development has been the rather barren field of antibacterial drugs. Among the 2014 approvals are three new antibacterial drugs – Dalvance, Sivextro and Orbactiv – to treat skin infections, specifically acute bacterial skin and skin structure infections (ABSSSI). These drug approvals represent a welcome but modest increase in activity in this product area. Prior to 2014, only five new systemic antibacterial drugs were approved during the period from 2004 – 2013.

 

Together with Margaret A. Hamburg, M.D., who wrote the blog, we want to congratulate the management and review staff at CDER for these very impressive accomplishments.

 

Green & White Cauliflower with Truffle Oil

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Delicious, healthy and easy to make – ©Joyce Hays, Target Health Inc.

 

Ingredients

 

1 large or medium head of white cauliflower

1 large or medium head of green cauliflower

5 (Five) cloves peeled garlic

1/3 cup nonfat buttermilk

1 teaspoon extra-virgin olive oil

3 or 4 teaspoons white truffle oil

Pinch salt

Pinch chili flakes

Pinch Fine black pepper

Chopped fresh parsley or cilantro for garnish (optional)

 

 

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Before you do anything else, get all the ingredients together. Otherwise, if you have to rush out to pick up some buttermilk, like I did, you will get upset even before you begin. ©Joyce Hays, Target Health Inc.

 

Directions

 

1. Clean the cauliflower and break apart large chunks.

2. Place cauliflower florets and garlic in a steamer basket over boiling water, cover and steam until tender, 10 to 15 minutes. Check with a fork so not too soft and mushy.

3. Put the steamed green florets aside

 

 

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4. After steaming, puree only the white cauliflower in a food processer with the other ingredients. Keep the green florets separate

5. Place only the white cooked cauliflower and garlic in a food processor. Add buttermilk, 3 or 4 teaspoons truffle oil, pinch salt and pinch pepper and pinch chili flakes (optional); pulse several times, then process until smooth and creamy.

6. Transfer to a serving bowl. Add the green florets, (steamed but not pureed) on top of the white puree. Bring the serving bowl to the table before stirring the green florets into the white puree, simply because it’s so pretty that way. As you serve the cauliflower, it will mix together automatically.

6. Sprinkle parsley on top (optional)

 

 

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©Joyce Hays, Target Health Inc.

 

We started this meal with a wonderful fresh-tasting salad with ugli tomatoes, thin-skin cucumbers, avocados, sliced endive and green olives. The dressing was fresh lemon juice and olive oil. This is one of our favorite salads.

 

Then came the truffle cauliflower puree and yummy baked halibut with a yogurt scallion sauce on top. A few red seedless grapes gave a sweet contrast to the fish and cauliflower. When our LA son studying architecture, was here recently, the truffle cauliflower dish was gone by the end of each meal, it was served at. Bowl was finger-lickin’ clean.

 

During the holidays we managed to go to the theater three times and the MetOpera, once. Jules and our son would only recommend, “The Curious Incident of the Dog in the Nighttime“ I didn’t like it that much. I liked, “The River“ with Hugh Jackman. None of us liked the new Sting musical, “The Last Ship“ and I guess that was the common feeling, since this show has recently closed. None of us like the opera on New Year’s eve, “The Merry Widow,“ a new production that left us feeling that the whole first act could have been eliminated. Not even the beautiful voices of Renee Fleming and Nathan Gunn could save it. Nevertheless, no matter what the MetOpera does, it’s wonderfully festive going there no matter what.

 

Regarding the terrible terrorist shootings in France, we agree with some comments, that tolerance makes living together easier. However, as we look back at the thousands of years of war and killing in human history, we cannot marvel enough at the human crafting of “freedom of expression,“ which allows ideas and words to be used like bullets, instead of the brutality of swords, missiles and bullets. Let us not undo, what has taken humans so long to create.

 

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With the baked halibut and truffle cauliflower, we had chilled Orvieto wine from Italy. Cheese and more grapes for dessert.  ©Joyce Hays, Target Health Inc.

 

From Our Table to Yours!

 

Bon Appetit!