To all of our friends and colleagues, from all of us from Target Health, we wish you all a Happy Holiday and a Happy, Healthy and Successful New Year. We will take a holiday break, as we are sure you all will be doing, and will see you again in 2013.
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
HealthCare in Iran (Persia)
Imam Khomeini hospital in Tehran
University of Isfahan, Isfahan, Iran
This is the city where Avicenna, (Abu Ali al-Husayn ibn Abd Allah ibn Sina) great
ancient Persian physician and scholar, settled towards the last part of his life
Health care in Iran and medical sector’s market value was almost US $24 billion in 2002 and was forecast to rise to US $31 billion by 2007. With a population of 75 million (2012), Iran is one of the most populous countries in the 1) ___ ___. The country faces the common problem of other young demographic nations in the region, which is keeping pace with growth of an already huge demand for various public services. The young population will soon be old enough to start new families, which will boost the population growth rate and subsequently the need for public health infrastructures and services. Total healthcare spending is expected to rise from $24.3 billion in 2008, to $50 billion by 2013, reflecting the increasing demand on medical services. Total health spending was equivalent to 4.2% of GDP in Iran in 2005. 73% of all Iranians have health care coverage.
The Iranian constitution entitles its citizens to basic 2) ___ ___, and most receive subsidized prescription drugs and vaccination programs. An extensive network of public clinics offers basic care at low cost, and general and specialty hospitals operated by the Ministry of Health and Medical Education (MOHME) provide higher levels of care. In most large cities, well-to-do persons use private clinics and hospitals that charge high fees. About 73% of all Iranian workers have health care and social security coverage. In 2000, 94% of the population could access local health services, according to the WHO. Access ranged from 86% in rural areas to 100% in urban areas. Between 80% and 94% of the population could access affordable essential medicines in 1999. Since 2009, a new government plan called “the comprehensive insurance plan” provides basic 3) ___ to all Iranians.
The World Health Organization in the last report on health systems ranks Iran’s performance on health level 58th, and its overall health system performance 93rd among the world’s 4) ___. The health status of Iranians has improved over the last two decades. Iran has been able to extend public health preventive services through the establishment of an extensive Primary Health Care Network. As a result child and maternal mortality rates have fallen significantly, and life expectancy at birth has risen remarkably. Infant (IMR) and under-five (U5MR) mortality have decreased to 28.6 and 35.6 per 1,000 live births respectively in 2000, compared to an IMR of 122 per 1,000 and a U5MR of 191 per 1,000 in 1970. Immunization of children is accessible to most of the urban and rural population.
Although overall improvements have been achieved in all health areas since the 1979 revolution, the present challenging economic conditions of the country, combined with rapid advances in medical technology and information technology, individuals’ expectations, and the young demographic of the population will undoubtedly challenge the sustainability of past improving trends. In this regard, Iran is implementing a reform that places preventive medicine, the family doctor and the patient’s electronic medical history at the center of Iran’s health care system. Moreover there is a considerable variation in the human development index and the human poverty index across different provinces in the country. Iran is the 19th country in medical 5) ___ and is set to become the 10th within 10 years (2012).
Iran is also among the 12 countries with biological medicines technology and can serve as a health tourism center. 30,000 people come to Iran each year to receive medical treatment (2012).
The pharmaceutical industry in Iran began in its modern form in 1920 when the Pasteur Institute was founded. Iran has a well-developed pharmaceutical production capability, however, the country still relies on imports for raw materials and many specialized 6) ___. The standards regarding pharmaceutical products in Iran are determined and modified by the Pharmacopeia Council. Iran’s Ministry of Health and Medical Education (MOHME) has a mission to provide access to sufficient quantities of safe, effective and high quality medicines that are affordable for the entire population. Since the 1979 revolution, Iran has adopted a full generic-based National Drug Policy (NDP), with local production of essential drugs and vaccines as one of the main goals.
Although over 85% of the population use an insurance system to reimburse their drug expenses, the government heavily subsidizes pharmaceutical production/importation in order to increase affordability of 7) ___, which tends also to increase overconsumption, overprescription and misuse of drugs, such as antibiotics. The regulatory environment of the country is rather strict on the import of drugs and pharmaceuticals towards companies that intend to enter into the market for the first time. The Ministry of Health and Medical Education is the main stakeholder of pharmaceutical affairs in the country.
There are 92 companies in Iran that are active in the pharmaceutical industry. The Social Security Investment Co. (SSIC), Iran’s largest holding company, which is affiliated to the Ministry of Welfare, presently owns and controls 22 pharmaceutical manufacturing companies and possesses a 40% share of total pharmaceutical production in Iran.
The leading pharmaceuticals company is Darou Pakhsh, which is majority-owned by the Social Security Organization. The company manufactures, distributes, imports and exports finished products and pharmaceutical raw materials. Darou Pakhsh has an annual turnover of US$400m and claims to have the largest research and development operation of any Iranian drug firm. The company formed a plasmapheresis joint venture with a German medical firm, Biotest AG, in early 2004. As of 2010, 50% of raw materials and chemicals used in the drug manufacturing sector are 8) ___.
ANSWERS: 1) Middle East; 2) healthcare; 3) coverage; 4) nations; 5) research; 6) drugs; 7) medicines; 8) imported
Avicenna: Full name: Abu Ali al-Husayn ibn Abd Allah ibn Sina
Born: 980CE in Afshana (in present-day Uzbekistan)
Each part of the Fravahar signifies an idea or a philosophy
Some of the earliest records of history of Ancient Iranian medicine can be found in Avesta, the primary collection of sacred texts of Zoroastrianism. Two streamers, above, which extend outward from the central disc illustrate Zoroastrian ethics. They symbolize the two choices humans have between good or evil, or that one should proceed toward good and turn away from bad. The three-layered wings, above, symbolize “good thoughts, good words, and good deeds”, the Threefold Path of Zoroastrianism.
The practice and study of medicine in Persia has a long and prolific history. The Iranian academic centers like Jundishapur University (3rd century CE) were a breeding ground for the union among great scientists from different civilizations. These centers successfully followed their predecessors’ theories and greatly extended their scientific research through history.
The painting above depicts Persian-born physician Rhazes (circa 865-925 CE) at the bedside of a young patient afflicted with measles. First to describe measles and smallpox with clinical accuracy, and first to observe and report pupillary reaction to light, Rhazes wrote the earliest known book on pediatric care. His accomplishments, more than a thousand years ago, represent Persian medicine at its best.
King Darius I (550-486 BCE), third King of Persia , had an interest in medicine, so great that he re-established the school of medicine in Sais, Egypt, which previously had been destroyed, restoring its books and equipment. The first teaching hospital where medical students methodically practiced on patients under the supervision of physicians was the Academy of Gundishapur in the Persian Empire. Some experts go so far as to claim that: “to a very large extent, the credit for the whole hospital system must be given to Persia”.
Persian physicians, for proof of proficiency, had to cure three patients and if they failed they could not practice medicine. Physicians were taught to remove any mental barriers and to treat adversaries as well as friends. A physician’s fee for service was based on the patient’s income.
A 500 year old Latin translation of the Canon of Medicine by Avicenna
Iranian science was interrupted by the Arab invasion of 630 CE. Many schools, universities and libraries were destroyed, books were burned and scholars killed. Nevertheless, the Iranian scientists carried on and the science of Persia resurfaced during the Islamic period. To save the books from the Arab carnage, many Pahlavi scripts were translated into the Arabic, and Iran produced physicians and scientists as Abu Ali al-Ḥusayn ibn Abd Allah ibn Sina, Muhammad ibn Zakariya al-Razi and mathematicians as Kharazmi and Omar Khayyam. They collected and systematically expanded the Greek, Indian, and Persian ancient medical heritage and made further discoveries.
The Islamic Golden Age is an Abbasid historical period lasting until the Mongol conquest of Baghdad in 1258. The Islamic Golden Age was inaugurated by the middle of the 8th century by the ascension of the Abbasid Caliphate and the transfer of the capital from Damascus to Baghdad. In the 14th century, the Persian language medical work Tashrih al-badan (Anatomy of the body), by Mansur ibn Ilyas (c. 1390), contained comprehensive diagrams of the body’s structural, nervous and circulatory systems.
Evidence of surgery dates to the 3rd century BCE, when the first cranial surgery was performed in the Shahr-e-Sukhteh (Burnt City) in south-eastern Iran. The archaeological studies on the skull of a 13-year-old girl suffering from hydrocephaly indicated that she had undergone cranial surgery to take a part of her skull bone and the girl lived for at least about 6 months after the surgery.
Several documents still exist from which the definitions and treatments of the headache in medieval Persia can be ascertained. These documents give detailed and precise clinical information on the different types of headaches. Antiepileptic drug therapy plan in Medieval Iranian medicine is individualized, given different single and combined drug-therapy with a dosing schedule for each of those. Physicians stress the importance of dose, and route of administration and define a schedule for drug administration. Recent animal experiments confirm the anticonvulsant potency of some of the compounds which are recommended by Medieval Iranian practitioners in epilepsy treatment.
One of the main roles played by medieval Iranian scholars in the scientific field was the conservation, consolidation, coordination and development of ideas and knowledge in ancient civilizations. Some Iranian Hakim (practitioners) such as Fakhr al-Din al-Razi, Muhammad ibn Zakariya ar-Razi, known to the West as Rhazes, and Ibn Sina, better known as Avicenna, were not only responsible for accumulating all the existing information on medicine of the time, but adding to this knowledge by their own astute observations, experimentation and skills. “Qanoon fel teb of Avicenna” (“The Canon”) and “Kitab al-hawi of Razi” (“Continens”) were among the central texts in Western medical education from the 13th to the 18th centuries.
The most famous works of Avicenna are The Book of Healing, a vast philosophical and scientific encyclopedia, and The Canon of Medicine, which was a standard medical text at many medieval universities. The Canon of Medicine was used as a text-book in the universities of Montpellier and Leuven as late as 1650. Avicenna’s Canon of Medicine provides a complete system of medicine according to the principles of Galen (and Hippocrates).
The Canon of Medicine agrees with Aristotle (and disagrees with Hippocrates) that tuberculosis was contagious, a fact which was not universally accepted in Europe until centuries later. It also describes the symptoms and complications of diabetes. Both forms of facial paralysis were described in-depth.
The Canon of Medicine discussed how to effectively test new medicines:
- The drug must be free from any extraneous accidental quality.
- It must be used on a simple, not a composite, disease.
- The drug must be tested with two contrary types of diseases, because sometimes a drug cures one disease by its essential qualities and another by its accidental ones.
- The quality of the drug must correspond to the strength of the disease. For example, there are some drugs whose heat is less than the coldness of certain diseases, so that they would have no effect on them.
- The time of action must be observed, so that essence and accident are not confused.
- The effect of the drug must be seen to occur constantly or in many cases, for if this did not happen, it was an accidental effect.
- The experimentation must be done with the human body, for testing a drug on a lion or a horse might not prove anything about its effect on man.
Avicenna created an extensive corpus of works during what is commonly known as Islam’s Golden Age, in which the translations of Greco-Roman, Persian, and Indian texts were studied extensively. Greco-Roman (Mid- and Neo-Platonic, and Aristotelian) texts by the Kindi school were commented, redacted and developed substantially by Islamic intellectuals, who also built upon Persian and Indian mathematical systems, astronomy, algebra, trigonometry and medicine. The Samanid dynasty in the eastern part of Persia, Greater Khorasan and Central Asia as well as the Buyid dynasty in the western part of Persia and Iraq provided a thriving atmosphere for scholarly and cultural development. Under the Samanids, Bukhara (ancient birthplace of Avicenna) rivaled Baghdad as a cultural capital of the Islamic world.
A drawing of Avicenna from 1271
Avicenna’s first appointment was that of physician to the emir, who owed him his recovery from a dangerous illness in 997. Avicenna’s chief reward for this service was access to the royal library of the Samanids, well-known patrons of scholarship and scholars. When the library was destroyed by fire not long after, the enemies of Avicenna accused him of burning it, in order for ever to conceal the sources of his knowledge. After the death of his father, Avicenna proceeded westwards to Urgench in modern Turkmenistan, where, as a scholar, he was able to receive a small monthly stipend. However, he continued wandering from place to place seeking an opening for his talents. Avicenna was stricken by a severe illness in 1012. Finally, near the Caspian Sea, Avicenna met with a friend and patron, who encouraged Avicenna to give lectures and to spend time writing. Several of Avicenna’s treatises were written for this patron; and the commencement of his Canon of Medicine started at this time.
An Arabic edition of the Canon appeared at Rome in 1593, and a Hebrew version at Naples in 1491. Of the Latin version there were about thirty editions, founded on the original translation by Gerard de Sabloneta. In the 15th century a commentary on the text of the Canon was composed. Other medical works translated into Latin are the Medicamenta Cordialia, Canticum de Medicina, and the Tractatus de Syrupo Acetoso.
The remaining ten or twelve years of Ibn Sins’s life were spent in the service of Abu Ja’far ‘Ala Addaula, the well known prefect of the dynamic city of Isfahan, whom he accompanied as physician and general literary and scientific adviser, even in his numerous war and/or political campaigns. A severe colic, seized him during an army march against Hamadan. Avicenna took remedies but the illness was so violent that Avicenna could scarcely stand. He eventually recovered but during another war situation, the disease returned, stronger than before. His friends advised him to slow down and take life moderately. He refused, stating that: “I prefer a short life with width to a narrow one with length.” On his deathbed he bestowed his goods on the poor, restored unjust gains, freed his slaves. He died in June 1037, in his fifty-eighth year, and was buried in Hamadan, Iran.
Experimental Antidepressant Works Like Ketamine with Fewer Side Effects
Existing antidepressants available through prescription, which work through the brain’s serotonin system, take a few weeks to work, imperiling severely depressed patients, who can be at high risk for suicide. Ketamine also works in hours, but its usefulness is limited by its potential for dissociative side-effects, including hallucinations. It is being studied mostly for clues to how it works.
According to a study published online in Biological Psychiatry (30 November 2012), a drug that works through the same brain mechanism as the fast-acting antidepressant ketamine, improved treatment-resistant depression symptoms in minutes, with minimal untoward side effects. The experimental agent, called AZD6765, acts through the brain’s glutamate chemical messenger system. AZD6765, like ketamine, works by blocking glutamate binding to a protein on the surface of neurons, called the NMDA receptor. It is a less powerful blocker of the NMDA receptor, which may be a reason why it is better tolerated than ketamine.
Results showed that about 32% of 22 treatment-resistant depressed patients infused with ASD6765 showed a clinically meaningful antidepressant response at 80 minutes after infusion. The effect lasted for about half an hour, with residual antidepressant effects lasting two days for some. In contrast, 52% of patients receiving ketamine show a comparable response, with effects still detectable at seven days.
When both drugs are compared, it was demonstrated that a single infusion of ketamine produces more robust and sustained improvement, but most patients continue to experience some symptoms with both drugs. However, the authors deemed it noteworthy that depression rating scores were significantly better among patients who received AZD6765 than in those who received placebos, because, on average, these patients had failed to improve in seven past antidepressant trials, and nearly half failed to respond to electroconvulsive therapy (ECT). In addition, patients receiving ASD6765 reported only minor side effects, such as dizziness and nausea, which were not significantly different from those experienced with the placebo.
According to the authors, the results warrant further trials with AZD6765, testing whether repeated infusions a few times per week or higher doses might produce longer-lasting results.
Empiric Deworming to Delay HIV Disease Progression Does Not Work
Co-infection with HIV and helminth worms is common in sub-Saharan Africa, and findings from previous studies have suggested that anthelmintic treatment might delay immunosuppression in people with HIV. As a result, a study published in The Lancet Infectious Diseases (2012;12:925-932), was performed to assess the efficacy of empiric deworming of adults with HIV in in order to delay disease progression.
In this non-blinded randomized trial, adults 18 year of age or greater with HIV, who did not meet criteria for the initiation of antiretroviral treatment from three sites in Kenya, were enrolled in the study. Using a computer-generated sequence, eligible subjects were randomized to either empiric albendazole every 3 months plus praziquantel annually (anthelmintic treatment group), or to standard care (control group). Participants were followed up for 24 months. CD4 cell counts were measured every 6 months and plasma HIV RNA annually. The primary endpoints were a CD4 count of less than 350 cells per uL and a composite endpoint consisting of the first occurrence of a CD4 count of less than 350 cells per uL, first reported use of antiretroviral treatment, and non-traumatic deaths.
Between 6 February 2008, and 21 June 2011, the study enrolled and followed-up 948 participants; 469 were allocated to the treatment group and 479 to the control group. All participants were provided with the antimicrobial co-trimoxazole (a combination of trimethoprim and sulfamethoxazole) prophylaxis. Results showed that median baseline CD4 cell counts and HIV RNA concentrations did not differ between groups. No statistically significant difference was observed between the treatment and control groups in the number of people reaching a CD4 count of fewer than 350 cells per uL (41.6 events per 100 person-years vs. 46.2 events per 100 person-years; hazard ratio 0.89) or the composite endpoint (44.0 events per 100 person-years vs. 49.8 events per 100 person-years; 0.88). Serious adverse events, none of which thought to be treatment-related, occurred at a similar frequency in both groups.
According to the authors, the findings do not suggest an effect of empiric deworming in the delaying of HIV disease progression in adults with HIV in an area where helminth infection is common, and that alternative approaches are needed to delay HIV disease progression in areas where co-infections are common.
Efficacy of a Clinical Decision-Support System in an HIV Practice
Data to support improved patient outcomes from clinical decision-support systems (CDSSs) are lacking in HIV care. As a result, a study published in Annals of Internal Medicine (2012; 157:757-766) was performed to test the efficacy of a CDSS in improving HIV outcomes in an outpatient clinic. The investigation was a randomized, controlled trial, which included HIV care providers and their patients.
For the study, computer alerts were generated for virologic failure (HIV RNA level >400 copies/mL after a previous HIV RNA level <400 copies/mL), evidence of suboptimal follow-up, and 11 abnormal laboratory test results. Providers received interactive computer alerts, facilitating appointment rescheduling and repeated laboratory testing, for half of their patients and static alerts for the other half. The primary end point was change in CD4 cell count. Other end points included time to clinical event, 6-month suboptimal follow-up, and severe laboratory toxicity.
In terms of results, 33 HIV care providers followed 1,011 patients with HIV. In the intervention group, the mean increase in CD4 cell count was greater (0.0053 vs. 0.0032 x109 cells/L per month; difference, 0.0021 x109 cells/L per month [95% CI, 0.0001 to 0.004]; P=0.040) and the rate of 6-month suboptimal follow-up was lower (20.6 vs. 30.1 events per 100 patient-years; P=0.022) than those in the control group. Median time to next scheduled appointment was shorter in the intervention group than in the control group after a suboptimal follow-up alert (1.71 vs. 3.48 months; P<0.001) and after a toxicity alert (2.79 vs. >6 months; P=0.072). More than 90% of providers supported adopting the CDSS as part of standard care.
According to the authors, CDSS using interactive provider alerts improved CD4 cell counts and clinic follow-up for patients with HIV and that wider implementation of such systems can provide important clinical benefits.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.
Public-Private Partnership to Develop Regulatory Science to Speed Patient Access to New Medical Device Technologies
Regulatory science – the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products – is critical to the medical device industry and to public health. Advancements in regulatory science not only aim to improve how products are developed and evaluated, but also could reduce the cost and time it takes for a promising device to come to market. For example, a computer model might be developed to test an implant on a virtual patient before a manufacturer spends the time and budget to study that product in a clinical trial.
The FDA announced that it is part of the first public-private partnership to promote medical device regulatory science with a focus on speeding the development, assessment, and review of new medical devices. The new Medical Device Innovation Consortium (MDIC) is an independent, nonprofit corporation, created by LifeScience Alley (LSA), a biomedical science trade association. The MDIC will receive input from industry, government, and other nonprofit organizations. MDIC will prioritize the regulatory science needs of the medical device community and fund projects to help simplify the process of medical device design and pathway to market for these innovations.
The MDIC will bolster the country’s investment in regulatory science research by pooling people, funding, resources, and ideas to develop new tools, models, and methods that may be utilized to better and more efficiently evaluate new devices. FDA staff may collaborate with the MDIC on MDIC-supported research and other projects.
According to Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health (CDRH), “By sharing and leveraging resources, MDIC may help industry to be better equipped to bring safe and effective medical devices to market more quickly and at a lower cost,” said.
Persian Pomegranate Pistachio Meatballs
My dear husband was the guinea pig for this recipe, as he is for all of them. After he helped himself to the dinner spread, laid out, there was a pause, and great suspense, waiting for a reaction as he raised his fork. Before I could say one word, he let out sounds of high satisfaction. Happily, he loved the lamb meatballs and I hope you will too! This was definitely one way to my husband’s heart.
1 onion, chopped well
4 garlic cloves, chopped
1 1/2 cups raw pistachios
1/4 cup almond flour)
1 cup fresh parsley, chopped
1 cup fresh tarragon, chopped
1 cup fresh cilantro, chopped
1 Tablespoon fresh lime juice
1 teaspoon red pepper flakes (too spicy for us)
1 teaspoon fresh ground black pepper
1 tablespoon ground cumin (or turmeric)
1 teaspoon salt (optional)
1.5-2 pounds of ground lamb
1/2 cup canola oil or 1/2 cup olive oil
3/4 cup pomegranate molasses (I got it from Amazon.com)
1/4 cup honey
1 teaspoon salt
1/2 teaspoon fresh ground black pepper
1/2 teaspoon red pepper flakes (optional)
2 tablespoons chopped pistachios
1 sprig basil
1 cup fresh pomegranate arils
1. To make the meatballs: Pulse all the ingredients, except the meat and egg, in a food processor until you have a grainy paste.
2. Transfer to a large mixing bowl and add the meat and egg. Lightly knead with your hands for a few minutes (do not over mix).
3. Cover and place in the refrigerator for 30 minutes and up to 24 hours. (For best mix of flavors refrigerate for 24 hours
4. Preheat the oven to 500F. Generously oil a baking dish wide enough to fit 24 meatballs, about 12×14 inches) and set aside.
5. Remove the paste from the refrigerator and shape into bite-sized balls (about 1 1/2 tablespoons each, you can use an ice cream scoop) and place the meatballs in the baking dish and brush with oil. Bake in the oven for 10 minutes.
6. Meanwhile, in a mixing bowl combine all the ingredients for the glaze. It is important that you taste the glaze and be sure that it has a good balance between sweet and sour—add more honey if the pomegranate molasses you have used is too sour.
7. Reduce the oven to 400F. Brush the glaze over each meatball and bake for another 5 minutes to infuse them with the flavor of the pomegranate. Keep warm in the oven until ready to serve.
8. Place the meatballs with its sauce in deep serving dish and garnish.
9. These lamb meatballs keep very well for about a week in a good fridge; in fact, as the flavors merge, they are better the next day.
Serve these delicious meatballs with Basmati or Jasmine rice, a simple tossed salad, warm pita bread and one of the following wines: red Zinfandel, Shiraz, or an excellent Chardonnay.
Grape (Vitis) Zinfandel grapes ripening on the vine
Europe (6000 BCE – 1870)
Archaeological evidence indicates that domestication of Vitis vinifera occurred in the Caucasus region around 6000 BCE, and winemaking was discovered shortly after. Cultivation of the vine subsequently spread to the Mediterranean and surrounding regions. Croatia once had several indigenous varieties related to Zinfandel, which formed the basis of its wine industry in the 19th century. This diversity suggests that the grapes existed in Croatia longer than anywhere else. However, these varieties were almost entirely wiped out by the phylloxera epidemic of the late 19th century, reducing Zinfandel to just nine vines of locally-known “Crljenak Kaštelanski” discovered in 2001 on the Dalmatian coast of Croatia.
The first documented use of the term Primitivo appears in Italian governmental publications of the 1870s. The name derives from the terms primativus or primaticcio, which refer to the grape’s tendency to ripen earlier than other varieties. This name’s appearance 40 years after the first documented use of the term Zinfandel was previously thought to suggest that Primitivo was introduced to Italy from across the Atlantic; however, this hypothesis became unlikely since the discovery of the vine’s Croatian origin.
Primitivo is now thought to have been introduced as a distinct clone into the Puglia region of Italy in the 18th century. Don Francesco Filippo Indellicati, the priest of the church at Gioia del Colle near Bari, selected an early (“primo”) ripening plant of the Zagarese variety and planted it in Liponti. This clone ripened at the end of August and became widespread throughout northern Puglia. Cuttings came to the other great Primitivo DOC (denominazione di origine controllata or “denomination of controlled origin”) as part of the dowry of the Countess Sabini of Altamura when she married Don Tommaso Schiavoni-Tafuri of Manduria in the late 19th century.
Mark Horn MD Presents at Bloomberg on Behalf of THI
Dr. Mark Horn, our esteemed Chief Medical Officer, will present at a forum sponsored by Bloomberg Government. Dr. Horn will review a body of work PIPC (see below) has done to facilitate the participation of physicians and patients in defining PCORI’s (see below) research priorities and helping achieve the goal of genuinely patient centered research. The objectives include both identifying the issues these key constituencies deem most important and addressing them in ways that translate into improved health outcomes. What an honor for Mark Horn to represent Target Health at this forum.
Holiday Time at Target Health Inc.
For those who have not yet visited Target Health, we are located at 261 Madison Avenue in Manhattan (NYC) and have two floors there. On the 23rd floor, we have our Statistics, Data Management and IT Departments; and on the 24th floor we have our Clinical, Regulatory, HR and Business Departments.
Decorations at the Target Health 23rd floor conference room
Decorations at the entrance to the Target Health IT Department, on the 23rd floor
Decorations at the spacious reception area on the 24th floor, with reception desk to the right, and the 24th floor conference room, barely visible, to the left
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.
Alert: Mixing Grapefruit with Certain Medications can be Deadly
Editor’s note: We all sort of know this about grapefruit, but a recent study shows that we need to be more aware than we have been.
Grapefruit lovers beware: Mixing the tart citrus with certain drugs can be deadly, according to a new study published Monday in the Canadian Medical Association Journal. There are 84 drugs that interact 1) ___ with grapefruit in its various forms, even when patients don’t consume much of it, according to this recent study. It was also found that the number of common prescription drugs that can cause dangerous interactions with grapefruit is 2) ___.
Twenty-six new drugs that can cause serious 3) ___ when mixed with grapefruit have been introduced in the past four years alone, bringing the total to 43, said Dr. David Bailey, a clinical pharmacologist at the Lawson Health Institute Research Center in London, Ontario. That’s an average of more than six new drugs a year. “It’s hard to avoid putting a 4) ___ out on the market that is not affected by grapefruit juice.” However, not all have serious consequences. Those that do, however, can cause problems, such as acute kidney failure, respiratory failure, gastric bleeding and worse. For example, the heart drug dronedarone, or Multaq, has a very high risk of interaction when taken with grapefruit, which may cause a rare form of ventricular tachycardia or rapid 5) ___ rhythm. Another example is mixing grapefruit with the prescription painkiller 6) ___ which can cause serious breathing problems. Also, adding grapefruit to a dose of the popular statin simvastatin, or Zocor, can lead to rhabdomyolysis, a breakdown of muscle fibers that can lead to kidney damage.
The problem with mixing grapefruit and some medications has been known for two decades, ever since Bailey and his colleagues first discovered that ingestion of the fruit with certain prescription drugs can concentrate the 7) ___ in a patient’s bloodstream.
Drinking less than a cup of grapefruit juice once a day for three days, for instance, can lead to a 330% concentration of simvastatin. And it doesn’t matter whether the 8) ___ is consumed hours before the pills. The problem is caused by an active ingredient in some citrus fruits, including grapefruit, limes and pomelos. Even the Seville oranges used in marmalades can trigger it. The fruits produce organic chemical compounds called furanocoumarins, which interfere with a human digestive enzyme. That enzyme, called CYP3A4, helps metabolize toxic substances to keep them from getting into the 9) ___. Typically, that means the enzyme inactivates the effects of about 50% of all medications. Doctors can, theoretically, adjust for that when prescribing drugs.
However, when the furanocoumarins in citrus inhibit that enzyme, the drugs can become concentrated in a patient’s system. In some cases, it can be like getting a triple or quadruple dose of medication. Drugs known to interact with grapefruit do carry warnings, but Bailey said he believes that neither doctors nor patients may take the threat seriously enough. “Basically, most people are sort of aware of grapefruit juice drug interactions, but I don’t think it’s in the forefront of their mind on a regular basis,” he said. It’s not clear how many people actually are harmed by grapefruit interactions, mostly because the side 10) ___ are often not recognized as being related to the citrus, said Bailey, who included eight case reports in his study. Part of the concern lies in the fact that people older than 45 are most likely to consume grapefruit juice — and to take prescription drugs. Seniors older than 70 years of age have the most trouble tolerating excessively high levels of drugs.
Patients worried about the interaction of grapefruit with their medications should talk with their doctors, Bailey said. And doctors should make sure to ask about grapefruit consumption when prescribing drugs.
Some grapefruit lovers may have cut back already because of the risk of drug 11) ___. Consumption of grapefruit juice has dropped in the past decade, falling from .44 gallons of juice per person per year in 2000 to 0.15 gallons per person in 2011, according to figures from the Florida Department of Citrus. Officials there say that although some drugs do interact with grapefruit, most do not. In most cases, doctors can prescribe drugs in the same class that don’t interact, noted Karen Mathis, a department spokeswoman. “These medications often can provide the same therapeutic effect with no need to avoid grapefruit juice,” she said in a statement. And not all citrus poses a problem, Bailey noted. Sweet oranges, such as navel and Valencia varieties, don’t contain the damaging compound. “You have an alternative there,” he suggested. “If you want to take your medications with 12) ___ juice, you’re home free.”
ANSWERS: 1) negatively; 2) rising; 3) harm; 4) drug; 5) heart; 6) oxycodone; 7) medication; 8) grapefruit; 9) bloodstream; 10) effects; 11) interaction; 12) orange