NDA Under Review With 7 Studies All with eSource using Target eClinical Trial Record (Target e*CTR®)

 

Target Health is pleased to announce that the NDA submitted in November 2015 containing 7 studies, all using direct data entry at the time of the clinic visit and risk-based monitoring, is under active review by FDA. The pivotal trial included 22 study sites. For all studies, greater than 90% of the data were entered in real time. This is the 2ndprogram submitted to FDA where the Target Health web-based eSource solution was used. The first submission resulted in an FDA clearance for marketing of a de novo 510(k) for a novel device to prevent hair loss in women undergoing breast cancer chemotherapy. This study was performed at 6 medical centers throughout the United States with flawless FDA inspections of both the sites and Target Health.

 

Texas Blue Bonnets

 

 

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Texas Blue Bonnets ©Vanessa Hays, Target Health Inc.

 

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. 165). 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

 

Foot Health Care: Going Barefoot and Worse

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Ancient Olympic discus thrower; Photo credit: Livioandronico, 2013

Own work, CC BY-SA 4.0,

 

People in ancient times, such as the Egyptians, Hindus and Greeks often went barefoot, as the inhabited terrain mostly mandated no practical necessity for footwear. The Egyptians and Hindus made some use of ornamental footwear, such as a soleless sandal known as a Cleopatra, which did not provide any practical protection for the foot. Athletes in the Ancient Olympic Games participated barefoot and generally unclothed. Even the gods and heroes were primarily depicted barefoot, the hoplite warriors fought battles in bare feet, and Alexander the Great operated barefoot armies. The Romans, who eventually conquered the Greeks and adopted many aspects of their culture, did not adopt the Greek perception of footwear and clothing. Roman clothing explicitly including footwear was seen as a sign of power and as a necessity of living in a civilized world, accordingly slaves usually were to remain barefoot. There are many references to shoes being worn in the Bible. During weddings of this period, a father would give his son-in-law a pair of shoes to symbolize the transfer of authority.

 

During the Middle Ages, both men and women wore pattens in Europe, commonly seen as the predecessor of the modern high-heeled shoe, while menial classes usually wore hand-made footwear out of available materials. Going barefoot was avoided, if possible, as this was seen as a token of the lowest social status and as such an earmark of imprisoned people. In the 15th century, chopines were created in Turkey and were usually 7-8 inches (17.7-20.3 cm) high. These shoes became popular in Venice and throughout Europe as a status symbol revealing wealth and social standing. During the 16th century, royalty started wearing high-heeled shoes to make them look taller or larger than life, such as Catherine de Medici or Mary I of England. By 1580, even men wore them, and a person with authority or wealth was often referred to as “well-heeled“.

 

The phrase Barefoot and pregnant was used to illustrate a woman’s traditional role as a homemaker and thus her lack of opportunities to socialize or to have a career outside of the home. It was first used in the early 20th century, possibly by Dr. Arthur E. Hertzler (also known as the “Kansas Horse-and-Buggy Doctor“), promoting a hypothesis that:

 

“The only way to keep a woman happy is to keep her barefoot and pregnant.“

 

Bare feet have come to symbolize innocence or childhood in a glorifying perception of freedom from real-life requirements. The connection to childhood and innocence, as well as the simple joys of country life, are embodied in the poem “The Barefoot Boy“ by John Greenleaf Whittier, published in 1855. Additionally, the book Dancing Barefoot by Star Trek: The Next Generation actor Wil Wheaton features five short stories that chronicle his journey from childhood and youth through to maturity and self-acceptance. In most religions, the exposure of bare feet is regarded as a sign of humility and subjection. Some religious practitioners have taken a vow of Gospel poverty, while there are certain convents where going barefoot is obligatory (Convent of Las Descalzas Reales, Poor Clares, Colettine Poor Clares). With regard to the use of footwear as a display of status, the religious and common art of many cultures throughout the world shows a person without shoes symbolizing either extreme poverty or the state of captivity and unfree servitude. In Thailand, Master Jinshen, a Buddhist monk, walks 20 kilometers (12 mi) per day barefoot as a reminder to others who pursue a material life to protect and be concerned for Mother Nature. He states that he does this to follow Buddhist rules, to lead the people to the path of virtue, and to develop his Buddhist spirit. It is customary in Judaism and some Christian denominations to go barefoot while mourning. Some Christian churches practice barefoot pilgrimage traditions, such as the ascent of Croagh Patrick in Ireland at night while barefoot (although the nighttime part is no longer encouraged). In many religions, it is common to remove shoes when entering a place considered holy. For example, in the Book of Exodus, Moses was instructed to remove his shoes before approaching the burning bush:

 

“Put off thy shoes from off thy feet, for the place whereon thou standest [is] holy ground (Exodus 3:5).“

 

Everyone entering a mosque or a Hindu temple, including visitors, is expected to remove his or her shoes; racks for the storage of shoes are usually provided at the entrance. Foot washing, or ceremonial washing of others’ feet, is associated with humility in Christianity, and Jesus Christ is recorded in the New Testament as washing the feet of his disciples to serve them during the Last Supper. Christians who practice foot washing today do so to bring them closer to Jesus and to fill them with a sense of humility and service. Roman Catholics show their respect and humility for the Pope by kissing his feet. In a similar manner, Hindus show love and respect to a guru by touching his bare feet (called pranam). It is customary to show one’s respect by walking barefoot around Raj Ghat, the monument to Mahatma Gandhi. Both United States President George W. Bush and Pope John Paul II paid him this honor. During the Imperial Japanese period, removing one’s shoes in the presence of a person of higher status was a sign of showing one’s own humility, subordination and respect towards their status. Christian congregations of men and women that go entirely barefoot or wear sandals include the Discalced, like the Discalced Carmelites (1568), the Feuillants(Cistercians, 1575), the Trinitarians (1594), the Mercedarians (1604), and the Passionists. In many branches of Romani culture across the world, it is traditional for women to dance barefoot.

 

Firewalking is the practice of walking barefoot over hot coals. It has been practiced by many people and cultures in all parts of the world, with the earliest known reference dating back to the Iron Age, around 1200 BC. This practice is often used as a rite of passage, as a test of an individual’s strength and courage, or, in religion, as a test of one’s faith. Today, it is often used in corporate and team-building seminars and self-help workshops as a confidence-building exercise. Firewalking implies the belief that the feat requires the aid of a supernatural force, strong faith, or on an individual’s ability to focus on “mind over matter“. Modern physics has largely debunked this, showing that the amount of time the foot is in contact with the ground is not enough to induce a burn, combined with the fact that coal is not a very good conductor of heat.

 

 

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A woman with her feet unwrapped. Public Domain:

 

 

Foot binding (also known as “lotus feet“) was the custom of applying painfully tight binding to the feet of young girls to prevent further growth. The practice possibly originated among upper-class court dancers during the Five Dynasties and Ten Kingdoms period in Imperial China (10th or 11th century), then became popular during the Song dynasty and eventually spread to all social classes. Foot binding became popular as a means of displaying status (women from wealthy families, who did not need their feet to work, could afford to have them bound) and was correspondingly adopted as a symbol of beauty in Chinese culture. Its prevalence and practice however varied in different parts of the country. The Manchu Kangxi Emperor tried to ban foot binding in 1664 but failed. In the later part of the 19th century, Chinese reformers challenged the practice but it was not until the early 20th century that foot binding began to die out as a result of anti-foot-binding campaigns. Foot-binding resulted in lifelong disabilities for most of its subjects, and a few elderly Chinese women still survive today with disabilities related to their bound feet. There are many suggestions for the origin of footbinding. One story relates that during the Shang dynasty, the concubine Daji, who was said to have clubfoot, asked the Emperor to make footbinding mandatory for all girls in court so that her own feet would be the standard of beauty and elegance. Another story tells of a favorite courtesan of Emperor Xiao Baojuan. Pan Yu’er, had delicate feet, and danced bare foot over a floor decorated with a golden lotus flower design. The emperor expressed admiration and said that “lotus springs from her every step!“ a reference to the Buddhist legend of Padmavati under whose feet lotus springs forth. This story may have given rise to the terms “golden lotus“ or “lotus feet“ used to describe bound feet, there is however no evidence that Pan Yu’er ever bound her feet. The general consensus is that the practice is likely to have originated from the time of Emperor Li Yu (Southern Tang of the Ten Kingdoms, just before the Song dynasty). Emperor Li Yu created a six-foot tall golden lotus decorated with precious stones and pearls, and asked his concubine Yao Niang (zh) to bind her feet in white silk into the shape of the crescent moon, and perform a dance, ballet-like, on the points of her feet on the lotus. Yao Niang’s dance was said to be so graceful that others sought to imitate her. The binding of feet was then replicated by other upper-class women and the practice spread.

 

The practice of foot binding became popular during the Song dynasty, and the earliest known writings and references to footbinding appeared in the late eleventh century. In the 12th century, Zhang Bangji (zh) considered that a bound foot should be arched-shaped and small. A thirteenth-century writer, Che Ruoshui (zh), complained that “little children not yet four or five years old, who have done nothing wrong, nevertheless are made to suffer unlimited pain to bind their feet small. I do not know what use this is“. Evidence from archaeology indicates that footbinding was practiced among the wives and daughters of officials in the 13th century. However, the style of bound feet found in Song Dynasty tombs, where the big toe was bent upwards, appears to be different from the norm of subsequent eras, and the excessive smallness of the feet, the “three-inch golden lotus“, may be a later development in the 16th century. The practice became increasingly common in the following centuries among the gentry families, later spreading to the general population. By the end of the Song dynasty, men would drink from a special shoe whose heel contained a small cup. During the Yuan dynasty, some would also drink directly from the shoe itself. This louche practice was called “toast to the golden lotus“ and lasted until the late Qing dynasty. By the 19th century, it was estimated that 40-50% of Chinese women had bound feet, and among upper class Han Chinese women, the figure was almost 100%. Bound feet became a mark of beauty and was also a prerequisite for finding a husband. It also became an avenue for poorer women to marry into money; for example, in Guangdong in the late 19th century, it was customary to bind the feet of the eldest daughter of a lower-class family who was intended to be brought up as a lady. Her younger sisters would grow up to be bond-servants or domestic slaves and be able to work in the fields, but the eldest daughter would assume to never have the need to work. Women, their families, and their husbands took great pride in tiny feet, with the ideal length, called the “Golden Lotus“, being about three Chinese inches long (around 4 inches (10 cm) in Western measurement). This pride was reflected in the elegantly embroidered silk slippers and wrappings girls and women wore to cover their feet. Walking on bound feet necessitated bending the knees slightly and swaying to maintain proper movement and balance, a dainty walk that was also considered erotic to some men. Many women with bound feet were in fact able to walk and work in the fields, albeit with greater limitation than their non-bound counterparts. In the 19th and early 20th century, dancers with bound feet were very popular, as were circus performers who stood on prancing or running horses. Women with bound feet in one village in Yunnan Province even formed a regional dance troupe to perform for tourists in the late twentieth century, though age has since forced the group to retire. In other areas, women in their 70s and 80s could be found providing limited assistance to the workers in the rice fields well into the 21st century.

 

The process was started before the arch of the foot had a chance to develop fully, usually between the ages of 4 and 9. Binding usually started during the winter months since the feet were more likely to be numb, and therefore the pain would not be as extreme. First, each foot would be soaked in a warm mixture of herbs and animal blood; this was intended to soften the foot and aid the binding. Then, the toenails were cut back as far as possible to prevent in-growth and subsequent infections, since the toes were to be pressed tightly into the sole of the foot. Cotton bandages, 3m long and 5cm wide (10ft by 2 in), were prepared by soaking them in the blood and herb mixture. To enable the size of the feet to be reduced, the toes on each foot were curled under, then pressed with great force downwards and squeezed into the sole of the foot until the toes broke. The broken toes were held tightly against the sole of the foot while the foot was then drawn down straight with the leg and the arch of the foot was forcibly broken. The bandages were repeatedly wound in a figure-eight movement, starting at the inside of the foot at the instep, then carried over the toes, under the foot, and around the heel, the freshly broken toes being pressed tightly into the sole of the foot. At each pass around the foot, the binding cloth was tightened, pulling the ball of the foot and the heel together, causing the broken foot to fold at the arch, and pressing the toes underneath the sole. The binding was pulled so tightly that the girl could not move her toes at all and the ends of the binding cloth were then sewn so that the girl could not loosen it.

 

 

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An X-ray of two bound feet

 

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Schema of an x-ray comparison between an unbound and bound foot

 

 

The girl’s broken feet required a great deal of care and attention, and they would be unbound regularly. Each time the feet were unbound, they were washed, the toes carefully checked for injury, and the nails carefully and meticulously trimmed. When unbound, the broken feet were also kneaded to soften them and the soles of the girl’s feet were often beaten to make the joints and broken bones more flexible. The feet were also soaked in a concoction that caused any necrotic flesh to fall off. Immediately after this agonizing pedicure, the girl’s broken toes were folded back under and the feet were rebound. The bindings were pulled even tighter each time the girl’s feet were rebound. This unbinding and rebinding ritual was repeated as often as possible (for the rich at least once daily, for poor peasants two or three times a week), with fresh bindings. It was generally an elder female member of the girl’s family or a professional foot binder who carried out the initial breaking and ongoing binding of the feet. It was considered preferable to have someone other than the mother do it, as she might have been sympathetic to her daughter’s pain and less willing to keep the bindings tight. For most the bound feet eventually became numb. However, once a foot had been crushed and bound, attempting to reverse the process by unbinding is painful, and the shape could not be reversed without a woman undergoing the same pain all over again. The most common problem with bound feet was infection. Despite the amount of care taken in regularly trimming the toenails, they would often in-grow, becoming infected and causing injuries to the toes. Sometimes for this reason the girl’s toenails would be peeled back and removed altogether. The tightness of the binding meant that the circulation in the feet was faulty, and the circulation to the toes was almost cut off, so any injuries to the toes were unlikely to heal and were likely to gradually worsen and lead to infected toes and rotting flesh. If the infection in the feet and toes entered the bones, it could cause them to soften, which could result in toes dropping off; although, this was seen as a benefit because the feet could then be bound even more tightly. Girls whose toes were more fleshy would sometimes have shards of glass or pieces of broken tiles inserted within the binding next to her feet and between her toes to cause injury and introduce infection deliberately. Disease inevitably followed infection, meaning that death from septic shock could result from foot-binding, and a surviving girl was more at risk for medical problems as she grew older. It is thought that as many as 10% of girls may die from gangrene and other infections due to footbinding. At the beginning of the binding, many of the foot bones would remain broken, often for years. However, as the girl grew older, the bones would begin to heal. Even after the foot bones had healed, they were prone to re-breaking repeatedly, especially when the girl was in her teenage years and her feet were still soft. Older women were more likely to break hips and other bones in falls, since they could not balance securely on their feet, and were less able to rise to their feet from a sitting position. Other issues that might arise from foot binding included paralysis and muscular atrophy.

 

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A comparison between a woman with normal feet (left) and a woman with bound feet in 1902. By C.H. Graves. – This image is available from the United States Library of Congress’s Prints and Photographs division under the digital ID cph.3a49263. Public Domain,

 

 

In the United States and Europe, the case against wearing high heels is based almost exclusively on health and practicality reasons, including that they can:

 

1. cause foot and tendon pain;

2. increase the likelihood of sprains and fractures;

3. create foot deformities, including hammer toes and bunions;

4. cause an unsteady gait;

5. render the wearer unable to run;

6. exacerbate lower back pain;

7. alter forces at the knee so as to predispose the wearer to degenerative changes in the knee joint;

8. can result after frequent wearing, in a higher incidence of degenerative joint disease of the knees.

 

 

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21st Century shoe fetish. Wikipedia commons: by MusicNewz – Own work, CC BY-SA 3.0,

 

 

Modern day foot binding: Despite the risks, 21st Century women are increasingly requesting cosmetic foot procedures — including shortening their toes, adding collagen to their heels and even removing their pinky toe — in order to fit into sky-high stilettos. Others opt to lop parts off in order to fit into a smaller size.

 

 

 

QUIZ

Filed Under News | Leave a Comment

Think Before You Go – Barefoot, That Is

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(Left) plaster cast of an adult foot that has never worn shoes displaying natural splayed toes (Right) cast of boy showing damage and inward-turned toes after wearing shoes for only a few weeks. Photo credit: (Wikipedia commons) Phil. Hoffmann – Conclusions Drawn From a Comparative Study of Barefoot and Shoe-Wearing Peoples, The Journal of Bone & Joint Surgery. 1905; s2-3:105-136, PD-US,

 

 

1) ___ is the most common term for the state of not wearing any footwear. Barefootedness is not regarded as unusual in many domestic environments, but is subject to criticism in public spaces in many urban cultures. Urban environments are generally not where people go barefoot, for obvious reasons of cleanliness and danger of cuts, etc. Wearing footwear is an exclusively 2) ___ characteristic. It has been normal in cold climates since early antiquity, and has since become a convention in most cultures. This is particularly the case in most urban situations, where going barefoot is unusual. While footwear is generally worn for functional, fashion, and societal reasons, many people do not wear shoes at home.

 

There are health benefits and risks associated with going barefoot. Footwear provides protection from cuts, abrasions, bruises and impacts from objects on the ground or the ground texture itself, as well as from frostbite and parasites like hookworm in extreme situations. However, shoes can limit the flexibility and mobility of the foot and can lead to higher incidences of flexible flat foot, bunions, hammer toe and Morton’s neuroma. Walking barefoot results in a more natural gait, allowing for a more rocking motion of the foot, eliminating the hard heel strike hereby generating less collision force in the foot and lower 3) ___. There are many sports that are performed barefoot, most notably gymnastics and martial arts, but also beach volleyball, barefoot running and water skiing. In modern language, someone who tends not to wear shoes in public or is participating in the sports, mentioned above, may be described as a barefooter.

 

Although, footwear provides some protection from puncture wounds from glass, nails, rocks, or thorns as well as abrasions, bruises, and frostbite? studies of people who habitually walk barefoot have consistently found that these problems are minimal, with only about 0.89% of barefoot people having any kind of foot complaint linked to walking barefoot (including temporary conditions such as abrasions) or having the tops of the feet uncovered. Feet that have never worn shoes rarely exhibit problems such as bunions, corns, and ?fallen 4) ___‘, aren’t prone to more than ordinary foot eversion on standing and walking due to the associated weakness or stiffness of the joints of the foot and weakness of the muscles controlling them, as well as having a much reduced incidence of problems such as callouses. A 2006 study found that shoes may increase stress on the knee and ankle, and suggested that adults who walked barefoot may have a lower rate of osteoarthritis, although more study is required to elucidate the factors that distribute loads in shod and barefoot walking. A 2007 study examined 180 modern humans and compared their feet with 2,000-year-old skeletons. They concluded that, before the invention of shoes, humans overall had healthier 5) ___.

 

A 1991 study found that children who wore shoes were three times more likely to have flat feet than those who did not, and suggested that wearing shoes in early childhood can be detrimental to the longitudinal arch of the foot. Children who habitually go barefoot were found to have stronger feet, with better flexibility and mobility, fewer deformities like flat feet or toes that curve inwards, and fewer complaints. Walking barefoot enables a more natural gait, eliminating the hard heel strike and instead, allowing for a rocking motion of the foot from heel to 6) ___. Similarly, barefoot running usually involves an initial forefoot strike, instead of on the rear of the foot, generating smaller collision forces. Since there is no artificial protection of the bare foot, other additional issues include poisonous plants, animals, or parasites that can enter the body through the cuts on an injured bare foot. In people who are not habitually barefoot, Athlete’s foot is spread by 7) ___fungal spores coming into contact with skin that has been weakened and made moist. The fungus is known to only affect around 0.75% of habitually barefoot people in one study and can be prevented by reducing shoe use and keeping the feet dry, particularly after walking through a damp environment where people communally walk barefoot as the fungus only develops under the right conditions, such as when people fail to properly dry their feet after swimming or showering and then put on shoes. Wearing shoes such as flip flops or sandals in these areas can reduce the risk. As such, the fungus is very unlikely to develop on a person who goes barefoot all the time.

 

The Hookworm parasite, is found only in warm, moist climates where human feces contaminated with Hookworm larvae has been left in places where it might come into contact with human skin. This parasite, can burrow through a bare human foot (or any part of the body that comes into contact with it). However, as the 8) ___ tends to occur mainly in mud and cesspools, its spread cannot be stopped by most standard shoes since the larvae can penetrate fabric and small holes. The parasite may spread through contaminated material coming into contact with any part of the body, such as through flecks of mud splashing on an ankle or leg. The Hookworm parasite is relatively mild, has few symptoms, and can pass completely unnoticed when the infestation level is low enough. Since the 9) ___ infection is very cheap and easy to treat, and since it requires infected feces to come into contact with human skin within a particular time period, eradicating hookworm is mainly a matter of hygiene (including the building of proper toilet and waste-disposal facilities) and mass-treatment. In very cold weather, shoes can provide thermal insulation, protecting against frostbite. Individuals with diabetes or other conditions that affect sensation in the feet are at greater risk of injury while barefoot. The American Diabetes Association recommends that diabetics wear 10) ___ and socks at all times.

 

ANSWERS: 1) Barefoot; 2) human; 3) leg; 4) arches; 5) feet; 6) toe; 7) fungal; 8) parasite; 9) hookworm; 10) shoes

 

Suicide Risk in Children with Cushing Syndrome

 

Cushing syndrome results from high levels of the hormone cortisol and affects both adults and children. Long-term complications of the syndrome include obesity, diabetes, bone fractures, high blood pressure, kidney stones and serious infections. Cushing’s syndrome may be caused by tumors of the adrenal glands or other parts of the body that produce excess cortisol. It also may be caused by a pituitary tumor that stimulates the adrenal glands to produce high cortisol levels. Treatment usually involves stopping excess cortisol production by removing the tumor. A recent study estimated that in the United States, there are eight cases of Cushing syndrome per 1 million people per year.

 

According to an article published in the journal Pediatrics (April 2016), children with Cushing syndrome may be at higher risk for suicide as well as for depression, anxiety and other mental health conditions long after their disease has been successfully treated. According to the authors, the results indicate that physicians who care for young people with Cushing syndrome should screen their patients for depression-related mental illness after the underlying disease has been successfully treated. The authors added that while patients may not tell their doctors that they’re feeling depressed, it’s a good idea for physicians to screen their patients proactively for depression and related conditions.

 

The study reviewed the case histories of all 149 children and youth treated for Cushing syndrome at NIH from 2003 to 2014. Results showed that months after treatment, nine children (roughly 6%) had thoughts of suicide and experienced outbursts of anger and rage, depression, irritability and anxiety. Of these, seven experienced symptoms within seven months of their treatment. Two others began experiencing symptoms at least 48 months after treatment. The authors also noted that children with Cushing syndrome often develop compulsive behaviors and tend to become over-achievers in school. After treatment, however, they can become depressed and anxious. This is in direct contrast to adults with Cushing syndrome, who tend to become depressed and anxious before treatment and gradually overcome these symptoms after treatment.

 

The authors stated that health care providers might try to prepare children with Cushing syndrome before they undergo treatment, letting them know that their mood may change after surgery and may not improve for months or years. Similarly, providers should consider screening their patients periodically for suicide risk in the years following their treatment.

 

Effectiveness of NSAIDs for the Treatment of Pain in Knee and Hip Osteoarthritis

 

Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. As a result, a study published online in The Lancet: (17 March 2016) aimed to assess the effectiveness of different preparations and doses of NSAIDs on osteoarthritis pain in a network meta-analysis.

 

For this network meta-analysis, the authors considered randomized trials comparing any of the following interventions: NSAIDs, paracetamol (acetaminophen), or placebo, for the treatment of osteoarthritis pain. The Cochrane Central Register of Controlled Trials (CENTRAL) was searched and the authors used the reference lists of relevant articles for trials published between January 1, 1980, and February 24, 2015, with at least 100 patients per group. The pre-specified primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven time points after the start of treatment. An extension of multivariable Bayesian random effects models was used for mixed multiple treatment comparisons with a random effect at the level of trials. For the primary analysis, a random walk of first order was used to account for multiple follow-up outcome data within a trial. Preparations that used different total daily dose were considered separately in the analysis. To assess a potential dose-response relation, the study used preparation-specific covariates assuming linearity on log relative dose.

 

The authors identified 8,973 manuscripts of which 74 randomized trials with a total of 58,556 patients were included in this analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo were considered. All preparations, irrespective of dose, improved point estimates of pain symptoms when compared with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a pre-specified minimum clinically important effect for pain reduction was at least 95%. Among maximally approved daily doses, diclofenac 150 mg/day and etoricoxib 60 mg/day had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference. Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for celecoxib (p=0.030), diclofenac (p=0.031), and naproxen (p=0.026). There was no evidence that treatment effects varied over the duration of treatment. All trials were deemed to have a low risk of bias for blinding of patients.

 

According to the authors, on the basis of the available data, there is no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose, but there is sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function. Nevertheless, in view of the safety profile of these drugs, physicians need to consider the results together with all known safety information when selecting the preparation and dose for individual patients.

 

First Treatment for Hepatic Veno-Occlusive Disease (VOD) in Patients Receiving Stem Cell Transplant from Blood or Bone Marrow

 

Hematopoietic stem cell transplantation (HSCT) is a procedure performed in some patients to treat certain blood or bone marrow cancers. Immediately before an HSCT procedure, a patient receives chemotherapy. Hepatic VOD can occur in patients who receive chemotherapy and HSCT. Hepatic veno-occlusive disease (VOD) is a condition in which some of the veins in the liver become blocked, causing swelling and a decrease in blood flow inside the liver, which may lead to liver damage. In the most severe form of hepatic VOD, the patient may also develop failure of the kidneys and lungs. Fewer than 2% of patients develop severe hepatic VOD after HSCT, but as many as 80% of patients who develop severe hepatic VOD do not survive.

 

The FDA has approved Defitelio (defibrotide sodium) to treat adults and children who develop VOD with additional kidney or lung abnormalities after they receive HSCT. This is the first FDA-approved therapy for treatment of severe hepatic VOD. The efficacy of Defitelio was investigated in 528 patients treated in three studies: two prospective clinical trials and an expanded access study. The patients enrolled in all three studies had a diagnosis of hepatic VOD with liver or kidney abnormalities after HSCT. The studies measured the percentage of patients who were still alive 100 days after HSCT (overall survival). In the three studies, 38-45% of patients treated with Defitelio were alive 100 days after HSCT. Based on published reports and analyses of patient-level data, the expected survival rates 100 days after HSCT would be 21-31% for patients with severe hepatic VOD who received only supportive care or interventions other than Defitelio.

 

The most common side effects of Defitelio include abnormally low blood pressure (hypotension), diarrhea, vomiting, nausea and nosebleeds (epistaxis). Serious potential side effects of Defitelio that were identified include bleeding (hemorrhage) and allergic reactions. Defitelio should not be used in patients who are having bleeding complications or who are taking blood thinners or other medicines that reduce the body’s ability to form clots.

 

The FDA granted the Defitelio application priority review status, which facilitates and expedites the development and review of certain drugs in light of their potential to benefit patients with serious or life-threatening conditions. Defitelio also received orphan drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for exclusivity to assist and encourage the development of drugs for rare diseases.

 

Defitelio is marketed by Jazz Pharmaceuticals based in Palo Alto, California.

 

Oregano Potatoes Roasted with Garlic & Olive Oil

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You won’t believe how flavorful and addictive this simple recipe is. ©Joyce Hays, Target Health Inc. Jules gives it 5 stars! We couldn’t stop eating it; plus we’ve had it three more times this week. I’ve experimented a lot with potatoes (stuffed with broccoli; with tuna; with kale; mashed with garlic & truffle oil, etc. This is the very best potato combo, I’ve ever come up with. Is it the multitude of garlic? Fresh oregano instead of dried? The best extra virgin olive oil? Whatever it is, you’ve got to give it a try.

 

Ingredients

 

2 1/2 pounds red new potatoes (about 6 medium), unpeeled (DON’T PEEL) and cut into 1-inch cubes

20 fresh garlic cloves, sliced but not thin slices

3 heaping Tablespoons fresh (not dried) oregano, well chopped

Pinch salt

Pinch black pepper

Pinch chili flakes

1/2 cup extra virgin olive oil

 

 

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Fresh simple organic ingredients. ©Joyce Hays, Target Health Inc.

 

 

Directions

 

1. Preheat oven to 425 degrees

 

2. Scrub potatoes, LEAVE THE SKINS ON, then cut into (approx) 1 inch cubes.

 

 

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These red skins are healthy, tasty and attractive. ©Joyce Hays, Target Health Inc.

 

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Try to get organic oregano. And, less of a carbon footprint if it’s grown locally. At least this oregano is grown on the East coast. ©Joyce Hays, Target Health Inc.

 

 

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Fresh oregano and dried oregano have completely different flavors. Both are wonderful to cook with, but in this recipe, only use the fresh. Try to use organic. ©Joyce Hays, Target Health Inc.

 

 

3. Wash the fresh oregano, then chop it well.

 

 

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Isn’t 20 garlic cloves a lot“, you ask? The answer is that garlic offers many options. When you roast it, as we’re doing in this recipe, it takes on a delicious sweet flavor. 20 cloves of raw garlic would be a different story. ©Joyce Hays, Target Health Inc.

 

 

4. Peel the 20 garlic cloves, then cut them into thick slices

 

5. In a large roasting pan, combine potato cubes, garlic, oregano and extra virgin olive oil. Stir until potatoes are well-coated, and spread them evenly in pan.

 

 

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Everything is all mixed together and about to go into the oven. ©Joyce Hays, Target Health Inc.

 

 

6. Place in oven, and roast until golden brown and crispy, 40 minutes to an hour. (If the potatoes are crowded in the pan, they will take longer to crisp.)

 

7. Remove potatoes and garlic from oven, and transfer to a serving dish. Sprinkle with salt (optional) to taste, and serve immediately.

 

This veggie side dish is good with beef, poultry, fish, seafood. If you want to go veggie only, serve the roasted potatoes with a Caesar salad, or your own favorite crispy salad, and warm grain bread and/or rolls that you dip in the garlic-y olive oil from the potatoes. You are going to have a fantastic treat with this recipe. Be prepared to want only this dish, until it’s quickly disappeared.

 

 

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Gone in 30 minutes. ©Joyce Hays, Target Health Inc.

 

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We’re drinking chilled Santa Margherita Pinot Grigio. The cute frog planter is from our daughter who always comes up with the most original gifts. We love this frog. ©Joyce Hays, Target Health Inc.

 

We went to the MetOpera again this weekend (such a magical place) and saw “Butterfly.”

 

As our friends and colleagues know, we are highly critical of the MetOpera set designs; however, in this production, the extremely good lighting design made up for the sets. A big plus for this production was very creative use of Bunraku puppeteers dressed in black so that they blended into the background and could barely be seen.Bunraku, or Japanese puppet theater, is probably the most developed form of puppetry in the world. Incorporating sophisticated Japanese puppetry into this opera, added greatly, to the overall experience. Finally, it was a great treat to hear Latvian soprano, Kristine Opolais sing the lead role. She has a gorgeous voice as well as a natural passion for the roles she plays. If you haven’t seen this production, try to get tickets, if you can.  This production was sold out. Beautiful music needs to be shared. Below are my two favorite pieces from this beautiful opera, as well as a short video about Bunraku.

 

Kristine Opolais, Madama Butterfly, – Un bel di vedremo, by Giacomo Puccini

 

Famous Humming Chorus from Madama Butterfly by Giacomo Puccini

 

Example of Bunraku

 

 

 

From Our Table to Yours !

 

Bon Appetit!