Publications From Target Health

 

As a science- and data-based eCRO, we are committed to sharing our results with the broader pharmaceutical, biotechnology and medical device community.  Thus, we are pleased to announce that the following manuscripts have been accepted for publication this year. We will let you know when they are published.  For other publications, please visit our website.

 

“21st Century Approaches to QA Oversight of Clinical Trial Performance and Clinical Data Integrity,” has been peer reviewed and accepted for publication in The Monitor, journal of the Association of Clinical Clinical Research Professionals (ACRP).

 

“How Direct Data Entry at the Time of the Patient Visit is Transforming Clinical Research – Perspective from the Clinical Trial Research Site” has been peer reviewed and accepted for publication in Clinical Trials, the journal of the Society for Clinical Research Sites.

 

“Risk Based Approaches: Best Practices for Ensuring Clinical Data Quality,” a collaborative article by the eClinical Forum, has been peer reviewed and accepted for publication in Applied Clinical Trials.

 

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.

San Joaquin Valley Fever

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Last week it was reported that because of a contagious airborne fungus disease, called Valley Fever, all of the prison inmates near the Mohave Desert in California had to be moved to a new location. Due to climate change, this drought area, has become even more parched (dry soil is the ecologic niche for the fungus) and therefore, dustier. Now, the constant winds are whipping up the dust, making the fungus spores airborne and a danger to 1) ___ and other animals.

 

In California, the number of annually reported coccidioidomycosis cases more than tripled from 2000-2006, rising from 2.4 to 8 cases per 100,000 population. The annual incidence was highest in Kern County (150 cases per 100,000 population), with the hospitalization rate highest among non-Hispanic blacks, increasing from 3 cases to 7.5 cases per 100,000 population. Arizona, where coccidioidomycosis is a reportable condition, has the greatest number of cases. This likely represents symptomatic cases only. More than 5,000 cases are reported annually in Arizona, and the state has noted a steady increase in cases, with 7 cases per 100,000 persons in 1990, increasing to 15 cases per 100,000 persons in 1995and an estimated 75 cases per 100,000 persons in 2007. There was an outbreak in the summer of 2001 in Colorado, away from where the endemic is persistent. A group of archeologists visited Dinosaur National Monument, and eight members of the crew, along with two National Park Service workers were diagnosed with valley fever. Perhaps, they dug into, or disturbed the dusty soil without wearing the recommended partial face mask.

 

Coccidioidomycosis is caused by Coccidioides immitis, a soil 2) ___ native to the San Joaquin Valley of California (see the image below), and by C posadasii, which is endemic to certain arid-to-semi-arid areas of the southwestern US, northern portions of Mexico, and scattered areas in Central America and South America. Although genetically distinct, the 2 species are morphologically identical.

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A Coccidioides immitis spherule containing daughter cysts. Courtesy of Thomas Matthew.

 

Few immunologic differences are noted between the 2 species of Coccidioides, and the manifestations of infection with either organism are assumed to be identical.

 

Coccidioidomycosis is typically transmitted by 3) ___ of airborne spores of C immitis or C posadasii. Infection occurs in endemic areas and is most commonly acquired in the summer or the late fall during outdoor activities. Travelers to endemic areas are at risk for contracting the 4) ___, which may not become clinically evident until after they have returned home. In addition, infection may be acquired outside of endemic areas via transport of contaminated material. Diagnosis often is delayed in nonendemic areas because coccidioidal infection initially is not considered in the differential. In most patients with coccidioidal infection, the primary infection is in the lungs. In 60-65% of cases, this infection is asymptomatic. In other cases, a mild influenza-like illness develops 1-4 weeks after exposure. The symptoms are indistinguishable from other respiratory illnesses, with fever, sore throat, cough, headache, fatigue, and pleuritic chest pain. Resolution typically occurs over several weeks (although fatigue may persist for months), and 95% or more of patients recover without any further sequelae. A more involved presentation, with the constellation of fever, arthralgias, erythema nodosum or erythema multiforme, and chest pain is commonly referred to as San Joaquin Valley fever (or simply 5) ___ fever) or desert rheumatism.

 

Coccidioidomycosis spreads beyond the 6) ___ in approximately 0.6% of the infections in the general population. Most extrapulmonary disseminated infections are a result of hematogenous spread. Dissemination can be rapid and fatal. Virtually any organ of the body can be involved (e.g., endocrine glands, eye, liver, kidney, prostate, peritoneal cavity), but Coccidioides species has a predilection for the lungs, skin, soft tissue, joints, and CNS, especially the meninges. Meningitis is a grave complication. Disseminated disease may occur in an otherwise healthy individual, but the risk is significantly higher in individuals with altered cellular immunity due to disease (e.g., HIV infection, lymphoma), medical treatment (e.g., corticosteroid therapy), or pregnancy. In addition, risk of dissemination or progressive pulmonary disease is higher in certain racial groups (e.g., Filipinos, blacks). Extrapulmonary primary infections can occur with trauma causing a puncture wound from a contaminated object. Laboratory workers and children are especially at risk for cutaneous or soft 7) ___ lesions, including chancres, with regional lymphadenitis.

 

Diagnosis requires isolation of the organism in culture, identification on histologic specimens, or serologic testing. Most patients infected with Coccidioides are asymptomatic or have self-limited symptoms and require only supportive care. Symptomatic patients usually come to medical attention because of 8) ___ tract or systemic manifestations. Management in symptomatic patients varies with the clinical syndrome. Amphotericin and oral azoles are the mainstays of antifungal 9) ___ for coccidioidomycosis. Duration of therapy for the infection is often prolonged and may last several months to years, with lifelong suppression needed in certain patients.

 

The vast majority of coccidioidal infections result from airborne transmission. Pulmonary infection can result from inhalation of a single spore in humans, but high inoculum exposures are more likely to result in symptomatic disease. Inhaled C immitis or C posadasii arthroconidia (ie, spores; see the image below) are deposited into the terminal bronchiole.

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Arthroconidia become airborne and infect the human host to begin the parasitic phase of its life cycle. The arthroconidia develop into spherules containing endospores, which propagate infection in human tissues.

 

In the bronchioles, the arthroconidia enlarge to form spherules, which are round double-walled structures measuring approximately 20-100 um in diameter. The spherules undergo internal division within 48-72 hours and become filled with hundreds to thousands of offspring (i.e., endospores). Rupture of the spherules leads to the release of endospores, which mature to form more spherules.As an arthroconidium transforms into a spherule, the resulting inflammation results in a local pulmonary lesion. Extracts of C immitis organisms react with complement, leading to the release of mediators of chemotaxis for neutrophils. Some of the endospores are engulfed by macrophages, initiating the acute inflammation phase. If the infection is not cleared during this process, a new set of lymphocytes and histiocytes descend on the infection site, leading to granuloma formation with the presence of giant cells. This is the chronic inflammation phase. People with severe disease may have both acute and chronic forms of inflammation.

 

Numerous studies have established that immunity mediated by T 10) ___ is critical to controlling the infection.The innate cellular response (neutrophils, macrophages mononuclear cells, NK cells) also contributes to host defense. T-cell activation and cytokine formation stimulate inflammatory cells and facilitate killing of the organism. T-helper type 1 (Th-1) cytokines, particularly interferon-gamma, promote macrophage killing of endospores. A failure of the host to respond appropriately indicates either a specific or a generalized deficiency in cell-mediated immunity. This is clinically overt in patients who have conditions that impair cell-mediated immunity and in those who are using agents that interfere with T-cell function. Other factors, such as immune-complex formation and antigen overload, can also cause failure of host response. Some of the phagocytized arthroconidia are theorized to be transported back to draining lymph nodes by macrophages and can cause lymphangitis. The inoculating dose responsible for infection is small and may be 10 or fewer arthroconidia. The presence of spherules triggers an acute inflammatory reaction. Spherules react with complement and promote chemotaxis of neutrophils and eosinophils. A mononuclear infiltrate may develop followed by subsequent conversion to polymorphonuclear predominance. Pathogenicity of the organism is largely related to the resistance of the spherule to eradication by host defenses. Spherules and endospores produce no known toxins, and as new spherules are propagated in infected tissue, progressive suppuration and tissue necrosis occur. Neutrophils and mononuclear cells attempt phagocytosis of the organism, and giant cells are formed to attack larger fungal structures. The body responds to the presence of the endospores with activation of complement and release of chemotactic factors. An intense, primarily neutrophilic, inflammatory reaction follows; however, the recruited neutrophils and macrophages are unable to kill the organisms because the spherules are resistant to phagocytosis. T-cell mediated immunity is important for killing and clearing of the organism; therefore, deficiencies in this arm of the immune system render the host of the fungus extremely vulnerable to disease and dissemination.

 

Case reports have documented rare instances of coccidioidomycosis transmitted through other modes. These include transplantation of organs from infected 11) ___ and sexually transmitted cases. Coccidioides infection can involve virtually any organ system. At autopsy, involvement of the liver, spleen, kidney, adrenal glands, psoas muscle, heart, thyroid, and prostate has been noted. These infected sites rarely are responsible for the presenting signs or symptoms.

 

Approximately 50% of patients with disseminated coccidioidomycosis acquire CNS disease. It can occur acutely with primary infection or later with dissemination. The meninges can be the only site of dissemination, in which case the patients is at increased risk of complications and death.

Coccidioidal meningitis can present as an acute process but it is usually chronic with insidious onset, in contrast to meningitis from bacterial causes. Of the clinical syndromes, mortality is highest in coccidioidal meningitis. If left untreated, meningitis is fatal in 90% of patients within 1 year and is universally fatal within 2 years. Mortality rates can be 20-40%, even with treatment. Symptoms related to increased intracranial pressure (e.g., nausea, vomiting, altered mental status) are relatively common. Less-common presentations include focal neurologic deficits, cranial nerve palsies, tremulousness, intention tremor, papilledema, gait abnormalities, seizure, and coma. Typically a granulomatous and suppurative basilar process, coccidioidal meningitis can also involve the brain parenchyma and spinal cord with granulomas and abscesses. Hydrocephalus is a common sequela and is often present at initial diagnosis in 12) ___. Septic shock generally develops in older individuals or immune-compromised patients. For example, patients with advanced HIV disease may present with a fulminant picture of respiratory failure, diffuse pneumonia, fungemia, and septic shock that resembles a gram-negative infection.

 

The ecologic niche of Coccidioides is in the lower Sonoran life zone. This zone is characterized by low elevations (below 3700 feet), scant rainfall (5-20 inches/year), mild winters (40-54°F) and hot summers, and sandy alkaline soil with increased salinity. Lower Sonoran life zones are found in areas of the Western Hemisphere from latitudes 40° north to 40° south.The endemic areas for Coccidioides in the United States include Arizona, south central California (San Joaquin Valley), Nevada, New Mexico, certain parts of Utah, and the western half of Texas. Other endemic areas are the regions of 13) ___ that border the western United States. The fungi also are endemic to some Central American countries, including Guatemala, Honduras, and Nicaragua. Certain desert regions of South America (Brazil, Argentina, Paraguay, Venezuela) also are endemic.

 

There is currently no practical preventative measures available for people who live or travel through Valley Fever endemic areas. It is recommended to avoid airborne dust or dirt, though this is not a guaranteed manner of prevention. People in certain occupations may be advised to wear face 14) ___.

 

ANSWERS: 1) humans; 2) fungus; 3) inhalation; 4) disease; 5) Valley; 6) lungs; 7) tissue; 8) respiratory; 9) therapy; 10) cells; 11) donors; 12) children; 13) Mexico; 14) masks

Hans E. Einstein MD (1923-2012), San Joaquin Valley Fever

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Hans Einstein MD, pioneered research on San Joaquin Valley Fever

 

Drs. Wernicke and Posadas first described a case of coccidioidomycosis in 1892 in South America, in an Argentinean soldier with predominantly cutaneous manifestations. Two years later in the United States, a patient with disseminated coccidioidomycosis was first reported in California in 1894. In 1896, Drs. Rixford and Gilchrist reported a few cases in which they identified the infecting agent as a protozoan-like organism and named it Coccidioides immitis. Ophuls further described the fungal life cycle and pathology of C immitis in 1905.

 

The disease was considered rare and uniformly fatal until 1929, when a Stanford University medical student, Harold Chope, accidentally inhaled a culture of Coccidioides and developed a nonfatal pulmonary illness accompanied by erythema nodosum. This case sparked interest that resulted in researchers uncovering the association between C immitis and the clinical condition known as San Joaquin Valley fever. Charles E. Smith and colleagues subsequently developed coccidioidin skin test and serologic testing for coccidioidomycosis.

 

The importance of the illness increased during the 1930s and 1940s, starting with the influx of immigrants from the Midwest who arrived in the San Joaquin Valley of California to escape drought and to seek agricultural employment. The thousands of military personnel building airstrips and participating in desert combat training during World War II led to many important studies on the pathogenic organisms and the epidemiology, clinical features, and diagnosis of coccidioidomycosis by the military health services. Interest in coccidioidomycosis has been renewed because of massive migration to the Sunbelt states. Areas that were once sparsely populated are now major cities, which increases the population at risk for the disease. Phoenix and Tucson, Arizona; Bakersfield and Fresno, California; and El Paso, Texas, are prime examples. These locales also have a growing population of individuals who are unusually susceptible to the most serious consequences of infection, due to advanced age or being immunocompromised. Interest also has increased because of an explosion in the number of cases that occurred during the great coccidioidomycosis outbreak in California in 1991-1994.

 

Hans E. Einstein (February 3, 1923 – August 11, 2012) was the foremost authority on the lung disease, Valley Fever. He lived in Bakersfield, California, USA. He was related to Albert Einstein: Hans’s grandfather and Albert were first cousins. Einstein was born in Berlin, the son of Josefa Spiero Einstein Warburg and Dr. Fritz Einstein. He spent his childhood in Hamburg, Germany as Nazism gradually took hold. His parents were Quakers, but of Jewish origin. A year after Hitler took power in 1934, his mother moved Einstein and his sister to the Netherlands, leaving his father behind. He finished high school at Eerde, a boarding school in the Netherlands at age 16 and moved to the United States as an exchange student. He attended Furman University in Greenville, South Carolina. One of the first things he did upon arriving was look up his last name in the phone book. The only Einstein he found was a relative: Albert Einstein’s son, Hans Albert Einstein. They became friends and he was often invited over whenever Albert visited. He earned his medical degree from New York Medical College in 1946 and did his internship at Paterson General Hospital in Paterson, New Jersey. Following that, he became a medical officer in the United States Army. He then completed residencies in Internal Medicine and Pulmonary Diseases at the New York Veterans Hospitals.

 

In 1951, he drove across the United States to Kern General Hospital (now Kern Medical Center) in Bakersfield, California. After completing his residency, Einstein became the assistant medical director of the Kern County tuberculosis sanitarium in Keene. While there, he realized that some patients had Valley Fever rather than Tuberculosis. This spurred his lifelong interest in the endemic disease Valley Fever. A Southern California resident since 1951, Dr. Einstein has devoted more than half a century to developments and improvements in diagnosing and treating many well-known and costly diseases, including tuberculosis, AIDS and Valley Fever. A local medical legend and international expert in Valley Fever, Dr. Einstein was instrumental in spreading knowledge of the disease to the Southern California community, as it is a disease endemic to the geographic area. He oversaw clinical trials that resulted in one of the disease’s most effective treatments to date, and he continues to devote his time to the development of a vaccine to help further control this serious disease.

 

Einstein subsequently opened a private practice in Bakersfield, specializing in Internal Medicine. While maintaining his private practice, he gave weekly lectures and led grand rounds at Los Angeles County+USC Medical Center starting in 1962. In 1978, Einstein was offered the Barlow Chair at USC, which he agreed to do for ten years. He closed his private practice and left Bakersfield to become Medical Director and CEO of Barlow Respiratory Hospital in Los Angeles, CA. He also was a physician and educator at the USC School of Medicine and even served on the Board of Directors for the hospital until 2012. While living in Los Angeles, he also spent time directing staff and education programs at Los Angeles Good Samaritan Hospital, served as President of the LA chapter of the American Lung Association for one year, opened an early AIDS treatment center at Barlow Respiratory Hospital. After In 1988, Einstein was offered the position of Medical Director at both Los Angeles Good Samaritan and Bakersfield Memorial Hospitals. He chose to move back to Bakersfield to be near his long-time friends, also promising them only ten years. He was Medical Director at Bakersfield Memorial Hospital until his retirement in 1999. After this, he continued treating patients at the Kern County Public Health Department’s Tuberculosis Clinic. He also treated patients at the Valley Fever Clinic by Kern Medical Center, started the Respiratory Technician program at San Joaquin Valley College, taught at California State University, Bakersfield, and established a need and academic based scholarship for pre-medical students at CSUB. An international consultant, Dr. Einstein also recently was invited by China to visit and serve as an advisor to recommend changes to the hospital and healthcare system in Macao.

 

The first effective therapy for coccidioidomycosis, intravenous amphotericin B, was first used in 1957. Since the 1980s, various oral antifungal agents, including ketoconazole, itraconazole, and fluconazole, have led to further advances in the treatment of coccidioidomycosis. The roles of newer agents (eg, voriconazole, posaconazole, caspofungin) are still being explored. The disease can strike anyone. On location in California, during the filming of two Hollywood films, “Exorcist II: The Heretic” and Indiana Jones, the director of one and the cinematographer of the other, came down with Valley Fever, long enough to delay the completion of both films.

ONCOLOGY

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Serum miR-21 as a Diagnostic and Prognostic Biomarker in Colorectal Cancer

 

The oncogenic microRNAs (miRNAs) miR-21 and miR-31 negatively regulate tumor-suppressor genes. However, their potential as serum biomarkers has not been determined in human colorectal cancer (CRC). As a result, a study published online in the Journal National Cancer Institute (23 May 2013) was performed to determine whether miR-21 and miR-31 are secretory miRNAs.

 

To accomplish this, first expression in medium from 2 CRC cell lines was screened followed by serum analysis from 12 CRC patients and 12 control subjects. Validated expression of candidate miRNAs in serum samples was obtained from an independent cohort of 186 CRC patients, 60 postoperative patients, 43 advanced adenoma patients, and 53 control subjects. The authors analyzed miR-21 expression in 166 matched primary CRC tissues to determine whether serum miRNAs reflect expression in CRC. Patient survival analyses were performed by Kaplan–Meier analyses and Cox regression models. All statistical tests were two-sided.

 

Results showed that although miR-21 was secreted from CRC cell lines and upregulated in serum of CRC patients, no statistically significant differences were observed in serum miR-31 expression between CRC patients and control subjects. In the validation cohort, miR-21 levels were statistically significantly elevated in preoperative serum from patients with adenomas (P<0.001) and CRCs (P<0.001). Importantly, miR-21 expression dropped in postoperative serum from patients who underwent curative surgery (P<0.001). Serum miR-21 levels robustly distinguished adenoma (area under the curve [AUC] = 0.813); and CRC (AUC = 0.919) patients from control subjects. High miR-21 expression in serum and tissue was statistically significantly associated with tumor size, distant metastasis, and poor survival. Moreover, serum miR-21 was an independent prognostic marker for CRC (hazard ratio = 4.12; P=0.03).

 

The authors concluded that serum miR-21 is a promising biomarker for the early detection and prognosis of CRC.

Estrogen Therapy Has No Long-Term Effect on Cognition in Younger Postmenopausal Women

 

An earlier Women’s Health Initiative Memory Study (WHIMS) linked estrogen therapy to cognitive decline and dementia in older postmenopausal women. Now, a randomized clinical trial of estrogen therapy in younger postmenopausal women, aged 50-55, has found no long-term risk or benefit to cognitive function. The National Institutes of Health-supported study, reported in JAMA Internal Medicine (24 June 2013, looked at women taking conjugated equine estrogens, the most common type of postmenopausal hormone therapy in the US.

 

The new findings come from the Women’s Health Initiative Memory Study of Younger Women (WHIMSY) trial and were reported by our colleague Mark A. Espeland, Ph.D., Wake Forest School of Medicine, Winston-Salem, N.C., on behalf of the academic research centers involved in the study.

 

“The [original] WHIMS study found that estrogen-based postmenopausal hormone therapy produced deficits in cognitive function and increased risk for dementia when prescribed to women 65 and older,” said NIA Director Richard J. Hodes, M.D. “Researchers leading the WHIMSY study wanted to expand on those results by exploring the possibility of a window of opportunity whereby hormone therapy might promote or preserve brain health when given to younger women.”

 

“In contrast to findings in older postmenopausal women, this study tells women that taking these types of estrogen-based hormone therapies for a relatively short period of time in their early postmenopausal years may not put them at increased risk for cognitive decline over the long term,” said Susan Resnick, Ph.D., chief of the Laboratory of Behavioral Neuroscience, in NIA’s Intramural Research Program and a co-author of the study. “Further, it is important to note that we did not find any cognitive benefit after long-term follow-up.”

 

WHIMSY is an extension of WHIMS, which was conducted as part of the Women’s Health Initiative (WHI). WHI enrollment took place from 1993-1998 at 40 academic research centers. Participants were randomized to one of two groups: women who had had a hysterectomy received conjugated equine estrogens alone; women with a uterus received estrogens plus a synthetic progestin (medroxyprogesterone acetate). There were companion control groups which received placebos. WHIMSY enrolled 1,326 women who started WHI treatment when they were between 50 and 55 and continued it for an average of seven years. The women were approached to participate in a telephone assessment of cognition an average of seven years after that.

 

Phone interviews on cognitive function were conducted with 1,168 women. The primary outcome was global cognitive function, which includes measures of memory, problem-solving skills and other cognitive abilities. The authors also measured specific cognitive functions — verbal memory, attention, executive function, verbal fluency and working memory. The first cognitive assessment was performed when participants’ average age was 67.2 years and the second at an average age of 68.1 years.

 

The authors found no meaningful difference in the average global cognitive function scores between women who had been assigned to hormone therapy vs. placebo. This finding applied to women regardless of whether their treatment included the synthetic progestin.

 

The WHIMSY research team will continue to follow the women in the study with annual telephone interviews to learn whether previous hormone therapy has longer term effects on how cognitive function changes over time. Women considering hormone therapy should consult their physician about how best to treat or prevent menopause symptoms or diseases for which they are at risk.

Only Half of U.S. Youth Meet Physical Activity Standards

 

According to an article published online in the Journal of Adolescent Health (1 May 2013), it was reported that only about half of U.S. adolescents are physically active five or more days of the week, and fewer than 1 in 3 eat fruits and vegetables daily. In a survey of youth in 39 states, the authors questioned nearly 10,000 students between 11 and 16 years old about their activity levels and eating habits. They also asked the students to describe their emotional health, body image, and general satisfaction with life.

 

The authors also found that the adolescents’ diet and activity habits could be classified into three general categories. They described the first group as unhealthful. This group accounted for 26% of participants. The second group, classified as healthful, accounted for 27%. Because it was the largest group — including 47% of participants — the authors classified the third group as typical.

 

The researchers surveyed participants about: their daily amount of physical activity, the amount of time they spent in front of a computer screen or other electronic screen, and the amount of healthy and unhealthy foods they consumed. Other questions sought information on symptoms of depression and self-satisfaction with their bodies. Results showed that the typical youth were least likely to exercise five or more days each week or to eat fruits and vegetables at least once a day. They were more likely to spend time watching television, playing video games or on a computer than the healthful group, and less likely to do so than the unhealthful group. They infrequently ate fruits and vegetables but also infrequently ate sweets, chips or fries, or had soft drinks. Youth in this group were more likely than youth in the other two groups to be overweight or obese and to be dissatisfied with the appearance of their bodies.

 

The unhealthful group consumed the most sweets, chips, French fries, and soft drinks. They also were more likely than the other groups to report watching TV, playing video games and using a computer more than two hours a day. Despite the caloric foods they consumed, youth in the unhealthful group were more likely to be underweight and to report needing to put on weight. Youth in this group also were more likely to report symptoms of depression and of poor physical health, such as backaches, stomachaches, headaches or feeling dizzy.

 

Nearly 65% of students in the group that the authors termed healthful reported exercising five or more days per week-the highest rate of the three groups. These students were least likely to spend time in front of a screen and were most likely to report eating fruits and vegetables at least once a day. Students in this group also were least likely to consume sweets, soft drinks, chips and French fries. They reported the lowest rates of depressive symptoms and the highest life satisfaction ratings.

 

According to the authors, all 3 groups could stand to improve their health habits, whether walking or biking between home and school or eating more fresh produce each day.

 

According to the U.S. Department of Health and Human Services’ Physical Activity Guidelines for Americans, children and adolescents should get one hour or more of moderate or vigorous aerobic physical activity a day, including vigorous intensity physical activity at least three days a week.

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

 

FDA Approves First Recombinant Coagulation Factor IX that is Specifically Indicated for Routine Use in Preventing Bleeding Episodes (Prophylaxis)

 

An inherited blood clotting disorder mainly affecting males, Hemophilia B is caused by mutations in the Factor IX gene and leads to deficiency of Factor IX. Hemophilia B affects about 3,300 people in the United States. Individuals with Hemophilia B can experience potentially serious bleeding, mainly into the joints, which can be destroyed by such bleeding.

 

The FDA has approved Rixubis [Coagulation Factor IX (Recombinant)] for use in people with hemophilia B who are 16 years of age and older. Rixubis is indicated for the control and prevention of bleeding episodes, perioperative (period extending from the time of hospitalization for surgery to the time of discharge) management, and routine use to prevent or reduce the frequency of bleeding episodes (prophylaxis).

 

Rixubis is a purified protein produced by recombinant DNA technology. It does not contain human or animal proteins. It is supplied in single-use vials of freeze-dried powder and is administered by intravenous injection after reconstitution with sterile water for injection. When used for the routine prevention of bleeding episodes, it is administered twice weekly.

 

The efficacy of Rixubis was evaluated in a multicenter study in which a total of 73 male patients between 12 and 65 years of age received Rixubis for routine prophylaxis or as needed in response to symptoms of bleeding (on-demand). Overall, patients in the prophylaxis study had a 75% lower annual bleeding rate when compared to patients who have historically received on-demand treatment. An additional study in a pediatric population is currently ongoing.

 

Although serious side effects including anaphylaxis (life-threatening allergic reactions) can occur, the most common side effects observed in patients in clinical studies were dysgeusia (distorted taste), pain in an extremity, and atypical blood test results.

 

Rixubis is manufactured by Baxter Healthcare Corporation, Westlake Village, California

Brazilian Mango Salad

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Photo:  courtesy of Jules Mitchel

 

The decision to adapt this Brazilian salad from a Grand Hyatt Hotel recipe, was made this week, when my husband at the Annual DIA Meeting in Boston ordered room service, one warm night and what you see, above, is what arrived and what he photographed. He liked it so much, that he sent me the photo, after I agreed to do my best to duplicate it when he returned home, in Manhattan.

 

Before, he returned, I made a first attempt which we had on Thursday night. We both agreed that it was too mushy. That’s because I pureed 2 mangos for the dressing and I used Bartlett pear instead of Asian pear, which is firmer.  Friday, on the second try, the Brazilian salad was pretty good, so the recipe, below, is exactly what I did. So-o, don’t puree the mango. The black sesame seeds were used, instead of the white, to give extra color to this dish. Doing this recipe was a lot of fun. Friday, was a hot day, so the Brazilian salad was served with simple barbecued chicken, and some delicious salmon patties. Dessert was plump, fresh sweet blueberries with a dollop of fat-free cool whip. With this summer meal serve icy beer or chilled white or rose wine.

 

Happiness is being married to your best friend!

Ingredients

 

2 ripe, but not mushy, Avocados sliced

1/2 can of Hearts of palm, drained. Dry on paper towel; cut into bite size pieces

1 fresh orange, separated into segments & cut in half, pits removed

3/4 cup chopped Brazil nuts

1 Asian pear, sliced

1 cup Arugula, wash well, drain on paper towel, tear into pieces

1 cup Frisee, wash, drain, tear into pieces

1 Endive, cut in half, then tear into pieces, but not too small

1/2 English cucumber, sliced thin

1/2 head Radicchio, wash, drain well, slice thinly

2 Mangos, sliced

1 cup green seedless grapes, cut in half

1/2 cup pumpkin seeds

 

DRESSING

 

2 garlic cloves, juiced

2 Tablespoons Olive oil

1/2 cup black sesame seeds

1 lemon, all the juice + more if you need it

Salt (optional)

Pinch of black pepper

1 teaspoon turmeric

1/3 cup fresh cilantro, chopped well

 

Directions

1. Chop the Brazil nuts so they are slightly larger than pine nuts

2. Make the dressing: In a small bowl, add all the dressing ingredients and whip by fork, or tiny wire whisk, until everything is well combined.

3. Put all other salad ingredients in a large bowl. Pour the dressing over the salad and toss so that all of the greens, fruit and nuts are covered with the dressing. Serve.

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Enjoy!