Happy New Year to All !


All of us at Target Health want to wish our over 4,600 readers a very Happy, Healthy and Successful New Year.


Our major accomplishments of 2012:


1.  Target e*CRF used in 3 regulatory approvals (2 in the US and 1 in Europe).


2.  FDA approval of ELELYSO™ (taliglucerase alfa; Protalix Biotherapeutics). Since 2004, Target Health was the lead CRO with responsibilities for strategic planning, regulatory affairs, clinical research, data management, biostatistics and medical writing.

Target e*CRF®


3.  FDA approval of Pertzye (pancrelipase delayed-release capsules; Digestive Care Inc.). Since 1998, Target Health has been working closely with our good friend and colleague Dr. Tibor Sipos, President of DCI on this and many other programs. We have assisted in the areas of strategic planning, regulatory affairs, clinical research, data management, biostatistics and medical writing and NDA Preparation.


Some of our plans for the New Year include:


1. Submission of the first NDA in the US and Canada that utilizes risk-based and centralized monitoring, together with Target e*CTR® (eClinical Trial Record), our eSource software solution, fully integrated with Target e*CRF® (EDC)


2. Release of Target e*Studio™ Version 2, our technology transfer cost-effective EDC solution


3. Initiation of multiple clinical trials using Target e*CTR


4. Initiation of a program to integrate the electronic health record (EHR) with EDC


5. And yes, have some fun


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


Study Suggests Lower Mortality Risk for People Deemed to Be Overweight


CJ is nearly “obese” or….not?


215 lbs.
BMI 29.2


A century ago, Elsie Scheel was the perfect woman. So said a 1912 article in The New York Times about how Miss Scheel, 24, was chosen by the “medical examiner of the 400 ‘co-eds’” at Cornell University as a woman “whose very presence bespeaks perfect 1) ___.” Miss Scheel, however, was hardly model-thin. At 5-foot-7 and 171 pounds, she would, by today’s medical standards, be clearly overweight. Her BMI (2) ___ ___ ___) was 27 and 25 to 29.9 is considered to be overweight.)


But a new report suggests that Miss Scheel may have been onto something. The report on nearly three million people found that those whose B.M.I. ranked them as 3) ___ had less risk of dying than people of normal weight. And while obese people had a greater mortality risk over all, those at the lowest obesity level (B.M.I. of 30 to 34.9) were not more likely to die than normal-weight people. The report, although not the first to suggest this relationship between B.M.I. and 4) ___, is by far the largest and most carefully done, analyzing nearly 100 studies.


But don’t scrap those New Year’s weight-loss resolutions and start gorging on fried Belgian waffles or triple cheeseburgers. Experts not involved in the research said it suggested that overweight people need not panic unless they have other indicators of poor health and that depending on where fat is in the 5) ___, it might be protective or even nutritional for older or sicker people. But overall, piling on pounds and becoming more than slightly obese remains dangerous.


“We wouldn’t want people to think, ‘Well, I can take a pass and gain more 6) ___,’” said Dr. George Blackburn, associate director of Harvard Medical School’s nutrition division. Rather, he and others said, the report, in The Journal of the American Medical Association, suggests that B.M.I., a ratio of 7) ___ to weight, should not be the only indicator of healthy weight. “Body mass index is an imperfect 8) ___ of the risk of mortality,” and factors like blood pressure, cholesterol and blood sugar must be considered, said Dr. Samuel Klein, director of the Center for Human Nutrition at Washington University School of Medicine in St. Louis. Dr. Steven Heymsfield, executive director of the Pennington Biomedical Research Center in Louisiana, who wrote an editorial accompanying the study, said that for overweight people, if indicators like cholesterol “are in the abnormal range, then that weight is affecting you,” but that if indicators are normal, there’s no reason to “go on a crash diet.”


Experts also said the data suggested that the definition of “normal” B.M.I., 18.5 to 24.9, should be revised, excluding its lowest weights, which might be too 9) ___. The study did show that the two highest obesity categories (B.M.I. of 35 and up) are at high risk. “Once you have higher obesity, the fat’s in the fire,” Dr. Blackburn said.


But experts also suggested that concepts of fat be refined. “Fat per se is not as bad as we thought,” said Dr. Kamyar Kalantar-Zadeh, professor of medicine and public health at the University of California, Irvine. “What is bad is a type of 10) ___ that is inside your belly,” he said. “Non-belly fat, underneath your skin in your thigh and your butt area — these are not necessarily bad.” He added that, to a point, extra fat is accompanied by extra muscle, which can be healthy. Still, it is possible that overweight or somewhat 11) ___ people are less likely to die because they, or their doctors, have identified other conditions associated with weight gain, like high cholesterol or diabetes. “You’re more likely to be in your doctor’s office and more likely to be treated,” said Dr. Robert Eckel, a past president of the American Heart Association and a professor at University of Colorado.


Some experts said fat could be protective in some cases, although that is unproven and debated. The study did find that people 65 and over had no greater mortality risk even at high obesity. “There’s something about extra body fat when you’re older that is providing some reserve,” Dr. Eckel said. And studies on specific illnesses, like heart and kidney disease, have found an “obesity paradox,” that heavier patients are less likely to 12) ___. Still, death is not everything. Even if “being overweight doesn’t increase your risk of dying,” Dr. Klein said, it “does increase your 13) ___ of having diabetes” or other conditions. Ultimately, said the study’s lead author, Katherine Flegal, a senior scientist at the Centers for Disease Control and Prevention, “the 14) ___ weight might depend on the situation you’re in.”


Take the perfect woman, Elsie Scheel, in whose “physical makeup there is not a single defect,” the Times article said. This woman who “has never been ill and doesn’t know what fear is” loved sports and didn’t consume candy, coffee or tea. But she also ate only three meals every two days, and loved beefsteak. Maybe such seeming contradictions made sense against the societal inconsistencies of that time. After all, her post-college plans involved tilling her father’s farm, but “if she were a man, she would study mechanical engineering.”


JS is 5 lbs. shy of “obese”…………………….or not?

170 lbs.
BMI 29.2


ANSWERS: 1) health; 2) body mass index; 3) overweight; 4) mortality; 5) body; 6) weight; 7) height; 8) measure; 9) thin; 10) fat; 11) obese; 12) die; 13) risk; 14) best

Adolphe Quetelet (1796-1874) Father of the BMI


Creator, 181 years ago, of the body mass index (BMI)



The quest for a practical index of relative body weight that began shortly after actuaries reported the increased mortality of their overweight policyholders culminated after World War II, when the relationship between weight and cardiovascular disease became the subject of epidemiological studies. It became evident then that the best index was the ratio of the weight in kilograms divided by the square of the height in meters, or the Quetelet Index described in 1832. Adolphe Quetelet (1796-1874) was a Belgian mathematician, astronomer and statistician, who developed a passionate interest in probability calculus that he applied to study human physical characteristics and social aptitudes. His pioneering cross-sectional studies of human growth led him to conclude that other than the spurts of growth after birth and during puberty, ‘the weight increases as the square of the height’, known as the Quetelet Index until it was termed the Body Mass Index in 1972 by Ancel Keys (1904-2004).


For his application of comparative statistics to social conditions and moral issues, Quetelet is considered a founder of the social sciences. His principal work, “A Treatise of Man and the Development of his Faculties” published in 1835 is considered one of the greatest books of the 19th century. A tireless promoter of statistical data collection based on standard methods and definitions, Quetelet organized in 1853 the first International Statistical Congress, which launched the development of a “uniform nomenclature of the causes of death applicable to all countries”, progenitor of the current International Classification of Diseases.


Obesity as a disease, with well-defined complications, is approximately one century old. For much of human history, corpulence was considered a sign of good health and fat an advantage. The impact of gross obesity on quality of life began to be appreciated late in the 18th century and on ill health in the middle of 19th century, but it was only in the first decades of the 20th century that the morbid complications and increased mortality of obesity began to be documented by the insurance industry. What has made the problem alarming is the exponential increase in the prevalence and incidence of obesity over the past few decades; this increase has led the World Health Organization (WHO) to declare it a global epidemic and worldwide public health crisis.


The need for an index of normal relative body weight was recognized soon after the actuaries noted the increased death claims of their obese policyholders. Louis I. Dublin (1882-1969), a statistician and vice president of the Metropolitan Life Insurance Company, was the first to lead the development of tables of normal weights, based on the average weights recorded for a given height. However, as data accrued, he noted a rather wide range of weights for persons of the same sex and height, which he attributed to differences in body ‘shape’ or ‘frame’. To resolve the problem, he divided the distribution of weight at a given height into thirds, and labeled them ‘small’, ‘medium’ and ‘large’ frames. The average weights of those thirds were then termed ‘ideal’ weights, later less presumptuously labeled ‘desirable’ weight, for each of the three frame types. For purposes of insurance, undesired weight was considered at 20-25%, and morbid obesity at 70-100% above the desirable weight for a given frame.


As the relation between body weight and mortality, particularly cardiac disease and diabetes, gradually became a medical concern following the Second World War, the quest for a reliable and practical index of relative weight began to assume increasing importance in the epidemiological and clinical studies that were being initiated. In exploring various indices combining weight and height, it became evident in the 1960s that, in adults, normal body weight in kilograms was proportional to the square of the height in meters.


Stamp issued by Belgium to commemorate the centenary of the death of Adolphe Quetelet



One of the first studies to confirm the validity of the Quetelet Index in epidemiological studies comprised data gathered during the fourth examination of the Framingham study. In a subsequent comparative study of available indices of relative weight and obesity published in 1972, Ancel Keys (1904-2004) confirmed the validity of the Quetelet Index and named it the Body Mass Index (BMI). Since then, as evidence of the association of obesity with various diseases continues to accrue, the BMI has been used as an expression to report the link of excess relative weight to morbidity and mortality. Primarily derived from data obtained on Anglo-Saxon populations, the generalizibility and applicability of the BMI and its cut-off points to other populations has been questioned and its sensitivity as a measure of excess fat queried. Nevertheless, it remains a dependable value and the basis of much of the associations reported heretofore with obesity, including its detrimental effect on normal kidney function and the course of chronic kidney disease.


Born in the historic Belgian town of Gent on 22 February 1796, the fifth child of a family of nine children, Quetelet grew in politically challenging and intellectually stimulating times. An exceptionally talented student, his mathematical abilities were evident early, when he received prizes in algebra, geometry, grammar and drawing in secondary school at the Lycée de Gent. But it was his love of the humanities that dominated his early years. He published poetry, exhibited his paintings, studied sculpture, co-authored the libretto of an opera and translated Byron and Schiller into French. Following graduation from the lycée in 1813, and after a year of teaching at a private college in Audernarde, he returned to teach in Gent until 1817, when he entered the new University of Gent founded by order of William I of Orange-Nassau, the then king of the Netherlands, to which the Belgian provinces had been granted by the Congress of Vienna in 1815. The university was inaugurated on 9 October 1817, with an entering class of 190 students and a professional staff of 16 members. Quetelet elected to pursue his university studies with one of the newly recruited ordinary professors, Jean Guillaume Garnier (1766-1840), a mathematician who had been a professor and examiner at the Ecole Polytechnique in Paris. Having served as one of Garnier’s teaching assistants, Quetelet successfully argued with the authorities that as a teacher, he should be exempt from regular examinations and proceed directly with defending his thesis, which he did on 24 July 1819, thereby becoming the first recipient of a doctorate in science from the University of Gent, when he was only 23 years old.


Recruited to teach mathematics at the Athenee in Brussels, he soon conceived the need for an observatory and convinced the government to fund his trip to Paris in 1823 to study astronomical activities. That was a defining moment in his life, for while in Paris he met Joseph Fourier (1768-1830), Simeon Poisson (1781-1840) and Pierre Laplace (1749-1827), became impassioned by the subject of probability, and went on to put it to practical use in the study of the human body, a subject in which he had developed an early interest as a painter and sculptor. In doing so, he became the first to develop height and weight tables to study their relationships, and a pioneer in the application of mathematical analysis to the study of man.


Quetelet’s interest in the subject was kindled when on his return from Paris, he got involved in a national population census of the Netherlands and argued that a random sample from a representative diversified group could be used to estimate the total population. His subsequent conceptual evolution in the study of man evolved from the study of averages (physical characteristics), to rates (birth, marriage, growth) and ultimately distributions (around an average, over time, between regions and countries). The latter was the basis of one of his contributions to statistics; the demonstration that the normal Gaussian distribution, typical throughout nature, applied equally to physical attributes of humans, including body parts, derived from large-scale population studies. After that, he saw bell-shaped curves everywhere he looked, including in social phenomena and the variables that determine character and aptitudes.


To his credit, he realized the limitation of deriving conclusions from cross-sectional homogeneous data and in his attempts to analyze causes, referred to variables that may affect them, by classifying them as due to systematic or constant (terrain), random or variable (weather), and occasional or accidental (war) causes. Importantly, he persistently emphasized the accuracy and reliability of the data used in his tables and figures.


Quetelet’s diagram showing the distribution of crime by age in Belgium.



The figure sums the principal contributions of Quetelet: the concept of an average, the fitting of the distribution around the average and the applicability of the calculus of probabilities to social data. In addition, as the data presented for both men (bold line) and women (dotted line) illustrates Quetelet analyzed data from both genders and highlighted differences where they existed; despite his exclusive use of the singular masculine in the title of his book and writings.


The construction of the observatory that launched his statistical career did not begin until 1826 and was completed in 1832, after Belgium had achieved its independence from the Netherlands in 1830, with Quetelet as its director. One year after obtaining his doctorate, Quetelet was elected to the Royal Academy of Sciences, served as its president from 1832-1834 and from 1834, as its permanent secretary for 40 years. It is from these two positions, director of the observatory and permanent secretary of the academy, that Quetelet conducted his subsequent groundbreaking studies. He died on 17 February 1874, 5 days before his 78th birthday.


In developing his index, Quetelet had no interest in obesity. His concern was defining the characteristics of ‘normal man’ and fitting the distribution around the norm. Much like Dublin a century later, he encountered difficulty in fitting the weight to height relationship into a Gaussian curve and began his quest for a solution. In 1831-1832, he conducted what has been considered the first cross-sectional study of newborns and children based on height and weight, and extended it to the study of adults. In 1832, he published his studies in the Proceedings of the Academy of Sciences as an article entitled ‘Recherches sur le poids de l’homme aux different ages’ (Research on the weight of man at different ages), and subsequently published it as a book.


In 1835, he collated all his studies in a book entitled A Treatise on Man and the development of his aptitudes. Divided into three books, Chapter 2 of the second book of the ‘Treatise on Man’ is entitled “Of the development of weight, and of its relation to the development of the height of the body.” The first half of the chapter is devoted to the changes of height and weight at different ages, wherein he discusses the variable rates of growth (height and weight) following birth, at puberty and the age when they stabilize in males and females. The second half of the chapter is on the relation between the weight and height, principally after growth is stabilized. The introductory paragraph to this section succinctly summarizes Quetelet’s observations in his own words, ‘If man increased equally in all dimensions, his weight at different ages would be as the cube of his height. Now, this is not what we really observe. The increase of weight is slower, except during the first year after birth; then the proportion we have just pointed out is pretty regularly observed. But after this period, and until near the age of puberty, weight increases nearly as the square of the height. The development of weight again becomes very rapid at puberty, and almost stops after the twenty-fifth year. In general, we do not err much when we assume that during development the squares of the weight at different ages are as the fifth powers of the height; which naturally leads to this conclusion, in supporting the specific gravity constant, that the transverse growth of man is less than the vertical’


The ‘Treatise on Man’ was translated into several languages. The English translation, from which the above quote is cited, was published in Edinburgh in 1842 under the direction of Dr Robert Knox, Fellow of the Royal Society of Edinburgh and Lecturer of Anatomy in Edinburgh. Knox is better known for his involvement in the case of Burke and Hare, the body snatchers who supplied him with cadavers and were apprehended when the body of a Mrs Docherty was discovered in Knox’s cellars. Knox served as the character of the doctor in the movie script of Dylan Thomas (1914-1953), ‘The doctor and the devils’ and in the play of Jamie Bridie (1888-1951), ‘The Anatomist’


Quetelet was invited to write a preface to the English edition of 1842, in which he states his goal as ‘the analysis of normal man through his actions and of intellectual man through his productions’ which explains the subtitle of the original French version of his book, Essai de Physique Sociale (Essays on Social Physics).


Essentially, in the course of time, Quetelet had extended his mathematical analysis of the demographic and anthropometric characteristics of man to that of the other aptitudes of man, such as behavior, mind and soul. In doing so, he demonstrated for the first time the value of comparative statistics in understanding social conditions and the application of the calculus of probability to moral and social issues. For this he is considered a founder of social sciences.


George Sarton (1884-1956), himself a 1911 graduate with a PhD in mathematics from the University of Gent, a founding father of the history of science, and biographer of Quetelet called the Treatise of Man one of the greatest books of the 19th century. An opinion shared by Florence Nightingale (1820-1910), who was greatly influenced by the work of Quetelet, read and annotated his book, maintained a correspondence with him, used his statistical methods to argue for the radical innovations she introduced in nursing care, and in her eulogy of him characterized him as ‘the founder of the most important science in the world.’


Pleased and encouraged by the reception of his book and strengthened by the evolution of his thinking, Quetelet, in 1869, published an expanded version of the book for which he reversed the title and subtitle of the 1835 version, now termed ‘Social Physics or an Assay on the Development of the Faculties of Man’


Prior to the appearance of the ‘Treatise on Man’, Quetelet had already attained a high reputation for his cautious, accurate, comprehensive and innovative studies. As a result, he was instrumental in founding the Statistical Section of the British Association for the Advancement of Science at Cambridge in 1833, and within a year, the Statistical Society of London, predecessor of the present Royal Statistical Society. With the increased fame achieved by his book and as a tireless promoter of accurate statistical data collection based on standard methods and definitions, Quetelet conceived, organized, hosted and presided over the First International Statistical Congress (ISC) in Brussels, in 1853. At this meeting, William Farr (1807-1883) of London and Marc D’Espine (1806-1860) of Geneva were appointed to prepare a ‘uniform nomenclature of the causes of death applicable to all countries.’ Their report at the second ISC in Paris, in 1855, is the progenitor of the current International Classification of Diseases (ICD), the name it assumed after the successor of the ISC in 1885, the International Statistical Institute, began to cooperate with the WHO in developing a uniform nomenclature of diseases.


Quetelet’s studies are said to have influenced the thinking of Charles Darwin, who was familiar with his works. But it is Darwin’s cousin, Francis Galton (1822-1911), who fully recognized and cited extensively the contributions of Quetelet and pursued the application of the bell-shaped curve with even greater enthusiasm. The difference between them being that where Quetelet saw homogeneity and applied it to define the norm, Galton saw heterogeneity and applied it to the study of the abnormal in his search for ‘nature’s preeminently nobles’, a field he termed eugenics. Interestingly, the person to question the validity of the bell-shaped curve, Karl Pearson (1857-1936), was in fact the Galton Professor of Eugenics at the University College of London.


The life and work of Quetelet are closely related to the events of society in the first half of the 19th century. The French Revolution and Napoleonic wars had shaken the roots of Europe, and after the Congress of Vienna in 1815, a new Europe began to take shape. The social and economic structure of Europe was undergoing dramatic changes due to industrialization, mechanization and urban migrations. It was a time of burgeoning research in several fields of knowledge, the establishment and growth of national academies, and the foundation of higher institutions of research. This was the fertile environment that nurtured the creative mind and scientific entrepreneurial spirit of Quetelet. From the perspective of nephrology, it was also the time that Richard Bright (1789-1858), a contemporary of Quetelet, began to publish his reports on proteinuria and kidney disease. Source: Garabed Eknoyan, MD, Department of Medicine (523-D), BaylorCollege of Medicine,



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Gene Variation May Shape Bladder Cancer Treatment


Every gene contains a very long string of DNA components termed nucleotides (referenced commonly as T, C, G or A). A single letter variation in the string of letters can lead to changes in cell development, resulting in cancer.


In 2012 in the United States alone, there were an estimated 73,510 new cases of bladder cancer and 14,880 deaths. The recurrence rate of bladder cancer is between 50 and 70%, and patients require life-long surveillance and treatment, making it an expensive cancer to live with and a major economic burden on the health care system and patients. Up to 75% of bladder cancer patients carry this genetic variant.


According to an article published in the Journal National Cancer Institute 3 January 2013), patients who have inherited a specific common genetic variant, develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA).  PSCA is also expressed in many pancreatic and prostate tumors, according to research at the National Institutes of Health.


A therapy targeting the PSCA protein on the tumor cell surface is under evaluation in clinical trials for prostate and pancreatic cancer. The authors hope that this therapy will be tested in bladder cancer patients with the genetic variant, which could help to reduce potentially harmful side-effects, lower costs, and improve treatment efficacy.


In a previous study, the authors identified a variant located in the PSCA gene on chromosome 8 as associated with bladder cancer susceptibility. The gene determines whether the corresponding protein is expressed in bladder tumor tissue. In the latest report, they found that the ‘T’ nucleotide that comprises a gene variant called rs2294008 is a strong predictor of PSCA protein expression. The variant results in increased delivery of the protein to the cell surface, where it is involved in signaling and promotes tumor growth.


The authors have been pursuing this mechanism for some time. It started with their early results from the initial genome-wide association study that revealed a marker in the PSCA gene related to bladder cancer risk. This latest work reveals how a specific letter change in DNA influences protein expression at the cell surface. The big payoff is that a simple genetic test can determine which patients could benefit from anti-PSCA therapy.


According to the authors, this is one of the first studies to show direct clinical implications of a genetic variant identified through genome-wide association studies for common cancers. The authors note that additional work is needed to develop alternative drugs targeting PSCA, and to evaluate drug delivery methods, such as systemic delivery for advanced muscle-invasive tumors and local, inter-bladder delivery in the case of non-muscle invasive tumors. Anti-PSCA therapy is likely to be effective only against tumors that express PSCA. A genetic test for the “T” nucleotide of this genetic variant can identify bladder cancer patients who could benefit from this treatment.

Benefits of Higher Oxygen Breathing Device Persist After Infancy


According to an article published in the New England Journal of Medicine (2012; 367:2495-2504), it was reported that by the time they reached toddlerhood, very preterm infants originally treated with higher oxygen levels continued to show benefits when compared to a group treated with lower oxygen levels. Moreover, infants treated with a respiratory therapy commonly prescribed for adults with obstructive sleep apnea fared as well as those who received the traditional therapy for infant respiratory difficulties,.


In the original study of infants born between 24 to 27 weeks of gestation, investigators in the Neonatal Research Network found:


1.  Infants were more likely to survive if they had received higher oxygen levels, although they were at higher risk of an eye condition that can impair vision or lead to blindness.


2.  Continuous positive airway pressure (CPAP), a treatment typically reserved for adults with obstructive sleep apnea, was as effective as standard therapy with a ventilator and surfactant (a sticky substance that coats the inside of the lungs).


More than 1,300 preterm infants born between 2005 and 2009 were included in the current study. Between 18 and 22 months after the infants’ original due date, authors assessed whether the children had cerebral palsy as well as any impairment of vision, hearing, physical mobility and cognitive development. The re-evaluation of the original study treatment groups examined children treated with: 1) oxygen saturation levels that were either low (85% to 89%) or high (91% to 95%) and 2). CPAP therapy and 3) a ventilator and surfactant.


The study evaluated the results in terms of a combined primary outcome. This primary outcome took into account two possibilities: whether an infant either died in the first or second year of life or had a neurodevelopmental impairment – any of a number of conditions affecting the nervous system. These included cerebral palsy, blindness, hearing loss or low scores on tests of infant mental and motor development. This outcome was selected because infants who died before 18 months of age could not be classified as having a neurodevelopmental impairment. Results showed that there were no differences between the groups in terms of the primary outcome.


However, when outcome measures were evaluated separately, higher survival rates were observed among children who received oxygen with higher saturation rates. The study’s original findings showed that survivors in this group also had a greater risk of developing retinopathy of prematurity, an eye condition that can impair vision or cause blindness. Although those receiving higher oxygen levels were more likely to have had corrective eye surgery, by the time the children reached 18 to 22 months corrected age — their age had they been born at the approximate time they were due. However, no differences were observed in the rate of vision problems between the two groups.


According to the authors, while CPAP for infants has been available since the 1970s, this is the first study to compare surfactant treatment to CPAP in a large group of infants. The authors added that the current results reassure us that CPAP is as good a choice in the first hour of life as traditional methods for very preterm babies who need help breathing and that higher oxygen targets improve survival and don’t appear to threaten survivors’ vision in the longer term.”

Prevalence of Vitamin D Deficiency Among Overweight and Obese US Children


Adequate vitamin D is essential for skeletal health in developing children. Although excess body weight is associated with risk of vitamin D deficiency, the national prevalence of and risk factors associated with vitamin D deficiency in overweight and obese children are unknown. As a result, a study published in Pediatrics (2013;1:152-161) evaluated the prevalence of vitamin D deficiency (defined as 25-hydroxyvitamin-D <20 ng/mL) in a sample of 6- to 18-year-old children who were enrolled in a cross-sectional study (the 2003–2006 National Health and Nutrition Examination Survey). For the study, based on their actual height and weight, children were classified as healthy-weight, overweight, obese, or severely obese by using recommended age- and gender-specific BMI-percentile cut points. Associations between BMI-percentile classification and vitamin D deficiency were examined after adjustment for relevant confounders. Sample weights were used to generate nationally representative estimates.


Results showed that the prevalence of vitamin D deficiency in healthy-weight, overweight, obese, and severely obese children was 21%, 29%, 34%, and 49%, respectively. The prevalence of vitamin D deficiency in severely obese white, Latino, and African-American children was 27%, 52%, and 87%, respectively. Compared with healthy-weight children, overweight, obese, and severely obese children had significantly greater adjusted odds of vitamin D deficiency. Modifiable factors associated with vitamin D deficiency in overweight/obese children were identified.


According to the authors, vitamin D deficiency is highly prevalent in overweight and obese children and that the particularly high prevalence in severely obese and minority children suggests that targeted screening and treatment guidance is needed.

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


FDA Approves Treatment for Multi-Drug Resistant TB


Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis and is one of the world’s deadliest diseases. It is spread from person to person through the air and usually affects the lungs, but it can also affect other parts of the body such as the brain and kidneys. According to the Centers for Disease Control and Prevention, nearly 9 million people around the world and 10,528 people in the United States became sick with TB in 2011.


FDA has approved Sirturo (bedaquiline) as part of combination therapy to treat adults with multi-drug resistant pulmonary tuberculosis (TB) when other alternatives are not available. Multi-drug resistant TB occurs when M. tuberculosis becomes resistant to isonazid and rifampin, two powerful drugs most commonly used to treat TB.


Sirturo is the first drug approved to treat multi-drug resistant TB and should be used in combination with other drugs used to treat TB. Sirturo works by inhibiting an enzyme needed by M. tuberculosis to replicate and spread throughout the body.


Sirturo was approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides patients earlier access to promising new drugs while the company conducts additional studies to confirm the drug’s clinical benefit and safe use.


The FDA also granted Sirturo fast track designation, priority review and orphan-product designation. The drug demonstrated the potential to fill an unmet medical need, has the potential to provide safe and effective treatment where no satisfactory alternative therapy exists, and is intended to treat a rare disease, respectively.


Sirturo carries a Boxed Warning alerting patients and health care professionals that the drug can affect the heart’s electrical activity (QT prolongation), which could lead to an abnormal and potentially fatal heart rhythm. The Boxed Warning also notes deaths in patients treated with Sirturo. Nine patients who received Sirturo died compared with two patients who received placebo. Five of the deaths in the Sirturo group and all of the deaths in the placebo arm seemed to be related to tuberculosis, but no consistent reason for the deaths in the remaining Sirturo-treated patients could be identified.


Sirturo’s manufacturer, Janssen Therapeutics, will distribute the drug from a single source and will provide educational materials to help ensure the drug is used appropriately.


Sirturo’s safety and effectiveness were established in 440 patients in two Phase 2 clinical trials. Patients in the first trial were randomly assigned to be treated with Sirturo plus other drugs used to treat TB, or a placebo plus other drugs used to treat TB. All patients in the second trial, which is ongoing, received Sirturo plus other TB drugs. Both studies were designed to measure the length of time it took for a patient’s sputum to be free of M. tuberculosis (sputum culture conversion, or SCC). Results from the first trial showed patients treated with Sirturo combination therapy achieved SCC in a median time of 83 days, compared with 125 days in patients treated with placebo combination therapy. Results from the second trial showed the median time to SCC was 57 days, supporting the efficacy findings of the first trial.


Common side effects identified in the clinical trials include nausea, joint pain, and headache.


Janssen Therapeutics, a division of Janssen Products LP, is based in Titusville, N.J.

Stay-Fit Cauliflower Mac and Cheese


Before you make this dish, be sure you can get hold of the three colors of cauliflower.  It adds to the flavor and the presentation, when you use the three cauliflower varieties.  Wait to make it, until you get all of the right ingredients.





4 packages wide noodle Shirataki soy pasta
1 head white cauliflower, cut onto florets (cut stems into pieces)
2 cups steamed, but keep crunchy, green (1 cup) and purple cauliflower florets (1 cup)
8 ounces sharp Soy Cheddar cheese, grated
1 ounce Parmesan cheese, grated
1 garlic clove, juiced (throw pulp away)
1/2 cup almond milk
Pinch of salt and pinch of black pepper (to your taste)
1 1/2 teaspoon chopped fresh flat-leaf parsley
1 cup Panko bread crumbs




1.  Make the Shirataki Soy pasta according to the package directions until al dente. Drain and set aside.
2.  Steam the white cauliflower, for 5 to 7 minutes, or until soft. Drain. Place all the white cauliflower, including pieces of stem, in a blender and puree. Steam the green & purple cauliflower separately and set aside.  Keep the green and purple, crunchy and not mushy.
3.  In a medium pan over medium heat, place the cooked Shirataki soy pasta, the white cauliflower puree, squeeze the garlic juice directly into this pan, the soy and parmesan cheeses, and the almond milk. Stir gently to combine and continue stirring until the cheese is melted.
4.  Season with salt and pepper. Mix in the green and purple cauliflower florets.
5.  Transfer to casserole dish. Sprinkle Panko bread crumbs on top, and place under broiler until browned, about 5-7 minutes.
6.  Sprinkle the chopped parsley over the Mac and Cheese and serve immediately.


Joyce Hays adapted this recipe from Michelle Obama’s White House holiday menu of 2012.  The photo (above) was in an email from the White House


This particular dish is very versatile and would be great for brunch, lunch or dinner.


If you want to keep your meal vegetarian, then serve the Cauliflower Mac & Cheese with warm whole wheat or 7-grain rolls, a tossed salad and a chilled Pinot Gris or Pinot Grigio. We love Santa Margherita Pinot Grigio. Here is another good one:


2005 Domaine Stirn Cuvee Prestige Sigolsheim – This family-owned Alsace producer has been fashioning wines in the tiny town of Sigolsheim since 1450, among them this honeysuckle-scented cuvee.


Wine snobs scorn Pinot Grigio, but there are plenty of people with very positive feelings about this wine. After all, it’s one of the most popular imported wine in this country. Sales of Pinot Grigio rose almost 40% and have likely grown larger yet, as a boom in domestic Pinot Grigio gets under way (more than 7,000 acres of Pinot Grigio have been planted in California).Pinot Grigio may soon be more fashionable than Chardonnay or Sauvignon Blanc, a grape that’s been planted in just about every viable piece of vineyard land in the world (Uruguayan Sauvignon, anyone?).