New Publication – How Electronic Data Capture (EDC) Can Be Integrated Into The Data Monitoring Plan (DMP)

Target Health is pleased to announce that an article entitled “How Electronic Data Capture (EDC) Can Be Integrated Into The Data Monitoring Plan (DMP)“ has been accepted for publication by the Society for Clinical Data Management. If you would like a copy, please contact  Dr. Jules T. Mitchel. For other publications by Target Health, please visit our website.

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. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website. 

Salmonella Outbreaks Spur Nationwide Egg Recall

Salmonella

 

1) ___ are behind a nationwide salmonella outbreak that caused hundreds of illnesses each week in June and July, with more outbreaks in August. The nationwide egg recall involves more than a dozen major brands that got eggs from Wright County Egg in Galt, Iowa. CDC and state investigators in California, Colorado, and Minnesota found clusters of 2) ___ food poisoning among people who ate eggs at the same restaurants. Those restaurants got eggs that came from Wright County Egg.

Investigations continue in Arizona, Connecticut, Massachusetts, Maryland, North Carolina, Nevada, Oregon, Pennsylvania, Tennessee, and Texas. Meanwhile, the FDA is conducting a thorough investigation of the Iowa firm to which the contaminated eggs were traced. The company says it already has sent all its remaining eggs to a breaker, where they will be 3) ___ to kill any salmonella.

Shell eggs included in the recall were shipped since May to food wholesalers, distribution centers, and food service companies in eight states, from which they were distributed nationwide. The brand names included in the recall are Lucerne, Albertson, Mountain Dairy, Ralph’s, Boomsma’s, Sunshine, Hillandale, Trafficanda, Farm Fresh, Shoreland, Lund, Dutch Farms, and Kemps. Recalled eggs are in six, dozen, and 18-egg cartons.

Stamped on the end of the recalled egg cartons are Julian dates ranging from 136 to 225 and plant numbers 1026, 1413, and 1946. The plant number begins with the letter P and then the number. The Julian date follows the plant number, for example: P-1946 223. Recalled eggs may be returned to the store for a full 4) ___.

The salmonella strain causing the outbreak is Salmonella Enteritidis, the most common salmonella strain. Usually the 5) ___ gets about 50 reports a week of Salmonella Enteritidis food poisoning; beginning in May there was a fourfold increase in salmonella reports. Each week in late June and early July the CDC received some 200 salmonella samples isolated from patients, all with the same DNA fingerprint.

Symptoms of infection begin 12 to 72 hours after consuming contaminated foods or beverages and include fever, abdominal cramps, and diarrhea. Symptoms usually last four to seven days. Most people recover without 6) ___ treatment, but severe cases can be fatal. People prone to severe illness — particularly severe diarrhea – include the elderly, infants, and those with impaired immune systems, including people on immune suppressive therapy such as cancer chemotherapy.

 

ANSWERS: 1) eggs; 2) salmonella; 3) pasteurized; 4) refund; 5) CDC; 6) antibiotic

Avoid Salmonella: Protect Yourself With Knowledge

 

How to Avoid Food Poisoning From Eggs

If you like your eggs prepared over easy, you may want to change your egg-eating habits. Here’s the CDC’s advice on how to avoid food poisoning from eggs:

  • Don’t eat recalled eggs or products containing recalled eggs. Recalled eggs might still be in grocery stores, restaurants, and homes. Consumers who have recalled eggs should discard them or return them to their retailer for a refund.
  • People who think they might have become ill from eating recalled eggs should consult their health care providers.
  • Keep eggs refrigerated at least to 45 degrees F at all times.
  • Discard cracked or dirty eggs.
  • Wash hands, cooking utensils, and food preparation surfaces with soap and water after contact with raw eggs.
  • Eggs should be cooked until both the white and the yolk are firm and eaten promptly after cooking.
  • Do not keep eggs warm or at room temperature for more than two hours.
  • Refrigerate unused or leftover egg-containing foods promptly.
  • Avoid eating raw eggs.
  • Avoid restaurant dishes made with raw or undercooked, unpasteurized eggs. Restaurants should use pasteurized eggs in any recipe (such as Hollandaise sauce or Caesar salad dressing) that calls for raw eggs.
  • Consumption of raw or undercooked eggs should be avoided, especially by young children, elderly people, and people with weakened immune systems or debilitating illness.

Daniel Elmer Salmon (1850-1914) – Discover of Salmonella

Daniel Elmer Salmon, D.V.M.

 

Daniel Elmer Salmon was the son of Daniel Landon and Eleanor (Flock) Salmon. His early education was at the Mount Olive District School, Chester Institute, and Eastman Business College. In 1868 Salmon was enrolled in the first class at Cornell University, which had been established three years earlier in New York. He graduated from Cornell as bachelor of veterinary science in 1872.

After graduation, Salmon married Mary Thompson Corning from Ithaca, New York, and settled as a veterinary in Newark, New Jersey. For reasons of health he moved to Asheville, North Carolina, situated in the Blue Ridge Mountains at an altitude of 600 meters and known for its mild climate. Two years later he gave a series of lectures on veterinary medicine at the University of Georgia, and the same time commenced a special study of diseases of hogs. Daniel Salmon was granted a doctoral degree in veterinary medicine from Cornell University in 1876. This was the first DVM degree to be awarded in the United States of America.

In 1879 Salmon distinguished himself as a key participant in the New York State campaign to wipe out pleuro-pneumonia in cattle. After this effort he was selected by the Department of Agriculture to study the widespread problem of livestock disease in the south, particularly Texas fever. In 1883 Salmon was asked to organize a veterinary department, thus becoming founding director of the Bureau of Agriculture under the Department of Agriculture. Already the next year this institution was made into the Bureau of Animal Industry, headed by Salmon. He held this position until 1905, when a dispute with the head of the Department of Agriculture in Washington forced him to resign. During his tenure as bureau chief Salmon made epoch-making contributions to veterinary medicine, also becoming a leader in the field of public health administration.

Early in his career Salmon had been a skilled laboratory technician, but administrative duties gradually removed him from the daily details of research work. As head of the bureau he governed its policy, planned the assistants’ work and found time to write close to one hundred articles, alone or in collaboration with others. Together they cover almost the entire field of research in veterinary medicine in this period. One reason for the successful research being done despite Salmon’s administrative duties was the fact that he was probably quite a genius when it came to choosing assistants. Among them was Theobald Smith (1859-1934), one of the greatest names in American medical science who is today best remembered for his research on anaphylaxis (acquired hypersensitivity against proteins that are normally tolerated without problems). Anaphylaxis was long referred to as Theobald Smith’s phenomenon.

The relationship between Salmon and Smith, however, was less than heartily, because Salmon insisted on standing as the sole senior author of several research reports, including the one on the hog cholera bacillus – Salmonella cholerae-suis, which was first discovered by Theobald Smith. Nevertheless, together Salmon and Smith made a major discovery which, today, is still saving children from death or crippling disease. During the study of hog cholera they demonstrated that dead (heat killed) organisms could immunize animals against living organisms. This was the foundation for the development of a vaccine against typhus and Jonas Salk’s (1914-1995) production of polio vaccine.

Kabuki Syndrome Disease Gene Identified

Kabuki syndrome, which has an estimated incidence of 1 in 32,000 births, was originally described by Japanese scientists in 1981. Patients with the disorder often have distinct facial features that resemble the make-up worn by actors of Kabuki, a Japanese theatrical form.

According to an article published in the advanced online edition of Nature Genetics (15 August 2010), using a new, rapid and less expensive DNA sequencing strategy, the genetic alterations that account for most cases of Kabuki syndrome, a rare disorder that causes multiple birth defects and mental retardation, have been discovered. Instead of sequencing the entire human genome, the new approach sequences just the exome, the 1-2 percent of the human genome that contains protein-coding genes.

The study sequenced the exomes of 10 unrelated individuals with Kabuki syndrome. Beginning with the premise that Kabuki syndrome is caused by alterations in just a single gene, the study compared the exomes of the 10 patients to the human genome sequence to look for differences shared by the affected individuals. Initially, none were identified. The study then tested the hypothesis that Kabuki syndrome is more genetically heterogeneous than originally assumed, and that multiple genes could potentially cause the disorder. Looking for novel variants in genes that were shared among subsets of the 10 patients’ exomes, novel, matching variants were found that were shared in three genes in nine of the patient’s exomes, shared in six genes in at least eight exomes, and shared in 16 genes among seven exomes.

With no obvious way to rank these gene candidates, the authors categorized each Kabuki case based on a subjective assessment of how well the patient matched the characteristics of Kabuki syndrome. The authors also looked in particular for variants in genes that led to a loss of function. The combined analysis pointed to gene called MLL2.

It was found novel variants which lead to a loss of function in the MLL2 gene in the four highest ranked cases, and in three of the remaining six cases. The variants were nonsense and frameshift mutations. The nonsense mutation substituted a single nucleotide (a molecule that links to form DNA) in the gene code, while the frameshift mutation resulted in a four nucleotide deletion in the gene. In these cases, each nonsense and frameshift mutation resulted in the production of a shortened, nonfunctional protein. The MLL2 gene normally encodes a protein important in the regulation of chromatin, a protein that helps package the DNA in a compact form and allows the chromosome to fit in the cell nucleus. Changes in chromatin structure are associated with DNA replication and turning genes on or off.

The findings were then validated using Sanger sequencing in 43 additional Kabuki syndrome cases. Novel MLL2 variants were found in 26 of the 43 cases. In the end, a total of 33 distinct MLL2 mutations were found in 35 of 53, or 66%, of patients with Kabuki syndrome. The authors also discovered that in each of the 12 cases for which DNA from both parents was available, the MLL2 variants reflected new mutations within the affected individual’s genome and were not present in either parent’s genomes.

Discovery Opens Door To Therapeutic Development For FSH Muscular Dystrophy

Facioscapulohumeral Muscular Dystrophy (FSHD) affects about 1 in 20,000 people, and is named for progressive weakness and wasting of muscles in the face, shoulders and upper arms. Although not life-threatening, the disease is disabling. The facial weakness in FSHD, for example, often leads to problems with chewing and speaking.

According to an article published in Science (19 August 2010) we are closer to understanding what triggers muscle damage in in FSHD. The new research was funded in part by the National Institutes of Health. Until now, there were few clues to the mechanism of FSHD and essentially no leads for potential therapies, beyond symptomatic treatments and this study presents a model of the disease that ties together many complex findings, and should allow researchers to test new theories and potential new treatments.

In the early 1990s, researchers found that FSHD is associated with a shortened DNA sequence located on chromosome 4. Experts predicted that discovery of one or more FSHD genes was imminent, but while a handful of candidate genes gradually emerged, none of them were found to have a key role in the disease. The mysteries surrounding FSHD deepened in 2002 when researchers, led by Silvere van der Maarel, Ph.D., at Leiden University in the Netherlands, found that the shortened DNA sequence on chromosome 4 is not enough to cause FSHD. They discovered that the disease occurs only among people who have the shortened DNA sequence plus other sequence variations on chromosome 4. That work was funded in part by NIH, the FSH Society and the Muscular Dystrophy Association.

The new study proposes a model that explains how the previous findings fit together. At one end of chromosome 4 is a chunk of repetitive DNA, called a tandem repeat array. Normally this region contains 10-100 repeating units of DNA, but in most people with FSHD, the array is smaller, with fewer than 10 repeats. Within each repeating unit is a gene called DUX4. The authors found that in people with FSHD, the DUX4 gene generates a piece of RNA that is toxic to muscle cells. RNA is a sister molecule to DNA with many critical functions. The authors also discovered that variations on chromosome 4 are important because they affect the durability of DUX4 RNA. People with FSHD have chromosome variations that add a trailing segment to the RNA called a poly(A) tail. With the poly(A) tail attached, the RNA is more stable and more likely to cause damage.

The authors came to these conclusions by creating artificial DNA constructs containing the short repeat array, in combination with different variations on chromosome 4. They inserted these constructs into muscle cells, and analyzed how the chromosome 4 variations affected the level of DUX4 RNA. They also studied FSHD families with unique chromosome rearrangements and showed that all families with FSHD shared chromosome 4 sequences encoding the poly(A) tail. In another set of experiments, they found they could detect DUX4 RNA in muscle cells from individuals with FSHD but not in cells from unaffected individuals. Meanwhile, previous studies have shown that DUX4 can trigger muscle cell death.

According to the authors, the study provides evidence that DUX4 RNA is likely a key part of the disease process in FSH muscular dystrophy, and justifies further investigation of its role and how to silence its effects.

Change in Prevalence of Hearing Loss in US Adolescents

Hearing loss is common and, in young persons, can compromise social development, communication skills, and educational achievement. As a result, a study published in the Journal of the American Medical Association (2010;304:772-778) was performed to examine the current prevalence of hearing loss in US adolescents and determine whether it has changed over time.

The study involved a cross-sectional analyses of US representative demographic and audiometric data derived from The Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994, and NHANES 2005-2006 Survey. The  NHANES III trial examined 2,928 participants and NHANES 2005-2006 examined 1,771 participants, all aged 12 to 19 years.

For the study, the prevalence of hearing loss was determined in study participants after accounting for the complex survey design. Audiometrically determined hearing loss was categorized as either unilateral or bilateral for low frequency (0.5, 1, and 2 kHz) or high frequency (3, 4, 6, and 8 kHz), and as slight loss (>15 to <25 dB) or mild or greater loss (25 dB) according to hearing sensitivity in the worse ear. The prevalence of hearing loss from NHANES 2005-2006 was compared with the prevalence from NHANES III (1988-1994). The study also examined the cross-sectional relations between several potential risk factors and hearing loss.

Results showed that the prevalence of any hearing loss increased significantly from 14.9% in 1988-1994 to 19.5% in 2005-2006 (P = .02). In 2005-2006, hearing loss was more commonly unilateral (prevalence, 14.0% vs. 11.1%; P = .005). Individuals from families below the federal poverty threshold had significantly higher odds of hearing loss than those above the threshold.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.

Developing Products for Rare Diseases and Conditions

The FDA has charged the Office of Orphan Products Development (OOPD) to dedicate its mission to promoting the development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. In fulfilling that task, OOPD interacts with the medical and research communities, professional organizations, academia, governmental agencies, and the pharmaceutical industry, as well as rare disease groups.

The OOPD administers the major provisions of the Orphan Drug Act (ODA) which provide incentives for sponsors to develop products for rare diseases. The ODA has been very successful – more than 200 drugs and biological products for rare diseases have been brought to market since 1983. In contrast, the decade prior to 1983 saw fewer than ten such products come to market. 

In addition, the OOPD administers the Orphan Products Grants Program which provides funding for clinical research in rare diseases. The Office Of Orphan Products Development will also administer a new grant program, the Pediatric Device Consortia (PDC) Grant Program. The PDC Grant Program solicits grant applications from institutions/organizations that propose to develop nonprofit consortia to facilitate pediatric medical device development. FDA will provide grants to consortia whose business model and approach to device development will either result in, or substantially contribute to, market approval of medical devices designed specifically for use in children. Although administered by the OOPD, this grant program is intended to encompass devices used in all pediatric diseases, not just rare diseases.

For more information about our expertise in Medical Affairs, contact Dr. Mark Horn. For Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

Target Health (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND (eCTD), IDE, NDA (eCTD), BLA (eCTD), PMA (eCopy) and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, EDC utilizing Target e*CRF®, and Medical Writing.

Target Health has developed a full suite of eClinical Trial software including:

1) Target e*CRF® (EDC plus randomization and batch edit checks)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target Newsletter®

6) Target e*CTR™ (electronic medical record for clinical trials).

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Science Weekly: Questioning gravity

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The big questions about our universe; a sex scientist; zombie ants; plus, is the moon really getting smaller?