Science Weekly: Smellycast

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The complex world of odours; what the outcome of Britain’s general election could mean for science; and an unknown human ancestor

Coming in May, Publication on Electronic Medical Records and EDC

Applied Clinical Trials Publication on Medical Records and EDC

Target Health is pleased to announce our new publication, entitled : “The New eFrontier,” will be published in the May edition of Applied Clinical Trials. The article, co-authored by Dr. Jules Mitchel and our EDC/EMR team at Target Health, addresses the challenges and opportunities of integrating electronic data capture with electronic health records. The article presents the history of paper CRFs, Remote Data Entry, EDC and now the fully paperless clinical trial. The article also addresses regulatory issues and electronic source documents.

Please contact Dr. Mitchel if you would like a copy, or a link to the article once it “hits the press.” This will be a must read

For more information about Target Health and our software tools for paperless clinical trials, please contact Warren Pearlson (212-681-2100 ext 104) or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com

 

Freezing Gas Kills Breast Cancer Cells

A new technique of freezing away breast 1) ___ offers hope of a safe non-surgical cure for the disease. The technique involves inserting several needle-like “cryoprobes” into the 2) ___ and passing super-cold gas through them. An “ice ball“ is rapidly created around each site which kills off the cancerous 3) ___. Unlike earlier versions of freezing therapy for breast cancer, the procedure is minimally invasive and requires no 4) ___. Results from the first long term study of “image-guided multi-probe cryotherapy“ for breast cancer highlighted its potential as a curative treatment. Thirteen women with breast cancer who received the therapy remained cancer-free up to five years later. There was no sign of the disease returning and noted no significant complications. Lead researcher Dr Peter Littrup, from the Barbara Ann Karmanos Cancer Institute in Detroit, US, said: “Minimally-invasive cryotherapy opens the door for a potential new 5) ___ for breast cancer and needs to be further tested.“ “When used for local control and/or potential cure of breast cancer, it provided safe and effective breast conservation with minimal discomfort for a group of women who refused invasive surgery or had a local recurrence and needed additional management.“ “This is the first reported study of successfully 6) ___ breast cancer without having to undergo surgery afterward to prove that it was completely treated.“ Each year more than 45,000 women in the UK, alone, are diagnosed with breast cancer and around 12,000 die from the disease. The “gold standard“ treatment for breast cancer is surgery, which offers the best chance of a cure. But removal of one of more 7) ___, and even surgery to cut out malignant tissue, can have a profound psychological impact on patients. 8) ___ and radiotherapy also have serious drawbacks in the form of complications and side effects. Some women with breast cancer refuse to have surgery or harsh therapies, despite the consequent risks. Freezing therapy for breast cancer is not new, but has been slow to develop. Generally the technique has involved an operation and been applied by surgeons. Only in the last few years have the cryoprobes become small enough to be inserted through a small nick in the skin without the need for surgery. During the procedure the physician is guided by ultrasound or CT (computerized tomography) X-ray scans. Previous cryotherapy studies had all used a single 9) ___ and suggested that tumors larger than 1.5 cms could not be adequately treated. This was surprising bearing in mind the way men with 10) ___ cancer are treated with cryotherapy. Prostate treatment used more than six probes to freeze the entire gland, which measures around five centimeters across. “We simply translated this concept to breast cancer in order to assure deadly temperatures well beyond all apparent tumor margins in order to generate successful use of 11) ___ in women,“ said Dr Littrup. “This emphasizes the important role of an interventional 12) ___ in pioneering image-guided therapy by appropriately using established treatment technology – let alone emerging ones – to deliver a sufficient treatment dose, rather than only relying on the organ-specific expertise of other sub-specialized physicians.“ A total of 25 tumor sites were treated in the thirteen patients using only local anesthesia with mild 13) ___. Where appropriate, surgery remains a gold standard treatment and surgical techniques continue to improve all the time. Currently cryoablation is used to treat cancers of the 14) ___ and prostate, plus various cancers that have spread to the liver and bone.

ANSWERS

1) cancer; 2) tumor; 3) cells; 4) surgery; 5) treatment; 6) freezing; 7) breasts; 8) Chemotherapy; 9) cryoprobe; 10) prostate; 11) cryotherapy; 12) radiologist; 13) sedation; 14) kidney

Henrietta Lacks’ First Human Cells Grown in a Lab (an immortal cell line)

Henrietta Lacks (August 1, 1920 – October 4, 1951), was the unwitting donor of cells from her cancerous tumor, which were cultured by George Otto Gey to create an immortal cell line for medical research. This is now known as the HeLa cell line. On February 1, 1951, just days after a march for a cure for polio in New York City, Lacks visited Johns Hopkins because of a painful “knot” in her cervix and a bloody discharge. That day, she was diagnosed with cervical cancer, and the appearance of the tumor was very unusual. Prior to receiving treatment, cells were removed for research purposes without her knowledge or permission, which was standard procedure at that time. Lacks was treated with radium tube inserts, sewn in place, a common treatment for these types of cancers in 1951. However, in spite of the treatment her condition worsened and the Hopkins doctors treated her with antibiotics, thinking that her problem might be complicated by an underlying venereal disease (she had neurosyphilis and presented with acute gonorrhea). In significant pain and without improvement, Lacks returned to Hopkins demanding to be admitted. Though she received treatment and blood transfusions, she died of uremic poisoning on October 4, 1951 at the age of thirty-one. A subsequent partial autopsy showed that the cancer had metastasized throughout her body. Mrs. Lacks was buried without a tombstone in a family cemetery in Lackstown, Virginia. Her exact burial location is not known. Lackstown is the name of the land that has been held by the (black) Lacks family since they received it from the (white) Lacks family, who had owned the ancestors of the black Lackses when slavery was legal. The cells from Henrietta’s tumor were given to researcher George Gey, who “discovered that [Henrietta’s] cells did something they’d never seen before: They could be kept alive and grow.“ Gey named the sample “HeLa“, after the initial letters of Henrietta Lacks. As the first human cells that could be grown in a lab and were “immortal” (did not die after a few cell divisions), they could then be used for conducting many experiments. This represented an enormous boon to medical and biological research. By 1954, HeLa was being used by Jonas Salk to develop a vaccine for polio. To test Salk’s new vaccine, the cells were quickly put into mass production in the first-ever cell production factory. Demand for the HeLa cells quickly grew. Since they were put into mass production, Henrietta’s cells have been mailed to scientists around the globe for research into cancer, AIDS, the effects of radiation and toxic substances, gene mapping, and countless other scientific pursuits. HeLa cells have also been used to test human sensitivity to tape, glue, cosmetics, and many other products. Scientists have grown some 50 million metric tons of her cells. In 1996 Morehouse School of Medicine in Atlanta, Georgia and the mayor of Atlanta recognized the late Henrietta Lacks’ family for her posthumous contributions. Her life was commemorated annually by Turners Station residents for a few years after Morehouse’s commemoration. A Congressional resolution in her honor was presented by Robert Ehrlich following soon after the first commemoration of her family, and her contributions to science in Turners Station. In 1998, Modern Times: The Way of All Flesh, a one-hour BBC documentary on Lacks and HeLa directed by Adam Curtis, won the Best Science and Nature Documentary at the San Francisco International Film Festival. In 2001, it was announced that the National Foundation for Cancer Research would be honoring the late Henrietta Lacks for the contributions made to cancer research and modern medicine. Events in the Turners Station’s community have also commemorated the contributions of others including Mary Kubicek, the laboratory assistant who discovered that HeLa cells could live outside the body, as well as Dr. Gey and his nurse wife, Margaret Gey, who together after over 20 years of attempts were eventually able to grow human cells outside of the body. For their part, members of the Lacks family were kept in the dark about the existence of the tissue line, and when its existence was revealed, family members were confused about how Henrietta’s cells could have been taken without consent and how they could still be alive 50 years after her death.

Chocolate Lovers, Chocolate Consumption in Relation to Blood Pressure and Risk of Cardiovascular Disease

According to an article published online in the European Heart Journal (31 March 2010), a study was performed to investigate the association of chocolate consumption with measured blood pressure (BP) and the incidence of cardiovascular disease (CVD). For the study, dietary intake, including chocolate, and BP were assessed at baseline (1994-98) in 19,357 participants (aged 35-65 years) of the Potsdam arm of the European Prospective Investigation into Cancer and Nutrition. All subjects were free of myocardial infarction (MI) and stroke and not using antihypertensive medication. Incident cases of MI (n = 166) and stroke (n = 136) were identified after a mean follow-up of 8 years. Mean systolic BP was 1.0 mmHg and mean diastolic BP 0.9 mmHg lower in the top quartile compared with the bottom quartile of chocolate consumption. The relative risk of the combined outcome of MI and stroke for top vs. bottom quartiles was 0.61 (P linear trend = 0.014). Baseline BP explained 12% of this lower risk. The inverse association was stronger for stroke than for MI. According to the authors, chocolate consumption appears to lower CVD risk, in part through reducing BP and that the inverse association may be stronger for stroke than for MI. The authors stated that further research is needed, in particular randomized trials. 

Risk of Newborn Heart Defects Increases with Maternal Obesity

Congenital heart defects are the most common type of birth defect, affecting 8 in every 1,000 newborns. These defects consist of a number of problems in the structure of the heart and range from minor to life threatening. Previous studies have shown that maternal obesity during pregnancy is associated with complications for mothers and infants. Obesity increases the risk for pregnancy-induced hypertension, preeclampsia (a serious form of hypertension during pregnancy), gestational diabetes, and cesarean delivery. Infants born to women who were obese during pregnancy are themselves at increased risk for overweight and type II diabetes later in life. Previous research has also shown an association between maternal obesity and birth defects, such as neural tube defects which are serious malformations of the spinal column. In the US, 1 in 5 women are obese at the beginning of pregnancy. According to an article published online in the American Journal of Clinical Nutrition (7 April 2010), the more obese a woman is when she becomes pregnant, the greater the likelihood that she will give birth to an infant with a congenital heart defect. The study was a collaboration with the National Institutes of Health and the New York State Department of Health. For the study, data were analyzed from the New York State Congenital Malformations Registry, a repository of case reports on children born with birth defects in New York State, excluding New York City. Using 1.53 million births that took place in the state over the course of 11 years, the study compared the records of mothers of 7,392 of children born with major heart defects to those of more than 56,000 mothers of infants born without birth defects. The study calculated the mothers’ body mass index (BMI), a measure of an individual’s proportion of body fat to her height. A normal BMI is 18.5 to 24.9; overweight is 25 to 29.9 and obese is 30 and above. Results showed that the obese mothers were 15% more likely than mothers with normal BMI to have children with heart defects. Women classified as morbidly obese – with a BMI of 40 or higher – were 33% more likely than women with normal BMI to have children with heart defects. The risk of heart defects increased sharply at a BMI of 30 and was progressively higher with each increase in BMI. On average, women who were overweight but not obese had no increased risk. The study also examined records of infants after they had been born and for this reason it cannot conclusively prove that obese women who lose weight before they conceive will reduce their infants’ risks of heart defects. For conclusive proof, a study would need to enroll obese women who were not yet pregnant, follow those who succeed in losing weight before conceiving, and then determining the frequency of heart defects among the children subsequently born to them. However, until such a study can be conducted, the authors believe it is reasonable to assume that attaining a healthy weight before conception will reduce the risk for heart defects.

Healthcare Utilization Rates, More Than Biology, Explain Colorectal Cancer Disparities

In the United States, colorectal cancer disproportionally affects blacks, who have higher incidence and mortality rates compared to whites. From 2002 to 2006, the average annual incidence rate for colorectal cancer was 48.6 per 100,000 for white men and women combined, compared to 59.9 per 100,000 for black men and women. The annual mortality rates for the same time period were 17.7 per 100,000 for white men and women, and 25.4 per 100,000 for black men and women. Several studies have found that blacks are more likely than whites to be diagnosed with advanced colorectal cancer, which is more difficult to treat and has worse survival outcomes. According to an article published online in the Journal of National Cancer Institute (April 6, 2010), higher rates of colorectal cancer incidence and mortality experienced by African-Americans may be driven largely by differences in health care utilization, and less by biology. In a study involving more than 60,000 people who were screened for colorectal cancer, it was found that blacks and whites were equally likely to need a follow-up colonoscopy after a screening sigmoidoscopy, but blacks were less likely to actually receive the follow-up procedure. These lower rates of follow-up could lead to delayed diagnosis and treatment and higher mortality. Participants in this study were part of the ongoing Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a multi-center, randomized, controlled screening trial designed to evaluate the effect of screening on cancer mortality. At the start of the colorectal cancer part of the study, participants were offered a screening flexible sigmoidoscopy, which is used to examine the lower, or sigmoid, portion of the colon. Subjects who had polyps or lesions detected during the sigmoidoscopy were referred to their personal physician for follow-up colonoscopy, the cost of which was not covered by the study. In a colonoscopy, the entire colon, which is about five feet in length, is examined. During a sigmoidoscopy, only about the last two feet of the colon is viewed. The records of the follow-up colonoscopies were collected and reviewed to determine which subjects had received them. Those results were analyzed to determine whether utilization of follow-up colonoscopy and likelihood of adenomas (pre-cancerous lesions) or colorectal cancer varied by race. In their analysis, to reduce the possibility that other factors were influencing the outcome of the study, the researchers documented age, education, gender, body mass index, smoking, family history of colorectal cancer, colon cancer screening within the previous three years, personal history of polyps, and center where the participant was screened. Of the 60,572 study participants who received flexible sigmoidoscopy (57,561 whites and 3,011 blacks) at the start of the study, 23.9% of the white participants and 25.5% of the black participants had abnormal results. Among those with abnormal results, 72.4% of whites and 62.6% of blacks received a follow-up colonoscopy to determine whether cancer was present. The study found no statistically significant differences in the presence of adenomas, advanced adenomas, or cancer by race. It should be noted, however, that black participants were more likely to have cancer in the upper part of the colon, which would not be viewed during a sigmoidoscopy. Overall, a total of 156 colorectal cancers were diagnosed among the participants who received a follow-up colonoscopy. Most of the cancers (75.6%) were stage I or II tumors, which are considered early stage disease. There was no statistically significant difference in the risk of colorectal cancer by race. Among white participants, women and people with a family history of colorectal cancer were more likely than men or those without a family history to undergo a follow-up colonoscopy. Among black participants, those with a personal history of colon polyps were more likely to undergo follow-up colonoscopy than those without such a history. The reasons behind the lower follow-up rates among black men and women in this study are unknown. It is possible that lower socioeconomic status may have affected health care utilization due to the direct and indirect costs of care, such as copays and lost wages. Although the authors did not have direct information on the socioeconomic status of study participants, the overall educational level-an indicator of socioeconomic status-was lower in black participants than white participants. In addition, the need for multiple tests, including colonoscopy, following abnormal results of a screening sigmoidoscopy, and the cost and preparation required for those tests, could have deterred some people from receiving follow-up colonoscopies. Finally, a lack of knowledge about cancer prevention among patients and a lack of cultural competence on the part of the health care providers could be barriers to health care utilization. When the authors analyzed the rate of follow-up colonoscopies by educational attainment, they observed differences at all educational levels, but the differences were only statistically significant among participants with a high school education or less. Because black participants in the PLCO study were, on average, more educated and health conscious than comparable members of the general population, the authors stated that it is possible that their findings of lower health care utilization among blacks may actually be an underestimation of what would be seen in the general population.

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.

FDA Requires Device Manufacturers to Include Information on Pediatric Populations

The FDA announced that it will begin implementing a requirement that device manufacturers provide readily available information in certain premarket applications on pediatric patients who suffer from the disease or condition that the device is intended to treat, diagnose, or cure, even if the device is intended for adult use. Very few devices are developed or assessed specifically for use in pediatric patients, those 21 or younger at the time of treatment or diagnosis. This effort will provide a better understanding of which devices developed for use in adults should be assessed or modified for use in pediatric populations. The requirements, contained in the Food and Drug Administration Amendments Act of 2007, will also improve the agency’s ability to track the number of approved devices for which there is a pediatric subpopulation who could benefit and the number of approved devices labeled for use in pediatric patients. Under the 2007 legislation, manufacturers must provide certain pediatric information, if readily available, with each premarket approval application or supplement, humanitarian device exemption request, or product development protocol. Manufacturers now must include a description of any pediatric subpopulations that suffer from the disease or condition that the device is intended to treat, diagnose, or cure. Manufacturers also must include the number of affected pediatric patients. If the manufacturer does not submit such information, the FDA may not approve the application until the required information is provided.

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.

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