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The Promise of Personalized Medicine

Posted in FDA Regulatory Affairs, Genome Biology, Genomic Testing: Methodology for Diagnosis, Health Economics and Outcomes Research, Health Law & Patient Safety, Molecular Genetics & Pharmaceutical, Nanotechnology for Drug Delivery, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Population Health Management, Genetics & Pharmaceutical, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , , , , on March 3, 2013| 1 Comment »

The Promise of Personalized Medicine

Reporter: Larry H Bernstein, MD, FCAP

 

 Realizing the Promise of Personalized Medicine

Harvard Business Review
MG Aspinal, RG Hamermesh
Obsolete business models, regulations, reimbursement systems, and physicians stand in the way
NewYear for Angels

NewYear for Angels (Photo credit: Wikipedia)

BusinessModel

BusinessModel (Photo credit: Wikipedia)

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Mobilizing Scientific Societies: Editorial by Science Editor-in-Chief Dr. Bruce Alberts

Posted in Health Economics and Outcomes Research, HealthCare IT, Interviews with Scientific Leaders, Scientist: Career considerations, tagged , , , , , , , , , , , on February 24, 2013| Leave a Comment »

Mobilizing Scientific Societies: Editorial by Science Editor-in-Chief Dr. Bruce Alberts

Reporter: Stephen J. Williams, Ph.D

This image has an empty alt attribute; its file name is ArticleID-28.png

WordCloud Image Produced by Adam Tubman

In a weekly editorial, Dr. Bruce Alberts, Editor-in –Chief of the journal Science discussed issues pertaining to science education in the United States[1].  He suggests the US science education system may need to be more flexible in its approach to science education in grade and high school.  He considers the one major problem is the “broad coverage of each subject, which kills student interest and makes genuine comprehension impossible.  Dr. Alberts suggest that state-based textbooks and the inability of the scientific community to understand teacher’s needs is driving this inadvertent problem.  The current textbooks used for scientific education focus more on memorization of a multitude of scientific terms than on concept development, experimentation and inquisition, and conclusion.  Materials are desperately needed for teachers to guide students to confront the overall concept, and working in teams, design potential methods to further explore these concepts.  He suggest this style of teaching would require close partnerships between top-notch teachers , educational  experts and scientific societies in order to research the effect of current curriculum materials but also develop  new Web-based  curriculum.

In a recent interview in the March 2013 issue of Wired magazine with Clayton Christensen, Ph.D. the author of the famed book The innovator’s Dilemma,  Dr. Christensen forwqarns the impending changes in higher education due to increased availability of online learning.  As he states, universities are on the precipice of a collapse in the future and those which survive will evolve hybrid models of education, part online and part classroom but will provide more specialized offerings to fit current needs.  Indeed, as listed below these changes and suggestions in science education may well be underway.  Below is a brief listing of scientific societies who have undertaken these challenges and formed extensive programs in STEM education.

FASEB (Federation of American Societies for Experimental Biology) programs such as:

Resources for Faculty and K-12 Teachers

APS Frontiers in Physiology Program – Provides professional development for middle and high school teachers by providing them with tools and resources and connecting them with researchers on-line and through workshops.

APS Physiology Understanding Week – Fosters relationships among teachers, students, and physiologists. PhUn Week encourages member physiologists across the nation to volunteer and work with teachers in their local community to visit a classroom during the first week in November.

Leap to the Top in Science Classes  from AAAS found at:

http://news.aaas.org/2013_annual_meeting/0214leap-to-the-top-in-science-classes.shtml

A progress report from the 2013 AAAS meeting follows:

Often, in the daily grind of slogging through a difficult science class, students see fully formed scientists and their discoveries as a distant blur. Remote men and women somehow make advanced science happen.

New efforts aim to bring students face to face with creative, imaginative scientists right in their classroom.

With a lifetime of scientific contributions at their back, many retired scientists, engineers, and physicians are returning to school, not as pupils or as instructors, but as classroom volunteers in public elementary, middle, and high schools.

This week over 400 teachers and scientists gathered in Boston for the first International Teacher-Scientist Partnership Conference, organized by AAAS Education and Human Resources and the University of California, San Francisco Science & Health Education Partnership, sponsored by the National Science Foundation. Presenters are scheduled to share a range of partnership models over three days, from scientists generating digital education tools, to teachers participating in research.

Throughout the first day of the conference, the conversation turned to the idea of bringing scientists into the classroom to work directly with the students.

Virginia Shepherd from Vanderbilt University shared a comprehensive analysis of the university’s nearly 20-year-old Graduate STEM Fellows in K-12 Education program. Presentation attendees duly applauded the success of the program but said that they had trouble establishing similar programs in their state for lack of funding.

A handful of organizations represented at the conference have found that an affordable way to bring scientists into the classroom is to recruit retired scientists.

Volunteers at Northeastern University’s Retirees Enhancing Science Education through Experiments and Demonstrations program, or RE-SEED, spend at least one day a week in an elementary, middle, or high school classroom in Massachusetts helping students conduct experiments as part of the existing curriculum.

“Retired scientists and engineers have a lot of experience from a lifetime of working in laboratories. They can make what the students are learning relevant,” said Christos Zahopoulos, a professor of education and engineering at Northeastern University.

Since founding RE-SEED in 1991, Zahopoulos has helped to start similar programs in 15 states, conducting on-site trainings for volunteers. While such programs start out strong, many of them have since faded, with only a handful remaining, he said.

Even though retirees are offering a free service to the schools, getting them trained and placed takes a certain amount of funding, Zahopoulos says. He has been fortunate to fund RE-SEED with private donations. Many programs were not so lucky.

AAAS’ Senior Scientists and Engineers (SSE), a service-oriented organization for retired scientists and engineers, has managed to sustain a similar program for seven years. In 2005, Zahopoulos helped SSE establish its own volunteer program.

Donald Rea, a former research chemist for NASA’s Jet Propulsion Laboratory and SSE volunteer coordinator for Virginia, hopes that helping to reinforce science education will enhance the public understanding of science in years to come.

“If you want to have an influence on science literacy, you want to get [kids] while they are young. So we work in classrooms as young as second grade,” Rea said.

This kind of investment takes many years to fully mature. So, how do Rea and Zahopoulos measure success? They look to their teachers, volunteers, and students.

Rea said he measures success by the eagerness of schools and teachers to participate year after year.

For Zahopoulos, hints of success sometimes come in the mail. He says one student wrote in to RE-SEED upon graduating from high school, several years after any contact with a RE-SEED volunteer, to say that she had decided to major in biology and had enrolled in a pre-medicine program.

Both Rea and Zahopoulos said they have been amazed at the dedication and eagerness of volunteers.

“When we first started, we asked volunteers to commit to one day a week for one year. Now we have volunteers who have been with us for 18 years and some volunteer as many as 4 times per week,” Zahopoulos said.

Ron McKnight, a former Department of Energy physicists and SSE volunteer has recently taken on the task of coordinating volunteers living in Montgomery County, Md. He still volunteers in middle school science classrooms and is considering taking on another assignment.

When asked what he loves about volunteering, he replied, “Whenever a kid I’m working with asks a really good question, that’s when I have a really good day.”

National Science Foundation (NSF) Research on Learning in Formal and Informal Settings (DRL)

Information can be found at http://www.nsf.gov/div/index.jsp?div=DRL

DRL invests in projects to improve the effectiveness of STEM learning for people of all ages. Its mission includes promoting innovative research, development, and evaluation of learning and teaching across all STEM disciplines by advancing cutting-edge knowledge and practices in both formal and informal learning settings. DRL also promotes the broadening and deepening of capacity and impact in the educational sciences by encouraging the participation of scientists, engineers, and educators from the range of disciplines represented at NSF. Therefore, DRL’s role in the larger context of Federal support for education research and evaluation is to be a catalyst for change—advancing theory, method, measurement, development, and application in STEM education. The Division seeks to advance both early, promising innovations as well as larger-scale adoptions of proven educational innovations. In doing so, it challenges the field to create the ideas, resources, and human capacity to bring about the needed transformation of STEM education for the 21st century.

Society of Toxicology K-12 Educational Outreach for Scientists

http://www.toxicology.org/ai/k12o/k-12scientists.asp

This sites contains multiple .pdf  files on volunteering and mentoring topics including

  • Scientist Mentor Ideas
  • Links to Other Mentoring Sites
  • Resources for toxicologists to use in K-12 Outreach
  • Regional Chapter K-12 Outreach

References:

1.         Alberts B: Mobilizing scientific societies. Science 2012, 338(6113):1396.

for high school teachers please see https://www.teachercertificationdegrees.com/top-blogs/science-teacher/

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State of the art in oncologic imaging of Lymphoma.

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, Ecosystems & Industrial Concentration in the Medical Device Sector, Health Economics and Outcomes Research, Imaging-based Cancer Patient Management, Liver & Digestive Diseases Research, Medical Devices R&D and Inventions, Personalized and Precision Medicine & Genomic Research, Statistical Methods for Research Evaluation, Stem Cells for Regenerative Medicine, tagged , , , , , , , on February 3, 2013| Leave a Comment »

State of the art in oncologic imaging of Lymphoma.

Author and Curator: Dror Nir, PhD

Article 11.3.6 State of the art in oncologic imaging of Lymphoma

This is the last post in a series in which I will address the state of the art in oncologic imaging based on a review paper; Advances in oncologic imaging†‡ that provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, colorectal cancers, and lymphoma. This paper is published at CA Cancer J Clin 2012. © 2012 American Cancer Society.

The paper gives a fair description of the use of imaging in interventional oncology based on literature review of more than 200 peer-reviewed publications. In this post I summaries the chapter on imaging used in management of Lymphoma.

The traditional tasks of imaging in the management of lymphoma include: staging, assessing response to therapy and confirming it reaching an end-point and detecting recurrence. The leading imaging modality is PET/CT. In their literature review the authors include several references claiming that the clinical outcome of lymphoma patients has improved significantly due to better prognosis – largely related to better disease characterization and identification of prognostic markers in recent years. Adoption of functional imaging that improved pre-treatment staging and assessment of the response to treatment contributed as well to this outcome 178 .179 “Most of the recent progress in management of lymphoma occurred after the widespread introduction of [18F]FDG PET and PET/CT. Accordingly, [18F]FDG PET is now part of the revised lymphoma response criteria.180 “

 

A 46-year-old male with diffuse large B cell lymphoma, stage IV was studied. Baseline maximum intensity projection (MIP) positron emission tomography (PET) image with [18F]fluorodeoxyglucose ([18F]FDG) (A) shows widespread disease, which is essentially resolved on interim scan after 4 cycles of chemotherapy (B). The interim scan also shows increased [18F]FDG uptake in bone marrow related to administration of granulocyte colony-stimulating factor (GCSF). (C,D) Transaxial CT and PET/CT fusion images at baseline show abnormal [18F]FDG uptake in extensive mediastinal and hilar lymphadenopathy as well as in bone lesions in a right rib and the right scapula. On interim scan (E,F) abnormal [18F]FDG uptake at all of these sites has resolved although residual enlarged lymph nodes remain. The sites are better seen on a contrast-enhanced CT (G) and measure up to 5.3 cm × 3.6 cm. Chemotherapy was continued for a total of 8 cycles. At the time of writing, the patient remained disease-free after 9 years of follow-up.

A 46-year-old male with diffuse large B cell lymphoma, stage IV was studied. Baseline maximum intensity projection (MIP) positron emission tomography (PET) image with [18F]fluorodeoxyglucose ([18F]FDG) (A) shows widespread disease, which is essentially resolved on interim scan after 4 cycles of chemotherapy (B). The interim scan also shows increased [18F]FDG uptake in bone marrow related to administration of granulocyte colony-stimulating factor (GCSF). (C,D) Transaxial CT and PET/CT fusion images at baseline show abnormal [18F]FDG uptake in extensive mediastinal and hilar lymphadenopathy as well as in bone lesions in a right rib and the right scapula. On interim scan (E,F) abnormal [18F]FDG uptake at all of these sites has resolved although residual enlarged lymph nodes remain. The sites are better seen on a contrast-enhanced CT (G) and measure up to 5.3 cm × 3.6 cm. Chemotherapy was continued for a total of 8 cycles. At the time of writing, the patient remained disease-free after 9 years of follow-up.

 

Subsequent to their acknowledgment of PET/CT as the most promising imaging modality for management of Lymphoma, the authors focused their review to on its role in this disease pathway. It being well understood that the clinical utility of [18F]FDG PET in lymphoma “depends on the intensity of radiotracer uptake in disease sites, which will affect the test accuracy for staging and characterizing residual masses after completion of therapy, as well as the role of the test in response assessment. The intensity of [18F]FDG uptake in lymphoma is determined by tumor histology, grade (eg, indolent versus aggressive NHL)”,181, 182  At the end of their extensive review the authors do mention that PET/MRI might become an important player in the management of this disease, especially in pediatric cases.

 Other research papers related to the management of Lymphoma were published on this Scientific Web site:

Imatinib (Gleevec) May Help Treat Aggressive Lymphoma: Chronic Lymphocytic Leukemia (CLL)

Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine – Part 1

Predicting Tumor Response, Progression, and Time to Recurrence

Cancer Innovations from across the Web

 

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State of the art in oncologic imaging of breast.

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, Computational Biology/Systems and Bioinformatics, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA Regulatory Affairs, Health Economics and Outcomes Research, HealthCare IT, Imaging-based Cancer Patient Management, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Nanotechnology for Drug Delivery, Personalized and Precision Medicine & Genomic Research, Population Health Management, Genetics & Pharmaceutical, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Reproductive Biology & Bio Instrumentation, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , , , , , , , , , , , , , , , , on January 21, 2013| 2 Comments »

State of the art in oncologic imaging of breast.

Author-Writer: Dror Nir, PhD

Screen Shot 2021-07-19 at 7.28.07 PM

Word Cloud By Danielle Smolyar

In the coming posts I will address the state of the art in oncologic imaging based on a review paper; Advances in oncologic imaging†‡ that provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, colorectal cancers, and lymphoma. This paper is published at CA Cancer J Clin 2012. © 2012 American Cancer Society.

The paper gives a fair description of the use of imaging in interventional oncology based on literature review of more than 200 peer-reviewed publications.

In this post I summaries the chapter on breast cancer imaging.

Breast Cancer Imaging

As a start the authors describes the evolution in the ACS imaging guidelines for breast cancer screening. Most interesting to learn is how age limits are changing. The most recent: “In 2010, the Society of Breast Imaging and the Breast Imaging Commission of the ACS issued recommendations for breast cancer screening to provide guidance in light of the controversies and emerging technologies.5 These recommendations were based on multiple prospective randomized trials as well as population-based experience.

Recommendations for screening with non-mammographic imaging are based not on evidence showing mortality reduction but largely on surrogate indicators, i.e., tumor size and nodal status, suggesting improved survival compared with women who are not screened.” I have referred to these guidelines in my recent post: Not applying evidence-based medicine drives up the costs of screening for breast-cancer in the USA.

As long as imaging interpretation is based mainly on observations related to lesion morphology:

“The imaging characteristics of malignant lesions are nonspecific and usually do not allow a definitive diagnosis. When a biopsy is recommended based on mammography, it has a 25% to 45% likelihood of resulting in a diagnosis of carcinoma.11 Similar positive predictive values are reported for biopsies recommended based on MRI.”

It is worthwhile noting that these results do not reflect purely the specificity of the imaging device but rather the specificity of the whole workflow; i.e imaging, biopsy and histopathology. All imaging techniques have false negatives: Mammography screening of general population misses approximately 20% of the cancers. This rate increases as breast density increases. MRI is not applied to general population. When applied to highly suspicious cases MRI misses ~10% of the invasive cancers. Although ultrasound has proven to be useful in detecting cancer especially in women with dense breasts: Automated Breast Ultrasound System (‘ABUS’) for full breast scanning: The beginning of structuring a solution for an acute need! Based on the literature reviewed by the authors of this paper they do not recommend routine sonography for these women.

For women with locally advanced breast cancer (Fig. 2) who undergo neoadjuvant therapy before breast surgery, the authors recommends post-treatment staging using MRI, which has been found to predict complete response with sensitivity above 60% and specificity as high as 90%.26

A 27-year-old female with locally advanced poorly differentiated invasive ductal carcinoma underwent evaluation of extent of disease before starting neoadjuvant chemotherapy. Sagittal fat-suppressed T1-weighted postcontrast MR images demonstrate an almost 6-cm heterogeneously enhancing mass (A) involving the skin of the lower breast (arrow) with (B) right axillary (arrow) and (C) right internal mammary adenopathy (arrow).

A 27-year-old female with locally advanced poorly differentiated invasive ductal carcinoma underwent evaluation of extent of disease before starting neoadjuvant chemotherapy. Sagittal fat-suppressed T1-weighted postcontrast MR images demonstrate an almost 6-cm heterogeneously enhancing mass (A) involving the skin of the lower breast (arrow) with (B) right axillary (arrow) and (C) right internal mammary adenopathy (arrow).

Same is recommended for women who have undergone lumpectomy if the surgical margins are positive. As post therapy follow-up, a new baseline mammogram of the treated breast is recommended followed by annual mammography.

In regards to emerging technology the following are discussed: Mammographic tomosynthesis – see also Improving Mammography-based imaging for better treatment planning

Contrast-enhanced digital mammography – “involves the injection of iodinated contrast material, as is done for computed tomography (CT); this enables hypervascular lesions to be seen with modified mammography technology, potentially providing the same information obtained through MRI. Little has been published on the clinical application of this technology, but diagnostic accuracy better than that of mammography and approaching that of MRI has been reported.31, 32”

MR choline spectroscopy – has been shown to improve the positive predictive value of breast MRI and may be useful in reducing the number of lesions that require biopsy (Fig. 4).33 Studies of spectroscopy have reported sensitivities of 70% to 100% and specificities of 67% to 100% in the detection of breast cancer. Decreasing choline concentrations may also be a useful indication of tumor response to treatment before any change in tumor volume can be detected.34, 35 Technical factors have limited the use of spectroscopy to lesions 1 cm in size or larger.”

Sagittal fat-suppressed T1-weighted postcontrast MR image is shown (A) of the right breast of a 48-year-old female who was status post–contralateral mastectomy for DCIS with the spectroscopy voxel placed over an enhancing mass (arrow). The magnified spectrum (B) demonstrated no choline peak. Biopsy yielded fibroadenoma.

Sagittal fat-suppressed T1-weighted postcontrast MR image is shown (A) of the right breast of a 48-year-old female who was status post–contralateral mastectomy for DCIS with the spectroscopy voxel placed over an enhancing mass (arrow). The magnified spectrum (B) demonstrated no choline peak. Biopsy yielded fibroadenoma.

Diffusion-weighted MRI (DW-MRI) – “adding DW-MRI data to other imaging characteristics of lesions on breast MRI may increase the positive predictive value of the examination, in turn decreasing the number of benign lesions requiring biopsy for diagnosis.” See also Imaging: seeing or imagining? (Part 2).

Axial T1-weighted fat-suppressed postcontrast MR image is shown (A) of the left breast of a 42-year-old female with biopsy-proven contralateral cancer undergoing evaluation of disease extent. An enhancing mass (arrow) was seen in the left breast. This mass (arrow) was also demonstrated on the axial diffusion-weighted MR image (B). Biopsy yielded fibroadenoma with atypical ductal hyperplasia and lobular carcinoma in situ.

Axial T1-weighted fat-suppressed postcontrast MR image is shown (A) of the left breast of a 42-year-old female with biopsy-proven contralateral cancer undergoing evaluation of disease extent. An enhancing mass (arrow) was seen in the left breast. This mass (arrow) was also demonstrated on the axial diffusion-weighted MR image (B). Biopsy yielded fibroadenoma with atypical ductal hyperplasia and lobular carcinoma in situ.

Ultrasound-elastography – “Ultrasound elastography has been reported to differentiate benign from malignant breast lesions with sensitivities of 78% to 100% and specificities of 21% to 98%.39 When added to other US techniques, it may improve radiologists’ performance in distinguishing malignant breast lesions.”

Positron emission tomography (PET) – “alone or combined with CT, allows noninvasive, quantitative assessment of biochemical and functional processes at the molecular level in the body. It is most often performed with the radiolabeled glucose analogue [18F] fluorodeoxyglucose ([18F]FDG) to detect the elevated glucose metabolism that is a hallmark of cancer. In breast cancer, its utility depends on the pretest probability for advanced disease, and thus the clinical stage.” The authors found that the use of [18F] FDG PET to patients with stage I and II disease is “limited”. Specifically, they claim that it is not sufficiently accurate for axillary nodal staging in this subset of patients.40 The did find enough evidence to recommend the use of FDG PET in patients with advanced disease: “where it accurately defines disease extent,41 and frequently eliminates the need for other imaging tests, and provides an early readout of treatment response as well as prognostic information.”

Combined PET/MRI is mentioned as a promising technology for predicting response to therapy “but this remains to be proven”.

Positron emission mammography (PEM) – “adapts full-body PET imaging to the breast. In a multicenter study, the interpretation of PEM in conjunction with mammographic and clinical findings yielded a sensitivity of 91% and a specificity of 93% for breast cancer.47 “. However, the authors mention that its use for screening (applying to healthy women) has been criticized because of the need to administer a radioactive tracer.

Lung Cancer Imaging

To be followed…

Other research papers related to the management of breast cancer were published on this Scientific Web site:

The unfortunate ending of the Tower of Babel construction project and its effect on modern imaging-based cancer patients’ management

 Automated Breast Ultrasound System (‘ABUS’) for full breast scanning: The beginning of structuring a solution for an acute need!

Introducing smart-imaging into radiologists’ daily practice.

Will Bio-Tech make Medical Imaging redundant?

Improving Mammography-based imaging for better treatment planning

Not applying evidence-based medicine drives up the costs of screening for breast-cancer in the USA.

New Imaging device bears a promise for better quality control of breast-cancer lumpectomies – considering the cost impact

Harnessing Personalized Medicine for Cancer Management, Prospects of Prevention and Cure: Opinions of Cancer Scientific Leaders @ http://pharmaceuticalintelligence.com

Predicting Tumor Response, Progression, and Time to Recurrence

“The Molecular pathology of Breast Cancer Progression”

Personalized medicine gearing up to tackle cancer

Whole-body imaging as cancer screening tool; answering an unmet clinical need?

What could transform an underdog into a winner?

Mechanism involved in Breast Cancer Cell Growth: Function in Early Detection & Treatment

Nanotech Therapy for Breast Cancer

A Strategy to Handle the Most Aggressive Breast Cancer: Triple-negative Tumors

Optical Coherent Tomography – emerging technology in cancer patient management

Breakthrough Technique Images Breast Tumors in 3-D With Great Clarity, Reduced Radiation

Closing the Mammography gap

Imaging: seeing or imagining? (Part 1)

Imaging: seeing or imagining? (Part 2)

 

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Introducing Dr. Tim Wu – Interventional Cardiologist, Inventor and Entrepreneur

Posted in Cardiac & Vascular Repair Tools Subsegment, Drug Delivery Platform Technology, Frontiers in Cardiology and Cardiovascular Disorders, Interviews with Scientific Leaders, Medical Devices R&D and Inventions, Medical Devices R&D Investment, PCI, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Stents & Tools, tagged , , , , , , , , , , , , , , , , , , , , on January 14, 2013| 2 Comments »

Introducing Dr. Tim Wu – Interventional Cardiologist, Inventor and Entrepreneur

 

Author: Ed Kislauskis, PhD

Article ID #18: Introducing Dr. Tim Wu – Interventional Cardiologist, Inventor and Entrepreneur. Published on 1/14/2013

WordCloud Image Produced by Adam Tubman

 

Welcome readers to the first in a series of interviews with future scientific leaders in biotechnology and medicine.  In this post I interview a close colleague and clinical scientist who appears to be on a fast-track to achieving his vision for the future of interventional cardiology – at the very vanguard of applied nanotechnology.

Tim (Tiangen) Wu, M.D has graciously accepted my invitation to answer a few questions about how his career path and primary goal to develop and commercialize his first product, a fully-biodegradable drug-eluting stent he calls the PowerStent® Absorb (see insert).  This technology combines three especially innovations:  a unique balloon-expandable stent design (PowerStent®), a bioabsorbable nanoparticle composition (BioDe®), and a formulation of two commercially-available anti-restenosis drugs (Combo®).

Stent

About the Subject

Dr. Wu received his clinical education in China and research training in the USA. In 1988, he graduated with an MD from the prestigious Linyli Medical School and completed a fellowship in clinical cardiology at the Tonji Medical University.  In 1993, presented with an opportunity to travel to the US, he uprooted to accept a position as visiting scholar, and ultimately post-doctoral fellow,in Jeffrey Isner’s lab at St. Elizabeth Hospital (Tufts University) and the Beth Israel Medical Center (Harvard Medical).  There he investigated the biology of stenosis, and directed sponsored research projects to evaluate the safety and efficacy of the latest commercially-developed drug-coated stents (DES) in animals.

After  a decade in academia, Dr. Wu made the successful transition to industry and joined Nitromed Inc. as a Research Scientist.  His next stop was as a Research Director at Biomedical Research Models, Inc (2000-2006) where we met and collaborated on developing and characterizing macrovascular disease in an inbred, type 2 diabetic rat model.  After a 20 year career, and upon gaining additional qualification in Mechanical Engineering (Wentworth Institute), Business Administration (MIT), Clinical Research Affairs (Mass. Biotech Council), and Medical Device Regulatory Affairs (North Eastern Univ.), he was ready to take the entrepreneurial leap.  His first company, VasoTech would aim to re-engineer the clinical standards of stent design and drug delivery.

In 2007, Dr. Wu founded VasoTech, Inc. from inside his home garage. Less than a year later, VasoTech received a $1.5M SBIR fast-track grant award from the NIH.  With funding, VasoTech joined the newly announced M2D2 facility on the University of Massachusetts Lowell campus, and expanded operations in China.  With the support of one of his closest advisors, Dr. Stephen McCarthy and other research faculty, Dr. Wu was appointed as an adjunct faculty in the Dept. of BioMedical Engineering at the UMass/Lowell where he mentored a number of talented graduate students.  Dr. Wu is recognized as a senior reviewer on the NIH Bioengineering, Surgical Science and Technology Study Section, and Biomaterials, Delivery Systems and Nanotechnology Special Emphasis Panels servicing the  Small Business Innovation Research (SBIR) grant program.

Dr. Wu’s work at Vasotech is devoted to developing a 3rd generation of fully biodegradable DES coronary stents to solve two major complications associated with stenting, restenosis and late-stage thrombosis. Thusfar, his ideas have attracted well over $1.5 Million (USD) in Small Business Innovation Research (SBIR) grant awards from the National Institute of Diabetes and Digestive and Kidney Diseases, and $1million (USD) from China Innovative Talent Leadership Program.  Through his efforts VasoTech is well positioned to attract the strategic partnerships and venture capital investments necessary to translate his research through clinical stages of development both in China and the US.

The Interview

Kislauskis:  Please help our readers understand the current clinical approach to CAD.

Wu:  Most patients with advanced atherosclerosis diseases are at risk for occlusive coronary arterial disease and stroke. Consequently, it is recommended they undergo a percutaneous intervention (PCI); essentially, balloon angioplasty followed by instillation of one or more expandable metal stents. A properly expanded stent will dilate the vessel and increase blood flow to cardiac muscle tissue. Current 2nd generation drug-eluting-stents (DES) release drugs to inhibit the process of vascular remodeling leading to restenosis. Because the DES approach is remarkably successful and lowers the rate of restenosis to < 10%, DESs is now performed in 85% of the 2 million percutaneous coronary interventions (PCI) procedures annually in the U.S.

Kislauskis:  What is your impression of the recent 5 yr update of the FREEDOM trial comparing effectiveness of coronary artery bypass grafting (CABG) to PCI among diabetics? 1

Wu:  It makes perfect sense. There are other reports evaluating PCI in patients within high risk categories, including those with small diameter vessels, diabetes, and extensive, systemic vascular disease, showing unacceptably high rates of restenosis with bare metal stents (30%-60%) and DESs (6%-18%) 2-4.  We also know first-hand using an inbred rat strain that develops macrovascular disease 4 months after onset of spontaneous diabetes.  In our experiment model, just 4weeks following balloon-induced injury to the coratid artery (PTCA),  we observed 2x greater restenosis in female obese rats, and 4x greater stenosis in obese, diabetic rats  littermates (syndrome X) relative to the non-obese, non-diabetic littermates.  These results predicted that obesity (dyslipidemia) and diabetes (severe hyperglycemia) were major risk factors promoting the complication of restenosis (Wu and Kislauskis, unpublished).

Kislauskis: Can you tell our readers a bit more about the significance of restenosis and thrombosis and the concept behind your approach.

Wu: Two significant drawbacks to conventional PCI are the need for costly, long-term anti-platelet therapy; and having a metal artifact within the coronary vessel. In fact, once installed, the purpose of DES is to maintain patency and provide a scaffold until remodeling is complete, maybe 6 months.  The period of drug elution is typically shorter in duration.  In the event of restenosis, a second DES procedure is recommended and performed with satisfactory results.  However, leaving another metal artifact is problematic.

Most concerning to PCI patients, however, should be an increased risk of sudden death from heart attack from a clot (thrombosis) and tissue ischemia (myocardial infarction).  No available DES technology (eg. Cypher®or Taxus® DES) demonstrates any advantage over bare metal stents in this regard 5-7.  So the thinking is a metal artifact create an irregular vessel surface and micro-eddys in blood flow which ultimately result in late-stage thrombosis, particularly in patients who go off anti-their platelet therapy too soon 8.  Therefore and conceptually, by combining potent DES technology with a fully-biodegradable scaffold, designed to be absorbed fully into the tissue, likely will reduce the rate in-stent stenosis and prevents late-stage thrombosis.

Kislauskis: How did you come up with your unique polymer formulation?

Wu: It turns out that through a process of trial and error in the lab I was able to identify a biodegradable formulation which reduces the local inflammatory response common to all DES formulations while improving the stent’s radial strength.  With a stable drug delivery platform (BioDe®), the process of remodeling will contribute far less to restenosis.  Furthermore, and unlike all prior art, my BioDe® formulation can neutralize acidic intermediates generated during stent degradation that induce inflammation.  The combination of anti-restenosis drugs (Combo®) also is effective at inhibiting signaling pathways that contribute to restenosis.

Kislauskis:  How did you come to design the PowerStent®?

Wu: Again, a long process of trial and error, initially using computer applied design (CAD) principals I learned while earning attending a mechanical engineering certificate program at Wentworth Institute of Technology in Boston. Elements behind my concept for BioDe® came to me while I was involved in a home renovation project, working with grout.  Although the formulation is simple and may be duplicated, the process of manufacturing is complicated.

Kislauskis: So it’s your trade secret.

Wu: Absolutely.

Kislauskis: Can you summary its other advantages and your plans to commercialize the PowerStent®?

Wu: Preclinical, short duration (30 day) studies in porcine models with the PowerStent® Absorb deployed indicate that it will be non-inferior to the current metal DES and competing biodegradable stent technologies. Important functional attributes of the BioDe® polymer include better biocompatibility (less inflammatory), excellent radial strength, potent anti-restenosis activity, and a unique microporous surface that promotes integration into neointimal layer of stented vessel.  Ongoing and much longer duration studies may also support our contention that this design can reduce risks of late-stage in-stent thrombosis.

Kislauskis: What path and difficulties to you foresee in obtaining a regulatory approval to conduct clinical trials with the PowerStent® Absorb?

Wu:  FDA Guidance to commercialize conventional DES technology is available. Unfortunately, no guidance is published for a fully-biodegradable stent.  Therefore, I anticipate seeking advice from the regulatory bodies prior to petitioning for approval to perform clinical trials.  It will no doubt be a complicated process as this technology involves a novel drug combination (albeit FDA-approved drugs), and a novel formulation (albeit FDA-approved components), and a novel indwelling and bioabsorbable medical device (stent).  We are presently completing several required engineering studies for the final phase of pre-clinical safety and efficacy testing, in China. The goals are to obtain FDA pre-market and NDA approvals, and to receive a CE mark from major international markets including Europe and the BRICK nations.

Kislauskis: How will you commercialize this 3rd generation, fully-biodegradable stent?

Wu: There are likely 3 scenarios to complete development and commercialization.  One involves securing bridge funding from the NIH SBIR program, supplemented with angel financing to complete preclinical program. I project that a minimum of $6 Million (USD) will be required to complete regulatory approval and pivotal clinical trials.  Therefore, it is conceivable that a Series A round of equity financing from venture capitalists, in either US or China, will be required. A third scenario is to partner or sell the technology to a major player in this space to complete clinical testing and commercialization. Potential partners include Boston Scientific Company, J&J, etc. Any of these partners could facilitate the processes of regulatory approval, manufacturing, global distribution and marketing.  Discussions are underway with one such prospective partner and with several VC groups.

Kislauskis: What is its likely impact of this product on patient care and the field of interventional cardiology?

Wu: According to US statistics, approximately 14 million Americans suffer from CAD, and 500,000 people die from acute myocardial infarction. One million more survive but with a 1.5 to 15 times greater risk of mortality or morbidity than the rest of the population each year.  In the U.S., the annual health care costs of CAD are estimated to be in excess of $112 billion, and the estimated annual total direct cost associated with PCI with stents is over $2 billion.  I anticipate that our PowerStent® Absorb stent will be competitive in a marketplace estimated to be over $5 billion in 2010. Although CAD patients are the primary market, other related applications for our PowerStent Absorb technology include peripheral arteries, intracerebral vascular and small vessels which are also significant.

Kislauskis:  Thank you for your contribution to this site.  For more information about MMG, LLC and Dr. Wu’s technology please refer to his publications 9-13 or contact him directly at tiangenwu@yahoo.com.

REFERENCES

1.   Mark A. Hlatky, M.D. Compelling Evidence for Coronary-Bypass Surgery in Patients with Diabetes.   N Engl J Med 2012; 367:2437-2438.

2.  Stamler, J. (1989) Epidemiology.  Established major risk factors, and the primary prevention of coronary heart disease. In: Chatterjee K, Karliner J, Rapaport E, Cheitlin MD, Parmlee WW, Sheinman, M eds. Cardiology, Philadelphia Penn: JB Lippincott, 1991, 7.2-7.35. (volume 2).

3. Tanabe, K, Regar, E et al.  Sirolimus-eluting stent for treatment of in-stentrestenosis: One-year angiographic and intravascular ultrasound follow-up. J. Am Col.Cardi.   (2003) 41: 12A.

4. Grube, Eberhard;  Silber, Sigmund.  Six- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation 2003: 107, 38-42.

5.  Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126–2130.

6.  Ong AT, McFadden EP, Regar E, et al. Late angiographic stent thrombosis (LAST) events with drug-eluting stents. J Am Coll Cardiol 2005;45:2088–2092.

7. Wang F, Stouffer GA, Waxman S, et al. Late coronary stent thrombosis: Early vs late stent thrombosis in the stent era. Catheter Cardiovasc Interven 2002;55:142–147.

8. McFadden EP, Stabile E, Regar E, et al. Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 2004;364:1519–1521.

9. Ma X, Oyamada S, Wu T, Robich MP, Wu H, Wang X, Buchholz B, McCarthy S, Bianchi CF, Sellke FW, Laham R. In vitro and in vivo degradation of poly(D, L-lactide-co-glycolide)/amorphous calcium phosphate copolymer coated on metal stents. J Biomed Mater Res A. 2011 Mar 15;96(4):632-8. doi: 10.1002/jbm.a.33016. Epub 2011 Jan 25.

10. Oyamada S, Ma X, Wu T, Robich MP, Wu H, Wang X, Buchholz B, McCarthy S, Bianchi CF, Sellke FW, Laham R. Trans-iliac rat aorta stenting: a novel high throughput preclinical stent model for restenosis and thrombosis. J Surg Res. 2011 Mar;166(1):e91-5. Erratum in: J Surg Res. 2012 May 1;174(1):184.

11. Ma X, Oyamada S, Gao F, Wu T, Robich MP, Wu H, Wang X, Buchholz B, McCarthy S, Gu Z, Bianchi CF, Sellke FW, Laham R Paclitaxel/sirolimus combination coated drug-eluting stent: in vitro and in vivo drug release studies. J Pharm Biomed Anal. 2011 Mar 25;54(4):807-11. Erratum in: J Pharm Biomed Anal. 2012 Feb 5;59:217.

12. Ma X, Wu T, Robich MP, Wang X, Wu H, Buchholz B, McCarthy S. Drug-eluting stents. Int J Clin Exp Med. 2010 Jul 15;3(3):192-201.

Other articles related to this subject were published in this Open Access OnlIne Scientific Journal:

Lev-Ari, A. (2012aa). Renal Sympathetic Denervation: Updates on the State of Medicine

http://pharmaceuticalintelligence.com/2012/12/31/renal-sympathetic-denervation-updates-on-the-state-of-medicine/

 

Lev-Ari, A. (2012U). Imbalance of Autonomic Tone: The Promise of Intravascular Stimulation of Autonomics

http://pharmaceuticalintelligence.com/2012/09/02/imbalance-of-autonomic-tone-the-promise-of-intravascular-stimulation-of-autonomics/

Lev-Ari, A. (2012R). Coronary Artery Disease – Medical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents http://pharmaceuticalintelligence.com/2012/08/13/coronary-artery-disease-medical-devices-solutions-from-first-in-man-stent-implantation-via-medical-ethical-dilemmas-to-drug-eluting-stents/

 

Lev-Ari, A. (2012K). Percutaneous Endocardial Ablation of Scar-Related Ventricular Tachycardia

http://pharmaceuticalintelligence.com/2012/07/18/percutaneous-endocardial-ablation-of-scar-related-ventricular-tachycardia/

 

Lev-Ari, A. (2012C). Treatment of Refractory Hypertension via Percutaneous Renal Denervation

http://pharmaceuticalintelligence.com/2012/06/13/treatment-of-refractory-hypertension-via-percutaneous-renal-denervation/

Lev-Ari, A. (2012D). Competition in the Ecosystem of Medical Devices in Cardiac and Vascular Repair: Heart Valves, Stents, Catheterization Tools and Kits for Open Heart and Minimally Invasive Surgery (MIS)

http://pharmaceuticalintelligence.com/2012/06/22/competition-in-the-ecosystem-of-medical-devices-in-cardiac-and-vascular-repair-heart-valves-stents-catheterization-tools-and-kits-for-open-heart-and-minimally-invasive-surgery-mis/

Lev-Ari, A. (2012E). Executive Compensation and Comparator Group Definition in the Cardiac and Vascular Medical Devices Sector: A Bright Future for Edwards Lifesciences Corporation in the Transcatheter Heart Valve Replacement Market

http://pharmaceuticalintelligence.com/2012/06/19/executive-compensation-and-comparator-group-definition-in-the-cardiac-and-vascular-medical-devices-sector-a-bright-future-for-edwards-lifesciences-corporation-in-the-transcatheter-heart-valve-replace/

 

Lev-Ari, A. (2012F). Global Supplier Strategy for Market Penetration & Partnership Options (Niche Suppliers vs. National Leaders) in the Massachusetts Cardiology & Vascular Surgery Tools and Devices Market for Cardiac Operating Rooms and Angioplasty Suites

http://pharmaceuticalintelligence.com/2012/06/22/global-supplier-strategy-for-market-penetration-partnership-options-niche-suppliers-vs-national-leaders-in-the-massachusetts-cardiology-vascular-surgery-tools-and-devices-market-for-car/

 

Lev-Ari, A. (2012G).  Heart Remodeling by Design: Implantable Synchronized Cardiac Assist Device: Abiomed’s Symphony

http://pharmaceuticalintelligence.com/2012/07/23/heart-remodeling-by-design-implantable-synchronized-cardiac-assist-device-abiomeds-symphony/

 

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FDA Guidelines For Developmental and Reproductive Toxicology (DART) Studies for Small Molecules

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, BioSimilars, Chemical Biology and its relations to Metabolic Disease, Disease Biology, Small Molecules in Development of Therapeutic Drugs, FDA Regulatory Affairs, Health Economics and Outcomes Research, Health Law & Patient Safety, Pharmaceutical Industry Competitive Intelligence, Population Health Management, Genetics & Pharmaceutical, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Reproductive Biology & Bio Instrumentation, Uncategorized, tagged , , , , , , , , , , , , , on November 20, 2012| 3 Comments »

FDA Guidelines For Developmental and Reproductive Toxicology (DART) Studies for Small Molecules. Author-Writer: Stephen J. Williams, Ph.D.

This posting is a follow-up on the Report on the Fall Mid-Atlantic Society of Toxicology Meeting “Reproductive Toxicology of Biologics: Challenges and Considerations post and gives a brief synopsis of the current state of FDA regulatory guidelines with respect to DART studies on small molecule (non-biological based) therapeutics.    The following is adapted from the book Principles and Methods of Toxicology by Dr. A Wallace Hayes (1) and is an excellent reference on reproductive toxicology and testing methods.

Chemical insult occurs to the human reproductive system at a multitude of stages in development and the life cycle, leading to the extensive testing which must be performed to diligently the reproductive and development toxicity of a chemical/drug.  Abnormalities and toxic manifestations in the offspring may result from insult to the adult reproductive (either female or male) and neuroendocrine systems, as well as damage to the embryo resulting in embryolethality, fetus at any period during organogenesis, juvenile development or, in the case of certain antibody therapies, immune system development.  The latter, toxic insult to the developing immune system could possibly be manifested as either an immune defect in the newborn or, later in life, as tolerance to said therapy.  It is estimated that exposure to the pregnant woman, of either environmental contaminants or drug, is significant.  It is estimated that a mother may be taking an average of 8-9 different drug preparations, mostly over the counter preparations such as antacids, vitamin preparations, cathartics etc. with the maximal drug intake occurring between 24 and 36 weeks of gestation.

Toxic insult to the developing embryo is dependent on

  • Fetal development stage during drug/chemical exposure
  • Maternal/placental xenobiotic metabolism
  • Pharmacokinetic parameters affecting bioavailability and fetal/maternal drug binding

The following table shows the dependency of developmental stage to teratogenicity: adapted from J. Manson, H. Zenick, and R.D. Costlow from Principles and Methods of Toxicology.

Developmental Stage Major Susceptibility
Preimplantation Embryolethality
Organogenesis Births defects; embryolethality
Fetal Growth retardation, fetal death, functional deficits
Neonatal Growth retardation, nervous system alterations, immune and endocrine systems

It is not generally accepted that there is a dose dependency of teratogenesis however most teratogens have specific mechanisms of action and teratogenic effects occur at much lower doses than result in maternal toxicity.   However, the developmental toxicity may be manifested later in life, including as reproductive toxicity affecting adult fertility and familial generations.

FDA Guidelines for DART Studies on Non-Biologics (Small Molecule Therapeutics)

The basic design for DART studies incorporate the aforementioned principles of tetralogy:

  • developmental stage of fetal exposure
  • parental effects on reproduction and development
  • toxicity may be manifested over multiple generations including fertility rates

Therefore two designs are generally used for DART studies

  1. exposure across several generations
  2. exposure during one generation

FDA requires one control group and two treatment groups, and evaluation of at least two species.  However, most studies will use two rodent and one nonrodent species.

Multigenerational Design

Multigenerational DART studies are conducted for compounds likely to concentrate in the body following long-term exposure.  Examples of types of compounds include pesticides and food additives.

Figure 1.  General Design of a Multigenerational DART study.  Weanlings (30-30 days of age) from the parental generation are treated for a period up to 60 days. At 100-120 days of parental generation, animals are mated.  Fx = filialx .

Three Segment, Single Generation Tests

The single generation design is more suitable for DART studies on drugs, as most therapeutic would be taken over short periods (during pregnancy) and have relatively short half-lives in the body.  FDA guidelines separate these studies in three phases:

I.            Phase I: evaluation of fertility and general reproductive performance

II.            Phase II: assessment of teratogenicity and embryotoxicity

III.            Phase III: peri- and postnatal evaluations.

All figures are adapted from Principles and Methods of Toxicology.(1)

FDA guidelines Guidance for Industry Reproductive and Developmental Toxicities —Integrating Study Results to Assess Concerns can be found at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm079240.pdf

FDA Guideline for reproductive toxicity testing for small molecule therapeutics can be found at:

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm074950.pdf

1.            Hayes, A. W. (1986) Principles and Methods of Toxicology, Raven Press, New York

Other research papers on Pharmaceutical Intelligence and Reproductive Biology, Bio Insrumentation, Endocrinology Genetics were published on this Scientific Web site as follows

Non-small Cell Lung Cancer drugs – where does the Future lie?

Reboot evidence-based medicine and reconsider the randomized, placebo-controlled clinical trial

Every sperm is sacred: Sequencing DNA from individual cells vs “humans as a whole.”

Leptin and Puberty

Gene Trap Mutagenesis in Reproductive Research

Genes involved in Male Fertility and Sperm-egg Binding

Hope for Male Contraception: A small molecule that inhibits a protein important for chromatin organization can cause reversible sterility in male mice

Pregnancy with a Leptin-Receptor Mutation

The contribution of comparative genomic hybridization in reproductive medicine

Sperm collide and crawl the walls in chaotic journey to the ovum

Impact of evolutionary selection on functional regions: The imprint of evolutionary selection on ENCODE regulatory elements is manifested between species and within human populations

Biosimilars: CMC Issues and Regulatory Requirements

Biosimilars: Intellectual Property Creation and Protection by Pioneer and by Biosimilar Manufacturers

Assisted Reproductive Technology Cycles and Cumulative Birth Rates

Innovations in Bio instrumentation in Reproductive Clinical and Male Fertility Labs in the US

Increased risks of obesity and cancer, Decreased risk of type 2 diabetes: The role of Tumor-suppressor phosphatase and tensin homologue (PTEN)

Guidelines for the welfare and use of animals in cancer research

Every sperm is sacred: Sequencing DNA from individual cells vs “humans as a whole.”

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Today’s fundamental challenge in Prostate cancer screening

Posted in Imaging-based Cancer Patient Management, tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , on September 2, 2012| 12 Comments »

Today’s fundamental challenge in Prostate cancer screening

Author and Curator: Dror Nir, PhD

Article 8.2.Todays fundamental challenge in Prostate cancer screening

The management of men with prostate cancer is becoming one of the most challenging public health issues in the Western world. It is characterized by: over-diagnosis; over-treatment; low treatment efficacy; treatment related toxicity; escalating cost; and unsustainability [Bangma et al, 2007; Esserman et al, 2009]. How come? Well, everyone accepts that most prostate cancers are clinically insignificant. It is well known that all men above 65 harbor some sort of prostate cancer. Due to the current aggressive PSA-based screening, one in six men will be diagnosed with prostate cancer. Yet, the lifetime risk of dying of prostate cancer is only 3%. The problem is that, once diagnosed with prostate cancer, there is no accurate tool to identify those men that will die of the disease (in my previous post I mentioned 1:37). Currently, screening practices for prostate cancer are relying on the very unspecific prostate-specific-antigen (PSA) bio-marker test to determine which men are at higher risk of harboring prostate cancer and therefore need a biopsy. The existing diagnostic test is a transrectal ultrasound (TRUS) guided prostate biopsy aimed at extracting representative tissue from areas where cancer usually resides. This procedure suffers from several obvious faults:

1. Since the imaging tool used (B-mode ultrasound) is poor at detecting malignancies in the prostate, the probability of hitting a clinically significant cancer or missing a clinically insignificant cancer is subject to random error.

2. TRUS biopsy is also subjected to systematic error as it misses large parts of the prostate which might harbor cancer (e.g. apex and anterior zones).
3. TRUS guided biopsies are often unrepresentative of the true burden of cancer as either the volume or grade of cancer can be underestimated.

In the last ten years I was leading the development of an innovative ultrasound-based technology, HistoScanningTM, aimed at improving the aforementioned faults;

Among the other most popular imaging modalities aimed at better prostate cancer detection in routine use are: MRI, Elastography, Contrast Enhanced Ultrasound etc…

In my future posts I will go into more detail on how these imaging modalities fit into routine workflow, how much they stay within budget constraints and what level of promise they bear for promoting personalized medicine. Stay tuned… Footnote: According to the final report by an advisory panel to the USA government: Doctors should no longer offer the PSA prostate cancer screening test to healthy men because they’re more likely to be harmed by the blood draw, and the chain of medical interventions that often follows than be helped; (http://www.usatoday.com/news/health/story/2012-05-21/prostate-cancer-screening-test-harmful/55118036/1) But then; what should be offered instead?

Other posts on this Scientific Website addressing Prostate Cancer

Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?

http://pharmaceuticalintelligence.com/2012/07/31/prostate-cancers-plunged-after-uspstf-guidance-will-it-happen-again/

New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

http://pharmaceuticalintelligence.com/2012/05/27/new-prostate-cancer-screening-guidelines-face-a-tough-sell-study-suggests/

ROLE OF VIRAL INFECTION IN PROSTATE CANCER

http://pharmaceuticalintelligence.com/2012/09/01/role-of-viral-infection-in-prostate-cancer/

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Know How We ALL, Knowingly or Unknowingly, Consume Antibiotics and How it Effects Our Health

Posted in Infectious Disease & New Antibiotic Targets, tagged , , , , , , , on August 29, 2012| 3 Comments »

 

Curated and Reported by: Dr. Venkat S. Karra, Ph.D.

Know How We ALL Knowingly or Unknowingly Consume Antibiotics and How it Effects Our Health

Billions of microbial cells live in the guts of humans and other animals. Research on these vast bacterial populations, called microbiomes, is just getting started, but scientists already know that some microbial boarders play a crucial role in breaking down nutrients in our diet. Some have also suspected that low-dose antibiotics, given to farm animals to make them grow bigger, could work by altering the gut microbiome.

To test this hypothesis, a team led by microbiologist Martin Blaser of the New York University School of Medicine in New York City added antibiotics to the drinking water of mice that had just been weaned. The medicine—either penicillin, vancomycin, a combination of the two, or chlortetracycline—was given at doses comparable to those approved by the U.S. Food and Drug Administration as growth promoters in farm animals. After 7 weeks, the group of mice on antibiotics had significantly more fat than a control group drinking plain water, the team reports online today in Nature. “This confirms what farmers have shown for 60 years, that low-dose antibiotics cause their animals to grow bigger,” Blaser says.

Read more at:  The Global Innovations

Now, Researchers at the University of Copenhagen, Denmark, and University College Cork, Ireland, found that antibiotic concentrations within limits set by US and European Union (EU) regulators are high enough to slow fermentation, the process that acidifies the sausages and helps destroy foodborne pathogens like Salmonella or E. coli.

“At low concentrations and at regulatory levels set by authorities, they could see that the lactic acid bacteria are more susceptible to the antibiotics than the pathogens are.

“Residual antibiotics in the meat can prevent or reduce fermentation by the lactic acid bacteria, but these concentrations do not effect survival or even multiplication of pathogens.”

Antibiotics used as growth promoters or to treat disease in livestock can eventually end up in meat, and regulators in the US and EU have set limits on the concentrations of antibiotics in meat for consumption by humans.

Researchers say that fermented sausages occasionally cause serious bacterial infections, but it’s never been understood why that might be….

Read more at: sciencecodex

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Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections: an update to CDC’s 2010 STD guidelines

Posted in Infectious Disease & New Antibiotic Targets, tagged , , , , , , , , , , , , , , , on August 28, 2012| 1 Comment »

Reported by: Dr. Venkat S. Karra, Ph.D.

Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections: an update to CDC‘s 2010 STD guidelines.

Gonorrhea is a major cause of serious reproductive complications in women and can facilitate human immunodeficiency virus (HIV) transmission (1). Effective treatment is a cornerstone of U.S. gonorrhea control efforts, but treatment of gonorrhea has been complicated by the ability of Neisseria gonorrhoeae to develop antimicrobial resistance. This report, using data from CDC’s Gonococcal Isolate Surveillance Project (GISP), describes laboratory evidence of declining cefixime susceptibility among urethral N. gonorrhoeae isolates collected in the United States during 2006–2011 and updates CDC’s current recommendations for treatment of gonorrhea (2). Based on GISP data, CDC recommends combination therapy with ceftriaxone 250 mg intramuscularly and either azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days as the most reliably effective treatment for uncomplicated gonorrhea. CDC no longer recommends cefixime at any dose as a first-line regimen for treatment of gonococcal infections. If cefixime is used as an alternative agent, then the patient should return in 1 week for a test-of-cure at the site of infection.

Infection with N. gonorrhoeae is a major cause of pelvic inflammatory disease, ectopic pregnancy, and infertility, and can facilitate HIV transmission (1). In the United States, gonorrhea is the second most commonly reported notifiable infection, with >300,000 cases reported during 2011. Gonorrhea treatment has been complicated by the ability of N. gonorrhoeae to develop resistance to antimicrobials used for treatment. During the 1990s and 2000s, fluoroquinolone resistance in N. gonorrhoeae emerged in the United States, becoming prevalent in Hawaii and California and among men who have sex with men (MSM) before spreading throughout the United States. In 2007, emergence of fluoroquinolone-resistant N. gonorrhoeae in the United States prompted CDC to no longer recommend fluoroquinolones for treatment of gonorrhea, leaving cephalosporins as the only remaining recommended antimicrobial class (3). To ensure treatment of co-occurring pathogens (e.g., Chlamydia trachomatis) and reflecting concern about emerging gonococcal resistance, CDC’s 2010 sexually transmitted diseases (STDs) treatment guidelines recommended combination therapy for gonorrhea with a cephalosporin (ceftriaxone 250 mg intramuscularly or cefixime 400 mg orally) plus either azithromycin orally or doxycycline orally, even if nucleic acid amplification testing (NAAT) for C. trachomatis was negative at the time of treatment (2). From 2006 to 2010, the minimum concentrations of cefixime needed to inhibit the growth in vitro of N. gonorrhoeae strains circulating in the United States and many other countries increased, suggesting that the effectiveness of cefixime might be waning (4). Reports from Europe recently have described patients with uncomplicated gonorrhea infection not cured by treatment with cefixime 400 mg orally (5–8).

GISP is a CDC-supported sentinel surveillance system that has monitored N. gonorrhoeae antimicrobial susceptibilities since 1986, and is the only source in the United States of national and regional N. gonorrhoeae antimicrobial susceptibility data. During September–December 2011, CDC and five external GISP principal investigators, each with N. gonorrhoeae–specific expertise in surveillance, antimicrobial resistance, treatment, and antimicrobial susceptibility testing, reviewed antimicrobial susceptibility trends in GISP through August 2011 to determine whether to update CDC’s current recommendations (2) for treatment of uncomplicated gonorrhea. Each month, the first 25 gonococcal urethral isolates collected from men attending participating STD clinics (approximately 6,000 isolates each year) were submitted for antimicrobial susceptibility testing. The minimum inhibitory concentration (MIC), the lowest antimicrobial concentration that inhibits visible bacterial growth in the laboratory, is used to assess antimicrobial susceptibility. Cefixime susceptibilities were not determined during 2007–2008 because cefixime temporarily was unavailable in the United States at that time. Criteria for resistance to cefixime and ceftriaxone have not been defined by the Clinical Laboratory Standards Institute (CLSI). However, CLSI does consider isolates with cefixime or ceftriaxone MICs ≥0.5 µg/mL to have “decreased susceptibility” to these drugs (9). During 2006–2011, 15 (0.1%) isolates had decreased susceptibility to cefixime (all had MICs = 0.5 µg/mL), including nine (0.2%) in 2010 and one (0.03%) during January–August 2011; 12 of 15 were from MSM, and 12 were from the West and three from the Midwest.* No isolates exhibited decreased susceptibility to ceftriaxone. Because increasing MICs can predict the emergence of resistance, lower cephalosporin MIC breakpoints were established by GISP for surveillance purposes to provide greater sensitivity in detecting declining gonococcal susceptibility than breakpoints defined by CLSI. Cefixime MICs ≥0.25 µg/mL and ceftriaxone MICs ≥0.125 µg/mL were defined as “elevated MICs.” CLSI does not define azithromycin resistance criteria; CDC defines decreased azithromycin susceptibility as ≥2.0 µg/mL.

Evidence and Rationale

The percentage of isolates with elevated cefixime MICs (MICs ≥0.25 µg/mL) increased from 0.1% in 2006 to 1.5% during January–August 2011 (Figure). In the West, the percentage increased from 0.2% in 2006 to 3.2% in 2011 (Table). The largest increases were observed in Honolulu, Hawaii (0% in 2006 to 17.0% in 2011); Minneapolis, Minnesota (0% to 6.9%); Portland, Oregon (0% to 6.5%); and San Diego, California (0% to 6.4%). Nationally, among MSM, isolates with elevated MICs to cefixime increased from 0.2% in 2006 to 3.8% in 2011. In 2011, a higher proportion of isolates from MSM had elevated cefixime MICs than isolates from men who have sex exclusively with women (MSW), regardless of region (Table).

The percentage of isolates exhibiting elevated ceftriaxone MICs increased slightly, from 0% in 2006 to 0.4% in 2011 (Figure). The percentage increased from <0.1% in 2006 to 0.8% in 2011 in the West, and did not increase significantly in the Midwest (0% to 0.2%) or the Northeast and South (0.1% in 2006 and 2011). Among MSM, the percentage increased from 0.0% in 2006 to 1.0% in 2011.

The 2010 CDC STD treatment guidelines (2) recommend that azithromycin or doxycycline be administered with a cephalosporin as treatment for gonorrhea. The percentage of isolates exhibiting tetracycline resistance (MIC ≥2.0 µg/mL) was high but remained stable from 2006 (20.6%) to 2011 (21.6%). The percentage exhibiting decreased susceptibility to azithromycin (MIC ≥2.0 µg/mL) remained low (0.2% in 2006 to 0.3% in 2011). Among 180 isolates collected during 2006–2011 that exhibited elevated cefixime MICs, 139 (77.2%) exhibited tetracycline resistance, but only one (0.6%) had decreased susceptibility to azithromycin.

Ceftriaxone as a single intramuscular injection of 250 mg provides high and sustained bactericidal levels in the blood and is highly efficacious at all anatomic sites of infection for treatment of N. gonorrhoeae infections caused by strains currently circulating in the United States (10,11). Clinical data to support use of doses of ceftriaxone >250 mg are not available. A 400-mg oral dose of cefixime does not provide bactericidal levels as high, nor as sustained as does an intramuscular 250-mg dose of ceftriaxone, and demonstrates limited efficacy for treatment of pharyngeal gonorrhea (10,11). The significant increase in the prevalence of U.S. GISP isolates with elevated cefixime MICs, most notably in the West and among MSM, is of particular concern because the emergence of fluoroquinolone-resistant N. gonorrhoeae in the United States during the 1990s also occurred initially in the West and predominantly among MSM before spreading throughout the United States within several years. Thus, observed patterns might indicate early stages of the development of clinically significant gonococcal resistance to cephalosporins. CDC anticipates that rising cefixime MICs soon will result in declining effectiveness of cefixime for the treatment of urogenital gonorrhea. Furthermore, as cefixime becomes less effective, continued use of cefixime might hasten the development of resistance to ceftriaxone, a safe, well-tolerated, injectable cephalosporin and the last antimicrobial that is recommended and known to be highly effective in a single dose for treatment of gonorrhea at all anatomic sites of infection. Maintaining effectiveness of ceftriaxone for as long as possible is critical. Thus, CDC no longer recommends the routine use of cefixime as a first-line regimen for treatment of gonorrhea in the United States.

Based on experience with other microbes that have developed antimicrobial resistance rapidly, a theoretical basis exists for combination therapy using two antimicrobials with different mechanisms of action to improve treatment efficacy and potentially delay emergence and spread of resistance to cephalosporins. Therefore, the use of a second antimicrobial (azithromycin as a single 1-g oral dose or doxycycline 100 mg orally twice daily for 7 days) is recommended for administration with ceftriaxone. The use of azithromycin as the second antimicrobial is preferred to doxycycline because of the convenience and compliance advantages of single-dose therapy and the substantially higher prevalence of gonococcal resistance to tetracycline than to azithromycin among GISP isolates, particularly in strains with elevated cefixime MICs.

Recommendations

For treatment of uncomplicated urogenital, anorectal, and pharyngeal gonorrhea, CDC recommends combination therapy with a single intramuscular dose of ceftriaxone 250 mg plus either a single dose of azithromycin 1 g orally or doxycycline 100 mg orally twice daily for 7 days (Box).

Clinicians who diagnose gonorrhea in a patient with persistent infection after treatment (treatment failure) with the recommended combination therapy regimen should culture relevant clinical specimens and perform antimicrobial susceptibility testing of N. gonorrhoeae isolates. Phenotypic antimicrobial susceptibility testing should be performed using disk diffusion, Etest (BioMérieux, Durham, NC), or agar dilution. Data currently are limited on the use of NAAT-based antimicrobial susceptibility testing for genetic mutations associated with resistance in N. gonorrhoeae. The laboratory should retain the isolate for possible further testing. The treating clinician should consult an infectious disease specialist, an STD/HIV Prevention Training Center (http://www.nnptc.orgExternal Web Site Icon), or CDC (telephone: 404-639-8659) for treatment advice, and report the case to CDC through the local or state health department within 24 hours of diagnosis. A test-of-cure should be conducted 1 week after re-treatment, and clinicians should ensure that the patient’s sex partners from the preceding 60 days are evaluated promptly with culture and treated as indicated.

When ceftriaxone cannot be used for treatment of urogenital or rectal gonorrhea, two alternative options are available: cefixime 400 mg orally plus either azithromycin 1 g orally or doxycycline 100 mg twice daily orally for 7 days if ceftriaxone is not readily available, or azithromycin 2 g orally in a single dose if ceftriaxone cannot be given because of severe allergy. If a patient with gonorrhea is treated with an alternative regimen, the patient should return 1 week after treatment for a test-of-cure at the infected anatomic site. The test-of-cure ideally should be performed with culture or with a NAAT for N. gonorrhoeae if culture is not readily available. If the NAAT is positive, every effort should be made to perform a confirmatory culture. All positive cultures for test-of-cure should undergo phenotypic antimicrobial susceptibility testing. Patients who experience treatment failure after treatment with alternative regimens should be treated with ceftriaxone 250 mg as a single intramuscular dose and azithromycin 2 g orally as a single dose and should receive infectious disease consultation. The case should be reported to CDC through the local or state health department.

For all patients with gonorrhea, every effort should be made to ensure that the patients’ sex partners from the preceding 60 days are evaluated and treated for N. gonorrhoeae with a recommended regimen. If a heterosexual partner of a patient cannot be linked to evaluation and treatment in a timely fashion, then expedited partner therapy should be considered, using oral combination antimicrobial therapy for gonorrhea (cefixime 400 mg and azithromycin 1 g) delivered to the partner by the patient, a disease investigation specialist, or through a collaborating pharmacy.

The capacity of laboratories in the United States to isolate N. gonorrhoeae by culture is declining rapidly because of the widespread use of NAATs for gonorrhea diagnosis, yet it is essential that culture capacity for N. gonorrhoeae be maintained to monitor antimicrobial resistance trends and determine susceptibility to guide treatment following treatment failure. To help control gonorrhea in the United States, health-care providers must maintain the ability to collect specimens for culture and be knowledgeable of laboratories to which they can send specimens for culture. Health-care systems and health departments must support access to culture, and laboratories must maintain culture capacity or develop partnerships with laboratories that can perform culture.

Treatment of patients with gonorrhea with the most effective therapy will limit the transmission of gonorrhea, prevent complications, and likely will slow emergence of resistance. However, resistance to cephalosporins, including ceftriaxone, is expected to emerge. Reinvestment in gonorrhea prevention and control is warranted. New treatment options for gonorrhea are urgently needed.

Reported by

Carlos del Rio, MD, Rollins School of Public Health, Emory Univ, Atlanta, Georgia. Geraldine Hall, PhD, Dept of Clinical Pathology, Cleveland Clinic, Cleveland, Ohio. King Holmes, MD, Olusegun Soge, PhD, Dept of Medicine, Univ of Washington. Edward W. Hook, MD, Div of Infectious Diseases, Univ of Alabama at Birmingham. Robert D. Kirkcaldy, MD, Kimberly A. Workowski, MD, Sarah Kidd, MD, Hillard S. Weinstock, MD, John R. Papp, PhD, David Trees, PhD, Thomas A. Peterman, MD, Gail Bolan, MD, Div of Sexually Transmitted Diseases Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC.Corresponding contributor: Robert D. Kirkcaldy, rkirkcaldy@cdc.gov, 404-639-8659.

Acknowledgments

Collaborating state and local health departments. Baderinwa Offut, Emory Univ, Atlanta, Georgia. Laura Doyle, Cleveland Clinic, Ohio. Connie Lenderman, Paula Dixon, Univ of Alabama at Birmingham. Karen Winterscheid, Univ of Washington, Seattle. Tamara Baldwin, Elizabeth Delamater, Texas Dept of State Health Svcs. Alesia Harvey, Tremeka Sanders, Samera Bowers, Kevin Pettus, Div of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC.

References

  1. Fleming D, Wasserheit J. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999;75:3–17.
  2. CDC. Sexually transmitted diseases treatment guidelines, 2010. MMWR 2010;59(No. RR-12).
  3. CDC. Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR 2007;56:332–6.
  4. CDC. Cephalosporin susceptibility among Neisseria gonorrhoeae isolates—United States, 2000–2010. MMWR 2011;60:873–7.
  5. Unemo M, Golparian D, Syversen G, Vestrheim DF, Moi H. Two cases of verified clinical failures using internationally recommended first-line cefixime for gonorrhea treatment, Norway, 2010. Euro Surveill 2010;15(47):pii:19721.
  6. Ison C, Hussey J, Sankar K, Evans J, Alexander S. Gonorrhea treatment failures to cefixime and azithromycin in England, 2010. Euro Surveill 2011;16(14):pii:19833.
  7. Unemo M, Golparian D, Stary A, Eigentler A. First Neisseria gonorrhoeae strain with resistance to cefixime causing gonorrhea treatment failure in Austria, 2011. Euro Surveill 2011;16(43):pi:19998.
  8. Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A, Sednaoui P. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother 2012;56:1273–80.
  9. National Committee for Clinical Laboratory Standards. Approved Standard M100-S20 performance standards for antimicrobial susceptibility testing; twentieth informational supplement. Wayne, PA: Clinical and Laboratory Standards Institute; 2010.
  10. Moran JS, Levine WC. Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin Infect Dis 1995;20(Suppl 1):S47–65.
  11. Handsfield HH, McCormack WM, Hook EW 3rd, et al. A comparison of single-dose cefixime with ceftriaxone as treatment for uncomplicated gonorrhea. The Gonorrhea Treatment Study Group. New Engl J Med 1991;325:1337–41.

* U.S. Census regions. Northeast: Connecticut, Maine, Massachusetts, New Jersey, New Hampshire, New York, Pennsylvania, Rhode Island, and Vermont; Midwest: Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; South:Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, New Mexico, Nevada, Oregon, Utah, Washington, and Wyoming.

TABLE. Percentage of urethral Neisseria gonorrhoeae isolates with elevated cefixime MICs (≥0.25 µg/mL), by U.S. Census region and gender of sex partner — Gonococcal Isolate Surveillance Project, United States, 2006–August 2011
Region 2006 2009 2010 2011*
% (95% CI) % (95% CI) % (95% CI) % (95% CI)
West† (total) 0.2 (0.1–0.4) 1.9 (1.4–2.6) 3.3 (2.6–4.0) 3.2 (2.3–4.2)
MSM 0.1 (0.0–0.6) 2.6 (1.7–3.8) 5.0 (3.8–6.5) 4.5 (3.1–6.3)
MSW 0.2 (0.0–0.6) 1.4 (0.7–2.3) 1.3 (0.7–2.2) 1.8 (0.9–3.1)
Midwest§ (total) 0.0 (0.0–0.3) 0.5 (0.2–1.0) 0.5 (0.2–1.1) 0.6 (0.2–1.5)
MSM 0.0 (0.0–2.8) 2.3 (0.6–5.7) 3.4 (1.1–7.7) 4.9 (1.4–12.2)
MSW 0.0 (0.0–0.3) 0.3 (0.1–0.7) 0.1 (0.0–0.6) 0.0 (0.0–0.6)
Northeast and South¶ (total) 0.1 (0.0–0.3) 0.0 (0.0–0.2) 0.1 (0.0–0.4) 0.3 (0.1–0.8)
MSM 0.6 (0.0–3.0) 0.3 (0.0–1.9) 0.9 (0.2–2.5) 1.5 (0.4–3.9)
MSW 0.0 (0.0–0.2) 0.0 (0.0–0.2) 0.0 (0.0–0.2) 0.1 (0.0–0.4)
Abbreviations: CI = confidence interval; MICs = minimum inhibitory concentrations; MSM = men who have sex with men; MSW = men who have sex exclusively with women.

* January–August 2011.

† Includes data from Albuquerque, New Mexico; Denver, Colorado; Honolulu, Hawaii; Las Vegas, Nevada; Los Angeles, California; Orange County, California; Phoenix, Arizona; Portland, Oregon; San Diego, California; San Francisco, California; and Seattle, Washington.

§ Includes data from Chicago, Illinois; Cincinnati, Ohio; Cleveland, Ohio; Detroit, Michigan; Kansas City, Missouri; and Minneapolis, Minnesota.

¶ Includes data from Atlanta, Georgia; Baltimore, Maryland; Birmingham, Alabama; Dallas, Texas; Greensboro, North Carolina; Miami, Florida; New Orleans, Louisiana; New York, New York; Oklahoma City, Oklahoma; Philadelphia, Pennsylvania; and Richmond, Virginia.

FIGURE. Percentage of urethral Neisseria gonorrhoeae isolates (n = 32,794) with elevated cefixime MICs (≥0.25 µg/mL) and ceftriaxone MICs (≥0.125 µg/mL) — Gonococcal Isolate Surveillance Project, United States, 2006–August 2011

The figure shows the percentage of Neisseria gonorrhoeae isolates (n = 32,794) with elevated cefixime MICs (≥0.25 μg/mL) and ceftriaxone MICs (≥0.125 μg/mL) in the United States during 2006-August 2011, according to the Gonococcal Isolate Surveillance Project. The percentage of isolates with elevated cefixime MICs (MICs ≥0.25 μg/mL) increased from 0.1% in 2006 to 1.5% during January-August 2011.

Abbreviation: MICs = minimum inhibitory concentrations.

* Cefixime susceptibility not tested during 2007–2008.

† January–August 2011.

Alternate Text: The figure above shows the percentage of Neisseria gonorrhoeae isolates (n = 32,794) with elevated cefixime MICs (≥0.25 μg/mL) and ceftriaxone MICs (≥0.125 μg/mL) in the United States during 2006-August 2011, according to the Gonococcal Isolate Surveillance Project. The percentage of isolates with elevated cefixime MICs (MICs ≥0.25 μg/mL) increased from 0.1% in 2006 to 1.5% during January-August 2011.

BOX. Updated recommended treatment regimens for gonococcal infections
Uncomplicated gonococcal infections of the cervix, urethra, and rectum

Recommended regimen

Ceftriaxone 250 mg in a single intramuscular dose

PLUS

Azithromycin 1 g orally in a single dose

or doxycycline 100 mg orally twice daily for 7 days*

 

Alternative regimens

If ceftriaxone is not available:

Cefixime 400 mg in a single oral dose

PLUS

Azithromycin 1 g orally in a single dose

or doxycycline 100 mg orally twice daily for 7 days*

PLUS

Test-of-cure in 1 week

 

If the patient has severe cephalosporin allergy:

Azithromycin 2 g in a single oral dose

PLUS

Test-of-cure in 1 week

 

Uncomplicated gonococcal infections of the pharynx

Recommended regimen

Ceftriaxone 250 mg in a single intramuscular dose

PLUS

Azithromycin 1 g orally in a single dose

or doxycycline 100 mg orally twice daily for 7 days*

 

* Because of the high prevalence of tetracycline resistance among Gonococcal Isolate Surveillance Project isolates, particularly those with elevated

 

NOTE: THIS IS FOR YOUR INFORMATION ONLY, BUT “NOT A MEDICAL ADVISE”.

 

source

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6131a3.htm?s_cid=mm6131a3_w

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The Incentive for “Imaging based cancer patient’ management”

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, FDA Regulatory Affairs, Health Economics and Outcomes Research, HealthCare IT, Imaging-based Cancer Patient Management, International Global Work in Pharmaceutical, Medical Devices R&D Investment, Personalized and Precision Medicine & Genomic Research, Pharmaceutical R&D Investment, Population Health Management, Genetics & Pharmaceutical, Scientist: Career considerations, Statistical Methods for Research Evaluation, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , on August 27, 2012| 15 Comments »

The Incentive for “Imaging based cancer patient’ management”

Author and Curator: Dror Nir, PhD

Article 11.1 Introduction by Dror Nir PhD

Image taken from http://www.breastthermography.com/breast_thermography_mf.htm

It is generally agreed by radiologists and oncologists that in order to provide a comprehensive work-flow that complies with the principles of personalized medicine, future cancer patients’ management will heavily rely on “smart imaging” applications. These could be accompanied by highly sensitive and specific bio-markers, which are expected to be delivered by pharmaceutical companies in the upcoming decade. In the context of this post, smart imaging refers to imaging systems that are enhanced with tissue characterization and computerized image interpretation applications. It is expected that such systems will enable gathering of comprehensive clinical information on cancer tumors, such as location, size and rate of growth.

What is the main incentive for promoting cancer patients’ management based on smart imaging? 

It promises to enable personalized cancer patient management by providing the medical practitioner with a non-invasive and non-destructive tool to detect, stage and follow up cancer tumors in a standardized and reproducible manner. Furthermore, applying smart imaging that provides valuable disease-related information throughout the management pathway of cancer patient will eventually result in reducing the growing burden of health-care costs related to cancer patients’ treatment.

Let’s briefly review the segments that are common to all cancer patients’ pathway: screening, treatment and costs.

 

Screening for cancer: It is well known that one of the important factors in cancer treatment success is the specific disease staging. Often this is dependent on when the patient is diagnosed as a cancer patient. In order to detect cancer as early as possible, i.e. before any symptoms appear, leaders in cancer patients’ management came up with the idea of screening. To date, two screening programs are the most spoken of: the “officially approved and budgeted” breast cancer screening; and the unofficial, but still extremely costly, prostate cancer screening. After 20 years of practice, both are causing serious controversies:

In trend analysis of WHO mortality data base [1], the authors, Autier P, Boniol M, Gavin A and Vatten LJ, argue that breast cancer mortality in neighboring European countries with different levels of screening but similar access to treatment is the same: “The contrast between the time differences in implementation of mammography screening and the similarity in reductions in mortality between the country pairs suggest that screening did not play a direct part in the reductions in breast cancer mortality”.

In prostate cancer mortality at 11 years of follow-up [2],  the authors,Schröder FH et. al. argue regarding prostate cancer patients’ overdiagnosis and overtreatment: “To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected”.

The lobbying campaign (see picture below)  that AdmeTech (http://www.admetech.org/) is conducting in order to raise the USA administration’s awareness and get funding to improve prostate cancer treatment is a tribute to patients’ and practitioners’ frustration.

 

 

 

Treatment: Current state of the art in oncology is characterized by a shift in  the decision-making process from an evidence-based guidelines approach toward personalized medicine. Information gathered from large clinical trials with regard to individual biological cancer characteristics leads to a more comprehensive understanding of cancer.

Quoting from the National cancer institute (http://www.cancer.gov/) website: “Advances accrued over the past decade of cancer research have fundamentally changed the conversations that Americans can have about cancer. Although many still think of a single disease affecting different parts of the body, research tells us through new tools and technologies, massive computing power, and new insights from other fields that cancer is, in fact, a collection of many diseases whose ultimate number, causes, and treatment represent a challenging biomedical puzzle. Yet cancer’s complexity also provides a range of opportunities to confront its many incarnations”.

Personalized medicine, whether it uses cytostatics, hormones, growth inhibitors, monoclonal antibodies, and loco-regional medical devices, proves more efficient, less toxic, less expensive, and creates new opportunities for cancer patients and health care providers, including the medical industry.

To date, at least 50 types of systemic oncological treatments can be offered with much more quality and efficiency through patient selection and treatment outcome prediction.

Figure taken from presentation given by Prof. Jaak Janssens at the INTERVENTIONAL ONCOLOGY SOCIETY meeting held in Brussels in October 2011

For oncologists, recent technological developments in medical imaging-guided tissue acquisition technology (biopsy) create opportunities to provide representative fresh biological materials in a large enough quantity for all kinds of diagnostic tests.

 

Health-care economics: We are living in an era where life expectancy is increasing while national treasuries are over their limits in supporting health care costs. In the USA, of the nation’s 10 most expensive medical conditions, cancer has the highest cost per person. The total cost of treating cancer in the U.S. rose from about $95.5 billion in 2000 to $124.6 billion in 2010, the National Cancer Institute (www.camcer.gov) estimates. The true sum is probably higher as this estimate is based on average costs from 2001-2006, before many expensive treatments came out; quoting from www.usatoday.com : “new drugs often cost $100,000 or more a year. Patients are being put on them sooner in the course of their illness and for a longer time, sometimes for the rest of their lives.”

With such high costs at stake, solutions to reduce the overall cost of cancer patients’ management should be considered. My experience is that introducing smart imaging applications into routine use could contribute to significant savings in the overall cost of cancer patients’ management, by enabling personalized treatment choice and timely monitoring of tumors’ response to treatment.

 

 References

  1. 1.      BMJ. 2011 Jul 28;343:d4411. doi: 10.1136/bmj.d4411
  2. 2.      (N Engl J Med. 2012 Mar 15;366(11):981-90):

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