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Archive for May, 2012

Briefing on ILSI – BioMed Conference, May 21-23, 2012 in Tel Aviv, Israel

Posted in Aortic Valve: TAVR, TAVI vs Open Heart Surgery, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, HTN, Medical Devices R&D and Inventions, Mitral Valve: Repair and Replacement, Pharmacotherapy of Cardiovascular Disease, Stents & Tools, Valves & Tools, tagged , , , , , , on May 31, 2012| Leave a Comment »

Briefing on ILSI – BioMed Conference, May 21-23, 2012 in Tel Aviv

http://www2.kenes.com/BIOMED/CONFERENCE/Pages/Detailed_Program.aspx

Reporter: Aviva Lev-Ari, PhD, RN

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CARDIOLOGY SEMINAR — I attended the following on May 21, 2012 — will report on these topics in few posts to follow.

VALVES IN TLV (two-lung ventilation)
OPENING
Dr. Francesco Maisano
Dr. Michael Mack
Dr. David Brown

STRUCTURAL HEART DISEASE
LEFT ATRIAL APPENDAGE CLOSURE; NEW TOOLS AND TECHNIQUES
Dr. William Cohn, Texas Heart Institute, Houston, Texas

“OFF LABEL” PERCUTANEOUS VALVE IMPLANTATIONS – CONSIDERATIONS, CORONARIES AND IMAGING
Dr. Elchanan Bruckheimer, Rabin Medical Center, Israel

MITRAL VALVE
EVALVE: WHERE WE ARE? WHAT EVIDENCE IS AVAILABLE AND WHAT IS MISSING
Dr. Michael Mack, Baylor Heart Hospital, Dallas, USA

OTHER MITRAL VALVE TECHNOLOGIES: HYPE OR HOPE? (MITRALIGN, GDS)
Dr. Eberhard Grube, Bonn University Germany

VALTECH CARDIO: PROVIDING THE FULL SPECTRUM FOR INTERVENTIONAL CARDIOLOGY AND SURGERY
Dr. Francesco Maisano,  HSR Milan, Italy

MITRAL VALVE REPLACEMENT: WHERE ARE WE?
Dr. Michael Mack, Baylor Heart Hospital, Dallas, USA

NEOVASC: A NEW APPROACH TO TRANSCATHETER MITRAL VALVE REPLACEMENT
Prof. Shmuel Banai, Souraski Medical Center, Israel

TEN YEARS FOR TAVI (Transcatheter Aortic-Valve Implantation) –   
LESSONS LEARNED AND WHAT IS THE FUTURE           

EDWARDS SAPIEN: BALLOON EXPANDABLE VALVES: THE GOOD, THE BAD, THE DOUBTS
Dr. David Brown, Baylor Heart Hospital, Dallas, USA

COREVALVE: THE FIRST SELF EXPANDABLE VALVE: NEW FEATURES AND FUTURE DEVELOPMENTS
Dr. Eberhard Grube, Bonn University, Germany

PORTICO SAINT JUDE: NEXT GENERATION SELF EXPANDING VALVE
Dr. Greg Fontana, Lenox Hill New York, USA

SADRA MEDICAL: THE LONG ROAD TO SUCCESS
Prof. Eberhard Grube, Bonn University Germany

DIRECT FLOW: THE VALUE OF REPOSITIONABILITY
Francesco Maisano, HSR Milan, Italy

THINKING WAY OUTSIDE THE BOX
Dr. William Cohn, Texas Heart Institute, Houston, Texas, USA

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First Epigenome in Europe Completed

Posted in Biological Networks, Gene Regulation and Evolution, CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, tagged , , , , , , on May 31, 2012| 2 Comments »

Reporter: Prabodh Kandala, PhD

A study led by Manel Esteller, director of the Epigenetics and Cancer Biology Program at the Bellvitge Biomedical Research Institute (IDIBELL), professor of genetics at the University of Barcelona and ICREA researcher has completed the first epigenome in Europe.

The finding is published in the journalEpigenetics.

The genome of all cells in the human body is the same for all of them, regardless their aspect and functions. Therefore, genome cannot fully explain the activity of tissues and organs and their disorders in complex diseases like cancer. It takes a further explanation. Part of this explanation is provided by epigenetics, a field of biology that studies the heredity activity of DNA that does not involve changes in its sequence. That is, if genetics is the alphabet, epigenetics is the spelling that guides the activity of our cells.

Methylation

Epigenetics refers to chemical changes in our genetic material and proteins that regulate it. The best-known epigenetic mark is the methylation, the addition of a methyl chemical group (-CH3) in our DNA. The epigenome consists of all the epigenetic marks of a living being. The authors of the study have completed the epigenomes for all brands of methylation of DNA from white blood cells of two girls: a healthy one and a patient suffering from a rare genetic disease called Immunodeficiency, Centromere instability and Facial anomalies syndrome (ICF). This disease is caused by a mutation in a gene that causes the addition of a methyl chemical group in its DNA.

The analysis performed by the researchers reveals that the patient has an epigenomic defect that causes fragility of chromosomes, which thus can easily be broken. In addition, the study shows that the patient has a wrong epigenetic control of many genes related to the response against infection, which causes a severe immune deficiency. The study coordinator, Manel Esteller, emphasizes that due to this study, “we now know what happens in this type of rare diseases and we can start thinking about strategies for new treatments based on this knowledge.”

Dr. Esteller’s work has been crucial to show that all human tumours have in common a specific chemical alteration: the hypermethylation of tumour suppressor genes.

Ref:

http://www.sciencedaily.com/releases/2012/05/120530133722.htm

Heyn H, Vidal E, Sayols S, Sanchez-Mut Jv, Moran S, Medina I, Sandoval J, Simó-Riudalbas L, Szczesna K, Huertas D, Gatto S, Matarazzo Mr, Dopazo J, Esteller M.Whole-genome bisulfite DNA sequencing of a DNMT3B mutant patient. Epigenetics, 2012

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New Anti-Cancer Drug Developed

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, Disease Biology, Small Molecules in Development of Therapeutic Drugs, tagged , , , , , , on May 30, 2012| 1 Comment »

Reporter: Prabodh Kandala, PhD

A team of University of Hawaii Cancer Center scientists led by James Turkson, Ph.D. have created a new type of anti-cancer drug named BP-1-102. The drug, which can be orally administered, targets a key protein that triggers the development of many types of cancer including lung, breast and skin cancers.

The development of BP-1-102 was guided by the research teams computer based molecular analysis of the cancer causing Stat 3 protein that causes cancer by promoting abnormal cell growth in otherwise healthy cells.

“The molecular structure of the hyperactive Stat3 protein basically resembles two cars that are joined together side-by-side,” said Professor Turkson. “We then utilized a computer program that creates molecular models of potential drugs engaging in binding to the Stat3 protein to craft the BP-1-102 drug which literally pulls apart the Stat3 protein rendering it ineffective in causing cancer.”

A unique feature of BP-1-102 is that it remains highly effective against cancer even when administered in oral form. Presently, most anti-cancer drugs require intravenous (IV) administration in a clinic or hospital setting which increases the financial, physical and emotional burdens on cancer patients. In its experimental form, BP-1-102 has shown promise in treating breast and lung cancers.

Currently, breast and lung cancers are two of the most commonly diagnosed cancers accounting for nearly half a million cases per year in the United States with over 200,000 deaths attributed to these diseases. In Hawaii, there is an average of 1500 cases diagnosed and over 600 deaths attributed to breast and lung cancers every year.

Professor Turkson is a recent and welcomed addition to the UH Cancer Center faculty. His innovative and ground breaking research focuses on developing novel anticancer drugs based on targeting signal transduction and apoptosis pathways.

Ref:

http://www.sciencedaily.com/releases/2012/05/120522115252.htm

http://www.pnas.org/content/109/2/600

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Children Exposed to the Common Pollutant Naphthalene Show Signs of Chromosomal Damage

Posted in Cell Biology, Signaling & Cell Circuits, Disease Biology, Small Molecules in Development of Therapeutic Drugs, tagged , , , , , on May 30, 2012| 1 Comment »

Reporter: Prabodh Kandala, PhD

According to a new study, children exposed to high levels of the common air pollutant naphthalene are at increased risk for chromosomal aberrations (CAs), which have been previously associated with cancer. These include chromosomal translocations, a potentially more harmful and long-lasting subtype of CAs.

Researchers from the Columbia Center for Children’s Environmental Health (CCCEH) at the Mailman School of Public Health, Columbia University Medical Center, and the Centers for Disease Control and Prevention (CDC) report the new findings in Cancer, Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Naphthalene is found in both outdoor and indoor urban air. It is present in automotive exhaust, tobacco smoke, and is the primary component of household mothball fumes. Classified as a possible carcinogen by the International Agency for Cancer Research, naphthalene belongs to a class of air pollutants called polycyclic aromatic hydrocarbons (PAH). Prior research at the CCCEH has established a link between prenatal exposure to PAH and increased risk for childhood obesity, IQ deficits, and CAs. The new study is the first to present evidence in humans of CAs, including translocations, associated with exposure to one specific PAH — naphthalene — during childhood.

The researchers followed 113 children, age 5, who are part of a larger cohort study in New York City. They assessed the children’s exposure to naphthalene; a CDC laboratory measured levels of its metabolites — 1- and 2-naphthol — in urine samples. (Metabolites are products of the body’s metabolism, and can serve as marker for the presence of a chemical.) Researchers also measured CAs in the children’s white blood cells using a technique called fluorescent in situ hybridization. Chromosomal aberrations were present in 30 children; of these, 11 had translocations. With every doubling of levels of 1- and 2-naphthol, translocations were 1.55 and 1.92 times more likely, respectively, to occur.

CAs have been associated with increased cancer risk in adults. Translocations are of special concern as they result in a portion of one chromosome being juxtaposed to a portion of another chromosome, potentially scrambling the genetic script. “Translocations can persist for years after exposure. Some accumulated damage will be repaired, but not everyone’s repair capacity is the same. Previous studies have suggested that chromosomal breaks can double an adult’s lifetime risk for cancer, though implications for children are unknown,” says first author Manuela A. Orjuela, MD, ScM, assistant professor of clinical environmental health sciences and pediatrics (oncology) at Columbia University Medical Center and a pediatric oncologist at NewYork-Presbyterian Morgan Stanley Children’s Hospital.

To obtain a better sense of the long-term consequences of naphthalene exposure, Dr. Orjuela and other CCCEH investigators are following some of the children in the study as they reach fourth grade. While they expect to see further translocations, they do not expect to see any signs of cancer in the white blood cells. “So far, the translocations seem to be random, and there has been no evidence of the specific translocations that are known to be associated with leukemia. This is entirely expected; leukemia is very rare.” Frederica Perera, DrPH, senior author on the paper, adds that “the findings provide yet more evidence of the vulnerability of the young child to carcinogenic air pollutants.”

The researchers hypothesized that naphthalene exposure was primarily from mothballs, which can release high levels of the chemical. Furthermore, according to previous research, some Caribbean immigrant families use mothballs as an air freshener. Other important sources of naphthalene in indoor air are tobacco smoke, paint fumes, cooking, and heating. The new findings have implications beyond the urban environment as elevated levels of naphthalene metabolites have been documented in rural communities using biomass-burning stoves (coal, wood) — another source of PAH exposure.

 Ref:

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Commonly Used Painkillers May Protect Against Skin Cancer

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Disease Biology, Small Molecules in Development of Therapeutic Drugs, tagged , , , , , , on May 30, 2012| 1 Comment »

UPDATED on 2/25/2019

https://www.medpagetoday.com/cardiology/prevention/78202?xid=nl_mpt_SRCardiology_2019-02-25&eun=g99985d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=CardioUpdate_022519&utm_term=NL_Spec_Cardiology_Update_Active

Painkiller celecoxib (Celebrex) unexpectedly was linked to aortic stenosis in an observational study and in vitro experiments showing a possible mechanism of dystrophic calcification of aortic valve interstitial cells. (JACC: Basic to Translational Science)

Commonly Used Painkillers May Protect Against Skin Cancer

Reporter: Prabodh Kandala, PhD

A new study suggests that aspirin and other similar painkillers may help protect against skin cancer. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings indicate that skin cancer prevention may be added to the benefits of these commonly used medications.

Previous studies suggest that taking nonsteroidal anti-inflammatory drugs, or NSAIDs, which include aspirin, ibuprofen, and naproxen, as well as a variety of other nonprescription and prescription drugs, can decrease an individual’s risk of developing some types of cancer. Sigrún Alba Jóhannesdóttir, BSc, of Aarhus University Hospital in Denmark, and her colleagues looked to see if the medications might decrease the risk of the three major types of skin cancer: basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.

The researchers analyzed medical records from northern Denmark from 1991 through 2009 and identified 1,974 diagnoses of squamous cell carcinoma, 13,316 diagnoses of basal cell carcinoma, and 3,242 diagnoses of malignant melanoma. They compared information, including prescription data, from these patients with information from 178,655 individuals without skin cancer.

Individuals who filled more than two prescriptions for NSAIDs had a 15 percent decreased risk for developing squamous cell carcinoma and a 13 percent decreased risk for developing malignant melanoma than those who filled two or fewer prescriptions for the medications, especially when the drugs were taken for seven or more years or taken at high intensity. Individuals who took NSAIDs did not seem to benefit from a reduced risk of developing basal cell carcinoma in general, although they did have a 15 percent and 21 percent reduced risk of developing this type of cancer on less-exposed sites (body areas other than the head and neck) when they took them long term or at high intensity, respectively.

“We hope that the potential cancer-protective effect of NSAIDs will inspire more research on skin cancer prevention,” said Ms. Jóhannesdóttir. “Also, this potential cancer-protective effect should be taken into account when discussing benefits and harms of NSAID use.”

Ref:

http://www.sciencedaily.com/releases/2012/05/120529073847.htm

http://onlinelibrary.wiley.com/doi/10.1002/cncr.27406/abstract;jsessionid=5D858902700DB3FF54D77A74AD38E905.d01t04

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Too Much Vitamin D Can Be as Unhealthy as Too Little

Posted in Biological Networks, Gene Regulation and Evolution, Disease Biology, Small Molecules in Development of Therapeutic Drugs, tagged , , , , , , , on May 30, 2012| Leave a Comment »

Reporter: Prabodh Kandala, PhD

Scientists know that Vitamin D deficiency is not healthy. However, new research from the University of Copenhagen now indicates that too high a level of the essential vitamin is not good either. The study is based on blood samples from 247,574 Copenhageners. The results have just been published in the reputed scientific Journal of Clinical Endocrinology and Metabolism.

Vitamin D is instrumental in helping calcium reach our bones, thus lessening the risk from falls and the risk of broken hips. Research suggests that vitamin D is also beneficial in combating cardiac disease, depression and certain types of cancers. The results from a study conducted by the Faculty of Health and Medical Sciences now support the benefits of vitamin D in terms of mortality risk. However, the research results also show higher mortality in people with too high levels of vitamin D in their bloodstream:

“We have had access to blood tests from a quarter of a million Copenhageners. We found higher mortality in people with a low level of vitamin D in their blood, but to our surprise, we also found it in people with a high level of vitamin D. We can draw a graph showing that perhaps it is harmful with too little and too much vitamin D,” explains Darshana Durup, PhD student.

If the blood contains less than 10 nanomol (nmol) of vitamin per liter of serum, mortality is 2.31 times higher. However, if the blood contains more than 140 nmol of vitamin per liter of serum, mortality is higher by a factor of 1.42. Both values are compared to 50 nmol of vitamin per liter of serum, where the scientists see the lowest mortality rate.

More studies are needed

Darshana Durup emphasises that while scientists do not know the cause of the higher mortality, she believes that the new results can be used to question the wisdom of those people who claim that you can never get too much vitamin D:

“It is important to conduct further studies in order to understand the relationship. A lot of research has been conducted on the risk of vitamin D deficiency. However, there is no scientific evidence for a ‘more is better’ argument for vitamin D, and our study does not support the argument either. We hope that our study will inspire others to study the cause of higher mortality with a high level of vitamin D,” says Darshana Durup. She adds:

“We have moved into a controversial area that stirs up strong feelings just like debates on global warming and research on nutrition. But our results are based on a quarter of a million blood tests and provide an interesting starting point for further research.”

The largest study of its kind

The study is the largest of its kind — and it was only possible to conduct it because of Denmark’s civil registration system, which is unique in the Nordic countries. The 247,574 blood samples come from the Copenhagen General Practitioners Laboratory:

“Our data material covers a wide age range. The people who participated had approached their own general practitioners for a variety of reasons and had had the vitamin D level in their bloodstream measured in that context. This means that while the study can show a possible association between mortality and a high level of vitamin D, we cannot as yet explain the higher risk,” explains Darshana Durup.

Therefore in future research project scientists would like to compare the results with information from disease registers such as the cancer register. Financial support is currently being sought for such projects.

Ref:

http://www.sciencedaily.com/releases/2012/05/120529102346.htm

http://jcem.endojournals.org/content/early/2012/05/09/jc.2012-1176

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Engineered Microvessels Provide a 3-D Test Bed for Human Diseases

Posted in Biological Networks, Gene Regulation and Evolution, Cell Biology, Signaling & Cell Circuits, Disease Biology, Small Molecules in Development of Therapeutic Drugs, tagged , , , , , , , on May 30, 2012| Leave a Comment »

Reporter: Prabodh Kandala, PhD

Mice and monkeys don’t develop diseases in the same way that humans do. Nevertheless, after medical researchers have studied human cells in a Petri dish, they have little choice but to move on to study mice and primates.

University of Washington bioengineers have developed the first structure to grow small human blood vessels, creating a 3-D test bed that offers a better way to study disease, test drugs and perhaps someday grow human tissues for transplant.

The findings are published this week in the Proceedings of the National Academy of Sciences.

“In clinical research you just draw a blood sample,” said first author Ying Zheng, a UW research assistant professor of bioengineering. “But with this, we can really dissect what happens at the interface between the blood and the tissue. We can start to look at how these diseases start to progress and develop efficient therapies.”

Zheng first built the structure out of the body’s most abundant protein, collagen, while working as a postdoctoral researcher at Cornell University. She created tiny channels and injected this honeycomb with human endothelial cells, which line human blood vessels.

During a period of two weeks, the endothelial cells grew throughout the structure and formed tubes through the mold’s rectangular channels, just as they do in the human body.

When brain cells were injected into the surrounding gel, the cells released chemicals that prompted the engineered vessels to sprout new branches, extending the network. A similar system could supply blood to engineered tissue before transplant into the body.

After joining the UW last year, Zheng collaborated with the Puget Sound Blood Center to see how this research platform would work to transport real blood.

The engineered vessels could transport human blood smoothly, even around corners. And when treated with an inflammatory compound the vessels developed clots, similar to what real vessels do when they become inflamed.

The system also shows promise as a model for tumor progression. Cancer begins as a hard tumor but secretes chemicals that cause nearby vessels to bulge and then sprout. Eventually tumor cells use these blood vessels to penetrate the bloodstream and colonize new parts of the body.

When the researchers added to their system a signaling protein for vessel growth that’s overabundant in cancer and other diseases, new blood vessels sprouted from the originals. These new vessels were leaky, just as they are in human cancers.

“With this system we can dissect out each component or we can put them together to look at a complex problem. That’s a nice thing — we can isolate the biophysical, biochemical or cellular components. How do endothelial cells respond to blood flow or to different chemicals, how do the endothelial cells interact with their surroundings, and how do these interactions affect the vessels’ barrier function? We have a lot of degrees of freedom,” Zheng said.

The system could also be used to study malaria, which becomes fatal when diseased blood cells stick to the vessel walls and block small openings, cutting off blood supply to the brain, placenta or other vital organs.

“I think this is a tremendous system for studying how blood clots form on vessels walls, how the vessel responds to shear stress and other mechanical and chemical factors, and for studying the many diseases that affect small blood vessels,” said co-author Dr. José López, a professor of biochemistry and hematology at UW Medicine and chief scientific officer at the Puget Sound Blood Center.

Future work will use the system to further explore blood vessel interactions that involve inflammation and clotting. Zheng is also pursuing tissue engineering as a member of the UW’s Center for Cardiovascular Biology and the Institute for Stem Cell and Regenerative Medicine.

Ref: http://www.sciencedaily.com/releases/2012/05/120528154907.htm

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Pancrealipase DR for Exocrine Pancreatic Insufficieny (EPI)

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Health Economics and Outcomes Research, International Global Work in Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Industry Competitive Intelligence, Population Health Management, Genetics & Pharmaceutical, tagged , , , , , , on May 30, 2012| Leave a Comment »

Pancrealipase DR for Exocrine Pancreatic Insufficieny (EPI).

via Pancrealipase DR for Exocrine Pancreatic Insufficieny (EPI).

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

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What the Cardiologist Needs to Know

Posted in Cardiovascular Pharmacogenomics, Infectious Disease & New Antibiotic Targets, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, tagged , , , , , , , , , , , , on May 29, 2012| Leave a Comment »

Guidelines for the Diagnosis and Treatment of Endocarditis

from

British Society of Antimicrobial Chemotherapy (BSAC)

Clinicians who care for patients diagnosed with infective endocarditis (IE) are (un)fortunate to be able to refer to several guidelines about its diagnosis and treatment. The guidelines vary considerably, especially with regards to antibiotic prescribing recommendations, which generally reflect local practice and expert opinion in light of largely observational data. All guidelines recommend a multidisciplinary approach to the management of IE.

Infective endocarditis

Infective endocarditis (Photo credit: Wikipedia)

Echocardiography remains a cornerstone of IE diagnosis but is neither 100% sensitive nor specific and multiple scans may be needed to identify vegetations. Echocardiography should also be used in all patients with Staphylococcus aureus bacteraemia. The prevalence of IE among patients with S aureus bacteraemia is variable but was reported as 13% in one large prospective US study and 22% in a recent European study. Clinical assessment is unreliable in diagnosing IE in patients with S aureus bacteraemia and without echocardiography the diagnosis may be missed. Transoesophageal echocardiography is now recommended in most cases of suspected or confirmed IE but may be unnecessary in patients with right-sided valve involvement.

Establishing a microbiological diagnosis in an era of increasingly complex infections with unpredictable resistance patterns is important. However, traditional recommendations for blood culture sampling have been amended for patients with suspected IE and severe sepsis or septic shock. In this situation, two (rather than three) sets of blood cultures, taken at different times within an hour before the start of empirical treatment, are now advised. This is a pragmatic recommendation to avoid undue delay in starting empirical antimicrobial treatment. In other patients, the usual need for three sets of blood cultures is recommended but with at least 6 h between sampling times; an important aim of multiple sampling is to demonstrate the presence of a sustained or persistent bacteraemia, which is characteristic of IE. Identification of atypical micro-organisms using serology in culture-negative cases should be limited to Coxiella and Bartonella in the first instance—a reflection of the extremely small numbers of reported cases of IE caused by Mycoplasma, Brucella and Legionella.

Fungal causes of IE should be considered in culture-negative IE if serology is non-diagnostic and the patient is immunocompromised, has a prosthetic valve, is an intravenous drug user or is not responding to empirical antibacterial treatment. The application of broad-range (16S ribosomal RNA gene) PCR on surgically resected valves or embolic material should be used when culture has failed. False-negative 16S ribosomal RNA gene PCR reactions can occur in the presence of inhibitors of the DNA polymerase within clinical samples or as a result of the vagaries of sampling (ie, processing a piece of tissue that does not contain any bacteria). Bacterial DNA has been shown to be present within cardiac tissue several years after successful treatment of IE, so results should be interpreted with caution in a patient with a previous diagnosis of IE. Application of 16S ribosomal gene PCR to blood in patients with IE is problematic owing to the low levels of bacteria present (1–10 fu/ml) and subsequent difficulty in DNA extraction; as a result it is not currently available for routine clinical use.

Empirical treatment (that started before obtaining a microbiological diagnosis) is generally discouraged, except in those who are acutely unwell or shocked. There is no clear evidence that speeding up the diagnosis, and instigation of treatment, improves outcomes, although this would seem intuitive. Early treatment (started within days of onset of symptoms rather than weeks) is a laudable aim, but the few days delay in hospital while appropriate echocardiographic and microbiological tests are undertaken on a stable patient are unlikely to have a negative impact on outcome. Conversely, the administration of broad-spectrum antibiotics when the diagnosis of IE has not been considered (and often when inadequate samples have been obtained) may have considerable impact on the ability to establish the diagnosis and subsequently deliver effective treatment.

Outpatient antibiotic treatment (OPAT) for IE is included in the BSAC guidelines in response to increasing efforts to expand these services and manage more patients outside hospital. Patients who might be considered for OPAT include those who are stable and responding well to treatment, are without signs of heart failure and without any indications for surgery or uncontrolled extracardiac foci of infection. Delivery of OPAT requires appropriate funding, support and infrastructure, coupled with the ability to rapidly access inpatient services and obtain urgent expert advice if needed. This has been proved to be feasible and safe in the UK, even in high-risk IE cases.

Although the guidelines include recommendations for most causes of IE, the predominant pathogens remain staphylococci, streptococci and enterococci. Routine addition of gentamicin to flucloxacillin for the treatment of native valve staphylococcal IE is no longer recommended (see Table 1). This recommendation is unchanged from previous BSAC guidelines but the ESC continue to include gentamicin as an optional addition. Further evidence of the toxicity of gentamicin has been published, based on findings from a randomised controlled trial comparing daptomycin with either vancomycin or cloxacillin plus gentamicin for the treatment of S aureus bloodstream infection or IE Recommendations for meticillin-resistant staphylococci also differ from those of the ESC; although vancomycin is the primary agent in both sets of guidelines, rifampicin is recommended by BSAC in place of gentamicin because of concerns about efficacy and toxicity. Daptomycin, a recently licensed lipopeptide, is also recommended as an alternative agent for patients who are intolerant to vancomycin or have infection caused by vancomycin-resistant isolates.

Previous recommendations for treatment of streptococcal IE have been simplified, with greater emphasis placed on benzylpenicillin rather than amoxicillin as the primary agent to reduce risk of Clostridium difficile infection. Enterococcal treatment regimens are largely consistent with the ESC guidelines, though a low threshold for withdrawing gentamicin in patients with deteriorating renal function or other signs of toxicity is advised, based on observational data that shorter gentamicin courses are not associated with worse outcomes.

The timing of cardiac surgery in IE should be evaluated by the multidisciplinary team on a case by case basis. Attempts to advise whether cardiac surgery should be emergent, urgent or elective can seem artificial. The traditional indications for surgery in IE are well established but it is becoming apparent that patients with IE caused by S aureus, or patients with evidence of systemic embolisation, should also be considered for early surgery, which may confer a mortality benefit.

Device-related infections have been deliberately omitted from the current BSAC guidance as the challenges in preventing, diagnosing and treating cases of intracardiac device IE are different from ‘traditional’ native or prosthetic valve IE. Further specific device-related guidance is likely to be published in the future and a joint working party involving the BSAC, BCS and Heart Rhythm UK has been established. IE guidelines are always imperfect owing to the difficulties in studying this relatively uncommon condition and the scarcity of randomised trials. At present, we are uncertain of the incidence, risk factors, causative micro-organisms (and their antimicrobial sensitivities), and patient outcomes in IE affecting the UK population. A recently established national endocarditis database may help to answer some of these questions, but its success will be crucially determined by the degree of support and national participation. See http://www.neemo.leedsth.nhs.uk/ (only via the N3 network) for details.

see source for more

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

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Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes

Posted in Pharmaceutical Analytics, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, tagged , , , , , , , , , on May 29, 2012| 15 Comments »

Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes

Curator: Aviva Lev-Ari, PhD, RN

 

Excellent review of Hypertension Medications is provided in the following two short videos:

VIEW VIDEOS

Hypertension Explained Clearly! 1 of 2

Hypertension Explained Clearly! 2 of 2

 

http://www.drugs.com/clinical_trials/new-data-shows-investigational-triple-antihypertensive-combination-therapy-significantly-lowers-9712.html

Hypertension Treatment in the Last Decade

 The need for combination drug therapy was recognized in 2000, In Combination Antihypertensive Drugs: Recommendations for Use

NEIL S. SKOLNIK, M.D., JONATHAN D. BECK, M.D., MATHEW CLARK, M.D., Abington Memorial Hospital, Jenkintown, Pennsylvania

Am Fam Physician. 2000 May 15;61(10):3049-3056

Combination Medication: Impact on Compliance

Increased Compliance with fewer pills a favorable outcome of combination medication for Hypertension.

More medications, fewer pills: Combination medications for the treatment of hypertension Richard Lewanczuk, MD PhD1 and Sheldon W Tobe, MD2

Can J Cardiol. 2007 May 15; 23(7): 573–576.

Classification of Blood Pressure

Category SBP mmHg DBP mmHg

Normal <120 and <80

Prehypertension 120–139 or 80–89

Hypertension, Stage 1 140–159 or 90–99

Hypertension, Stage 2 ≥160 or ≥100

Principles of Hypertension Treatment

• Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients

with diabetes or chronic kidney disease.

• Majority of patients will require two medications to reach goal.

Without Compelling Indications

Stage 1

Hypertension

(SBP 140–159 or DBP

90–99 mmHg)

Thiazide-type diuretics

for most. May consider

ACEI, ARB, BB, CCB,

or combination.

 Stage 2

Hypertension

(SBP ≥160 or DBP

≥100 mmHg)

2-drug combination for

most (usually thiazidetype

diuretic and ACEI,

or ARB, or BB, or CCB).

Causes of Resistant Hypertension

• Improper BP measurement

• Excess sodium intake

• Inadequate diuretic therapy

• Medication

– Inadequate doses

– Drug actions and interactions (e.g., nonsteroidal anti-inflammatory drugs

(NSAIDs), illicit drugs, sympathomimetics, oral contraceptives)

– Over-the-counter (OTC) drugs and herbal supplements

• Excess alcohol intake

• Identifiable causes of hypertension (see reverse side)

Compelling Indications for Individual Drug Classes

 Compelling Indication  and Initial Therapy Options

• Heart failure THIAZ, BB, ACEI, ARB, ALDO ANT

• Post myocardial infarction BB, ACEI, ALDO ANT

• High CVD risk THIAZ, BB, ACEI, CCB

• Diabetes THIAZ, BB, ACEI, ARB, CCB

• Chronic kidney disease ACEI, ARB

• Recurrent stroke prevention THIAZ, ACEI

Key: THIAZ = thiazide diuretic, ACEI= angiotensin converting enzyme inhibitor, ARB = angiotensin receptor

blocker, BB = beta blocker, CCB = calcium channel blocker, ALDO ANT = aldosterone antagonist

http://www.nhlbi.nih.gov/guidelines/hypertension/phycard.pdf

JNC-7 on Treatment for Hypertension

According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, or JNC-7, most people require more than one medication to achieve treatment goals. Some medications are being manufactured in combinations, which reduces the number of pills a patient must take and may reduce costs.

http://www.livestrong.com/article/217562-combination-drugs-for-hypertension/#ixzz1wD1wneZg

All combination drugs for Hypertension are presented in

http://www.livestrong.com/article/217562-combination-drugs-for-hypertension/#ixzz1wD3dqnrl

JNC-7 lists the following Combinations of Drugs for Hypertension:

ACE Inhibitors and Calcium Channel Blockers

The angiotensin converting enzyme inhibitors, or ACEIs, are a group of drugs that work in the kidneys to block a reaction that leads to tightening of the blood vessels and retention of sodium and water. They lower blood pressure by counteracting these effects.

Calcium channel blockers, or CCBs, work by relaxing smooth muscle in the heart and blood vessels. One common side effect of this group of drugs is leg swelling. This can be lessened when they are used in combination with the ACEIs.
Amlodipine-benazepril, enalapril-felodipine and trandolapril-verapamil are examples of these medicines that have been combined into a single pill. Multiple dosing variations are available.

ACE Inhibitors and Diuretics

Diuretics are commonly known as “water pills” because they work by increasing urine output and lowering blood volume, and therefore blood pressure. Diuretics are generally inexpensive, work well to enhance the effects of other medicines and have a proven track record in preventing cardiovascular complications of hypertension, as discussed in JNC-7.

Many ACE inhibitors are available packaged with hydrochlorothiazide, or HCTZ. Benazepril, enalapril, lisinopril and others are commonly seen in this combination.

ARBs and Diuretics

The angiotensin receptor blockers, or ARBs, are related to the ACEIs, in that they work on the same renal pathway. However, the ARBs work farther down the process and often have fewer side effects. The beneficial effects on blood pressure are similar between the two groups.

Candesartan, losartan, telmesartan, valsartan and others are available as combination drugs with HCTZ.

Beta-blockers and Diuretics

Beta-blocking medications work in the peripheral nervous system to slow the heart rate and decrease adrenalin-type effects on the blood vessels. JNC-7 notes that the beta-blockers are especially useful in those with hypertension and heart disease or angina.

Atenolol is available with the diuretic chlorthalidone, which is similar to HCTZ. Bisoprolol, metroprolol, propranolol LA and timolol come in combination with HCTZ.

Centrally Acting Drugs and Diuretics

Methyldopa and reserpine affect the central nervous system to produce a lowering of blood pressure. They are not used often, but can be effective in the appropriate situation. Each come in a combination drug with HCTZ, while reserpine is also produced with chlorthalidone and chlorothiazide.

Diuretic Combinations

Various diuretics work in different locations of the kidneys to affect their anti-hypertensive properties. HCTZ tends to lower blood potassium, so is available in combination with spironolactone or triamterene, which are known to elevate potassium. The combination tends to be potassium neutral.

ARB and Calcium Channel Blocker and Diuretic

In July 2010, a triple combination drug for hypertension was approved by the US Food and Drug Administration. Tribenzor contains olmesartan medoxomil, amlodipine and hydrochlorothiazide, according to Monthly Prescribing Reference.

Three Combination Drug Therapy for Antihypertension from Daiichi Sankyo’s Portfolio of Products

Daiichi Sankyo has a
comprehensive portfolio of drugs offering a wide range of treatments for patients in a number of disease
categories including hypertension, heart disease and hyperlipidemia/atherosclerosis.

The discovery of epinephrine (also known as adrenaline) in 1889, to the development of the statin class of lipid-lowering agents and the development of the first glitazone, which revolutionized long-term control of type 2 diabetes.

New ideas and pairing of existing information with novel concepts, led to the  creation of  medicines as well as new methods of drug discovery and delivery.

Daiichi Sankyo products for hypertension, heart disease and hyperlipidemia/atherosclerosis which are currently marketed in the U.S. include several drug combinations for Cardiovascular disease.

http://dsi.com/c/document_library/get_file?uuid=5b356194-9d74-47ba-94a6-a82a7ea694cb&groupId=12065

TRIBENZOR is a Daiichi Sankyo’s product- ARB and Calcium Channel Blocker and Diuretic

How TRIBENZOR work

Tribenzor contains olmesartan medoxomil, amlodipine and hydrochlorothiazide. High blood pressure makes the heart work harder to pump blood through the body and causes damage to blood vessels. TRIBENZOR can help your blood vessels relax and reduce the amount of fluid in your blood. This can make your blood pressure lower. Medicines that lower blood pressure may lower your chance of having a stroke or a heart attack.

Some people may need more than 1—or even more than 2—medicines to help control their blood pressure. TRIBENZOR combines 3 effective medicines in 1 convenient pill. Read the following chart to learn how each medicine works in its own way to help lower blood pressure.

TRIBENZOR: 3 effective medicines in 1 pill

The medicine in TRIBENZOR How it works What it does
Angiotensin II receptor blocker Blocks a natural chemical in your body that causes blood vessels to narrow.

Lowers

Yours

blood

pressure
Calcium channel blocker Blocks the narrowing effect of calcium on your blood vessels. This helps your blood vessels relax.
Diuretic (water pill) Helps your kidneys flush extra fluid and salt from your body. This lowers the amount of fluid in your blood.

http://www.tribenzor.com/how_works.html

            Effectively lower blood pressure. People taking the 3 medicines in TRIBENZOR had greater reductions in blood pressure than did people taking any 2 of the medicines combined

            Start to work quickly. People taking TRIBENZOR saw results in as little as 2 weeks

AZOR is a Daiichi Sankyo’s product- ARB and Calcium Channel Blocker

How AZOR work

AZOR relaxes and widens blood vessels to help lower blood pressure.

You may have already tried another blood pressure medicine that works a certain way to lower blood pressure. But 1 blood pressure medicine may not be enough for you. You may find the help you need with the 2 effective medicines in AZOR.

AZOR combines 2 effective medicines in 1 convenient pill.

Learn how each medicine in AZOR works in its own way to help lower blood pressure.

The medicine in AZOR How it works What it does
Angiotensin II receptor blocker (ARB) Blocks a natural chemical in your body that causes blood vessels to narrow. This helps your blood vessels relax and widen.

Lowers

Your

Blood

pressure
Calcium channel blocker Blocks the narrowing effect of calcium on your blood vessels. This helps your blood vessels relax.

http://www.AZOR.com/how_works.html

 

Benicar and Benicar HCT are Daiichi Sankyo’s products an ARBs and Diuretics

How Benicar and Benicar HCT work

Benicar and Benicar HCT are prescription medicines used to lower high blood pressure (hypertension). They may be used alone or with other medicines used to treat high blood pressure. Benicar HCT is not for use as the first medicine to treat your high blood pressure.

 Lowering blood pressure with Benicar or Benicar HCT

There are many different choices to treat high blood pressure. You may have started with some lifestyle changes or different medicines to find what works for you. You and your doctor can talk about whether Benicar or Benicar HCT is a good choice for you.

The medicine in Benicar How it works

What it does
Angiotensin II receptor blocker (ARB) Blocks a natural chemical in the body that causes blood vessels to narrow. This helps the blood vessels relax and widen.

Lowers

your

blood

pressure

Some people may need more than 1 medicine to help manage high blood pressure. So doctors may choose to prescribe Benicar HCT. The 2 medicines in Benicar HCT help to lower blood pressure more than taking either medicine alone. You and your doctor can talk about what’s right for you.

The medicines in Benicar HCT How it works

What it does
Angiotensin II receptor blocker (ARB) Blocks a natural chemical in the body that causes blood vessels to narrow. This helps the blood vessels relax and widen.

Lowers

your

blood

pressure
Diuretic(a water pill) Helps your kidneys flush extra fluid and salt from your body. This lowers the amount of fluid in your blood.

Benicar and Benicar HCT are medicines that both

Block calcium

Block a chemical called angiotensin II

Block water and salt

There are no generic forms of Benicar or Benicar HCT

http://www.benicar.com/how_work.html

Risk of Antihypertensive drugs

Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study

BMJ 2012;344:d8190

Compatible with their urate lowering properties, calcium channel blockers and losartan are associated with a lower risk of incident gout among people with hypertension. By contrast, diuretics, β blockers, angiotensin converting enzyme inhibitors, and non-losartan angiotensin II receptor blockers are associated with an increased risk of gout.

http://www.bmj.com/content/344/bmj.d8190

Affordability of the Combination Medication for Hypertension from the Daiichi Sankyo’s product portfolio is supported by a Manufacturer Program to 2016.

There are no generic drugs for the Combination Medication for Hypertension from the Daiichi Sankyo’s product portfolio. Daiichi Sankyo, Inc., will cover up to $140 of the co-pay for BENICAR, BENICAR HCT, AZOR, and TRIBENZOR after the patient pays the first $25. Offer applies to patients with commercial insurance; $25 initial savings available for patients without insurance; offer expires 2016. If a retail or mail-order pharmacy does not accept the Savings That Last card, patients may obtain a Direct Member Reimbursement form by calling the number on the back of the card to receive instructions on how to obtain the savings benefit. Offer not valid for patients enrolled in a state or federal healthcare program including but not limited to Medicaid, Medicare, Veterans Administration, or TRICARE/CHAMPUS. Offer valid in the United States and Puerto Rico. Void where taxed, restricted, or prohibited by law. Void in Massachusetts, except for patients without insurance. Daiichi Sankyo, Inc., reserves the right to rescind, revoke, or amend this program, at any time, without notice.

 TRIBENZOR is preferred on some of the largest Medicare Part D plans.

http://www.tribenzorhcp.com/savings_that_last.html

Cost Savings Associated with Filling a 3-Month Supply of Prescription Medicines

http://ideas.repec.org/a/wkh/aheahp/v7y2009i4p255-264.html

 Out-of-pocket and Total Costs of Fixed-dose Combination Antihypertensives and Their Components

Atonu Rabbani1 and G. Caleb Alexander1,2,3,4

American Journal of Hypertension (2008); 21, 5, 509–513. doi:10.1038/ajh.2008.31

Given patient burden and non-adherence from out-of-pocket prescription costs, the clinical benefits of brand-named fixed-dose combination antihypertensive therapy should be balanced with their greater out-of-pocket costs.

http://www.nature.com/ajh/journal/v21/n5/abs/ajh200831a.html

 

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