Linaclotide for treatment of constipation - minimally absorbed peptide agonist of guanylate cyclase C receptor

Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor. It consists of 14 amino acids. The sequence is:

H–Cys1–Cys2–Glu3–Tyr4–Cys5–Cys6–Asn7–Pro8–Ala9–Cys10–Thr11–Gly12–Cys13–Tyr14–OH

Two randomized, 12-week trials included 1,300 patients with chronic constipation (NEJM, 2011). Patients received either placebo or linaclotide once daily for 12 weeks.

The incidence of adverse events was similar among all study groups, with the exception of diarrhea, which led to discontinuation of treatment in 4.2% of patients in linaclotide groups.

Linaclotide reduced bowel and abdominal symptoms in patients with chronic constipation. Additional studies are needed to evaluate the potential long-term risks of linaclotide in chronic constipation.

References:

Two Randomized Trials of Linaclotide for Chronic Constipation. N Engl J Med 2011; 365:527-536August 11, 2011.

Image source: Colon (anatomy), Wikipedia, public domain.

Depression treatment is as effective in older (over 65) as in younger adults

Depression in later life, traditionally defined as age older than 65, is associated with disability, increased mortality, and poorer outcomes.

Compared to younger adults with depression:

- cognitive and functional impairment and anxiety are more common in older adults

- older adults with depression are at increased risk of suicide

Depression is associated with cognitive impairment and an increased risk of dementia.

A selective serotonin reuptake inhibitor (SSRI) should be the first line pharmacological treatment for depression for most older adults.

Psychological and drug treatment is as effective in older as in younger adults

References:

Depression in older adults. Rodda et al. BMJ, 2011.

Image source: Vincent van Gogh's 1890 painting At Eternity's Gate. Wikipedia, public domain.

Essential tremor: what are the treatment options?

Essential tremor is a common neurologic problem. It should be differentiated from secondary causes of tremor and Parkinson disease.

Impact of essential tremor

Essential tremor causes motor dysfunction (e.g. a dentist may have to quit his/her job). However, more importantly, the tremor can have a psychological impact on the patient, especially since it usually gets worse in social situations.

Diagnosis

Essential tremor is a clinical diagnosis. A thorough review of the medical history and medication exposures is a good start. Laboratory and imaging tests may be ordered to rule out a secondary cause.

Treatment

The two first-line agents in drug therapy for essential tremor are:

- nonselective beta-blocker propranolol (Inderal)
- antiepileptic primidone (Mysoline)

They can be used alone or in combination.

Severe, resistant, or atypical cases should be referred to a specialist. Botulinum toxin injection and deep brain stimulation are reserved for resistant tremor or for patients who do not tolerate drug therapy.

Dr. Young from Swedish Medical Center discusses some of the new treatments for essential tremor in this video:



References:

Essential tremor: Choosing the right management plan for your patient. CCJM, 2011.

New treatment for dry eyes: "LipiFlow" uses heat and pressure to open blocked eyelid oil glands

The Meibomian glands (or tarsal glands) are sebaceous glands at the rim of the eyelids, responsible for the supply of meibum, an oily substance that prevents evaporation of the eye's tear film. They prevent tear spillage onto the cheek, trapping tears between the oiled edge and eyeball, and make the closed lids airtight. There are approximately 50 glands on the upper eyelids and 25 glands on the lower eyelids. The glands are named after Heinrich Meibom (1638–1700), a German physician (source: Wikipedia).

The LipiFlow Thermal Pulsation System uses heat and pressure to open blockages of the eyelid (Meibomian) glands. The treatment was approved by the FDA in 2011. Here is more information: http://lipiflow.com

Here is a Mayo Clinic video about the procedure:

Internet Addiction documentary shows Chinese boot-camp-style treatment

China's Web Junkies - Internet Addiction Documentary by the NYTimes about a Chinese boot-camp-style treatment center for young men "addicted" to the Internet. Read the story here: http://nyti.ms/1moCt4h



Compulsive Internet use has been categorized as a mental health issue in many countries, including the United States, but China was among the first to label “Internet addiction” a clinical disorder. This video shows the inner workings of a rehabilitation center where Chinese teenagers are “deprogrammed.”

There are now hundreds of treatment programs throughout China and South Korea. The first inpatient Internet addiction program in the United States recently opened in Pennsylvania. Here is the link to the CNN story about the program.

Is Internet addiction real?

According to The New York Times, Internet addiction affects 10 percent of the web users in the U.S. The so-called "Onlineaholics" spend endless hours surfing the web to the point that their Internet activity disturbs their daily life.

 A growing number of therapists are treating web addicts with the 12-step programs, used to treat chemical addictions. The condition is not officially recognized as a psychiatric disorder and insurance companies do not pay for treatment.

 The University of Massachusetts, Lowell has more information on the Internet addiction disorder: Take an Internet Addiction Survey Online

Online social networking may 'harm health' due to reduction of face-to-face contact

Aric Sigman pubslished his "warning" in Biologist, the journal of the Institute of Biology (click here for the original PDF). From BBC:

• Lack of face-to-face networking could alter the way genes work, upset immune responses, hormone levels, the function of arteries, and influence mental performance
  
  
• Number of hours people spend interacting face-to-face has fallen dramatically since 1987, as the use of electronic media has increased
  
  
• "One of the most pronounced changes in the daily habits of British citizens is a reduction in the number of minutes per day that they interact with another human being," he said.
  
  
• "In less than two decades, the number of people saying there is no-one with whom they discuss important matters nearly tripled."

"Netiquette" and married couples

From the study:

Men are more associated with activities that have been associated with internet addiction. Men usually take more risks in their online activity.

Women are more likely to have lower computer self-efficacy and less positive internet attitudes. Women are more aware of privacy and economic risks in online transactions.

6% of married internet users have met their partner online.

In 30% of the couples at least one person checked their partner’s emails or read their partner’s SMS messages without them knowing. In 20% of the couples at least one the partners had checked their spouse’s browser history.

References:

Hooked on the Web: Help Is on the Way. NYTimes, published: December 1, 2005
Is Internet addiction real? American Psychological Association
Netiquette within married couples
Helsper, E., & Whitty, M. (2010). Netiquette within married couples: Agreement about acceptable online behavior and surveillance between partners Computers in Human Behavior DOI: 10.1016/j.chb.2010.02.006
Online networking 'harms health.' BBC.

Controversies in COPD treatment

Chronic obstructive pulmonary disease (COPD) is a chronic disorder with high mortality rates (one of the top 5 causes of death).

COPD is expected to rise to the third leading cause of death worldwide by 2030. More than 25% of COPD patients have never been smokers.

Some important controversies in COPD management still exist:

- The classic way to define COPD has been based on spirometric criteria, but more relevant diagnostic methods are needed that can be used to describe COPD severity and comorbidity

- Initiation of interventions earlier in the natural history of the disease to slow disease progression is debatable

- There are controversies about the role of inhaled corticosteroids (ICS) in the management of COPD

- Long-term antibiotics for prevention of exacerbation have had a resurgence in interest

New drugs are urgently needed for management of COPD exacerbation.

COPD is a complex disease and consists of several phenotypes that in future would guide its management.



Asthma Inhalers (click to enlarge the image). Advair and Symbicort are FDA-approved for treatment of COPD in the U.S.



COPD Action Plan - National Jewish - YouTube http://buff.ly/1pwyHZL

References:

Controversies in treatment of chronic obstructive pulmonary disease. Prof Klaus F Rabe MD a , Jadwiga A Wedzicha MD b. The Lancet, Volume 378, Issue 9795, Pages 1038 - 1047, 10 September 2011.

New insights into the immunology of chronic obstructive pulmonary disease. The Lancet, Volume 378, Issue 9795, Pages 1015 - 1026, 10 September 2011.

COPD—more vigorous research needed. The Lancet, Volume 378, Issue 9795, Page 962, 10 September 2011.

Diagnosis and Management of COPD - Current Guidelines

Image source: Enlarged view of lung tissue showing the difference between healthy lung and COPD, Wikipedia, public domain.

Treatment Options for Osteoporosis

I selected a few excerpts from a patient information review in the New York Times:

What is osteoporosis

Osteoporosis is defined as having a bone mineral density T score of minus 2.5 or lower. Lesser degrees of bone loss, known as osteopenia, may not benefit from drug therapy.

Bisphosphonates

The first drug licensed to counter osteoporosis, Fosamax, is now available generically as alendronate, which can be taken once a day or, at a higher dose, once a week. A reluctance on the part of many patients to adhere to a daily or weekly regimen led to the development of Boniva (ibandronate), administered by an intravenous injection every three months. To further simplify the frequency of administration, Reclast (zoledronic acid) was developed as a once-a-year intravenous treatment.

Actonel, alendronate and Boniva have been shown in three-year studies of postmenopausal women to reduce vertebral fractures by 41-50%, and less for other kinds of fractures.

A three-year study of Reclast found it to be somewhat more effective, with a 70 percent reduction in vertebral fractures, 41 percent in hip fractures and 25 percent in other fractures in postmenopausal women with osteoporosis.

Side Effects of Bisphosphonates

In a large study of Reclast, there was also a worrisome increase in atrial fibrillation — an irregular heart rhythm — not known to occur with other bisphosphonates.

Low-trauma fracture with a delay in healing or complete failure may occur after many years on bisphosphonates.

These side effects have prompted a warning that after five years on bisphosphonates, people should take a break from the drugs for at least a year.

Evista (raloxifene)

Evista (raloxifene) has an added advantage of reducing the risk of breast cancer, but the disadvantage of increasing the risk of deep vein blood clots.

Calcitonin

Somewhat less effective at reducing vertebral fractures is calcitonin, a naturally occurring hormone sold as Fortical and Miacalcin.

Forteo (teriparatide)

Finally, there is the bone-building drug Forteo (teriparatide), which must be self-injected once a day. This human parathyroid hormone can reduce vertebral fractures by 65 percent and other fractures by 53 percent within 18 months in patients with osteoporosis.

Denosumab

Under study is an entirely new bone drug, denosumab, a human monoclonal antibody. The drug inhibits a receptor that activates cells called osteoclasts that break down bone. In a large three-year study, denosumab, given by injection every six months to postmenopausal women with osteoporosis, reduced vertebral fractures by 68 percent and hip fractures by 40 percent.

References:
Options for Bone Loss, but No Magic Pill. NYT, January 4, 2010.
Denosumab is a monoclonal antibody that reduces fractures in osteoporosis
Image source: Flickr, Creative Commons license.

30% of doctors have changed a patient's treatment as a result of an Internet search

From AMedNews:

86% of physicians use Internet to access health information. Why not 100%?

72% of physicians start their health information search with a search engine, 92% of those using Google.

A third of doctors have changed a patient's treatment as a result of an Internet search.

Consistent with other search engine research findings that users tend to click the most prominent links, 92% of physician searchers clicked on the links appearing at the top of the page, 46% clicked those in the middle of the page, and 24% clicked on those on the bottom. Also, 8% clicked on sponsored links.

References:
86% of physicians use Internet to access health information. AMedNews.
Image source: Doctors Using Google by Philipp Lenssen, used with permission.

Treatment options for migraine patients

From the NYTimes:

"Migraines are notoriously tricky to treat. Those who suffer from these disabling headaches often try a dozen or so medications before they find something that works.

“What might be a miracle drug for one person could be a dud for another.” Be prepared for a multi-tiered approach.

Doctors typically prescribe a triptan drug or an ergot-related drug to help people control infrequent migraine attacks. There are 7 types of triptans. The best-seller Imitrex (sumatriptan) is available in an affordable generic version (the chemical formula is shown above). Triptans are far more popular, but many people who do not respond well to triptans do well with the ergots, such as D.H.E. (dihydroergotamine), Dr. Saper said.

If you have migraines at least weekly your doctor may prescribe a preventative medicine. “Prescription preventatives are grossly underutilized. They can be extremely effective for some people.”

Preventive medicines, taken every day, include antiseizure drugs, beta blockers and tricyclic antidepressants."

References:
Migraines Force Sufferers to Do Their Homework
http://www.nytimes.com/2010/01/30/health/30patient.html
NYTimes, Patient Voices: Migraine
http://www.nytimes.com/interactive/2009/12/15/health/healthguide/TE_migraine.html

Triptans for Migraine: How should triptans be used? NEJM blog, 2010.

Image source: Sumatriptan, Wikipedia, public domain.

Related:

Migraine with aura is an independent risk factor for cardiovascular and all cause mortality in men and women http://goo.gl/kAxc

Migraine with aura might, in addition to ischaemic events, also be a risk factor for haemorrhagic stroke http://goo.gl/GQvf

Review: Which drugs are effective for preventing migraine headache? http://goo.gl/WXfEl

Migraine headaches are more common in patients with allergic rhinitis - immunotherapy decreases headache frequency http://goo.gl/XEIBq

Pharmacological prevention of migraine - BMJ review http://goo.gl/Q5K2m

Oral Tolvaptan (Samsca) Is Safe and Effective Treatment for Chronic Hyponatremia

Vasopressin antagonists increase the serum sodium concentration in patients who have euvolemia and hypervolemia with hyponatremia in the short term (30 days), but their safety and efficacy with longer term administration is unknown.

In a study, 111 patients with hyponatremia received oral tolvaptan (Samsca) for 700 days.

The most common adverse effects attributed to tolvaptan were pollakiuria, thirst, fatigue, dry mouth, polydipsia, and polyuria.

Mean serum sodium increased from 130.8 mmol/L at baseline to greater than 135 mmol/L throughout the observation period.

Responses were comparable between patients with euvolemia and those with heart failure but more modest in patients with cirrhosis.

In conclusion, prolonged administration of tolvaptan maintains an increased serum sodium with an acceptable margin of safety.

Samsca (tolvaptan) Black Box Warnings

Appropriate Use

Initiate and re-initiate tx only in hospital with serum Na monitoring.

Monitor Serum Sodium

Osmotic demyelination may occur w/ rapid correction of hyponatremia (faster than 12 mEq/L/24h), resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death; slower rates of correction advised in pts w/ severe malnutrition, alcoholism or advanced liver disease.

Cost comparison of conivaptan (Vaprisol) versus tolvaptan (Samsca)

Conivaptan is administered IV only, the average cost per day is $573.

Tolvaptan is administered PO only, the average cost per day is $300.

References:

Oral Tolvaptan Is Safe and Effective in Chronic Hyponatremia. Journal of the American Society of Nephrology, 2010.

Samsca (tolvaptan) Black Box Warnings. Epocrates.

Cost comparison of conivaptan (Vaprisol) versus tolvaptan (Samsca) (PDF).

Lowest sodium I have ever seen http://goo.gl/QgJmf

Image source: Tolvaptan, Wikipedia, public domain.

Comments from Twitter and Facebook:

@kidney_boy: tolvaptan is safe for the patient but not their wallet at $250 per pill!

Neil Mehta: "It costs a king's ransom to keep the sodium level up! Maybe we should just say "Let them eat Salt"!"

Updated: 10/28/2010

Norepinephrine Causes Fewer Adverse Events Than Dopamine in the Treatment of Shock

Both dopamine and norepinephrine (Levophed) are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other.

Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events.

References:

Comparison of Dopamine and Norepinephrine in the Treatment of Shock. NEJM, 2010.

Image source: Wikipedia, public domain.

New Developments in Treatment of Diabetes Type 2

From The Lancet theme issue on diabetes:

Diabetes confers a two-fold excess risk for a wide range of vascular diseases - heart disease and stroke. Adjusted HRs with diabetes were: 2·00 for coronary heart disease; 2·27 for ischaemic stroke; 1·56 for haemorrhagic stroke; 1·84 for unclassified stroke; and 1·73 for the aggregate of other vascular deaths. http://goo.gl/ucF0

Increased occurrence of cough and change in pulmonary function in the group receiving inhaled insulin - Lancet http://goo.gl/ve3G

Once weekly exenatide is an important therapeutic option for patients with type 2 diabetes http://goo.gl/UL3e

Dapagliflozin, sodium-glucose cotransporter-2 inhibitor (SGLT2 inhibitor), provides a new therapeutic option for type 2 diabetes http://goo.gl/FqIM

Cognitive behavioural treatment may work for low-back pain

Low-back pain is a common and costly problem. This study estimated the effectiveness of a group cognitive behavioural intervention in addition to best practice advice in people with low-back pain in primary care.

Over 1 year, the cognitive behavioural intervention had a sustained effect on troublesome subacute and chronic low-back pain at a low cost to the health-care provider.

References:

Group cognitive behavioural treatment for low-back pain in primary care: a randomised controlled trial and cost-effectiveness analysis. The Lancet, Volume 375, Issue 9718, Pages 916 - 923, 13 March 2010.

Image source: Different regions (curvatures) of the vertebral column, Wikipedia, public domain.

"Talk to Frank" - British government website for drug abuse prevention and treatment

Talk to Frank" is a British government-funded website for drug abuse prevention and treatment tips for the general public available at http://www.talktofrank.com

The "A to Z" list of substances explains appearance and use, effects, chances of getting hooked, health risks and the UK law. It also includes information on peer pressure, etc.

Diagnosis, treatment, and prognosis of glioma: 5 new things

5 new ideas that are changing the management of brain tumor patients:

1. Prognosis and glioma subtypes. The cell of origin of the glioblastoma has never been defined. In his pioneering work “Death Foretold,” Dr. Christakis says “prognosis gives diagnosis its affective component, striking fear in patients and physicians alike.” There has been a lot of therapeutic nihilism about the treatment of glioblastoma, but that is now changing. Image source: Sen. Ted Kennedy who died of glioma in 2009.

2. Diagnosis and imaging mimics. Acute stroke in the luxury perfusion stage is probably the most common mimic of a brain tumor. Diffusion MRI sequences and perfusion CT scan are helpful in differentiating stroke from tumor by showing hypoperfusion as would be expected, rather than hyperperfusion seen in tumors.

3. Treatment and pseudoprogression. Temozolomide is an oral drug, which is changed into MTIC (methyltriazeno-imidazole-carboxamide), a DNA-methylating drug. The concomitant use of radiation therapy and adjuvant temozolomide in glioblastoma patients showed a median survival of 14.6 months.

Increase in contrast enhancement and mass effect can mimic tumor progression. The term “pseudoprogression” describes the inflammatory reaction to effective treatment. Increasing steroid doses can control the edema.

4. Antiepileptic drugs. Prophylactic use of antiepileptic drugs (AEDs) is not recommended in patients with brain tumor due to lack of efficacy. The interactions between AEDs and chemotherapy can also be problematic.

5. Quality of life issues. The incidence of common symptoms reported was fatigue (90%–94%), sleep disturbance (32%–52%), headache (50%), and cognitive impairment (50%). Ritalin, modafinil, and Aricept have all been shown to have a positive effect on mood and cognition. Cause of death was presumed brain herniation 73% of the time.

References:

Diagnosis, treatment, and prognosis of glioma. Five new things. Lynne P. Taylor, MD. Neurology November 2, 2010 vol. 75 no. 18 Supplement 1 S28-S32.

Image source: Sen. Kennedy who died of glioma in 2009, Wikipedia, GNU Free Documentation license.

Romiplostim for Treatment on Immune Thrombocytopenia (ITP)

Romiplostim, a thrombopoietin mimetic, increases platelet counts in patients with immune thrombocytopenia, with few adverse effects.

In this open-label, 52-week study (funded by Amgen), 234 adult patients with immune thrombocytopenia, who had not undergone splenectomy, were randomized to receive the standard of care or weekly subcutaneous injections of romiplostim.

The rate of a platelet response in the romiplostim group was 2.3 times that in the standard-of-care group.

Patients receiving romiplostim had a significantly lower incidence of treatment failure [11%] than those receiving the standard of care [30%].

Splenectomy also was performed less frequently in patients receiving romiplostim [9%]) than in those receiving the standard of care [36%].

The romiplostim group had a lower rate of bleeding events, fewer blood transfusions, and greater improvements in the quality of life.

Romiplostim is a fusion protein analog of thrombopoietin. It is marketed under the trade name Nplate through a restricted usage program. Romiplostim was designated an orphan drug by the FDA in 2003, as the chronic ITP population in the USA is under 200,000.

In 2008, the FDA approved romiplostim as a long-term treatment for chronic ITP in adults who have not responded to other treatments, such as:

- corticosteroids

- intravenous immunoglobulin (IVIG)

- Rho(D) immune globulin

- splenectomy

References:

Romiplostim or Standard of Care in Patients with Immune Thrombocytopenia. NEJM, 2010.
Immune Thrombocytopenia - 2010 Review in Hematology http://goo.gl/tXT2U

Immune thrombocytopenia: No longer ‘idiopathic’ http://goo.gl/z2Ks0
Immune thrombocytopenia in adults: An update. CCJM, 2012. 

Image source: Nplate.com

Anxiety treatment app from Mayo Clinic: "Anxiety Coach" ($5)

"Mayo Clinic Anxiety Coach is designed to help people start mastering their fears and worries one step at a time. Watch this video to learn more about this iOS app and whether it might be helpful for you."



For more information go to: https://itunes.apple.com/us/app/anxietycoach/id565943257

Description

Mayo Clinic Anxiety Coach is a comprehensive self-help tool for reducing a wide variety of fears and worries from extreme shyness to obsessions and compulsions. Anxiety Coach helps you make a list of feared activities and then guides you through mastering them one by one. Through this experience you can increase your confidence as you become less fearful and worried.

Anxiety Coach was developed by two clinical psychologists recognized as experts in the treatment of anxiety disorders. Dr. Stephen P. H. Whiteside is the director of the Pediatric Anxiety Disorders Program at Mayo Clinic. Dr. Jonathan Abramowitz is an internationally known expert on adult anxiety disorders at the University of North Carolina.

The strategies used in Anxiety Coach are based on cognitive behavioral therapy (CBT), the most effective psychotherapy for fears and worries. In CBT people increase their confidence by gradually confronting situations that they have avoided out of fear. Research has demonstrated that CBT is more effective for anxiety than other approaches that rely on teaching people to relax.

With Mayo Clinic Anxiety Coach you can:

•Take a short self-test to measure the severity of your fears and worries
•Make a personal plan to target your individual fears and worries
•Browse a library of over 500 activities that other people have found help to master a wide variety of fears and worries including:
osocial anxiety, obsessions and compulsions, specific fears, separation anxiety, panic attacks, trauma related anxiety, and general worries.
•Track your anxiety while you’re challenging your fears and worries in real-life situations
•Record and view your progress
•Learn about when anxiety becomes a problem and how to seek treatment

Vedolizumab (anti-integrin) is effective for treatment of ulcerative colitis and Crohn's disease

The integrin superfamily consists of 30 proteins that promote cell-cell or cell-matrix interactions. The name integrins derives from the idea that they coordinate (i.e., "integrate") signals.

All integrins are cell surface proteins composed of 2 polypeptide chains, α and β. Integrins are classified into several subfamilies based on the β chains.



Lymphocyte Trafficking. This video describes how lymphocytes travel through the blood stream and into a lymph node. This video is from: Janeway's Immunobiology, 7th Edition, Murphy, Travers, & Walport. Source: Garland Science.

7 Integrin, a cell adhesion molecule, is present in the form of α4β7 integrin or αEβ7 integrin. α4β7 Integrin is expressed on most leucocytes and is essential for their migration to gut-associated lymphoid tissues by interacting with its primary ligand, mucosal addressin cell adhesion molecule-1, which is preferentially expressed in gut-associated lymphoid tissues.

Vedolizumab is a monoclonal antibody being developed by a subsidiary of Takeda Pharmaceuticals for the treatment of ulcerative colitis and Crohn's disease. It binds to integrin α4β7 (LPAM-1, lymphocyte Peyer's patch adhesion molecule 1). Blocking the α4β7 integrin results in gut-selective anti-inflammatory activity by blockade of lymphocyte trafficking.

Sunanda Kane, M.D., a gastroenterologist at Mayo Clinic specializing in the care and evaluation of patients with IBD, discusses two articles recently published in NEJM that found patients with ulcerative colitis or Crohn's disease benefited from treatment with vedolizumab compared with placebo. She discusses how vedolizumab is different than other drugs currently used to treat IBD.



Recruitment of Leukocytes to Sites of Infection can be remembered by the mnemonic: "SIP of wine":

Selectins
Integrins
Penetration of of the basement membrane (BM) by PMN

Selectins are first in the chain of events. They upregulate TNF and IL-1. Integrins cause release of VCAM and VLA.

Adhesion molecules, 3 groups are remembered by the mnemonic SIS:

Selectins
Integrins
Superfamily Ig

References:

http://www.ncbi.nlm.nih.gov/pubmed/21047673
http://www.nejm.org/doi/full/10.1056/NEJMe1307415
http://www.nejm.org/doi/full/10.1056/NEJMoa1215739
http://www.nejm.org/doi/full/10.1056/NEJMoa1215734

New hepatitis C treatment: 2 new medications may increase success rate to 70%

Mayo Clinic: Four million people in the U.S., 100 million worldwide, are infected with Hepatitis C. It's a virus you can get from blood transfusions given before 1990, shared needles, unclean tattoo needles and sometimes sex.

In many cases it leads to cirrhosis of the liver and eventually liver cancer. Standard treatment with interferon and ribavirin only cures about 45% of all patients. But thanks to two new medications, up to 70% of people with hepatitis C may be be cured. More than 40 medications are in development.

Celiprolol as treatment of choice to prevent complications in vascular Ehlers-Danlos syndrome

Vascular Ehlers-Danlos syndrome is a rare hereditary connective tissue disorder caused by mutations in the collagen type III gene ( COL3A1 ), which leads to a loss of tissue integrity in many organ systems.

Patients with vascular Ehlers-Danlos syndrome have weakened blood vessels and an increased risk of arterial dissection or rupture that can lead to early death.

The researchers assessed the ability of celiprolol, a β1-adrenoceptor antagonist with a β2-adrenoceptor agonist action, to prevent arterial dissections and ruptures in vascular Ehlers-Danlos syndrome.

Patients with clinical vascular Ehlers-Danlos syndrome were randomly assigned to 5 years of treatment with celiprolol or to no treatment.

33 patients were positive for mutation of collagen 3A1 (COL3A1). Celiprolol was uptitrated every 6 months by steps of 100 mg to a maximum of 400 mg twice daily. The primary endpoints were arterial events (rupture or dissection, fatal or not).

Mean duration of follow-up was 47 months, with the trial stopped early for treatment benefit.

The primary endpoints were reached by 20% in the celiprolol group and by 50% controls (hazard ratio [HR] 0·36).

Celiprolol might be the treatment of choice for physicians aiming to prevent major complications in patients with vascular Ehlers-Danlos syndrome.

References:

Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. The Lancet, Volume 376, Issue 9751, Pages 1476 - 1484, 30 October 2010.

Celiprolol therapy for vascular Ehlers-Danlos syndrome. The Lancet, Volume 376, Issue 9751, Pages 1443 - 1444, 30 October 2010.