Terlipressin v. hepatorenal syndrome
Hepatorenal syndrome (HRS) involves advancing renal failure in a patient with chronic liver disease, such as cirrhosis. HRS often presents itself with portal hypertension and ascites, and a significant percentage of cirrhosis patients with ascites end up developing HRS.
In October Dr. Didier Lebrec, senior past president of the International Association for the Study of the Liver and consultant at Hôpital Beaujon in France, spoke in a symposium during the Hepatology Society of the Philippines convention. Lebrec discussed the issues surrounding HRS, as well as the role of terlipressin in its management.
Lebrec noted that a third of patients with chronic cirrhosis ascites. Of those who develop ascites, 10 percent develop the refractory form of the disease while one percent end up having HRS. that patients with cirrhosis develop ascites approximately 1/3 of these patients.
Those who end up developing HRS usually have the following risk factors: low urinary sodium excretion (<5 mEq/L), low serum sodium, and low arterial blood pressure, among others.
One option that has shown significant promise is the use of sys-temic vasoconstrictors, specifically the vasopressin analog terlipressin.
Moreau and colleagues (2002), in a multicenter retrospective study involving 99 patients, evaluated the clinical course and predictive factors of survival in patients with type 1 hepatorenal syndrome treated with terlipressin. The study looked at how terlipressin improved renal function, which was defined as a decrease in serum-creatinine value to < 130 µmol/L ,or a decrease of about 20 percent at the end of treatment.
At the end of the study period, renal function improved 58 percent of the patients. Serum creatinine also decreased (46 percent ± 17 percent from 272 ± 114 µmol/L). Also, median survival rate at one month was 40 percent.
Still, Lebrec would like to stress the importance of prevention in HRS. SAID LEBREC: "We know that ... five percent of [patients admitted for variceal bleeding] develop hepatorenal syndrome. Following total paracentesis, approximately 10 percent develop hepatorenal syndrome. In patients admitted for acute alcoholic hepatitis, one out of four [develop HRS], and in patients with spontaneous bacterial peritonitis, 30 percent. Accordingly, you can see that you have to prevent this complication by preventing these complications."
M Gayleen Caballero
Sanofi-Aventis launches Solosamet
Current estimates by the International Diabetes Federation (IDF) pegs the global prevalence of type 2 diabetes mellitus at 250 million. If current trends don't change, the number of type 2 diabetes patients would hit the 380-million mark by 2025. In addition, the Philippines would enter the list of countries with the highest burden of type 2 diabetes.
The fact that uncontrolled type 2 diabetes could lead to serious complications does not only signify an overall increase in morbidity and mortality-it could also bring about significant socioeconomic consequences.
In a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes (Diab Care, 2006), the first step in controlling hyperglycemia involves lifestyle modification, to which metformin can be added. If the glycosylated hemoglobin is seven percent or higher, another treatment may have to be added-basal insulin, a sulfonylurea, or a glitazone.
However, considering that a great number of type 2 diabetes patients are overweight or obese, they may have to be immediately started on combination treatment, which may pose certain patient-related challenges, including cost and certain fears concerning the use of insulin injections.
During the annual convention of the Philippine Diabetes Association in November, Sanofi-Aventis launched its combination glimepiride/metformin (Solosamet) to address the treatment needs of patients with type 2 diabetes.
Dr. Araceli Panelo of the University of the East-Institute for the Study of Diabetes Foundation discussed the benefits of metformin, considered the "world's most widely used antidiabetic agent" for promoting insulin sensitivity.
Metformin has also been found to contribute to lowering of triglycerides and cholesterol, as well as promoting weight loss. Both effects are independent of the drug's role in preventing insulin resistance.
Meanwhile, Dr. Ruby Go, president of the Philippine Lipid and Atherosclerosis Society, said that the use of the sulfonylurea glimepiride has shown efficacy and safety as an insulin secretagogue and sensitizer. It has also been found to have significant effects on vasculature, since it inhibits the oxidative modification of low-density lipoproteins , a fact that is linked to the development of atherogenic lesions.
Glimepiride is also known to contribute to "ischemic precon-ditioning," which could protect myocardial function and prevent tissue damage. The new glimperide/metformin combination (Solosamet) aims to offer patients not only improved blood-sugar control, but also other independent benefits such as weight loss, lipid-lowering, and cardioprotection.
M
Prexige suspended in UK, Germany
ZURICH
Novartis announced its antiinflammatory drug lumiracoxib (Prexige) had been suspended from sale and marketing in Britain and Germany amid fears it can cause liver damage. Britain's Medicines and Healthcare Products Regulatory Agency said it was suspending the license of lumiracoxib "due to the safety concerns about possible liver damage for patients."
Novartis said it is informing regulatory agencies around the world of these changes, which come after similar actions in other countries in recent months. It said it will also comply with a request from the Austrian health authority to suspend sales pending a final decision by the Committee for Medicinal Products for Human Use, which reviews medicines in the European Union.
Germany and Austria have also taken similar steps, following suspensions earlier this year in Canada and Australia, Novartis said.
"Other EU countries may decide to independently suspend the marketing authorisation or sale of Prexige ahead of a decision" by the EU's medical regulator expected in December, it added.
The company said that "available data suggest that Prexige 100 mg once-daily for osteoarthritis is not associated with increased hepatic risk" compared with other painkillers.
The latest analysis of patients taking the Prexige 100-mg dose showed nine severe hepatic events reported worldwide. This corresponds to a rate of 5.19 events per 100,000 patient-years, which is within the rate expected for nonsteroidal antiinflammatory drugs (NSAIDs). Although a direct comparison cannot be made between spontaneous reports and epidemiological data, a major analysis of epidemiological studies on NSAID-induced liver injury resulting in hospitalization showed an incidence rate of between 3.1 and 23.4 per 100,000 patient-years, according to studies cited by Novartis.
Prexige is the only selective cyclooxygenase-2 inhibitor shown to demonstrate gastrointestinal (GI) benefit in patients with osteoarthritis in a large outcome study versus other NSAIDs, decreasing serious GI ulcer complications (including bleeds) by over 70 percent. NSAID-related serious GI ulcer complications occur more frequently than hospitalization for hepatic complications. Approximately 1,000 deaths related to GI ulcerations from NSAIDSs occur in the UK each year.
Novartis continues to believe Prexige is an important treatment option with a positive benefit/risk ratio when used in appropriate patients. Novartis will continue discussions with European health regulators, and with the United States Food and Drug Administration, following its decision in September not to approve Prexige, to determine how to make this treatment option available to appropriate patients. With a report from
M AFP
New drug helps cure liver disease
CHICAGO
A new drug offers promise of helping to cure patients suffering from hepatitis C and other liver diseases who otherwise would not have been able to get treatment. The drug, called eltrombopag, also appears to be an effective treatment for a common blood disorder that causes bruising and excessive bleeding. It could also eventually be used to help in cancer treatment.
Results of two studies published in the New England Journal of Medicine showed eltrombopag serves to boost blood platelet counts, a critical component to blood clotting. When platelet counts get too low there is a risk of serious bleeding. Patients with low platelet counts are often either deemed unfit for treatment or must receive costly and complex transfusions prior to undergoing surgery.
This is particularly problematic in the estimated 170 million patients worldwide infected with the hepatitis-C virus. The potentially fatal virus damages the liver and can also cripple the body's ability to manufacture platelets. Only about half of those diagnosed get cured with standard antiviral treatments.
"There's this huge group of patients with hepatitis C where we try to treat them and their platelet counts drop or we're afraid to treat them," said lead author John McHutchison, an Australian researcher at Duke University in North Carolina.
McHutchison and his colleagues have already started phase-III clinical trials to confirm the results and see if the drug is able to safely maintain platelet counts long enough for patients with hepatitis C to undergo a full course of treatment and be cured.
The double-blind study looked at 74 hepatitis-C patients in 22 centers in the US and Europe who had developed cirrhosis and had very low platelet counts. Platelet counts were raised significantly in at least 75 percent of those receiving the drug, which is taken orally once a day, while 95 percent of those receiving the highest dose saw their platelet counts jump in the four weeks of treatment.
The drug was also found to be effective in treating idiopathic thrombocytopenic purpura, which causes bleeding and bruising because the blood does not clot properly due to low platelet counts.
The second study found that eltrombopag was effective in significantly boosting the platelet counts and reducing bleeding incidents in 80 percent of patients receiving either 50 or 75 milligrams a day within 15 days of treatment.
M M. Oberman
New AIDS vaccine goes on trial
GENEVA
Swiss firm Mymetics said it will start in 2008 phase-I trials of a possible AIDS vaccine that seeks to produce mucosal antibodies that can resist HIV. The trials will take place in Belgium on a sample of 30 to 40 women, Mymetics' scientific director Sylvain Fleury said.
Over 85 percent of HIV infections are the result of genital or intestinal mucosa being exposed to the disease, he said. Any HIV vaccine that could successfully achieve antibody production into both genital and intestinal tracts might open the door to a new HIV vaccine approach, Mymetics said on its web site.
The Swiss company said it hopes to take its research further, and then either enter into a partnership with a larger company or sell the product technology to move to phase-III trials. Mymetics estimates the vaccine could produce annual sales revenue of between US$2 billion to US$4 billion per year.
M AFP
Out of HER reach
The advent in Philippine medical practice three years ago of a new diagnostic tool in breast cancer, HER2/neu (human epidermal-growth-factor-receptor 2) testing, is hailed as a breakthrough that will critically impact survival, especially with the high rate of advanced breast-cancer cases among Filipinas.
But whether it now comes in handy to improve prognosis of actual patients in the Philippines is a question freighted with more than just medical considerations, according to medical oncologist Antonio Villalon of the University of the Philippines-Philippine General Hospital at a recent breast-cancer forum organized by AstraZeneca.
By detecting HER2/neu overexpression in breast-cancer cells, HER2/neu testing determines how aggressive the disease is and what modes of treatment are appropriate. It is supposed to go in tandem with the more standard ER/PR (estrogen receptor/progesterone receptor) test which determines the eligibility of patient for hormone-based treatment (e.g. tamoxifen and aromatase inhibitors) as opposed to chemotherapy.
With less estrogen in them, more postmenopausal women-around 80 to 85 percent-tend to be receptive to hormone-based therapy, with its promise of a better prognosis, as compared with younger, still menstruating women among whom the cancer tends to be more aggressive. With an additional assay like the HER2/neu testing, the scale of survival is somewhat evened to favor younger, more vulnerable patients.
Radiation oncologist Enrico Tangco of The Medical City said that it is not the accessibility of the HER2/neu-testing facility per se that is at issue. He explained: "It's very easy to send the specimens to the hospital. Another problem actually is the expense for the tests. The FISH (fluorescence in situ hybridization) test alone costs about PhP12,000, not exactly the cheapest test to do but one that needs to be done anyway along with the ER/PR test if a patient wants to get the proper treatment."
Two levels of testing might be required. An immunohistochemistry test initially screens whether the patient is negative, positive, or equivocal. Equivocal cases are referred for a second round of examination using either the FISH or the CISH (chromogenic in situ hybridization) methods. FISH is more commonly used in the Philippines.
For HER2/neu positive cases, the eventual choice of medication is again to be dictated by economics because the recently introduced targeted therapy is also quite expensive. Traztuzumab (Herceptin), an antibody therapy that works in preventing HER2 receptors from receiving growth signals, is prescribed along with chemotherapy to HER2/neu-positive cases. But if money were an issue, the patient could always fall back on chemotherapy alone. "Even if the patient won't be able to afford Herceptin, the type of chemotherapy to be given will be more aggressive and of longer duration, in an effort to compensate for the lack of Herceptin," said Tangco.
Villalon noted that it all boils down to prioritizing early detection. "Treatment is very expensive and is getting expensive each year, especially as they discover more targeted therapy. It would be very difficult for developing countries."
M Grace Roxas
MSD launches Rotateq
Clinicians may be sounding the alarm for amoebiasis far more frequently than they should because of misleading circumstances among pediatric patients who show symptoms of gastric disturbances. This can result in faulty prescription such as giving antibiotics meant for parasitic or bacterial infections for what could in fact be a viral infection, says pediatrician Benjamin Co of the University of Santo Tomas Hospital.
Speaking during the launch of the new rotavirus vaccine by Merck, Sharpe & Dohme, Lim explained that the misdiagnosis is often precipitated by mistaking the consistency of the stool sample taken from patients, especially toddlers in diapers.
When the liquid part of watery stool-characteristic of viral infections-is absorbed by the diaper and only the solid portion is scraped and sent for stool examination, a wrong diagnosis of Entamoeba histolytica infection might be the result, if the laboratory is less than careful and misjudges the stool sample as solid.
"The only way a child can get E. histolytica is if the stool of the child is not watery," Lim said. "If it is watery, there's not time for the parasite to insist."
He added that amoebiasis is also usually associated with eating fresh garden vegetables, not exactly a common item in many toddlers' diet.
He said that rotavirus vaccination can do a lot to narrow down the margin of error in diagnosis by eliminating a leading cause of gastroenteritis from the equation. In the Philippines, studies that Lim cited place rotavirus-related diarrhea at 40 percent of the total diarrhea incidence.
Rotavirus is not only the most common viral cause of diarrhea but is also responsible for the most severe episodes among young children. It is highly contagious and is a hardy survivor not controlled by conventional sanitation or hygiene measures such as hand washing. Diarrhea itself ranks as the second highest cause of morbidity and mortality in children under five years of age.
Rotateq is the second rotavirus vaccine introduced in the Philippines, which is said to have a higher incidence of rotaviral infection than other developing countries such as Vietnam and Nepal. It is an oral vaccine effective against five serotypes of the virus.
"Global vaccination against rotavirus can hopefully prevent the severe episodes," said Lim, adding that the end point for the vaccine is the prevention of cases serious enough to require hospitalization and emergency-room visits. Rotavirus infection can recur several times, with each recurrence being less severe than the previous ones.
Lim also cited studies pegging the efficacy of the vaccine in preventing severe infections at 90 percent. Rotateq could also prevent rotaviral diarrhea of any severity by 74 percent, as well as reduce hospitalization by 96 percent.
With a greater take-up of the vaccine in the market, Lim believes that it will soon become more affordable. "Hopefully, all government programs will include rotavirus vaccines," he said. "When many people use a vaccine, the cost of the drug goes down eventually, like in the case of the chickenpox vaccine."
M Grace Roxas
Cervarix attacks HPV where it is
Beijing
Two years after the first of three doses, antibodies against the two most common cervical-cancer-causing virus types, induced by Cervarix, have been found where they are needed, in the cervix, according to new data presented at the International Papillomavirus Conference (IPC) in Beijing.
Cervarix has been shown to induce antibodies against the two most common cancer-causing virus types, 16 and 18, which were detectable in the cervix, where the virus infects and replicates. High correlation between the levels of antibodies in the bloodstream and in the cervix was observed up to two years after the first of three doses of the vaccine, in women aged 15 to 55 years.
"The human-papillomavirus (HPV) types that cause cervical cancer are particularly challenging-the virus can evade the immune system by replicating only in the cervix. This study shows that the vaccine is able to induce antibodies in the blood that can reach the cervix, where the virus infects and develops into cervical cancer and where protection is mostly needed" said Prof. Tino Schwarz of the Stiftung Juliusspital, Academic Teaching Hospital of the University of Wuerzburg, Germany.
"The high correlation between antibodies induced by Cervarix in the bloodstream and those able to reach the cervix provides further insights on the quality of the immune response induced by the vaccine, and also on how the vaccine may help provide protection against cancer-causing virus types," explained Dr. Hugues Bogaerts, vice president for worldwide medical affairs HPV at GlaxoSmithKline Biologicals.
"We expect this correlation to remain high in time, as we know the observation of cervical antibodies was made at 24 months, which is the time when levels of vaccine-induced antibodies in the bloodstream become stable and are maintained for at least five years, according to data from existing trials on our cervical cancer vaccine," concluded Bogaerts.
Cervarix is formulated with AS04, a novel adjuvant technology, specifically designed and selected to enhance the immune response against the human papillomavirus responsible for cervical cancer.
These data on antibody levels in the cervix are part of an ongoing study investigating the immune response induced by Cervarix in women 15 to 55 years of age.
Earlier data from this and other studies in girls and women between 10 and 55 years demonstrated that all women vaccinated with the vaccine had a strong immune response against the two most common cancer-causing HPV types. "This vaccine could potentially protect women of all age groups against cervical cancer" explained Schwarz.
A second study presented at IPC showed Cervarix induced consistently high levels of antibodies against virus types 16 and 18 for over 5.5 years in women 15 to 25 years old. The ongoing phase-II study also indicated 100-percent efficacy against precancerous lesions due to virus types 16 and 18 for over 5.5 years.
This is the longest duration of consistently high immune response shown by a cervical-cancer vaccine against the two most common cancer-causing virus types to date. Cervarix is the only one that has shown to induce high levels of antibodies against both virus types 16 and 18 over 5.5 years.
The burden of virus types 16 and 18 is huge, but the risk of cervical cancer extends beyond these two types. Cervarix has been tested in clinical trials involving over 18,000 females.
Phase-II data indicate that Cervarix provides strong protection specifically against incident infection caused by two additional cancer-causing virus types (31 and 45) for over 5.5 years, in addition to 100-percent protection against precancerous lesions due to virus types 16 and 18 over the same period of time.
Later phase-III data reinforced these findings by demonstrating that Cervarix provides 100-percent protection against advanced precancerous lesions caused by virus types 16 and 18, and significant protection against six-month persistent infection caused by virus types 45 and 31. The vaccine also demonstrated protection against 12-month persistent infection against 12 other cancer-causing HPV types other than types 16 and 18.
M
Vaccine v. Japanese encephalitis
PARIS
A prototype vaccine against Japanese encephalitis, a viral disease endemic in Southeast Asia and parts of South Asia, is safe and triggers a good immune response against the pathogen. The test vaccine, made by a Scottish subsidiary of Intercell AG, an Austrian company, was tested on 867 adults in the United States, Britain, and Austria. Response from antibodies was twice that for a existing vaccine against the disease and side effects "were generally mild," according to the study, which appears in The Lancet.
Around 50,000 cases of Japanese encephalitis occur each year, mainly in children under 10, according to the US Centers for Disease Control (CDC). An outbreak in northern India this year claimed more than 300 lives. The natural reservoir for the virus is pigs and wild birds.
The disease has been mainly fought using a vaccine derived from the brains of mice that have been infected with the virus. The virus is then inactivated using chemicals before it is introduced into the body. The problem, though, is that this vaccine is expensive, difficult to produce, needs three doses and has been associated with bad but rare, allergic responses. Some research has pointed the finger at pig gelatin stabilizers or residual mice proteins in the vaccine as the cause of these responses.
The test vaccine, delivered in two shots, is based on a purified but inactivated virus, grown in lab-dish cells, to prime the immune system. It is a promising candidate for travelers at risk and should be further studied for use among children in endemic countries, said Marc Fischer of the CDC and colleagues in a commentary.
An alternative, Chinese-made vaccine, based on virus grown in hamster cells, is also increasingly being used against the disease. Several Asian countries have licensed it, including Nepal and India, which used it to vaccinate 30 million children in 2006 and 2007. The Chinese formula needs fewer doses and is less expensive and easier to produce than the mouse-derived vaccine.
M AFP
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