精神科診斷標準出了新版

中國發佈的死亡率，毫不可靠! (一定要參看自由時報這篇報導:  http://tw.myblog.yahoo.com/ccshsu-clement/article?mid=10766&prev=10769&next=10764&l=a&fid=83)  我將下列comment寄到ProMED digest  (ISID發行的免費報導世界各地動植物傳染病狀況的，很有用newsletter) 負責人，但其主編回信寫了一大堆不相干的話，似乎是說我寄錯人了。我又再看到Medscape Daily Medical Newletter [http://www.medscape.com/viewarticle/804596?nlid=31385_1661&src=wnl_edit_dail&uac=131220CK] 報導同樣文章之後，再寫一篇回應如下。

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My understanding is that in China, they only test those
who developed pneumonia for the presence of H7N9 infection. And
those tested positive are counted as the infected, and used as the denominator
to figure out the "mortality rate". Those who are infected but
asymptomatic, or have minor symptoms were not even tested for the H7N9.   So the denominator will be erroneously low in
number, and the mortality rate is erroneously "very high".   No wonder 97.3% of those patients in this
report had findings consistent with pneumonia on chest radiography. 

This
is not a matter of whether H7N9 infection has high mortality or not.  The issue is how mortality rate of an infection
should be calculated.

Shouldn't
the mortality rate of H7N9 infection derived by the number of those who died
from H7N9 infection (the numerator), divided by the number of people who were
infected regardless of whether they developed pneumonia or not (the
denominator) ?

This
highly irregular, if not irresponsible, way of "enumerating the mortality
rate of H7N9 infection" was reported by two Taiwan epidemiologists who
were officially sent to visit Shanghai Health Bureau and two Infectious Disease
Hospitals for 4 days to understand the status of H7N9 infection the first-hand
in early part of April, this year.  Their
report was on the first page of the Liberty Times, with their photo, after
their return to Taiwan.

Please
check it out with the health officials in charge in China. Some basic concepts
need to be clarified with them.  I have
known from other sources that the medical management in China is still some
distance behind the US standard.

If
what those epidemiologists found after visiting Chinese health officials was
correct, I do have a question.  Why these
Taiwanese epidemiologists voice was not heard?  Whether Taiwan is a member country of WHO or
not, this is a matter that involves epidemics that know no boundary.

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WHO Says New Bird Strain Is 'One of Most Lethal' Flu Viruses

Apr 24, 2013

(Reuters) - A new bird flu strain that has killed 22 people in China is "one of the most lethal" of its kind and transmits more easily to humans than another strain that has killed hundreds since 2003, a World Health Organization (WHO) expert said on Wednesday.

The H7N9 flu has infected 108 people in China since it was first detected in March, according to the Geneva-based WHO.

Although it is not clear exactly how people are being infected, experts say they see no evidence so far of the most worrisome scenario - sustained transmission between people.

An international team of scientists led by the WHO and the Chinese government conducted a five-day investigation in China, but said they were no closer to determining whether the virus might become transmissible between people.

"The situation remains complex and difficult and evolving," said Keiji Fukuda, the WHO's assistant director-general for health security.

"When we look at influenza viruses, this is an unusually dangerous virus for humans," he said at a briefing.

Another bird flu strain - H5N1 - has killed 30 of the 45 people it infected in China between 2003 and 2013, and although the H7N9 strain in the current outbreak has a lower fatality rate to date, Fukuda said: "This is definitely one of the most lethal influenza viruses that we've seen so far."

Scientists who have analyzed genetic sequence data from samples from three H7N9 victims say the strain is a so-called "triple reassortant" virus with a mixture of genes from three other flu strains found in birds in Asia.

Recent pandemic viruses, including the H1N1 "swine flu" of 2009/2010, have been mixtures of mammal and bird flu - hybrids that are more likely to be milder because mammalian flu tends to make people less severely ill than bird flu.

Pure bird flu strains, such as the new H7N9 strain and the H5N1 flu, which has killed about 371 of 622 the people it has infected since 2003, are generally more deadly for people.

UNSETTLING

The team of experts, who began their investigation in China last week, said one problem in tracking H7N9 is the absence of visible illness in poultry.

Fukuda stressed that the team is still at the beginning of its investigation, and said that "we may just be seeing the most serious infections" at this point.

Based on the evidence, "this virus is more easily transmissible from poultry to humans than H5N1", he said.

Besides the initial cases of H7N9 in and around Shanghai, others have been detected in Beijing and five provinces. On Wednesday, Taiwan's Health Department said a businessman had contracted H7N9 while travelling in China and was in a serious condition in hospital.

Samples from chickens, ducks and pigeons from poultry markets have tested positive for H7N9, but those from migratory birds have not, suggesting that "the likely source of infection is poultry", said Nancy Cox, director of the influenza division at the U.S. Centers for Disease Control and Prevention.

John Oxford, a flu virologist at Queen Mary University of London, said the emergence of human H7N9 infections - a completely new strain in people - was "very, very unsettling".

"This virus seems to have been quietly spreading in chickens without anyone knowing about it," he told Reuters in London.

Flu experts say it is likely that more cases of human infection with H7N9 flu will emerge in the coming weeks and months, at least until the source of infection has been completely confirmed and effectively controlled.

Anne Kelso, the Melbourne-based director of the WHO Collaborating Centre for Reference and Research on Influenza said there has been a "dramatic slowdown of cases" in the commercial capital of Shanghai, which has recorded most of the deaths, something she described as "encouraging".

After Shanghai closed down its live poultry markets in early April, there was an almost immediate decline in new H7N9 cases, she said. "The evidence suggests that the closing of the live poultry markets was an effective way to reduce the risks."

Even so, the WHO's China representative, Michael O'Leary, issued figures last week showing that half of the patients analyzed had no known contact with poultry.

(Editing by Louise Ireland)

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H7N9 Influenza: Most Patients Critically Ill

Troy Brown

Apr 25, 2013

Most of the 82 patients studied who developed H7N9 became critically ill and were epidemiologically unrelated, according to an analysis of data obtained from field investigations of cases that occurred in China before April 17, 2013. Human-to-human transmission between close contacts has not been confirmed but could not be ruled out in 2 families in an analysis by a group of researchers from China and the Centers for Disease Control and Prevention.

Qun Li, MD, from the Public Health Emergency Center in China, and colleagues present their findings in an article published online April 24 in the New England Journal of Medicine.

The researchers defined a confirmed case as one verified by H7N9 virus presence by positive real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR), viral isolation, or serologic testing. Close contacts were observed for 7 days. The investigators obtained throat swabs from symptomatic contacts and tested for the H7N9 virus by real-time RT-PCR.

Among the 82 confirmed cases, the median age was 63 years (range, 2 - 89 years): 38 cases (46%) occurred in patients aged 65 years or older and 2 (2%) in children younger than 5 years. Both children had clinically mild upper respiratory illness. Two suspected cases were also found.

Of the confirmed cases, 73% were male, and 84% were urban residents. Of the 71 patients with available data, 54 (76%) had underlying medical conditions. Cases were reported in 6 areas of China.

Eighty-one patients with confirmed disease (99%) were hospitalized and 17 (21%) confirmed cases, and a single suspected case died of acute respiratory distress syndrome or multiorgan failure. A total of 60 confirmed cases and 1 suspected case remained critically ill as of April 17; 4 patients were discharged from the hospital, and 1 child was never hospitalized.

Animal Exposure

Animal exposure data were available for 77 of the confirmed cases. Of these patients, 59 (77%) had recent animal exposure: 45 (76%) to chickens, 12 (20%) to ducks, and 4 (7%) to swine. The individuals had either worked at or visited a live animal market. These patients also reported exposure to pigeons, geese, quail, wild birds, pet birds, cats, and dogs. History of animal exposure was unclear for the remaining 5 patients, in whom investigations were still ongoing.

The researchers estimated the median incubation period was 6 days in 23 patients for whom detailed data were available.

Of the 1689 close contacts, 1251 completed the 7-day monitoring period. A few (19; 1.5%) developed respiratory symptoms, but they all tested negative for the H7N9 virus.

There were 2 family clusters in which human-to-human transmission could not be ruled out. In one, a brother and his father were in prolonged, close contact with the index case. The father and brother cared for the index case and ate meals together. The index case had contact with live poultry, but the father and brother did not.

In the other family, a father had suspected illness and his daughter had prolonged, close, unprotected contact with him. She was later confirmed to have H7N9 illness. The father had contact with live poultry, but the daughter had no contact with poultry or pigs.

The investigators had data regarding oseltamivir administration for 64 patients, of whom 41 (64%) received oseltamivir starting a median of 6 days after illness onset.

"Although the risk of human-to-human transmission of H7N9 virus appears to be low, the actual risk is currently unknown, and the Chinese national guidelines recommend implementing control measures, such as prompt isolation of the patient, active monitoring of close contacts, and implementation of standard, contact, and droplet precautions by health care personnel in hospitals," the authors write.

"In addition, national guidelines recommend that antiviral treatment with oseltamivir should be administered as soon as possible in patients with suspected or confirmed cases of H7N9 virus infection," they conclude.

The China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases provided financial support to a number of individuals and institutions for travel and accommodation fees for fieldwork, attendance at an investigator meeting, equipment, and fees for manuscript preparation. Two researchers reported employment at Jiangsu Provincial Center for Disease Control and Prevention. Two researchers received consulting fees from and 2 researchers reported employment by the China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases. Two researchers reported receiving fees for travel to major meetings for the past 3 years.

N Engl J Med. Published online April 24, 2013.

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Confirmed: New H7N9 Bird Flu Comes From Chickens

Apr 25, 2013

By Kate Kelland

LONDON (Reuters) Apr 25 - Chinese scientists have confirmed for the first time that a new strain of bird flu that has killed 23 people in China has been transmitted to humans from chickens.

In a study published online today in the Lancet, the scientists echoed previous statements from the World Health Organization (WHO) and Chinese officials that there is as yet no evidence of human-to-human transmission of this virus.

The H7N9 strain has infected 109 people in China since it was first detected in March. The WHO warned on Wednesday that this strain is "one of the most lethal" flu viruses and is transmitted more easily than the H5N1 strain of bird flu, which has killed hundreds around the world since 2003.

Kwok-Yung Yuen of the University of Hong Kong, who led the study, said its findings that chickens in poultry markets were a source of human infections meant that controlling the disease in these places and in these birds should be a priority.

"Aggressive intervention to block further animal-to-person transmission in live poultry markets, as has previously been done in Hong Kong, should be considered," he said.

He added that temporary closure of live bird markets and comprehensive programs of surveillance, culling, biosecurity and segregation of different poultry species may also be needed "to halt evolution of the virus into a pandemic agent."

"The evidence ... suggests it is a pure poultry-to-human transmission and that controlling (infections in people) will therefore depend on controlling the epidemic in poultry," he said.

Yuen's findings do not mean all cases of human H7N9 infection come from chickens, or from poultry, but they do confirm chickens as one source.

The WHO has said 40% of people infected with H7N9 appear to have had no contact with poultry.

Other types of birds or mammals may be acting as so called "reservoirs" of the flu virus and investigators in China are working hard to try to find out.

CASE STUDIES

Yuen's team conducted detailed case studies on four H7N9 flu patients from Zhejiang, an eastern coastal province south of the commercial hub Shanghai.

All four patients had been exposed to poultry, either through their work or through visiting poultry markets.

To find out whether there was transmission of the virus from poultry to humans, the researchers took swabs from 20 chickens, four quails, five pigeons and 57 ducks, all from six markets likely to have been visited by the patients.

Two of the five pigeons and four of the 20 chickens tested positive for H7N9, but none of the ducks or quails.

After analyzing the genetic makeup of H7N9 virus in a sample isolated from one patient and comparing it to a sample from one of the chickens, the researchers said similarities suggest the virus is being transmitted directly to humans from poultry.

The team also checked more than 300 people who had had close contact with the four patients and found that none showed any symptoms of H7N9 infection within 14 days from the beginning of surveillance. This suggests the virus is not currently able to transmit between people, they said.

But they noted that previous genetic analysis shows H7N9 has already acquired some gene mutations that adapt it specifically to being more able to infect mammals - raising the risk that it could one day spread more easily between people.

"Further adaptation of the virus could lead to infections with less severe symptoms and more efficient person-to-person transmission," the scientists wrote.

Lancet 2013.

Boston Marathon Bombers and inescapable(?) human nature

 

When we see those Boston
Marathon Bombers, we start to wonder how could there be such a deviation in human minds
and behaviours. Those young men who committed the evil act (2 bombs resulting in 3 dead, near 200 injured, and about 10 amputations) had loving and
caring parents. They are not from broken families with psychological problems
during their childhood. They are the product of human hatreds out of religious
fanaticism.

 

I kept wondering what is the
religious fanaticism, the definition. Most of us are part of a religion. People
who believe in their own form of "god", may feel that they believe in
"true god", and most may feel that theirs is superior to other
"gods".      And here comes the difference. Most will keep the feeling to
themselves, because the religion is to heal one's own soul. There should not be
any comparisons with others. Why should you care? However, some will be more
vocal: loud chanting, persuasion of others that "you have been mistaken",
"repent and believe in our god", start calling others infidels,
pagan, or scoff with disdain, perhaps out of some feeling of inferiority deep
inside their own minds.    And, the religious extremism is the kind that put the
religious superiority into action and devote their lives to these actions,
hurting the other's soul or body.

 

Christian crudades in the past
continues into Islamic Jihad's terrorism in recent decades, the latter
probably mixed with some feelings out of jealousy of the Western prosperity, I
believe. Religious persecution has been going on for centuries in history.
Development of medicine has been hampered for more than 13-15 centuries because
of it. And behind all those religious superiority, there is the human ambition.
All religious leaders are humans and have the human instinct "to be better
than others", obviously or insidiously, consciously or unconsciously. As
long as we are human, we cannot escape from this "survival of the
fittest" instinct that came with the creation of the individualized life form.

 

However, there is still hope. We
have seen the amazing, heart-warming social advance during our lives. We saw
flagrant racial and sexual discrimination, and the discrimanation of the
physically handicapped, before 1960's, gradually disappear. The sympathy for the poor
and those stricken by natural disasters has been put into active
assistance by many organizations around the world. Though equality is not
universal yet, but it will be, sooner than we think because of the advance in
communicaiton technologies.

  

My classmate, dentist Johanna, has been working as a missionary in the underdeveloped part of Northen China for decades, soon after the passing of her husband, our classmate Francis.  She is one of the best models of unending human endeavor to do good for fellow human beings!  Hope for the future!

 

While we feel happy to be in the most advanced society in the world, we should help to eliminate this inequality in the world, bigotry of religion, as much as we can and as soon as possible.

 

 

To talk of models, here are the
Korean models competing to be a Miss Korea. Look at their pictures. You would
think they are from identical twins. Just cannot tell who is who. Though I feel
regret that they have lost their individuality, I can understand those ladies's
wish to have facial reconstrustion, which is so advanced in Korea. Which young
women do not want to look beautiful?

 

That is also a human nature.

 

 

 

美國眾議院亞太事務小組委員會無異議通過「台灣政策法」

Formosan Association for Public Affairs   552 7th Street. SE. Washington, DC 20003, USA

Support Democracy, Support Taiwan For Immediate Release Washington D C -  April 25th 2013 Contact: (202) 547-3686   FAPA Applauds Unanimous Passage of Taiwan Policy Act (TPA) in House Subcommittee   (Washington, D.C. – April 25th 2013) -- Today the Subcommittee on Asia and the Pacific of the United States House of Representatives unanimously passed HR419, aka the Taiwan Policy Act (TPA).     The TPA was introduced on January 25, 2013 by Rep. Ileana Ros-Lehtinen (R-FL) and co-chairs of the Congressional Taiwan Caucus Reps. Mario Diaz-Balart (R-FL), Gerald Connolly (D-VA), John Carter (R-TX) and Albio Sires (D-NJ) "to strengthen and clarify the commercial, cultural, and other relations between the people of the United States and the people of Taiwan."    It is a comprehensive bill that addresses over a dozen different aspects of the U.S.-Taiwan relationship, and updates the 1979 Taiwan Relations Act (TRA) to reflect the new realities in this U.S.-Taiwan relationship.  The TPA builds on the TRA (which has functioned effectively as the cornerstone of US-Taiwan relations over the past three decades). It does not amend or supersede the TRA.    The TPA had been introduced during the previous 112th Congress, was passed by the House Foreign Affairs Committee but did not make it to the floor by the time Congress adjourned for the year in the fall of 2012.    During the April 25 markup hearing, the following 8 Representatives attended the hearing: Steve Chabot (R-OH), Eni Faleomavaega (D-SA), Ileana Ros Lehtinen (R-FL), Mo Brooks (R-AL), Dana Rohrabacher (R-CA), Doug Collins (R-GA), Scott Perry (R-PA), Ami Bera (D-CA).    Chairman Chabot stated: "This bill strengthens the relations of our two nations.  And I want to emphasize "Two Nations" for Taiwan is a democracy, an old friend and ally, and it deserves to be treated as such by the U.S. government." Rep. Faleomavaega said: "Reason why we pass this Act, is that we want to achieve that the leaders of Taiwan can continue to practice their democracy."   Rep. Rohrabacher emphasized that Taiwan is a free and independent country. Rep.  Perry: "I believe we should break through the barrier of conventional wisdom in our relations with Taiwan and work towards the normalization of relations." Rep. Ros-Lehtinen concluded: "Taiwan continues to be such an essential alley to the United States. This bill reiterates our support, and tells the Taiwanese people just how deeply we value that friendship."     FAPA President Mark Kao, Ph.D. says: "This bill is one of the most significant pieces of legislation to address U.S.-Taiwan relations over the past decade and, if passed, will greatly bolster Taiwan's ability to preserve its freedom of action in the international community."    Dr. Kao concluded: "Next, the bill has to pass the House Foreign Affairs Committee, then the floor of the House to be followed by introduction in the Senate where the bill has to follow a similar path. We at FAPA will mobilize all our members all over the United States on the grassroots level to help ensure that this critically important bill becomes law at the earliest opportunity."

台灣人公共事務會讚許美國眾議院亞太事務小組委員會無異議通過「台灣政策法」  美國眾議院亞太事務小組委員會於4月25日無異議通過編號H.R.419的「台灣政策法」（Taiwan Policy Act, TPA）。  台灣政策法於1月25日由佛州共和黨眾議員羅斯雷提能（Ileana Ros-Lehtinen）及眾院台灣連線四位共同主席：佛州共和黨議員迪亞茲巴拉特（Mario Diaz-Balart）、維州民主黨議員康納利（Gerald Connolly）、德州共和黨議員卡特（John Carter），以及紐澤西州民主黨議員席瑞斯（Albio Sires），共同提出。  該法案包括台美關係中十幾項不同的議題，並更新1979年的「台灣關係法」（Taiwan Relations Act, TRA），使其更能反映台美關係的真實現況。台灣政策法是建基於過去三十年來台美關係的重要基石─台灣關係法─上，但並未修改，也不會凌駕於其上。  「台灣政策法」曾在第一百一十二屆美國國會中被提出，並通過外交事務委員會審查，但截至該屆國會於2012年秋天散會之前，該項法案並未送交眾院表決。  俄亥俄州共和黨議員夏波（Steve Chabot）、美屬薩摩亞民主黨代表法里歐馬維加（Eni Faleomavaega）、羅斯雷提能議員（Ileana Ros-Lehtinen）、阿拉巴馬州共和黨議員布魯克斯（Mo Brooks）、加州共和黨議員羅拉巴克（Dana Rohrabacher）、喬治亞州共和黨議員柯林斯（Doug Collins），以及賓州共和黨議員裴瑞（Scott Perry）等八位眾議員出席4月25日的審議聽證會。  小組委員會主席夏波議員說道：「此法案將強化我等兩國的關係，而在此我要特別強調『兩國』，因為台灣是一個民主國家及一個長期的美國盟友，而它也應該受到美國政府如是的對待。」法里歐馬維加代表說：「我們通過這項法案的原因，是因為我們要讓台灣可以持續保有其民主。」羅拉巴克議員強調台灣是一個民主自由之邦，而裴瑞議員則說：「我認為我們需要突破現有台美關係的框架，進而將台美關係正常化。」羅斯雷提能議員總結道：「台灣是美國重要的友邦，通過這項法案代表著我們的支持，也向台灣人重申我們是多麼重視台美友誼。」  台灣人公共事務會會長高龍榮博士表示：「這個法案是過去十年中，關於台美關係最重要的一件法案。若此法案通過，將更加保障台灣在國際社會的自由空間。」  高博士總結道：「法案通過小組委員會後，必須通過外交事務委員會，接著由眾議院投票表決，才能送交參議院，並在參院中再經過相似的程序。台灣人公共事務會將會動員全美的會員，發揮草根力量，確保這項重要的法案盡速通過立法。」 * * * * * * * * * * * * 113th CONGRESS 1st Session H. R. 419 To strengthen and clarify the commercial, cultural, and other relations between the people of the United States and the people of Taiwan, as codified in the Taiwan Relations Act, and for other purposes. _______________________________________________________________________ IN THE HOUSE OF REPRESENTATIVES January 25, 2013 Ms. Ros-Lehtinen (for herself, Mr. Sires, Mr. Diaz-Balart, Mr. Connolly, and Mr. Carter) introduced the following bill; which was referred to the Committee on Foreign Affairs, and in addition to the Committee on Ways and Means, for a period to be subsequently determined by the Speaker, in each case for consideration of such provisions as fall within the jurisdiction of the committee concerned _______________________________________________________________________ A BILL To strengthen and clarify the commercial, cultural, and other relations between the people of the United States and the people of Taiwan, as codified in the Taiwan Relations Act, and for other purposes. Be it enacted by the Senate and House of Representatives of the United States of America in Congress assembled, SECTION 1. SHORT TITLE. This Act may be cited as the ``Taiwan Policy Act of 2013''. SEC. 2. FINDINGS. Congress finds the following: (1) The Taiwan Relations Act (Public Law 96-8; 22 U.S.C. 3301 et seq.), enacted in 1979, has continued for 34 years to be the cornerstone of United States-Taiwan relations and has served as an anchor for peace and security in the Western Pacific region. (2) The Taiwan Relations Act, in furthering the national interests of the United States in the Western Pacific region, has mandated that the United States will make available to Taiwan such defense articles and defense services in such quantity as may be necessary to enable Taiwan to maintain a sufficient self-defense capability, thus allowing the people of Taiwan to preserve a peaceful, democratic, and prosperous way of life. (3) The future of Taiwan must be determined in a peaceful manner and with the assent of the people of Taiwan. (4) The Taiwan Relations Act declares that-- (A) peace and stability in the Western Pacific area are in the political, security, and economic interests of the United States, and are matters of international concern; (B) the United States decision to establish diplomatic relations with the People's Republic of China rests upon the expectation that the future of Taiwan will be determined by peaceful means; (C) the United States considers any effort to determine the future of Taiwan by other than peaceful means, including by boycotts or embargoes, a threat to the peace and security of the Western Pacific area and of grave concern to the United States; (D) the United States will maintain the capacity to resist any resort to force or other forms of coercion that would jeopardize the security, or the social or economic system, of the people on Taiwan; and (E) the preservation and enhancement of the human rights of all the people on Taiwan are reaffirmed as objectives of the United States. (5) In recent years United States-Taiwan relations have suffered from inattention and lack of strategic vision, thereby requiring the Congress to both clarify United States policy toward Taiwan and enhance its oversight role in the implementation of the Taiwan Relations Act. (6) In its China Military Power Report for 2012, Taiwan's Ministry of National Defense (MND) estimated that more than 1,600 ballistic and cruise missiles are now being aimed at Taiwan by the Second Artillery Corps of the People's Republic of China and other experts suggest that this number could increase to 1,800 in the near future. (7) The anti-secession law, passed by the National People's Congress of the People's Republic of China, was found by House Concurrent Resolution 98, passed in the House of Representatives on March 16, 2005, by a vote of 424-4, ``to create a legal framework for possible use of force against Taiwan'' and ``to provide a legal justification for the use of force against Taiwan, altering the status quo in the region, and thus is of grave concern to the United States.''. (8) The legislative requirement to make available defense articles and defense services should include the provision of new F-16 C/D aircraft and upgrades of existing F-16 A/B aircraft essential to Taiwan's security. (9) The 2012 Department of Defense's Annual Report to Congress on Military and Security Developments Involving the People's Republic of China noted that ``preparing for contingencies in the Taiwan Strait remains the principal focus and driver of much of China's military investment. In this context, over the past year, the [People's Liberation Army] continued to build the capabilities and develop the doctrine it considers necessary to deter Taiwan from declaring independence; to deter, delay, and deny effective U.S. intervention in a potential cross-Strait conflict; and to defeat Taiwan forces in the event of hostilities.''. (10) The language contained in the Joint Communique of the United States of America and the People's Republic of China, dated August 17, 1982, which states in part that ``arms sales to Taiwan will not exceed, either in qualitative or in quantitative terms, the level of those supplied in recent years'' shall not, to any degree, diminish the responsibility of the United States, as legislatively mandated in the Taiwan Relations Act, to ``make available to Taiwan such defense articles and defense services in such quantity as may be necessary to enable Taiwan to maintain a sufficient self- defense capability.''. (11) The United States has sought diplomatically to preserve Taiwan's international space, despite outside pressure and coercion, and has sought to secure Taiwan's meaningful participation in such international organizations as the World Health Organization (WHO). (12) Given the critical importance of airport security in a post-September 11th international environment, the United States recognizes it is crucial for Taiwan to be admitted to meaningful participation in the International Civil Aviation Organization (ICAO) so that Taiwan may contribute to the success of a global strategy to address aviation security threats based on effective international cooperation. (13) Recognizing that the Taiwan Relations Act stated that it is the policy of the United States ``to preserve and promote extensive, close, and friendly commercial, cultural, and other relations between the people of the United States and the people on Taiwan'' the Secretary of Homeland Security announced on October 2, 2012, ``the designation of Taiwan into the Visa Waiver Program (VWP)'' with eligible Taiwan passport holders able to travel on the VWP beginning November 1, 2012. (14) The conclusion of the Economic Cooperation Framework Agreement (ECFA) between Taiwan and the People's Republic of China in June 2010 or the adoption of any other cross-Strait economic measures shall not diminish in any degree the requirement contained in the Act to ``maintain the capacity of the United States to resist any resort to force or other forms of coercion that would jeopardize the security, or the social or economic system, of the people on Taiwan.''. (15) The theory recently put forward in certain academic circles that the United States should acquiesce to China's ascendancy in Asia and put aside the commitments made in the Taiwan Relations Act is based upon a false premise that ignores the example of a democratic Taiwan, the historic ties of friendship of the peoples of the United States and Taiwan, and the determination of the United States to remain as a Pacific power. (16) Total United States-Taiwan trade in 2011 was $67,200,000,000 and Taiwan was the 10th largest United States trading partner and the 6th largest market for United States agricultural exports. (17) It is in the economic interests of the United States and the national security interests of Taiwan for the peoples of the United States and Taiwan to further strengthen and revitalize their trade and investment ties, including through an expanded Trans-Pacific Partnership (TPP) Agreement or similar mechanism. SEC. 3. RULE OF CONSTRUCTION. Nothing in this Act shall be construed to amend or supersede the Taiwan Relations Act.                       TITLE I--POLITICAL RELATIONS SEC. 101. RELATIONS WITH THE PEOPLE OF TAIWAN. The following shall be the policies of the United States: (1) Supporting Taiwan, Taiwan's democracy, and the human rights of its people. (2) As noted in the Taiwan Relations Act, ``the absence of diplomatic relations or recognition shall not affect the application of the laws of the United States with respect to Taiwan, and the laws of the United States shall apply with respect to Taiwan in the manner that the laws of the United States applied with respect to Taiwan prior to January 1, 1979.''. (3) The United States Government shall respect the right of the Taipei Economic and Cultural Representative Office (TECRO) to display its flag on its premises and the American Institute in Taiwan (AIT) and the residence of its Director in Taipei shall, correspondingly, publicly display the United States flag in the same manner as United States embassies, consulates, and official residences throughout the world. (4) The Taipei Economic and Cultural Representative Office and all other instrumentalities established by Taiwan, including the Twin Oaks Estate, may conduct official business activities, including activities which involve participation by Members of the United States Congress and other representatives of the Federal, State, and local governments, without any impediment from the United States Government or any foreign power. SEC. 102. VISITS BY CABINET LEVEL OFFICIALS. (a) Findings.--Congress finds the following: (1) Visits by United States cabinet officials and other high-ranking visitors are an indicator of the breadth and depth of ties between the United States and Taiwan. (2) In December 1992, United States Trade Representative Carla Hills visited Taiwan, marking the first cabinet-level visit since 1979. (3) Over the next 8 years the Administrator of the Small Business Administration, the Secretary of Energy, and 2 Secretaries of Transportation visited Taiwan. (4) No United States cabinet secretary has visited Taiwan since July 2000. (5) In March 2008, candidate Barack Obama wrote in a message congratulating Ma Ying-jeou on his election victory that ``[t]he U.S. should reopen blocked channels of communication with Taiwan officials'', however no Cabinet-level visits to Taiwan have yet taken place. (b) Policy of the United States.--It shall be the policy of the United States to encourage visits by cabinet-level officials between the United States and Taiwan to foster commercial, technological, and people-to-people exchanges. SEC. 103. REVISION OF GUIDELINES FOR CONTACTS WITH TAIWAN. Notwithstanding the 1994 Taiwan policy review and current mandatory guidance from the Department of State regarding contacts with Taiwan, it shall be the policy of the United States to-- (1) permit senior leaders of Taiwan to enter the United States under conditions which demonstrate appropriate courtesy and respect for the dignity of such leaders; (2) permit meetings between high-level Taiwanese and United States officials in all United States executive departments; (3) allow official travel to Taiwan for Department of State and Department of Defense personnel above the rank of office director or, for uniformed military personnel, above the level of 06 (Colonel, Navy Captain); and (4) support a decision by Taiwan to change the name of the Taipei Economic and Cultural Representative Office to that of the Taiwan Representative Office. SEC. 104. REQUIREMENT FOR SENATE CONFIRMATION OF AN INDIVIDUAL APPOINTED TO SERVE AS THE DIRECTOR OF THE AMERICAN INSTITUTE IN TAIWAN. (a) In General.--Notwithstanding any other provision of law, the President shall appoint, by and with the advice and consent of the Senate, an individual to serve as the Director of the American Institute in Taiwan. (b) Transition.--The individual serving as the Director of the American Institute in Taiwan as of the date of the enactment of this Act may continue to serve in such capacity until such time as an individual is appointed and confirmed in accordance with subsection (a). SEC. 105. EXTRADITION AGREEMENT. (a) In General.--It shall be the policy of the United States to enhance judicial cooperation with Taiwan, currently conducted on the basis of the 2002 Agreement on Mutual Legal Assistance in Criminal Matters, by signing a comprehensive extradition agreement. (b) Report.--Not later than 180 days after the date of enactment of this Act, the President shall transmit to Congress a report that assesses whether a comprehensive extradition agreement between the United States and Taiwan may be submitted to the Senate for advice and consent as a treaty or whether, because of Taiwan's unique status, such agreement must be submitted to both the House of Representatives and Senate for legislative approval. SEC. 106. CONTINUATION OF THE SIX ASSURANCES AS GUIDELINES IN CONDUCTING UNITED STATES-TAIWAN RELATIONS. Notwithstanding any communiques entered into between the United States and the People's Republic of China, the United States continues to assent to the six assurances provided to Taiwan in July, 1982, including that the United States-- (1) has not agreed to set a date for ending arms sales to Taiwan; (2) has not agreed to hold prior consultations with the People's Republic of China on arms sales to Taiwan; (3) will not play any mediation role between Taipei and Beijing; (4) has not agreed to revise the Taiwan Relations Act; (5) has not altered its position regarding sovereignty over Taiwan; and (6) will not exert pressure on Taiwan to negotiate with the People's Republic of China. SEC. 107. INTERNATIONAL ORGANIZATIONS. (a) Annual Program.--To provide Taiwan with the international space it requires to function effectively in the world community, the Secretary of State shall direct the Department of State to continue its annual program to ensure meaningful participation by Taiwan in the World Health Assembly in Geneva, Switzerland, as well as meaningful participation for Taiwan in other relevant international organizations, such as the International Civil Aviation Organization (ICAO). (b) Meaningful Participation by Taiwan.--The Secretary of State shall direct the United States Permanent Representative to the United Nations to use the voice, vote, and influence of the United States at the United Nations to ensure meaningful participation for Taiwan in relevant United Nations Entities in which Taiwan has expressed an interest in participating. SEC. 108. REPORT ON TAIWAN'S PARTICIPATION IN ICAO. (a) In General.--The Secretary of State shall initiate a United States plan to endorse and obtain meaningful participation for Taiwan at the periodic Assemblies held by the International Civil Aviation Organization (ICAO) in Montreal, Canada, including the 38th Assembly to be held in September-October 2013, and in the meetings and activities of the ICAO and shall instruct the United States delegation to Montreal to implement such plan. (b) Report.--Not later than 180 days after the date of the enactment of this Act and annually thereafter, the Secretary of State shall submit to Congress a report containing the plan required under subsection (a). (c) Form.--The report required under subsection (b) shall be submitted in unclassified form, but may contain a classified annex if necessary. (d) Annual Briefing.--The Secretary of State should provide an annual briefing to or consult with Congress on any efforts conducted by the United States Government in support of Taiwan's progress toward meaningful participation in the ICAO.                       TITLE II--SECURITY RELATIONS SEC. 201. STRENGTHENING THE DEFENSE OF TAIWAN. (a) Maintenance of Sufficient Self-Defense Capabilities of Taiwan.--Congress finds that any determination of the nature and quantity of defense articles or defense services to be made available to Taiwan that is made on any basis other than the defense needs of Taiwan, whether pursuant to the August 17, 1982, Communique signed with the People's Republic of China, or any similar executive agreement, order, or policy would violate the intent of Congress specified in section 3(b) of the Taiwan Relations Act (22 U.S.C. 3302(b)). (b) Foreign Military Sales and Licensed Defense Exports Under the Arms Export Control Act.--Congress finds that, in accordance with the Taiwan Relations Act, the core purpose of foreign military sales and licensed commercial exports under the Arms Export Control Act should be to assist Taiwan in its ability to-- (1) deter coercion; (2) defend against a strategy of coercive diplomacy employing threats or limited force; (3) repel an invasion; and (4) partner with civil responders and friendly foreign militaries. (c) Defense Transfers.--In order to accomplish the purposes of this section, the President is authorized to make available to Taiwan defense articles or defense services, including the following: (1) Air and air defense capabilities, including-- (A) low-cost, survivable sensors; (B) command and control systems; (C) modern surface to air missiles; (D) upgrades to existing modern combat aircraft as well as new combat aircraft, including Vertical and Short Take-Off and Landing Aircraft (V/STOL); (E) radar, electronic warfare, and jamming capabilities; (F) passive defense measures (such as redundancy, dispersal, camouflage/deception, hardening, and rapid repair capabilities); and (G) access to satellites for remote sensing and communication. (2) Maritime capabilities, including-- (A) additional sensor capacity for comprehensive maritime domain awareness; (B) cost-effective submarines for anti-surface, anti-submarine warfare, and other missions; (C) mines and mine countermeasure vessels; and (D) anti-ship cruise missiles. (3) Ground capabilities, including-- (A) layers, short-range air defense; (B) critical infrastructure protection to ensure continuity of government; (C) air mobility; (D) unmanned air vehicles; and (E) accurate, GPS-guided short-range rockets. (4) Capacity for partnership with friendly foreign militaries, including-- (A) command, control, communications, computers, intelligence, surveillance, and reconnaissance situational awareness systems; (B) enhanced doctrine exchange; and (C) enhanced senior-level training. (d) Rule of Construction Relating to Arms Export Control Act.-- Nothing in this section shall be construed to supersede or modify section 36 of the Arms Export Control Act (22 U.S.C. 2776). SEC. 202. ADVANCED COMBAT AIRCRAFT FOR TAIWAN. (a) Statement of Policy.--Notwithstanding the upgrade of Taiwan's F-16 A/B aircraft, Taiwan will experience a growing shortfall in fighter aircraft, particularly as its F-5 aircraft are retired from service. (b) Authority To Accept Letter of Request.--Pursuant to the foreign military sales program authorized by the Arms Export Control Act, the President is authorized to accept a letter of request from Taiwan for price and availability data or for a formal sales offer with respect to the F-16C/D Fighting Falcon multirole fighter aircraft or other aircraft of similar capability, as may be necessary to enable Taiwan to maintain a sufficient self-defense capability. SEC. 203. CONSULTATIONS ON TAIWAN ARMS SALES. (a) Briefings.--Not later than 90 days after the date of the enactment of this Act and at least annually thereafter, the Secretary of State, in consultation with the Secretary of Defense, shall provide detailed briefings to Congress on-- (1) any discussions conducted between any executive branch agency and the Government of Taiwan during a covered period; and (2) any potential transfer to the Government of Taiwan of defense articles or defense services. (b) Definitions.--In this section and section 201: (1) Covered period.--The term ``covered period'' means, with respect to-- (A) the initial briefing required under subsection (a), the period beginning on the date of the enactment of this Act and ending on the date of such initial briefing; and (B) subsequent briefings required under such subsection, the period beginning on the day after the date of the most recent briefing and ending on the date of any such subsequent briefing. (2) Executive branch agency.--The term ``executive branch agency'' has the meaning given the term ``agency'' in section 551(1) of title 5, United States Code. (3) Defense article.--The term ``defense article'' has the meaning given such term in section 47 of the Arms Export Control Act (22 U.S.C. 2794). (4) Defense service.--The term ``defense service'' has the meaning given such term in section 47 of the Arms Export Control Act (22 U.S.C. 2794). SEC. 204. ANNUAL REPORT ON DEFENSE TRANSFERS TO TAIWAN. (a) In General.--Not later than 180 days after the date of the enactment of this Act and annually thereafter, the President shall transmit to Congress a report-- (1) detailing each of Taiwan's requests for purchase of defense articles and defense services during the immediately preceding one-year period, whether submitted through a letter of request (LOR) or conveyed by other authoritative means, except that the first report under this section shall cover the period 2006 through 2011; (2) describing the defense needs asserted by Taiwan as justification for such requests; (3) describing the decisionmaking process used to reject, postpone, or modify any such request, including-- (A) with respect to significant military equipment, the country team assessment and recommendation as to whether the United States should sell such equipment; and (B) for each request, the elapse of time between the submission of such request and the completion of the interagency review process by the United States; and (4) detailing those defense articles and defense services listed in the Arms Sale Proposal described in section 25 of the Arms Export Control Act (22 U.S.C. 2765), including a description of the rationale for including or not including in such Proposal, as the case may be, all sales and licensed exports to Taiwan under such Act of major weapons or weapons- related defense equipment for $7,000,000 or more, and the extent to which a decision to not include in such Proposal such sales to Taiwan is consistent with such section. (b) Form.--The report required under subsection (a) shall be submitted in unclassified form, but may contain a classified annex if necessary. SEC. 205. REPORT ON IMPLEMENTATION OF TAIWAN RELATIONS ACT. (a) In General.--Not later than 180 days after the date of the enactment of this Act, the President shall submit to Congress a report on implementation of United States security policy under the Taiwan Relations Act. (b) Matters To Be Included.--The report required under subsection (a) shall include, at a minimum, the following: (1) A review of the operational planning, policy reviews, and other preparations of the United States since 2000 to implement section 2(b)(6) and subsections (a), (b), and (c) of section 3 of the Taiwan Relations Act, including the extent to which the United States retains the capacity to resist any resort to force or other forms of coercion that would jeopardize the security, or the social or economic system, of the people of Taiwan. Such review shall take into account whether Taiwan's air and air defense forces retain the ability to effectively defend Taiwan against China's ballistic missile and air threats, and the extent to which the absence of credible Taiwanese air defense forces may complicate the ability of the United States to resist any resort to force that jeopardizes the security of Taiwan. (2) An evaluation of all gaps in relevant knowledge about the capabilities and intentions of the People's Republic of China as such capabilities and intentions might affect the current and future military balance between Taiwan and China, such as anti-access and area denial capabilities as well as anti-satellite and space warfare developments, including both classified United States intelligence information and Chinese open source writing. (c) Form.--The report required under subsection (a) shall be submitted in unclassified form, but may contain a classified annex if necessary. SEC. 206. NAVAL VESSEL TRANSFER AUTHORITY. (a) Transfer by Sale.--The President is authorized to transfer the OLIVER HAZARD PERRY class guided missile frigates USS TAYLOR (FFG-50), USS GARY (FFG-51), USS CARR (FFG-52), and USS ELROD (FFG-55) to the Taipei Economic and Cultural Representative Office of the United States (which is the Taiwan instrumentality designated pursuant to section 10(a) of the Taiwan Relations Act (22 U.S.C. 3309(a))) on a sale basis under section 21 of the Arms Export Control Act (22 U.S.C. 2761). (b) Costs of Transfers.--Any expense incurred by the United States in connection with a transfer authorized by this section shall be charged to the recipient notwithstanding section 516(e) of the Foreign Assistance Act of 1961 (22 U.S.C. 2321j(e)). (c) Repair and Refurbishment in United States Shipyards.--To the maximum extent practicable, the President shall require, as a condition of the transfer of a vessel under this section, that the recipient to which the vessel is transferred have such repair or refurbishment of the vessel as is needed, before the vessel joins the naval forces of that recipient, performed at a shipyard located in the United States, including a United States Navy shipyard. (d) Expiration of Authority.--The authority to transfer a vessel under this section shall expire at the end of the 3-year period beginning on the date of the enactment of this Act.                 TITLE III--ECONOMIC AND TRADE RELATIONS SEC. 301. TRADE AND INVESTMENT FRAMEWORK AGREEMENT. It is the sense of Congress that, at the earliest opportunity, the United States Trade Representative should seek to resume and successfully conclude negotiations of economic issues in the Trade and Investment Framework Agreement (TIFA) talks with Taiwan. SEC. 302. FREE TRADE AGREEMENT. (a) In General.--It is the sense of Congress that the ultimate goal of trade negotiations with Taiwan should be the negotiation of a free trade agreement with Taiwan. As building blocks toward that goal, the United States should study the feasibility of negotiating with Taiwan a bilateral-- (1) investment agreement; and (2) tax agreement. (b) Report.--Not later than 180 days after the date of enactment of this Act, the President shall transmit to Congress a report that assesses whether economic and trade agreements between the United States and Taiwan may be submitted to the Senate for advice and consent as a treaty or whether, because of Taiwan's unique status, such agreements must be submitted to both the House of Representatives and Senate for legislative approval.

Mediterranean diet 是否最好??

Mediterranean Diet: Better, Not Best?

Gayl J. Canfield, PhD, RD

Mar 19, 2013

Editor's Note: The author is Director of Nutrition at the Pritikin Longevity Center in Miami, Florida.

Mediterranean Diet Better Than Typical American Diet

In light of the recent media attention on the Mediterranean diet,^[1] you may find yourself fielding lots of questions from patients about which diet they should follow. Right now, we cannot say which diet is best because we still need rigorous studies of all of the popular diets that physicians routinely recommend to their patients. Moreover, we cannot unequivocally recommend the Mediterranean diet on the basis of the recently published study because this study was seriously flawed.

One major problem with the study was that the "low-fat" diet being used to compare against the Mediterranean diet was not, in fact, low in fats. The participants in this group started out with a diet that averaged 39% fat, and during the study period they decreased fat intake to just 37%.

Nor was this so-called low-fat diet a healthy, well-designed regimen. Many of the foods eaten by participants were artery-damaging foods such as red meat, commercially baked goods full of refined flour and fat, sugary sodas, and low-fat cheeses. (Though called "low-fat," these cheeses typically get 35% to 60% of their calories from fat.)

Moreover, the "low-fat" diet excluded an important food proven to protect against heart disease: omega 3-rich fish. This category of food is included in many healthy low-fat-diet plans.

The bottom line is that the study authors were not really comparing a Mediterranean diet with a nutritious low-fat diet. It would be much more accurate to say that they were comparing a Mediterranean diet with a typical American-style diet. But it did not do justice to a well-constructed low-fat diet.

Healthy "Low-Fat" Diets

A substantial body of research exists that has documented the heart-healthy benefits of 2 well-known low-fat diets, Pritikin and Ornish. In fact, the data are so strong that Medicare now covers cardiac rehabilitation programs based on the Pritikin and Ornish plans for people with a history of cardiovascular disease.^[2] Both programs also include exercise and lifestyle-change components.

The Ornish Program has been proven to regress heart disease,^[3,4] and the Pritikin Program has been proven to significantly reduce many modifiable risk factors for cardiovascular disease, including low-density lipoprotein (LDL) cholesterol, triglycerides, blood glucose, hypertension, inflammatory markers such as C-reactive protein, and excess weight/obesity.^[5-7]

Both programs recommend an eating plan with about 10% to 15% of calories coming from fat, and both emphasize hearty consumption of fruits, vegetables, whole grains, and legumes such as beans. The Ornish Program is completely vegetarian, whereas the Pritikin Program allows up to 4 oz of animal protein daily, such as omega-3-rich fatty fish, skinless white poultry, or lean meat such as bison.

Both of these programs are a far cry from the "low-fat" diets of the 1980s and 1990s, many of which were anything but healthy. Often, the "low-fat” and "fat-free" products people were eating (remember "fat-free" cookies?) were essentially junk food themselves -- very high in sugar, salt, and/or refined white flour.

Low-fat plans such as Pritikin and Ornish, by contrast, focus on real food -- whole, minimally processed, naturally fiber-rich foods that, as Michael Pollan wrote in his superb book In Defense of Food, "are foods our great grandmothers would have recognized as food."

Another low-fat diet that has proven to be particularly beneficial for blood pressure control is the DASH (Dietary Approaches to Stop Hypertension) diet. Several studies funded by the National Institutes of Health (NIH) have found that the DASH diet lowers blood pressure as well as or better than medications. DASH also promotes menus that are high in fruits, vegetables, whole grains, and beans; low in fats, salt, red meats, and sweets; and moderate in fish, poultry, nuts, and low-fat or nonfat dairy foods.

In one study, NIH researchers found that 8 weeks of following the DASH regimen resulted in reductions in blood pressure in all groups of men and women studied.^[8] Even those who started with a normal blood pressure (systolic pressure < 120 mm Hg) saw improvements. The biggest reductions in blood pressure were observed in the individuals who were hypertensive (systolic pressure >140 mm Hg), emphasizing the fact that diet is a major factor in determining blood pressure in most hypertensive patients.

In another DASH study, 3 groups of people followed the diet but took in varying levels of sodium (3300 mg, 2400 mg, or 1500 mg per day). The researchers found that the biggest drops in blood pressure occurred in the group on the 1500 mg/day diet.^[9]

Life Lessons

After nearly a decade of teaching healthy eating at the Pritikin Longevity Center, I can say with certainty that people can change. They really can revamp their behaviors and live better, healthier lives. But it takes much more, unfortunately, than simply handing them a diet pamphlet. What works is a solid education in several key skills for healthy living: classes in grocery shopping, reading food labels, cooking, and dining out healthfully. In addition, we provide classes that teach why these skills are so vital and how they benefit the body.

What matters, too, is taking time away from what I call the "American assault on our taste buds" -- a week or more spent eating foods that are completely free of salt, sugar, and grease, so that our palates have a chance to rediscover the good flavors of good food.

If, as a nation, we can institute educational programs like these, we can begin to empty our hospitals of patients needing angioplasties or coronary bypass surgeries; we can lighten the load of nursing facilities filled with people stricken with diabetic- and cardiovascular-related strokes, kidney failure, and amputations.

We know that the Mediterranean diet is better than the typical American diet. We also know that healthy, well-designed low-fat diets are better than the typical American diet. We need more research -- rigorous, randomized trials -- to identify not only the best diets but also the best ways to teach these diets.

In doing so, we can achieve real change across America, change that can not only curtail the staggering economic costs of chronic disease but also help people feel better and live better.

References

1. Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;DOI:10.1056/NEJMoa200303.

   
   

2. [No authors listed] Ornish, Pritikin get Medicare okay for cardiac rehab. Harv Heart Lett. 2010;21:7.

   
   

3. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet. 1990;336:129-133. Abstract

   
   

4. Chainani-Wu N, Weidner G, Purnell DM, et al. Changes in emerging cardiac biomarkers after an intensive lifestyle intervention. Am J Cardiol. 2011;108:498-507. Abstract

   
   

5. Barnard RJ. Effects of life-style modification on serum lipids. Arch Intern Med. 1991;151:1389-1394. Abstract

   
   

6. Sullivan S, Samuel S. Effect of short-term Pritikin diet therapy on the metabolic syndrome. J Cardiometab Syndr. 2006;1:308-312. Abstract

   
   

7. Wegge JK, Roberts CK, Ngo TH, Barnard RJ. Effect of diet and exercise intervention on inflammatory and adhesion molecules in postmenopausal women on hormone replacement therapy and at risk for coronary artery disease. Metabolism. 2004;53:377-381. Abstract

   
   

8. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997;336:1117-1124. Abstract

   
   

9. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3-10. Abstract

   
   

Medscape Diabetes & Endocrinology © 2013 WebMD, LLC

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Evidence Is Compelling' on Mediterranean Diet

Eric J. Topol, MD

Mar 07, 2013

Mediterranean Diet Study

Hello. I am Dr. Eric Topol, Editor-in-Chief of Medscape. I am thrilled to be the new editor-in-chief; this is an extraordinary way for information to be disseminated to the medical community, and I am hoping to contribute with all the staff and our physician colleagues working around the globe to take Medscape to an "über level."

In this brief segment today, I will talk about the Mediterranean diet study. This is a study that was published in the February 25 New England Journal of Medicine.^[1] I will try to get some commentary, either from myself or other colleagues, about really important studies, and I believe that this is one of them.

We don't talk enough about diet in medicine, but this is the largest randomized trial to date. The Mediterranean diet has been studied previously in randomized trials but not in a trial as large as this. It is fascinating that this was a study of more than 7400 individuals who were randomly assigned to 3 different diets. Two were Mediterranean diets enriched with either extra-virgin olive oil or nuts and other Mediterranean foods, both including more than 7 glasses of wine per week. The control diet was a low-fat diet, which some people have argued is not an ideal control. There was very good compliance with the diets in this large number of people for many years. The primary endpoint was death, heart attack, or stroke. There was a very important significant reduction of this cluster endpoint in the Mediterranean diet groups. Particularly noteworthy, even by itself, was the reduction in stroke.

Clinical Impact of the Mediterranean Diet Study

We now have dietary evidence that is fairly compelling. The absolute size reduction was not large, but the fact that the Mediterranean diets tested in this trial had such a positive impact gives us some anchoring about a diet that does lower critical cardiovascular endpoints. For many years, there has been discussion about this low-fat diet and whether it had a meaningful clinical impact. At one point, the Mediterranean diet was very much supported by the American Heart Association and other organizations. Now we see that it appears to be superior. The trial has had criticism, particularly honing in on the low-fat control arm of the study, but nonetheless, the evidence is compelling.

Why is this trial unique? It was funded by the Spanish government. This is a country that isn't known these days for having extraordinary resources to fund research, but the government of Spain got behind an important trial, perhaps the most impressive diet-randomized trial that has been performed. We have to give a lot of credit to them, because this trial was done with that level of funding and with superb investigators throughout the country of Spain, and it makes a lasting contribution. We are always in search of more information about what we eat, and this is welcome. It is particularly nice to know that you can have 7 glasses of wine or more each week and it might have a favorable effect.

We will be trying to highlight similar studies that are interesting, taking us across the whole spectrum of diagnostics, medical devices, genomics, wireless medicine, and topics such as diet and nutrition, to broaden some of the special coverage that we have at Medscape. Thanks very much for your attention.

References

1. Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013 February 25. [Epub ahead of print]. http://www.nejm.org/doi/full/10.1056/NEJMoa1200303 Accessed March 6, 2013.

   
   

Medscape Internal Medicine © 2013 WebMD,

An old drug for chronic urticaria and other skin conditions 蕁麻疹新藥

ASTERIA II: Omalizumab Calms Itch in Chronic Urticaria

Kate Johnson

Feb 24, 2013

SAN ANTONIO, Texas — Omalizumab (Xolair, Roche, Genentech, Novartis) appears to be safe and effective in the treatment of chronic idiopathic urticaria that is refractory to antihistamines, according to new phase 3 clinical trial results.

"I think there are a number of physicians who are very excited about these data," senior investigator Thomas Casale, MD, from Creighton University in Omaha, Nebraska, told Medscape Medical News in an interview.

The results of the study known as ASTERIA II were presented at a news conference today in advance of the presentation here at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2013 Annual Meeting and were simultaneously published in the New England Journal of Medicine.

The global, multicenter, randomized, double-blind, placebo-controlled study shows the immunoglobulin E monoclonal antibody currently approved for allergic asthma also diminishes the clinical symptoms of chronic urticaria.

The trial enrolled 323 patients with a history of at least 6 months of chronic idiopathic urticaria. Patients had itchy hives for at least 8 consecutive weeks despite the use of H₁-antihistamines.

The participants "pretty much fit the profile that we see for these patients," Dr. Casale said. "They tend to be adults, in their 40's, majority are female, and the duration of the disease can vary — the median was 3.3 years, but 1 patient had it for over 60 years."

Participants were randomly assigned to receive 3 subcutaneous injections at 4-week intervals of either omalizumab 75 mg, 150 mg, 300 mg, or placebo. This was followed by a 16-week observation period.

Change from baseline to week 12 in the weekly itch-severity score was the primary endpoint; secondary endpoints included safety, edema, hives, and quality of life.

Throughout the treatment and follow-up period, patients were allowed to remain on their regular antihistamine therapy, and they were also permitted to take rescue antihistamines.

The baseline itch-severity score was about 14 across all study groups.

Table. ASTERIA II: Mean Change From Baseline in Weekly Itch-Severity Score

Group	Mean Change	P-Value
Omalizumab 300 mg	-9.8	< .001
Omalizumab 150 mg	-8.1	= .001
Omalizumab 75 mg	-5.9	= .46
Placebo	-5.1	Not reported

"What was interesting is that you could see a really good dose-dependent effect for all the primary and secondary endpoints, and the rapidity of response was pretty amazing as well," said Dr. Casale.

"In the high-dose group, for example, patients had a clear drop in their symptoms in a week, and that was apparent at 2 weeks for the 150-mg dose. So it not only worked, but it worked fairly rapidly," he pointed out.

Secondary endpoints also improved in a similar dose-dependent fashion, Dr. Casale noted, the most noteworthy being the reduction in hives at the end of the treatment period.

Secondary Endpoints

"A post hoc analysis that was very impressive to me showed that over 40% of the patients that were on the high dose were completely hive and angioedema free at the end of the 12-week treatment period, which is a pretty remarkable hurdle to get to," he said.

Specifically, the post hoc analysis showed that at the end of treatment, 53% of patients receiving the high dose were completely free of hives compared with 23% in the 150-mg group, 18% in the low-dose group, and 10% in the placebo group.

Also, at the end of the treatment period, the mean change from baseline in weekly rescue diphenhydramine dosing was a decrease of 4.1 tablets in the 300-mg group (P = .01), a decrease of 3.7 tablets in the 150-mg group (P = .07), a decrease of 2.3 tablets in the 75-mg group (P = .91), and a decrease of 2.2 tablets in the placebo group.

"That's an important secondary endpoint because if you can achieve good improvement and do it with less rescue antihistamine, then you know you have an even better treatment," Dr. Casale commented.

During the 16-week follow-up period after treatment cessation, patients were permitted to continue their daily H₁-anthistamine therapy as well as rescue diphenhydramine 25 mg up to 3 times per day; however, symptoms slowly returned for most patients, he said.

"When they get off the study drug, they start developing a recurrence of symptoms so that by the end of the 16 weeks off treatment, they were close to those patients who were treated with placebo. That would suggest that in this particular study, the duration of treatment may have to be longer. We don't know how long, to reduce hopefully a more sustained remission."

In terms of safety, "the side-effect profile across the study was pretty consistent between the 3 active doses and placebo. There weren't any major safety signals," Dr. Casale said.

Side-Effect Profile

"A few more patients in the highest dose had serious adverse events compared to placebo, but none of those were thought to be related to study treatment," he reported. "There wasn't anything that signalled a safety issue, and certainly the profile of adverse events is very similar to what you see in the treatment of patients for asthma."

Asthma dosing for omalizumab is based on body weight and baseline immunoglobulin E level, whereas dosing for chronic urticaria "will probably be a single recommended dose on a once-a-month regimen," Dr. Casale noted. "The 300-mg dose would be in line with what an average asthma patient would take," he said, although asthma patients "are dosed every 2 to 4 weeks, and patients with urticaria would likely receive only 1 monthly dose."

The results of the study are significant. Dr. Wesley Burks

Asked by Medscape Medical News to comment on the findings, Wesley Burks, MD, president of AAAAI, said, "The results of the study are significant. Previous studies suggested this treatment might work, but this study shows us a definitive dose that actually reduces symptoms. Antihistamines and steroids have been the main treatments and do not work well or have major side effects."

Definitive Dose

Dr. Burks said, "The prevalence of chronic urticaria is significant, and until now, a good treatment to make the disease go away has not been available."

He added, "There are a lot of patients that we see with this problem, and it's one of those diseases where I walk in and tell a patient, 'Gee, I have nothing but bad news for you. You have hives, most of the time we don't find a cause, this could last for years, and we don't really have a treatment.' It's very frustrating."

Another recent study published in the Annals of Allergy, Asthma and Immunology suggested that in a small number of patients, long-term remission can be achieved for up to 9 months after treatment with 150 mg of omalizumab in chronic idiopathic urticaria, but both Dr. Casale and Dr. Burks say the numbers are too small to draw much conclusion from them.

Dr. Casale said that other phase 3 trials of omalizumab are finished, but the analyses have not yet been completed. "There might be another study needed to determine when or if you could come off the omalizumab and have a sustained remission. We don't really understand how omalizumab is working in this disease. Once we have more information, then I think we could design such a trial."

During the question period after the presentation, Sinisa Savic, MD, from St. James Hospital in Leeds, United Kingdom, said that post-treatment remission has been elusive for his patients. Despite success with omalizumab as a third-line treatment for chronic refractory urticaria, he has had problems weaning patients.

"We haven't been able to discontinue." Dr. Savic later told Medscape Medical News. "In the majority of patients, usually within 2 or 3 months of discontinuation, their symptoms return, so we just have to restart. We now have patients who have been on it for 12 months," he noted.

He said that stretching dosing to every 6 weeks, rather than every 4 weeks, can help reduce the cost, as can lowering the dose. "We use a dose between 150 mg and 300 mg — similar to asthma dosing — which is based on body weight and level of IgE."

"I haven't analyzed whether you get a better response with a higher dose, but our experience has been that it's very, very effective. They all responded very quickly, similar to the patients in this study, within a couple of weeks," Dr. Savic added.

First New Drug in a Decade

Session moderator Stephen Dreskin, MD, from the University of Colorado in Denver, pointed out that "this will be the first really new drug in 10 years, and may be the first new drug in decades that will go to the FDA for this indication." He noted that even cyclosporine is not currently approved for chronic idiopathic urticaria.

However, he predicts that "many insurance companies may still balk, waiting for FDA approval. It's only FDA-approved for asthma and, since it's expensive, insurance companies tend not to want to use it for something that it's not approved for."

Nevertheless, he says the new data are compelling. "It looks like the drug is effective as long as you stay on it. So far, there's no evidence that it's disease modifying...; cyclosporine is a more difficult drug to manage," Dr. Dreskin said. As far as long-term therapy, he noted that discontinuation might be a possibility after a longer duration of treatment.

"At least in asthma, it does look like patients who have been treated for a long period of time can come off the drug more easily than those who have been treated for a short period of time. We have no idea if that will be true for chronic urticaria," he explained.

This study was sponsored by Genentech and Novartis Pharma. Dr. Casale reports serving on advisory boards and receiving principal investigator grants from Novartis and Genentech. A number of the study's coauthors are employees of the companies. Dr. Burks reports working as a consultant for Novartis and other pharmaceutical companies. Dr. Dreskin reports receiving a research grant from Genentech to study omalizumab. Dr. Savic has disclosed no relevant financial relationships.

American Academy of Allergy Asthma & Immunology (AAAAI) 2013 Annual Meeting. Abstract L3. Presented February 24, 2013.

Medscape Medical News © 2013 WebMD,

 

Dapsone Resurrected for Chronic Urticaria

Kate Johnson

Mar 06, 2013

 SAN ANTONIO, Texas — Results from the first placebo-controlled clinical trial of dapsone suggest that the well-known agent is beneficial for chronic idiopathic urticaria.

"This is much cheaper than a lot of the other drugs because it's been around since the 1940s and it's generic," Andrew Cooke, MD, from the University of Texas Southwestern Medical Center in Dallas, told Medscape Medical News.

The results, presented here at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2013 Annual Meeting, show that the antibiotic originally used for leprosy relieves the symptoms of urticaria that is refractory to high-dose antihistamines.

"A lot of allergists have used dapsone — this isn't the first description of it — but this was a double-blind placebo-controlled study, which makes it a very robust study," Stuart Abramson, MD, head of the AAAAI scientific program committee, who is from Shannon Medical Center in San Angelo, Texas, told Medscape Medical News.

The study, presented as a featured poster at the meeting, involved 22 patients who had chronic idiopathic refractory urticaria with a median duration of 1.0 and 1.3 years. Patients with baseline chronic kidney disease or baseline liver disease were excluded from the study.

Investigators randomized patients to either dapsone 100 mg daily or placebo for 6 weeks, followed by a 2-week washout period and then a crossover to the other treatment.

"Because the patients who were on the placebo phase last continued to see the benefits of dapsone from the first phase, we actually had to analyze the trial by the first phase only," explained Dr. Cooke, who was brought into the study specifically for this purpose.

Dr. Cooke worked with the study's statistician to convert the trial from a crossover to a parallel design.

Antibiotic for Leprosy

The researchers found that treatment with dapsone resulted in a statistically significant improvement over placebo and over baseline, "which was surprising because that's not how the trial was originally designed. However, it points to the efficacy of this drug for urticaria," Dr. Cooke said.

After 6 weeks, there was no improvement from baseline in patients in the placebo group, whereas patients in the dapsone group showed a mean improvement of 2.3 points on a visual analog scale (P = .01), 4.8 points on a weekly itch scale (P = .001), and 3.5 points on a weekly hive scale (P = .02).

About a third of patients in the dapsone group had a reduction of at least 50% in weekly hive score, and 16% experienced complete resolution. In addition, 41% had a significant reduction in weekly itch score and 17% had complete resolution.

In terms of adverse effects, both hematocrit and hemoglobin dropped significantly (P < .001) in the dapsone group, but not in the placebo group.

Table. Mean Change in Hemoglobin and Hematocrit With Dapsone

Outcome	Baseline	Week 6
Hemoglobin (mg/dL)	13.6	11.8
Hematocrit (%)	40.5	34.8

"We saw about a 2-point drop in hemoglobin and a 6-point drop in hematocrit," Dr. Cooke reported. "This started at about 3 weeks, and went on until 5 weeks after the drug was stopped."

In addition, "we had a few patients who had vaginal candidiasis, 1 had mild neuropathy, and 2 had some mild nausea," he said. "You need to check glucose-6-phosphate dehydrogenase deficiency status, it can't be given to pregnant patients, and if they have a baseline anemia, I wouldn't use it," Dr. Cooke added.

Dr. Cooke explained that dapsone is used for pneumocystis pneumonia prophylaxis in patients who have HIV and very low CD4 counts, and "they tend to take it daily and probably for a long duration."

However, he emphasized that larger studies are needed to confirm these findings in chronic idiopathic urticaria and to investigate the optimal dose and duration — especially because the benefits of the drug continued for some time after it was stopped.

"It's an interesting drug and it has been something in our armamentarium," Dr. Abramson said. "I've had some patients that I've used it on for chronic urticaria and it's been very successful, although I start at a lower dose — 50 mg. The nice thing is that here we have a double-blind placebo-controlled study," he added.

This trial was funded by the National Institutes of Health. The investigators and Dr. Abramson have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2013 Annual Meeting: Abstract 508. Presented February 24, 2013 

 

Xolair: Not Just for Asthma

Gary J. Stadtmauer, MD

Jan 04, 2013

 Humanized monoclonal IgG anti-IgE is an effective biologic agent that has been in use for more than a decade to treat atopic asthma. The effect of omalizumab (Xolair®) IgE reduction alone from might explain why it alleviates respiratory allergy, but omalizumab has also been found to be effective for a range of other conditions through its other mechanisms of action.

For example, after just 3 months of treatment, the reduction in functional IgE leads to a more than 95% downregulation of the IgE receptor.^[1] This is seen in mast cells, basophils, and dendritic cells, which can explain the attenuation of the IgE-mediated response to allergens. The decreased antigen processing also results in less antigen presentation to Th2 cells -- hence, less cytokine stimulation of eosinophils. The clinical implications of this immunomodulation were highlighted in an excellent article by Sanchez and colleagues,^[1] which should be read by clinicians as a classic bench-to-bedside review.

Omalizumab and Chronic Urticaria

Although the most frequent adverse effect of omalizumab administration is urticaria that did not dissuade some from using this drug to treat chronic idiopathic urticaria -- with success. Numerous case reports (as well as this author's experience)^[2] support the efficacy of Xolair in chronic idiopathic urticaria. There are, however, no controlled trials to back these findings. Nonetheless, patients with various forms of urticaria, including autoimmune and idiopathic varieties of chronic urticaria as well as physical urticarias (cold, solar, and delayed pressure), have been reported to respond to omalizumab. Many of the studies were case reports, but a study of 12 patients with urticaria found that 7 of them responded within 4 months of treatment with omalizumab.^[3] The mechanism of action in these cases is proposed to be the effect of omalizumab on basophil and mast cell survival rather than its effect on IgE, which was low in some cases.

Atopic Dermatitis

At the opposite end of the total serum IgE spectrum are many patients with eczema, whose serum IgE level often exceeds 1000 kU/L -- greater than the threshold for Xolair dosing. A few cases of response to omalizumab monotherapy have been reported, but the only blinded, placebo-controlled trial was very small and did not yield positive results.^[4]

Idiopathic Anaphylaxis and Mastocytosis

IgE and the IgE receptor have been implicated in the pathogenesis of idiopathic anaphylaxis. Successful treatment of idiopathic anaphylaxis with omalizumab has been reported and is now the subject of an National Institutes of Health study. Although the mechanism of anaphylaxis is different than that of idiopathic anaphylaxis, mastocytosis-related anaphylaxis has also responded to Xolair in a few cases.

Omalizumab and Food Allergy

Patients receiving omalizumab for asthma have noted increased tolerance of foods that had previously caused IgE-mediated reactions. Controlled trials with food challenges have yet to be done. Studies of Xolair and eosinophilic gastrointestinal diseases are now under way.

Nonatopic Conditions

Omalizumab has worked as both monotherapy and as rescue therapy in refractory cases of Churg-Strauss syndrome. The impact of anti-IgE on allergic bronchopulmonary aspergillosis is unclear. Although it reduces total and Aspergillus-specific IgE levels, omalizumab has not been shown to improve clinical outcomes. Serum IgE is a marker of allergic bronchopulmonary aspergillosis activity, but if blocking IgE does not help then it would seem to only hinder monitoring of the disease state. Of note, a patient with Menière disease and mastocytosis experienced improvement in both conditions when treated with Xolair.

Conclusion

Over time, additional clinical applications for omalizumab will be identified. For less common conditions, it will be hard to conduct the proper trials to gain US Food and Drug Administration approval. The greatest obstacle may be cost of the drug. Some insurers will pay for Xolair on a case-by-case basis for chronic urticaria. And Genentech's Xolair Access Solutions has also been very supportive of doctors and patients who are unable to obtain coverage for nonasthmatic conditions.