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Virtual Users And Domains With Postfix, Courier, MySQL And SquirrelMail (Fedora 17 x86_64) - Page 2
This tutorial exists for these OS versions
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6 Set MySQL Passwords And Configure phpMyAdmin
Start MySQL:
systemctl enable mysqld.service
systemctl start mysqld.service
Then set passwords for the MySQL root account:
[root@server1 ~]# mysql_secure_installation
NOTE: RUNNING ALL PARTS OF THIS SCRIPT IS RECOMMENDED FOR ALL MySQL
In order to log into MySQL to secure it, we'll need the current
password for the root user. If you've just installed MySQL, and
you haven't set the root password yet, the password will be blank,
so you should just press enter here.
Enter current password for root (enter for none): <-- ENTER
OK, successfully used password, moving on...
Setting the root password ensures that nobody can log into the MySQL
root user without the proper authorisation.
Set root password? [Y/n] <-- ENTER
New password: <-- yourrootsqlpassword
Re-enter new password: <-- yourrootsqlpassword
Password updated successfully!
Reloading privilege tables..
... Success!
By default, a MySQL installation has an anonymous user, allowing anyone
to log into MySQL without having to have a user account created for
them. This is intended only for testing, and to make the installation
go a bit smoother. You should remove them before moving into a
production environment.
Remove anonymous users? [Y/n] <-- ENTER
... Success!
Normally, root should only be allowed to connect from 'localhost'. This
ensures that someone cannot guess at the root password from the network.
Disallow root login remotely? [Y/n] <-- ENTER
... Success!
By default, MySQL comes with a database named 'test' that anyone can
access. This is also intended only for testing, and should be removed
before moving into a production environment.
Remove test database and access to it? [Y/n] <-- ENTER
- Dropping test database...
... Success!
- Removing privileges on test database...
... Success!
Reloading the privilege tables will ensure that all changes made so far
will take effect immediately.
Reload privilege tables now? [Y/n] <-- ENTER
... Success!
Cleaning up...
All done! If you've completed all of the above steps, your MySQL
installation should now be secure.
Thanks for using MySQL!
[root@server1 ~]#
Now we configure phpMyAdmin. We change the Apache configuration so that phpMyAdmin allows connections not just from localhost (by commenting out the <Directory /usr/share/phpMyAdmin/> stanza):
vi /etc/httpd/conf.d/phpMyAdmin.conf
# phpMyAdmin - Web based MySQL browser written in php # # Allows only localhost by default # # But allowing phpMyAdmin to anyone other than localhost should be considered # dangerous unless properly secured by SSL Alias /phpMyAdmin /usr/share/phpMyAdmin Alias /phpmyadmin /usr/share/phpMyAdmin #<Directory /usr/share/phpMyAdmin/> # <IfModule mod_authz_core.c> # # Apache 2.4 # <RequireAny> # Require ip 127.0.0.1 # Require ip ::1 # </RequireAny> # </IfModule> # <IfModule !mod_authz_core.c> # # Apache 2.2 # Order Deny,Allow # Deny from All # Allow from 127.0.0.1 # Allow from ::1 # </IfModule> #</Directory> <Directory /usr/share/phpMyAdmin/setup/> <IfModule mod_authz_core.c> # Apache 2.4 <RequireAny> Require ip 127.0.0.1 Require ip ::1 </RequireAny> </IfModule> <IfModule !mod_authz_core.c> # Apache 2.2 Order Deny,Allow Deny from All Allow from 127.0.0.1 Allow from ::1 </IfModule> </Directory> [...]
Then we create the system startup links for Apache and start it:
systemctl enable httpd.service
systemctl start httpd.service
Now you can direct your browser to http://server1.example.com/phpMyAdmin/ or http://192.168.0.100/phpMyAdmin/ and log in with the user name root and your new root MySQL password.
7 Create The MySQL Database For Postfix/Courier
We create a database called mail:
mysqladmin -u root -p create mail
Next, we go to the MySQL shell:
mysql -u root -p
On the MySQL shell, we create the user mail_admin with the passwort mail_admin_password (replace it with your own password) who has SELECT,INSERT,UPDATE,DELETE privileges on the mail database. This user will be used by Postfix and Courier to connect to the mail database:
GRANT SELECT, INSERT, UPDATE, DELETE ON mail.* TO 'mail_admin'@'localhost' IDENTIFIED BY 'mail_admin_password';
GRANT SELECT, INSERT, UPDATE, DELETE ON mail.* TO 'mail_admin'@'localhost.localdomain' IDENTIFIED BY 'mail_admin_password';
Still on the MySQL shell, we create the tables that Postfix and Courier need:
USE mail;
CREATE TABLE domains (
domain varchar(50) NOT NULL,
PRIMARY KEY (domain) )
CREATE TABLE forwardings (
source varchar(80) NOT NULL,
destination TEXT NOT NULL,
PRIMARY KEY (source) )
CREATE TABLE users (
email varchar(80) NOT NULL,
password varchar(20) NOT NULL,
quota bigint(20) DEFAULT '10485760',
PRIMARY KEY (email)
) ENGINE=MyISAM;
CREATE TABLE transport (
domain varchar(128) NOT NULL default '',
transport varchar(128) NOT NULL default '',
UNIQUE KEY domain (domain)
) ENGINE=MyISAM;
As you may have noticed, with the quit; command we have left the MySQL shell and are back on the Linux shell.
The domains table will store each virtual domain that Postfix should receive emails for (e.g. example.com).
The forwardings table is for aliasing one email address to another, e.g. forward emails for [email protected] to [email protected].
|[email protected]
|[email protected]
The users table stores all virtual users (i.e. email addresses, because theemail address and user name is the same) and passwords (in encrypted form!) and a quota value for each mail box (in this example the default value is 10485760 bytes which means 10MB).
|[email protected]
|No9.E4skNvGa. ("secret" in encrypted form)
The transport table is optional, it is for advanced users. It allows to forward mails for single users, whole domains or all mails to another server. For example,
would forward all emails for example.com via the smtp protocol to the server with the IP address 184.108.40.206 (the square brackets [] mean "do not make a lookup of the MX DNS record" (which makes sense for IP addresses...). If you use a fully qualified domain name (FQDN) instead you would not use the square brackets.).
8 Configure Postfix
Now we have to tell Postfix where it can find all the information in the database. Therefore we have to create six text files. You will notice that I tell Postfix to connect to MySQL on the IP address 127.0.0.1 instead of localhost. This is because Postfix is running in a chroot jail and does not have access to the MySQL socket which it would try to connect if I told Postfix to use localhost. If I use 127.0.0.1 Postfix uses TCP networking to connect to MySQL which is no problem even in a chroot jail (the alternative would be to move the MySQL socket into the chroot jail which causes some other problems).
Now let's create our six text files.
vi /etc/postfix/mysql-virtual_domains.cf
user = mail_admin password = mail_admin_password dbname = mail query = SELECT domain AS virtual FROM domains WHERE domain='%s' hosts = 127.0.0.1
vi /etc/postfix/mysql-virtual_forwardings.cf
user = mail_admin password = mail_admin_password dbname = mail query = SELECT destination FROM forwardings WHERE source='%s' hosts = 127.0.0.1
vi /etc/postfix/mysql-virtual_mailboxes.cf
user = mail_admin password = mail_admin_password dbname = mail query = SELECT CONCAT(SUBSTRING_INDEX(email,'@',-1),'/',SUBSTRING_INDEX(email,'@',1),'/') FROM users WHERE email='%s' hosts = 127.0.0.1
vi /etc/postfix/mysql-virtual_email2email.cf
user = mail_admin password = mail_admin_password dbname = mail query = SELECT email FROM users WHERE email='%s' hosts = 127.0.0.1
vi /etc/postfix/mysql-virtual_transports.cf
user = mail_admin password = mail_admin_password dbname = mail query = SELECT transport FROM transport WHERE domain='%s' hosts = 127.0.0.1
vi /etc/postfix/mysql-virtual_mailbox_limit_maps.cf
user = mail_admin password = mail_admin_password dbname = mail query = SELECT quota FROM users WHERE email='%s' hosts = 127.0.0.1
chmod o= /etc/postfix/mysql-virtual_*.cf
chgrp postfix /etc/postfix/mysql-virtual_*.cf
Now we create a user and group called vmail with the home directory /home/vmail. This is where all mail boxes will be stored.
groupadd -g 5000 vmail
useradd -g vmail -u 5000 vmail -d /home/vmail -m
Next we do some Postfix configuration. Go sure that you replace server1.example.com with a valid FQDN, otherwise your Postfix might not work properly!
postconf -e 'myhostname = server1.example.com'
postconf -e 'mydestination = server1.example.com, localhost, localhost.localdomain'
postconf -e 'mynetworks = 127.0.0.0/8'
postconf -e 'virtual_alias_domains ='
postconf -e ' virtual_alias_maps = proxy:mysql:/etc/postfix/mysql-virtual_forwardings.cf, mysql:/etc/postfix/mysql-virtual_email2email.cf'
postconf -e 'virtual_mailbox_domains = proxy:mysql:/etc/postfix/mysql-virtual_domains.cf'
postconf -e 'virtual_mailbox_maps = proxy:mysql:/etc/postfix/mysql-virtual_mailboxes.cf'
postconf -e 'virtual_mailbox_base = /home/vmail'
postconf -e 'virtual_uid_maps = static:5000'
postconf -e 'virtual_gid_maps = static:5000'
postconf -e 'smtpd_sasl_auth_enable = yes'
postconf -e 'broken_sasl_auth_clients = yes'
postconf -e 'smtpd_sasl_authenticated_header = yes'
postconf -e 'smtpd_recipient_restrictions = permit_mynetworks, permit_sasl_authenticated, reject_unauth_destination'
postconf -e 'smtpd_use_tls = yes'
postconf -e 'smtpd_tls_cert_file = /etc/postfix/smtpd.cert'
postconf -e 'smtpd_tls_key_file = /etc/postfix/smtpd.key'
postconf -e 'transport_maps = proxy:mysql:/etc/postfix/mysql-virtual_transports.cf'
postconf -e 'virtual_create_maildirsize = yes'
postconf -e 'virtual_maildir_extended = yes'
postconf -e 'virtual_mailbox_limit_maps = proxy:mysql:/etc/postfix/mysql-virtual_mailbox_limit_maps.cf'
postconf -e 'virtual_mailbox_limit_override = yes'
postconf -e 'virtual_maildir_limit_message = "The user you are trying to reach is over quota."'
postconf -e 'virtual_overquota_bounce = yes'
postconf -e 'proxy_read_maps = $local_recipient_maps $mydestination $virtual_alias_maps $virtual_alias_domains $virtual_mailbox_maps $virtual_mailbox_domains $relay_recipient_maps $relay_domains $canonical_maps $sender_canonical_maps $recipient_canonical_maps $relocated_maps $transport_maps $mynetworks $virtual_mailbox_limit_maps'
postconf -e 'inet_interfaces = all'
Afterwards we create the SSL certificate that is needed for TLS:
cd /etc/postfix
openssl req -new -outform PEM -out smtpd.cert -newkey rsa:2048 -nodes -keyout smtpd.key -keyform PEM -days 365 -x509
Country Name (2 letter code) [XX]: <-- Enter your Country Name (e.g., "DE").
State or Province Name (full name) []: <-- Enter your State or Province Name.
Locality Name (eg, city) [Default City]: <-- Enter your City.
Organization Name (eg, company) [Default Company Ltd]: <-- Enter your Organization Name (e.g., the name of your company).
Organizational Unit Name (eg, section) []: <-- Enter your Organizational Unit Name (e.g. "IT Department").
Common Name (eg, your name or your server's hostname) []: <-- Enter the Fully Qualified Domain Name of the system (e.g. "server1.example.com").
Email Address []: <-- Enter your Email Address.
Then change the permissions of the smtpd.key:
chmod o= /etc/postfix/smtpd.key


text:
The online attacks against South Korean websites began Tuesday morning, local time, on the anniversary of the start of the Korean War (1950-'53). Targeted sites included the country's presidential office (known as Cheong Wa Dae or the Blue House), other government agencies as well as media groups, reported South Korean news agency Yonhap.
"It is verified that not only Cheong Wa Dae and the Prime Minister's office but also some media outlets were hacked," an official at the National Police Agency's cyber terror response team told Yonhap. "It seems that a massive cyber attack has started."
One of the hacked sites contained the following defacement: "Great leader Kim Jong-un," referring to the leader of the North Korean regime, which is based in Pyongyang. For a 10-minute period, another defacement included a picture of South Korean president Park Geun-hye with the following message: "We Are Anonymous. We Are Legion. We Do Not Forgive. We Do Not Forget. Expect Us."
[ This isn't the first time North Korean websites have been targeted. Read Anonymous Takes Down North Korean Websites. ]
South Korean government officials said none of the attacks had hacked into the country's military networks, and that they had yet to identify the attackers. But official Anonymous channels have denied having any involvement in the attacks. "We didn't Hack any #SouthKorea websites," announced the Japanese branch of Anonymous Tuesday in a tweet.
The obvious culprit in the attacks would be North Korea. A wiper malware attack against multiple South Korean banks and broadcasters in March 2013 that erased 48,000 hard drives, for example, was traced to a Pyongyang-based attacker. Previous online attacks against South Korean sites, in 2009 and 2011, were also traced to Pyongyang.
If North Korea did launch the most recent attacks, it may have been a preemptive move before planned Anonymous attacks, which began as scheduled Tuesday. The attacks were announced last week as part of the ongoing Anonymous "#OpNorthKorea" campaign. A list of targets published via Pastebin included multiple North Korean government websites, the official North Korean News Agency, airline Air Koryo and numerous businesses.
Anonymous recommended that attackers employ such distributed denial-of-service (DDoS) attack tools as Slow Loris for Python and Windows, the Low-Orbit Ion Canon, and what the group dubbed the "OWASP Layer 7 DDOS Tool."
As part of Tuesday's attacks, "independent penetration tester" JokerCracker, along with AnonymousTjTeam (aka Anonymous Tijuana), claimed via Twitter to have defaced more than 270 North Korean government website pages.
In a statement addressed "to the tyrants of the North Korean government," Anonymous repeated its demand for Kim Jong-un to step down. "The only power you have are missiles and nuclear," it said. "We are more powerful than that. You cannot destroy ideas with missiles."
According to an attack FAQ published in April, as part of #OpNorthKorea, Anonymous has claimed to be working with small cells in North Korea to create a "ninja gateway" that would bridge the country's quite small Internet -- known as "Kwangmyong" -- with the Internet at large.
Meanwhile, earlier this month Anonymous claimed to have completed the ninja gateway and to have infiltrated multiple North Korean sites. "We completed [several] attacks on your internal websites and inside your local intranets," read a statement released by Anonymous. None of those claims have been verified, but the group promised to release related documents Tuesday.

subset: commoncrawl


text:
Visit these transportation and safety-related web sites.
Federal and State Transportation Agencies
- U. S. Department of Transportation
- Federal Highway Administration
- Federal Motor Carrier Safety Administration
- National Highway Traffic Safety Information
- TEA-21 InformationThis site provides an in-depth description of the Transportation Efficiency Act for the 21st Century.
- Virginia Secretary of Transportation
- Virginia Department of Transportation
- Virginia Department of Rail and Public Transportation
- Virginia Port Authority
- Virginia State Police
- Virginia Department of Environmental Quality
Transportation Industry
- American Bus Association
- American Moving and Storage Association
- Virginia Trucking Associations
- National Limousine Association
- National Private Truck Council
- National Tank Truck Carriers
- Specialized Carriers & Rigging Association
- Truck Rental and Leasing Association
- Truckload Carriers Association
- United Motorcoach Association


text:
Translate urgencia to English
Spanish Word: urgencia
English Translation: exiguity, urgency
Popular Phrase: word for hot in | Spanish Lessons | Conjugated Verb: obedecer - to obey [ click for full conjugation ]
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text:
Learn About the Law
Get help with your legal needs
FindLaw's Learn About the Law features thousands of informational articles to help you understand your options. And if you're ready to hire an attorney, find one in your area who can help.
Appellant administrator brought this action in a Wisconsin state court to recover damages for the death of a decedent who was fatally injured in an automobile accident in Illinois. The complaint was based on the Illinois wrongful death statute, and named as defendants the allegedly negligent driver and an insurance company. Appellant, the decedent, and the individual defendant were residents of Wisconsin; appellant had been appointed administrator under Wisconsin laws; and the insurance company was a Wisconsin corporation. The trial court dismissed the complaint, pursuant to a Wisconsin statute which creates a right of action only for deaths caused in that State, and which establishes a local public policy against Wisconsin courts entertaining suits brought under the wrongful death acts of other states. Held: The statutory policy of Wisconsin which excludes from its courts this Illinois cause of action is in contravention of the Full Faith and Credit Clause of the Federal Constitution. Pp. 610-614.
Appellant's action in a Wisconsin court, to recover damages for a wrongful death arising out of an accident which occurred in Illinois, was dismissed pursuant to the provisions of a Wisconsin statute. The State Supreme Court affirmed. 257 Wis. 35, 42 N. W. 2d 452. On appeal to this Court, reversed and remanded, p. 614.
Samuel Goldenberg argued the cause and filed a brief for appellant.
Herbert L. Wible argued the cause for appellees. With him on the brief was Robert H. Hollander.
MR. JUSTICE BLACK delivered the opinion of the Court.
Basing his complaint on the Illinois wrongful death statute, 1 appellant administrator brought this action in the Wisconsin state court to recover damages for the death of Harold Hughes, who was fatally injured in an automobile accident in Illinois. The allegedly negligent driver and an insurance company were named as defendants. On their motion the trial court entered summary judgment "dismissing the complaint on the merits." It held that a Wisconsin statute, which creates a right of action only for deaths caused in that state, establishes a local public policy against Wisconsin's entertaining suits brought under the wrongful death acts of other states. 2 The Wisconsin Supreme Court affirmed, notwithstanding the contention that the local statute so construed violated the Full Faith and Credit Clause of Art. IV, 1 of the Constitution. 3 The case is properly here on appeal under 28 U.S.C. 1257. [341 U.S. 609, 611]
We are called upon to decide the narrow question whether Wisconsin, over the objection raised, can close the doors of its courts to the cause of action created by the Illinois wrongful death act. 4 Prior decisions have established that the Illinois statute is a "public act" within the provision of Art. IV, 1 that "Full Faith and Credit shall be given in each State to the public Acts . . . of every other State." 5 It is also settled that Wisconsin cannot escape this constitutional obligation to enforce the rights and duties validly created under the laws of other states by the simple device of removing jurisdiction from courts otherwise competent. 6 We have recognized, however, that full faith and credit does not automatically compel a forum state to subordinate its own statutory policy to a conflicting public act of another state; rather, it is for this Court to choose in each case between the competing public policies involved. 7 The clash of interests in cases of this type has usually been described as a conflict between [341 U.S. 609, 612] the public policies of two or more states. 8 The more basic conflict involved in the present appeal, however, is as follows: On the one hand is the strong unifying principle embodied in the Full Faith and Credit Clause looking toward maximum enforcement in each state of the obligations or rights created or recognized by the statutes of sister states; 9 on the other hand is the policy of Wisconsin, as interpreted by its highest court, against permitting Wisconsin courts to entertain this wrongful death action. 10
We hold that Wisconsin's policy must give way. That state has no real feeling of antagonism against wrongful death suits in general. 11 To the contrary, a forum is regularly provided for cases of this nature, the exclusionary rule extending only so far as to bar actions for death not caused locally. 12 The Wisconsin policy, moreover, cannot [341 U.S. 609, 613] be considered as an application of the forum non conveniens doctrine, whatever effect that doctrine might be given if its use resulted in denying enforcement to public acts of other states. Even if we assume that Wisconsin could refuse, by reason of particular circumstances, to hear foreign controversies to which nonresidents were parties, 13 the present case is not one lacking a close relationship with the state. For not only were appellant, the decedent and the individual defendant all residents of Wisconsin, but also appellant was appointed administrator and the corporate defendant was created under Wisconsin laws. We also think it relevant, although not crucial here, that Wisconsin may well be the only jurisdiction in which service could be had as an original matter on the insurance company defendant. 14 And while in the present case jurisdiction over the individual defendant apparently could be had in Illinois by substituted service, 15 in other cases Wisconsin's exclusionary statute might amount to a deprivation of all opportunity to enforce valid death claims created by another state.
Under these circumstances, we conclude that Wisconsin's statutory policy which excludes this Illinois cause of action is forbidden by the national policy of the Full Faith and Credit Clause. 16 The judgment is [341 U.S. 609, 614] reversed and the cause is remanded to the Supreme Court of Wisconsin for proceedings not inconsistent with this opinion.
[ Footnote 2 ] Wis. Stat., 1949, 331.03. This section contains language typically found in wrongful death acts but concludes as follows: "provided, that such action shall be brought for a death caused in this state."
[ Footnote 3 ] 257 Wis. 35, 42 N. W. 2d 452.
[ Footnote 4 ] The parties concede, as they must, that if the same cause of action had previously been reduced to judgment, the Full Faith and Credit Clause would compel the courts of Wisconsin to entertain an action to enforce it. Kenney v. Supreme Lodge, 252 U.S. 411 .
[ Footnote 5 ] E. g., Broderick v. Rosner, 294 U.S. 629, 644 ; Bradford Elec. Co. v. Clapper, 286 U.S. 145, 154 -155; John Hancock Ins. Co. v. Yates, 299 U.S. 178, 183 .
[ Footnote 6 ] E. g., Broderick v. Rosner, 294 U.S. 629, 642 -643; Converse v. Hamilton, 224 U.S. 243, 260 -261; cf. Kenney v. Supreme Lodge, 252 U.S. 411, 415 ; Angel v. Bullington, 330 U.S. 183, 188 . The reliance of the Supreme Court of Wisconsin on Chambers v. Baltimore & O. R. Co., 207 U.S. 142 , was misplaced. That case does not hold that one state, consistently with Art. IV, 1, can exclude from its courts causes of action created by another state for, as pointed out in Broderick v. Rosner, supra at 642, n. 3, in Chambers "no claim was made under the full faith and credit clause."
[ Footnote 7 ] E. g., Pink v. A. A. A. Highway Express, 314 U.S. 201, 210 -211; Pacific Ins. Co. v. Commission, 306 U.S. 493, 502 ; Alaska Packers Assn. v. Commission, 294 U.S. 532, 547 .
[ Footnote 8 ] See, e. g., Alaska Packers Assn. v. Commission, 294 U.S. 532, 547 -550.
[ Footnote 9 ] This clause "altered the status of the several states as independent foreign sovereignties, each free to ignore rights and obligations created under the laws or established by the judicial proceedings of the others, by making each an integral part of a single nation . . . ." Magnolia Petroleum Co. v. Hunt, 320 U.S. 430, 439 . See also Milwaukee County v. White Co., 296 U.S. 268, 276 -277; Order of Travelers v. Wolfe, 331 U.S. 586 .
[ Footnote 10 ] The present case is not one where Wisconsin, having entertained appellant's lawsuit, chose to apply its own instead of Illinois' statute to measure the substantive rights involved. This distinguishes the present case from those where we have said that "Prima facie every state is entitled to enforce in its own courts its own statutes, lawfully enacted." Alaska Packers Assn. v. Commission, 294 U.S. 532, 547 ; see also, Williams v. North Carolina, 317 U.S. 287, 295 -296.
[ Footnote 11 ] It may well be that the wrongful death acts of Wisconsin and Illinois contain different provisions in regard to such matters as maximum recovery and disposition of the proceeds of suit. Such differences, however, are generally considered unimportant. See cases collected 77 A. L. R. 1311, 1317-1324.
[ Footnote 12 ] See note 2, supra.
[ Footnote 13 ] See Broderick v. Rosner, 294 U.S. 629, 643 ; compare Anglo-American Provision Co. v. Davis Co., 191 U.S. 373 , with Kenney v. Supreme Lodge, 252 U.S. 411 .
[ Footnote 14 ] Cf. Tennessee Coal Co. v. George, 233 U.S. 354, 359 -360.
[ Footnote 15 ] Smith-Hurd's Ill. Ann. Stat., 1950, c. 95 1/2, 23.
[ Footnote 16 ] In certain previous cases, e. g., Pacific Ins. Co. v. Commission, 306 U.S. 493, 502 ; Alaska Packers Assn. v. Commission, 294 U.S. 532, 547 , this Court suggested that under the Full Faith and Credit Clause a forum state might make a distinction between statutes and judgments of sister states because of Congress' failure to prescribe the extra-state effect to be accorded public acts. Subsequent to these decisions the Judicial Code was revised so as to provide: "Such Acts [341 U.S. 609, 614] [of the legislature of any state] . . . and judicial proceedings . . . shall have the same full faith and credit in every court within the United States . . . as they have . . . in the courts of such State . . . from which they are taken." (Italics added.) 28 U.S.C. (1946 ed., Supp. III) 1738. In deciding the present appeal, however, we have found it unnecessary to rely on any changes accomplished by the Judicial Code revision.
MR. JUSTICE FRANKFURTER, whom MR. JUSTICE REED, MR. JUSTICE JACKSON, and MR. JUSTICE MINTON join, dissenting.
This is an action brought in the Wisconsin State courts to recover for the wrongful death of Harold G. Hughes. Hughes was killed in an automobile accident in Illinois. An Illinois statute provides that an action may be brought to recover damages for a wrongful death occurring in that State. Smith-Hurd's Ill. Ann. Stat., 1936, c. 70, 1, 2. A Wisconsin statute provides that an action may not be brought in the courts of that State for a wrongful death occurring outside Wisconsin. Wis. Stat., 1949, 331.03. The Wisconsin courts, obeying the command of the Wisconsin statute, dismissed the action. I cannot agree that the Wisconsin statute, so applied, is contrary to Art. IV, 1 of the United States Constitution: "Full Faith and Credit shall be given in each State to the public Acts, Records, and judicial Proceedings of every other State."
The Full Faith and Credit Clause was derived from a similar provision in the Articles of Confederation. Art. 4, 3. The only clue to its meaning in the available records of the Constitutional Convention is a notation [341 U.S. 609, 615] in Madison's Debates that "Mr. Wilson & Docr. Johnson [who became members of the committee to which the provision was referred] supposed the meaning to be that Judgments in one State should be the ground of actions in other States, & that acts of the Legislatures should be included, for the sake of Acts of insolvency &c - ." II Farrand, The Records of the Federal Convention, 447. This Court has, with good reason, gone far in requiring that the courts of a State respect judgments entered by courts of other States. Fauntleroy v. Lum, 210 U.S. 230 ; Kenney v. Supreme Lodge, 252 U.S. 411 ; Milwaukee County v. M. E. White Co., 296 U.S. 268 ; cf. Magnolia Petroleum Co. v. Hunt, 320 U.S. 430 . But the extent to which a State must recognize and enforce the rights of action created by other States is not so clear.
1. In the field of commercial law - where certainty is of high importance - we have often imposed a rather rigid rule that a State must defer to the law of the State of incorporation, or to the law of the place of contract. Thus, in Broderick v. Rosner, 294 U.S. 629 , we held that New Jersey could not close its courts to suits which involved stockholder liability arising under the laws of New York. We had already said, in Converse v. Hamilton, 224 U.S. 243, 260 , that such liability was "peculiarly within the regulatory power" of the State of incorporation; "so much so that no other State properly can be said to have any public policy thereon." In John Hancock Insurance Co. v. Yates, 299 U.S. 178 , we held that the Georgia courts had to give full faith and credit to a New York parole evidence statute which prevented recovery on an insurance contract made in New York. In both these cases, the Court, speaking through Mr. Justice Brandeis, emphasized that it was the particular relationship involved which made the Full Faith and Credit Clause applicable. [341 U.S. 609, 616]
In Pink v. A. A. A. Highway Express, 314 U.S. 201 , the Court found that the Full Faith and Credit Clause did not require the courts of the forum to enforce, against local policyholders, assessments valid under the laws of the state of incorporation of a mutual insurance company. In Griffin v. McCoach, 313 U.S. 498 , we decided that the forum may decline to enforce an insurance policy in favor of beneficiaries who have no insurable interest under local law. Order of Travelers v. Wolfe, 331 U.S. 586 , seems to have made it clear, however, that these decisions did not represent a radical departure from the earlier cases. We held in the Wolfe case that the forum was required to give full faith and credit to a law of the state of incorporation allowing a fraternal benefit society to limit the duration of its liability. It is not merely a bit of rhetoric to caution against imposing on the courts of the forum a "state of vassalage." Hawkins v. Barney's Lessee, 5 Pet. 457, 467, quoted in Order of Travelers v. Wolfe, supra, at 627 (dissenting opinion). But this consideration of autonomy is not sufficient to overcome the advantages to be obtained from a degree of certainty in corporate and commercial law.
2. In cases involving workmen's compensation, there is also a pre-existing relationship between the employer and employee that makes certainty of result desirable. The possible interest of the forum in protecting the workman, however, has made this Court reluctant to impose rigid rules. In Bradford Electric Co. v. Clapper, 286 U.S. 145 , suit was brought in New Hampshire to recover for the wrongful death of an employee occurring in New Hampshire. We held, in an opinion by Mr. Justice Brandeis, that the court sitting in New Hampshire would have to dismiss the action because workmen's compensation was an exclusive remedy under the laws of Vermont, where the contract of employment was made, where the employment was usually carried on, and where both the employer [341 U.S. 609, 617] and the employee were domiciled. Mr. Justice Stone concurred on the ground that the New Hampshire courts would apply the Vermont law on principles of comity. He thought the Full Faith and Credit Clause "should be interpreted as leaving the courts of New Hampshire free, in the circumstances now presented, either to apply or refuse to apply the law of Vermont, in accordance with their own interpretation of New Hampshire policy and law." 286 U.S. at 164-165.
In Alaska Packers Assn. v. Commission, 294 U.S. 532 , we held that California - where the contract of employment was entered into - was free to apply the terms of its own workmen's compensation statute to an employee injured in Alaska, although an Alaska statute purported to give an exclusive remedy to persons injured there. In Pacific Insurance Co. v. Commission, 306 U.S. 493 , we held that the California courts need not give full faith and credit to the exclusive remedy provisions of the Massachusetts Workmen's compensation statute, although Massachusetts was the place of contract and the usual place of employment.
Mr. Justice Stone, who wrote the opinions in the latter two cases, specifically limited the Clapper decision: "The Clapper case cannot be said to have decided more than that a state statute applicable to employer and employee within the state, which by its terms provides compensation for the employee if he is injured in the course of his employment while temporarily in another state, will be given full faith and credit in the latter when not obnoxious to its policy." 306 U.S. at 504.
3. In the tort action before us, there is little reason to impose a "state of vassalage" on the forum. The liability here imposed does not rest on a pre-existing relationship between the plaintiff and defendant. There is consequently no need for fixed rules which would enable parties, [341 U.S. 609, 618] at the time they enter into a transaction, to predict its consequences.
The Court, in the Clapper case, stressed that New Hampshire had opened its courts to the action, but had refused to recognize a substantive defense. Indeed, the Court indicated that a State may be free to close its courts to suits based on the tort liability created by the statutes of other States: "It is true that the full faith and credit clause does not require the enforcement of every right conferred by a statute of another State. There is room for some play of conflicting policies. Thus, a plaintiff suing in New Hampshire on a statutory cause of action arising in Vermont might be denied relief because the forum fails to provide a court with jurisdiction of the controversy; see Chambers v. Baltimore & Ohio R. Co., 207 U.S. 142, 148 , 149; compare Douglas v. New York, N. H. & H. R. Co., 279 U.S. 377 . . . . A State may, on occasion, decline to enforce a foreign cause of action. In so doing, it merely denies a remedy, leaving unimpaired the plaintiff's substantive right, so that he is free to enforce it elsewhere." 286 U.S. at 160.
This Court should certainly not require that the forum deny its own law and follow the tort law of another State where there is a reasonable basis for the forum to close its courts to the foreign cause of action. The decision of Wisconsin to open its courts to actions for wrongful deaths within the State but close them to actions for deaths outside the State may not satisfy everyone's notion of wise policy. See Loucks v. Standard Oil Co., 224 N. Y. 99, 120 N. E. 198 (1918). But it is neither novel nor without reason. Compare the similar Illinois statute which was before this Court in Kenney v. Supreme Lodge, supra. Wisconsin may be willing to grant a right of action where witnesses will be available in Wisconsin and the courts are acquainted with a detailed local statute and cases construing it. It may not wish to subject residents to [341 U.S. 609, 619] suit where out-of-state witnesses will be difficult to bring before the court, and where the court will be faced with the alternative of applying a complex foreign statute - perhaps inconsistent with that of Wisconsin on important issues - or fitting the statute to the Wisconsin pattern. The legislature may well feel that it is better to allow the courts of the State where the accident occurred to construe and apply its own statute, and that the exceptional case where the defendant cannot be served in the State where the accident occurred does not warrant a general statute allowing suit in the Wisconsin courts. The various wrongful death statutes are inconsistent on such issues as beneficiaries, the party who may bring suit, limitations on liability, comparative negligence, and the measure of damages. See Report of the Special Commission to Study the Method of Assessing Damages in Actions for Death (Mass. Sen. No. 430, Dec. 31, 1942) 21 et seq.; Note, 1950 Wis. L. Rev. 354, 360, 363. The measure of damages and the relation of wrongful death actions to actions for injury surviving death have raised extremely complicated problems, even for a court applying the familiar statute of its own State. See Note, 91 U. of Pa. L. Rev. 68 (1942); Oppenheim, The Survival of Tort Actions and the Action for Wrongful Death - A Survey and a Proposal, 16 Tulane L. Rev. 386 (1942). These diversities reasonably suggest application by local judges versed in them. Compare Burford v. Sun Oil Co., 319 U.S. 315 ; Alabama Public Service Comm'n v. Southern R. Co., 341 U.S. 341 .
No claim is made that Wisconsin has discriminated against the citizens of other States and thus violated Art. IV, 2 of the Constitution. Compare Douglas v. New York, N. H. & H. R. Co., 279 U.S. 377 . Nor is a claim made that the lack of a forum in Wisconsin deprives the plaintiff of due process. Compare Brinkerhoff-Faris Co. v. Hill, 281 U.S. 673 ; Missouri v. Lewis, 101 U.S. 22, 30 . [341 U.S. 609, 620] Nor is it argued that Wisconsin is flouting a federal statute. Compare Atlantic Coast Line R. Co. v. Burnette, 239 U.S. 199, 201 . The only question before us is how far the Full Faith and Credit Clause undercuts the purpose of the Constitution, made explicit by the Tenth Amendment, to leave the conduct of domestic affairs to the States. Few interests are of more dominant local concern than matters governing the administration of law. This vital interest of the States should not be sacrificed in the interest of a merely literal reading of the Full Faith and Credit Clause.
There is no support, either in reason or in the cases, for holding that this Court is to make a de novo choice between the policies underlying the laws of Wisconsin and Illinois. I cannot believe that the Full Faith and Credit Clause provided a "writer's inkhorn" so that this Court might separate right from wrong. "Prima facie every state is entitled to enforce in its own courts its own statutes, lawfully enacted. One who challenges that right, because of the force given to a conflicting statute of another state by the full faith and credit clause, assumes the burden of showing, upon some rational basis, that of the conflicting interests involved those of the foreign state are superior to those of the forum." Mr. Justice Stone, in Alaska Packers Assn. v. Commission, supra, at 547-548. In the present case, the decedent, the plaintiff, and the individual defendant were residents of Wisconsin. The corporate defendant was created under Wisconsin law. The suit was brought in the Wisconsin courts. No reason is apparent - and none is vouchsafed in the opinion of the Court - why the interest of Illinois is so great that it can force the courts of Wisconsin to grant relief in defiance of their own law.
Finally, it may be noted that there is no conflict here in the policies underlying the statute of Wisconsin and that of Illinois. The Illinois wrongful death statute has a proviso that "no action shall be brought or prosecuted [341 U.S. 609, 621] in this State to recover damages for a death occurring outside of this State where a right of action for such death exists under the laws of the place where such death occurred and service of process in such suit may be had upon the defendant in such place." Smith-Hurd's Ill. Ann. Stat., 1936, c. 70, 2. The opinion of the Court concedes that "jurisdiction over the individual defendant apparently could be had in Illinois by substituted service." Smith-Hurd's Ill. Ann. Stat., 1950, c. 95 1/2, 23. Thus, in the converse of the case at bar - if Hughes had been killed in Wisconsin and suit had been brought in Illinois - the Illinois courts would apparently have dismissed the suit. There is no need to be "more Roman than the Romans." *
[ Footnote * ] Compare Freund, Chief Justice Stone and the Conflict of Laws, 59 Harv. L. Rev. 1210, 1220 (1946). [341 U.S. 609, 622]
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text:
Full-Time Parenting: A Guide to Family-Based Discipleship. A typical working parent spends just 19 minutes a day looking after their children. In contrast, many children spend about 6 hours per day in school, plus over 7.5 hours per day in media consumption. Add to that the time children spend with their friends or on extra-curricular activities, and it is clear that most American children are not truly being raised by their own parents.
Consequently, studies indicate that as many as 65-88% of all Christian youth leave the faith around their freshman year of college (or before) and never return).
Increasingly, many parents are determining to take back the raising of their own children. They are not content to be a part-time babysitter for their child. They want to be Full-time Parents. Learn how to take the steps towards becoming a Full-time Parent, or learn how to be a better one.
Be the Parent
How I Taught My Children to Sit Still and Be Quiet
The Seven-Year Teaching Method
The Father's Role
Child Training
Helping the Hyperactive Child
The Perfect Family Syndrome
Family Culture vs. Pop Culture
Keeping Your Marriage Strong
Teaching Your Children about Purity
Hospitality: It's Not Just for Women Anymore!
Living on One Income (by Brook Wayne)
Considerations Before You Start a Family Business
A Christian Education Manifesto
Christian Schools vs. Homeschooling
Comfort & Advice for Single Parents (by Skeet Savage)
Why Some Children Leave the Faith
Passing the Baton
Parenting by Grace
"Israel is committed to serving others with integrity and diligence. He truly cares about the families he serves." Tracy Klicka (Author, Christian Leader, Mother of Seven)
Note: e-Book download contains both .epub, .mobi and .pdf versions of the book in a .zip folder.
The audiobook is a downloadable product with Mp3 files. No physical product will be shipped. Almost 6 1/2 hours of audio content.


text:
1954 Red Heart Dog Food
The 1954 Red Heart Dog Food Baseball Card Set consists of three series of eleven unnumbered cards, for a total of 33 cards. Each series in this 1954 Red Heart set has a specific color background—red, green, or blue behind a color photo of each player. The rarest background is red.
This 1954 Red Heart Baseball Card Set were issued via a mail-in offer through the makers of Red Heart dog food. The cards were still available to those who requested them as recently as the early 1970's. Important cards in the 1954 Red Heart Baseball Card Set are: Mickey Mantle, Stan Musial, and Duke Snider. Neither Mantle or Musial appeared the in 1954 Topps Set and Musial was not in the 1954 Bowman set either.
Click here to read about the 1954 Redheart!
CLICK HERE if you want to sell your 1954 Red Heart Dog Food cards.
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text:
Abbey Road Studios is a must-see on almost any Beatles aficionado's tour of London. Once there, a curious sort of tourist delirium seems to take hold. People feel absolutely compelled to recreate the iconic album cover, in the same way that visitors to Pisa just have to get a shot of of themselves holding up the leaning tower.
The only hitch? That famous zebra crossing actually goes across a fully functioning road — one with cars and buses holding people who, one would assume, have better things to do than watch you fiddle with your zoom lens.
Rachel in London was therefore more a little amused to see this note from a fellow local amongst the assorted "I <3 Paul" and "I am the Walrus"-type scrawls that cover the walls near the crossing. "I love the drawing, as it's so true," Rachel says. "It's just a crossing people!!! It's not like the Beatles are coming back to see you do this!"
Interestingly, while the Beatles themselves aren't likely to be watching, thanks to the existence of the (strangely hypnotic) 24-hour Abbey Road webcam, you can actually watch this idiocy as it happens — over and over and over again.
related: Meanwhile, on Portabello Road
extra credit: Photoclichés.com


text:
Steve Jobs, be damned!
Apple's CEO may not want to put Adobe Flash video on the iPhone, but Apple fans made it abundantly clear Wednesday they want access to Flash on their iOS devices.
A mobile Web browser called Skyfire, made by Skyfire Labs, made a brief appearance on the App Store Wednesday selling for $2.99. Skyfire for iPhone promises to transcode Web-based Flash video on the fly to an iPhone-friendly format. "Within 5 hours, Skyfire for iPhone became the top grossing app, the third highest paid app overall and the top application in the Utilities category," Skyfire Labs said in a blog post Wednesday. In other words, iPhone users were so desperate to watch Web-based Flash video on their devices they were willing to pay for the privilege in large numbers.
Skyfire Labs was caught off guard by the demand for its services, and the company was forced to stop selling the Skyfire browser on iTunes just hours after the app debuted.
Sold Out
"The user experience was performing well for the first few hours," Skyfire said. "But as the [iPhone] surge continued, the peak load on our servers and bandwidth caused the video experience to degrade." The Skyfire browser apparently relies on the company's back end servers to transcode Flash video from the Web before sending it back to your iPhone. "We are effectively 'sold out' and will temporarily not accept new purchases from the App Store," the company said. "We are working really hard to increase capacity and will be accepting new purchases from the App Store as soon as we can support it."
Earlier this year, Apple CEO Steve Jobs made it clear that his company is not interested in making the iPhone compatible with Flash video. In an open letter entitled, "Thoughts on Flash," Apple's chief pointed to several reasons he wanted to avoid Flash on the iPhone including security problems, reliability and Flash's poor battery performance on mobile devices.
Thoughts on Flash effectively killed any hopes that Flash would ever make it onto iOS devices. The letter followed years of speculation and grappling between the two companies about whether the Web's most popular video format, Flash, would one day be available to iPhone users.
Other smartphone makers, however, are embracing Flash with open arms. One of the big selling points for Google's Android OS 2.2 (Froyo) was that it would be compatible with Flash version 10.1 for smartphones. There is also some speculation that Flash will eventually make an appearance on Windows Phone 7.
Whatever the fate of Flash on other platforms, the immediate popularity of Skyfire for iPhone suggests that a good number of iPhone users really do want Flash on their handset.
I have reached out to both Adobe and Apple for comment, and will update this post if I hear back from either company.
Connect with Ian Paul (@ianpaul) on Twitter.


text:
Icahn Buys Nearly 13% of Herbalife (HLF)
Carl Icahn filed documents with the SEC which show he owns just short of 13% (12.98%) of Herbalife (NYSE: HLF). The news pushed shares up by as much as 20% after hours.
The actual parties holdings the stock include Icahn Enterprises G.P. Inc
Herbalife has been wrecked by accusations that it is a Ponzi operation, which has drawn the attention of federal regulators.
Filed under: 24/7 Wall St. Wire, Market Roundups Tagged: HLF


text:
For patients who did not meet inclusion criteria, and for each patient withdrawn from treatment after randomization, more than 1 reason could apply. Patients who withdrew their consent (1 in the midazolam group and 2 in the propofol group) denied any use of their data in the analyses.
In the MIDEX trial (midazolam vs dexmedetomidine), the median duration of mechanical ventilation was, for dexmedetomidine, 123 hours (interquartile range [IQR], 67-337 hours) and, for midazolam, 164 hours (IQR, 92-380 hours) (Gehan-Wilcoxon P = .03). The median length of stay in the intensive care unit (ICU) from randomization until the patient was medically fit for discharge was, for dexmedetomidine, 211 hours (IQR, 115-831 hours) and, for midazolam, 243 hours (IQR, 140-630 hours; Gehan-Wilcoxon P = .27). In the PRODEX trial (propofol vs dexmedetomidine), the median duration of mechanical ventilation was, for dexmedetomidine, 97 hours (IQR, 45-257 hours) and, for propofol, 118 hours (IQR, 48-327 hours) (Gehan-Wilcoxon P = .24). The median length of stay in the ICU from randomization until the patient was medically fit for discharge was, for dexmedetomidine, 164 hours (IQR, 90-480 hours) and, for propofol, 185 hours (93-520 hours; Cox's proportional hazards test P = .54). Study drugs were given for a maximum of 336 hours in both trials.
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Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine vs Midazolam or Propofol for Sedation During Prolonged Mechanical Ventilation: Two Randomized Controlled Trials. JAMA. 2012;307(11):1151–1160. doi:10.1001/jama.2012.304
© 2023
Author Affiliations: Department of Intensive Care Medicine, Bern University Hospital and University of Bern, Bern, Switzerland (Drs Jakob and Takala); Department of Anesthesiology and Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland (Dr Ruokonen); Adult Intensive Care Unit, St James Wing, St George's Hospital, London, United Kingdom (Dr Grounds); Orion Pharma, Espoo, Finland (Messrs Sarapohja, Garratt, and Bratty); and Medical Statistics Department, London School of Hygiene and Tropical Medicine, London, United Kingdom (Dr Pocock).
Context Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α2-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.
Objective To determine the efficacy of dexmedetomidine vs midazolam or propofol (preferred usual care) in maintaining sedation; reducing duration of mechanical ventilation; and improving patients' interaction with nursing care.
Design, Setting, and Patients Two phase 3 multicenter, randomized, double-blind trials carried out from 2007 to 2010. The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia. Included were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours (midazolam, n = 251, vs dexmedetomidine, n = 249; propofol, n = 247, vs dexmedetomidine, n = 251).
Interventions Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials.
Main Outcome Measures For each trial, we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation-Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were patients' ability to communicate pain (measured using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol population (midazolam, n = 233, vs dexmedetomidine, n = 227; propofol, n = 214, vs dexmedetomidine, n = 223).
Results Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% CI, 0.97-1.18) and dexmedetomidine/propofol, 1.00 (95% CI, 0.92-1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours [IQR, 67-337]) vs midazolam (164 hours [IQR, 92-380]; P = .03) but not with dexmedetomidine (97 hours [IQR, 45-257]) vs propofol (118 hours [IQR, 48-327]; P = .24). Patients' interaction (measured using VAS) was improved with dexmedetomidine (estimated score difference vs midazolam, 19.7 [95% CI, 15.2-24.2]; P < .001; and vs propofol, 11.2 [95% CI, 6.4-15.9]; P < .001). Length of ICU and hospital stay and mortality were similar. Dexmedetomidine vs midazolam patients had more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001).
Conclusions Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients' ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine.
Trial Registration clinicaltrials.gov Identifiers: NCT00481312, NCT00479661
Sedation in intensive care patients is assumed to reduce discomfort from care interventions, increase tolerance of mechanical ventilation, prevent accidental removal of instrumentation, and reduce metabolic demands during cardiovascular and respiratory instability.1 Long-term sedation may have serious adverse effects, such as prolonged mechanical ventilation,2 coma,3 delirium,4 delusional memories and posttraumatic stress disorder,5,6 impaired cognitive function,7 prolonged hospitalization,2,3,8,9 increased costs,2,3,8 and mortality.9 Daily sedation stops,3 sedation protocols,3,8 spontaneous breathing trials and early mobilization,9,10 or primary use of opiates without other sedation11 may help reduce these complications.
Current sedatives are problematic in long-term sedation. Benzodiazepines and propofol accumulate unpredictably.12,13 High-dose or prolonged propofol use may cause potentially fatal propofol infusion syndrome.14 Dexmedetomidine, a sedative with high α2-adrenoreceptor affinity and action in the locus ceruleus, is an alternative for sedation in intensive care units (ICUs). Dexmedetomidine may enhance patient safety and comfort in long-term sedation. It reduced the incidence of coma and delirium when compared with lorazepam15 and—in a pilot study—reduced duration of mechanical ventilation when compared with propofol or midazolam.16 A multicenter trial in predominantly medical ICU patients found earlier extubation and reduced delirium with dexmedetomidine compared with midazolam.17 However, a recent meta-analysis presented inconclusive results for the effect of dexmedetomidine on duration of mechanical ventilation and ICU stay.18 Most clinicians and centers do not consider midazolam and propofol as equivalent alternatives for long-term sedation.
We designed 2 large, parallel, randomized controlled multicenter trials to compare dexmedetomidine with either midazolam or propofol, according to the preferred usual sedation of study centers. The study designs were identical except for the usual-care control drug. We included higher doses and longer treatment than currently approved for dexmedetomidine. We assessed whether dexmedetomidine is noninferior to midazolam or propofol in maintaining mild to moderate sedation and offers benefits in terms of reduced mechanical ventilation and ICU stay and patients' ability to communicate during sedation.
These 2 phase 3, European, multicenter, randomized, double-blind studies conducted in 2007 through 2010 compared midazolam with dexmedetomidine (MIDEX trial; 44 centers in 9 European countries) and propofol with dexmedetomidine (PRODEX trial; 31 centers in 6 European countries and 2 in Russia) and were approved by the respective ethics committees (eAppendix). Written informed consent was obtained from the patient's family, a legal representative, or both. An independent data safety monitoring board had full access to the ongoing unblinded data and made regular recommendations to the sponsor and steering committee, based on the risk-benefit evaluation, regarding continuation, adjustment, or termination of the 2 trials.
The main inclusion criteria were age 18 years or older, invasive mechanical ventilation, clinical need for light to moderate sedation (target sedation Richmond Agitation-Sedation Scale [RASS] score was from 0, alert and calm, to −3, responds to verbal stimulation by movement or eye opening to voice but no eye contact19) using midazolam or propofol infusion expected to last for 24 hours or longer after randomization, and randomization within 72 hours of ICU admission and within 48 hours of starting continuous sedation.
The main exclusion criteria were acute severe neurological disorder, mean arterial pressure less than 55 mm Hg despite appropriate intravenous volume replacement and vasopressors, heart rate less than 50/min, atrioventricular-conduction grade II or III (unless pacemaker installed), and use of α2 agonists or antagonists within 24 hours prior to randomization. The most common reasons that patients were excluded were that they were not ventilated, they were expected to need less than 24 hours sedation, or they had an acute severe neurological disorder (complete list of exclusion criteria in eAppendix).
Eligible study participants were randomized 1:1 by a central interactive voice-response system funded by the sponsor to either continue their current standard care (midazolam [MIDEX trial] or propofol [PRODEX trial]) or switch to dexmedetomidine. Randomization was stratified for study center in blocks of 4. All patients and study personnel were masked to treatment allocation. Treatments were administered in a double-dummy design, with 0.9% sodium chloride as dummy for all treatments. Propofol and propofol dummy were prepared, connected, and removed by independent personnel and infused with nontransparent black syringes, infusion tubings, and connectors.
Study treatments were titrated to individual sedation targets. Depth of sedation was assessed using RASS scores,19 which range from −5 (unarousable) to +4 (combative) (eAppendix); target RASS score was determined before starting study treatment and at daily sedation stops. Assessment of RASS score was performed every 2 hours and prior to any dose of rescue therapy. Six dose levels of each study drug covered the full dose range (dexmedetomidine, 0.2-1.4 μg/kg per hour; midazolam, 0.03-0.2 mg/kg per hour; propofol, 0.3-4.0, mg/kg per hour). Study treatments were infused without loading dose at a dose matching the prerandomization dose of midazolam (MIDEX trial) or propofol (PRODEX trial) for 1 hour. Thereafter, study drugs were titrated by the patient's nurse stepwise to maintain the target RASS score (eAppendix).
Pain was treated with fentanyl boli. Rescue medication boli could be given if needed to achieve target RASS score (first-line rescue propofol in the MIDEX trial and midazolam in the PRODEX trial; further rescue medication decided by treating clinician). Need for resedation and continued ventilation was assessed after a daily sedation stop and spontaneous breathing trial. Study medication was continued up to a maximum of 14 days from randomization and stopped at the time of extubation. Patients were followed up for 45 days.
The first primary efficacy end point was the proportion of time in target sedation range (RASS score, 0 to −3) without use of rescue therapy of the total duration of study drug infusion; the other was duration of mechanical ventilation from randomization until patients were free of mechanical ventilation (including noninvasive) without reinstitution for the following 48 hours.
Secondary efficacy outcomes were length of ICU stay from randomization until medically fit for discharge and nurses' assessment of arousal, ability to cooperate with care, and ability to communicate pain16 using visual analogue scales (VAS). The follow-up visit occurred on day 45 after randomization. (Refer to the eAppendix for more prespecified end points and safety monitoring.)
The planned enrolment was 500 participants in each trial. Based on a pilot study,16 we assumed an overall 64% of time in target range of sedation without using rescue medication. A sample size of 450 in each trial gives 90% power to reject a 15% inferiority of dexmedetomidine to standard sedation using a 2-sided 95% confidence interval for the estimated ratio of dexmedetomidine to standard care.
Proportion of time within RASS target without rescue medication was analyzed in the per-protocol population to avoid bias toward noninferiority using a variance analysis model with fixed effects for treatment and country. Noninferiority margin was defined as 15%; ie, the lower 95% CI of the estimated dexmedetomidine-to-standard-care ratio of proportion of time in range must be above 0.85. Variance estimate of the ratio was calculated from the estimated covariance matrix. A sensitivity analysis using the intention-to-treat population was also performed.
The intention-to-treat population, including all randomized patients, was used for all other efficacy variables to analyze superiority. Safety was analyzed in patients who received any study drug. Length of ICU stay was until patients were judged medically fit for discharge. The primary analysis of the duration of mechanical ventilation, length of ICU stay, time to extubation, and length of hospital stay was based on a Cox proportional hazards regression model, stratified by country. The proportional hazards assumptions were only fulfilled for length of hospital stay and length of ICU stay in the propofol vs dexmedetomidine study. Use of alternative tests was predefined in the analysis plan; therefore, the Gehan-Wilcoxon test was used post hoc. Calculation of descriptive medians and interquartile ranges excluded censored cases. Results for the VAS were analyzed using analysis of covariance, adjusting for country and baseline value. (For imputation rules, see the eAppendix.) Proportional analyses for longitudinal data were based on a generalized estimating equation model with factors for treatment, time, and country.
All data are presented as median and interquartile range (IQR) unless indicated otherwise. A 2-sided significance level of .05 was used in all treatment comparisons. Proportionality assumption was tested on a .10 level. SAS statistics software version 9.1 was used.
The intention-to-treat populations included 249 and 251 patients in the dexmedetomidine and midazolam groups (MIDEX trial) and 251 and 247 patients in the dexmedetomidine and propofol groups (PRODEX trial), respectively (Figure 1). Diagnostic groups and severity of organ failures20 at baseline were comparable between the treatment groups (Table 1). In the MIDEX trial, 53 midazolam patients (21.1%) and 68 dexmedetomidine patients (27.3%) died between randomization and follow-up at day 45 (P = .12). In the PRODEX trial, 48 propofol patients (19.4%) and 43 dexmedetomidine patients (17.1%) died during this period (P = .56).
Patients in MIDEX received less dexmedetomidine compared with patients in PRODEX (Table 2). Noninferiority of dexmedetomidine vs standard care was confirmed in both studies (time at target sedation without rescue medication: midazolam, 56.6%, vs dexmedetomidine, 60.7%; propofol, 64.7%, vs dexmedetomidine, 64.6%). The estimated ratio of dexmedetomidine vs midazolam in time at target sedation was 1.07 (95% CI, 0.97-1.18; P = .15), and of dexmedetomidine vs propofol, 1.00 (95% CI, 0.92-1.08; P = .97) (eFigure 1). For the intention-to-treat population, the estimated ratios were dexmedetomidine/midazolam, 1.09 (95% CI, 0.99-1.19) and dexmedetomidine/propofol, 0.97 (95% CI, 0.89-1.04). Dexmedetomidine patients had higher actual RASS scores in both studies (P < .001) (Table 2 and eTable 1).
Study drug discontinuation rates were similar in dexmedetomidine and standard care patients (midazolam, 50/250 [20%], vs dexmedetomidine, 60/249 [24%]; propofol, 58/247 [23%], vs dexmedetomidine, 71/251 [28%]), but discontinuation due to lack of efficacy was more frequent in dexmedetomidine patients (midazolam, 10/250 [4%], vs dexmedetomidine, 23/249 [9%]; P = .02; propofol, 13/247 [5%], vs dexmedetomidine, 36/251 [14%]; P < .001). Lack of efficacy within the first 24 hours was less frequent in the midazolam vs dexmedetomidine study (5 of 23 instances) than in the propofol vs dexmedetomidine study (15 of 36 instances).
The median duration of mechanical ventilation (including noninvasive ventilation) in MIDEX was 164 hours (IQR, 92-380 hours) for midazolam and 123 hours (IQR, 67-337 hours) for dexmedetomidine (Gehan-Wilcoxon P = .03). In PRODEX, it was 118 hours (IQR, 48-327 hours) for propofol and 97 hours (IQR, 45-257 hours) for dexmedetomidine (Gehan-Wilcoxon P = .24) (Figure 2). The median time to extubation in MIDEX was 147 hours (IQR, 81-325 hours) for midazolam and 101 hours (IQR, 65-313 hours) for dexmedetomidine (Gehan-Wilcoxon P = .01). In PRODEX, it was 93 hours (IQR, 45-286 hours) for propofol and 69 hours (IQR, 39-184 hours) for dexmedetomidine (Gehan-Wilcoxon P = .04) (eFigure 2 and 3).
The median length of stay in the ICU from randomization until the patient was medically fit for discharge was not significantly different in the 2 studies (midazolam, 243 hours [IQR, 140-630 hours], vs dexmedetomidine, 211 hours [IQR, 115-831 hours]; propofol, 185 hours [IQR, 93-520 hours], vs dexmedetomidine, 164 hours [90-480 hours]) (Figure 2). There were no significant differences between dexmedetomidine and standard care in length of hospital stay (eAppendix and eTables 2 through 9).
Patients receiving dexmedetomidine were more arousable, more cooperative, and better able to communicate their pain than patients receiving either midazolam or propofol (P ≤ .001 for each component separately and for total VAS score) (Table 3).
Sedation stops in the MIDEX trial were performed on 93.3% (midazolam) and 89.7% (dexmedetomidine) of eligible study days when no contraindication existed; in the PRODEX trial, sedation stops were performed on 90.1% (propofol) and 89.0% (dexmedetomidine) of days (Table 2). The most common reasons to restart sedation after a sedation stop were poor tolerance of the endotracheal tube or mechanical ventilation, agitation or anxiety, and cardiovascular instability (eTable 10). Changes in serum glucose over time were not different between treatments in any of the studies (eTable 11).
In the MIDEX trial, the adverse event hypotension was recorded in 29 of 250 midazolam patients (11.6%) vs 51 of 247 dexmedetomidine patients (20.6%) (P = .007). Bradycardia was reported in 13 of 250 midazolam patients (5.2%) and in 35 of 247 dexmedetomidine patients (14.2%) (P < .001). In the PRODEX trial, hypotension and bradycardia were reported at similar rates in both groups. First-degree atrioventricular block in MIDEX was observed in 3 patients in each group and, in PRODEX, in 2 propofol patients (0.8%) and 9 dexmedetomidine patients (3.7%) (P = .04). There were no differences between dexmedetomidine and standard care in infectious adverse events. Critical illness polyneuropathy was less common in patients receiving dexmedetomidine than in those receiving propofol (2 patients vs 11 patients, respectively; P = .02). (For detailed adverse and serious adverse events refer to the eAppendix and eTables 12 through 15.)
In the MIDEX trial, rates of neurocognitive adverse events through 48 hours of follow-up (agitation, anxiety, delirium, etc) were not different between midazolam and dexmedetomidine patients. In PRODEX, neurocognitive adverse events were reported in 71 of 247 propofol patients (29%) and in 45 of 251 dexmedetomidine patients (18%) (P = .008); also, dexmedetomidine patients received concomitant treatment for agitation, anxiety, and delirium less frequently (eTable 15). In both studies, there were no differences between the treatments in number of patients needing reinstitution of sedation due to agitation and anxiety or in delirium assessed using the Confusion Assessment Method for ICU Patients (CAM-ICU)21 at 48 hours after stopping study sedation. Serious adverse events were equally common between treatment groups in both studies.
These 2 trials demonstrated that dexmedetomidine was not inferior to midazolam or propofol for long-term sedation in mechanically ventilated ICU patients. Dexmedetomidine's noninferiority compared with these standard sedation strategies in mild to moderate sedation was confirmed. Dexmedetomidine appeared to shorten mechanical ventilation compared with midazolam but not compared with propofol; however, time to extubation was reduced compared with both midazolam and propofol. Dexmedetomidine enhanced patients' ability to communicate pain to the nursing staff, possibly contributing to the earlier extubation. Accordingly, dexmedetomidine may provide clinically relevant benefits compared with standard sedation, even when measures to reduce the risks of oversedation are implemented. The better arousability and ability to communicate pain should allow more appropriate use of opioids and facilitate earlier mobilization and functional recovery.
We observed in our pilot study16 that dexmedetomidine was not suitable for deep sedation. Therefore, these pivotal trials focused on light to moderate sedation. Despite this, the study treatment was discontinued due to lack of efficacy more frequently in dexmedetomidine patients in both trials. With the current maximum dose, lack of efficacy can be expected in approximately 1 in every 8 to 10 patients. Whether higher doses of dexmedetomidine could safely be used should be addressed in future studies. Dexmedetomidine doses were substantially lower in the midazolam vs dexmedetomidine than in the propofol vs dexmedetomidine study despite similar sedation levels. This was likely due to the remaining effect of preceding midazolam sedation.
Dexmedetomidine has been proposed to reduce the duration of mechanical ventilation.16,17 Others observed earlier extubation with dexmedetomidine when compared with midazolam.17 We observed that the difference between dexmedetomidine and midazolam in the proportion of mechanically ventilated patients changed over time and was not statistically significant in the primary analysis. Because median length of study drug infusion in the midazolam vs dexmedetomidine study was only 42 to 47 hours, any effect of dexmedetomidine would be expected early in a large proportion of patients. Furthermore, since the study drug was limited to 14 days, but mechanical ventilation was considered up to 45 days, standard care given after dexmedetomidine may have reduced any benefit from dexmedetomidine. Also, imputation of length of mechanical ventilation to 45 days in patients who died may have confounded early treatment effects. Accordingly, the alternative statistical analysis indicated significantly shorter mechanical ventilation with dexmedetomidine than midazolam and earlier extubation in both studies. If only observed data are included, mechanical ventilation is significantly shorter with dexmedetomidine in both trials (eTable 5). The present and previous trials suggest that dexmedetomidine shortens mechanical ventilation compared with benzodiazepine infusions, even when frequent monitoring of sedation and sedation stops are used.
This is the first large-scale study comparing dexmedetomidine with propofol in long-term sedation. Main advantages of propofol are short duration of action and rapid awakening when sedation is stopped,3,22 unless used long-term in high doses.13 Mechanical ventilation was shorter with propofol than lorazepam.22 Our results indicate that duration of mechanical ventilation is similar with dexmedetomidine and propofol, but dexmedetomidine favors earlier extubation.
All sedatives have cardiovascular adverse effects. As an α2-adrenoreceptor agonist, dexmedetomidine can cause bradycardia and hypotension. As in previous studies,16,17 bradycardia was more common with dexmedetomidine. Hypotension and cardiovascular instability other than bradycardia rarely necessitated stopping the study in all study groups, despite severe cardiovascular dysfunction (cardiovascular Sequential Organ Failure Assessment score >2) in more than 60% of patients at the baseline. The exclusion of patients with a specific risk of adverse effects with dexmedetomidine—those with bradycardia and atrioventricular block—may have introduced some bias favoring dexmedetomidine.
The 45-day mortality was higher in the MIDEX study than the PRODEX study (P = .03). This was mainly related to the difference in mortality between the groups receiving dexmedetomidine (27.3% in MIDEX vs 17.1% in PRODEX), whereas standard-care group mortalities were comparable (21.1% with midazolam vs 19.4% with propofol). When all dexmedetomidine patients were compared with all standard-care patients, mortality was similar (22.2% vs 20.3%, P = .49). This is consistent with the only previous large study comparing dexmedetomidine with midazolam in long-term sedation (30-day mortality, 25% for midazolam vs 23% for dexmedetomidine17). The only trial reporting 1-year mortality after dexmedetomidine sedation found no difference between dexmedetomidine and lorazepam.15
Delirium is common during prolonged intensive care,4,7,9,15,17 and sedation may be an independent risk factor.4 Dexmedetomidine reduced the composite end point of delirium and coma as compared with lorazepam without sedation stops,15 and delirium as compared with midazolam.17 Our pilot study suggested increased delirium with dexmedetomidine.16 In the present studies, incidence of neurocognitive disorders, including delirium, was similar with dexmedetomidine and midazolam, whereas dexmedetomidine was associated with fewer neurocognitive disorders than propofol. Others have found that dexmedetomidine sedation—in contrast to propofol—preserved or even improved cognitive function in patients with decreased baseline cognition.23 These seemingly conflicting results may be related to the definition of delirium. We used the reported adverse events and assessed delirium using CAM-ICU only once, 48 hours after stopping study drugs. We found more clinically apparent critical illness polyneuromyopathy in propofol patients; this observation is inconclusive and should be studied further.
The main strengths of these studies are the large sample size, proof of noninferiority in maintaining sedation, use of double dummy to avoid unmasking, and frequent sedation assessment and daily sedation stops. There are several limitations. The standard sedation preceding randomization may have masked benefits of dexmedetomidine during shorter exposure. A change of drug may have increased the lack of efficacy early during dexmedetomidine infusion, which was observed in the PRODEX study. Because of clinical contraindications, scheduled sedation stops were not always performed: the rates are similar or slightly higher than those reported by others.9 Spontaneous breathing trials were performed only in about half of the sedation stops, as compared with approximately 60% of those screened in the Awakening and Breathing Controlled trial.9 The lack of a usual care control group including bolus administration of midazolam could be considered a study limitation. However, published surveys24,25 and the usual care in study centers indicate that midazolam infusion is very common. Weaning from mechanical ventilation and criteria for extubation were not standardized. The large sample size and randomization should minimize bias induced by different weaning practices. The effects of the study drugs should be interpreted with the concomitant use of opiates and rescue medications and the target of light to moderate sedation; however, this corresponds to their clinical use. Finally, we assessed sedation from the caregiver's perspective. Future studies should include the patient's perspective of quality of sedation as well.
In summary, dexmedetomidine was noninferior to propofol and midazolam in maintaining the target sedation level in a broad spectrum of ICU patients requiring prolonged mechanical ventilation. Dexmedetomidine appeared to reduce the duration of mechanical ventilation as compared with midazolam, reduced the time to extubation as compared with both midazolam and propofol, reduced delirium as compared with propofol, and was associated with improved patient communication with the nursing staff but had no effect on length of ICU or hospital stay. Incidences of hypotension and bradycardia were higher with dexmedetomidine than with midazolam but comparable with propofol. We conclude that dexmedetomidine is feasible for long-term sedation in intensive care patients and may provide clinically relevant benefits by reducing the duration of invasive ventilation and improving comfort.
Corresponding Author: Jukka Takala, MD, PhD, Department of Intensive Care Medicine, Bern Univer sity Hospital, CH-3010 Bern, Switzerland (firstname.lastname@example.com).
Author Contributions: Drs Jakob and Ruokonen contributed equally as first authors. Drs Ruokonen, Jakob, and Takala had full access to the study data. Dr Takala had the final responsibility for the decision to submit the manuscript. Drs Jakob and Ruokonen served as co–principal investigators and, with Dr Takala, conceived the original idea of the 2 studies.
Study concept and design: Jakob, Ruokonen, Grounds, Sarapohja, Garratt, Pocock, Bratty, Takala.
Analysis and interpretation of data: Jakob, Ruokonen, Sarapohja, Garratt, Pocock, Bratty, Takala.
Drafting of the manuscript: Jakob, Ruokonen, Grounds, Sarapohja, Garratt, Pocock, Bratty, Takala.
Critical revision of the manuscript for important intellectual content: Jakob, Ruokonen, Grounds, Sarapohja, Garratt, Pocock, Bratty, Takala.
Statistical analysis: Jakob, Ruokonen, Sarapohja, Pocock, Takala.
Obtained funding: Jakob, Takala.
Administrative, technical, or material support: Ruokonen, Sarapohja, Garratt, Bratty.
Study supervision: Jakob, Ruokonen, Takala.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. This study was sponsored by Orion Pharma, Espoo, Finland, through research contracts negotiated directly with the participating hospitals. Orion Pharma, Orion Corporation, is the originator of dexmedetomidine. On behalf of Drs Jakob and Takala, a grant and consulting fees were paid to the Bern University Hospital Department of Intensive Care Medicine to cover the costs of performing the study. The department was reimbursed for the authors' travel costs to publication committee meetings. Dr Jakob served as an expert for preparing the regulatory filing of the drug; the money was also paid into a departmental fund. Additionally, the Department of Intensive Care Medicine has, or has had in the past, research contracts with Abbott Nutrition International, B. Braun Medical, CSEM, Edwards Lifesciences Services, Kenta Biotech, Maquet Critical Care, and Omnicare Clinical Research and research and development or consulting contracts with Edwards Lifesciences, Maquet Critical Care, and Néstle. The money is or was paid into a departmental fund; no author received any personal financial gain. The department has received unrestricted educational grants from the following organizations for organizing a quarterly postgraduate educational symposium, the Berner Forum for Intensive Care: Fresenius Kabi, MSD, Lilly, Baxter, Astellas, AstraZeneca, B. Braun, CSL Behring, Maquet, Novartis, Covidien, Mycomed, and RobaPharma. Dr Grounds received a consulting fee from Orion Pharma during planning and execution of the study. He and members of his clinical staff at St George's Hospital received monetary support from Orion for travel to study-related meetings to ensure compliance with the study protocol. His department received payment of a fee per patient recruited to the study, as well as drugs used in the study and support personnel to assist with data input. Dr Ruokonen's institution, Kuopio University, received a grant from Orion to carry out the study, as well as consulting fees and reimbursement of travel funds. Messrs Sarapohja, Garratt, and Bratty were full-time employees of Orion Pharma throughout the period of the project. Their routine travel expenses were reimbursed as part of their employment. Dr Pocock of the London School of Hygiene and Tropical Medicine received a consulting fee from Orion in connection with the study, and his institution received a grant. London School of Hygiene and Tropical Medicine also received a grant for independent statistical review performed by Dr Duolao Wang.
Funding/Support: This study was sponsored by Orion Pharma, Espoo, Finland, through research contracts negotiated directly with the participating hospitals.
Role of the Sponsors: The original idea was presented to the sponsor by Drs Jakob and Takala. The sponsor and the principal investigators designed the study and the statistical analysis plan. Data were collected by the investigators using the electronic data capture system provided by the sponsor. Data collection and quality control were managed by the contract research organization. The database was managed by the sponsor. Primary analysis according to the statistical analysis plan was performed by the statistician of the sponsor (Mr Sarapohja) and was also confirmed by Dr Duolao Wang under supervision of Dr Pocock. Data were interpreted by the publication committee with members from the sponsor company (Messrs Sarapohja, Garratt, and Bratty). Preparation, review, or approval of the manuscript was performed only through the coauthor members of the publication committee; according to the study contracts, the sponsor had the right to comment on the draft, but the publication committee had the final decision, and the decision to submit the manuscript was the responsibility of the senior author.
Independent Statistical Analysis: Analysis was undertaken by Dr Duolao Wang (Medical Statistics Department, London School of Hygiene and Tropical Medicine, London, United Kingdom) under the supervision of Dr Pocock, Medical Statistics Department, London School of Hygiene and Tropical Medicine. Full access to all of the data used in the study was provided and an independent analysis of the primary and secondary end points reported in this article was performed by repeating the analyses and verifying P values and 95% confidence intervals. Consistency between the objectives set out in the protocol, the prespecified statistical analysis plan, and results of the statistical analysis produced by the sponsor was verified. No discrepancies were found. Drs Jakob, Ruokonen, and Takala also had full access to the data and performed the analyses independently from those of the sponsor. The results reported from these independent analyses were identical to those of the sponsor.
MIDEX Study Group Members: Belgium: Brussels: H. Spapen (UZ Brussel); J-L. Vincent (Université Libre de Bruxelles–Erasme University Hospital); Gent: K. Colpaert (Universitaer Ziekenhuis Gent); Liege: B. Lambermont (Department of Medicine, University Hospital of Liege). Estonia: Tallin: U. Kivistik (North Estonia Medical Centre Foundation); A. Saar (East Tallin Central Hospital); V. Toome (North Estonian Medical Centre); Tartu: K. Tamme (Tartu University Hospital). Finland: Tampere: J. Tenhunen (Tampere University Hospital); Oulu: T. Ala-Kokko (Oulu University Hospital). France: Paris: J-D. Chiche (Groupe Hospitalier Cochin); P. Montravers (Hôpital Bichat-Claude Bernard); Angers: A. Mercat (Centre Hospitalier Universitaire d'Angers); Argenteuil: H. Mentec (Centre Hospitalier Victor Dupouy); Grenoble: J-F. Timsit (Centre Hospitalier Universitaire de Grenoble); La Roche sur Yon: J. Reignier (Service de Réanimation, CHD Les Oudairies); Lille: F. Saulnier (Hôpital Albert Calmette); Limoges: A. Dugard (Centre Hospitalier Universitaire de Limoges); Orléans: T. Boulain (Centre Hospitalier Régional d'Orléans, Hôpital de La Source); Poitiers: R. Robert (Centre Hospitalier Universitaire de Poitiers); Tours: E. Mercier (Centre Hospitalier Régional et Universitaire–Hôpital Bretonneau). Germany: Bonn: C. Putensen (Universitätsklinikum Bonn); Greifswald: M. Grundling (Universitätsklinikum Greifswald); Tübingen: K. Unertl (Universitätsklinikum Tübingen). Netherlands: Zwolle: F. Snellen (Isala Klinieken); Amsterdam: A. Beishuizen (VU Medisch Centrum); Apeldoorn: P. Spronk (Gelre Hospital–Apeldoorn); Breda: B. van der Meer (Amphia Ziekenhuis); Dordrecht: A. Koopman-Van Gemert (Albert Schweitzer Hospital); Haarlem: N. Fennema (Kennemer Gasthuis); Tilburg: B. Speelberg (St Elisabeth Ziekenhuis); Venlo: N. Foudraine (Viecuri Medical Centre). Norway: Oslo: S. Walter and E. Helset (Ulleval University Hospital); R. Lovstad (Oslo University Hospital–Aker); A. Stubhaug (Oslo University Hospital, Rikshospitalet); Bergen: A. Guttormsen (Haukeland University Hospital). Switzerland: Bern: S. Jakob (Bern University Hospital [Inselspital] and University of Bern); Winterthur: A. Haller (Kantonsspital Winterthur); Zürich: M. Maggiorini (Universitätsspital Zürich). United Kingdom: Birmingham: G. Perkins (MIDRU, Heart of England NHS Foundation Trust); A. Whitehouse (Selly Oak Hospital); Plymouth: P. MacNaughton (Derriford Hospital).
PRODEX Study Group Members: Belgium: Aalst: I. Demeyer (Onze-Lieve-Vrouw, Ziekenhuis); Genk: R. de Jongh (Ziekenhuis Oost Limburg, Schiepse Bos); Gent: K. Colpaert (Universitaer Ziekenhuis Gent). Finland: Kuopio: I. Parviainen (Kuopio University Hospital); Espoo: T. Oksanen (HUCH, Jorvi Hospital); Helsinki: M. Kaukonen (HUCH, Meilahti Hospital); Joensuu: M. Reinikainen (North Karelia Central Hospital); Lahti: P. Loisa (Päïjät-Häme Central Hospital); Lappeenranta: S. Hovilehto (South Karelia Central Hospital); Seinäjoki: K. Saarinen (Seinäjoki Central Hospital); Tampere: J. Tenhunen (Tampere University Hospital). Germany: Berlin: C. Spies (Charité–Universitätsmedizin Berlin); Erlangen: J. Schuttler (Universitätsklinikum Erlangen); Frankfurt am Main: K. Zacharowski (Klinikum der J. W. Goethe-Universität); Giessen: T. Menges (University of Giessen and Marburg); Halle: J. Soukup (Universitätsklinikum Halle); Heidelberg: J. Motsch (Universitätsklinikum Heidelberg); Homburg/Saar: T. Volk (Universitätsklinikum des Saarlandes); Leipzig: U. Kaisers (University Leipzig, Medical Faculty); A. Sablotzki (Klinikum St Georg); Tübingen: K. Unertl (Universitätsklinikum Tübingen); Wetzlar: J. Engel (Klinikum-Wetzlar-Braunfels); Netherlands: Breda: B. van der Meer (Amphia Ziekenhuis); Hertogenbosch: F. Rozendaal (Jeroen Bosch Ziekenhuis); Hoorn: P. Knüpfer (Westfries Gasthuis); Tiel: M. van Iperen (Rivierenland Hospital). Russia: Kemerovo: E. Grigoryev (M. A. Podgorbunsky Municipal Clinical Hospital); Krasnodar: Zabolotskikh (Municipal Hospital No. 2, Krasnodar Diversified). Switzerland: Bern: S. Jakob (Bern University Hospital [Inselspital] and University of Bern). United Kingdom: London: R. Grounds (St George's Hospital); Bury St Edmunds: J. Cardy (West Suffolk Hospital NHS Trust); Edinburgh: T. Walsh (Edinburgh Royal Infirmary); Leeds: A. Mallick (Leeds General Infirmary); Livingston: L. Morrison (St John's Hospital).
Previous Presentation: The main results were presented orally at the 31st annual International Symposium on Intensive Care and Emergency Medicine (ISICEM); March 22-25, 2011; Brussels, Belgium.
Additional Contributions: We thank Jeannie Wurz, BA, a medical editor employed by the Department of Intensive Care Medicine at the Bern University Hospital, for editorial assistance. She did not receive compensation besides her salary.


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Many famous names in tea come from Wuyi — Red Cloak ( often wrongly translated as Red Robe ), Iron Buddha, Shuixian, Lapsang Souchong, Yancha, are a few. We screen the tens of varieties to offer some of the most distinctive and finest quality oolongs and black tea from this region.
Iron Buddha Supreme, Wuyi yancha oolongDenser Aromas, Fuller Bodies, Oolongs, Tea, Warm Energy, Wuyi-shan
Bamboo Forest Tiě Luohan:Overshadowed by the more promoted Red Cloak, Iron Buddha ( Tiě Luohan ) is actually as taste-worthy, if not more, than any of the so-called "famous" Wuyi oolongs. It is not proven that whether it is the oldest oolong cultivar in Wuyi as they say, but it is certainly one that is not the easiest to cultivate and to produce from. Finding a farmer to process it to the taste profile that befits its legend and our quality demand has been a challenge. It took us 15 years. Presenting Tea Hong's Iron Buddha Supreme, with that complex charcoal finish yet sweet floral aroma, stout yet lingering "rock tea" taste, delivered gently in a well-balanced infusion in a civilised way. This could very well be the only traditional style Wuyi that any connoisseur would fall in love with. Net weight: 40 g (1.4 oz) in Kraft-alu pack
USD 29.10Rated 5.00 out of 5 USD 29.10
Tongmuguan One, traditional black teaBlack teas, Floral Aromas, Fuller Bodies, Neutral-Warm Energy, Tea, Wuyi-shan
Rare Quality Meizhan Hong ChaNot many black teas can achieve a smooth and full body. To have a floral, yet warm aroma with spicy sweetness and complexity of dried fruit would be a luxury. Tongmuguan One makes it even better by delivering the whole package with a sophisticated balance and yet subtle uniqueness unfound in its peers. A very limited batch produced in the mecca of xiao zhong gungfu black tea, Tongmuguan, this finely processed leaves of Meizhan is precious not because it is rare, but because it is so demanding to produce to this quality. It is not every year that we can achieve a gem like this.Rated 5.00 out of 5USD 25.90
Red Cloak Grande, Wuyi yancha oolongDenser Aromas, Fuller Bodies, Oolongs, Tea, Warm Energy, Wuyi-shan
Centenary Bush Dahong Pao:The most revered amongst all Wuyi oolongs, Da Hongpao (translate: Big Red Cloak) from the pure pedigree grown in better horticultural environment mean significant difference and are most sought after. Tea Hong's Red Cloak Grande is an extremely limited production (10 kg/year) harvested from two second generation noble breed that are over 100 yrs old in the heights of Wuyi. Masterfully processed to best deliver the taste this name represents. Net weight: 40 g (1.4 oz) in Kraft-alu pack
USD 33.80Rated 4.40 out of 5 USD 33.80
Sacred Lily, Wuyi yancha oolongFloral Aromas, Fuller Bodies, Home, Neutral-Cool Energy, Oolongs, Tea, Wuyi-shan
Prime of Wuyi Pedigrees:Through years of researches a fine cultivar carrying the best traits of all the finest Wuyi natural cultivars is now mature and producing. Introducing Tea Hong's Sacred Lily. Perhaps the most beautiful of all Wuyi oolongs. Grown deep in the steep mountains away from the touristy spots and masterfully processed for subtlety, complexity, and smoothness in taste. A tea that no true oolong connoisseur should miss.
USD 27.10Rated 5.00 out of 5 USD 27.10
Lapsang Souchong Pristine, traditional black teaBlack teas, Floral Aromas, Fuller Bodies, Neutral-Warm Energy, Tea, Wuyi-shan
Tongmuguan* Original and Unsmoked:Presenting the original, authentic and prime quality Lapsang Souchong. Small, tightly rolled whole leaves with a black sheen. Non-smoked. 100% hand-plucked first flush. For a pure, fruity sweet and warmly aromatic cup of untainted black tea. Just like how they used to have it in the captain's cabin in an East Indian Trading clipper two centuries ago, when they had just loaded the ship with the year's fresh tea to race home for the eagerly awaiting tea merchants all over Europe. Net weight: 60 g (2.1 oz) in Kraft-alu packRated 5.00 out of 5USD 21.20
Cassia Extraordinaire, Wuyi yancha oolongFloral Aromas, Fuller Bodies, Home, Neutral Energy, Oolongs, Tea, Wuyi-shan
Tea Hong's Most Bouquet Wuyi OolongGreat discipline in the use of fire distinguishes Cassia Extraordinaire from most other Wuyi varieties with a supple, deliciously floral and delicate scent balanced with a full, lively body. Thanks to this masterful baking, this lighter style Wuyi oolong keeps well and improves with extended storage, as it should traditionally. This is our most "bouquet" style Wuyi oolong, being on the other end of the scale as the deep baked classic style Cassia Classic or Red Cloak Grande in Tea Hong's proud Wuyi repertoire. Net weight: 40 g (1.4 oz) in Kraft-alu packRated 5.00 out of 5USD 21.70
Cream Stout, Wuyi yancha oolongFloral Aromas, Fuller Bodies, Home, Neutral Energy, Oolongs, Tea, Wuyi-shan
Silk Finish Aijiao Wulong:No this is not the beer but 100% pure oolong. Wuyi classic oolongs in general distinguish themselves from other oolongs with a stout, rather immediate and powerful impact. Tea Hong's Cream Stout differs from the crowd with a soft creamy finish and a light tone of cream that is developed naturally in the tealeaves themselves. This is possible only with a new pedigree of tea cultivar, Aijiao Wulong. We believe you'll like the oolong much better than the beer, as we do. Net weight: 40 g (1.4 oz) in Kraft-alu packRated 5.00 out of 5USD 28.70
Lily Eccentric, Wuyi yancha oolongFloral Aromas, Fuller Bodies, Neutral Energy, Oolongs, Wuyi-shan
Wuyi Qi Lan PremiumOriginated in the south, Qi Lan cultivars attain new characters growing in the more rugged landscape of Wuyi. Since late last century, traders have taken advantage of its distinctive and pleasing aroma to mislabel it as the much demanded, but hugely misrepresented Red Cloak, Iron Buddha, or other famous Wuyi oolongs. Some blend it in other varieties for the same disguise purpose. Tea Hong's Qi Lan is a premium single batch production that is optimally fermented and baked to allow the full, glorious taste profile of the tea. Some say if one has not experienced Qi Lan, one will never know what Wuyi teas really are. We'd say this eccentric lily has its unique place in the great family of oolongs.
USD 26.80Rated 5.00 out of 5 USD 26.80
Wild Tree Black Tea, processed in the gongfu traditionBlack teas, Floral Aromas, Fuller Bodies, Home, Neutral Energy, Tea, Wuyi-shan
Deserted Old Farm:Wild Tree Black Tea is Tea Hong's very own product developed from the old tea bushes in a deserted farm we discovered for creating its smooth and pleasant taste profile. It offers a delicate floral character without being astringent; tastefulness while sweet. This is possible only by masterfully processing the first flush of this secret tea bush that we grow on the hills on the northern tip of Fujian, from which tribunal teas had once been the most prized for centuries. Net weight: 60 g (2.1 oz) in Kraft-alu pack
Cassia Classic, Wuyi yancha oolongDenser Aromas, Fuller Bodies, Oolongs, Tea, Warm Energy, Wuyi-shan
Classic Rougui CultivarCassia (Rougui) was the first tea variety that received popular praise in the recent few hundred years from the Wuyi region. Named after the tree bark spice, there is otherwise no biological relationship at all, although there is an aromatic component in the oolong that is akin to that of the spice. This classic version is a bit deeper baked than the supreme "Extraordinaire" version, as has traditionally been done for the past century, or longer. Net weight: 40 g (1.4 oz) in Kraft-alu pack
Gold Stallion, traditional black teaBlack teas, Fuller Bodies, Lighter Aromas, Neutral Energy, Tea, Wuyi-shan
Wuyi Jinjun Mei:Produced using a newly redeveloped cultivar in the deep mountains of Wuyi in the much renowned black tea origin, Xingcun, Gold Stallion may look like a finer version of golden tippy Yunnan black tea, but it actually has a much more sophisticated taste and aroma profile in the grand Northern Fujian black tea tradition. It has only recently been popularly available outside of the exclusive circle of the rich and powerful in China. Net weight: 60 g (2.1 oz) in Kraft-alu packUSD 18.10
Narcissus Classic, Wuyi yancha oolongDenser Aromas, Fuller Bodies, Oolongs, Tea, Warm Energy, Wuyi-shan
Dark Rock Shuixian:This tea may have the same name as some low quality tea used in dimsum restaurants but it certainly tastes differently. It is the ORIGINAL Shuixian, the famous oolong that grows on dark rock cliffs in the depth of Wuyi Mountains. Narcissus Classic, like most other deeper baked oolongs, goes well with a wide range of cuisines and desserts and is a great digestive. Also an adaptable tea for preparation with other ingredients, such as ginger and raw sugar, and a safer tea for the weaker stomach. Net weight: 40 g (1.4 oz) in Kraft-alu pack
USD 20.10Rated 2.00 out of 5 USD 20.10
Meizhan Classic, Wuyi yancha oolongDenser Aromas, Fuller Bodies, Home, Neutral Energy, Oolongs, Tea, Wuyi-shan
Wuyi's Secret IngredientLike Rou Gui and Shuixian, Meizhan has long been a major production cultivar in Wuyi. It has never attained that level of prestige like the other two though. Perhaps because traders want to hide a big secret. It is a major ingredient to blend with other varieties to produce what flood the high end market with labels of Red Cloak, Tieluohan, Shuijin Gui or such fancy traditional rare teas. We think it deserves a place of its own. Introducing Tea Hong's Wuyi Meizhan. Enjoy its sweet floral aroma uniquely finished with a just right Wuyi style firing. A great tea for all occasions. No fancy names, just pure quality at great value. Net weight: 40 g (1.4 oz) in Kraft-alu pack