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Chris Letterle: As a child, did you always want to be a snowboarder?
I didn't find snowboarding until I was around 11 or 12 years old. Before that I tried soccer, basketball, a lot of different team sports that didn't work out. Like, for soccer I played goalie, but it wasn't because I wanted to. It was because I was picked last and that was the only open position. So you can get the picture of what school was like. But then I found snowboarding, and I made a whole new set of friends. We all met on the mountain, just kids from different schools. After that I took the bus to the mountain every night, and it was the best vibe ever. I got hooked and that was it. Finding snowboarding was a serious life changer.
Todd Mcadam: What's your biggest career achievement?
Winning the Readers' Choice award for the first time. That was a big one because it seemed like it was a result of starting up my site [torstein.net] and putting a lot of riding out there. It was cool seeing the fan base build and was a statement that the site was working. Winning that award was really motivating to keep going and keep giving back, but winning it again this year was just unbelievable.
Kris Mosdale: How did you come up with the game In Your Face?
Damn, I can't remember how I came up with it really. I think I was just cruising one day, trying to play a SKATE type of game that wasn't just hiking a rail. I wanted to try a game where you could use the whole park and finish it a little bit faster. The name had a little bit to do with the spray too, you know? Honestly I didn't plan on keeping it going after the first time, but kids were super down with it. They hit me up all the time on Facebook, telling me that they're playing it and how it makes them better snowboarders. I think that's super cool.
Frederik van den Berg: How much has your online presence pushed your career? Is it another source of income, something your sponsors want, a fun pastime, or is it merely a PR tool?
Well, you might have noticed that I don't have many logos on my site or in the videos. I'll wear my sponsors' logos or have stickers on my board, but the site is all me. The first year I paid Toby, my filmer, out of my own pocket. That wasn't something I called my sponsors to do. The site came out of something that I felt was missing when I was growing up, just a way to give back to the kids. I wanted to try it and see what the response was; if it was a positive response, and I was getting inspired, I'd keep it going. And now 90 percent of the kids that hit me up when I'm on the mountain usually refer to the videos on my site. Like one in 10 will yell from the lift something like, "Yeah triple cork Torstein, yeah!" But the other nine will yell something like, "Truck that rail" or "What's up with Nicole, man." That really stokes me out.
Charlie Cilensek: Do you ride a rocker board or a cambered board?
Strictly camber. Except I did try a flat board at the end of the season, and I might try that out next year. But for the most part I need a cambered board. I like to ride a smaller board in the park. I ride a 147 to 150, and I try to ride that for everything. Sometimes when I need more support I'll ride a bigger board like a 154.
Mat Huber: Do you still name and treat your boards well?
Yes. Well, Nicole and I had a complicated situation after last season. We were on a break. She's going to come back soon I hope. Frank is an old buddy of mine, but I don't think I'm going to be cruising with him for a while…
Ryan Gormley: Do you think riding with a solid crew helps you push your riding, or do you prefer to ride alone?
A solid crew. Definitely a solid crew. It's the shit. Going through the season, filming those video projects, and doing all of those contests, I get to ride with a bunch of different people from all over the place. It's awesome.


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Join Date: May 2010
Posts: 1,111
radiator cap leaking
Never paid much attention to a radiator cap before but today fired the car up and instantly water was coming out the over flow. ran this cap and radiator last year no problems. Tried another cap laying around same thing. Engine cold and I squeeze a radiator hose water will come out the over flow.
On the bottom of cap there is the little washer is that suppose to be tight against the rubber seal?
Senior Member
Smoked Another SBC
Join Date: Jul 2008
Posts: 9,451
Re: radiator cap leaking
Start reading at Two Types of
Radiator Caps
The radiator cap is a very important part of a vehicle's cooling system, yet it is often overlooked when troubleshooting overheating or coolant loss problems. Consider the radiator cap's fourfold job:
1. It's the filler cap through which coolant is added to the cooling system. Although the cap does not have to be removed to check the coolant level inside the radiator on most passenger cars and light trucks today (that's done by simply checking the level in the coolant reservoir), it must come off when the coolant is changed (every 2 years is recommended).
The "earless" caps that are original equipment on many vehicles can be very difficult to remove. That's why Stant makes a unique easy-grip, Swiv-el® cap. The cap is designed so its internal parts swivel as the shell is turned, making the cap much, easier to install and remove.
2. It raises the boiling point of the coolant to prevent overheating and coolant loss. Pressurizing the cooling system raises the boiling point of the coolant the same as a pressure cooker raises the boiling temperature of water.
A 50/50 mixture of ethylene glycol antifreeze and water normally boils at 227 degrees F.; with 4 lbs. of cap pressure, the boiling point goes up to 239 degrees F.; with 7 lbs. of pressure it rises to 248 degrees F.; and with 14 lbs. of pressure it is increased to 263 degrees F.
3. It's a pressure relief valve that prevents a dangerous buildup of internal pressure within the cooling system. When an engine is shut off, a heat soak period follows during which pressure can build within the cooling system. The cap vents this pressure by allowing a small amount of coolant to overflow the radiator into the coolant reservoir. This prevents damage to the engine and the more vulnerable cooling system components such as the radiator, heater core, hoses and water pump seal, while preventing the loss of coolant that escapes from the radiator.
4. It's also a vacuum relief/siphon valve. As the engine cools, the coolant inside the radiator and engine, along with any vapor pockets that may have formed, begins to contract. This creates a vacuum within the cooling system. The vacuum relief function of the cap allows coolant to be siphoned from the reservoir back into the radiator to maintain the proper coolant level.
Cap Construction
Radiator caps are pretty simple in appearance, but looks can be deceiving. Each part of the cap performs a special function:
¨ Under the top of the cap is a spring disc diaphragm (and upper sealing gasket on closed system caps) that seals against the top of the radiator filler neck and provides friction to keep the cap from working loose.
¨ The big spring is what maintains pressure on the coolant. The spring holds the pressure valve and lower sealing gasket against the base of the radiator filler neck to raise the coolant's boiling temperature and to keep it from escaping. When the pressure rating of the spring is exceeded, the pressure valve opens venting coolant into the overflow reservoir.
¨ The lower sealing gasket is what keeps the coolant where it belongs. This gasket must be in excellent condition for the cap to seal tightly and do its job. If cracked, age-hardened or damaged, pressure and coolant can escape, allowing the engine to overheat.
¨ A vacuum valve in the bottom of the cap allows coolant to be siphoned back into the radiator when the engine cools down. This keeps the radiator full, which helps prevent overheating and the formation of steam pockets. On many domestic passenger car applications with pressure vent-type caps, the vacuum valve also vents pressure when the cooling system is under light load. This allows the cooling system to operate at atmospheric pressure until the expansion of coolant and the creation of pressure in the system closes the valve.
Two types of
Vacuum relief valves
To better understand the role of the vacuum relief valve, let's look at the two basic types: the "normally closed" or "spring pressed" type, and the "open' or "weighted' type.
The normally closed type of vacuum relief valve is used in a "Constant pressure" type cap. With this design, the vacuum valve is held shut by a very light spring, creating a totally sealed system. When the engine is started and begins to warm up, coolant pressure starts to rise immediately because the closed vacuum valve prevents pressure from escaping as the coolant expands.
With caps that have the open variety of vacuum valve (called "pressure vent" caps), there's no spring to hold the vacuum valve shut, only a small calibrated weight. When the engine is first started and under light operating conditions, pressure can vent through the vacuum valve. This allows the cooling system to operate at atmospheric or minimum pressure, which reduces strain on the water pump seals, hoses, radiator, and heater core. As the engine starts to heat up, the escaping steam or coolant pushes the vacuum valve up and shut. This seals the system tight and makes the cap function like a constant pressure type of cap.
When the engine is turned off and cools down, vacuum inside the radiator allows the weighted vacuum valve to reopen. This type of vacuum valve design can also allow the water pump to pull additional coolant into the radiator if the cap is located near the radiator hose that connects to the water pump inlet.
Cap removal & inspection
When changing coolant, performing routine cooling system maintenance or repairs, or when troubleshooting an overheating or loss of coolant problem, the radiator cap should always be inspected.
Do not attempt to remove the cap if the radiator is hot or warm to the touch. Wait until the radiator has cooled, or spray cool water on the radiator until the radiator is no longer hot or warm to the touch (never spray cold water on a hot engine!).
Place a rag over the cap to protect your hand, and then turn the cap counterclockwise (to the left) until it reaches the safety stop (about 1/4 turn). Then pause. Any residual pressure within the radiator will be vented at that point.
Wait until the hissing stops, then press down on the cap so the locking ears will clear the safety stop and continue turning until the cap comes off.
¨ Visually inspect the condition of the upper and lower sealing gaskets. Replace the cap if the gaskets are cracked, hardened or damaged.
¨ Look up the pressure, rating specified for the vehicle, and compare it with that printed on the cap. If incorrect, replace the cap.
¨ Pressure test the cap and cooling system with the Stant 12270 pressure tester. If the cap fails to hold the rated pressure for one minute, replace the cap.
¨ Repair all cooling system leaks found by pressure testing.
¨ Inspect the radiator filler neck sealing surfaces for nicks, dents or corrosion that could adversely affect sealing.
¨ Check the tube that runs from the radiator filler neck to the overflow reservoir to see that it is not loose, cracked, pinched or obstructed.
Safety caps
Stant's Safety Lev-R-Vent®
pressure caps are an excellent replacement alternative to standard radiator caps because they allow pressure to be vented with the flip of a lever.
The lever performs a two-fold function: it interlocks with the radiator filler neck to prevent cap removal until pressure has been vented, and raising the lever lifts the entire pressure valve off the lower seat, allowing steam to vent out through the overflow tube into the coolant reservoir.
The cooling and heating system experts at Stant have dozens of ideas to help you learn more and sell more. Your Stant supplier can provide more information.
Senior Member
Smoked another BBC
Join Date: May 2010
Posts: 1,111
Re: radiator cap leaking
At first thought that was going to be a pointless read but thanks for posting that. Didn't know there was 2 different style of vacuum relief valves.
Still don't understand why I never had this happen in the past. Same radiator and cap for 3 years
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New York City's WNYC radio recently published a map of the most popular dog names by ZIP code in New York City, based on 81,542 dog registration records from the city's Department of Health and Mental Hygiene. In honor of the Westminster Kennel Club Dog Show, which begins on Monday in New York, Yahoo News has repurposed that data (which WNYC generously published in its raw form) to show the 25 most popular dog names in New York since 2000.
If you're familiar with the Baby Name Wizard visualization of popular human monikers over time, this should look familiar. Like human names, dog names rise and fall in popularity, often in accordance with pop culture phenomena. It is surely no coincidence that "Bella" is also the name of the heroine in the "Twilight" vampire novels.
Of course, you might be wondering: Are New York dogs really a worthy sample of American canine culture? Are certain canine demographics underrepresented in registration data? The website Vetstreet published its own list of top dog names of 2012 in December, and "Bella" and "Max" topped its list as well. The 40 dogs named "Jeter" registered in New York, meanwhile, are probably not representative of the U.S.


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You can also search for your Florida Holiday online with The Co-operative Travel and get the latest prices, however with so many options with Florida holidays, we advise calling one of our experts to get the best advice and the most out of your trip.
Could it be that one place in the world has everything anyone could ever want when it comes to an all encompassing holiday experience. Yes it really is true, there is a place, and it only takes a short hop across the pond to get you and your family where all your dreams can come true.
Universal Orlando® Resort offers not one, but TWO amazing theme parks side-by-side, non-stop nightlife, and world-class on-site hotels, all within easy walking distance.
Jump right into the action of the movies at Universal Studios Florida®, the world's premier movie and TV-based theme park. Experience the thrills of Universal's Islands of Adventure®, where legendary stories and best-loved fictional characters come to life on the most innovative rides and attractions ever created. Plus, you can step into the magic and excitement of The Wizarding World of Harry PotterTM, now open at Universal's Islands of Adventure® theme park.
Enjoy live music, dining, dancing, shopping, movies and more at The Entertainment Capital of OrlandoSM, Universal CityWalk® - home of the incomparable Blue Man Group.
Adrenaline fuelled action is the order of the day in the myriad of theme parks across the sunshine state, so called due to its all year round glorious weather, just the trick to forget about those washed out weekends in old blighty. We all know about the amazing adventures, scream if you want to go faster white knuckle rides in Disneyworld Resort Florida, as well as the incredible scenes at Universal Orlando® Resort. While Florida offers this in spades there is so much more that several lifetimes wouldn't be enough to appreciate all it has to offer.
From the pearlescent soft sand of the Gulf coast to the Latin vibe of Miami there is so much to see and do in this huge playground that it really is time for family members of all ages to discover a destination that will draw you back time after time. Let us take you to a land where the sky is brighter the water is warmer and the experience is larger than life.
Whilst Florida holidays may be synonymous with the theme parks of Orlando but the glorious Sunshine State also offers many alternatives that those in the know have been secretly enjoying for years! Whether glorious breaks in the Florida Keys, city breaks in Miami or Gulf Coast holidays; there is much to do in Florida.
Undeniably the majority of package holidays to Florida are bound for Kissimmee and Orlando; home to Disney World and Universal Orlando® Resort and hundreds of associated attractions. Spread over 47 square miles Disney World Florida is an amalgamation of four enormous theme parks, two unique water parks, thousands of hotel rooms and many other attractions such as golf courses and shopping. Hotel accommodation at Disney ranges from the budget priced All-Star resorts to the ostentatious luxury of the Grand Floridian Resort & Spa, and other options include Villas.
Despite the on-site options the majority of tourists on Disney holidays to Florida opt for cheaper accommodation in nearby Kissimmee. There are thousands of bedrooms available at this all-year round popular destination where great deals are frequently on offer. Indeed, most of the cheap holidays to Florida will comprise breaks in the Orlando or Kissimmee area and many will be fly-drives picking up a hire a car at Sanford airport just outside Orlando. Having a hire car is a cheap option for getting around and allows visitors to take in other theme parks such as Universal Orlando® Resort.
Other favoured Florida destinations outside of Orlando include the magnificent coast around Tampa on the Gulf Coast. Stunning sunsets can be witnessed over the Gulf of Mexico, better still if observed from a beach bar sipping an exotic cocktail! Nearby St. Petersburg offers a massive choice of accommodation including motels, hotels and uniquely American 'efficiencies'. It is an ideal place to stay and from which to investigate the Gulf Coast.
Cosmopolitan Miami with its combination of impressive art deco architecture and unpredictable Latin ambience is a favoured destination for city breaks. Flights to Miami can also be the starting point for holidays to the Florida Keys and trips to the nearby Everglades National Park.
Whatever Florida holiday deals appeal to you check first at The Co-operative Travel; you could grab a fantastic bargain to the Sunshine State.


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Ride to Hell: Retribution
It's time for revenge! Jake Conway has just returned home from Vietnam when his younger brother is brutally murdered by a rival biker gang called The Devils Hand. Set in the outlaw era of America's Sixties, Jake takes on anyone or anything standing in the way of his bloody revenge fest - on bike, on foot and on fire.
If you're stuck in Ride to Hell: Retribution, ask your fellow GameFAQs members for help.
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we're headin south. no jobs and no beach here in pa.
anybody from there or hunt there? inland from there i mean
muleskinner wrote:you were born with a silver spoon in your mouth and a benalli in the other.
Return to South Carolina Duck Hunting
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Man Pays $1 Parking Ticket 35 Years Late
What would you do if you found a parking ticket from 1975? Probably throw it out right? Not if your name is Stanley Baker from Orlando, Florida. You would pay that ticket and ask for a receipt.
The parking ticket was written on November 7, 1975 and it was for parking in front of an expired meter. The fee was just $1 and evidently it went unpaid for many years until it fell into Baker's hands. Literally…it fell out of a book that he had bought at a garage sale.
When it fell into his lap though, he thought it was his duty to pay it. So he did…and he asked for a receipt as a bit of a joke.
The police got involved only because the original ticket was sent in with the original envelope to the department, where a room now used as an auditorium was then a night and traffic court.
Because the department doesn't keep records of parking tickets that date back that far, he didn't have to pay any extra late fees. Case closed!


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SW-MOTECH Bags-Connection
Motorcycle Luggage, Protection & More!
SW-MOTECH produces the toughest and most thoughtfully designed luggage, protection, and ergonomic accessories you can buy for your motorcycle. Specializing in parts for adventure, sport, and retro-style bikes, SW-MOTECH precision-manufactures its products in Germany.
SW-MOTECH Legend Gear LT1 Tank Bag | 3 - 5.5 Liter Expandable & Magnetic
The SW-MOTECH Legend Gear LT1 tank bag attaches to any metal fuel tank to feature up to 5.5 liters of expandable capacity using luxurious yet durable materials with a high quality fit and finish. Chic retro styling is achieved using Napalon synthetic leather combined with water resistant coated canvas. The sleek LT1 mounts to any metal fuel tank using a powerful magnet that allows quick access to the fuel filler. The base of the bag features a full circumference zipper that swiftly expands capacity from 3 liters to 5.5 liters! This swanky tank bag is compatible with other Legend Gear accessories like the LA3 Smartphone Bag that mounts directly to the top permitting easy access to your device. Add instant versatility with dashing style by using the Legend Gear LT1 tank bag on your motorcycle!
The cotton canvas is wax coated to protect against UV damage while repelling dirt and water. To maintain a like new appearance, wax regularly and avoid storage in direct sunlight. For a vintage faded look, wax less often with direct exposure to sunlight.Learn More$136.95 $110.95
SW-MOTECH Legend Gear Black Edition LT1 Tank Bag | 3-5.5 Liter Magnetic, Expandable & Water Resistant
The SW-MOTECH Legend Gear Black Edition LT1 tank bag | 3-5.5 liter magnetic, expandable & water resistant adds convenient storage capacity with an unmistakable classic style. Premium materials are utilized for an elegant feel, durable performance and fashionable appearance. This handsome tank bag uses strong sewn in magnets to mount securely to most steel fuel tanks and comes with four optional accessory straps for additional fitment on non-magnetic tanks. Attractive Napalon synthetic leather and wax coated canvas construction provides reliable support for your gear with water resistance to keep things dry (a waterproof rain cover is included for added protection in heavy storms).
Internal volume can be increased from the standard 3 liters to 5.5 liters with a quick un-zip of the lower expansion panel. Versatility is further complimented with a MOLLE (Modular Lightweight Load-carrying Equipment) military fastening system that allows fastening of additional small item compartments or smartphone holders like the LA1/LA2 accessory pouch and LA3 smartphone case. This Black Edition tank bag is a special release from SW-MOTECH and is available in limited quantities. Fit and finish is top notch and characteristic of classic German engineering and design. Conveniently keep your goods within reach while enhancing the style of your motorcycle with the Legend Gear Black Edition LT1 tank bag!Learn More$110.95


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There are times in life when absurdity is more real than reality. To be a member of the human race is to be a member of an incredible traveling circus of freaks and nuts who display grotesque faces of mirth and sorrow. There are times in life when it is clear that anyone who has been a professional athlete possesses the desire for money and more money and more fame than is found within normal humans. We pamper and idolize grown men who have certain athletic capacities so they emerge believing themselves not bound by any set of rules other than those emerging from the belief that money always is the supreme goal of life. One could readily imagine former NBA star Dennis Rodman organizing a basketball game in Dachau to celebrate the birthday of his friend, Adolf Hitler. Gee, he was simply attempting to bring together the warring nations of the world by having everyone play basketball together! When all is said and done by Dennis, basketball and the beloved dollar bill are all that counts to enjoy a wonderful life in this world.
Dennis encountered a new playmate, a fan who regards him as still an important person. The cheers no longer ring in his ear so it is sweet and exhilarating to hear them from people in a gym in North Korea who were ordered to CHEER or face the prospect of a labor camp. Dennis sweet talked a group of ignorant former NBA players into playing a basketball game in some place called, North Korea. As Dennis told the media who questioned playing basketball for the most tyrannical blood soaked ruler in the world who starves thousands to their death, Dennis had a response: "I don't give a rat's ass what you think" and he pointed to his companions who had risked their lives to play a basketball game in order to bring peace to the world.
Dennis, there are millions of people in North Korea who eat rats for dinner. Care to join them? I can assure Dennis his friend, Kim Jong-un will not be at this dinner!


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Characteristics Predictive of Pessary Success
This study has been completed.
University of California, Irvine
Information provided by (Responsible Party):
Karen Noblett, University of California, Irvine
ClinicalTrials.gov Identifier:
First received: May 12, 2010
Last updated: June 27, 2013
Last verified: June 2013
|Tracking Information
|First Received Date ICMJE
|May 12, 2010
|Last Updated Date
|June 27, 2013
|Start Date ICMJE
|January 2008
|Primary Completion Date
|August 2011 (Final data collection date for primary outcome measure)
|Current Primary Outcome Measures ICMJE
|Not Provided
|Original Primary Outcome Measures ICMJE
|Not Provided
|Change History
|Complete list of historical versions of study NCT01123213 on ClinicalTrials.gov Archive Site
|Current Secondary Outcome Measures ICMJE
|Not Provided
|Original Secondary Outcome Measures ICMJE
|Not Provided
|Current Other Outcome Measures ICMJE
|Not Provided
|Original Other Outcome Measures ICMJE
|Not Provided
|Descriptive Information
|Brief Title ICMJE
|Characteristics Predictive of Pessary Success
|Official Title ICMJE
|Characteristics Predictive of Pessary Success
|Brief Summary
|Pessaries are mechanical support devices worn vaginally to treat the symptoms of pelvic organ prolapse, such as vaginal pressure or a vaginal bulge. Pessaries are one of the options along with surgery and expectant management for pelvic organ prolapse. As the aging population grows, more patients will need treatment for pelvic organ prolapse. Various studies have been conducted previously to identify patient parameters predictive of successful pessary fitting and continued use. Our study is a retrospective chart review to identify patient characteristics predictive of successful pessary fitting and use, specifically focusing on the parameters of POPQ, pelvic organ prolapse quantification exam, and the ratio of the genital hiatus, which is the length of the vaginal opening, and total vaginal length.
|Detailed Description
|Not Provided
|Study Type ICMJE
|Study Design ICMJE
|Observational Model: Case-Only
Time Perspective: Retrospective
|Target Follow-Up Duration
|Not Provided
|Not Provided
|Sampling Method
|Non-Probability Sample
|Study Population
|All patients who have undergone a pessary fitting by physicians in the division of Urogynecology between the years of 2000 to 20008 will be eligible.
|Condition ICMJE
|All Patients Who Have Undergone a Pessary Fitting.
|Intervention ICMJE
|Not Provided
|Study Groups/Cohorts
|Not Provided
|Publications *
|Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Information
|Recruitment Status ICMJE
|Enrollment ICMJE
|Completion Date
|August 2011
|Primary Completion Date
|August 2011 (Final data collection date for primary outcome measure)
|Eligibility Criteria ICMJE
Inclusion Criteria:
Exclusion Criteria:
|Child, Adult, Senior
|Accepts Healthy Volunteers
|Contacts ICMJE
|Contact information is only displayed when the study is recruiting subjects
|Listed Location Countries ICMJE
|United States
|Removed Location Countries
|Administrative Information
|NCT Number ICMJE
|Other Study ID Numbers ICMJE
|Has Data Monitoring Committee
|U.S. FDA-regulated Product
|Not Provided
|Plan to Share Data
|Not Provided
|IPD Description
|Not Provided
|Responsible Party
|Karen Noblett, University of California, Irvine
|Study Sponsor ICMJE
|University of California, Irvine
|Collaborators ICMJE
|Not Provided
|Investigators ICMJE
|PRS Account
|University of California, Irvine
|Verification Date
|June 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP


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Review: TC Electronic Sub 'n' Up Octaver Pedal
There is no better way to add meaty heft to your guitar or bass signal than an octave pedal. Of the many pedals available in this category, I really dig TC Electronic's brand new Sub 'n' Up Octaver.
Meet Epiphone's Brent Hinds Flying V Custom
If you're a fan of the Flying V or Mastodon lead singer/guitarist Brent Hinds, chances are you already said, "Shut up and take my money!" the second that you laid eyes on this beautiful Epiphone...
Chris Broderick Talks Jackson Signature Soloist Hardtails
Act of Defiance guitarist Chris Broderick recently unveiled his new signature guitars by Jackson—a USA Signature Soloist HT6 and a USA Signature Soloist HT7.
Rivera Announces Mini-RockRec Speaker Simulator
Rivera has announced the Mini-RockRec, a loadbox/speaker simulator with six speaker voicings.
$150 Guitar Vs. $5,000 Martin: Put Their Tones to the Test
Which guitar sounds better—a $150 Motion TD-107 or a $5,000 Martin D-42?
Paul Reed Smith Discusses PRS Guitars McCarty 594
Last month, PRS Guitars hosted its annual "Experience PRS" event in Stevensville, Maryland.
Kirk Hammett's KHDK Electronics Introduces Scuzz Box
Kirk Hammett's KHDK Electronics has unveiled its latest guitar pedal, the Scuzz Box. Available for pre-order through select dealers, the Scuzz Box is KHDK's geranium-voiced fuzz pedal, designed as...
Pete Townshend Collaborates on Limited Fender Strat
Fender has announced it will release a limited-edition Custom Shop Stratocaster designed in collaboration with Who guitarist Pete Townshend.
Esoterik Guitars Unveils LK27 Baritone Model
Esoterik Guitars has just released its first 27" scale length neck thru baritone model, the LK27.
Things You Might Not Know About the Vai JEM
Phillip McKnight is back with another great video. This time he shares "Seven Things You May Not Know About the Ibanez JEM," Steve Vai's groundbreaking signature guitar.
Meet John Petrucci's New Signature Guitar
I've previously compared several of Ernie Ball Music Man's John Petrucci signature model guitars to sports cars for their style and fast performance, but another way that the company's John...
D'Addario to Provide String-Recycling Boxes in Philly
D'Addario is proud to provide two string recycling boxes backstage at WXPN/Philadelphia's XPoNential Music Festival presented by Subaru this year – allowing all the artists to deposit their used...
The 10 Hottest Mini Pedals in Guitardom
No room on your pedalboard? Consolidate your gear with these hot new mini-pedals. They cover distortion to delay, tuning to looping and everything in between.


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From the Department of Clinical Epidemiology and Biostatistics (Drs Guyatt, Akl, Cook, Schulman, and Schünemann) and Department of Medicine (Drs Guyatt, Schulman, Hirsh, Crowther, Eikelboom, Cook, and Schünemann), McMaster University Faculty of Health Sciences, Hamilton, ON, Canada; Department of Medical Informatics and Clinical Epidemiology (Drs Norris and McDonagh), Oregon Health & Science University, Portland, OR; Division of General Internal Medicine and Center for Clinical Effectiveness (Dr Eckman), University of Cincinnati, Cincinnati, OH; Departments of Medicine and Family Medicine (Dr Akl), State University of New York, Buffalo, NY; Department of Medicine Gjøvik-Innlandet Hospital Trust and Norwegian Knowledge Centre for the Health Services (Dr Vandvik), Oslo, Norway; Evidence-Based Clinical Practice Guidelines and Clinical Standards (Dr Lewis), American College of Chest Physicians, Northbrook, IL; and Cardiovascular Research Center (Dr Gutterman), Medical College of Wisconsin, Milwaukee, WI.
Correspondence to: Gordon H. Guyatt, MD, FCCP, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, L8N 3Z5, Canada; e-mail: firstname.lastname@example.com
Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants was also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.
Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).
To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists.
Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence-based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion.
One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance.
AT9 methodology reflects the current science of evidence-based clinical practice guideline development, with reliance on high-quality systematic reviews, a standardized process for quality assessment of individual studies and the body of evidence, an explicit process for translating the evidence into recommendations, disclosure of financial as well as intellectual conflicts of interest followed by management of disclosed conflicts, and extensive peer review.
This article describes the methodology used for the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (AT9). This methodology incorporates current evidence-based approaches to the appraisal and synthesis of evidence and to the formulation of clinical practice recommendations. The process thus ensures explicit, transparent, evidence-based clinical practice guidelines.
The objective of AT9 is to optimize patient-important health outcomes and the processes of care for patients who have experienced or are at risk for thrombotic events. The targeted users of these guidelines are health-care providers in both primary and specialty care who assist patients in making treatment choices that optimize benefits, minimize harms and burdens, and are consistent with patient values and preferences.
Figure 1 summarizes the process for the development of the AT9 recommendations. The primary responsibility for AT9 rests with the American College of Chest Physicians (ACCP) AT9 Executive Committee. This committee includes two methodologist-clinicians from the previous iteration, Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) (AT8), published in 20081 (Dr Guyatt, Panel Chair, and Dr Schünemann, Vice Chair of Methodology); a third methodologist-clinician (Dr Akl); a leading thrombosis expert (Dr Crowther, Vice Chair for Thrombosis); and two liaisons with the ACCP Health and Science Policy (HSP) Committee who had also served on the previous guideline Executive Committee (Dr Gutterman, Vice Chair and HSP Liaison, and Dr Lewis, Project Manager).
Articles within AT9 are defined by broad populations (eg, pediatric, obstetric) or clinical conditions (eg, prevention of VTE in medical patients or stroke prophylaxis in atrial fibrillation). In addition, AT9 includes three articles addressing the basic science of oral and parenteral anticoagulants and platelet-active drugs and an article addressing new antithrombotic and thrombolytic drugs.
The ACCP AT9 Executive Committee selected panel members for each article. A topic editor and a deputy editor led each of the AT9 panels issuing recommendations. The topic editor was the person primarily responsible for each article and was required to be a methodologist without serious financial or intellectual conflict of interest for any of the article's recommendations. In all but one case, the topic editor also was a clinician. The Executive Committee chose these individuals on the basis of their previous experience with guideline development and, in particular, their familiarity with methods developed by the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) Working Group.2 These topic editors and all panel members were approved by the ACCP HSP Committee after review of their conflict of interest disclosures (see section 7.0 "Disclosing and Managing Conflicts of Interest").
Criteria for selection of the remainder of the panel members, including the deputy editor-thrombosis expert, were an established record in the relevant clinical or research area, international and gender representation, and an absence of financial conflicts of interest that were judged unacceptable. Some of the panelists had prior experience on ACCP guidelines in this area and represented the thrombosis community, but there was substantial turnover from the previous edition. After an international request for applications broadcast through multiple medical societies, the Executive Committee nominated individual topic editors and deputy editors and collaborated with them to identify and nominate other topic panel members.
The ACCP HSP Committee reviewed all nominees and approved all panel members after review of their curricula vitae and conflict of interest disclosures. Of 150 nominees, 137 were approved, 18 were approved with management of conflicts of interest (ie, regular disclosures and review of ongoing conflicts as the process progressed), and 13 were disapproved as a result of the magnitude of financial conflicts of interest. Articles associated with recommendations included from seven to 14 panel members. We did not include patients or representatives of specific stakeholder groups on topic panels.
Each topic panel also included a frontline physician working in the relevant area who was neither an expert in thrombosis nor a methodologist or clinical investigator. These individuals were chosen in consultation with the topic editors and the ACCP HSP Committee. These clinicians were charged with the following: (1) proposing important real-world clinical questions on the prevention, diagnosis, and treatment of thrombosis that were not addressed in AT8 and (2) reviewing the draft manuscripts and recommendations to assess the usability of the guidelines and the feasibility of implementation of AT9 recommendations.
To address issues of economic efficiency we included six health economist-physicians on the AT9 topic panels charged with making recommendations. These resource consultants were selected and approved through identical procedures to those for topic editors and panel members. We describe their roles more fully later in this discussion.
We used a number of strategies to ensure consistency across articles, and one of us (M. C.) participated extensively in the formulation of clinical questions for each article. To ensure consistency of judgments regarding bleeding, one of us (S. S.) was responsible for standardizing the approach to bleeding outcomes and participated in multiple topic panels (described in more detail later in this article). Additionally, to ensure consistency in the trade-offs between thrombotic and bleeding events, all articles used the same ratings of values and preferences (also described in more detail later). Because some of the same evidence summaries were relevant to several articles, five individuals were chosen to participate in each of the articles addressing coronary artery disease, stroke, and peripheral arterial disease.
In AT9, prevention of VTE is addressed in three articles as opposed to a single article as was done in AT8. The prevention topic editors and deputy editors and those of the stroke article (which includes thromboprophylaxis recommendations) participated in multiple conference calls to develop and harmonize the approach to prevention and to ensure consistency among final recommendations.3 Topic editors consulted with one another when issues overlapped. For example, the decision regarding the use of a vitamin K antagonist, aspirin, and clopidogrel simultaneously in patients with atrial fibrillation, valvular disease, and intravascular stents is relevant for the atrial fibrillation, coronary, and peripheral arterial disease articles. Topic panels deferred to the Evidence-Based Management of Anticoagulant Therapy AT9 topic panel for recommendations related to the dosing and monitoring of anticoagulation therapies.
The AT9 Executive Committee met at least once a month and regularly issued statements of clarification of methods to topic editors and deputy editors (eg, use of fixed- or random-effects models for meta-analysis), conflict of interest, preparation of tables, and issues of style and presentation. All these statements were communicated directly to the topic editors and deputy editors and made available in a central repository accessible to all AT9 panelists. The chair of the Executive Committee (G. H. G.) was available for resolving any challenging issues related to the aforementioned topics. Between September 2009 and September 2010, two members of the Executive Committee (E. A. A. and S. Z. L.) held regular (every 3 months), separate conference calls with each topic editor and deputy editor during which they addressed questions and concerns. Finally, the chair of the Executive Committee reviewed every article to ensure consistency of evidence presentation, evaluation, and writing style.
In terms of writing style, we used consistent language to describe effects that did not reach statistical significance. The approach was as follows:
For adverse outcomes (such as thrombosis and bleeding), "A is associated with a trend toward reduced thrombosis" if the lower boundary of the CI around a relative effect is ≤ 0.7 and the upper boundary of the CI is ≤ 1.1 or if the lower boundary of the CI is ≤ 0.8 and the upper boundary of the CI is ≤ 1.05. If the point estimate is > 1.0, the language used was, "A is associated with a trend toward increased bleeding" if the lower boundary of the CI around a relative effect is > 0.9 and the upper boundary of the CI is > 1.3 or if the lower boundary of the CI is > 0.95 and the upper boundary of the CI is > 1.2.
"A appears to have little or no effect on thrombosis" if the above conditions are not met, and the boundaries of the CI lie between 0.80 and 1.2.
For all other results that fail to exclude a relative risk of 1.0, the language was, "Results failed to demonstrate or exclude a beneficial effect or detrimental effect of A on thrombosis." Alternative wording with regard to an association is "failed to establish or refute."
The thrombosis expert on the Executive Committee (M. C.) along with the deputy editors took primary responsibility for defining the scope of the clinical questions that each article would address. For each question, the topic editor and deputy editor defined the relevant population, alternative management strategies (intervention and comparator), and the outcomes (ie, population, intervention, comparator, and outcome [PICO] format). Each clinical question provided the framework for formulating study inclusion and exclusion criteria and guided the search for relevant evidence (systematic reviews and original studies). Panels typically restricted included studies to randomized controlled trials (RCTs) for intervention questions but included observational studies when there was a paucity of RCT data addressing an intervention and for questions of risk assessment. Readers can find these PICO questions in the first table of each article. One or more recommendations could be formulated for each clinical question. The next subsections (3.2-3.5) deal with the approach to selection of outcomes.
The outcomes for each clinical question were chosen by the topic editors and their panel members and were generally consistent across articles. Outcomes were restricted to those of importance to patients.4 Panels considered the burden of anticoagulation therapy as a patient-important outcome when its consideration could tip the balance of benefits and harms. If we found no data for an outcome considered at the outset as patient-important, we nevertheless included uncertainty about the effects of the intervention on that outcome when weighing its benefits and harms.
In the absence of data on patient-important outcomes, surrogates could contribute to the estimation of the effect of an intervention on the outcomes that are important. Examples of surrogate outcomes include asymptomatic venous thrombosis detected by venographic or ultrasound surveillance and the percentage of time that an international normalized ratio was in therapeutic range (used as a surrogate for bleeding and thrombosis in the assessment of the effectiveness of centralized anticoagulation services).
The issue of asymptomatic thrombosis detected by venographic or ultrasound surveillance presented particular challenges to the articles addressing VTE prevention in orthopedic and nonorthopedic surgery populations, an article addressing nonsurgical prophylaxis, and an article addressing stroke prevention. We were explicit in considering the trade-offs between VTE and bleeding events. An article by Guyatt et al3 in this supplement addresses these issues in some detail.
Options considered in summarizing mortal events were (1) all-cause mortality and (2) mortality related to antithrombotic therapy (ie, deaths from pulmonary emboli and deaths from bleeding). Advantages of the former include its being the most patient-important outcome and the difficulty of ascertaining cause of death. Difficulties ascertaining cause of death may be particularly problematic when adjudication is unblinded and therefore open to bias.
The disadvantage of all-cause mortality is that the signal from antithrombotic therapy-related deaths may be lost in noise from deaths due to other causes. The decision about which mortal outcome to use (all-cause mortality or antithrombotic therapy-related morality) was left to the authors of individual articles. Availability of data sometimes forced the choice of less satisfactory mortal outcomes (eg, if death related to pulmonary embolus but not death related to bleeding was reported). When mortality was one of the selected outcomes, we avoided double-counting by documenting nonfatal events for the remaining outcomes (eg, nonfatal thrombosis, nonfatal major bleeding) rather than all such events (fatal and nonfatal).
Many of the primary studies we reviewed, particularly in the cardiovascular area, presented evidence in the form of composite end points.5 Particularly when the patient importance of the component end points and the magnitude of effect of the intervention on the components differ, composite end points can be misleading.6,7 Therefore, we present results and base inferences on the effect of interventions on individual outcomes.
In view of the wide variation in how bleeding was assessed and reported in the included primary studies across chapters, one individual (S. S.) was responsible for standardizing the approach to bleeding outcomes. He worked closely with the Executive Committee and the topic editors and deputy editors to ensure the uniform application of the approaches that were developed.
We began by specifying the bleeding outcomes that we believe patients consider important. We did not consider minor bleeding as incurring a burden that was important in comparison with symptomatic thromboembolic events.
We reported fatal hemorrhage as well as fatal stroke or pulmonary embolism in treatment-related or all-cause mortality. Likewise, hemorrhagic stroke and ischemic stroke were reported as "stroke." We specified in footnotes the events attributable to each component.
We avoided any double-counting of events; for example, a fatal hemorrhagic stroke would only be reported under mortality. We also attempted to report more specific and homogeneous bleeding outcomes than "major bleeding," which includes events with a wide range of patient importance and which investigators have defined in different ways. For example, in Falck-Ytter et al8 in this supplement, bleeding outcomes of primary interest were (1) bleeding requiring reoperation and (2) other major bleeding. Because some authors, particularly in older studies, failed to define subsets of major bleeding, we were not always able to achieve the desired specificity.
To identify the relevant evidence, a team of methodologists and medical librarians at the Oregon Health & Science University Evidence-based Practice Center conducted literature searches of Medline, the Cochrane Library, and the Database of Abstracts of Reviews of Effects. For each article, the team conducted a search for systematic reviews and another for original studies encompassing the main populations and interventions for that article. These searches included studies indexed from week 1, January 2005, forward because AT8 searches were carried out up to that date (search strategies are available on request). Many articles supplemented these searches with more-focused searches addressing specific clinical questions. When clinical questions had not been covered in AT8, searches commenced at a date relevant to each intervention.
Titles and abstracts retrieved from bibliographic database searches generally were screened in duplicate, and full-text articles were retrieved for further review. Consensus on whether individual studies fulfilled inclusion criteria was achieved for each study between two reviewers. If consensus could not be achieved, the topic editor and other topic panelists were brought into the discussion. Deputy editors reviewed lists of included studies from the database searches in order to identify any potentially missed studies. Additional studies identified were then retrieved for further evaluation.
Topic panels also searched the same bibliographic databases for systematic reviews addressing each PICO question. The quality of reviews was assessed using principles embodied in prior instruments addressing methodologic quality of systematic reviews,9,10 and wherever possible, current high-quality systematic reviews were used as the source of summary estimates. Reviews were also used to identify additional studies to complement the database searches.
We developed and applied uniform criteria for evaluating the risk of bias associated with individual RCTs based on the criteria recommended by the Cochrane Collaboration11 (Table 1). Although all authors assessed risk of bias for individual studies, because of resource limitations, we summarized the results of the risk of bias (eg, Table 112) for only a minority of the recommendations. Readers can find these assessments in the online data supplements. For most recommendations for which we did not develop such tables, we developed Evidence Profiles (see Table 213‐15) that typically provide information on the risk of bias in footnotes.
CALISTO = Comparison of ARIXTRA in Lower Limb Superficial Thrombophlebitis with placebo; DY = definitely yes; ITT = intent to treat; PN = probably no; PY = probably yes; RCT = randomized controlled trial.
LMWH = low-molecular-weight heparin; PTS = postthrombotic syndrome; RCT = randomized control trial; RR = risk ratio; VKA = vitamin K agonist. (Kearon C, unpublished data).h
Limited to LMWH regimens that used ≥ 50% of the acute treatment dose during the extended phase of treatment.
Time frame is 6 mo for all outcomes except PTS, which is 2 y.
One study did not report deaths: borderline decision.
Control event rates from cohort study by Prandoni et al,13 adjusted to 6-mo time frame.
Outcome less subjective: borderline decision.
Control event rates from cohort studies by Prandoni et al13 and Beth et al14 adjusted to 6-mo time frame.
Control event rate comes from observational studies in review by Kahn et al15 adjusted to 2-y time frame. All patients wore pressure stockings.
Meta-analysis is based on RCTs as referenced in the article text. The control event rate for mortality comes from this meta-analysis.
We also developed specific criteria for assessing the risk of bias of observational studies (cohort studies with concurrent controls, cohort studies with historical controls, case-control studies, or case series). Again, these were based on the evidence-based domains recommended by the Cochrane Collaboration for observational studies (eg, Table 316‐18).
APTT = activated partial thromboplastin time; HIT = heparin-induced thrombocytopenia.
APTT adjusted to 1.5 to 2.5 times baseline APTT (or the mean laboratory normal range if the baseline APTT was unavailable).
APTT adjusted to 1.5 to 3.0 times baseline APTT.
Studies without internal comparisons were termed "cohort studies without internal controls" if they met the following criteria:
A protocol existed before the date of commencement of data collection.
A definition of inclusion and exclusion criteria was available.
The study reported the number of excluded patients.
The study conducted a standardized follow-up, including description of all of the following: schedule of follow-up, investigation of suspected outcomes, and criteria used to define outcomes.
The study reported all losses to follow-up.
We labeled studies that did not meet these criteria as "case series." We did not make a distinction between prospective and retrospective studies because although prospective studies may on average be of higher quality, individual prospective studies may have a significant risk of bias and specific retrospective studies may not. For questions related to risk assessment, we evaluated the risk of bias of individual studies using the following criteria: valid outcome assessment, including blinding when appropriate; adjustment for between-group differences; and minimal loss to follow-up.
We assessed evidence across studies on an outcome-by-outcome basis using criteria suggested by the GRADE Working Group.19 We defined quality of evidence as our confidence in the estimate of the effect to support a recommendation.19 RCTs start as high-quality evidence and observational studies as low-quality evidence (Fig 2). Additional factors that affect this rating of quality include the risk of bias (as detailed earlier in this article); precision, consistency, and directness of results; likelihood of publication bias; and presence of very large effects.19 The ACCP adaptation of the GRADE system (Table 4) differs only in that the quality of a body of evidence can be high (A), moderate (B), or low (C) (Fig 2); GRADE also provides a category for very-low-quality evidence.
Often, we found that the quality of the evidence differed across outcomes. For example, in assessing the quality of evidence for thienopyridines vs warfarin in patients undergoing percutaneous coronary interventions, we determined the evidence to be of moderate quality for mortality, nonfatal myocardial infarction, and revascularization but of low quality for major bleeding.
We then made a rating of the quality of the entire body of evidence bearing on the effect of alternative management strategies for each clinical question. In other words, we assessed the quality across outcomes, including both benefits and harms. Quality for each recommendation was the lowest quality rating of the outcomes judged as critical (as opposed to important, but not critical).19
Most patient-important outcomes in this guideline are binary or yes-no outcomes (death, stroke, VTE, myocardial infarction, bleeding). In general, relative effects are similar across subgroups of patients, including those with varying baseline risk.20,21 The evidence summaries (Evidence Profiles and Summary of Findings tables described later in this article), therefore, include a presentation of relative effects (where possible as relative risks because they are easier to understand than ORs) of intervention vs control management strategies.
Trading off desirable and undesirable consequences (eg, thrombosis vs bleeding) requires, however, estimates of absolute effect. For example, in patients with atrial fibrillation, warfarin results in a 66% relative risk reduction in nonfatal stroke. This comes at a cost of inconvenience, lifestyle restrictions, and risk of bleeding. For patients with a CHADS (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke) score of ≥ 3, the 66% relative risk reduction translates into an absolute reduction of 6.3% (63 in 1,000) per year. Virtually all patients will consider this worthwhile. On the other hand, for patients with a CHADS score of 0, the 66% reduction translates into an absolute risk reduction of only 0.5% (5 in 1,000) per year. Many patients may consider this reduction not worth the undesirable consequences of warfarin use.
We calculated absolute effects by applying relative risks to estimates of control group risk. For instance, if control group risk of thrombosis is 4% and relative risk with an intervention is 50%, then the absolute difference between intervention and control is 4% of 50% or 2%, and the number needed to treat to prevent an episode of thrombosis is 100/2 or 50. In many cases, the Summary of Findings tables present effects as events prevented (or caused) per 1,000 patients. In this hypothetical example, the effect would be 20 events per 1,000 patients.
Whenever valid prognostic data were available from observational studies, they were used to estimate control group risks. When credible results from observational and prognostic studies were not available, risk estimates from control groups of RCTs were used.
Whenever we identified credible evidence that the relative effects vary across distinguishable subgroups of patients (ie, interaction between the intervention and a patient characteristic), we considered the respective relative effects separately. We then calculated the associated absolute effects.
Even when the relative effect is the same, the absolute magnitude of treatment effects may differ in patients with varying levels of risk. For instance, although the relative risk reduction of warfarin vs aspirin in stroke prevention for patients with atrial fibrillation is likely close to 50% across risk groups, this translates into an absolute risk reduction of < 1% per year in the lowest-risk groups and ∼ 5% per year in the highest-risk groups.
We included control group risks and absolute effect estimates for different groups in the summaries of effect when (and only when) two conditions were present. First, we required validated prognostic models or, at the very least, credible strategies for clinicians to easily identify higher- and lower-risk patients. Second, we identified varying risk groups only when recommendations differed in strength or direction between groups. Both conditions were met, for instance, in the atrial fibrillation recommendations in which strong recommendations in favor of anticoagulation were restricted to the higher-risk patients.
When pooled estimates of effects were not available from existing high-quality systematic reviews, we performed meta-analyses if the data were sufficiently homogeneous. When pooling two studies, we used a fixed-effects model. When three or more studies were available for generating a pooled estimate, we used a random-effects model as the primary analysis and a fixed-effects model as a secondary analysis. If there were discrepancies between the two, we considered the following reasons: If there was substantial heterogeneity leading to wider CIs with the random-effects model, we considered that model more trustworthy, and if the discrepancy was due to a single large dominant study with a result substantially different from smaller studies, we considered the fixed-effects model more trustworthy. We also assessed statistical heterogeneity using both a χ2 test and I2 as well as assessed possible explanations of heterogeneity considering a priori-generated hypotheses.22
When resources permitted, we used a standardized approach for summarizing the evidence and methodology of individual studies (examples in Tables 1, 2, 5). These summaries appear in the online data supplements. Wherever possible, we report nonfatal events (eg, nonfatal stroke) so that there is no overlap with the number of fatal events reported.
-Composite of symptomatic events up to day 47: death from any cause, symptomatic DVT or PE, symptomatic extension to the saphenofemoral junction, recurrence of SVT
-Symptoms > 3 wk
-DVT or PE at presentation
-SVT following sclerotherapy, IV line
-SVT within 3 cm of the saphenofemoral junction
-SVT within the past 3 mo, DVT or PE within the past 6 mo
-Treated for cancer within the past 6 mo
-Antithrombotic therapy for > 48 h or NSAID for > 72 h for current episode of SVT
-Ligation or stripping
-Major surgery within 3 mo
-Bleeding risk
-Pregnant or childbearing age women not using reliable contraception
-Composite of symptomatic events up to day 77
-Each component of primary efficacy outcomes
-Composite of symptomatic PE or DVT
-Surgery for SVT
-Major bleeding
-Nonmajor, minor, total bleeding
-Arterial thromboembolic event
GCS = graduated compression stockings; NSAID = nonsteroidal antiinflammatory drug; PE = pulmonary embolism; RR = risk ratio; SVT = superficial vein thrombosis. See Table 1 for expansion of other abbreviation.
For a large number of recommendations, we summarized the quality of the body of evidence (Fig 2) and estimates of relative and absolute effect of alternative management strategies using the methods of the GRADE Working Group.23 Evidence Profiles summarize the quality of the body of evidence and when evidence comes from randomized trials, generally include a presentation of reviewer assessment of risk of bias, precision, consistency, directness, and publication bias associated with each outcome (eg, see Table 2). As specified in GRADE methodology,19 the overall quality of evidence represents the lowest quality of any critical outcome.
Evidence Profiles can be found in the online data supplement. The format for these tables was determined through a formal survey of panelists that evaluated the panelists' preferences for alternative presentations and the impact of these presentations on their understanding of the evidence. The text in the printed version of the AT9 recommendations includes more succinct Summary of Findings tables (eg, see Table 624), which include the overall quality assessment as well as the relative and absolute effect sizes for each outcome. Use of an associated computer program facilitated the production of the Evidence Profiles and Summary of Findings tables.25
The anticipated absolute effect is expressed as risk difference (and its 95% CI) and is based on the baseline risk in the comparison group and the relative effect of the intervention (and its 95% CI). High quality indicates further research is very unlikely to change our confidence in the estimate of effect; moderate quality, further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low quality, further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; and very-low quality, we are very uncertain about the estimate. ACS = acute coronary syndromes; CABG = coronary artery bypass graft; GRADE = Grades of Recommendations, Assessment, Development, and Evaluation; MI = myocardial infarction; PCI = percutaneous coronary intervention; RR = risk ratio; TIMI = thrombolysis in myocardial infarction.
Making trade-offs between desirable and undesirable consequences of alternative management strategies—the fundamental process of making recommendations—requires making value and preference judgments. For antithrombotic therapy guidelines, this trade-off involves, in most instances, a reduction in thrombotic events compared with an increase in bleeding events. Ideally, the values and preferences applied to this decision would be the average values and preferences of the patient population. We know, however, that patient values for health outcomes vary substantially from patient to patient. Knowledge of the extent to which patient values and preferences vary is one factor in deciding on the strength of a recommendation. The greater the variability in values and preferences, the more likely a weak recommendation is appropriate.23
To inform these decisions, we conducted a systematic review of the literature bearing on patient values and preferences regarding antithrombotic therapy.26 The methodology of conducting such studies remains to be fully developed, and the area remains underinvestigated. Nevertheless, the results of the review provided guidance for the values and preferences that we adopted for these guidelines.26
As an additional strategy for achieving meaningful value and preference decisions by each topic panel and to facilitate consistency across articles, we conducted a values rating exercise. Topic editors and deputy editors constructed patient scenarios for key outcomes of thrombosis and bleeding relevant to their articles. Then informed by the systematic review of values and preferences, panelists used these scenarios to rate each outcome from 0 (death) to 100 (full health). The mean values of these ratings guided the trade-offs between thrombotic and bleeding events and, thus, the determination of strong vs weak recommendations. The scenarios and results of the rating exercise are available in the online data supplements.
The introductory section in each chapter includes a summary, quantitative wherever possible, of the key values and preferences underlying the recommendations. Where value and preference judgments were particularly relevant or controversial, explicit statements of values and preferences accompany individual recommendations.
The literature review26 revealed extensive heterogeneity of results across studies of patient values and preferences—variability that often is difficult to explain. Both the variability between studies and the considerable variability in values and preferences among patients within studies, mandated circumspection in making strong recommendations. Therefore, we restricted strong recommendations to situations in which the desirable consequences of an intervention substantially and convincingly outweighed the undesirable consequences (or the reverse) and to unusual situations in which there was reason to believe that values and preferences are relatively uniform.
In addressing resource use (cost) issues in AT9, we followed previously developed principles.27 In particular, we restricted economic evaluation to recommendations in which it was plausible that resource use considerations might change the direction or strength of the recommendation and in which high-quality economic evaluations were available. When this was not the case, we did not consider resource use in the recommendations.
Six clinicians with the requisite expertise in decision and economic analyses participated in the guideline development process; each article had the benefit of one of these experts as a full committee member. In the following subsections, we present key points in the process of considering resource allocation issues in the recommendations.
Panelists, in consultation with resource use consultants, determined questions for which resource use might change the direction or strength of recommendations. For those questions, we sought high-quality economic analyses. If such analyses were available, we applied the evidence regarding resource use to the relevant recommendation. If net costs or marginal cost-effectiveness ratios were very high, panelists considered rating down the quality of evidence for an intervention from high to low or possibly changing the direction of the recommendation using guides described in section 6.4 "Criteria for Resource Allocation Issues to Affect Recommendations—Thresholds for Cost-Effectiveness."
The Oregon Health & Science University Evidence-based Practice Center conducted thorough literature searches for economic analyses relevant to the different AT9 articles. The resource use experts supplemented these by searches focused on the specific questions of interest for each article. The searches were conducted in Medline and the Cochrane Central Register of Clinical Trials. On the basis that data from studies appreciably more than a decade old would not reflect the current situation, searches were restricted to published studies from 1999 forward. Thus, bibliographic database searches encompassed publications from January 1999 forward: The end date varied across articles and ranged between November 2009 and March 2010 when the searches were executed.
A standardized data extraction form was used to ensure uniform evaluation of the quality of relevant economic analyses. Quality assessment was based on published criteria27‐33 and included specification of perspective of analysis (eg, societal, health system), appropriateness of time horizon (preferably lifetime), use of high-quality evidence for probabilities and rates, use of high-quality sources for costs (eg, primary data, Medicare payments, claims data as proxies), use of appropriate methods for measurement of preferences, and performance of sensitivity analyses to explore uncertainty (both deterministic and probabilistic).
The results of economic analyses may either increase the strength of an otherwise weak recommendation or weaken the strength of a strong recommendation. If cost-effectiveness studies bolstered an already strong recommendation, no change to the recommendation was necessary. We chose the following thresholds for cost-effectiveness considerations affecting recommendations:
When the clinical evidence warrants a strong recommendation for A over B:
Strong recommendation favoring A when high-quality evidence from economic evaluations shows that A costs < 3 times the gross domestic product (GDP) per capita (approximately US $150,000)34 per quality-adjusted life year (QALY) gained relative to B
Weak recommendation favoring A when high-quality evidence from economic evaluations shows that A costs 3 to 5 times the GDP per capita (∼$150,000-$250,000) per QALY gained relative to B
Weak recommendation favoring B when high-quality evidence from economic evaluations shows that A costs > 5 times the GDP per capita (∼$250,000) per QALY gained relative to B
When the clinical evidence warrants a weak recommendation for A over B:
Strong recommendation favoring A if A results in cost savings of > 10% to 20% of the GDP per capita (∼$5,000-$10,000) relative to B (Cost savings must represent all downstream costs and not just the actual cost of the intervention, and analysis must demonstrate a high level of confidence that there is a cost savings.)
Continued weak recommendation favoring A when B is marginally more costly than A (< 10% the GDP per capita)
Continued weak recommendation favoring A when A costs 0 to 5 times the GDP per capita per QALY gained relative to B
Weak recommendation favoring B if A costs > 5 times the GDP per capita (∼$250,000) per QALY gained relative to B
Although certain interventions may be cost-effective in high-income countries (eg, < $20,000 per QALY gained), in poor countries, $20,000 gained per QALY may be prohibitive. The choice of a threshold will vary depending on who is making resource allocation decisions. To facilitate the use of already published cost-effectiveness analyses, the World Health Organization (WHO), through its WHO-CHOICE (Choosing Interventions that are Cost Effective) program35 has used criteria suggested by the Commission on Macroeconomics and Health.36 Interventions that cost < 1 times the average per-capita income for a given country or region per QALY gained are considered very cost-effective. Interventions that cost up to three times the average per-capita income per QALY gained are still considered cost-effective, whereas those that exceed this level are not considered to be cost-effective. To facilitate this process, WHO has developed tables of such threshold values for different regions and countries around the world.37 Thus, the thresholds discussed in the previous section have been defined in terms of GDP per capita. Although referencing thresholds for cost-effectiveness to average per-capita income in middle- and low-income countries can help to extend results of economic analyses performed in high-income countries, such analyses may be less relevant in low-income countries because of significantly different material and labor costs and, thus, may be difficult to extrapolate. Furthermore, the comparator strategies may not be feasible or customary in these locales.
All panelists were required to disclose both financial conflicts of interest, such as receipt of funds for consulting with industry, and intellectual conflicts of interest, such as publication of original data bearing directly on a recommendation. Financial and intellectual conflicts of interest were classified as primary (more serious) or secondary (less serious).38 The operational definition of primary intellectual conflicts of interest included authorship of original studies and peer-reviewed grant funding (government, not-for-profit organizations) directly bearing on a recommendation. The operational definition of primary financial conflicts of interest included consultancies, advisory board membership, and the like from industry. Topic editors had no primary conflicts of interest, as noted. Some deputy editors, who were clinical experts in the topic of the article, had relevant primary conflicts of interest. The ACCP HSP Committee deemed some of these conflicts serious enough to require "management." Management involved more frequent updates of disclosures than required of the approved panelists without any conflicts and recusal from activities relevant to that conflict.
Topic panel members, including the deputy editor, with primary conflicts related to a particular recommendation did not participate in the final deliberations that led to the decision regarding the direction or strength of a recommendation, nor did they vote on recommendations for which they were primarily conflicted. Panelists with primary conflicts could, however, participate in discussions and offer their opinions on interpretations of the evidence. Readers will find a record of panelist conflicts of interest on a recommendation-by-recommendation basis in the online data supplement.
Following approaches recommended by the GRADE Working Group,23 the topic editor, in some cases aided by a panelist without conflicts, formulated the draft recommendations. The formulation of recommendations considered the balance between the desirable and undesirable consequences of an intervention; the quality of evidence; the variability in patient values and preferences; and, on occasion, resource use issues. The recommendations were graded as strong when desirable effects were much greater than undesirable effects or vice versa. Strong recommendations were worded as "We recommend" and labeled 1. Recommendations were graded as weak when desirable effects were not clearly greater or less great than undesirable effects. Weak recommendations were worded as "We suggest" and labeled 2. The rating of the quality of the evidence—high, A; moderate, B; or low, C—is provided with the strength of each recommendation.
After completing the steps described previously, the topic panel members without primary conflicts discussed draft recommendations (Fig 1). Initial discussions generally led to a consensus at the article level on the quality of evidence and the direction and strength of recommendations. At least two members of the Executive Committee reviewed in detail drafts of articles, including recommendations. Written critiques were prepared and returned to the authors for revision. Articles were then made available to the entire AT9 panel.
Recommendations on which topic panels had difficulty coming to a consensus were discussed at a final conference in February 2011 attended by the topic editors and deputy editors and at least one other panel member from each article. Prior to the conference, all AT9 panelists updated their conflict of interest disclosures. The ACCP invited a number of clinical organizations with interest in the guideline topic to attend the final conference as observers.
At this final conference, a representative of each article presented potentially controversial issues in their article's recommendations. Following discussion, which included those present and those attending by videoconference, all panelists without primary conflicts of interest voted on each recommendation. The voting process used a GRADE grid and required that for a strong recommendation, ≥ 80% of those voting had to agree that a strong recommendation was appropriate.39
The AT9 Executive Committee members (G. H. G., M. C., E. A. A., and D. D. G.) harmonized the articles and resolved remaining disagreements among them through facilitated discussion with topic editors and deputy editors without primary conflicts. All major correspondence and decisions at the final conference were recorded in written and audio formats and are available on request to firstname.lastname@example.com.
The ACCP HSP Committee established a process for the thorough review of all ACCP evidence-based clinical practice guidelines. After final review by the AT9 Executive Committee, the guidelines underwent review by the Cardiovascular and Pulmonary Vascular NetWorks of the ACCP, the HSP Committee, and the ACCP Board of Regents. The latter two groups had the right of approval or disapproval but usually worked with the topic panelists and editors to make necessary revisions prior to final approval. Both the HSP Committee and the Board of Regents identified primary reviewers who read the full set of articles, and the remaining HSP Committee members were responsible for reviewing several articles each. The reviewers considered both content and methodology as well as whether there was balanced reporting and adherence to HSP Committee processes. All reviewers were vetted through the same conflict of interest disclosure and management process as described previously. Finally, the Editor in Chief of CHEST read and forwarded the manuscripts for independent, external peer review prior to acceptance for publication. No recommendations or assessments of the quality of the evidence could be changed without the express approval of the topic panel members, AT9 Executive Committee, HSP Committee, and ACCP Board of Regents.
In order to provide a transparent, explicit link among PICO questions, evidence, tables, and recommendations, the section numbering in each article corresponds to numbers in Table 1 in each article, which specifies the patients, interventions, and outcomes for each question. The section numbering also corresponds to the numbering of the recommendations themselves. Evidence Profiles and other tables include these corresponding numbers in brackets in the title, as is true for the online data supplement tables.
AT9 includes improvements from AT8 that reflect the evolution of the science of systematic reviews and clinical practice guidelines. In this supplement,40 some of these improvements include augmented provisions to decrease the likelihood of conflict of interest influence, more stringent application of GRADE criteria for evidence and recommendations (both facilitated by methodologists without primary conflicts taking the role of topic editor), and a systematic review of values and preferences to guide the recommendations.
Although encouraged to use Evidence Profiles and Summary of Findings tables for all recommendations, there were some for which the authors were unable to produce such tables. However, those recommendations used an evidence-based systematic review and assessment of relevant studies. Some recommendations would have benefited from meta-analyses that would have clarified aspects of the evidence. Although panelists were instructed in completing the value and preference rating exercise to estimate patient values and preferences rather than to use their own, we cannot be assured that they succeeded in all instances.41
We plan to continue the tradition of the antithrombotic guidelines to update recommendations when important new studies are published that might change the current recommendations. In March 2011, the ACCP Board of Regents approved a proposal to revise the guideline development and updating process to a "living guidelines" process, whereby the evidence-based guidelines will be periodically assessed and updated as the literature warrants. From 1 year after the publication of this ninth edition onward, all clinical questions or sets of related questions will become their own units. This process will be discussed in greater depth in future publications.
In addition to the published guidelines, ACCP has historically provided clinical resources, including a quick reference to the recommendations, patient education materials, and slide sets for presentations. These resources will continue to be based on the guidelines, but they will be accessed online through the ACCP Web site. In addition, there will be related resources, tools, and links to make the content more easily useful and searchable.
For AT9, we used an explicit, transparent process that seeks to produce highly relevant and unbiased recommendations for clinical practice. This process involved the a priori specification of clinical questions in the PICO format along with study inclusion and exclusion criteria, an exhaustive search for relevant literature, an evaluation of the risk of bias of included studies, and a rigorous and standardized assessment of the quality of the body of evidence and its translation into recommendations using GRADE Working Group methodologies. We incorporated specification of values and preferences and resource considerations into recommendations where particularly relevant and when such data were available. Finally, we sought to minimize bias potentially introduced by intellectual and financial conflicts of interest by comprehensive disclosure requirements and aggressive management of relevant conflicts.
Author contributions: Authors contributed to the AT9 guideline process in the roles described in the article. As Topic Editor and Chair of the guideline, Dr Guyatt oversaw the development of this article.
Dr Guyatt: produced the first draft and was responsible for the final article.
Dr Norris: undertook a major revision of a late draft of the article.
Dr Schulman: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Hirsh: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Eckman: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Akl: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Crowther: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Vandvik: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Eikelbloom: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr McDonagh: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Lewis: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Gutterman: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Cook: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Dr Schünemann: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.
Financial/nonfinancial disclosures: In summary, the authors have reported to CHEST the following conflicts of interest: Dr Eckman has received the following university grants: "Using Decision Analytic Modeling to Guide the ACCP Guideline Development Process for Antithrombotic Therapy in Atrial Fibrillation" (Foundation for Informed Medical Decision Making; October 2011-September 2013; $185,000); "Cost-Effectiveness of Screening for Chronic Hepatitis C Infection" (Merck/Schering-Plough; October 2011- September 2012; $58,000); "Greater Cincinnati BEACON Collaborative" (Office of the National Coordinator for Health Information Technology [90BC0016/01]; September 2010-March 2012; ∼15% effort); "Cincinnati Center for Clinical and Translational Science and Training (CTSA) ARRA Supplement for Development of Distance Learning Program in Medical Informatics" (National Institutes of Health [NIH]/National Center for Research Resources [NCRR] [UL1 RR026314-01S1]; August 2009-August 2011; ∼20% effort); "Cincinnati Center for Clinical and Translational Science and Training (CTSA)" (NIH/NCRR [1U54 RR 025216]; January 2009-February 2014; ∼15% effort); "A Patient Specific Decision Support Tool for Bariatric Surgery" (National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK075599]; August 2007-June 2012; no financial support); National Heart, Lung, and Blood Institute (K23 HL085387; June 2008-March 2013; no financial support); and "Cost-Effectiveness of Screening for Chronic Hepatitis B Infection" (Gilead Sciences Inc; March 2008-August 2010; ∼$56,000). He has also served as consultant for Savient Pharmaceuticals ("Cost Effectiveness Analysis of Gout Medication"; 2010; ∼$300) and as editorial consultant for the ACCP ("Physicians' Information and Education Resource [PIER]: Module on Pre-Operative Assessment for Bleeding Disorders"; 2006-present; ∼$250/y). Dr Crowther has served on various advisory boards, has assisted in the preparation of educational materials, and has sat on data safety and management boards. His institution has received research funds from the following companies: Leo Pharma A/S, Pfizer Inc, Boerhinger Ingelheim GmbH, Bayer Healthcare Pharmaceuticals, Octapharm AG, CSL Behring, and Artisan Pharma. Personal total compensation for these activities over the past 3 years totals less than US $10,000. Dr Eikelboom has received consulting fees and honoraria from AstraZeneca; Boehringer-Ingelheim GmbH; Bristol-Myers Squibb; Corgenix; Daiichi-Sankyo, Inc; Eisai Co, Inc; Eli Lilly and Company; GlaxoSmithKline plc; Haemonetics Corp; McNeil Consumer Healthcare; and Sanofi-Aventis LLC and grants and in-kind support from Accumetrics, Inc; AspirinWorks; Bayer Healthcare Pharmaceuticals; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Corgenix; Dade Behring Inc; GlaxoSmithKline plc; and Sanofi-Aventis LLC. Dr Gutterman has had the following relationships that are entirely unrelated to the AT9 guidelines: ACCP President, GlaxoSmithKline plc grant to study vasodilation in adipose tissue, National Institutes of Health grant to study human coronary dilation, and GE Healthcare consultation on a study for ECG evaluation of chronic heart disease. Drs Guyatt and Schünemann are co-chairs of the GRADE Working Group, and Drs Akl and Vandvik are members and prominent contributors to the Grade Working Group. Dr Lewis is a full-time employee of the ACCP. Drs Norris, Schulman, Hirsh, McDonagh, and Cook have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Role of sponsors: The sponsors played no role in the development of these guidelines. Sponsoring organizations cannot recommend panelists or topics, nor are they allowed prepublication access to the manuscripts and recommendations. Guideline panel members, including the chair, and members of the Health & Science Policy Committee are blinded to the funding sources. Further details on the Conflict of Interest Policy are available online at http://chestnet.org.
Endorsements: This guideline is endorsed by the American Association for Clinical Chemistry, the American College of Clinical Pharmacy, the American Society of Health-System Pharmacists, the American Society of Hematology, and the International Society of Thrombosis and Hematosis.
American College of Chest Physicians
Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
gross domestic product
Grades of Recommendation, Assessment, Development, and Evaluation
Health and Science Policy
population, intervention, comparator, and outcome
quality-adjusted life year
randomized controlled trial
World Health Organization
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