YorkieTalk.com Forums - Yorkshire Terrier Community


Welcome to the YorkieTalk.com Forums Community - the community for Yorkshire Terriers.

You are currently viewing our boards as a guest which gives you limited access to view most discussions and access our other features. By joining our free community you will have access to post topics, communicate privately with other members (PM), respond to polls, upload content and access many other special features. You will be able to chat with over 35,000 YorkieTalk members, read over 2,000,000 posted discussions, and view more than 15,000 Yorkie photos in the YorkieTalk Photo Gallery after you register. We would love to have you as a member!

Registration is fast, simple and absolutely free so please, join our community today!

If you have any problems with the registration process or your account login, please click here to contact us.

Go Back   YorkieTalk.com Forums - Yorkshire Terrier Community > YorkieTalk > Yorkie Health & Diet
Register Blogs FAQ Calendar

Reply
 
LinkBack Thread Tools
Old 02-02-2014, 07:04 AM   #1
Furbutts = LOVE
Donating Member
Moderator
 
Wylie's Mom's Avatar
 
Join Date: Jan 2005
Location: Phoenix, AZ
Posts: 35,889
Blog Entries: 2
Default Article: Pet Lovers Beware: When The Drugs Don't Work

This article was emailed to me by a YT friend....quite an interesting read, especially as compared to how human medicine works, and the risks we take w/ side effects. This is the link: https://medium.com/evidence-base/95ea62df3951

Pet Lovers Beware: When The Drugs Don’t Work
We pour our hearts into caring for our animals, and spend small fortunes on their meds. What if the drugs are worthless?

by Peter Aldhous in Evidence Base

Kaleb, I hope you’ll agree, is a handsome beast. In his youth, he cut an athletic figure, and was quite the wanderer. Indeed, without his lust for independent travel, he’d never have come into our lives. Having roamed once too often from owners who showed little interest in taking him back, he ended up in a rescue shelter in Ithaca, New York, and was adopted in 2005 by my girlfriend, Nadia.

Now in his twilight years, Kaleb doesn’t get around so well. He’s part German Shepherd, and is afflicted by the breed’s curse: hip dysplasia and osteoarthritis. In plain English: his hip joints are loose, which leads to cartilage damage and inflammation. It’s painful to watch him struggling to his feet, and while he still loves to go for a walk, his back legs start to give out before too long. But at least he’s getting the best possible veterinary care, we told ourselves.

At least we did, until an email hit my inbox some weeks back, sent to a discussion list of science writers. It referred to a study indicating that two food supplements—glucosamine and chondroitin—do little to help cats with disintegrating joints. I recognized the names as ingredients in Kaleb’s breakfast: Our dog-feeding ritual involves taking a chew containing these nutrients, then adding a dollop of peanut butter containing a couple of pills of a painkiller called tramadol.

Chondroitin is an important component of cartilage, and glucosamine a potential building block for its repair, so it makes sense that they might help his aching joints. But I’ll take hard facts over intuition any day, so I forwarded the email to Nadia and started to look at what studies on dogs with osteoarthritis have to say.

What I found was eye-opening. There’s scant evidence that either the supplements or the painkillers are doing much to ease Kaleb’s suffering. There is a treatment that clearly could do some good: a non-steroidal anti-inflammatory drug, or NSAID. But we’d rejected that after discussion with his vet a year or so ago because of fears—possibly overblown—that it might damage his kidneys.

If you have a pet, this should be a cautionary tale. Americans spent $14.2 billion on veterinary care for their pets in 2013—and that doesn’t include proprietary health diets and food supplements. Put another way, pet owners pay about $850 annually in veterinary expenses per dog, and about $575 per cat. Factor in the emotional energy we invest in keeping our companion animals healthy, and you’d hope for high confidence in the end results. But as I’ve learned, much of veterinary medicine is based on shaky scientific foundations: The drugs prescribed for your dog or cat may work no better than those we’ve been giving to Kaleb.

Before you get angry, realize that mostly this isn’t your vet’s fault. The biggest problem is that their medicine cabinets are relatively bare. Like it or not, most of what we know about whether drugs work and are safe comes from clinical trials conducted by pharmaceutical companies to win marketing approval. Even though the sums we spend on our pets’ health may seem lavish, they’re a fraction of the budgets involved in human medicine, making it hard for companies to justify the costs of developing new veterinary drugs. That’s why the U.S. Food and Drug Administration’s database of approved human drugs contains more then 6,500 entries, and the list for dogs fewer than 650.

If it’s on the approved list for animals, you can be reasonably confident that a drug does what it says on the label. Most worming tablets, for example, have been well tested for their ability to clear parasites from dogs or cats. But things can get murky with many commonly prescribed drugs, including antibiotics and painkillers, which have not specifically been approved for use in animals and where practice is based on extrapolations from human medicine—which may or may not be relevant to creatures with subtly different physiology, prone to different diseases.

Still, vets could make better use of the available scientific knowledge. Today, most doctors treating human patients accept the principles of evidence-based medicine, where best practice is based on data from multiple scientific studies. But many vets are reluctant to jump on that bandwagon, arguing that there’s not enough data on animals to justify this approach. “A lot of vets think that it will undermine client confidence,” says Brennen McKenzie, president of the Evidence-Based Veterinary Medicine Association and a vet at the Adobe Animal Hospital in Los Altos, California.

Think about what he’s saying: Some vets are reluctant to delve into what science has to say, out of fear that they’ll have to admit that they don’t know for sure how to make our pets well. A comment added to one of McKenzie’s blog posts, from a vet who had learned that glucosamine does little for osteoarthritis, underlines the point. “I can tell you it was hard for me to stop selling the stuff,” the vet wrote. “I was making money, the clients thought it was working … and I did not want to fess up and tell them they had bought something from me that was a waste of money.”

My own journey of discovery about Kaleb’s treatment began at a website called BestBETs for Vets, where the Centre for Evidence-based Veterinary Medicine at the University of Nottingham helps vets to ask the right questions—and shows them how to find answers in the scientific literature. Its examples include one relevant to Kaleb, considering the effectiveness of glucosamine and chrondroitin versus an NSAID called carprofen in treating dogs with osteoarthritis. The bottom line: “Carprofen is superior to glucosamine/chrondroitin supplements in reducing the clinical signs.”
Out and about: Regular short walks with our other canine companion, Posie, should help

So are Kaleb’s supplements doing anything at all? He started taking glucosamine and chrondroitin in 2007, advised by vets in Ithaca who hoped that they might help stave off joint damage. But now that he’s already arthritic, there’s little evidence that they will help, according to a recent systematic review of available studies. (In this case, human medicine provided a good guide to the likely effects in dogs: A huge clinical trial concluded in 2006 that the supplements don’t reduce arthritic knee pain.) If we want to work on Kaleb’s diet, the same review suggested, we might try formulas rich in fish oils, which have promising results in placebo-controlled trials. (And if you’re wondering why placebo controls are needed in veterinary studies, read the note to the right.)

So much for glucosamine and chondroitin. Now I needed to find out about tramadol, the painkiller that we add to Kaleb’s breakfast. I turned to Steve Budsberg of the University of Georgia, who specializes in canine osteoarthritis. “That’s too bad,” he responded, when I told him that Kaleb was taking the drug. “I think it just gets the dogs high.”

Digging into the scientific literature, I learned why Budsberg is skeptical. Tramadol is an opioid—essentially a synthetic version of morphine—and its painkilling effects in people depend largely on its conversion in the body to a substance called M1. But dogs don’t seem to convert tramadol to M1 as well as humans. I found just one controlled trial comparing carpofren and tramadol to treat dogs with osteoarthritis. The drugs were given for only a couple of weeks, and the main conclusions were that placebo effects are large, and that findings vary depending on how you measure a dog’s symptoms.

Why is tramadol widely prescribed to dogs with Kaleb’s condition, when the best evidence indicates that NSAIDs like carpofren are the most effective option? Fear of liver and kidney damage, two known dangers of NSAIDs, seems to be the main reason. But Budsberg believes this concern is overplayed, and worries that the vogue for tramadol has achieved little apart from reassuring vets and dog owners that they aren’t risking side effects. “They’re treating themselves,” he says.

As you can imagine, Nadia and I aren’t feeling so good about ourselves right now. Each of us has a PhD in biology, and yet we’d failed to ask all of the right questions about Kaleb’s treatment. We plan to get some fresh tests to see how stable his kidney function is, and talk to our current vet in San Francisco about whether it’s time to try carprofen. (Warning: asking more questions may mean spending more money.)

I’m pleased that we’re seeking better answers for Kaleb, but the big question remains: Why are vets recommending treatments that probably don’t work? One explanation is what psychologists call confirmation bias: Once we get an idea into our heads, we tend to pay attention to information that supports it, and dismiss facts that don’t. Vets aren’t immune, so it’s easy to see how initial positive experiences with a drug could color their judgment. They’re especially likely to be fooled into overestimating a drug’s impact on a condition like arthritis, which can wax and wane of its own accord.

[CONTINUED BELOW]
__________________
~ A friend told me I was delusional. I nearly fell off my unicorn. ~

°¨¨¨°ºOº°¨¨¨° Ann | Pfeiffer | Marcel Verdel Purcell | Wylie | Artie °¨¨¨°ºOº°¨¨¨°
Wylie's Mom is offline   Reply With Quote
Welcome Guest!
Not Registered?

Join today and remove this ad!

Old 02-02-2014, 07:04 AM   #2
Furbutts = LOVE
Donating Member
Moderator
 
Wylie's Mom's Avatar
 
Join Date: Jan 2005
Location: Phoenix, AZ
Posts: 35,889
Blog Entries: 2
Default

[CONTINUED]

If you’re a cat lover, you may be wondering if things are any better in feline medicine. Sadly not. There are even fewer studies on cats, which suffer from a number of mysterious conditions that are hard to treat. Particularly distressing is feline gingivostomatitis, a severe inflammation of the gums that occurs when the immune system overreacts to plaque in the mouth. “It’s a terrible thing,” says Karen Langeman, who runs the Porte Veterinary Hospital in Campbell, California, and sees one or two cases each month. Eating becomes very painful, and some cats have to have all their teeth pulled.

What triggers this exaggerated immune response is unclear, although it’s most common in cats with viral or bacterial infections. And without a good understanding of the cause, vets can do little but try to ease the symptoms with corticosteroids and painkillers.

Mysteries like these could be solved by more research, but how can we get vets to pay attention to the studies that have been done? It would help if professional bodies took a strong evidence-based stand. Sadly, the American Veterinary Medical Association flunked a test of its commitment to scientific principles in January, when its governing body voted down a resolution rejecting homeopathy as an “ineffective practice.” The association’s Australian and British counterparts already discourage homeopathy because of a lack of evidence for therapeutic effects—not to mention the absence of a good explanation of how the extremely dilute solutions used in homeopathic remedies might work. Yet the AVMA’s leadership feared the resolution was divisive, and argued that evaluating specific therapies isn’t its job.

You and I can also make a difference, by pressing vets to consider the evidence that does exist. I’m not suggesting repeating my exercise of digging into the research literature; that’s heavy-going, even for someone who makes his living writing about science. But we can keep our vets on their toes by asking better questions. “Very few of my clients come to me wanting to know what my rationale is for doing what I’m doing,” McKenzie says.

So ask your vet why they think the drugs your animal is being given will work. We’re going to have to confront our own psychological biases, here: research shows that people prefer confident advice, sometimes even when we know those giving it have been wrong before. And good answers to these questions will inevitably be hedged with caveats about the small number of studies that have been done, and their limitations. If all you get from your vet is a bland assurance that they’ve been doing this for years, and see great results, get them to talk you through the scientific evidence. If they can’t do so, that should be a warning sign: It might be time to look for another vet.

Our companion animals do great things for us, improving not just our psychological well-being but also our physical health through knock-on effects like reduced blood pressure. The least we can do in return is to challenge vets to base their decisions on the best available science.

Kaleb, buddy, we owe you one.
__________________
~ A friend told me I was delusional. I nearly fell off my unicorn. ~

°¨¨¨°ºOº°¨¨¨° Ann | Pfeiffer | Marcel Verdel Purcell | Wylie | Artie °¨¨¨°ºOº°¨¨¨°
Wylie's Mom is offline   Reply With Quote
Old 02-02-2014, 07:53 AM   #3
Resident Yorkie Nut Donating YT 20K Club Member
 
ladyjane's Avatar
 
Join Date: Sep 2006
Location: Texas
Posts: 27,450
Default

Interesting article.

The board certified surgeon I use told me some time ago that any evidence that glucosamine and chondroitin work is anecdotal.

My general vet has always prescribed NSAIDS for arthritis.

As for Tramadol, the only time it has been prescribed for my pups is after surgery.

I think many vets are simply doing what people are pushing them to do. I hear people rave about glucosamine and chondroitin all of the time; and I have once in a while said something, but it is met with arguments so I just leave it alone. It is not hurting dogs but I just don't see how it is helping except for what people believe. Someone recently asked me about using it for collapsed trachea....someone had posted it here....but there is no scientific data that says it works. At least none that I have been shown.
ladyjane is offline   Reply With Quote
Old 02-02-2014, 10:29 AM   #4
Donating YT 500 Club Member
 
yorkiemini's Avatar
 
Join Date: Sep 2010
Location: USA
Posts: 4,285
Default

Awsome article.
Bottom line is that evidence based practice in animals is not what is driving the treatment regimens. I'm guessing the research thT is required for evidence based practice for vets may be considered too expensive so therefore we continue with trial-and-error and doing what we have always done instead.

This is scary and demands that we as pet owners demand and expect more. The main lesson here is ask questions and stay informed.

Places like Yorkie Talk will be clear centers for this type of activity. I know my vet considers me a pain in the butt at times, but they also always answer my questions and give me copies of research articles that back up their decisions.

Maybe we need an EVIDENCED BASED forum to put these articles we find so all can have access to them.

Thanks for bringing this to the forefront !
__________________
. Cali , and Cali's keeper and staff, Jay
No, not a "mini" Yorkie - She loves to motor in her Mini Cooper car
yorkiemini is offline   Reply With Quote
Old 02-02-2014, 12:42 PM   #5
Donating YT 1000 Club Member
 
MauiGirl's Avatar
 
Join Date: May 2008
Location: Maui, Hawaii
Posts: 7,740
Default

Very interesting, and I just hope more studies will be done to open up more drug treatment options.
__________________
SANDY, MOM TO TIKI , KAYLA , KARLEE , R.I.P. MEIKA
MauiGirl is offline   Reply With Quote
Old 02-02-2014, 10:02 PM   #6
kjc
I♥PeekTinkySaph&Finny
Donating Member
 
kjc's Avatar
 
Join Date: May 2009
Location: Baltimore, Maryland
Posts: 18,866
Default

IDK...Gluc and Chon are questionable even in human use. Some folks swear by it for themselves, and others swear by it for their dogs. It did nothing for me and I did not notice a big change in the dogs I've used it on. But hey, I guess it's worth a try.

And for some reason, not all meds work the same on kitties as they do dogs, or people. Penicillin is toxic to Guinea pigs, so you can't go by that. It would not surprise me at all if that feline gingivostomatitis is a result of over vaccination in cats, as that's all about over taxing the immune response.

IDK, but my vet takes into consideration my pet and it's health issues, age, etc. when prescribing drugs, weighs the pros and cons and makes the best choice for my pet. After all, that's a major part of their job. We try new drugs and also use the old standbys depending on the situation. And if one doesn't perform as expected, we try something else.

What are they asking for in this article anyway? Disease x, take drug X? That doesn't even work for people. Most pain meds do not work for me, nor the arthritis meds (prescription or OTC). I've even had 3 or 4 diagnostic tests (MRIs and Laparoscopies) that did not reveal the extent of the problems I had/have resulting in what should have been a one hour surgery extended to 3 or 4 hours in two different instances, and my last MRI showed no problem, even though I've had chronic pain in my neck from an injury 4 years ago.

Did I miss something here? Lol!
__________________
Kat Chloe Lizzy
PeekABooTinkerbell SapphireInfinity
kjc is offline   Reply With Quote
Old 02-03-2014, 12:08 AM   #7
YT 1000 Club Member
 
Join Date: Jun 2013
Location: NJ
Posts: 1,354
Default

Anecdotal, but glucosamine and chondroitin really seemed to help my grandmom's poodle.

She was 13,a bit overweight, and started having issues with stiff joints; I decided to try glucosamine and chondroitin and it really helped. I started her in the winter and she ended up doing better that winter than she had been during the summer, the next summer was better too.
She got around much easier and wasn't as crabby on the medicine. We went into it thinking it wouldn't do much and were surprised when it helped.

Basically I think it's worth a try.
ShowGirlLola is offline   Reply With Quote
Old 02-03-2014, 06:14 AM   #8
♥ Love My Tibbe! ♥
Donating Member
 
yorkietalkjilly's Avatar
 
Join Date: Feb 2011
Location: D/FW, Texas
Posts: 22,140
Default

Glucosamine and chondroitin helped my hip for a while and then didn't, so might have been placebo effect but it sure got better for a while early on in my post-traumatic arthritis of the hip. After a time, there didn't seem to be any positive effect.

Still, as studies are done in supplements and vitamins, seems like a lot of things are turning out not to be as efficacious as advertised in humans or even potentially harmful so I'd wondered about certain pet supplements, particularly G&C. And am certainly glad to know about this study for future reference as Tibbe ages and faces arthritis. What's the point of giving him something if it just doesn't work, especially with his compromised liver?

GTK about both the Tramadol and Carprofen info! Scary to think about how little some vets are up on the latest studies about medicine and supplements they are prescribing!

Thanks for taking the time to post this article for us.
__________________
Jeanie and Tibbe
One must do the best one can. You may get some marks for a very imperfect answer: you will certainly get none for leaving the question alone. C. S. Lewis
yorkietalkjilly is offline   Reply With Quote
Old 02-03-2014, 06:47 AM   #9
Furbutts = LOVE
Donating Member
Moderator
 
Wylie's Mom's Avatar
 
Join Date: Jan 2005
Location: Phoenix, AZ
Posts: 35,889
Blog Entries: 2
Default

Quote:
Originally Posted by yorkiemini View Post
Awsome article.
Bottom line is that evidence based practice in animals is not what is driving the treatment regimens. I'm guessing the research thT is required for evidence based practice for vets may be considered too expensive so therefore we continue with trial-and-error and doing what we have always done instead.

This is scary and demands that we as pet owners demand and expect more. The main lesson here is ask questions and stay informed.


Places like Yorkie Talk will be clear centers for this type of activity. I know my vet considers me a pain in the butt at times, but they also always answer my questions and give me copies of research articles that back up their decisions.

Maybe we need an EVIDENCED BASED forum to put these articles we find so all can have access to them.

Thanks for bringing this to the forefront !
EXACTLY!! What's concerning is the extent to which 'emotions' are driving the drug choices, and that's never a good thing.

What also was deeply concerning to me was the extent to which vets are exceedingly cautious about potential (stress potential!) side effects. In humans, we have potential SE as well, but we still take major meds despite this bc they're the best meds to take. It seems that w/ pets, they're sacrificing the meds more often based upon potential SE, much more than in humans. That's very odd to me. NSAIDs are amazing meds, and we shouldn't be SO cautious with them bc of potential SE, we should be reasonably cautious and be mitigating the risks, and that's it.
__________________
~ A friend told me I was delusional. I nearly fell off my unicorn. ~

°¨¨¨°ºOº°¨¨¨° Ann | Pfeiffer | Marcel Verdel Purcell | Wylie | Artie °¨¨¨°ºOº°¨¨¨°
Wylie's Mom is offline   Reply With Quote
Old 02-03-2014, 04:09 PM   #10
Don't Litter Spay&Neuter
Donating Member
 
mimimomo's Avatar
 
Join Date: Jan 2009
Location: So Cal
Posts: 9,874
Default

Ok, so they're saying G&C are not good for arthritis? Bc I've read so many positive reviews on here of pups taking cosequin or dasuquin, who's joints have greatly improved, they stopped lifting their leg when walking/running & doesn't seem to be in pain. Confusing. So does it help w/joint issues but not arthritis, is that what they're saying?
__________________
Jenny Mimi Momo Princess Turbo
Madan Pin Brush: www.toplinepet.com
mimimomo is offline   Reply With Quote
Reply

Bookmarks




Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is Off
HTML code is Off
Trackbacks are On
Pingbacks are On
Refbacks are Off




Google
 

SHOP NOW: Amazon :: eBay :: Buy.com :: Newegg :: PetStore :: Petco :: PetSmart


All times are GMT -8. The time now is 09:15 PM.


Powered by vBulletin® Version 3.8.9
Copyright ©2000 - 2024, vBulletin Solutions, Inc.
Copyright ©2003 - 2018 YorkieTalk.com
Privacy Policy - Terms of Use

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 628 629 630 631 632 633 634 635 636 637 638 639 640 641 642 643 644 645 646 647 648 649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 696 697 698 699 700 701 702 703 704 705 706 707 708 709 710 711 712 713 714 715 716 717 718 719 720 721 722 723 724 725 726 727 728 729 730 731 732 733 734 735 736 737 738 739 740 741 742 743 744 745 746 747 748 749 750 751 752 753 754 755 756 757 758 759 760 761 762 763 764 765 766 767 768 769 770 771 772 773 774 775 776 777 778 779 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 810 811 812 813 814 815 816 817 818 819 820 821 822 823 824 825 826 827 828 829 830 831 832 833 834 835 836 837 838 839 840 841 842 843 844 845 846 847 848 849 850 851 852 853 854 855 856 857 858 859 860 861 862 863 864 865 866 867 868 869 870 871 872 873 874 875 876 877 878 879 880 881 882 883 884 885 886 887 888 889 890 891 892 893 894 895 896 897 898 899 900 901 902 903 904 905 906 907 908 909 910 911 912 913 914 915 916 917 918 919 920 921 922 923 924 925 926 927 928 929 930 931 932 933 934 935 936 937 938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953 954 955 956 957 958 959 960 961 962 963 964 965 966 967 968 969 970 971 972 973 974 975 976 977 978 979 980 981 982 983 984 985 986 987 988 989 990 991 992 993 994 995 996 997 998 999 1000 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 1018 1019 1020 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044 1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1164 1165 1166 1167