Advertisement

Drug Safety

, Volume 10, Issue 2, pp 170–181 | Cite as

Epidemiology of Gastrointestinal Damage Associated with Nonsteroidal Anti-Inflammatory Drugs

  • Laura Rees Willett
  • Jeffrey L. Carson
  • Brian L. Strom
Review Article Pharmacoepidemiology

Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with significant upper gastrointestinal (GI) toxicity, with a relative risk of approximately 3. This is supported by evidence drawn from randomised controlled trials [of aspirin (acetylsalicylic acid)], cohort studies and case-control studies. The risk is increased with higher doses of medication, shorter treatment duration and concomitant corticosteroid use. Elderly patients and those with a history of GI illness are also at increased risk. Ibuprofen may be associated with a lower, and piroxicam with a higher, risk of complications. There are only preliminary data regarding an association between NSAIDs and small and large intestinal complications.

Therapeutic alternatives which may confer a lower risk of significant GI toxicity include enteric-coated preparations, non-acetylated salicylates, and NSAIDs taken in conjunction with misoprostol. Epidemiological data regarding these alternatives are sparse.

Keywords

Aspirin Misoprostol Nsaid User Gastrointestinal Damage Salsalate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abeles M, Gordon R, Johnson J, Labowitz R, Lowenstein M, et al. A double-blind multi-investigator study of Trilisate versus acetylsalicylic acid tablets in patients with rheumatoid arthritis: final clinical summary. In Ehrlich (Ed.) The resurgence of salicylates in arthritis therapy, pp. 104–109, Science Media Communications, Norwalk, 1983Google Scholar
  2. Agrawal NM, Roth S, Graham DY, White RH, Germain B, et al. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. Annals of Internal Medicine 115: 195–200, 1991PubMedGoogle Scholar
  3. Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. New England Journal of Medicine 327: 749–754, 1992aPubMedCrossRefGoogle Scholar
  4. Allison MC. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. Letter. New England Journal of Medicine 327: 1883, 1992bCrossRefGoogle Scholar
  5. Armstrong CP, Blower AL. Non-steroidal anti-inflammatory drugs and life threatening complications of peptic ulceration. Gut 28: 527–532, 1987PubMedCrossRefGoogle Scholar
  6. Bartle WR, Gupta AK, Lazor J. Nonsteroidal anti-inflammatory drugs and gastrointestinal bleeding. A case-control study. Archives of Internal Medicine 146: 2365–2367, 1986PubMedCrossRefGoogle Scholar
  7. Beard K, Walker AM, Perera DR, Jick H. Nonsteroidal anti-inflammatory drugs and hospitalization for gastroesophageal bleeding in the elderly. Archives of Internal Medicine 147: 1621–1623, 1987PubMedCrossRefGoogle Scholar
  8. Beardon PHG, Brown SV, McDevitt DG. Gastrointestinal events in patients prescribed non-steroidal anti-inflammatory drugs: a controlled study using record linkage in Tayside. Quarterly Journal of Medicine 71: 497–505, 1989PubMedGoogle Scholar
  9. Berkowitz JM, Rogenes PR, Sharp JT, Warner CW. Ranitidine protects against gastroduodenal mucosal damage associated with chronic aspirin therapy. Archives of Internal Medicine 147: 2137–2139, 1987PubMedCrossRefGoogle Scholar
  10. Bollini P, Garcia Rodriguez LA, Gutthann SP, Walker AM. The impact of research quality and study design on epidemiologic estimates of the effect of nonsteroidal anti-inflammatory drugs on upper gastrointestinal tract disease. Archives of Internal Medicine 152: 1289–1295, 1992PubMedCrossRefGoogle Scholar
  11. Bradley JD, Brandt KD, Katz BP, Kalasinski LA, Ryan SI. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. New England Journal of Medicine 325: 87–91, 1991PubMedCrossRefGoogle Scholar
  12. Caldwell JR, Roth SH, Wu WC, Semble EL, Castell DO, et al. Sucralfate treatment of nonsteroidal anti-inflammatory drug-induced gastrointestinal symptoms and mucosal damage. American Journal of Medicine 83 (suppl. 3B): 74–82, 1987PubMedCrossRefGoogle Scholar
  13. Campbell KL, De Beaux AC. Nonsteroidal anti-inflammatory drugs and appendicitis in patients aged over 50 years. British Journal of Surgery 79: 967–968, 1992PubMedCrossRefGoogle Scholar
  14. Cairns JA, Gent M, Singer J, Finnie KJ, Froggatt GM, et al. Aspirin, sulfinpyrazone, or both in unstable angina. New England Journal of Medicine 313: 1369–1375, 1985PubMedCrossRefGoogle Scholar
  15. Carson J, Notis WM, Orris ES. Colonic ulceration and bleeding during diclofenac therapy. New England Journal of Medicine 323: 135, 1990PubMedCrossRefGoogle Scholar
  16. Carson JL, Strom BL, Morse ML, West SL, Soper KA, et al. The relative gastrointestinal toxicity of the nonsteroidal anti-inflammatory drugs. Archives of Internal Medicine 147: 1054–1059, 1987aPubMedCrossRefGoogle Scholar
  17. Carson JL, Strom BL, Soper KA, West SL, Morse ML. The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding. Archives of Internal Medicine 147: 85–88, 1987bPubMedCrossRefGoogle Scholar
  18. Coggon D, Langman MJS, Spiegelhalter D. Aspirin, paracetamol, and haematemesis and melena. Gut 23: 340–344, 1982PubMedCrossRefGoogle Scholar
  19. Cohen A, Garber HE. Comparison of choline magnesium trisalicylate and acetylsalicylic acid in relation to fecal blood loss. Current Therapeutic Research 23: 187–193, 1978Google Scholar
  20. Committee on Safety of Medicines. Nonsteroidal anti-inflammatory drugs and serious gastrointestinal adverse reactions — 2. British Medical Journal 292: 1190–1191, 1986CrossRefGoogle Scholar
  21. Day TK. Intestinal perforation associated with osmotic slow release indomethacin capsules. British Medical Journal 287: 1671–1672, 1983PubMedCrossRefGoogle Scholar
  22. Department of Clinical Epidemiology and Biostatistics, McMaster University Health Sciences Centre. How to read clinical journals IV. To determine etiology or causation. Canadian Medical Association Journal 124: 985–990, 1981Google Scholar
  23. Duggan JM, Dobson AJ, Johnson H, Fahey P. Peptic ulcer and nonsteroidal anti-inflammatory agents. Gut 27: 929–933, 1986PubMedCrossRefGoogle Scholar
  24. Dutch TIA Trial Study Group. A comparison of two doses of aspirin (30 mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. New England Journal of Medicine 325: 1261–1266, 1991CrossRefGoogle Scholar
  25. Ehrlich GE, Miller SB, Zeiders RS. Choline magnesium trisalicylate versus ibuprofen in rheumatoid arthritis. Rheumatology and Rehabilitation 19: 30–41, 1980PubMedCrossRefGoogle Scholar
  26. Ehsanullah RSB, Page MC, Tildesley G, Wood JR. Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. British Medical Journal 297: 1017–1021, 1988PubMedCrossRefGoogle Scholar
  27. Faulkner G, Prichard P, Somerville K, Langman MJS. Aspirin and bleeding peptic ulcers in the elderly. British Medical Journal 297: 1311–1313, 1988PubMedCrossRefGoogle Scholar
  28. Fries JF, Miller SR, Spitz PW, Williams CA, Hubert HB, et al. Toward an epidemiology of gastropathy associated with nonsteroidal anti-inflammatory drug use. Gastroenterology 96: 647–655, 1989PubMedGoogle Scholar
  29. Furst DE, Blocka K, Cassell S, Harris ER, Hirschberg JM, et al. A controlled study of concurrent therapy with a nonacetylated salicylate and naproxen in rheumatoid arthritis. Arthritis and Rheumatism 30: 146–154, 1987PubMedCrossRefGoogle Scholar
  30. Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis. Annals of Internal Medicine 115: 787–796, 1991PubMedGoogle Scholar
  31. Gibson GR, Whitacre EB, Ricotti CA. Colitis induced by nonsteroidal anti-inflammatory drugs. Archives of Internal Medicine 152: 625–632, 1992PubMedCrossRefGoogle Scholar
  32. Goldenberg A, Rudnicki RD, Koonce ML. Clinical comparison of efficacy and safety of choline magnesium trisalicylate and indomethacin in treating osteoarthritis. Current Therapeutic Research 24: 245–260, 1978Google Scholar
  33. Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. Lancet 2: 1277–1280, 1988aPubMedCrossRefGoogle Scholar
  34. Graham DY, Smith JL, Dobbs SM. Gastric adaptation occurs with aspirin administration in man. Digestive Diseases and Sciences 28: 1–6, 1983PubMedCrossRefGoogle Scholar
  35. Graham DY, Smith JL, Spjut HJ, Torres E. Gastric adaptation. Studies in humans during continuous aspirin administration. Gastroenterology 95: 327–333, 1988bGoogle Scholar
  36. Graham DY, White RH, Moreland LW, Schubert TT, Katz R, et al. Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Annals of Internal Medicine 119: 257–262, 1993PubMedGoogle Scholar
  37. Griffin MR, Piper JM, Daugherty JR, Snowden M, Ray WA. Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Annals of Internal Medicine 114: 257–263, 1991PubMedGoogle Scholar
  38. Griffin MR, Ray WA, Schaffner W. Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Annals of Internal Medicine 109: 359–363, 1988PubMedGoogle Scholar
  39. Guess HA, West R, Strand LM, Heiston D, Lydick EG, et al. Fatal upper gastrointestinal hemorrhage or perforation among users and nonusers of nonsteroidal anti-inflammatory drugs in Saskatchewan, Canada 1983. Journal of Clinical Epidemiology 41: 35–45, 1988PubMedCrossRefGoogle Scholar
  40. Henry DA, Dobson A, Turner C. Variability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs. Gastroenterology, in press, 1994Google Scholar
  41. Henry DA, Johnston A, Dobson A, Duggan J. Fatal peptic ulcer complications and the use of non-steroidal anti-inflammatory drugs, aspirin, and corticosteroids. British Medical Journal 295: 1227–1229, 1987PubMedCrossRefGoogle Scholar
  42. Hoftiezer JW, Silvoso GR, Burks M, Ivey KJ. Comparison of the effects of regular and enteric-coated aspirin on gastroduodenal mucosa of man. Lancet 2: 609–612, 1980PubMedCrossRefGoogle Scholar
  43. Holvoet J, Terriere L, Van Hee W, Verbist L, Fierens E, et al. Relation of upper gastrointestinal bleeding to nonsteroidal anti-inflammatory drugs and aspirin: a case-control study. Gut 32: 730–734, 1991PubMedCrossRefGoogle Scholar
  44. Jick H. Effects of aspirin and acetaminophen in gastrointestinal hemorrhage. Archives of Internal Medicine 141: 316–321, 1981PubMedCrossRefGoogle Scholar
  45. Jick SS, Perera DR, Walker AM, Jick H. Non-steroidal anti-inflammatory drugs and hospital admission for perforated peptic ulcer. Lancet 2: 380–382, 1987PubMedCrossRefGoogle Scholar
  46. Jiranek GC, Kimmey MB, Saunders DR, Willson RA, Shanahan W, et al. Misoprostol reduces gastroduodenal injury from one week of aspirin: an endoscopic study. Gastroenterology 96: 656–661, 1989PubMedGoogle Scholar
  47. Juul-Moller S, Edvardsson N, Jahnmatz B, Rosen A, Sorensen S, et al. Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. Lancet 340: 1421–1425, 1992PubMedCrossRefGoogle Scholar
  48. Kaufman DW, Kelly JP, Sheehan JE, Laszlo A, Wiholm BE, et al. Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding. Clinical Pharmacology and Therapeutics 53: 485–494, 1993PubMedCrossRefGoogle Scholar
  49. Kilander A, Dotevall G. Endoscopic evaluation of the comparative effects of acetylsalicylic acid and choline magnesium trisalicylate on human gastric and duodenal mucosa. British Journal of Rheumatology 22: 36–40, 1983PubMedCrossRefGoogle Scholar
  50. Kurata JH, Abbey DE. The effect of chronic aspirin use on duodenal and gastric ulcer hospitalizations. Journal of Clinical Gastroenterology 12: 260–266, 1990PubMedCrossRefGoogle Scholar
  51. Lanas A, Sekar MC, Hirschowitz BI. Objective evidence of aspirin use in both ulcer and nonulcer upper and lower gastrointestinal bleeding. Gastroenterology 103: 862–869, 1992PubMedGoogle Scholar
  52. Lancaster-Smith MJ, Jaderberg ME, Jackson DA. Ranitidine in the treatment of nonsteroidal anti-inflammatory drug associated gastric and duodenal ulcers. Gut 32: 252–255, 1991PubMedCrossRefGoogle Scholar
  53. Langman MJS, Morgan L, Worrall A. Use of anti-inflammatory drugs by patients admitted with small or large bowel perforations and haemorrhage. British Medical Journal 290: 347–349, 1985PubMedCrossRefGoogle Scholar
  54. Lanza FL, Aspinall RL, Swabb EA, Davis RE, Rack MF, et al. Double-blind, placebo-controlled endoscopic comparison of the mucosal protective effects of misoprostol versus cimetidine on tolmetin-induced mucosal injury to the stomach and duodenum. Gastroenterology 95: 289–294, 1988PubMedGoogle Scholar
  55. Lanza FL, Fakouhi D, Rubin A, Davis RE, Rack MF, et al. A double-blind placebo-controlled comparison of the efficacy and safety of 50, 100, and 200 micrograms of misoprostol qid in the prevention of ibuprofen-induced gastric and duodenal mucosal lesions and symptoms. American Journal of Gastroenterology 84: 633–636, 1989PubMedGoogle Scholar
  56. Lanza FL, Rack MF, Wagner GS, Balm TK. Reduction in gastric mucosal hemorrhage and ulceration with chronic high-level dosing of enteric-coated aspirin granules two and four times a day. Digestive Diseases and Sciences 30: 509–512, 1985PubMedCrossRefGoogle Scholar
  57. Lanza FL, Royer GL, Nelson RS. Endoscopic evaluation of the effects of aspirin, buffered aspirin, and enteric-coated aspirin on gastric and duodenal mucosa. New England Journal of Medicine 303: 136–138, 1980PubMedCrossRefGoogle Scholar
  58. Laporte JR, Carne X, Vidal X, Moreno V, Juan J. Upper gastrointestinal bleeding in relation to previous use of analgesics and nonsteroidal anti-inflammatory drugs. Lancet 337: 85–89, 1991PubMedCrossRefGoogle Scholar
  59. Larkai EN, Smith JL, Lidsky MD, Graham DY. Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic nonsteroidal anti-inflammatory drug use. American Journal of Gastroenterology 82: 1153–1158, 1987PubMedGoogle Scholar
  60. Larkai EN, Smith JL, Lidsky MD, Sessoms SL, Graham DY. Dyspepsia in NSAID users: the size of the problem. Journal of Clinical Gastroenterology 11: 158–162, 1989PubMedCrossRefGoogle Scholar
  61. Levy M. Aspirin use in patients with major upper gastrointestinal bleeding and peptic-ulcer disease. New England Journal of Medicine 290: 1158–1162, 1974PubMedCrossRefGoogle Scholar
  62. Levy M, Miller DR, Kaufman DW, Siskind V, Schwingl P, et al. Major upper gastrointestinal tract bleeding. Relation to the use of aspirin and other nonnarcotic analgesics. Archives of Internal Medicine 148: 281–285, 1988PubMedCrossRefGoogle Scholar
  63. Manniche C, Malchow-Moller A, Andersen JR, Pedersen C, Hansen TM, et al. Randomised study of the influence of non-steroidal anti-inflammatory drugs on the treatment of peptic ulcer in patients with rheumatic disease. Gut 28: 226–229, 1987PubMedCrossRefGoogle Scholar
  64. Martio J. The influence of antirheumatic drugs on the occurrence of peptic ulcers. Scandinavian Journal of Rheumatology 9: 55–59, 1980PubMedGoogle Scholar
  65. McIntosh JH, Byth K, Piper DW. Environmental factors in aetiology of chronic gastric ulcer: a case control study of exposure variables before the first symptoms. Gut 26: 789–798, 1985PubMedCrossRefGoogle Scholar
  66. McLaughlin G. Choline magnesium trisalicylate vs. naproxen in rheumatoid arthritis. Current Therapeutic Research 32: 579–585, 1982Google Scholar
  67. Mitchell DM, Spitz PW, Young DY, Bloch DA, McShane DJ, et al. Survival, prognosis, and causes of death in rheumatoid arthritis. Arthritis and Rheumatism 29: 706–714, 1986PubMedCrossRefGoogle Scholar
  68. Morris AJ, Madhok R, Sturrock RD, Capell HA, MacKenzie JF. Enteroscopic diagnosis of small bowel ulceration in patients receiving non-steroidal anti-inflammatory drugs. Lancet 337: 520, 1991PubMedCrossRefGoogle Scholar
  69. Multicenter Salsalate/Aspirin Comparison Study Group. Does the acetyl group of aspirin contribute to the antiinflammatory efficacy of salicylic acid in the treatment of rheumatoid arthritis? Journal of Rheumatology 16: 321–327, 1989Google Scholar
  70. Peoples JB. Peptic ulcer disease and the nonsteroidal anti-inflammatory drugs. American Surgeon 51: 358–362, 1985PubMedGoogle Scholar
  71. Persantine-Aspirin Reinfarction Study Research Group. Persantine and aspirin in coronary heart disease. Circulation 62: 449–461, 1980CrossRefGoogle Scholar
  72. Piper DW, Mclntosh JH, Ariotti DE, Fenton BH, MacLennan R. Analgesic ingestion and chronic peptic ulcer. Gastroenterology 80: 427–432, 1981PubMedGoogle Scholar
  73. Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Annals of Internal Medicine 114: 735–740, 1991PubMedGoogle Scholar
  74. Riddell RH, Tanaka M, Mazzoleni G. Non-steroidal anti-inflammatory drugs as a possible cause of collagenous colitis: a case-control study. Gut 33: 683–686, 1992PubMedCrossRefGoogle Scholar
  75. Robinson MG, Griffin JW, Bowers J, Kogan FJ, Kogut DG, et al. Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal anti-inflammatory drugs. Digestive Diseases and Sciences 34: 424–428, 1989PubMedCrossRefGoogle Scholar
  76. Rossi AC, Hsu JP, Faich GA. Ulcerogenicity of piroxicam: an analysis of spontaneously reported data. British Medical Journal 294: 147–149, 1987PubMedCrossRefGoogle Scholar
  77. Roth S, Agrawal N, Mahowald M, Montoya H, Robbins D, et al. Misoprostol heals gastroduodenal injury in patients with rheumatoid arthritis receiving aspirin. Archives of Internal Medicine 149: 775–779, 1989PubMedCrossRefGoogle Scholar
  78. Roth SH, Bennett RE, Mitchell CS, Hartman RJ. Cimetidine therapy in nonsteroidal anti-inflammatory drug gastropathy. Archives of Internal Medicine 147: 1798–1801, 1987PubMedCrossRefGoogle Scholar
  79. Sabesin SM, Boyce HW, King CE, Mann JA, Ruoff G, et al. Comparative evaluation of gastrointestinal intolerance produced by plain and tri-buffered aspirin tablets. American Journal of Gastroenterology 83: 1220–1225, 1988PubMedGoogle Scholar
  80. Savage RL, Moller PW, Ballantyne CL, Wells JE. Variation in the risk of peptic ulcer complications with nonsteroidal antiinflammatory drug therapy. Arthritis and Rheumatism 36: 84–90, 1993PubMedCrossRefGoogle Scholar
  81. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Archives of Internal Medicine 153: 1665–1670, 1993PubMedCrossRefGoogle Scholar
  82. Silvoso GR, Ivey KJ, Butt JH, Lockard OO, Holt SD, et al. Incidence of gastric lesions in patients with rheumatic disease on chronic aspirin therapy. Annals of Internal Medicine 91: 517–520, 1979PubMedGoogle Scholar
  83. Soll AH, Weinstein WM, Kurata J, McCarthy D. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Annals of Internal Medicine 114: 307–319, 1991PubMedGoogle Scholar
  84. Somerville K, Faulkner G, Langman M. Non-steroidal anti-inflammatory drugs and bleeding peptic ulcer. Lancet 1: 462–464, 1986PubMedCrossRefGoogle Scholar
  85. Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing Physicians’ Health Study. New England Journal of Medicine 321: 129–135, 1989CrossRefGoogle Scholar
  86. SALT Collaborative Group. Swedish Aspirin Low-dose Trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebro-vascular ischaemic events. Lancet 338: 1345–1349, 1991CrossRefGoogle Scholar
  87. Tronstad RI, Aadland E, Holler T, Olaussen B. Gastroscopic findings after treatment with enteric-coated and plain naproxen tablets in healthy subjects. Scandinavian Journal of Gastroenterology 20: 239–242, 1985CrossRefGoogle Scholar
  88. UK-TIA Study Group. United Kingdom transient ischaemic attack (UK-TIA) aspirin trial interim results. British Medical Journal 296: 316–320, 1988CrossRefGoogle Scholar
  89. Vandenbroucke JP, Hazevoet HM, Cats A. Survival and cause of death in rheumatoid arthritis: a 25-year prospective followup. Journal of Rheumatology 11: 158–161, 1984PubMedGoogle Scholar
  90. Walan A, Bader JP, Classen M, Lamers CBHW, Piper DW, et al. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. New England Journal of Medicine 320: 69–75, 1989PubMedCrossRefGoogle Scholar
  91. Walt RP. Misoprostol for the treatment of peptic ulcer and anti-inflammatory-drug-induced gastroduodenal ulceration. New England Journal of Medicine 327: 1575–1580, 1992PubMedCrossRefGoogle Scholar
  92. Wilson RG, Smith AN, Macintyre IMC. Complications of diverticular disease and non-steroidal anti-inflammatory drugs: a prospective study. British Journal of Surgery 77: 1103–1104, 1990PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Laura Rees Willett
    • 1
  • Jeffrey L. Carson
    • 1
  • Brian L. Strom
    • 2
  1. 1.Division of General Internal MedicineUniversity of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical SchoolNew BrunswickUSA
  2. 2.Center for Clinical Epidemiology and BiostatisticsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

Personalised recommendations