ACP J Club. 1996 Sept-Oct;125:A14. doi:10.7326/ACPJC-1996-125-2-A14
Evolution can only be appreciated by viewing phenomena over time. Darwin was able to develop his views on evolution, in part, through his observation of species change in the Galapagos Islands. On the "front lines," medical knowledge seems to come at clinicians in moment-to-moment bits. If we step back from the everyday news of medical advances, can we discern any patterns or broad themes? Would knowledge of these themes help us to understand the evolution of medical knowledge?
A popular feature of the American College of Physicians' (ACP) Annual Session is the Update in General Internal Medicine. Highlights of the 1994 and 1995 Updates have been published (1, 2). We wondered what we could learn about the evolution of medical knowledge by reviewing the contents of successive presentations that contain "the most clinically important advances for practicing general internists."
General internal medicine has a wide array of topics that could be included in an Update. Nonetheless, each year the Update has been restricted to advances in just 7 or 8 areas. The areas that were present in all 3 years included coronary artery disease and congestive heart failure (CHF), hypertension, thromboembolic diseases, disease prevention and screening, and Helicobacter pylori and duodenal ulcer. Asthma, diabetes, and various viral diseases (including HIV) appeared in 2 of 3 years. Most of the areas chosen reflect both the core work of the general internist—management of common chronic diseases—the emergence of clinically important advances. These areas present key opportunities for us to improve our care of patients.
For heart disease, advances fall into 2 areas: 1) interventional and risky therapies that are designed to disrupt coronary artery occlusive lesions and 2) long-term management strategies. For patients who have had acute myocardial infarction, we now know that thrombolysis works best when administered as soon as possible after onset of symptoms of occlusion (3) and that differences in efficacy among thrombolytic agents are not as great as differences caused by the timeliness of intervention (4, 5). Emergent percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction is also effective (6, 7) but clearly requires the availability of expert teams and catheterization suites.
For longer-term management, angiotensin-converting enzyme (ACE) inhibitors have clearly established themselves as agents with life-prolonging efficacy in the management of CHF and should be considered for all patients who can tolerate them (8). The evidence that decreasing cholesterol levels with statin drugs prevents progression of arteriosclerotic vascular disease has become more convincing with time (9). Finally, the use of hormonal replacement therapy with or without progestin by postmenopausal women can be recommended as safe and generally favorable in terms of reduction of cardiovascular risk (10).
Practical information on managing thromboembolic disease is readily discernible from research advances reported in each of the 3 Updates. A combination of clinical findings and duplex ultrasonography effectively diagnoses or rules out most cases of suspected deep venous thrombosis (DVT). Invasive studies can be reserved for times when the clinical picture and ultrasonographic results are discordant (11). The most important factor determining bleeding complications is warfarin dose (12). Much research has addressed dose and duration of warfarin therapy. We know that 6 weeks' duration is insufficient compared with 6 months' duration after DVT or pulmonary embolus, regardless of the existence of predisposing factors (13). The question of whether lower-intensity or 3-month regimens are as effective and safe will probably be answered in the near future. Research continues to show the efficacy of low-molecular-weight heparin (LMWH) compared with unfractionated heparin in the treatment of DVT. 2 studies with perhaps the highest likelihood of changing practice showed that home management with LMWH and no monitoring of coagulation status was as effective as (and probably less costly than) in-hospital unfractionated heparin therapy for DVT (14, 15). We predict that in many communities, selected patients with DVT will soon be cared for with LMWH at home. Finally, the factor V Leiden point mutation, which confers resistance to activated protein C, is the most common inherited risk factor yet identified for thromboembolic disease (16, 17). Future investigations will probably define specific management strategies for detecting and managing patients with this abnormality.
Our understanding of duodenal ulcer has changed dramatically. The bacterium H. pylori is the most common cause of duodenal ulcer disease. Eradication leads to cure (18). We also know that noninvasive diagnostic tests (including measurement of H. pylori serum IgG levels or the urea breath test) are as effective as invasive tests (19). So-called triple antibiotic regimens (bismuth, metronidazole, and tetracycline plus omeprazole; omeprazole, clarithromycin, and amoxacillin or metronidazole) can produce 90% eradication (cure) rates, whereas double-agent regimens (considered in the past year to be an effective alternative ) eradicate the organism in only 35% to 70% of patients (20-24). Abdominal pain and diarrhea are common side effects of the 1- to 2-week treatment regimens, but "cured" patients do not require long-term acid suppression and have low recurrence rates.
Clinicians can now offer treatments that have favorable effects on many viral diseases. Influenza vaccine not only reduces the risk for influenzal illness in elderly persons but also reduces illness and the number of workdays lost in working-age adults (25), particularly when epidemic influenza occurs. Famciclovir reduces the duration of postherpetic neuralgia in patients with herpes zoster who are older than 50 years of age (26), and acyclovir reduces viral shedding in genital herpesvirus infections (27). Interferon-α appears to have favorable effects for persons with chronic, progressive hepatitis C (28).
Clinicians can help their patients achieve better control of asthma and of non-insulin-dependent diabetes mellitus. Long-acting inhaled corticosteroids are now the cornerstone of asthma therapy (29). Metformin is useful for monotherapy or as an adjunct to glyburide in the management of non-insulin-dependent diabetes mellitus (30). It is important that metformin has not been associated with lactic acidosis.
The recurring items that emerge from our review of 3 annual Updates of advances are the changes in the therapeutics of chronic diseases. We have mainly reported information that allows clinicians to make better choices among already existing therapies, essentially improving therapeutic precision. We judge that the most striking advance during the past few years is that H. pylori causes duodenal ulcer and that eradication cures duodenal ulcer. Chemotherapy of viral diseases offers examples of other new treatments now available to patients. Randomized trials are the primary way in which important advances in the management of chronic diseases are shown. All told, review of these 3 years shows that additions to the knowledge base of general internists—if accompanied by changes in the way we practice—offer important new benefits to our patients.
2. Larson EB, McGee SR.Update in general internal medicine [editorial]. ACP J Club. 1995 Sep-Oct;123:A12-4.
3. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' Collaborative Group. Lancet. 1994;343:311-22.
5. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. The GUSTO Angiographic Investigators. N Engl J Med. 1993;329:1615-22.
6. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med. 1993;328:673-9.
8. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza dell'infarto Miocardico. Lancet. 1994; 343:1115-22.
9. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301-7.
10. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. The Writing Group for the PEPI Trial. JAMA. 1995;273:199-208.
13. Schulman S, Rhedin AS, Lindmarker P, et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. N Engl J Med. 1995;332:1661-5.
14. Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med. 1996;334:677-81.
15. Koopman MM, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med. 1996; 334: 682-7.
16. Ridker PM, Hennekens CH, Lindpaintner K, et al. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med. 1995;332:912-7.
17. Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Buller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet. 1996;346:1593-6.
20. al-Assi MT, Cole RA, Karttunen TJ, et al. Treatment of Helicobacter pylori infection with omeprazole-amoxicillin combination therapy versus ranitidine/sodium bicarbonate-amoxicillin. Am J Gastroenterol. 1995;90:1411-4.
21. Saberi-Firoozi M, Massarrat S, Zare S, et al. Effect of triple therapy or amoxicillin plus omeprazole or amoxicillin plus tinidazole plus omeprazole on duodenal ulcer healing, eradication of Helicobacter pylori, and prevention of ulcer relapse over a 1-year follow-up period: a prospective, randomized, controlled study. Am J Gastroenterol. 1995;90:1419-23.
22. de Boer WA, Driessen WM, Jansz AR, Tytgat GN. Quadruple therapy compared with dual therapy for eradication of Helicobacter pylori in ulcer patients: results of a randomized prospective single-centre study. Eur J Gastroenterol Hepatol. 1995;7:1189-94.
23. Thijs JC, van Zwet AA, Moolenaar W, et al. Triple therapy vs. amoxicillin plus omeprazole for treatment of Helicobacter pylori infection: a multicenter, prospective, randomized, controlled study of efficacy and side effects. Am J Gastroenterol. 1996;91:93-7.
26. Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Herpes Zoster Study Group. Ann Intern Med. 1995;123:89-96.
28. Nishiguchi S, Kuroki T, Nakatani S, et al. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet. 1995;346:1051-5.
29. Greening AP, Ind PW, Northfield M, Shaw G. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hamburys Limited UK Study Group. Lancet. 1994;334:219-24.