Abstract Objective: To determine the effects of “prolonged” antiplatelet therapy (that is, given for one month or more) on “vascular events” (non-fatal myocardial infarctions, non-fatal strokes, or vascular deaths) in various categories of patients. Design: Overviews of 145 randomised trials of “prolonged” antiplatelet therapy versus control and 29 randomised comparisons between such antiplatelet regimens. Setting: Randomised trials that could have been available by March 1990. Subjects: Trials of antiplatelet therapy versus control included about 70 000 “high risk” patients (that is, with some vascular disease or other condition implying an increased risk of occlusive vascular disease) and 30 000 “low risk” subjects from the general population. Direct comparisons of different antiplatelet regimens involved about 10 000 high risk patients. Results: In each of four main high risk categories of patients antiplatelet therapy was definitely protective. The percentages of patients suffering a vascular event among those allocated antiplatelet therapy versus appropriately adjusted control percentages (and mean scheduled treatment durations and net absolute benefits) were: (a) among about 20 000 patients with acute myocardial infarction, 10% antiplatelet therapy v 14% control (one month benefit about 40 vascular events avoided per 1000 patients treated (2P< 0.00001)); (b) among about 20 000 patients with a past history of myocardial infarction, 13% antiplatelet therapy v 17% control (two year benefit about 40/1000 (2P<0.00001)); (c) among about 10 000 patients with a past history of stroke or transient ischaemic attack, 18% antiplatelet therapy v 22% control (three year benefit about 40/1000 (2P<0.00001)); (d) among about 20 000 patients with some other relevant medical history (unstable angina, stable angina, vascular surgery, angioplasty, atrial fibrillation, valvular disease, peripheral vascular disease, etc), 9% v 14% in 4000 patients with unstable angina (six month benefit about 50/1000 (2P<0.00001)) and 6% v 8% in 16 000 other high risk patients (one year benefit about 20/1000 (2P<0.00001)). Reductions in vascular events were about one quarter in each of these four main categories and were separately statistically significant in middle age and old age, in men and women, in hypertensive and normotensive patients, and in diabetic and non: diabetic patients. Taking all high risk patients together showed reductions of about one third in non-fatal myocardial infarction, about one third in non-fatal stroke, and about one sixth in vascular death (each 2P<0.00001). There was no evidence that non-vascular deaths were increased, so in each of the four main high risk categories overall mortality was significantly reduced. The most widely tested antiplatelet regimen was “medium dose” (75-325 mg/day) aspirin. Doses throughout this range seemed similarly effective (although in an acute emergency it might be prudent to use an initial dose of 160-325 mg rather than about 75 mg). There was no appreciable evidence that either a higher aspirin dose or any other antiplatelet regimen was more effective than medium dose aspirin in preventing vascular events. The optimal duration of treatment for patients with a past history of myocardial infarction, stroke, or transient ischaemic attack could not be determined directly because most trials lasted only one, two, or three years (average about two years). Nevertheless, there was significant (2P<0.00001) further benefit between the end of year 1 and the end of year 3, suggesting that longer treatment might well be more effective. Among low risk recipients of “primary prevention” a significant reduction of one third in non: fatal myocardial infarction was, however, accompanied by a non-significant increase in stroke. Furthermore, the absolute reduction in vascular events was much smaller than for high risk patients despite a much longer treatment period (4.4% antiplatelet therapy v 4.8% control; five year benefit only about four per 1000 patients treated) and was not significant (2P=0.09). Conclusions: Among a much wider range of patients at high risk of occlusive vascular disease than is currently treated routinely, some years of antiplatelet therapy - with aspirin 75-325 mg/day or some other antiplatelet regimen (provided there are no contraindications) - offers worthwhile protection against myocardial infarction, stroke, and death. Significant benefit is evident not only among patients with unstable angina, suspected acute myocardial infarction, or a past history of myocardial infarction, stroke, or transient ischaemic attack, but also among many other categories of high risk patients (such as those having vascular procedures and those with stable angina or peripheral vascular disease). There is as yet, however, no clear evidence on the balance of risks and benefits of antiplatelet therapy in primary prevention among low risk subjects.

Collaborative overview of randomized trials of antiplatelet therapy .1. prevention of death, myocardial-infarction, and stroke by prolonged antiplatelet therapy in various categories of patients

Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery,* Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation

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ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic)

Recommended standards for reports dealing with lower extremity ischemia: Revised version

Anesthesiology. First of two parts.

Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial.

Central venous pressure, blood volume determinations, and the effects of vasoactive drugs in hypovolemic shock.

Background: The past decade has seen an increasing prevalence of prophylactic mastectomy with decreasing ages of patients treated for breast cancer. Data are limited on the fiscal impacts of contralateral prophylactic mastectomy trends, and no study has compared bilateral prophylactic mastectomy with reconstruction to surveillance in high-risk patients. Methods: Lifetime third-party payer costs over 30 years were estimated with 2013 Medicare reimbursement rates. Costs were estimated for patients choosing contralateral or bilateral prophylactic mastectomy versus surveillance, with immediate reconstructions using a single-stage implant, tissue expander, or perforator-based free flap approach. Published cancer incidence rates predicted the percentage of surveillance patients that would require mastectomies. Sensitivity analyses were conducted that varied cost growth, discount rate, cancer incidence rate, and other variables. Lifetime costs and present values (3 percent discount rate) were estimated. Results: Lifetime prophylactic mastectomy costs were lower than surveillance costs, $1292 to $1993 lower for contralateral prophylactic mastectomy and $15,668 to $21,342 lower for bilateral prophylactic mastectomy, depending on the reconstruction. Present value estimates were slightly higher for contralateral prophylactic mastectomy over contralateral surveillance but still cost saving for bilateral prophylactic mastectomy compared with bilateral surveillance. Present value estimates are also cost saving for contralateral prophylactic mastectomy when the modeled contralateral breast cancer incidence rate is increased to at least 0.6 percent per year. Conclusions: These findings are consistent with contralateral and bilateral prophylactic mastectomy being cost saving in many scenarios, regardless of the reconstructive option chosen. They suggest that physicians and patients should continue to receive flexibility in deciding how best to proceed clinically in each case. (Plast. Reconstr. Surg. 136: 730e, 2015.)

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Lifetime Costs of Prophylactic Mastectomies and Reconstruction versus Surveillance.

A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 but not C4 genetic knockout mice are protected from permeability edema. Using mast cell-deficient mice (W/W v ), we tested the hypothesis that mast cells mediate complement activation after acid aspiration. Tracheostomy tubes were placed in anesthetized mice and 2 mUkg 0.1 N HCL was instilled in the trachea. After 4 h, extravasation of 125 I-albumin was used to calculate lung vascular permeability. The serum alternative complement pathway hemolytic activity was examined, and lung immunohistochemistry was performed. Lung permeability in W/W v mice was 62% less than that of mast cell sufficient (+/+) animals and similar to +/+ mice treated with the chymase inhibitor chymostatin (65% decrease). Treatment of +/+ mice with D-PRO 2 , D-TRP 7,9 -Substance P, an antagonist to the neuropeptide substance P, reduced injury by 66%. Serum complement hemolytic activity was intact in injured W/W v mice and +/+ animals treated with chymostatin or dpdt-sp, but was decreased to 65% in the injured untreated +/+ group. Alveolar C3 deposition was intense in injured untreated +/+ mice but absent in the other groups. We interpret these data to indicate that mast cells mediate complement activation, via chymase degranulation, after acid aspiration. This mast cell activity likely is regulated by the release of substance P.

Mast cells mediate complement activation after acid aspiration.

The direct measurement of femoral blood flow in man: patterns of flow and pressure in patients with normal and diseased aortic valves.

A careful solvent-exchange procedure followed by liquid-phase reaction of ethyleneimine with cellulose film in a nonpolar solvent provides an effective method of uniformly aminoethylating cellulose The protonated aminoethyl groups on the cellulose can then ionically bind heparin, a blood anticoagulant Heparinized aminoethylated cellulose tubing at low levels of aminoethylation (ca 02–03% nitrogen) exhibited excellent antithrombogenic properties as well as excellent mechanical strength properties The in vitro tests demonstrated indefinitely long whole-blood clotting times with normal thrombin times In the in vivo experiments, the heparinized aminoethylated cellulose tubing provided extended patency when implanted intravascularly in the regions of low blood flow rate (infra renal inferior vena cava of dogs) A principal use of this film is in the artificial kidney

William G. Austen

Papers

Central venous pressure, blood volume determinations, and the effects of vasoactive drugs in hypovolemic shock.

Lifetime Costs of Prophylactic Mastectomies and Reconstruction versus Surveillance.

Mast cells mediate complement activation after acid aspiration.

The direct measurement of femoral blood flow in man: patterns of flow and pressure in patients with normal and diseased aortic valves.

Antithrombogenic cellulose film