Background: Superficial thrombophlebitis can produce pain and result in a deep vein thrombosis (DVT) if not treated. Conservative therapies including prescription of non-steroidal anti-inflammatory drugs (NSAID) and heat have been standard care. Recently, studies have been published reporting efficacy and safety of low-molecular-weight heparin for the treatment of superficial thrombophlebitis. However, there are few comparative trials to conservative therapy. We studied the effectiveness and safety of treatment with dalteparin compared with ibuprofen in patients with confirmed superficial thrombophlebitis. Methods: Consecutive patients were randomized to receive daily dalteparin vs. ibuprofen three times daily for up to 14 days. The primary outcome measure was the incidence of extension of thrombus or new symptomatic venous thromboembolism during the 14-day and 3-month follow-up period. The secondary outcome was a reduction in pain. The outcome measure of safety was the incidence of major and minor bleeding. Results: Of 302 consecutive patients screened, 72 were enrolled. Four patients receiving ibuprofen compared with no patients receiving dalteparin had thrombus extension at 14 days (P = 0.05), however, there was no difference in thrombus extension at 3 months. Both treatments significantly reduced pain. There were no episodes of major or minor bleeding during the treatment period. Conclusions: Dalteparin is superior to the NSAID ibuprofen in preventing extension of superficial thrombophlebitis during the 14-day treatment period with similar relief of pain and no increase in bleeding. However, questions concerning the optimal treatment duration should be explored in future trials.

Background: Upper extremity deep vein thrombosis (DVT) can result in fatal pulmonary embolism if not treated. Patients with malignancy may be at particularly high risk. Heparin or low-molecular-weight heparin followed by warfarin has been used as standard treatment for lower extremity DVT. However, a paucity of studies exist reporting the efficacy and safety of these regimens in patients with upper extremity DVT. We studied the effectiveness and safety of treatment with dalteparin sodium followed by warfarin and also dalteparin sodium monotherapy for 3 months in patients with confirmed upper extremity DVT. Methods: Consecutive patients with confirmed upper extremity DVT received daily dalteparin sodium for 5-7 days followed by warfarin therapy for 3 months (phase I) or dalteparin sodium monotherapy for 3 months (phase II). The primary outcome measure was the incidence of new symptomatic venous thromboembolism during the 3-month follow-up period. The outcome measure of safety was the incidence of major and minor bleeding. Results: Of 631 consecutive patients screened, 74 were eligible and 67 enrolled. No patients receiving either phase I (0%; 95% CI, 0-12%) or phase II (0%; 95% CI, 0-9%) therapy had venous thromboembolism on 3-month follow-up. One patient (4%; 95% CI, 0-18%) receiving phase I therapy experienced major bleeding. Five patients died during the follow-up period; none were attributed to pulmonary embolism. Conclusions: Patients with upper extremity DVT may be treated safely with either dalteparin sodium followed by warfarin or dalteparin sodium monotherapy for 3 months with a good prognosis.

Varicose veins (VVs) are associated with lifestyle-limiting symptoms and complications. Patients who fail compression therapy are candidates for more invasive treatments. This study evaluates the efficacy and safety of endovenous foam sclerotherapy (EFS) for the treatment of VVs in a US academic center. We reviewed medical records of a consecutive cohort of patients who underwent EFS over a 2-year period. The primary outcome measure was obliteration of VVs. The secondary outcome measures were symptomatic improvement, ulcer healing, recurrence, and adverse events. A total of 166 patients (217 legs) underwent EFS for pain (81%), pruritis (41%), swelling (17%), ulcerations (17%), thrombophlebitis (14%), and varix rupture (3%). Complete (65%) or near-complete (34%) obliteration was achieved in 215 (99%) legs after one injection. Additional injections achieved complete obliteration in 39 of 53 legs. Ninety-three percent (27/29) of active ulcers healed or were decreasing in size. Five ulcers and 11 VVs recurred. Common adverse events included pain and hyperpigmentation. Thrombosis, hematoma, skin necrosis, and neurologic events were rare. In conclusion, EFS appears to be a safe and effective outpatient therapy for the treatment of symptomatic and complicated VVs.

The venoarterial reflex, or postural vasoconstriction reflex, is the decline in limb blood flow in the dependent position due to an increase in pre-capillary vascular resistance.1 Impairment of the venoarterial reflex may be a cause of unexplained leg swelling. The venoarterial reflex prevents loss of fluid to the extravascular space when the legs are dependent. Testing of this reflex evaluates the ability of the cutaneous pre-capillary sphincters to constrict in response to dependency or elevated venous pressure and modulate the hydrostatic pressure.1 The mechanism of this autoregulation is threefold: a local sympathetic axonal reflex, an arteriolar-mediated myogenic response, and a minor central sympathetic efferent nerve component.1 The impaired venoarterial reflex may explain swelling in patients receiving calcium channel blockers.2 It is a cause of swelling in diabetics or patients with spinal degeneration that have neuropathy.3 It may explain edema in women during the luteal phase of their menstrual cycle.4 Attenuation of the reflex with higher skin temperatures may contribute to swelling experienced in hot climates.5 With the patient in a supine position, photoplethysmography (PPG) probes are applied to the great toe (Panel A) to monitor capillary flow at baseline showing normal amplitude pulsatile flow. One leg is then lowered 50 cm off the side of the exam table (Panel B). If the reflex is intact, there is an immediate reduction in the amplitude of the PPG pulsations (Panel C). If the reflex is absent or impaired, there will be no appreciable reduction in the pulsations (Panel D) compared to the supine leg position. Treatment of leg swelling caused by an impaired venoarterial reflex is application of prescription knee length compression hose (20–30 mmHg) daily. Use of diuretics is minimally helpful. Evaluation of the venoarterial reflex is an inexpensive, simple test for excluding this abnormality as a cause of otherwise unexplained leg swelling. Panel A Panel B

PURPOSE: Anticoagulant prophylaxis in patients with central venous catheters is controversial. We performed a meta-analysis of randomized controlled trials of anticoagulant prophylaxis in patients with central venous catheters.METHODS: MEDLINE and EMBASE were searched up to May 2006, supplemented by manual searches of conference proceedings and bibliographies.RESULTS: Fifteen trials were included. Unfractionated heparin infusion, oral fixed low-dose vitamin K antagonist, and subcutaneous low-molecular-weight heparin were evaluated. For all catheter-associated deep vein thrombosis (symptomatic and asymptomatic combined), the summary relative risks ranged from 0.31 to 0.73 (all achieved statistical significance). For symptomatic deep vein thrombosis, the summary relative risks ranged from 0.28 to 0.72, but did not achieve statistical significance for any individual regimen.CONCLUSION: Anticoagulant prophylaxis is effective for preventing all catheter-associated deep vein thrombosis in patients with central venous catheters. The effectiveness for preventing symptomatic venous thromboembolism, including pulmonary embolism, remains uncertain. (c) 2007 Elsevier Inc. All rights reserved.

Objective: Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol response to caffeine challenge after controlled levels of caffeine intake. Methods: Men (N = 48) and women (N = 48) completed a double-blind, crossover trial conducted over 4 weeks. On each week, subjects abstained for 5 days from dietary caffeine and instead took capsules totaling 0 mg, 300 mg, and 600 mg/day in 3 divided doses. On day 6, they took capsules with either 0 mg or 250 mg at 9:00 AM, 1:00 PM, and 6:00 PM, and cortisol was sampled from saliva collected at 8 times from 7:30 AM to 7:00 PM. Results: After 5 days of caffeine abstinence, caffeine challenge doses caused a robust increase in cortisol across the test day (p < .0001). In contrast, 5 days of caffeine intake at 300 mg/day and 600 mg/day abolished the cortisol response to the initial 9:00 AM caffeine dose, although cortisol levels were again elevated between 1:00 PM and 7:00 PM (p = .02 to .002) after the second caffeine dose taken at 1:00 PM. Cortisol levels declined to control levels during the evening sampling period. Conclusion: Cortisol responses to caffeine are reduced, but not eliminated, in healthy young men and women who consume caffeine on a daily basis. ANOVA = analysis of variance; C = caffeine; HPAC = hypothalamic-pituitary-adrenocortical axis; P = placebo; ACTH = adrenocorticotropin.

A 50 years old Caucasian female with history of Hepatitis C presented to the emergency room with complaints of fever, abdominal pain, abdominal distension and lower extremity swelling. On examination, patient had signs of chronic liver disease including chest wall spider angiomas, ascites, splenomegaly and lower extremity edema. Laboratory data showed leukocyte count of 12,500 cells per cubic millimeter, hemoglobin 11 grams per deciliter, platelets 47,000 cells per cubic millimeter, PT 37.8 seconds, INR 3.6, albumin 1.6 grams per deciliter, AST 47 units per liter, ALT 102 units per liter and alkaline phosphatase 195 units per liter. Patient underwent midline abdominal wall diagnostic paracentesis, for evaluation of spontaneous bacterial peritonitis (SBP), by emergency room physician. Peritoneal fluid analysis was not consistent with SBP. Patient underwent abdominal CT-Scan for further evaluation of abdominal pain. CT-Scan showed ascites, cirrhotic liver, splenomegaly and an incidental 8.7 × 8.5 × 8.3 cm pelvic mass. For further evaluation of the pelvic mass, patient had transvaginal abdominal ultrasound and duplex vascular study done, which showed an 8.1 × 8.2 cm ovarian cyst in open communication with a dilated varicose vein, with venous flow within the cyst. This was thought to be traumatic venous leak, by midline paracentesis, from the distended variceal vein into the ovarian cyst giving rise to pseudoaneurysm of the variceal vein. This ovarian cyst and venous communication was successfully obliterated with ultrasound guided thrombin injection into the cyst. To the best of our knowledge this type of complication from mid line paracentesis and than complete obliteration with thrombin injection has not been reported.

Blood pressure (BP) and cardiovascular hemodynamics were assessed at baseline and after caffeine administration in a 4-week, placebo-controlled, double-blind, randomized, crossover trial of caffeine tolerance formation. Half of the subjects developed tolerance to the pressor effect of caffeine, whereas the other half continued to show increases in BP after caffeine ingestion (F = 16.7, p < 0.0001). In the subjects who did not develop tolerance, peripheral resistance increased incrementally as the daily dose of caffeine increased (F = 2.8, p = 0.05). (c) 2005 by Excerpta Medica Inc.

Objectives To evaluate the efficacy and safety of prophylactic anticoagulant treatment in the primary prevention of venous thromboembolism in patients with central venous catheters (CVC). Data Sources MEDLINE (1964-2004), EMBASE (1980-2004), Current Contents, Premedline, the Cochrane Controlled Trials Registry (2004), ACP Journal Club (2003), the Database of Reviews of Effects (2003), and the Cochrane Database of Systematic Reviews (2004) were searched using truncated keyword searches for thrombosis, anticoagulation, and central venous catheterization. Article retrieval was supplemented by crosschecking bibliographies of relevant studies. Study Selection All prospective studies of adult patients receiving systemic anticoagulant prophylaxis compared with a concurrent control group and with outcomes evaluated using venograms and/or duplex ultrasonography were selected for review. Retrospective studies, review articles, case reports, and studies evaluating dialysis patients were excluded. Data Extraction Two reviewers independently assessed each article using predefined criteria for study validity and recorded efficacy and safety results. A third reviewer resolved disagreements by adjudication. Data Synthesis Thirteen studies were evaluated. Eight studies were randomized controlled trials. Only three studies found a significant absolute risk reduction (ARR) in deep vein thrombosis using prophylactic anticoagulation: 55.3% ARR with 2500 IU daily of dalteparin, 28.0% ARR using 1 mg of warfarin daily, and 11.1% ARR using continuous infusion of heparin at 1000 IU/kg/day. No study met all of the predefined criteria for adequately evaluating safety. Conclusion Limited data from randomized controlled trials suggest that heparin dalteparin and warfarin are effective in the prevention of DVT in patients with CVC. Bleeding risk cannot be precisely estimated from the available data. The efficacy and safety of anticoagulant prophylaxis should be evaluated by randomized trials of sufficient size to make valid conclusions.

Background: Caffeine in dietary doses is a well-established pressor agent. Tolerance to this pressor effect occurs in only about half of regular consumers in acute laboratory tests. The clinical significance of this incomplete tolerance depends on whether the pressor effect is maintained throughout the day with repeated intake. Therefore, we examined the ability of a standard dose of caffeine (250 mg x 3) to maintain a blood pressure (BP) elevation during 18 hours of ambulatory BP monitoring (ABPM) after 5 days of regular daily intake of varying background doses.Methods: Eighty-five men and women completed a four-week double blind, crossover trial. During each week, subjects consumed capsules totaling 0, 300, or 600 mg/day of caffeine in 3 divided doses. On day 6, they consumed capsules with either 0 or 250 mg at 9:00 am and 1:00 pm, in the laboratory, and again at 6:00 pin during ABPM. Tolerance was defined as a reduction in the diastolic BP response to two challenge doses given in the lab in response to increasing daily intake. Data were analyzed using multivariate repeated measures analysis of variance.Results: BP responses to caffeine above those found on placebo-placebo (P-P) week were found for both tolerance groups when caffeine was consumed after a week of receiving a placebo. However, only the low tolerance group showed increases, above those found on P-P week, after 300 mg/day in systolic/diastolic BP during the waking hours (mean standard error of the mean = 2.8 &PLUSMN; 1. 1, P = .01/2.2 &PLUSMN; 0.9, P = .02) and in systolic BP during sleep (2.3 &PLUSMN; 1, P = .03).Conclusions: Persistent elevations in BP occurring on a daily basis in some habitual caffeine consumers may hold clinical significance. &COPY; 2005 American Journal of Hypertension, Ltd.

Background: All of the available diagnostic tests for deep venous thrombosis (DVT) have limitations for excluding acute recurrent DVT. Measurement of plasma D-dimer by using an automated quantitative assay may be useful as a rapid exclusion test in patients with suspected recurrent DVT.Objective: To test the safety of withholding additional diagnostic testing and heparin treatment in patients who have a negative D-dimer result at presentation (using the automated quantitative assay STA-Liatest D-di), regardless of their symptoms.Design: Prospective cohort study.Setting: Academic medical center in the United States.Patients: 300 consecutive patients with suspected recurrent DVT.Intervention: Patients underwent D-dimer testing at presentation. In patients with negative D-dimer results, heparin therapy was withheld, and no further diagnostic testing for DVT was done as part of the initial evaluation. Patients with positive D-dimer results underwent compression ultrasonography.Measurements: The primary outcome measure was a diagnosis of new symptomatic venous thromboembolism confirmed by diagnostic testing during the 3-month follow-up period.Results: Of the 300 study patients, the D-dimer result was negative at presentation in 134 patients (45%; negative cohort) and positive at presentation in 166 patients. Of the 166 patients, compression ultrasonography documented new DVT in 54 patients. Compression ultrasonography findings were normal in 79 patients and were inconclusive in 33 patients. After 3 months of follow-up, 1 of 134 patients in the negative cohort had confirmed venous thromboembolism (0.75% [95% Cl, 0.02% to 4.09%]). Venous thromboembolism on follow-up could not be definitively excluded in 5 patients with recurrent leg symptoms and in 1 patient who died. If these patients are considered to have venous thromboembolism, the incidence during the 3-month follow-up period would be 6.0% (Cl, 2.6% to 11.4%) (8 of 134 patients).Limitations: There is no accepted diagnostic reference standard for recurrent DVT. The precision of the estimate of the incidence of venous thromboembolism on follow-up and the generalizability to settings other than an academic health center should be evaluated.Conclusions: Measurement of plasma D-dimer by using the automated quantitative assay STA-Liatest D-di seems to provide a simple method for excluding acute recurrent DVT in symptomatic patients.

Caffeine acutely raises blood pressure (BP). The clinical significance of this effect depends on whether BP responses persist in persons who consume caffeine on a daily basis. Accordingly, the ability of caffeine to raise BP after 5 days of regular daily intake was tested in a randomized controlled trial. Individual differences in tolerance formation were then examined. Men (n=49) and women (n=48) completed a double-blind, crossover trial conducted over 4 weeks. During each week, subjects abstained for 5 days from dietary caffeine and instead used capsules totaling 0 mg, 300 mg, and 600 mg of caffeine per day in 3 divided doses. On day 6, in the laboratory, they used capsules with either 0 mg or 250 mg of caffeine at 9:00 am and 1:00 pm. Systolic/diastolic BP increases as a result of 250 mg of caffeine remained significant (P<0.006/0.001) at all levels of previous daily consumption. Individual difference comparisons found that although half the subjects had complete loss of systolic and diastolic BP responses to the challenge doses, the other half showed no loss in BP response, even after using 600 mg of caffeine per day for the previous 5 days (F >7.90, P <0.001). The sexes did not differ in degree of tolerance formation. Daily caffeine consumption failed to eliminate the BP response to repeated challenge doses of caffeine in half of the healthy adults who were tested. Caffeine may therefore cause persistent BP effects in persons who are regular consumers, even when daily intake is at moderately high levels.

BACKGROUND The diagnosis of pulmonary embolism is difficult because the clinical diagnosis is nonspecific and all of the objective tests have limitations. The assay for plasma d-dimer may be useful as an exclusion test if results are negative. We conducted a prospective cohort study that evaluated the clinical utility (usefulness) of an automated quantitative d-dimer test in the diagnosis of patients with suspected pulmonary embolism. METHODS Consecutive eligible patients who had clinically suspected PE with nondiagnostic lung scans or negative helical CT scan of the chest results underwent d-dimer testing. RESULTS The d-dimer results were negative in 11 of 103 inpatients (10.6%, 95% confidence interval [CI], 5.5 to 18.3%) and 7 of 22 outpatients (31.8%, 95% CI, 13.9 to 54.9%; p = 0.02). CONCLUSIONS Measurement of plasma d-dimer is of limited clinical utility for inpatients with clinically suspected pulmonary embolism and nondiagnostic lung scans or negative helical CT results at a US academic health center.

Caffeine increases blood pressure (BP). In men, acute BP elevations after caffeine intake are due to an increase in vascular resistance, with no change in cardiac output. The hemodynamic effects of caffeine have not been studied in women. Accordingly, BP and hemodynamic responses to caffeine were measured in a double-blind trial comparing age-matched men and women at rest and during mental stress. Caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of brewed coffee) or placebo was given to separate groups of women (n = 21 and 21) and men (n = 16 and 19) (mean ages 29 and 27 years, respectively). BP, cardiac output, and vascular resistance were observed at rest, during a stressful public-speaking simulation, reading aloud, and recovery. Caffeine caused nearly identical systolic and diastolic BP elevations in women (4.5 and 3.3 mm Hg, respectively) and men (4.1 and 3.8 mm Hg, respectively). Men given caffeine versus placebo showed the expected elevation in vascular resistance throughout the remainder of the protocol (p <0.001), with no difference in cardiac output. In contrast, women responded to caffeine with increases in stroke volume (p <0.001) and cardiac output (p <0.001), with no difference in vascular resistance from women taking placebo. Men and women have similar BP responses to caffeine, but the BP responses may arise from different hemodynamic mechanisms. Women who consume a dietary dose of caffeine showed an increase in cardiac output, whereas men showed increased vascular resistance.

Objectives: To determine the sensitivity and specificity of ultrasonography in the diagnosis of upper extremity deep vein thrombosis and to determine the safety of withholding anticoagulant therapy in patients with negative ultrasonographic results.Data Sources: The MEDLINE database was searched for literature published from January 1, 1980, to December 31, 2000, that evaluated ultrasonography for the diagnosis of upper extremity deep vein thrombosis. Bibliographies of the retrieved articles were cross-checked to identify additional studies. Study Selection: All prospective English-language studies were selected. Retrospective studies, review articles, and case reports were excluded.Data Extraction: Two of us (B.O.M. and S.W.R.) used predefined criteria to independently assess each study. Data on sensitivity and specificity and the associated 95% confidence intervals were recorded when available.Data Synthesis: Only one study met all of the pre-defined criteria for adequately evaluating sensitivity and specificity. The sensitivity of duplex ultrasonography ranged from 56% to 100%, and the specificity ranged from 94% to 100%. No study evaluated the safety of withholding anticoagulant therapy without additional testing in patients with negative ultrasonographic results.Conclusion: The safety of withholding anticoagulant treatment in a patient with suspected upper extremity deep vein thrombosis and negative ultrasonographic results is uncertain.