The effectiveness of eHealth interventions on physical activity and measures of obesity among working-age women: a systematic review and meta-analysis.

Physical inactivity and obesity are modifiable risk factors for cardiovascular disease, particularly in women. eHealth interventions may increase physical activity and improve obesity-related outcomes among women. The objective of this study was to review the evidence of the effectiveness of eHealth interventions to increase moderate-to-vigorous physical activity among working-age women. The secondary objective was to examine their effectiveness on improving obesity-related outcomes. A comprehensive search strategy was developed for eight electronic databases; through July 2016. All studies consisting of >80% women of working-age (18-65 years) in high income countries were included. Multiple unblinded reviewers determined study eligibility and extracted data. Risk of bias was evaluated using the Cochrane Risk of Bias Tool and data quality using the Grading of Recommendations Assessment, Development and Evaluation approach. Data were pooled using a random-effects model. Sixty studies were included in the review of which 20 were in the meta-analysis. The meta-analysis demonstrated eHealth interventions improved moderate-to-vigorous physical activity (standard mean difference = 1.13, 95% confidence interval: 0.58, 1.68, P < 0.0001); an increase of ~25 min week-1 . No changes were observed in obesity-related outcomes; waist circumference (P = 0.06), body mass (P = 0.05) and body mass index (P = 0.35). eHealth interventions are effective at increasing min week-1 of moderate-to-vigorous physical activity among working-age women from high income countries.

Pulmonary hypertension: clinical manifestations, classification and diagnosis.

Dyspnoea on exertion is the most common presenting symptom of pulmonary hypertension (PH), often a progressive and ultimately fatal condition. However, the presenting manifestations are protean, and more subtle features such hoarseness (caused by compression of the left recurrent laryngeal nerve) challenge master clinicians. Clinician scientists have refined the clinical classification in a manner that aids in accurate diagnosis and facilitates communication among healthcare providers and research investigators. Diagnostic algorithms emphasize confirmation and characterization of PH by catheterisation as well as differentiating between the current classes based upon essential and contingent diagnostic tests.

Treatment with epoprostenol of pulmonary arterial hypertension following mitral valve replacement for mitral stenosis.

Pulmonary hypertension frequently complicates mitral stenosis. Increased pulmonary artery pressure results from raised left atrial pressure, pulmonary arteriolar constriction, and obliterative changes in the pulmonary vascular bed, and usually responds to surgical relief of mitral stenosis. However, severe pulmonary hypertension may persist after surgical treatment of mitral stenosis. We describe a patient whose severe pulmonary hypertension following mitral valve replacement was treated successfully with continuous intravenous epoprostenol.

Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia.

BACKGROUND: Mutations of the transforming growth factor beta (TGFbeta) receptor components ENDOGLIN and ALK-1 cause the autosomal dominant vascular disorder hereditary haemorrhagic telangiectasia (HHT). Heterozygous mutations of the type II receptor BMPR2 underlie familial primary pulmonary hypertension. OBJECTIVE: To investigate kindreds presenting with both pulmonary hypertension and HHT. METHODS: Probands and families were identified by specialist pulmonary hypertension centres in five countries. DNA sequence analysis of ALK-1, ENDOGLIN, and BMPR2 was undertaken. Cellular localisation was investigated by heterologous overexpression of mutant constructs in both BAEC and HeLa cells. The impact of a novel sequence variant was assessed through comparative analysis and computer modelling. RESULTS: Molecular analysis of 11 probands identified eight missense mutations of ALK-1, one of which was observed in two families. Mutations were located within exons 5 to 10 of the ALK-1 gene. The majority of ALK-1 mutant constructs appeared to be retained within the cell cytoplasm, in the endoplasmic reticulum. A novel GS domain mutation, when overexpressed, reached the cell surface but is predicted to disrupt conformational changes owing to loss of a critical hydrogen bond. Two novel missense mutations were identified in ENDOGLIN. CONCLUSIONS: The association of pulmonary arterial hypertension and HHT identifies an important disease complication and appears most common among subjects with defects in ALK-1 receptor signalling. Future studies should focus on detailed molecular analysis of the common cellular pathways disrupted by mutations of ALK-1 and BMPR2 that cause inherited pulmonary vascular disease.

Tetracycline aspiration. Case report and review of the literature.

A 74-year-old woman presented with a 2-day history of cough, dyspnea and wheezing following aspiration of a tetracycline tablet. She developed a left lower lobe pneumonitis, and bronchoscopy revealed left main bronchus narrowing and exudate. The course of this patient is discussed in reference to the available literature on toxic aspirations.

Pulmonary embolism diagnosis in hospitalized and intensive care unit patients.

The diagnosis of acute pulmonary embolism (PE) remains difficult, and diagnostic strategies must consider the unique challenges of hospitalized and critically ill patients. Diagnostic algorithms that are effective and safe for outpatients may not be effective and safe for inpatients or patients in intensive care units. For example, serial compression ultrasonography (US) of the lower extremities may allow physicians to avoid pulmonary angiography for stable inpatients or outpatients, but this strategy is not validated for patients who require intensive care for serious underlying cardiopulmonary disease. Helical computed tomography (CT) is particularly suited for the evaluation of suspected PE for inpatients with serious cardiopulmonary disease. However, the safety of withholding treatment when a helical CT pulmonary angiogram is negative remains to be demonstrated. Lung perfusion and ventilation scans combined with an assessment of pretest probability remain important objective tests for the evaluation of many hospitalized patients.

Chest radiographs in acute pulmonary embolism. Results from the International Cooperative Pulmonary Embolism Registry.

OBJECTIVES: To characterize chest radiographic interpretations in a large population of patients who have received a diagnosis of acute pulmonary embolism and to estimate the sensitivity and specificity of chest radiographic abnormalities for right ventricular hypokinesis that has been diagnosed by echocardiography. DESIGN: A prospective observational study at 52 hospitals in seven countries. PATIENTS: A total of 2,454 consecutive patients who had received a diagnosis of acute pulmonary embolism between January 1995 and November 1996. RESULTS: Chest radiographs were available for 2,322 patients (95%). The most common chest radiographic interpretations were cardiac enlargement (27%), normal (24%), pleural effusion (23%), elevated hemidiaphragm (20%), pulmonary artery enlargement (19%), atelectasis (18%), and parenchymal pulmonary infiltrates (17%). The results of chest radiographs were abnormal for 509 of 655 patients (78%) who had undergone a major surgical procedure within 2 months of the diagnosis of pulmonary embolism: normal results for chest radiograph often accompanied pulmonary embolism after genitourinary procedures (37%), orthopedic surgery (29%), or gynecologic surgery (28%), whereas they rarely accompanied pulmonary emboli associated with thoracic procedures (4%). Chest radiographs were interpreted to show cardiac enlargement for 149 of 309 patients with right ventricular hypokinesis that was detected by echocardiography (sensitivity, 0.48) and for 178 of 485 patients without right ventricular hypokinesis (specificity, 0.63). Chest radiographs were interpreted to show pulmonary artery enlargement for 118 of 309 patients with right ventricular hypokinesis (sensitivity, 0.38) and for 117 of 483 patients without right ventricular hypokinesis (specificity, 0.76). CONCLUSIONS: Cardiomegaly is the most common chest radiographic abnormality associated with acute pulmonary embolism. Neither pulmonary artery enlargement nor cardiomegaly appears sensitive or specific for the echocardiographic finding of right ventricular hypokinesis, an important predictor of mortality associated with acute pulmonary embolism.

Ardeparin sodium for extended out-of-hospital prophylaxis against venous thromboembolism after total hip or knee replacement. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: The optimal duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain. OBJECTIVE: To determine the efficacy and safety of extended out-of-hospital prophylaxis with low-molecular-weight heparin (ardeparin sodium). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 33 community, university, or university-affiliated hospitals. PATIENTS: 1195 adults who had elective total hip or knee replacement and completed 4 to 10 days of postoperative ardeparin prophylaxis. INTERVENTION: Daily subcutaneous ardeparin (100 anti-Xa IU/kg of body weight) or placebo from time of hospital discharge to 6 weeks after surgery. MEASUREMENTS: Symptomatic, objectively documented venous thromboembolism or death, along with major bleeding, from time of hospital discharge to 12 weeks after surgery. RESULTS: Patients who received ardeparin (n = 607) and those who received placebo (n = 588) did not differ significantly in the cumulative incidence of venous thromboembolism or death (9 cases [1.5%] compared with 12 cases [2.0%]; odds ratio, 0.7 [95% CI, 0.3 to 1.7]; P > 0.2; absolute difference, -0.56 percentage points [CI, -2.2 to 1.1 percentage points]) or major bleeding (2 cases [0.3%] compared with 3 cases [0.5%]). CONCLUSIONS: Among patients who had total knee or total hip replacement and received 4 to 10 days of postoperative ardeparin prophylaxis, the cumulative incidence of symptomatic venous thromboembolism or death after hospital discharge was not significantly reduced by extended out-of-hospital ardeparin prophylaxis. Extended ardeparin use could provide a maximum 2.2-percentage point true reduction in such events. The benefit of extended ardeparin use is not clinically important for most patients. Future research should identify high-risk patients who would benefit most from extended prophylaxis.

Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.

BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.

The diagnostic approach to deep venous thrombosis.

Accurate diagnosis of deep vein thrombosis is important because untreated deep vein thrombosis can cause death or permanent impairment and because effective treatments are available. The approach to the diagnosis of deep vein thrombosis varies because of differences in local resources and expertise. Duplex ultrasonography with venous compression is the preferred initial test for the majority of outpatients who present with symptoms and signs that suggest acute deep vein thrombosis. Clinical outcome studies have shown the safety of withholding anticoagulants when two compression ultrasonography examinations are negative over a 5- to 7-day period. Alternative strategies, for example, combining clinical scores and D-dimer with compression ultrasonography, may also prove effective. In unusual circumstances, venography or even magnetic resonance imaging may be necessary.

Calf-thigh sequential pneumatic compression compared with plantar venous pneumatic compression to prevent deep-vein thrombosis after non-lower extremity trauma.

OBJECTIVE: To compare the effectiveness of calf-thigh sequential pneumatic compression devices with the effectiveness of plantar venous intermittent pneumatic compression devices in prevention of venous thrombosis after major trauma. SUBJECTS AND METHODS: We evaluated 181 consecutive patients after major trauma without lower extremity injuries that precluded the use of pneumatic compression devices. We randomly assigned 149 patients to either calf-thigh sequential pneumatic compression or plantar venous pneumatic compression. After blinding the observers to the method of prophylaxis against deep-vein thrombosis, we performed bilateral compression ultrasonography on or before day 8 after randomization. RESULTS: Among 149 randomized patients, 62 who received calf-thigh sequential pneumatic compression and 62 who received plantar venous intermittent pneumatic compression devices completed the trial. Thirteen patients randomized to plantar venous intermittent pneumatic compression (21.0%) and 4 patients randomized to calf-thigh sequential pneumatic compression (6.5%) had deep-vein thrombosis (p = 0.009). Seven of 13 patients with deep-vein thrombosis after prophylaxis with plantar venous intermittent pneumatic compression had bilateral deep-vein thromboses, whereas all 4 patients with deep-vein thrombosis after prophylaxis with calf-thigh sequential pneumatic compression had unilateral deep-vein thrombosis. CONCLUSION: Calf-thigh sequential pneumatic compression prevents deep-vein thrombosis more effectively than plantar venous intermittent pneumatic compression after major trauma without lower extremity injuries.

Factor V Leiden is not common in patients diagnosed with primary pulmonary hypertension.

Substantial evidence suggests that thrombosis contributes to the pathogenesis of primary pulmonary hypertension (PPH). An abnormal factor V (factor V Leiden) may contribute to thrombosis in the pulmonary microcirculation of PPH patients. A point mutation in which adenine is substituted for guanine at nucleotide 1691 (1691A) alters factor V so that it resists cleavage by activated protein C. Heterozygosity for the 1691A mutation is more common (2-8%) in Caucasian Europeans and Americans than in Africans (1%) and Asians (<1%). The aim of the study was to examine the prevalence of the mutation that codes for factor V Leiden in individuals with PPH. We identified 42 Caucasians diagnosed with PPH. We extracted deoxyribonucleic acid (DNA) from whole blood and assayed DNA samples for the point mutation (1691 A) that codes for factor V Leiden. One out of 42 (2.4%; 95% confidence interval=0.1-12.6) Caucasians diagnosed with PPH was heterozygous for the normal 1691G and mutant 1691A allele. All 10 individuals with familial PPH were homozygous for the normal 1691G allele. The prevalence of heterozygosity for the 1691A allele and the normal 1691G allele does not differ from that observed in reference (control) populations. The low prevalence of the 1691A mutation among individuals diagnosed with primary pulmonary hypertension provides evidence that factor V Leiden does not contribute to the pathogenesis of the disease in most patients.

Increased mortality of older patients with acute respiratory distress syndrome.

OBJECTIVE: To examine the relationship between age and mortality in ARDS patients and evaluate the importance of factors that increase the mortality of older ARDS patients. DESIGN: Prospective inception cohort study. SETTING: Community-based referral hospital. PATIENTS: Two hundred fifty-six ARDS patients identified from May 1987 to December 1990. ARDS was defined by the following: (1) PaO2/PAO2 < or = 0.2; (2) pulmonary capillary wedge pressure < or = 15 mm Hg; (3) total static thoracic compliance < or = 50 mL/cm H2O; (4) bilateral infiltrates on chest radiograph; and (5) an appropriate clinical setting for ARDS. MAIN OUTCOME MEASURES: Comparison of organ failure, incidence of sepsis, patient demographics, arterial oxygenation, and level of support in those 55 years and younger and those older than 55 years of age. Withdrawal of support in patients who died. RESULTS: Seventy-two of 112 patients older than 55 years (64%) died vs 65 of 144 patients 55 years and younger (45%) (p = 0.002). Examination of patient groups using age identified older than 55 years as a "cutpoint" above which mortality was greater (p = 0.002). Older nonsurvivors did not differ from nonsurvivors 55 years or younger with respect to gender, smoking history, ARDS risk factors, ARDS identifying characteristics, APACHE II (acute physiology and chronic health evaluation), number of organ failures, or the incidence of sepsis. In the 48 h prior to death, nonsurvivors 55 years and younger had more organ failure (3.4 +/- 0.2 vs 2.8 +/- 0.2; p = 0.03), higher fraction of inspired oxygen (0.82 +/- 0.03 vs 0.68 +/- 0.03; p = 0.008), and higher positive end-expiratory pressure levels (13 +/- 1 vs 8 +/- 1; p = 0.001) than older nonsurvivors. Despite more severe expression of disease, only 32 (50%) nonsurvivors 55 years and younger had support withdrawn. Significantly more nonsurvivors older than 55 years (73%) had support withdrawn (p = 0.009). Even in the absence of chronic disease states, withdrawal was more likely for patients older than 55 years (21/51) than in those 55 years and younger (3/32; p < 0.001). CONCLUSIONS: Mortality is significantly higher for patients with ARDS older than 55 years. Decisions to withdraw support are made more often in ARDS patients older than 55 years. These data suggest that age bias may influence decisions to withdraw support.

Treatment of proximal vein thrombosis with subcutaneous low-molecular-weight heparin vs intravenous heparin. An economic perspective.

BACKGROUND: Subcutaneous low-molecular-weight heparin is at least as effective and safe as classic intravenous heparin therapy for the treatment of proximal vein thrombosis. Anticoagulant monitoring is not required with low-molecular-weight heparin. OBJECTIVE: To perform an economic evaluation of these therapeutic approaches by comparing cost and effectiveness. PATIENTS AND METHODS: A randomized trial in 432 patients with proximal vein thrombosis that compared intravenous heparin and low-molecular-weight heparin with objective documentation of clinical outcomes provided the opportunity to perform an analysis of cost-effectiveness to rank these alternative therapies in terms of both their cost and effectiveness. The economic viewpoint of this analysis was that of a third-party payer (ie, a ministry of health in Canada or an insurance company in the United States). RESULTS: In the intravenous heparin-treated group, the cost incurred for 100 patients was $414,655 (Canadian dollars) or $375,836 (US dollars), with a frequency of objectively documented venous thromboembolism of 6.9%. In the low-molecular-weight heparin-treated group, the cost incurred for 100 patients was $399,403 (Canadian dollars) or $335,687 (US dollars), with a frequency of objectively documented venous thromboembolism of 2.8%, thus providing a cost saving of $15,252 (Canadian dollars) or $40,149 (US dollars). Multiple sensitivity analyses were performed, and these procedures did not alter the findings of the study. CONCLUSIONS: The findings indicate that low-molecular-weight heparin therapy is at least as effective and safe but less costly than intravenous heparin treatment. The potential for outpatient therapy in up to 37% of patients who are receiving low-molecular-weight heparin would substantially augment the cost saving.

Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep vein thrombosis after hip or knee implantation. An economic perspective.

BACKGROUND: Postoperative venous thrombosis and pulmonary embolism present a major clinical threat to patients undergoing total hip or knee arthroplasty. We performed an economic evaluation of warfarin sodium and subcutaneous low-molecular-weight heparin sodium prophylaxis comparing cost and effectiveness. METHODS: A consecutive series of 1436 patients who underwent hip or knee arthroplasty comparing these 2 regimens in a randomized trial with objective documentation of outcomes provided the opportunity to perform economic evaluations for Canada and the United States. RESULTS: Deep vein thrombosis was documented in 231 (37.4%) of 617 patients given warfarin and in 185 (31.4%) of 590 patients given low-molecular-weight heparin (P = .03). In Canada, warfarin and low-molecular-weight heparin (tinzaparin sodium) incurred costs per 100 patients of $11,598 and $9,197, respectively, providing a cost savings of $2,401 for the low-molecular-weight heparin group. The drug cost of low-molecular-weight heparin (tinzaparin) was $6 per day and for warfarin was $0.32 per day. Sensitivity analysis showed that low-molecular-weight heparin is more costly if drug costs are increased by 1.5-fold (ie, the cost of tinzaparin is increased from $6 per day to $8.82 per day or more). In the United States, the analysis was also not definitive; low-molecular-weight heparin was more costly than warfarin at drug costs of $15 and $2.01 per day, respectively. CONCLUSIONS: Our findings indicate that the decision to use low-molecular-weight heparin or warfarin prophylaxis in patients undergoing major joint replacement surgery is a finely tuned trade-off. Prophylaxis with low-molecular-weight heparin is equally or more effective than the more complex prophylaxis with warfarin. Major bleeding is uncommon but less frequent with warfarin use. The most significant parameters that influence the comparative cost-effectiveness are the cost of the drug, the cost of international normalized ratio monitoring, and the costs associated with major bleeding. The analysis also demonstrates that the results are health care system dependent (Canada vs US). In Canada, low-molecular-weight heparin (tinzaparin) is less costly because it avoids the need for international normalized ratio monitoring. In the United States, the drug cost for low-molecular-weight heparin will likely be the principal determinant of relative cost-effectiveness.

Efficacy and safety of low molecular weight heparin (ardeparin sodium) compared to warfarin for the prevention of venous thromboembolism after total knee replacement surgery: a double-blind, dose-ranging study. Ardeparin Arthroplasty Study Group.

UNLABELLED: We performed a double-blind, randomized clinical trial to compare the efficacy and safety of three different subcutaneous (s.c.) low molecular weight heparin doses (ardeparin sodium 25, 35, or 50 anti-Xa U/kg twice daily [BID]) to adjusted-dose warfarin (international normalized ratio [INR] = 2.0 to 3.0), as venous thromboembolism prophylaxis after total knee replacement surgery. The primary endpoint was total venous thromboembolism prevalence, defined as deep vein thrombosis discovered at postoperative venography of the operated leg, or symptomatic, objectively-documented pulmonary embolism. Of 860 patients randomized, 680 (79%) had an evaluable venogram or pulmonary embolism. The total venous thromboembolism prevalence was significantly greater among patients prophylaxed with warfarin compared to ardeparin 50 BID (38% vs 27%, p = 0.019); the prevalence among ardeparin 25 BID (37%) and 35 BID (28%) patients was similar to warfarin and ardeparin 50 BID patients, respectively. Overt bleeding occurred in 22 (7.9%) ardeparin 50 BID patients compared to 12 (4.4%) warfarin patients (p = 0.08), and in seven ardeparin 25 and 35 BID patients each (5.2% and 5.0%, respectively). Compared to the warfarin group, blood loss was significantly greater in the ardeparin 50 and 25 BID groups, and not different in the ardeparin 35 BID group. CONCLUSIONS: Postoperative, unmonitored, fixed-dose ardeparin 50 anti-Xa U/kg s.c. BID is significantly more effective than adjusted-dose warfarin for this indication. Although overt bleeding among warfarin and ardeparin 50 BID patients did not differ significantly, ardeparin 50 BID patients had significantly greater blood loss. Ardeparin 35 anti-Xa U/kg s.c.BID may provide efficacy similar to ardeparin 50 anti-Xa U/kg s.c. BID but with reduced bleeding.

Embolectomy, catheter extraction, or disruption of pulmonary emboli: editorial review.

Hippocrates said, "For extreme illness, extreme measures are warranted." Massive pulmonary embolism is an uncommon clinical problem for which extreme measures, such as surgical embolectomy, appear warranted. Since the application of cardiopulmonary bypass to surgical embolectomy in 1961, a number of uncontrolled retrospective case series suggest that nearly one half of patients survive when they undergo emergent embolectomy, in spite of preoperative cardiac arrest. Transvenous catheter embolectomy or catheter disruption of thrombi offers alternatives for hypotensive patients who do not require cardiopulmonary resuscitation. In addition, pulmonary artery stent placement can improve pulmonary artery flow for selected patients who have massive pulmonary embolism.

Physician-guided treatment compared with a heparin protocol for deep vein thrombosis.

BACKGROUND: Effective heparin therapy, defined by therapeutic prolongation of the activated partial thromboplastin time (APTT), decreases the risk of recurrent venous thromboembolism. Achieving therapeutic prolongation of the APTT within 24 hours of the start of heparin therapy has proved difficult. We hypothesized that a protocol that delivered high initial heparin infusions to patients without identifiable risk for bleeding complications would decrease the time to achieve a therapeutic anticoagulant effect without increasing the incidence of major bleeding complications. METHODS: To test this hypothesis, we studied concurrent patient cohorts. We defined a therapeutic anticoagulant effect (APTT > 55 seconds) to be an APTT more than 1.5 times the upper limit of normal. Twenty patients with acute symptomatic deep vein thrombosis received a 5000-U heparin bolus, followed by 1680 U/h (low risk to bleed) or 1240 U/h (high risk to bleed), adjusted by protocol-directed response to APTT results. Forty-eight patients with deep vein thrombosis were treated by their physicians. The Kaplan-Meier method was used to examine the proportion of patients who achieved an APTT greater than 55 seconds as a function of time. RESULTS: The two study cohorts did not differ with respect to age, weight, or risk factors for venous thromboembolism. Analysis of Kaplan-Meier curves showed that the heparin protocol decreased the time to achieve a therapeutic anticoagulant effect (P = .025). Ten (91%) of 11 patients (95% confidence interval, 59% to 100%) without risks to bleed who were treated by the heparin protocol and 29 (60%) of 48 patients (95% confidence interval, 45% to 74%) not treated by the protocol had an initial therapeutic APTT (P = .006). CONCLUSION: A protocol that delivers higher initial heparin infusions to patients without identifiable risks for bleeding decreases the time needed to achieve therapeutic prolongation of APTT, when compared with nonprotocol physician management.