Intensities Of Treatment Research Articles

Comparative effects of more versus less aggressive treatment with statins on the long-term outcome of patients with acute ischemic stroke

Background and aimsThere are no studies that compared the effects of different intensities of statin treatment on the long-term outcome of patients with recent ischemic stroke. We aimed to evaluate these effects. MethodsWe prospectively studied 436 consecutive patients who were discharged after acute ischemic stroke (39.2% males, age 78.6 ± 6.7 years). Statin treatment was categorized in equipotent doses of atorvastatin. One year after discharge, the functional status was assessed with the modified Rankin scale (mRS). Adverse outcome was defined as mRS between 2 and 6. The occurrence of ischemic stroke, myocardial infarction and death was recorded. ResultAdverse outcome rates were lower in patients treated with atorvastatin 20 mg/day or more potent doses of statins than in patients treated with atorvastatin 10 mg/day (63.5, 38.2 and 48.2%, respectively; p = 0.004). In binary logistic regression analysis, independent predictors of adverse outcome were the mRS at discharge (relative risk (RR) 2.33, 95% confidence interval (CI) 1.77–3.07, p < 0.001) whereas more aggressive treatment with statins independently predicted favorable outcome (atorvastatin 20 vs. 10 mg/day, RR 0.30, 95% CI 0.11–0.87, p = 0.026; atorvastatin 40 mg/day or more potent dose of statins vs. atorvastatin 10 mg/day, RR 1.66, 95% CI 0.62–4.44, p = NS). The incidence of cardiovascular events and all-cause mortality showed a trend for being lower in patients treated with atorvastatin 40–80 mg/day or rosuvastatin 10–40 mg/day than in those treated with less potent doses of statins. ConclusionMore aggressive statin treatment improves the long-term functional outcome of patients with acute ischemic stroke more than less aggressive treatment.

Effect of Magnetic Water Supplied to Trickle Source on the Water Movement and Moisture Content Distribution in Soil

Many new studies suggest into the possibility of obtaining positive results when exposing the water to the magnetic field of the particular iceberg, where this lead to change some properties of the water, and that the main objective for the design of systems of drip irrigation is to reduce the losses water that occur as a result of deep penetration or surface runoff. The objective of this research is to study the effect of treatment magnetism on the movement of water and the distribution of moisture in the soil, where this study included a 17 tests using three rates of addition of water (1.8, 2.4, 3.0) cm3/min/cm and four intensities of magnetic water treatment (500, 1000, 1500, 2000), in addition to the use of normal salty water and salty water treated magnetically. The results show that the wetting front of water treated magnetically, whether sweet or salty, progressing faster through the soil than the wetting front of normal water (without treatment) at all adding rates of water, where the increasing percent in the size of the wetted area of soil when using the magnetically treated water with intensity of 2000 gauss is 12 % and 18 % and 15.3 % for adding rates 1.8 and 2.4 and 3.0 cm3/min /cm , respectively, also, the moisture content of the soil as well as the proliferation and homogeneity was higher in the case of the using magnetically treated water.

Realidad virtual con fines terapéuticos en pacientes con ictus: revisión sistemática

IntroductionVirtual reality (VR) is used in the field of rehabilitation/physical therapy to improve patients’ functional abilities.The last 5 years have yielded numerous publications on the use of VR in patients with neurological disease which aim to establish whether this therapeutic resource contributes to the recovery of motor function. DevelopmentThe following databases were reviewed: Cochrane Original, Joanna Briggs Connect, Medline/Pubmed, Cinahl, Scopus, Isi Web of Science, and Sport-Discus.We included articles published in the last 5 years in English and/or Spanish, focusing on using RV to improve motor function in patients with stroke.From this pool, we selected 4 systematic reviews and 21 controlled and/or randomised trials. Most studies focused on increasing motor function in the upper limbs, and/or improving performance of activities of daily living. An additional article examines use of the same technique to increase motor function in the lower limb and/or improve walking and static-dynamic balance. Discussion and conclusionsStrong scientific evidence supports the beneficial effects of VR on upper limb motor recovery in stroke patients. Further studies are needed to fully determine which changes are generated in cortical reorganisation, what type of VR system is the most appropriate, whether benefits are maintained in the long term, and which frequencies and intensities of treatment are the most suitable.

Systemic Vascular Safety of Ranibizumab for Age-Related Macular Degeneration: Systematic Review and Meta-analysis of Randomized Trials

We conducted a meta-analysis of randomized trials of ranibizumab for age-related macular degeneration (AMD) to elucidate systemic vascular risk. Although intravitreal vascular endothelial growth factor inhibitors are widely used to treat AMD, whether they produce systemic adverse effects remains uncertain. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials through March 2014 to identify the randomized trials that compared systemic safety among different intensities of ranibizumab treatment for AMD. The outcome measures were the incidence of cerebrovascular accidents (CVAs), myocardial infarctions, nonocular hemorrhages, overall arterial thromboembolic events (ATEs), and all-cause mortality. We calculated the Peto odds ratio (OR) with 95% confidence interval for the comparisons between different intensities of regimens in terms of dose and retreatment frequency. Eleven trials comprising 6596 patients with AMD were included in the meta-analysis. A significant increase was observed in the following comparisons: 0.5 versus 0.3/0.0 mg for CVA (OR, 1.86; 95% CI, 1.05-3.29; P = 0.03), monthly versus pro re nata (PRN)/0.0 mg for CVA (OR, 1.89; 95% CI, 1.06-3.38; P = 0.03), and 0.3/0.5 versus 0.0 mg for nonocular hemorrhage (OR, 1.57; 95% CI, 1.01-2.44; P = 0.04). A nonsignificant increase was observed in the following comparisons: 0.5 versus 0.0 mg for CVA (OR, 2.27; 95% CI, 0.90-5.69; P = 0.08), monthly versus PRN for CVA (OR, 2.04; 95% CI, 0.94-4.45; P = 0.07), 0.5 versus 0.0 mg for nonocular hemorrhage (OR, 1.68; 95% CI, 0.98-2.88; P = 0.06), 0.3 versus 0.0 mg for nonocular hemorrhage (OR, 1.68; 95% CI, 0.95-2.98; P = 0.07), monthly versus PRN/0.0 mg for nonocular hemorrhage (OR, 1.54; 95% CI, 0.98-2.42; P = 0.06), monthly versus PRN for ATE (OR, 1.58; 95% CI, 0.96-2.61; P = 0.07), and monthly versus PRN/0.0 mg for ATE (OR, 1.42; 95% CI, 0.99-2.05; P = 0.06). Among the other analyses, no protective or harmful effects of ranibizumab were observed. In ranibizumab treatment for patients with AMD, a possible relationship of more intensive treatment to more systemic vascular adverse events was identified, but no relationship with mortality was identified.

Influence of the Addition of Extruded Flours on Rice Bread Quality

AbstractThe extrusion may improve coeliac bread quality by modifying the functional properties of flour. This study investigates the influence of the substitution of 10% of rice flour by extruded rice flours (three intensities of treatment and two particle sizes) on the characteristics of gluten‐free bread (specific volume and texture) at constant consistency. The microstructure and rheology of the doughs obtained and their behavior during fermentation have also been analyzed. The extruded flours increase dough consistency, and the effect is more noticeable with increasing intensities of treatment. The use of extruded flours requires the addition of a larger volume of water to obtain a constant consistency. The addition of extruded flour decreases dough development, producing a lower specific volume and greater bread hardness. This effect is minimized by increasing the particle size. The staling of bread from 24 to 72 h is less noticeable with a larger particle size.Practical ApplicationsThis study evidences that the use of extruded flours in rice bread making allows increasing dough hydration and therefore the bread yield while decreasing bread staling. However, the correct selection of extrusion treatment and flour particle size is essential to achieve appropriate results, being preferable the use of coarse flours with more intense extrusion treatment.

Entry regulation and entrepreneurship: a natural experiment in German craftsmanship

This paper uses the 2004 amendment to the German Trade and Crafts Code as a natural experiment for assessing the causal effects of this reform on the probabilities of being self-employed and of transition into and out of self-employment. This is achieved by using repeated cross-sections (2002–2009) of German microcensus data. I apply the difference-in-differences technique for three groups of craftsmen which were subject to different intensities of treatment. The results show that the complete exemption from the educational entry requirement has fostered self-employment significantly by substantially increasing the entry probabilities, while exit rates have remained unaffected. I find similar, though weaker relative effects for the treatment groups that were subject to a reduction of entry costs or a partial exemption from the entry requirements. Moreover, I consider effect heterogeneity within each of the treatment groups with respect to gender and vocational training, and show that the deregulation of entry requirements has been most effective for untrained workers.

Conservative treatment options for women with stress urinary incontinence: clinical update

Conservative treatment options for women with stress urinary incontinence include lifestyle changes, pelvic floor muscle training, behavioural techniques, electrical stimulation and drugs, and combinations of these individual therapies. It would be very helpful to patients, primary care clinicians, and commissioners of services to know the relative worth of the wide variety of types and intensities of treatment currently offered to achieve greatest benefit from allocated resources. This article summarises the results of a recent Health Technology Assessment (HTA) commissioned by the UK Government’s National Institute for Health Research.1 ### Lifestyle For women who are overweight then participation in a supported weight-loss programme may improve incontinence. Other common-sense advice in terms of modification of fluid intake, smoking cessation, and resolving constipation may be worthwhile but lacks high-level evidence of benefit. ### Pelvic floor muscle training Pelvic floor muscle training (PFMT) aims to condition and strengthen the striated pelvic floor muscles through regular exercise in order to improve the urethral sphincter closure mechanism. The degree of patient training, supervision, intensity of exercise protocols, and follow-up varies, often related to local service provision and available expertise. In the UK the typical treatment protocol is two supervised sessions per month for 3 months.2 ### Vaginal cones Women can be instructed to retain graded weights (cones) for timed periods within the vagina as a conditioning exercise to improve pelvic floor muscle strength. The ability to retain increasing weights for longer and with added provocation gives an element of biofeedback as well as exercise. ### Behavioural therapy Bladder training is often used to help women regain continence particularly for those with mixed symptoms of stress and urgency …

Influence of technological processing on the allergenicity of tomato products

Tomato contains at least two different lipid transfer proteins (LTPs) that are responsible for the oral allergy syndrome. In this paper, our attention was addressed on the influence of two technological treatments (chemical peeling and thermal treatment) on IgE-binding capacity of tomato LTP. Chemical peeling did not significantly alter IgE-binding capacity of tomato LTP. IgE immunoblotting of whole fresh tomato and of the same after chemical peeling showed the same protein bands able to bind patients’ IgE. Furosine, an indicator of intensities of thermal treatment sustained by the products, was analyzed in some commercial tomato products of different types. Products with furosine index between 2.8 and 17.6 substantially presented the same immunoblotting pattern. The heat resistance of tomato LTP confirms once again the extreme stability of this allergen.

A Systematic Review of Common Physiotherapy Interventions in School-Aged Children with Cerebral Palsy

ABSTRACTThis systematic review focused on the common conventional physiotherapy interventions used with children with cerebral palsy (CP), aged 4 to 18 years, and critically appraised the recent evidence of each of these interventions using the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The search strategy yielded 34 articles after inclusion and exclusion criteria were applied. The investigated physiotherapy interventions included strength and functional training, weight-supported treadmill training (WBSTT), and neurodevelopmental treatment (NDT). A category of treatment dosage was also included. Strength training was the most studied intervention with significant improvements found in the strength of selected muscle groups using dynamometry, with fewer studies showing significant improvement in function. Functional training showed improvements in gross motor function, endurance, and temperospatial measures, such as gait speed and stride length. Nonsignificant trends of improvement on the Gross Motor Function Measure (GMFM) and gait velocity were found for WBSTT by a few studies with low levels of evidence (case series). Of three studies that evaluated NDT, one high-level evidence study, i.e., randomized controlled trial (RCT) found significant improvements on the GMFM. All studies reviewing treatment dosage had high levels of evidence (RCTs), yet found no significant differences for different intensities of treatment. These results indicate that the levels of evidence for physiotherapy interventions, particularly strengthening and to a lesser extent functional training, in school-aged children with CP has improved; however, further high-level evidence is needed for other interventions.

Effectiveness of Three Intensities of Smoking Cessation Treatment in Primary Care

The purpose of this study was to compare the effectiveness of three smoking cessation programs of varying intensity applied in a primary care setting. Participants were 89 individuals randomly assigned to one of three treatment groups: brief counseling plus information pamphlet, self-help program with telephone follow-up, and intensive behavioral treatment. At the 12-mo. follow-up, intensive behavioral treatment (42.8% abstinence) was more effective than the self-help program (27.5%), which was in turn more effective than counseling (12.9%). Continued abstinence was also higher in the intensive treatment group (37.9%) than in the self-help (17.2%) and the counseling groups (9.7%), although these differences only reached statistical significance in the first and third of these groups. Treatment adherence was higher in the intensive behavioral group (82.8% of participants attended all the sessions) than in the self-help group (61.8% completed the program). The results appear to confirm a dose-response effect in the treatment of smokers and indicate satisfactory acceptability of intensive behavioral programs applied in primary care.

Living tissue under treatment of cold plasma atmospheric jet

The interaction of the cold atmospheric plasma jet with fibroblast cells was studied. Plasma jet was initiated in the helium flow blowing through the syringe by application of high ac voltage to the discharge electrodes. The plasma jet had a length of 5cm and a diameter of 1.5–2mm in ambient air. Treatment of cells with plasma jet resulted in decreasing of cell migration rate, cell detachment, and appearance of “frozen” cells, while treatment with helium flow (no plasma) resulted in appearance of frozen cells only. A variety of cellular responses was explained by different intensities of treatment.

Effects of Pulsed Low-Intensity Ultrasound on Human Child Chondrocytes

The effect of pulsed low-intensity ultrasound (PLIUS) on human articular chondrocytes was evaluated in an in vitro 3-D agarose gel culture model. Chondrocytes isolated from young children's articular cartilage of ablated polydactylia were embedded in gel after expansion and exposed to PLIUS on the third day after embedding. Another group of cells was exposed to sham PLIUS as a control. Different intensities of PLIUS treatment—18 mW/cm 2, 48 mW/cm 2, 72 mW/cm 2 and 98 mW/cm 2 (1.0 MHz, with burst duration of 200 μs repeated at 1.0 kHz)—were administered for 20 min/d, and the medium was replaced twice a week. The cultures were evaluated for aggrecan synthesis by enzyme-linked immunosorbent assay (ELISA), type II collagen production by Western blotting or ELISA and cell proliferation by total DNA measurement. The PLIUS was found to increase aggrecan synthesis in a time-dependent manner. The maximal response was observed at an intensity of 48 mW/cm 2. After 14 d of exposure at this intensity, the aggrecan synthesis was 214 ± 26% of control, and type II collagen synthesis was 148.5 ± 8.0% of control. However, PLIUS treatment revealed no significant influence on cell proliferation, confirming that the stimulation of aggrecan and type II collagen synthesis by PLIUS was not the result of an increase in chondrocyte cell proliferation. In addition, it was found that human chondrocytes harvested from older donors become less responsive to PLIUS. From this in vitro 3-D study of cultured human chondrocytes, our findings suggest that PLIUS may be applied to the tissue engineering of cartilage constructs. (E-mail: d740113@kmu.edu.tw)

Microenvironments for Forest-Farming of Medicinal Herbs in Varying Forest Structures of the Midwestern USA

ABSTRACT To examine the potential for forest-farming production of medicinal plants in the temperate hardwood forests of the eastern US, forest floor microenvironments were examined in a chronosequence of even-aged forests and in canopy gaps of an uneven-aged forest in the midwestern US. Measurements of light, air and soil temperature, relative humidity, and vapor pressure deficit were taken on a diurnal basis several times each month during the growing season. In canopy gaps, measurements were taken along transects from the gap center into interior forest cover. Results showed that all of the microenvironmental variables are influenced by stand structure and age and thus influence the growth environment for forest-farming production. Soil and air temperatures were the most stable parameters with greater diurnal variation in air temperatures, relative humidity, and vapor pressure deficits. Light was the most variable parameter measured in both forest structures, ranging from near full sunlight in canopy gaps to less than 2% of full sunlight under the canopies of older forests. Spatial variability of light was very high in uneven-aged forest, and interior conditions were found beyond 8 m from a gap center. Temporal variability in both forest structures was also significant, with daily and seasonal patterns for most microenvironmental variables. Significant interactions among structural, spatial, and temporal variables precluded simple summarization of main parameter effects. With both even and uneven-aged stand structures, silvicultural manipulation would likely be needed to optimize conditions for a range of understory plants that could be produced on a commercial basis. However, the different structures imply different treatments and intensities of treatment, with scheduling being a function of the microenvironmental requirements of specific forest-farming crops.

Growth inhibition of high-intensity focused ultrasound on hepatic cancerin vivo

To investigate the damaging effect of high-intensity focused ultrasound (HIFU) on cancer cells and the inhibitory effect on tumor growth. Murine H22 hepatic cancer cells were treated with HIFU at the same intensity for different lengths of time and at different intensities for the same length of time in vitro, the dead cancer cells were determined by trypan blue staining. Two groups of cancer cells treated with HIFU at the lowest and highest intensity were inoculated into mice. Tumor masses were removed and weighed after 2 wk, tumor growth in each group was confirmed pathologically. The death rate of cancer cells treated with HIFU at 1 000 W/cm2 for 0.5, 1, 2, 4, 8, and 12 s was 3.11+/-1.21%, 13.37+/-2.56%, 38.84+/-3.68%, 47.22+/-5.76%, 87.55+/-7.32%, and 94.33+/-8.11%, respectively. A positive relationship between the death rates of cancer cells and the length of HIFU treatment time was found (r = 0.96, P<0.01). The death rate of cancer cells treated with HIFU at the intensity of 100, 200, 400, 600, 800, and 1 000 W/cm2 for 8 s was 26.31+/-3.26%, 31.00+/-3.87%, 41.97+/-5.86%, 72.23+/-8.12%, 94.90+/-8.67%, and 99.30+/-9.18%, respectively. A positive relationship between the death rates of cancer cells and the intensities of HIFU treatment was confirmed (r = 0.98, P<0.01). The cancer cells treated with HIFU at 1 000 W/cm2 for 8 s were inoculated into mice ex vivo. The tumor inhibitory rate was 90.35% compared to the control (P<0.01). In the experimental group inoculated with the cancer cells treated with HIFU at 1 000 W/cm2 for 0.5 s, the tumor inhibitory rate was 22.9% (P<0.01). By pathological examination, tumor growth was confirmed in 8 out of 14 mice (57.14%, 8/14) inoculated with the cancer cells treated with HIFU at 1 000 W/cm2 for 8 s, which was significantly lower than that in the control (100%, 15/15, P<0.05). HIFU is effective on killing or damage of H22 hepatic cancer cells in vitro and on inhibiting tumor growth in mice ex vivo.

Does intensive rehabilitation improve the functional outcome of patients with traumatic brain injury? Interim result of a randomized controlled trial

To evaluate the effects of intensive rehabilitation on the functional outcome in patients with traumatic brain injury (TBI), we carried out a randomized controlled assessor-blind trial, comparing two groups of patients receiving different intensities of rehabilitation treatment (2 versus 4 h per day). Patients with moderate and severe TBI, aged from 12 to 65 years, were included. Glasgow Outcome Scale (GOS) and Functional Independent Measurement (FIM) were assessed monthly. The interim results of 36 cases showed that there was a trend of more patients in the study group achieving full FIM scores, and good GOS at 2 and 3 months, but the control group appeared to be catching up towards 6 months. Intensive rehabilitation may improve the early functional outcome of TBI patients. The interim results indicate that the study should be continued.

The effectiveness of two intensities of psychosocial treatment for cocaine dependence

Structured treatments for cocaine dependence have been shown to be effective despite high attrition rates. What is unclear is what level of treatment intensity is needed to improve and sustain patient outcomes, especially among low SES urban residents. This study evaluated whether there were differences between two levels of treatment intensities for cocaine dependence in reducing substance use and improving health and social indicators. Ninety-four cocaine dependent predominantly African-American male veterans were randomly assigned to either a 12 h/week day hospital program (DH12) or a 6 h/week outpatient program (OP6) and were evaluated at baseline, during treatment and at 4 and 7 months post-treatment. Both treatments stressed abstinence, behavior change and prosocial adjustment and only differed in level of treatment intensity. During treatment measures included urine toxicologies, program attendance, treatment completion and aftercare attendance. Participants reported a 52% reduction in days of cocaine use and experienced significant improvements in employment and psychiatric functioning at seven months post-treatment. However, there was no significant difference between the DH12 and OP6 programs in terms of abstinence during treatment, treatment completion, treatment or aftercare attendance or any Addiction Severity Index (ASI)-related variable assessing level of functioning at 4 and 7 months. While future research with a larger community-based sample that includes female clients is necessary, the current findings demonstrate that a 6 h/week program is just as effective and thus has a significant cost savings compared to a 12 h/week treatment modality for cocaine dependence.

Biologic factors determine prognosis in infants with stage IV neuroblastoma: A prospective Children's Cancer Group study.

A prospective Children's Cancer Group study, CCG-3881, has been completed to determine if a more accurate prediction of prognosis by biologic features can identify subgroups of infants with stage IV neuroblastoma (NBL) who require differing intensities of treatment. One hundred thirty-four infants were registered from June 1989 to August 1995, with a median follow-up of 47.1 months (range, 0 to 88 months). The biologic factors examined were tumor MYCN copy number, Shimada histopathologic classification, serum ferritin, and bone marrow immunocytology (sensitivity, one tumor cell per 10(5) bone marrow cells). Patients treated on CCG-3881 (n = 116) received four-drug chemotherapy for 9 months (cisplatin, cyclophosphamide, doxorubicin, and etoposide), with surgery and local radiation to residual disease. After January 1991, all subsequent infants with tumor MYCN amplification (n = 18) were transferred after one cycle of therapy to the high-risk CCG-3891 protocol (open January 1991 to April 1996) for more intensive treatment. The 3-year event-free survival (EFS) and overall survival (mean +/- SD) for the 134 infants were 63% +/- 5% and 71% +/- 5%, respectively. Patients whose tumors were without MYCN amplification had a 93% +/- 4% 3-year EFS, whereas those with amplified MYCN had a 10% +/- 7% 3-year EFS (P <. 0001). Each of the other biologic features studied had prognostic significance in univariate analysis but not after stratifying by MYCN copy number. Infants less than 1 year of age at diagnosis with stage IV NBL have a much improved outcome compared with children >/= 1 year of age. Nonamplified MYCN tumors identify a group of infants with a 93% +/- 4% EFS, whereas amplified MYCN copy number clearly identifies patients who are unlikely to survive despite intensive chemotherapy.

Energetic approach to kinetics of batch ball milling

Kinetics of batch milling is proposed to express with respect to energy instead of time. A model is applicable to various processes taking place in a mill (size reduction, mechanochemical transformation, etc.). A model is similar to classical chemical kinetics with the time substituted by the energy, and the temperature substituted by the intensity of treatment. Definition of the intensity is proposed for drum mills with loose ball media (tumbling, vibratory, planetary, and stirred mills). The general rate constant is introduced as a product of the temperature-dependent conventional rate constant and the intensity-dependent factor of energetic efficiency. A technique for determination of the energetic efficiency is proposed and illustrated with experiments. The energy-scaled model of milling kinetics makes possible the comparability of experimental data obtained in various mills under different intensities of treatment and, therefore, the mills scaling-up.

Energetic Approach to Kinetics of Mechanochemical Process

Kinetics of a mechanochemical process is proposed to describe quantitatively with a problem set-up scaled to energy instead of time. This makes possible the comparability of experimental data obtained in machines with different intensities of treatment.

Relation Between the Time to Achieve the Lower Limit of the APTT Therapeutic Range and Recurrent Venous Thromboembolism During Heparin Treatment for Deep Vein Thrombosis

Randomized trials have demonstrated the importance of achieving adequate heparinization early in the course of therapy. Recently, some authors reported a pooled analysis of selected studies in the literature that suggested that there is no convincing evidence that the risk of recurrent venous thromboembolism is critically dependent on achieving a therapeutic activated partial thromboplastin time result at 24 to 48 hours. We provide the analyses of patient groups entered into our series of 3 consecutive double-blind randomized trials evaluating initial heparin therapy for proximal deep venous thrombosis. Logistic regression analysis of the patient groups receiving the less intense initial intravenous heparin dose of 30,000 U/24 h demonstrated that subtherapy for 24 hours predicted the onset of venous thromboembolic events. Failure to achieve a therapeutic activated partial thromboplastin time by 24 hours was associated with a 23.3% frequency of venous thromboembolism vs 4% to 6% for those whose activated partial thromboplastin time exceeded the therapeutic threshold by 24 hours (P=.02). Time-to-event analysis shows the increased frequency of recurrent venous thromboembolic events during the period of study in patients who were subtherapeutic for 24 hours compared with those who were therapeutic (P=.001). Our findings reaffirm the clinical importance of rapidly achieving therapeutic levels of heparin. Patients who failed to achieve the therapeutic threshold by 24 hours were at an increased risk of subsequent recurrent venous thromboembolism. These findings are independently supported by the results of a randomized trial comparing different intensities of initial heparin treatment by continuous infusion.