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Biomedical subjects

P S Wells

Publications and source records attributed to P S Wells.

At least 19 recordsLinked to original sources

Protein C and protein S levels can be accurately determined within 24 hours of diagnosis of acute venous thromboembolism.

In the 50% of cases of acute idiopathic venous thromboembolism, laboratory testing for inherited causes is often performed. Most physicians are under the impression that assays for protein C and protein S should not be measured at the time of diagnosis because of a high false positive rate. We performed a prospective cohort study from two outpatient thromboembolism clinics on consecutive patients with an objectively confirmed diagnosis of first acute idiopathic venous thromboembolism. Assays for protein C and protein S were performed prior to the initiation of oral anticoagulation therapy and within 24 h of diagnosis of venous thromboembolism. Abnormal results were repeated when patients discontinued oral anticoagulant therapy. Of 253 patients tested for both protein C and protein S, 229 (91%; 95% confidence interval 87-94%) were negative and 484 of 508 (95%) tests were normal. Of the 24 initial abnormal results, 21 were repeated and 10 (48%; 95% confidence interval 26-70%) were still abnormal. Overall, 97.8% of initial protein C and protein S results were accurate. If protein C and protein S are measured at the time of diagnosis of acute venous thromboembolism, the majority of the results will be normal and false positives are uncommon.

Acute Disease↗

Accuracy of coding for possible warfarin complications in hospital discharge abstracts.

BACKGROUND: Hospital discharge abstracts could be used to identify complications of warfarin if coding for bleeding and thromboembolic events are accurate. OBJECTIVES: To measure the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9CM) codes for bleeding and thromboembolic diagnoses. SETTING: University affiliated, tertiary care hospital in Ottawa, Canada. PATIENTS: A random sample of patients discharged between September 1999 and September 2000 with an ICD-9-CM code indicating a bleeding or thromboembolic diagnosis. METHODS: Gold-standard coding was determined by a trained chart abstractor using explicit standard diagnostic criteria for bleeding, major bleeding, and acute thromboembolism. The abstractor was blinded to the original coding. We calculated the sensitivity, specificity, positive, and negative predictive values of the original ICD-9CM codes for bleeding or thromboembolism diagnoses. RESULTS: We reviewed 616 medical records. 361 patients (59%) had a code indicating a bleeding diagnosis, 291 patients (47%) had a code indicating a thromboembolic diagnosis and 36 patients (6%) had a code indicating both. According to the gold standard criteria, 352 patients experienced bleeding, 333 experienced major bleeding, and 188 experienced an acute thromboembolism. For bleeding, the ICD-9CM codes had the following sensitivity, specificity, positive and negative predictive values [95% CI]: 93% [90-96], 88% [83-91], 91% [88-94], and 91% [87-94], respectively. For major bleeding, the ICD-9CM codes had the following sensitivity, specificity, positive and negative predictive values: 94% [91-96], 83% [78-87], 87% [83-90], and 92% [88-95], respectively. For thromboembolism, the ICD-9CM codes had the following sensitivity, specificity, positive and negative predictive values: 97% [94-99], 74% [70-79], 62% [57-68], and 98% [96-99], respectively. By selecting a sub-group of ICD-9CM codes for thromboembolism, the positive predictive value increased to 87%. CONCLUSION: In our centre, the discharge abstract could be used to identify and exclude patients hospitalized with a major bleed or thromboembolism. If coding quality for bleeding is similar in other hospitals, these ICD-9-CM diagnostic codes could be used to study population-based warfarin-associated hemorrhagic complications using administrative databases.

Anticoagulants↗

A decision aid for autologous pre-donation in cardiac surgery--a randomized trial.

OBJECTIVES: The objective of this randomized, controlled study was to determine the usefulness of a decision aid on pre-donation of autologous blood before elective open heart surgery. METHODS: The decision aid (DA) group received a tape and booklet which described the options for peri-operative transfusion in detail. The no decision aid (NDA) group received information usually given to patients about autologous donation. RESULTS: A total of 120 patients were randomized. The DA group rated themselves better prepared for decision making and showed significant improvements in knowledge (p = 0.001) and realistic risk perceptions (p = 0.001). In both groups there was an increase in the proportion of patients choosing allogeneic blood between baseline and follow-up (p = 0.001). Patients in the DA group were significantly more satisfied with the amount of information they received, how they were treated and with the decision they made, than patients in the NDA group. CONCLUSION: The decision aid is useful in preparing patients for decision making. PRACTICE IMPLICATIONS: The next stage is to explore strategies to make it available to all appropriate patients.

Adult↗

The safety of dosing dalteparin based on actual body weight for the treatment of acute venous thromboembolism in obese patients.

Data evaluating the safety of using weight-based low-molecular-weight heparin in the treatment of obese patients with acute venous thromboembolism are limited. The product monograph of dalteparin suggests the maximum dose should be limited to 18,000 U subcutaneously once daily. There are no specific data regarding the risk of recurrence or bleeding in patients given dalteparin in a weight-based dose of 200 IU kg(-1). We report a retrospective chart review of 193 obese patients who weighed more than 90 kg and who received dalteparin at or near to 200 IU kg(-1) actual body weight for 5-7 days for acute venous thromboembolism with 90 day follow-up information. Of the patients, 77% had idiopathic venous thromboembolism, 16% had an underlying malignancy, and 7% had a transient risk factor. Warfarin was initiated within 2 days with a target International Normalized Ratio range of 2.0-3.0. All patients were followed for 12 weeks post diagnosis. Only two patients had a major hemorrhage, 4 and 8 weeks from diagnosis. This study supports the safety of dosing dalteparin based on actual body weight in obese patients.

Adult↗

Does the type of hormone replacement therapy influence the risk of deep vein thrombosis? A prospective case-control study.

BACKGROUND: Although hormone replacement therapy (HRT) is associated with an increased risk of deep vein thrombosis (DVT), it is not clear if the risk differs in users of combined estrogen-progestin HRT and estrogen-only HRT. METHODS: We prospectively studied postmenopausal women with suspected DVT in whom HRT use status was ascertained and who subsequently had objective diagnostic testing to confirm or exclude DVT. Cases were patients with idiopathic DVT, in whom there were no DVT risk factors, and controls were patients without DVT, in whom there were also no DVT risk factors. The risk of DVT was determined in users of estrogen-progestin HRT and estrogen-only HRT by comparing the prevalence of current HRT use in cases with idiopathic DVT and controls without DVT (reference group). Multivariable regression analysis was done to adjust for factors that might confound an association between HRT use and the risk of DVT. RESULTS: One thousand one hundred and sixty-eight postmenopausal women with suspected DVT were assessed, from whom 95 cases of idiopathic DVT and 610 controls without DVT and no DVT risk factors were identified. Estrogen-only HRT was associated with an increased risk for DVT that was not statistically significant [odds ratio (OR) = 1.22; 95% confidence interval (CI) 0.57, 2.61]. Estrogen-progestin HRT was associated with a greater than 2-fold increased risk for DVT (OR = 2.70; 95% CI 1.44, 5.07). CONCLUSION: The risk of developing DVT may be higher in users of combined estrogen-progestin HRT than in users of estrogen-only HRT.

Aged↗

Single-arm study of bridging therapy with low-molecular-weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin.

BACKGROUND: When warfarin is interrupted for surgery, low-molecular-weight heparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the efficacy and safety of bridging therapy with low-molecular-weight heparin initiated out of hospital. METHODS AND RESULTS: This was a prospective, multicenter, single-arm cohort study of patients at high risk of arterial embolism (prosthetic valves and atrial fibrillation with a major risk factor). Warfarin was held for 5 days preoperatively. Low-molecular-weight heparin was given 3 days preoperatively and at least 4 days postoperatively. Patients were followed up for 3 months for thromboembolism and bleeding. Eleven Canadian tertiary care academic centers participated; 224 patients were enrolled. Eight patients (3.6%; 95% CI, 1.8 to 6.9) had an episode of thromboembolism, of which 2 (0.9%; 95% CI, 0.2 to 3.2) were judged to be due to cardioembolism. Of these 8 episodes of thromboembolism, 6 occurred in patients who had warfarin deferred or withdrawn because of bleeding. There were 15 episodes of major bleeding (6.7%; 95% CI, 4.1 to 10.8): 8 occurred intraoperatively or early postoperatively before low-molecular-weight heparin was restarted, 5 occurred in the first postoperative week after low-molecular-weight heparin was restarted, and 2 occurred well after low-molecular-weight heparin was stopped. There were no deaths. CONCLUSIONS: Bridging therapy with subcutaneous low-molecular-weight heparin is feasible; however, the optimal approach for the management of patients who require temporary interruption of warfarin to have invasive procedures is uncertain.

Anticoagulants↗

Use of elastic compression stockings after deep venous thrombosis: a comparison of practices and perceptions of thrombosis physicians and patients.

Daily long-term use of elastic compression stockings (ECS) by patients with deep venous thrombosis (DVT) may help to prevent the post-thrombotic syndrome (PTS). However, the effectiveness of ECS in clinical practice is difficult to predict, since the practices and perceptions of patients and thrombosis physicians regarding ECS have not been documented. The objectives were to survey DVT patients and thrombosis physicians on their practices and perceptions regarding use of ECS after DVT, and to evaluate whether physician perceptions are supported by patient responses. Two surveys were conducted. The first was sent to 38 Canadian thrombosis physicians. The second was administered to 80 DVT patients attending Thrombosis Clinic at one of two Canadian university-affiliated hospitals. Most physicians believed that ECS were useful in preventing PTS and in managing venous symptoms. However, there was a lack of consensus regarding the optimal timing of initiation of ECS, duration of therapy, and compression strength, and only one-third routinely prescribed ECS to asymptomatic patients to prevent PTS. Most DVT patients who were prescribed ECS purchased them, 87% wore them daily, and most reported that ECS relieved swelling and symptoms. Physicians underestimated the degree of patient compliance with ECS, but correctly identified the main reasons for non-compliance. There is a lack of consensus among thrombosis physicians regarding ECS use after DVT. Patients with DVT are willing to comply with ECS therapy and most find them to be helpful. Our findings suggest that long-term study of the optimal use of ECS after DVT is both necessary and feasible.

Adult↗

Combined use of clinical assessment and d-dimer to improve the management of patients presenting to the emergency department with suspected deep vein thrombosis (the EDITED Study).

Suspected deep vein thrombosis (DVT) is a common problem facing emergency physicians. Timely diagnostic testing must be performed to accurately identify patients with DVT. The purpose of this study was to evaluate the safety and effectiveness of a management strategy that combined consideration of clinical pretest probability and a d-dimer test to evaluate patients presenting to the emergency department with suspected deep vein thrombosis (DVT). A prospective cohort study was performed in the emergency departments of four tertiary care institutions involving 1075 patients with suspected DVT. An emergency physician determined the pretest probability for DVT to be low, moderate, or high using an explicit clinical model. A blood sample was taken for d-dimer testing. Subsequent investigations (compression ultrasound, venography) were performed based upon the pretest probability and the d-dimer result. Patients considered at low pretest probability with negative d-dimer had no further diagnostic testing performed. All patients in whom the diagnosis of DVT was excluded by the algorithm did not receive anticoagulant therapy and were followed up for 90 days for the development of proximal DVT or pulmonary embolism. Overall, 195 (18.1%; 95% CI 15.9% to 20.6%) of 1075 patients were confirmed to have proximal DVT. Of the 882 patients who had proximal DVT excluded during the initial evaluation period using the algorithms, four (0.5%; 95% CI 0.1% to 1.2%) were subsequently diagnosed with proximal DVT in the follow-up period, including three patients in the low pretest probability group (1.0%; 95% CI 0.2% to 2.1%) who had normal d-dimer and no additional diagnostic testing performed. None of the 882 patients (0%: 95% CI 0% to 0.5%) developed pulmonary embolism in the follow-up period. A diagnostic strategy for the evaluation of patients with suspected DVT based on pretest probability and d-dimer is safe and feasible in the emergency department setting.

Adult↗

Gas-liquid chromatography with a volatile "stationary" liquid phase.

A unique type of gas-liquid chromatography is described in which both mobile and "stationary" phases are composed of synthetic mixtures of helium and carbon dioxide. At temperatures below the critical point of the binary mixture and pressures above the vapor pressure of pure liquid carbon dioxide, helium and carbon dioxide can form two immiscible phases over extended composition ranges. A binary vapor phase enriched in helium can act as the mobile phase for chromatographic separations, whereas a CO2-rich liquid in equilibrium with the vapor phase, but condensed on the column wall, can act as a pseudostationary phase. Several examples of chromatographic separations obtained in "empty" capillary columns with no ordinary stationary liquid phase illustrate the range of conditions that produce such separations. In addition, several experiments are reported that confirm the proposed two-phase hypothesis. The possible consequences of the observed chromatographic phenomenon in the field of supercritical fluid chromatography with helium headspace carbon dioxide are discussed.

Journal Article↗

Pre-operative autologous donation for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Public concerns regarding the safety of transfused blood have prompted re-consideration of the indications for the transfusion of allogeneic red cells (blood from an unrelated donor), and a range of techniques designed to minimise transfusion requirements. OBJECTIVES: To examine the evidence for the efficacy of pre-operative autologous blood donation (PAD) in reducing the need for peri-operative allogeneic red blood cell (RBC) transfusion. SEARCH STRATEGY: Articles were identified by: computer searches of OVID MEDLINE, EMBASE, and Current Contents (to March 2001) and web sites of international health technology assessment agencies (to January 2001). References in the identified trials were checked and authors contacted to identify additional studies. SELECTION CRITERIA: Randomised controlled trials with a concurrent control group in which adult patients, scheduled for non-urgent surgery, were randomised to PAD, or to a control group who did not receive the intervention. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al (1995) and Jadad et al (1996). The principle outcomes were: the number of patients exposed to allogeneic red blood cells, and the amount of blood transfused. Other clinical outcomes are detailed in the review. MAIN RESULTS: Overall PAD reduced the risk of receiving an allogeneic blood transfusion by a relative 63% (RR=0.37: 95%CI:0.26,0.54). The absolute reduction in risk of allogeneic transfusion was 43.8% (RD=-0.438: 95%CI: -0.607,-0.268). In contrast the results show that the risk of receiving any blood transfusion (allogeneic and/or autologous) is actually increased by pre-operative autologous blood donation (RR=1.29: 95%CI: 1.12,1.48). Trials were unblinded and allocation concealment was not described in 87.5% of the trials. REVIEWER'S CONCLUSIONS: Although the trials of PAD showed a reduction in the need for allogeneic blood the methodological quality of the trials was poor and the overall transfusion rates (allogeneic and/or autologous) in these trials were high, and were increased by recruitment into the PAD arms of the trials. This raises questions about the true benefit of PAD. In the absence of large, high quality trials using clinical endpoints, it is not possible to say whether the benefits of PAD outweigh the harms.

Blood Transfusion, Autologous↗

Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study.

OBJECTIVES: To determine the association between inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding. DESIGN: Retrospective cohort study from population based databases. SETTING: Ontario, Canada. PARTICIPANTS: 317 824 elderly people observed for more than 130 000 person years. The patients started taking an antidepressant between 1992 and 1998 and were grouped by how much the drug inhibited serotonin reuptake. Patients were observed until they stopped the drug, had an upper gastrointestinal bleed, or died or the study ended. MAIN OUTCOME MEASURE: Admission to hospital for acute upper gastrointestinal bleeding. RESULTS: Overall, 974 bleeds were observed, with an overall bleeding rate of 7.3 per 1000 person years. After controlling for age or previous gastrointestinal bleeding, the risk of bleeding significantly increased by 10.7% and 9.8%, respectively, with increasing inhibition of serotonin reuptake. Absolute differences in bleeding between antidepressant groups were greatest for octogenarians (low inhibition of serotonin reuptake, 10.6 bleeds/1000 person years v high inhibition of serotonin reuptake, 14.7 bleeds/1000 person years; number needed to harm 244) and those with previous upper gastrointestinal bleeding (low, 28.6 bleeds/1000 person years v high, 40.3 bleeds/1000 person years; number needed to harm 85). CONCLUSIONS: After age or previous upper gastrointestinal bleeding were controlled for, antidepressants with high inhibition of serotonin reuptake increased the risk of upper gastrointestinal bleeding. These increases are clinically important for elderly patients and those with previous gastrointestinal bleeding.

Acute Disease↗

Diagnosis of pulmonary embolism.

Pulmonary embolism (PE) is a common, lethal yet treatable disease. The clinical diagnosis of PE remains to be a problem due to the nonspecific presenting signs, symptoms, electrocardiographic findings, arterial blood gas abnormalities and chest X-ray changes. Despite these nonspecific clinical findings, clinicians are adept at assigning pretest probability using overall clinical assessment. Clinical models have been developed to improve the accuracy of pretest probability assessment. D-dimers are becoming a widely available clinical tool useful in the diagnostic management of suspected PE. The limitations of the imaging modalities for PE [ventilation-perfusion (V/Q) scanning, spiral computerised tomography, pulmonary angiography and venous leg imaging] necessitate the use of these tests in series and in combination with clinical pretest probability assessment and D-dimer in diagnostic management algorithms. These algorithms permit safe diagnostic management of patients with suspected PE while limiting invasiveness, inaccessibility and expense.

Algorithms↗

Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer.

BACKGROUND: The limitations of the current diagnostic standard, ventilation-perfusion lung scanning, complicate the management of patients with suspected pulmonary embolism. We previously demonstrated that determining the pretest probability can assist with management and that the high negative predictive value of certain D -dimer assays may simplify the diagnostic process. OBJECTIVE: To determine the safety of using a simple clinical model combined with D -dimer assay to manage patients presenting to the emergency department with suspected pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Emergency departments at four tertiary care hospitals in Canada. PATIENTS: 930 consecutive patients with suspected pulmonary embolism. INTERVENTIONS: Physicians first used a clinical model to determine patients' pretest probability of pulmonary embolism and then performed a D -dimer test. Patients with low pretest probability and a negative D -dimer result had no further tests and were considered to have a diagnosis of pulmonary embolism excluded. All other patients underwent ventilation-perfusion lung scanning. If the scan was nondiagnostic, bilateral deep venous ultrasonography was done. Whether further testing (by serial ultrasonography or angiography) was done depended on the patients' pretest probability and the lung scanning results. MEASUREMENTS: Patients received a diagnosis of pulmonary embolism if they had a high-probability ventilation-perfusion scan, an abnormal result on ultrasonography or pulmonary angiography, or a venous thromboembolic event during follow-up. Patients for whom the diagnosis was considered excluded were followed up for 3 months for the development of thromboembolic events. RESULTS: The pretest probability of pulmonary embolism was low, moderate, and high in 527, 339, and 64 patients (1.3%, 16.2%, and 37.5% had pulmonary embolism), respectively. Of 849 patients in whom a diagnosis of pulmonary-embolism had initially been excluded, 5 (0.6% [95% CI, 0.2% to 1.4%]) developed pulmonary embolism or deep venous thrombosis during follow-up. However, 4 of these patients had not undergone the proper diagnostic testing protocol. In 7 of the patients who received a diagnosis of pulmonary embolism, the physician had performed more diagnostic tests than were called for by the algorithm. In 759 of the 849 patients in whom pulmonary embolism was not found on initial evaluation, the diagnostic protocol was followed correctly. Only 1 (0.1% [CI, 0.0% to 0.7%]) of these 759 patients developed thromboembolic events during follow-up. Of the 437 patients with a negative D -dimer result and low clinical probability, only 1 developed pulmonary embolism during follow-up; thus, the negative predictive value for the combined strategy of using the clinical model with D -dimer testing in these patients was 99.5% (CI, 99.1% to 100%). CONCLUSION: Managing patients for suspected pulmonary embolism on the basis of pretest probability and D -dimer result is safe and decreases the need for diagnostic imaging.

Adolescent↗

Extended outpatient therapy with low molecular weight heparin for the treatment of recurrent venous thromboembolism despite warfarin therapy.

PURPOSE: The optimal management of patients who have recurrent thromboembolism while being treated with oral anticoagulation therapy is unknown. This study reports managing such patients with extended duration low molecular weight heparin therapy. SUBJECTS AND METHODS: This study was a retrospective review of the prospective databases of three tertiary care teaching hospitals over a 27-month period. All patients who had recurrent symptomatic thromboembolism while being treated with warfarin were identified. All patients were treated with low molecular weight heparin (dalteparin), 200 U/kg daily. Data were collected for recurrent venous thromboembolism, bleeding, and survival. RESULTS: Eight hundred eighty-seven patients were managed for acute thromboembolism. In 32 patients, symptomatic, objectively documented thromboembolism recurred while they were taking warfarin; 63% of the patients with recurrence had cancer, compared with 30% of patients without recurrence. All recurrences were treated with dalteparin. In 3 patients (9% [95% confidence interval: 2% to 25%]), symptomatic recurrence developed while they were being treated with low molecular weight heparin. Nineteen patients (59%) died while receiving anticoagulation therapy; all deaths but 1 were due to malignancy, and none was due to pulmonary embolism or bleeding. CONCLUSIONS: These results suggest that recurrent venous thromboembolism is more likely to develop in cancer patients while being treated with warfarin and that long-term therapy with low molecular weight heparin may be effective in managing warfarin-failure thromboembolic disease.

Adolescent↗

A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism.

We compared three rapid D-dimer methods for the diagnosis of venous thromboembolism. Patients presenting to four teaching hospitals with the possible diagnosis of deep vein thrombosis or pulmonary embolism were investigated with a combination of clinical likelihood, D-dimer (SimpliRED) and initial non-invasive testing. Patients were assigned as being positive or negative for deep vein thrombosis or pulmonary embolism based on their three-month outcome and initial test results. The three D-dimer methods compared were: (a) Accuclot D-dimer (b) IL-Test D-dimer (c) SimpliRED D-dimer. Of 993 patients, 141 had objectively confirmed deep vein thrombosis or pulmonary embolism. The sensitivity of SimpliRED, Accuclot and IL-Test were 79, 90 and 87% respectively. All three D-dimer tests gave similar negative predictive values. The SimpliRED D-dimer was found to be less sensitive than the Accuclot or IL-Test. When combined with pre-test probability all three methods are probably acceptable for use in the diagnosis of venous thromboembolism.

Fibrin Fibrinogen Degradation Products↗

Clinical and laboratory diagnosis of deep vein thrombosis: new cost-effective strategies.

Diagnosis of deep vein thrombosis (DVT) has been made easier, less invasive, and somewhat safer over the past 2 decades. This has been due mainly to the development of venous compression ultrasonography (US). The prevalence of the disease in patients clinically suspected of DVT has steadily decreased during the past 10 years, likely as a consequence of the accurate noninvasive test, ultrasound imaging. This has led to the development of diagnostic tools that aim at reducing the number of unnecessary US exams. These include clinical probability assessment and fibrin D-dimer. Several strategies combining these tools have been validated in large-outcome studies and compared in a formal cost-effectiveness analysis. The results indicate that they should now be implemented in daily practice, taking into account local facilities and expertise.

Algorithms↗