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Biomedical subjects

Susan R Kahn

Publications and source records attributed to Susan R Kahn.

At least 19 recordsLinked to original sources

Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis.

OBJECTIVE: To assess the strength of association between recurrent fetal loss (RFL) and presence of antiphospholipid antibodies (aPL) in women without autoimmune disease, and to examine whether magnitude of association varies according to type or titer of antibody and timing of fetal loss. METHODS: We searched Medline and Current Contents for articles published between 1975 and 2003 with terms denoting early (less than 13 weeks) and late (less than 24 weeks) RFL associated with various aPL. Published case-control, cohort, and cross-sectional studies rated moderate or strong were included in our metaanalysis. Pooled odds ratios with 95% CI were generated using the random-effects models with Cochrane Review Manager software. RESULTS: Our analysis included 25 studies. Lupus anticoagulant (LAC) was associated with late RFL (OR 7.79, 95% CI 2.30-26.45); the association of LAC was stronger than that of any other aPL. IgG anticardiolipin antibodies (aCL), when combining all titers, were associated with both early (OR 3.56, 95% CI 1.48-8.59) and late RFL (OR 3.57, 95% CI 2.26-5.65). Restricting analysis to include only women with moderate to high titers increased the strength of association (OR 4.68, 95% CI 2.96-7.40). It was not possible to extract data on isolated low IgG aCL positivity. IgM aCL were associated with late RFL (OR 5.61, 95% CI 1.26-25.03). There was no association found between early RFL and anti-Beta2-glycoprotein I antibodies (OR 2.12, 95% CI 0.69-6.53). CONCLUSION: The magnitude of the association between aPL and RFL varies according to type of aPL. More data on the relationship between recurrent fetal loss and isolated IgM aCL as well as with low titer IgG aCL would be useful. The place of testing for anti-Beta2-glycoprotein I antibodies remains to be determined.

Abortion, Habitual↗

The post-thrombotic syndrome: progress and pitfalls.

The post-thrombotic syndrome (PTS) develops in up to one half of patients after symptomatic deep venous thrombosis (DVT) and is the most common complication of DVT. Typical features of PTS include chronic pain, swelling, heaviness, oedema and skin changes in the affected limb. In severe cases, venous ulcers may develop. The frequency of PTS is likely to be reduced by preventing DVT with the use of effective thromboprophylaxis in high-risk patients and settings and by minimising the risk of ipsilateral DVT recurrence. Use of compression stockings for 2 years after DVT appears to reduce the incidence and severity of PTS but issues remain regarding their use and effectiveness. Future research should focus on elucidating the pathophysiology and risk factors for PTS, assessing the safety and effectiveness of catheter-directed thrombolysis to prevent PTS and evaluating the optimal use of compression stockings to prevent and treat PTS. In addition, new therapies to treat PTS should be sought and evaluated.

Bandages↗

VEINES-QOL/Sym questionnaire was a reliable and valid disease-specific quality of life measure for deep venous thrombosis.

OBJECTIVE: To assess the validity of VEINES-QOL/Sym, a patient-reported questionnaire to evaluate quality of life and symptoms in patients with deep venous thrombosis (DVT). STUDY DESIGN AND SETTING: Psychometric study within the Venous Thrombosis Outcomes (VETO) Study, a prospective cohort study of long-term outcomes after DVT. A total of 359 English- and French-speaking patients with acute, objectively diagnosed DVT were recruited at seven hospitals in Quebec, Canada. The VEINES-QOL/Sym questionnaire, a 26-item patient-reported measure that generates separate summary scores for symptoms (VEINES-Sym) and quality of life (VEINES-QOL) was evaluated for acceptability, reliability, validity, and responsiveness in VETO Study subjects. RESULTS: Standard psychometric tests confirmed the acceptability (missing data, item endorsement frequencies, floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest), validity (content, construct, convergent, discriminant, known groups), and responsiveness to clinical change of the VEINES-QOL/Sym in patients with DVT. CONCLUSION: The VEINES-QOL/Sym is a practical and scientifically sound patient-reported measure of outcomes that was developed using gold-standard methods. VEINES-QOL/Sym is valid and reliable for use as a measure of quality of life and symptoms in patients with acute DVT and provides a rigorous tool to allow more comprehensive evaluation of outcomes in clinical trials and epidemiological studies of patients with DVT.

Acute Disease↗

Intra- and interobserver agreement and statistical clustering of placental histopathologic features relevant to preterm birth.

OBJECTIVE: Many previous studies of agreement in identifying placental histopathologic lesions have been based on small sample sizes, and none has examined whether individual histologic features cluster robustly together within and between observers. STUDY DESIGN: We studied 767 placental specimens from case-control studies of preterm birth and preeclampsia nested within a prospective cohort of pregnant women recruited from 4 large Montreal maternity hospitals. The specimens were fixed, embedded, stained, and examined using a standardized protocol; a 10% random sample (n = 81) was then blindly reexamined at least 6 months later by the same pathologist and a second pathologist. RESULTS: Intra- and interobserver agreement were high (kappa > or = 0.50) for membrane inflammation, funisitis, and umbilical cord vasculitis, and these 3 features were robustly clustered statistically, consistent with an underlying mechanism of ascending infection. Agreement and clustering were also high or moderate for features of placental underperfusion: infarction, decidual vasculopathy, and syncytial knotting. CONCLUSION: Our results should help researchers to interpret future findings relating placental histopathology to preterm birth, preeclampsia, and other adverse pregnancy outcomes, and to their etiologic determinants and causal pathways.

Case-Control Studies↗

Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada.

BACKGROUND: Venous thromboembolism (VTE) prophylaxis in acutely ill medical patients has been shown to be safe and effective. Underutilization of this patient safety practice may result in avoidable mortality and morbidity. OBJECTIVES: We aimed to determine the proportion of hospitalized, acutely ill medical patients across Canada who were eligible to receive thromboprophylaxis and to evaluate the frequency, determinants and appropriateness of its use. PATIENTS/METHODS: CURVE is a national, multicenter chart audit of 29 Canadian hospitals. Data were collected on consecutive patients admitted to hospital for an acute medical illness during a defined 3-week study period. Information on demographic and clinical characteristics, risk factors for VTE and bleeding and use of VTE prophylaxis were recorded. The indications for and appropriateness of VTE prophylaxis were assessed using pre-specified criteria based on international consensus guidelines. Multivariable analyses were performed to identify determinants of prophylaxis use. RESULTS: Of the 4124 medical admissions screened over the study period, 1894 patients (46%) were eligible for study inclusion. The most common specified admitting diagnoses were severe infection (28%), COPD exacerbation or respiratory failure (12%), malignancy (9%) and congestive heart failure (8%). Thromboprophylaxis was indicated in 1702 (90%) study patients. Overall, some form of prophylaxis was administered to 23% of all patients. However, only 16% received appropriate thromboprophylaxis. Factors independently associated with greater use of prophylaxis included internist (vs. other specialty) as attending physician (OR 1.33, 95% confidence interval (CI) [1.03, 1.71]), university-associated (vs. community) hospital (OR 1.46, 95% CI [1.03, 2.07]), immobilization (per day) (OR 1.60, 95% CI [1.45, 1.77]), presence of >or=1 VTE risk factors (OR=1.78, 95% CI [1.35, 2.34]) and duration of hospitalization (per day of stay) (OR 1.05, 95% CI [1.03, 1.07]), however, use of prophylaxis was unacceptably low in all groups. Patients with cancer had a significantly reduced likelihood of receiving prophylaxis (OR=0.40, 95% CI [0.24, 0.68]). Presence of risk factors for bleeding did not influence the use or choice of prophylaxis. CONCLUSION: Most patients hospitalized for medical illness had indications for thromboprophylaxis, yet only 16% received appropriate prophylaxis. Efforts should be made to elucidate the reasons that underlie the very low rate of thromboprophylaxis in medical patients and to develop and test strategies to improve implementation of this patient safety practice.

Acute Disease↗

The post-thrombotic syndrome: the forgotten morbidity of deep venous thrombosis.

The postthrombotic syndrome (PTS) is the most common complication of deep venous thrombosis (DVT) yet has received little attention from clinicians and researchers. Clinically, PTS is characterized by chronic pain, swelling, heaviness and other signs in the affected limb. In severe cases, venous ulcers may develop. PTS is burdensome and costly to patients and society because of its high prevalence, severity and chronicity. Preventing DVT with the use of effective thromboprophylaxis in high-risk patients and settings and minimizing the risk of ipsilateral DVT recurrence are likely to reduce the frequency of PTS. Compression stockings worn daily after DVT appear to reduce the incidence and severity of PTS but questions regarding their use and effectiveness remain. Future research should focus on identifying patients at high risk for PTS, assessing the role of thrombolysis in preventing PTS and evaluating the optimal use of compression stockings in preventing and treating PTS. In addition, new therapies to treat PTS should be sought and evaluated.

Humans↗

Frequency and determinants of the postthrombotic syndrome after venous thromboembolism.

PURPOSE OF REVIEW: Postthrombotic syndrome (PTS) is the most common complication of deep venous thrombosis (DVT). Identifying which patients are at high risk of developing PTS would help improve the management of patients with DVT and allow physicians to provide patients with individualized information on their expected prognosis. This review discusses the knowledge gained from key studies over the last decade on the incidence and determinants of PTS, with special emphasis on published studies from the last 2 years. RECENT FINDINGS: About a third to half of DVT patients will develop PTS, in most cases within 1-2 years of acute DVT. Important risk factors for PTS appear to be ipsilateral recurrence of DVT, poor quality of initial anticoagulation for the treatment of DVT and increased body mass index. SUMMARY: Preventing DVT recurrence by providing adequate intensity and duration of anticoagulation for the initial DVT and using effective thromboprophylaxis in high-risk settings is likely to reduce the frequency of PTS. Despite some advances in identifying risk factors for PTS, however, it is still not possible to reliably predict an individual patient's risk of developing PTS after an episode of DVT. Further studies of clinical determinants and biological markers of increased risk of PTS are needed to ultimately improve long-term prognosis after DVT.

Biomarkers↗

The post-thrombotic syndrome after upper extremity deep venous thrombosis in adults: a systematic review.

BACKGROUND: Post-thrombotic syndrome is a chronic, potentially debilitating complication of deep vein thrombosis (DVT) of the lower extremity. Comparatively little is known about post-thrombotic syndrome after upper extremity DVT (UEDVT). OBJECTIVE: To perform a systematic review of clinical studies that have examined the incidence, clinical features, risk factors and management of post-thrombotic syndrome after UEDVT. METHODS: Using combinations of keywords venous thrombosis, postphlebitic syndrome, thrombophlebitis, arm swelling, post-thrombotic syndrome, UEDVT, Paget-Schroetter syndrome, thoracic outlet syndrome, axillary vein, subclavian vein, and central venous catheter, the MEDLINE database was searched for English language articles published between January 1967 and December 2004. Retrieval and review of articles were restricted to clinical studies in humans that described long-term outcomes after objectively confirmed UEDVT. RESULTS: Seven studies were reviewed. The frequency of PTS after UEDVT ranges from 7-46% (weighted mean 15%). Residual thrombosis and axillosubclavian vein thrombosis appear to be associated with an increased risk of PTS, whereas catheter-associated UEDVT may be associated with a decreased risk. There is currently no validated, standardized scale to assess upper extremity PTS, and little consensus regarding the optimal management of this condition. Quality of life is impaired in patients with upper extremity PTS, especially after DVT of the dominant arm. CONCLUSIONS: PTS is a frequent complication of UEDVT, yet little is known regarding risk factors and optimal management. A standardized means of diagnosis would help to establish better management protocols. The impact of upper extremity PTS on quality of life should be further quantified.

Adult↗

Prospective evaluation of health-related quality of life in patients with deep venous thrombosis.

BACKGROUND: To our knowledge, the burden of deep venous thrombosis from the patient's perspective has not been quantified. We evaluated health-related quality of life (QOL) after deep vein thrombosis and compared results with general population norms. METHODS: This was a multicenter prospective cohort study of 359 consecutive eligible patients with deep vein thrombosis recruited at 7 Canadian hospital centers. Quality of life was assessed at baseline and at 1 and 4 months after diagnosis using generic (36-Item Short-Form Health Survey) and disease-specific (Venous Insufficiency Epidemiological and Economic Study [VEINES]-QOL and VEINES symptom [VEINES-Sym] questionnaires) measures. Changes in QOL scores during the 4-month period were calculated, and determinants of lack of improvement in QOL were evaluated. RESULTS: During the 4 months, mean 36-Item Short-Form Health Survey physical and mental component summary scores improved by 5.1 and 4.6 points, respectively, and VEINES-QOL and VEINES-Sym scores improved by 3.1 and 2.2 points, respectively (P < .001 for time trend for all measures). However, about one third of patients had worsening of QOL during follow-up. Multivariate analyses showed that worsening of the postthrombotic syndrome score was an independent predictor of worsening of 36-Item Short-Form Health Survey physical component summary (P = .04), VEINES-QOL (P < .001), and VEINES-Sym (P < .001) scores. The 36-Item Short-Form Health Survey physical component summary scores were lower than population norms at all points assessed. CONCLUSIONS: On average, QOL improves during the 4 months following deep vein thrombosis. However, in about one third of patients, QOL deteriorates, and at 4 months, average QOL remains poorer than population norms. Worsening of the postthrombotic syndrome score is associated with worsening of QOL.

Acute Disease↗

Influence of warfarin on symptoms of fatigue: findings of a randomized trial.

BACKGROUND: Some patients develop fatigue while taking warfarin, but causality is uncertain. OBJECTIVE: To assess whether warfarin use is associated with fatigue. METHODS: This investigation was a substudy of a randomized double-blind trial in 13 outpatient thromboembolism clinics. Subjects who had received one month of open-label warfarin therapy for venous thromboembolism due to a transient risk factor were randomly assigned to receive warfarin or placebo for 2 months and followed for another 9 months after stopping the study drug. Fatigue was measured using a Likert scale, and change of fatigue was measured by the patient's global rating. RESULTS: In 87 subjects, the overall ratings of fatigue were 0.1 unit lower (95% CI 0.6 units lower to 0.4 units higher) while taking warfarin. Global rating for change in fatigue intensity showed no increase of fatigue with warfarin use. CONCLUSIONS: The short-term use of warfarin was not associated with symptoms of fatigue.

Analysis of Variance↗

Post-thrombotic syndrome, functional disability and quality of life after upper extremity deep venous thrombosis in adults.

The post-thrombotic syndrome (PTS) after upper extremity deep venous thrombosis (UEDVT) has not been well characterized. The objective of our study was to describe and quantify residual symptoms, functional disability and quality of life associated with PTS after UEDVT in adults. Twenty-four patients with objectively diagnosed UEDVT (bilateral in 1 patient) at least 6 months previously were recruited from two Canadian thrombosis clinics. Data were collected on demographic characteristics, DVT risk factors and affected venous segments. The Villalta PTS scale, modified for the upper extremity, was used to diagnose PTS. Patients completed questionnaires on degree of functional disability (DASH questionnaire), and generic (SF-36) and disease-specific (VEINES-QOL) quality of life. Results were compared in patients with and without PTS. Patients were assessed a median of 13 months after the diagnosis of UEDVT. Daily ipsilateral arm or hand swelling was reported by 52% of patients and daily ipsilateral arm pain by 20% of study patients, compared with 0% and 0%, respectively, in the contralateral arm. PTS was present in 11/25 (44%) limbs (11/24 patients). One patient had severe PTS. Patients with PTS, compared with those without PTS, had significantly more functional disability (mean DASH score 20.9 vs. 3.7, p=0.009) and poorer quality of life (mean VEINES-QOL score 45.6 vs. 53.6; p=0.001; mean SF-36 Physical Component Score (PCS) 40.8 vs. 50.2; p=0.12). PTS scores were higher and quality of life was poorer when PTS involved the dominant arm. In conclusion, PTS occurs frequently after UEDVT and is associated with significant functional disability and reduced quality of life. Patients with dominant arm PTS appear to fare worse than those with non-dominant arm PTS. Larger, prospective studies to identify prognostic factors that lead to PTS after UEDVT are warranted.

Activities of Daily Living↗

The relationship between inflammation and venous thrombosis. A systematic review of clinical studies.

During the past decade, the role of inflammation in the pathophysiology of arterial thrombosis has been elucidated. However, comparatively little is known about the relationship between inflammation and venous thrombosis. The aim of this study was to perform a systematic review of clinical studies that have examined the association between inflammation and venous thrombosis, specifically: (1) the value of inflammatory markers in predicting the future development of venous thrombosis; (2) test characteristics of markers of inflammation in the diagnosis of acute venous thrombosis; and (3) effect of venous thrombosis on blood levels of inflammatory markers. Using keywords venous thrombosis, venous thromboembolism, inflammation, acute phase markers, C-reactive protein (CRP), interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1, PubMed and Medline computerized databases were searched for English language articles published after 1980. Search results were restricted to clinical studies in humans that used study designs that were appropriate to address the above objectives. Results show that plasma CRP levels do not appear to predict risk of future venous thrombosis (two studies; N = 41,308). Four studies (N=562) have examined the utility of plasma CRP in the diagnosis of venous thrombosis; pooled positive and negative predictive values were 53% (95% CI:47%,59%) and 85% (95% CI: 81%, 89%), respectively. A two- to six-fold increase in the risk of deep vein thrombosis (DVT) is associated with elevations in plasma levels of CRP, IL-6, IL-8, MCP-1 or TNF-alpha (three studies). We can conclude that the nature of the relationship between inflammation and clinical venous thrombosis is not yet established. CRP does not appear to be useful in predicting future venous thrombosis or in the diagnosis of acute venous thrombosis. While several markers of inflammation are elevated in acute venous thrombosis, further research is needed to determine the precise relationship between these markers and venous thrombosis. The identification and elucidation of inflammatory markers relevant to venous thrombosis could provide targets for future therapy.

Adult↗

Effect of physical activity after recent deep venous thrombosis: a cohort study.

PURPOSE: To determine whether increased physical activity 1 month after deep vein thrombosis (DVT) led to worsening of venous symptoms and signs within the subsequent 3 months. METHODS: By a multicenter prospective cohort study of patients with acute DVT, we used validated questionnaires at baseline, 1 month, and 4 months post-DVT for each exposure, using the Godin Questionnaire to measure physical activity, the VEINES-QOL to measure disease severity, and the postthrombotic syndrome (PTS) scale to measure symptoms and signs usually attributed to sequelae of DVT. RESULTS: Of 301 patients followed for 4 months, 25% were inactive and 25% were only mildly active before their DVT. In univariate analysis, physical activity at 1 month was not associated with a change in PTS score between 1 month and 4 months (P=0.42). After adjusting for the potential confounders of age, sex, pre-DVT physical activity, and disease severity at 1 month, the results suggested that higher physical activity levels at 1 month may be protective against worsening of the PTS score over the subsequent 3 months. Compared with those who were inactive at 1 month, the adjusted OR was 0.93 (95%CI: 0.47, 1.87) for mildly to moderately active persons, and 0.52 (95%CI: 0.24, 1.15) for highly active persons. Among patients who were active pre-DVT (N=220), 55.5% had returned to their previous levels of physical activity or greater within 4 months. CONCLUSIONS: For most persons, exercise at 1 month post-DVT does not appear to worsen venous symptoms and signs over the subsequent 3 months, and more than 50% resume their usual level of activity within 4 months.

Epidemiologic Methods↗

Identifying orthopedic patients at high risk for venous thromboembolism despite thromboprophylaxis.

OBJECTIVE: To evaluate risk factors for venous thromboembolism (VTE) despite thromboprophylaxis in major orthopedic surgery patients at a tertiary care hospital. METHODS: Charts from consecutive patients who underwent total hip replacement (THR), total knee replacement (TKR), or hip fracture surgery (HFS) [hip pinning or hemiarthroplasty] from August 1, 1999, to April 30, 2000, at a large Canadian teaching hospital were abstracted using standardized case report forms. Data were collected on patient characteristics, surgical characteristics, and thromboprophylaxis regimen. Results of tests performed for suspected VTE were documented. Associations between characteristics of interest and objectively confirmed VTE were examined in multivariate analysis. RESULTS: Over the study period, 310 patients underwent major orthopedic surgery and received standard thromboprophylaxis with either dalteparin or enoxaparin (mean duration of prophylaxis, 7 days). Of these, 34% underwent THR, 30% underwent TKR, and 36% underwent HFS. Of 83 suspected cases of VTE, 44 cases (7 proximal and 37 distal deep venous thrombosis [DVT]); 14% of study population) were confirmed with objective testing. Multivariate analyses revealed that knee surgery (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.3 to 10.1) and type of low molecular weight heparin (LMWH) [enoxaparin (more protective): OR, 0.39; 95% CI, 0.20 to 0.80] independently predicted VTE. No patient characteristics (including previous VTE, malignancy, hormonal therapy, postoperative complications) were associated with VTE. CONCLUSION: Despite standard thromboprophylaxis, symptomatic breakthrough VTE, primarily distal DVT, developed in 14% of patients undergoing major orthopedic surgery. Factors that independently predicted VTE in our population were TKR surgery and type of LMWH. TKR patients may warrant more aggressive postoperative physiotherapy and ambulation and adjunctive prophylactic measures such as pneumatic compression. Due to the heterogeneity of different LMWH compounds, direct comparison of the effectiveness of enoxaparin with dalteparin for orthopedic prophylaxis in prospective, randomized trials seems warranted.

Adult↗

Relationship between deep venous thrombosis and the postthrombotic syndrome.

The postthrombotic syndrome (PTS) is a frequent complication of deep venous thrombosis (DVT). Clinically, PTS is characterized by chronic, persistent pain, swelling, and other signs in the affected limb. Rarely, ulcers may develop. Because of its prevalence, severity, and chronicity, PTS is burdensome and costly. Preventing DVT with the use of effective thromboprophylaxis in high-risk patients and settings and minimizing the risk of ipsilateral DVT recurrence are likely to reduce the risk of development of PTS. Daily use of compression stockings after DVT might reduce the incidence and severity of PTS, but consistent and convincing data about their effectiveness are not available. Future research should focus on standardizing diagnostic criteria for PTS, identifying patients at high risk for PTS, and rigorously evaluating the role of thrombolysis in preventing PTS and of compression stockings in preventing and treating PTS. In addition, novel therapies should be sought and evaluated.

Bandages↗

Relationship between clinical classification of chronic venous disease and patient-reported quality of life: results from an international cohort study.

OBJECTIVES: The CEAP (clinical, etiologic, anatomic, pathophysiologic) clinical classification for chronic venous disease (CVD) is based on physician-evaluated clinical signs of CVD. The relationship between CEAP clinical classification and patient-perceived quality of life (QOL) has not been evaluated, but is important for the selection and interpretation of outcomes in clinical studies of patients with CVD. The purpose of this study was to evaluate whether CVD, as classified with CEAP, is related to patient-reported QOL, and to identify patient characteristics associated with CEAP class and QOL that need to be considered when interpreting outcomes in CVD. METHODS: The Venous Insufficiency Epidemiologic and Economic Study (VEINES) population is an international cohort of 1531 patients with CVD recruited in Belgium, France, Italy, and Canada. At the baseline visit patients were categorized into one of seven CEAP clinical categories on the basis of a clinical examination, and completed standardized generic (Short-Form Health Survey, 36 items [SF-36]) and venous disease-specific (QOL [VEINES-QOL] and symptom severity [VEINES-Sym]) QOL questionnaires. Multivariate analyses were used to examine the relationship between CEAP class and QOL. RESULTS: The proportion of patients in the seven CEAP classes (class 0-6) was 3.8%, 13.3%, 24.1%, 12.8%, 36.4%, 7.3%, and 2.3%, respectively. In univariate analyses, SF-36 Physical Component Summary scores and VEINES-QOL and VEINES-Sym scores decreased significantly (ie, poorer QOL) with increasing CEAP class. Multivariate analyses controlling for age, sex, country, education, body mass index, years since CVD onset and comorbid conditions confirmed findings for VEINES-QOL and VEINES-Sym (P<.0001 and P<.0001, respectively). CONCLUSIONS: Physician-evaluated clinical category, based on the CEAP classification, predicts patient-reported QOL and symptom severity in CVD.

Adult↗