Akbar Panju

Heparin for 5 Days as Compared with 10 Days in the Initial Treatment of Proximal Venous Thrombosis

It is common practice to begin anticoagulant treatment of deep-vein thrombosis with a 10-day course of intravenous heparin, with warfarin added on day 5 to 10 and continued for several months. We performed a randomized, double-blind trial comparing a shorter course of continuous intravenous heparin (5 days, with warfarin sodium begun on the first day) with the conventional 10-day course of heparin (with warfarin sodium begun on the fifth day) in the initial treatment of 199 patients with acute proximal venous thrombosis documented by venography. The frequency of objectively documented recurrent venous thromboembolism was low and essentially the same in the two groups (7.1 percent in the short-course group vs. 7.0 percent in the long-course group). Because the observed difference between the groups was 0.1 percent in favor of the long-course group, it is unlikely (P less than 0.05) that a true difference in favor of this group would be greater than 7.5 percent; the difference could be as much as 7.3 percent in favor of the short-course group. Major bleeding episodes were infrequent, and the rate was similar in both groups. We conclude that a five-day course of heparin is as effective as a 10-day course in treating deep venous thrombosis. Furthermore, using the shorter course would permit earlier discharge from the hospital and thus offer substantial cost savings.

A Novel and Rapid Whole-Blood Assay for D-Dimer in Patients With Clinically Suspected Deep Vein Thrombosis

BACKGROUND The clinical utility of using a novel whole blood assay for D-dimer (SimpliRED), alone or in combination with impedance plethysmography (IPG), was investigated in a two-center, prospective cohort study of 214 consecutive patients with clinically suspected deep vein thrombosis (DVT). METHODS AND RESULTS All patients underwent the SimpliRED D-dimer assay, contrast venography, and IPG. According to the results of venography, 43 patients had proximal DVT (popliteal and/or more proximal veins), 10 had isolated calf DVT, and 161 had DVT ruled out. The D-dimer had a sensitivity of 93% for proximal DVT and of 70% for calf DVT, an overall specificity of 77%, and a negative predictive value of 98% for proximal DVT. The sensitivity and specificity of IPG for proximal DVT were 67% and 96%, respectively. When analyzed in combination with the IPG results, it was determined that (1) the combination of a negative D-dimer and a normal IPG had a negative predictive value of 97% for all DVT and of 99% for proximal DVT and occurred in 58% of patients (likelihood ratio, 0.1) and (2) the combination of a positive D-dimer and an abnormal IPG had a positive predictive value of 93% for any DVT and of 90% for proximal DVT and occurred in 14% of patients (likelihood ratio, 42.6). When the D-dimer and IPG results were discordant, it was not possible to exclude or diagnose DVT reliably; discordant results occurred in 28% of patients. CONCLUSIONS The SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within 5 minutes, has great potential in patients with clinically suspected DVT, especially for ruling out DVT, and is complementary to IPG. The assay should be evaluated in large clinical management studies.

Use of Hirulog in the prevention of venous thrombosis after major hip or knee surgery.

BACKGROUND The study objective was to determine whether Hirulog, a direct thrombin inhibitor, has potential efficacy and safety in the prevention of deep vein thrombosis (DVT) in orthopedic patients. A phase 2 open-label, dose-escalating design was used to study 222 unselected patients undergoing major hip or knee surgery in tertiary-care, university-affiliated hospitals. METHODS AND RESULTS Subcutaneous Hirulog was initiated postoperatively. Patients were evaluated for bleeding and symptomatic pulmonary embolism, and mandatory bilateral venography was performed before discharge. Dose escalations were made on the basis of observed rates of bleeding and venous thrombosis. There were five dosage regimens used: 0.3 mg/kg every 12 hours, 0.6 mg/kg every 12 hours, 1.0 mg/kg every 12 hours for 3 days followed by 0.6 mg/kg every 12 hours for up to 11 days, 1.0 mg/kg every 12 hours, and 1.0 mg/kg every 8 hours. One hundred seventy-seven patients who had technically adequate bilateral venography or objectively documented pulmonary embolism were included in the primary analysis of efficacy. The highest dosage regimen (1.0 mg/kg every 8 hours) provided the lowest rates of total DVT (17%) and proximal DVT (2%), both of which were significantly lower (P = .010 and P = .023, respectively) than the pooled rates of total (43%) and proximal (20%) DVT seen with the first four regimens. Bleeding rates were low (< 5%) with all regimens. CONCLUSIONS This study demonstrates that 1.0 mg/kg Hirulog every 8 hours started postoperatively is potentially efficacious and safe for the prevention of DVT after major hip or knee surgery.

Chronic pain syndromes after ischemic stroke: PRoFESS trial

Background and Purpose— Chronic pain syndromes are reported to be common after stroke, but most previous epidemiological studies have generally included small cohorts of patients with relatively short-term follow-up. In a large cohort with ischemic stroke (Prevention Regimen for Effectively avoiding Second Stroke [PRoFESS] trial), we determined the prevalence, risk factors, and clinical consequence of new poststroke pain syndromes. Methods— Within the PRoFESS trial (mean follow-up 2.5 years), a standardized chronic pain questionnaire was administered (at the penultimate follow-up visit) to all participants who reported chronic pain since their stroke and did not have a history of chronic pain before their index stroke. Multivariable logistic regression analyses were used to determine risk factors for poststroke pain (and pain subtypes), and the association between poststroke pain and cognitive (≥3 reduction in Mini-Mental State Examination score) and functional decline (≥1 increase in m-Rankin). Results— In total, 15 754 participants were included; of which 1665 participants (10.6%) reported new chronic poststroke pain, and included 431 participants (2.7%) with central poststroke pain, 238 (1.5%) with peripheral neuropathic pain, 208 (1.3%) with pain from spasticity, and 136 participants (0.9%) with pain from shoulder subluxation. More than 1 pain subtype was reported in 86 participants (0.6%). Predictors of poststroke pain included increased stroke severity, female sex, alcohol intake, statin use, depressive symptoms, diabetes mellitus, antithrombotic regimen, and peripheral vascular disease. A new chronic pain syndrome was associated with greater dependence (odds ratio, 2.16; 95% confidence interval, 1.82–2.56). Peripheral neuropathy and pain from spasticity/shoulder subluxation were associated with cognitive decline. Conclusions— Chronic pain syndromes are common after ischemic stroke and are associated with increased functional dependence and cognitive decline.

Does This Patient With Diabetes Have Large-Fiber Peripheral Neuropathy?

CONTEXT Diabetic peripheral neuropathy predisposes patients to foot ulceration that heals poorly and too often leads to amputation. Large-fiber peripheral neuropathy (LFPN), one common form of diabetic neuropathy, when detected early prompts aggressive measures to prevent progression to foot ulceration and its associated morbidity and mortality. OBJECTIVE To systematically review the literature to determine the clinical examination findings predictive of asymptomatic LFPN before foot ulceration develops. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION MEDLINE (January 1966-November 2009) and EMBASE (1980-2009 [week 50]) databases were searched for articles on bedside diagnosis of diabetic peripheral neuropathy. Included studies compared elements of history or physical examination with nerve conduction testing as the reference standard. DATA SYNTHESIS Of 1388 articles, 9 on diagnostic accuracy and 3 on precision met inclusion criteria. The prevalence of diabetic LFPN ranged from 23% to 79%. A score greater than 4 on a symptom questionnaire developed by the Italian Society of Diabetology increases the likelihood of LFPN (likelihood ratio [LR], 4.0; 95% confidence interval [CI], 2.9-5.6; negative LR, 0.19; 95% CI, 0.10-0.38). The most useful examination findings were vibration perception with a 128-Hz tuning fork (LR range, 16-35) and pressure sensation with a 5.07 Semmes-Weinstein monofilament (LR range, 11-16). Normal results on vibration testing (LR range, 0.33-0.51) or monofilament (LR range, 0.09-0.54) make LFPN less likely. Combinations of signs did not perform better than these 2 individual findings. CONCLUSIONS Physical examination is most useful in evaluating for LFPN in patients with diabetes. Abnormal results on monofilament testing and vibratory perception (alone or in combination with the appearance of the feet, ulceration, and ankle reflexes) are the most helpful signs.

Management of Central Poststroke Pain Systematic Review of Randomized Controlled Trials

Background and Purpose— Central poststroke pain is a chronic neuropathic disorder that follows a stroke. Current research on its management is limited, and no review has evaluated all therapies for central poststroke pain. Methods— We conducted a systematic review of randomized controlled trials to evaluate therapies for central poststroke pain. We identified eligible trials, in any language, by systematic searches of AMED, CENTRAL, CINAHL, DARE, EMBASE, HealthSTAR, MEDLINE, and PsychINFO. Eligible trials (1) enrolled ≥10 patients with central poststroke pain; (2) randomly assigned them to an active therapy or a control arm; and (3) collected outcome data ≥14 days after treatment. Pairs of reviewers, independently and in duplicate, screened titles and abstracts of identified citations, reviewed full texts of potentially eligible trials, and extracted information from eligible studies. We used a modified Cochrane tool to evaluate risk of bias of eligible studies, and collected patient-important outcomes according to recommendations by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. We conducted, when possible, random effects meta-analyses, and evaluated our certainty in treatment effects using the Grading of Recommendations Assessment, Development, and Evaluation System. Results— Eight eligible English language randomized controlled trials (459 patients) tested anticonvulsants, an antidepressant, an opioid antagonist, repetitive transcranial magnetic stimulation, and acupuncture. Results suggested that all therapies had little to no effect on pain and other patient-important outcomes. Our certainty in the treatment estimates ranged from very low to low. Conclusions— Our findings are inconsistent with major clinical practice guidelines; the available evidence suggests no beneficial effects of any therapies that researchers have evaluated in randomized controlled trials.

Management of anti-thrombin III deficiency during pregnancy without administration of anti-thrombin III

We report a patient with hereditary antithrombin III deficiency who was successfully treated with heparin throughout pregnancy. Functional antithrombin III levels fell to 0.32 U/ml during heparin treatment, but it was possible to achieve a heparin effect, measured by the activated partial thromboplastin time, thrombin clotting time and heparin assay with subcutaneous heparin in doses of 30,000 U to 35,000 U/24 hours. This achieve an long term heparin effect was obtained without the need for antithrombin III infusions.

Management of chronic neuropathic pain: a protocol for a multiple treatment comparison meta-analysis of randomised controlled trials.

Introduction Chronic neuropathic pain is associated with reduced health-related quality of life and substantial socioeconomic costs. Current research addressing management of chronic neuropathic pain is limited. No review has evaluated all interventional studies for chronic neuropathic pain, which limits attempts to make inferences regarding the relative effectiveness of treatments. Methods and analysis We will conduct a systematic review of all randomised controlled trials evaluating therapies for chronic neuropathic pain. We will identify eligible trials, in any language, by a systematic search of CINAHL, EMBASE, MEDLINE, AMED, HealthSTAR, DARE, PsychINFO and the Cochrane Central Registry of Controlled Trials. Eligible trials will be: (1) enrol patients presenting with chronic neuropathic pain, and (2) randomise patients to alternative interventions (pharmacological or non-pharmacological) or an intervention and a control arm. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible trials and extract information from eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias of eligible studies, recommendations from the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes we will collect, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate our confidence in treatment effects. When possible, we will conduct: (1) in direct comparisons, a random-effects meta-analysis to establish the effect of reported therapies on patient-important outcomes; and (2) a multiple treatment comparison meta-analysis within a Bayesian framework to assess the relative effects of treatments. We will define a priori hypotheses to explain heterogeneity between studies, and conduct meta-regression and subgroup analyses consistent with the current best practices. Ethics and Dissemination We do not require ethics approval for our proposed review. We will disseminate our findings through peer-reviewed publications and conference presentations. Trial registration number PROSPERO (CRD42014009212).

Heparin and graduated compression stockings in patients undergoing fractured hip surgery.

Despite evidence that effective regimens are available for the prevention of venous thrombosis in fractured hip patients, many centers do not use prophylaxis. In order to evaluate the efficacy and safety of heparin and graduated compression stockings, we conducted a cohort study of 55 consecutive fractured hip patients treated postoperatively with heparin, 5,000 U every 12 h, and graduated compression stockings. The rates of venous thromboembolism and bleeding were compared with an historical cohort from Hamilton. Before discharge, 51 patients underwent bilateral venography. Deep venous thrombosis (DVT) occurred in 10 of the 51 patients (incidence of 20%); three had proximal DVT (incidence of proximal DVT was 6%). DVT was seen in 29 of the 63 control patients (incidence 46%); 19 had proximal DVT (incidence of proximal DVT was 30%). The differences in the rates of DVT and proximal DVT are statistically significant (p < 0.01). Bleeding occurred in one patient in the treatment group (incidence 2%) and five patients in the control group (incidence 8%). This study confirms that therapy with heparin and graduated compression stockings is effective, inexpensive, and convenient for the prevention of venous thrombosis in fractured hip patients and is associated with a low bleeding risk.

Can troponin I measurement predict short-term serious cardiac outcomes in patients presenting to the emergency department with possible acute coronary syndrome?

OBJECTIVE To determine the ability of troponin I (TnI) measurement to predict the likelihood of a serious cardiac outcome over the subsequent 72 hours in patients presenting to the emergency department (ED) with symptoms suggestive of an acute coronary syndrome. METHODS This prospective observational study enrolled consecutive patients presenting to 2 urban tertiary care hospital EDs over a 5-week period. Eligible patients included those for whom a TnI test was ordered within 24 hours of arrival and in whom no serious cardiac outcome occurred before the test result was available. Patients were followed for 72 hours and serious cardiac outcomes documented; these included cardiovascular death, myocardial infarction, congestive heart failure, serious arrhythmia and refractory pain. We calculated likelihood ratios (LRs) to describe the association of the TnI result with serious cardiac outcomes. RESULTS Of the 352 enrolled patients, 20 had a serious cardiac outcome within 72 hours of ED presentation. The derived LRs (and 95% confidence interval [CI]) were 0.5 (0.3-0.9) for TnI values <0.5 microg/L, 1.6 (0.4-6.5) for TnI values from 0.5 to 2.0 microg/L, 5.8 (1.7-19.5) for TnI values from >2.0 to 10.0 microg/L and 14.4 (4.8-42.9) for TnI values >10.0 microg/L. CONCLUSIONS TnI values >2.0 microg/L are associated with an increased probability of serious cardiac outcomes within 72 hours. TnI values between 0.5 and 2.0 microg/L are weakly positive predictors. TnI values <0.5 microg/L have LRs in the range of 0.5 and thus are weakly negative predictors, not substantially decreasing the likelihood of serious cardiac outcomes, particularly in patients with a moderate or high pretest probability.