Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients

BACKGROUND: Venous thromboembolism (VTE) prophylaxis in medically ill patients has received a level 1A recommendation in previously published clinical guidelines. Pharmacologic prophylaxis for VTE includes unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and fondaparinux. Few direct comparisons between anticoagulants exist in medically ill patients. OBJECTIVE: This meta-analysis was conducted to assess UFH and LMWH (including the selective factor Xa inhibitor fondaparinux) in the reduction of in-hospital VTE in unselected medically ill patients. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Registry databases from January 1981 through September 2007 (English language) for randomized controlled trials using the following terms: dalteparin, enoxaparin, fondaparinux, nadroparin, and heparin. References of included articles and key review papers for additional studies were also searched. Data from studies were included in the analysis if the studies included medically ill patients with risk factors for VTE who had been followed up for 7 to 21 days. RESULTS: A total of 12,391 patients (of whom 8357 were in placebo-controlled trials) from 9 studies were included. Mean age for the entire cohort was 72.8 years; mean (SD) body mass index, 25.6 kg/m2; and mean (SD) actual body weight, 68.2 kg. Deep vein thrombosis (DVT) was significantly reduced with the addition of an LMWH compared with placebo (odds ratio [OR], 0.60; 95% CI, 0.47-0.75; P < or = 0.001), but rates of DVT were similar when comparing LMWH with UFH (OR, 0.92; 95% CI, 0.56-1.52). No significant differences in pulmonary embolism (PE) or death were found among the UFH, LMWH, and placebo groups. LMWH was associated with a significant increased risk for minor bleeding compared with placebo (OR, 1.64; 95% CI, 1.18-2.29; P = 0.003). However, no significant difference was found between LMWH and UFH (OR, 0.68; 95% CI, 0.27-1.70). Major bleeding events were similar among all groups: LMWH/fondaparinux versus placebo, OR, 1.65 (95% CI, 0.8-3.4); LMWH/fondaparinux versus UFH, OR, 0.69 (95% CI, 0.29-1.68); LMWH/fondaparinux versus UFH or placebo, OR, 1.16 (95% CI, 0.66-2.04). CONCLUSIONS: This analysis suggests that VTE prophylaxis with an LMWH (including fondaparinux) or UFH is effective in reducing the rate of DVT, but this benefit did not extend to enhanced protection against PE. Additionally, LMWH and UFH had similar bleeding outcomes.     

The Effect of Frailty on Discharge Location for Medicare Beneficiaries After Acute Stroke

ObjectiveTo examine the effect of frailty on poststroke discharge location with respect to stroke severity and create a risk-adjusted model for understanding the effects of frailty on discharge to an inpatient rehabilitation facility.DesignRetrospective cohort.SettingA 2014 5% Medicare sample.ParticipantsPatients hospitalized for a first-time acute ischemic stroke (N=7258).InterventionsNot applicable.Main Outcome MeasuresA prehospitalization 6-month baseline was used to calculate a frailty score. Logistic regression to predict odds of discharge to inpatient rehabilitation was used to calculate for 3 levels of baseline frailty, controlling for patient demographics, stroke severity, and comorbidities.ResultsAbout 1603 patients were discharged to inpatient rehabilitation. Patients who were nonfrail (odds ratio [OR] 1.716; 95% confidence interval [95% CI], 1.463-2.013) or prefrail (OR 1.519; 95% CI, 1.296-1.779) were more likely to be discharged to inpatient rehabilitation. The final logistic regression model had a C-statistic of 0.63. Most of the patients discharged to inpatient rehabilitation were nonfrail (44.2%) and had moderate strokes (38.9%). Individuals who were frail and suffered a moderate (OR 0.78; 95% CI, 0.558-1.091) or severe stroke (OR 0.509; 95% CI, 0.358-0.721) were less likely to be discharged to an inpatient rehabilitation facility.ConclusionsA lack of a claims-based measure for prestroke functional ability makes it difficult to understand discharge decision-making patterns for individuals’ poststroke. Prestroke frailty was found to have a significant effect on predicating inpatient rehabilitation discharge after an acute stroke when controlling for stroke severity, comorbidities, and age. Further investigation is warranted to examine differences in rehabilitation utilization based on frailty and to quantify the effect of rehabilitation on frailty status in individuals poststroke.     

Venous thromboembolism after spinal cord injury: incidence, time course, and associated risk factors in 16,240 adults and children

OBJECTIVE: To analyze the incidence of venous thromboembolism (VTE) after spinal cord injury (SCI). DESIGN: Retrospective cohort analysis of all SCI cases (16,240) in California from 1991 through 2001. SETTING: All public hospitals in California. PARTICIPANTS: Subjects (cases) coded as having complete or incomplete SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Diagnosis of VTE or death within 91 days of the day of hospital admission. RESULTS: For all cases, the 91-day cumulative incidence of VTE was 5.4%. In a multivariate model, significant predictors of VTE included male sex (odds ratio [OR]=1.4; 95% confidence interval [CI], 1.2-1.7), African-American race (OR=1.6; 95% CI, 1.3-1.9), complete paraplegia versus tetraplegia (OR=1.8; 95% CI, 1.4-2.3), and presence of 3 or more comorbid conditions versus none (OR=1.6; 95% CI, 1.3-2.1). Age less than 14 years was predictive of not developing VTE (OR=0.2; 95% CI, 0.1-0.7). The incidence of VTE did not change significantly over the 11-year time period (P=.07), and VTE was not a significant predictor of death in the first 91 days after hospitalization. CONCLUSIONS: The incidence of VTE in SCI patients in California did not change between 1991 and 2001. We identified specific risk factors for VTE. Further studies are needed to determine if prompt initiation of medical prophylaxis in high risk subjects reduces the incidence of symptomatic VTE.     

Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients

Summary.  Background:  Cancer patients with venous thromboembolism (VTE) are at high risk of recurrent VTE despite standard anticoagulation. To date, very little published literature is available to guide the treatment of cancer patients with recurrent VTE. Objectives:  To evaluate the benefit and risk of low molecular weight heparin (LMWH) dose escalation in cancer patients with recurrent VTE. Patients and methods:  This was a retrospective cohort study of consecutive cancer outpatients referred for management of a symptomatic, recurrent VTE while receiving an anticoagulant. Confirmed episodes of recurrent VTE were treated with either dose escalation of LMWH in patients already anticoagulated with LMWH, or initiation of therapeutic dose LMWH in patients who were taking a vitamin K antagonist (VKA). All patients were followed for a minimum of 3 months after the index recurrent VTE unless they died during this period. Results:  Seventy cancer patients with a recurrent VTE despite ongoing anticoagulation were included. At the time of the recurrence, 67% of patients were receiving LMWH, and 33% were receiving a VKA. A total of six patients [8.6%; 95% confidence interval (CI) 4.0–17.5%] had a second recurrent VTE during the 3-month follow-up period, at an event rate of 9.9 per 100 patient-years (95% CI  2.0–17.8%). Three patients (4.3%; 95% CI  1.5–11.9%), or 4.8 per 100 patient-years (95% CI  0.0–10.3%) of follow-up, had bleeding complications. The median time between the index recurrent VTE to death was 11.4 months (range, 0–83.9 months). Conclusions:  Cancer patients with recurrent VTE have a short median survival. Escalating the dose of LMWH can be effective for treating cases that are resistant to standard, weight-adjusted doses of LMWH or a VKA.     

Mobility status after inpatient stroke rehabilitation: 1-year follow-up and prognostic factors

OBJECTIVES: To evaluate the stability of mobility status achieved by stroke patients during hospital rehabilitation treatment over time and to identify reliable prognostic factors associated with mobility changes. DESIGN: Follow-up evaluation in consecutive first-ever stroke patients 1 year after hospital discharge. Multiple logistic regressions were used to analyze increases and decreases in Rivermead Mobility Index (RMI) scores (dependent variables) between discharge and follow-up. Independent variables were medical, demographic, and social factors. SETTING: Rehabilitation hospital. PATIENTS: A cohort of 155 patients with sequelae of first stroke, with a final sample of 141. MAIN OUTCOME MEASURES: Mobility status at 1-year follow-up, as measured by the RMI, and odds ratios (OR) for improvement and decline in mobility. RESULTS: Functionally, 19.9% improved the mobility levels achieved during the inpatient rehabilitation treatment; levels of 42.6% worsened. Patients with global aphasia (OR = 5.66; 95% confidence interval [CI], 1.50-21.33), unilateral neglect (OR = 3.01; 95% CI, 1.21-7.50), and age 75 years or older (OR = 5.77; 95% CI, 1.42-23.34) had a higher probability of mobility decline than the remaining patients. Postdischarge rehabilitation treatment (PDT), received by 52.5% of the final sample, was significantly and positively associated with mobility improvement (OR = 5.86; 95% CI, 2.02-17.00). Absence of PDT was associated with a decline in mobility (OR = 3.73; 95% CI, 1.73-8.04). CONCLUSIONS: In most cases, mobility status had not yet stabilized at hospital discharge. PDT was useful in preventing a deterioration in mobility improvement achieved during inpatient treatment and in helping increase the likelihood of further mobility improvement.     

Prevention of venous thromboembolism in critically ill medical patients: a Franco-Canadian cross-sectional study

BACKGROUND: Medical intensive care unit (ICU) patients are at moderate risk of venous thromboembolism (VTE) and prophylaxis against VTE is recommended. OBJECTIVES: To observe the range and frequency of VTE prophylaxis administered to medical ICU patients and to determine factors associated with different strategies in French and Canadian ICUs. DESIGN: Prospective cross-sectional observational study. RESULTS: 113/251 (45.0%) French and 29/30 (96.6%) Canadian ICUs agreed to participate. Of 1,222 critically ill medical patients, most were mechanically ventilated (62.5%). Overall, heparin VTE prophylaxis was administered to 63.9% patients, similarly between the 2 countries. Excluding patients with contraindications to heparin and those receiving therapeutic anticoagulation, 91.7% of medical ICU patients appropriately received either low dose unfractionated heparin (UFH) or low molecular weight heparin (LMWH) prophylaxis. Independent predictors of heparin prophylaxis were invasive mechanical ventilation (odds ratio [OR]; 95%CI, 2.4 (1.4-4.3) and obesity (OR 3.1; 1.1-8.8). LMWH was less likely to be prescribed for patients with renal failure (OR 0.1; 0.0009-0.9), or receiving antiembolic stockings (OR 0.4, 0.1-0.9), and much more likely to be prescribed in French ICUs (OR 9.2; 5.0-16.9); however, among patients receiving LMWH, high doses were more likely to be prescribed in Canadian ICUs (OR 8.7; 2.0-37.6). Patients who were pregnant or postpartum (OR 7.7, 1.3-44.3), had neurologic failure (OR 2.1, 1.3-3.4), or were Canadian (OR 3.0, 2.1-4.4) were most likely to receive mechanical VTE prophylaxis (with antiembolic stockings or pneumatic compression devices), whereas those who were already receiving heparin were less likely to receive mechanical prophylaxis (OR 0.5, 0.3-0.7). CONCLUSIONS: In this binational cross-sectional observational study of medical ICU patients, we found that 92% of eligible patients received either UFH or LWMH for VTE prophylaxis. Differences in prescribing between countries include significantly greater use of LMWH in France, but use of lower doses than in Canada, and greater use of mechanical VTE prophylaxis in Canada. More randomized trials of VTE prophylaxis in critically ill medical patients would better inform practice.     

New oral anticoagulants in the ED setting: a review

Background

Emergency department (ED) clinicians are not typically involved in the long-term management of patients' anticoagulation therapy, but they are responsible for decision making for emergency conditions requiring anticoagulation, such as acute venous thromboembolism (VTE). In addition, emergency physicians are often faced with patients who present first to the ED with conditions that may prompt long-term anticoagulation upon hospital discharge, such as atrial fibrillation (AF), or who have acute or potential bleeding complications from anticoagulation.

Objective

In this review, clinical trials of new oral anticoagulants evaluated for treatment of VTE and stroke prophylaxis in AF, as well as practical management aspects, will be discussed. In addition, clinical trials evaluating the adjunctive use of the new oral anticoagulants with antiplatelet therapy in patients who have experienced acute coronary syndrome will be explored.

Discussion

Both dabigatran etexilate and rivaroxaban have successfully completed phase III trials for acute VTE treatment and are currently approved for the reduction of risk of stroke and systemic embolism in patients with nonvalvular AF. In a recently completed phase III trial, apixaban also demonstrated promising efficacy and safety in that indication. Rivaroxaban represents the only new anticoagulant to date to have shown promising phase III results as an adjunct to antiplatelet therapy after acute coronary syndrome.

Conclusion

Knowledge of the appropriate clinical use and safety concerns of the new anticoagulants is imperative as they become more frequently prescribed, and their potential uses in the ED setting represent an important aspect of continuing education for emergency physicians.     

Incidence and severity of shoulder pain does not increase with the use of circuit class therapy during inpatient stroke rehabilitation: a controlled trial

QUESTIONS: Does circuit class therapy result in a greater incidence or severity of shoulder pain compared with individual therapy? Is the incidence influenced by the degree of active shoulder control? DESIGN: Controlled trial with intention-to-treat analysis. PARTICIPANTS: Sixty-eight people (6 drop-outs) undergoing inpatient rehabilitation after stroke. INTERVENTION: Participants received either individual therapy or group circuit class therapy. OUTCOME MEASURES: Incidence of shoulder pain over the previous 24 hours was measured as a yes/no response while severity of shoulder pain was measured using a visual analogue scale at admission, Week 4, and discharge. RESULTS: There was no greater chance of participants receiving circuit class therapy having shoulder pain at Week 4 (OR 0.95, 95% CI 0.32 to 2.80) or discharge (OR 0.38, 95% CI 0.11 to 1.45) than participants receiving individual therapy. Of those participants who reported pain, there was no difference between groups in the severity of pain at Week 4 (mean difference -0.2 cm, 95% CI -3.2 to 2.7) or discharge (mean difference -2.1 cm, 95% CI -4.8 to 0.6). There was a greater chance of participants who had no active shoulder control having shoulder pain at Week 4 (OR 5.8, 95% CI 1.6 to 20.4) and at discharge (OR 3.8, 95% CI 1.0 to 13.9) than participants who had active shoulder control. CONCLUSION: The incidence and severity of shoulder pain was influenced by degree of active shoulder control but not by type of physiotherapy service delivery. Concerns regarding shoulder pain should not be a barrier to the implementation of circuit class therapy during inpatient stroke rehabilitation.     

Falls sustained during inpatient rehabilitation after lower limb amputation: prevalence and predictors

OBJECTIVE: The purpose of this study is to identify risk factors for falling and fall-related injury among a group of inpatients undergoing rehabilitation after major lower limb amputation. DESIGN: Retrospective cohort. RESULTS: Out of 1267 patients, 260 (20.5%) fell at least once. There were a total of 374 falls, 67 (17.9%) of which resulted in one or more injuries. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated for factors significantly associated with falling, including age of > or =71 yrs (OR = 1.40, 95% CI = 1.02-1.89), lengths of stay of 22-35 days (OR = 2.97, 95% CI = 1.14-7.72) or >5 wks (OR = 6.07, 95% CI = 2.34-15.71), four or more comorbidities (OR = 1.93, 95% CI = 1.09-3.41), cognitive impairment (OR = 1.68, 95% CI = 1.02-2.78), two or more as-needed medications (OR = 1.81, 95% CI = 1.02-3.21), benzodiazepines (OR = 2.22, 95% CI = 1.24-3.96), and opiates (OR = 5.76, 95% CI = 3.29-10.09). Factors significantly associated with fall-related injuries included bilateral amputation (OR = 3.68, 95% CI = 1.49-9.05) and falls during the day shift (OR = 2.63, 95% CI = 1.24-5.57). CONCLUSIONS: One in five patients with lower limb amputation will likely experience at least one fall during inpatient rehabilitation, with 18% sustaining an injury. Ongoing research is required to develop appropriate intervention strategies to ameliorate the risk of falling during inpatient rehabilitation.     

New anticoagulants

The limitations of heparin and warfarin have prompted the development of new anticoagulant drugs for prevention and treatment of venous and arterial thromboembolism. Novel parenteral agents include synthetic analogs of the pentasaccharide sequence of heparin that mediates its interaction with antithrombin. Fondaparinux, the first synthetic pentasaccharide, is licensed for prevention of venous thromboembolism (VTE) after major orthopedic surgery and for initial treatment of patients with VTE. Idraparinux, a long-acting pentasaccharide that is administered subcutaneously once-weekly, is being compared with warfarin for treatment of VTE and for prevention of cardioembolic events in patients with atrial fibrillation. New oral anticoagulants include direct inhibitors of thrombin, factor Xa and factor IXa. Designed to provide more streamlined anticoagulation than warfarin, these agents can be given without routine coagulation monitoring. Ximelagatran, the first oral direct thrombin inhibitor, is as effective and safe as warfarin for prevention of cardioembolic events in patients with atrial fibrillation. However, ximelagatran produces a three-fold elevation in alanine transaminase levels in 7.9% of patients treated for more than a month, the long-term significance of which is uncertain. Whether other direct thrombin inhibitors or inhibitors of factors Xa or IXa also have this problem is under investigation. After a brief review of coagulation pathways, this paper focuses on new anticoagulants in advanced stages of clinical testing.     

Do EMS Providers Accurately Ascertain Anticoagulant and Antiplatelet Use in Older Adults with Head Trauma?

Objective: Prehospital provider assessment of the use of anticoagulant or antiplatelet medications in older adults with head trauma is important. These patients are at increased risk for traumatic intracranial hemorrhage and therefore field triage guidelines recommend transporting these patients to centers capable of rapid evaluation and treatment. Our objective was to evaluate EMS ascertainment of anticoagulant and antiplatelet medication use in older adults with head trauma. Methods: A retrospective study of older adults with head trauma was conducted throughout Sacramento County. All 5 transporting EMS agencies and all 11 hospitals in the county were included in the study, which ran from January 2012 to December 2012. Patients ≥55 years who were transported to a hospital by EMS after head trauma were included. We excluded patients transferred between two facilities, patients with penetrating head trauma, prisoners, and patients with unmatched hospital data. Anticoagulant and antiplatelet use were categorized as: warfarin, direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, and apixaban), aspirin, and other antiplatelet agents (e.g., clopidogrel and ticagrelor). We calculated the percent agreement and kappa statistic for binary variables between EMS and emergency department (ED)/hospital providers. A kappa statistic ≥0.60 was considered acceptable agreement. Results: After excluding 174 (7.6%) patients, 2,110 patients were included for analysis; median age was 73 years (interquartile range 62–85 years) and 1,259 (60%) were male. Per ED/hospital providers, the use of any anticoagulant or antiplatelet agent was identified in 595 (28.2%) patients. Kappa statistics between EMS and ED/hospital providers for the specific agents were: 0.76 (95% CI 0.71–0.82) for warfarin, 0.45 (95% CI 0.19–0.71) for DOAC agents, 0.33 (95% CI 0.28–0.39) for aspirin, and 0.51 (95% CI 0.42–0.60) for other antiplatelet agents. Conclusions: The use of antiplatelet or anticoagulant medications in older adults who are transported by EMS for head trauma is common. EMS and ED/hospital providers have acceptable agreement with preinjury warfarin use but not with DOAC, aspirin, and other antiplatelet use.     

Venous Thromboembolism: Exploring Incidence and Utility of Screening in Individuals With Brain Injury

ObjectiveTo determine the incidence of VTE in the population with brain injuries (BIs) using ultrasonography, and to assess the risk of pulmonary embolism (PE) development and/or bleeding complications related to anticoagulation.DesignRetrospective study.SettingAcute rehabilitation hospital.Participants238 individuals with moderate to severe BI who were routinely screened for VTE with ultrasonography on admission to rehabilitation (N=238).InterventionsNot applicable.Main Outcome MeasuresRetrospective chart review was performed to identify individuals who were diagnosed with VTE at the following 3 time points: in acute care prior to admission to rehabilitation, at the time of admission diagnosed via screening examination, and after admission to rehabilitation. Additionally, risk factors for VTE, PE, and incidence of bleeding complications related to therapeutic anticoagulation were assessed.Results123 deep vein thromboses (DVTs) were identified with 38.2% in acute care (n=47), 69.1% on admission to rehabilitation (n=85), and 7.3% during the course of rehabilitation stay (n=9). Risk factors for development of VTE included age at injury, body mass index, injury etiology, history of neurosurgical procedure, and surgery during inpatient rehabilitation. Of those who were placed on therapeutic anticoagulation due to admission diagnosis of VTE (n=50), 2% developed recurrent DVT and 2% had bleeding complications. There was zero incidence of PE.ConclusionWe demonstrated a high prevalence of VTEs identified on screening ultrasonography on admission to inpatient rehabilitation among individuals with moderate to severe BIs, and low complications related to anticoagulation. Given the findings of this study, prospective research in ultrasonography screening for VTE in moderate to severe BI is needed.     

Obesity and risk of venous thromboembolism among postmenopausal women: differential impact of hormone therapy by route of estrogen administration. The ESTHER Study

BACKGROUND: Oral estrogen use and elevated body mass index (BMI) increase the risk of venous thromboembolism (VTE). Recent data suggest that transdermal estrogen might be safe with respect to thrombotic risk. However, the impact of transdermal estrogen on the association between overweight (25 kg m(-2) < BMI < or = 30 kg m(-2)) or obesity (BMI >30 kg m(-2)) and VTE risk has not been investigated. METHODS: We carried a multicenter case-control study of VTE among postmenopausal women aged 45-70 years, between 1999 and 2005, in France. Case population consisted of women with a first documented idiopathic VTE. We recruited 191 hospital cases matched with 416 hospital controls and 62 outpatient cases matched with 181 community controls. RESULTS: The odds ratio (OR) for VTE was 2.5 [95% confidence interval (CI):1.7-3.7] for overweight and 3.9 (95% CI: 2.2-6.9) for obesity. Oral, not transdermal, estrogen was associated with an increased VTE risk (OR = 4.5; 95% CI: 2.6-7.7 and OR = 1.1; 95% CI: 0.7-1.7, respectively). Compared with non-users with normal weight, the combination of oral estrogen use and overweight or obesity further enhanced VTE risk (OR = 10.2; 95% CI: 3.5-30.2 and OR = 20.6; 95% CI: 4.8-88.1, respectively). However, transdermal users with increased BMI had similar risk as non-users with increased BMI (OR = 2.9; 95% CI: 1.5-5.8 and OR = 2.7; 95% CI: 1.7-4.5 respectively for overweight; OR = 5.4; 95% CI: 2.1-14.1 and OR = 4.0; 95% CI: 2.1-7.8 respectively for obesity). CONCLUSIONS: In contrast to oral estrogen, transdermal estrogen does not confer an additional risk of idiopathic VTE in women with increased BMI. The safety of transdermal estrogen on thrombotic risk has to be confirmed.     

Ciprofloxacin vs an aminoglycoside in combination with a beta-lactam for the treatment of febrile neutropenia: a meta-analysis of randomized controlled trials

OBJECTIVE: To compare the effectiveness and toxicity of ciprofloxacin vs an aminoglycoside, both in combination with a beta-lactam, for the treatment of febrile neutropenia in the inpatient setting. METHODS: For this meta-analysis of randomized controlled trials (RCTs) that compared the ciprofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination for the treatment of febrile neutropenia and reported data on effectiveness, mortality, and/or toxicity, we searched PubMed (1950-2004), Current Contents, Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles, including review articles, as well as abstracts presented at international conferences. Data for 3 primary and 2 secondary outcomes were extracted by 2 investigators. RESULTS: Eight RCTs were included in the analysis. Comparable or better outcomes were observed with the ciprofloxacin/beta-lactam combination vs an aminoglycoside/beta-lactam combination: clinical cure without modification of the initial regimen (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.00-1.74; P=.05), clinical cure in the subset of patients with documented Infections (OR, 1.56; 95% CI, 1.05-2.31; P=.03), all-cause mortality (OR, 0.85; 95% CI, 0.54-1.35; P=.49), withdrawal of the study drugs due to toxicity (OR, 0.87; 95% CI, 0.57-1.32; P-.51), and nephrotoxicity (OR, 0.30; 95% CI, 0.16-0.59; P<.001). The ciprofloxacin/beta-lactam combination was also associated with better clinical cure compared to the aminoglycoside/beta-actam combination in the subset of RCTs with non-low-risk patients (OR, 1.38; 95% CI, 1.01-1.88; P=-.04), as well as in the subset of studies that included the same beta-lactam in both treatment arms (OR, 1.47; 95% CI, 1.06-2.05; P=.02). CONCLUSION: The combination of ciprofloxacin with a beta-actam antibiotic should be considered an important therapeutic option in hospitalized febrile neutropenic patients who have not received a quinolone for prevention of infections and in settings in which quinolone resistance is not common.     

Effect of pharmacological therapies for stroke prevention on major gastrointestinal bleeding in patients with atrial fibrillation

Various antiplatelet and anticoagulation options are available for stroke prevention in patients with atrial fibrillation (AF). Currently, it is unclear whether these agents differ in their propensity to cause major gastrointestinal bleeding (MGIB). To our knowledge, no systematic evaluation of MGIB rates from randomised controlled trials (RCTs) of pharmacological stroke prevention in patients with AF has been conducted. Two independent investigators conducted systematic literature searches in MEDLINE and CENTRAL from the earliest possible date through November 2010. To be included, RCTs had to evaluate an adult population with AF or flutter and report data on the incidence of MGIB. Peto's odds ratios (ORs) with associated 95% confidence intervals (CIs) were calculated for all possible pair-wise comparisons of pharmacological stroke prevention alternatives. A total of 16 unique trials (n = 42,983) met inclusion criteria. The reported incidence of MGIB in placebo or control arms of identified trials was as high as 1.5%. Upon pair-wise meta-analysis of different pharmacological strategies, adjusted-dose vitamin K antagonists (VKAs) were found to be associated with a higher odds of MGIB compared with placebo/control (OR 3.21, 95% CI 1.32-7.82) and aspirin (or triflusal or indobufen) (OR 1.92, 95% CI 1.08-3.41). The addition of aspirin (or triflusal) to an adjusted-dose VKA resulted in greater odds of MGIB compared with aspirin alone (OR 4.72, 95% CI 1.35-16.49) and adjusted-dose VKA alone (OR 2.66, 95% CI 1.05-6.74). While aspirin increased the odds of MBIG by 3.23-fold compared with placebo/control, this finding did not reach statistical significance. The combination of aspirin and clopidogrel increased patients' odds of MGIB compared with aspirin alone (OR 1.93, 95% CI 1.46-2.56). Dabigatran was associated with a 30% increased odds of MGIB compared with adjusted-dose VKA (OR 1.30, 95% CI 1.06-1.59); however, ximelagatran was not. Low-intensity VKA therapy, alone or in combination with aspirin, was not associated with increased odds of MGIB compared with any (active-) comparator. The MGIB is a concern for patients with AF receiving pharmacological stroke prevention. Current RCT data suggest that dabigatran and adjusted-dose VKA therapy are associated with the highest odds of MGIB. Aspirin was not found to increase patients' odds of MGIB; however, this finding may be the result of type 2 error. Dual therapy resulting from the addition of an antiplatelet agent was typically associated with further increased odds of MGIB compared with monotherapy.     

Factors Associated With Home Discharge Among Veterans With Stroke

Objective

To determine which patient-, treatment-, and facility-level characteristics were associated with home discharge among patients hospitalized for stroke within the Department of Veterans Affairs.

Design

Retrospective observational study.

Setting

Veterans Affairs facilities nationwide.

Participants

Veterans hospitalized for stroke during fiscal year 2007 to fiscal year 2008 (N=12,565).

Intervention

Not applicable.

Main Outcome Measure

Discharge location after hospitalization.

Results

There were 10,130 (80.6%) veterans discharged home after hospitalization for acute stroke. Married veterans were more likely than nonmarried veterans to be discharged home (odds ratio [OR]=1.23; 95% confidence interval [CI]=1.11–1.35). Compared with veterans admitted to the hospital from home, patients admitted from extended care were less likely to be discharged home (OR=.04; 95% CI=.03–.07). Compared with those with occlusion of cerebral arteries, patients with intracerebral hemorrhage (OR=.61; 95% CI=.50–.74) or other central nervous system hemorrhage (OR=.78; 95% CI=.63–.96) were less likely to be discharged home, whereas patients with occlusion of precerebral arteries (OR=1.36; 95% CI=1.07–1.73) were more likely to return home. Evidence of congestive heart failure (OR=.85; 95% CI=.76–.95), fluid and electrolyte disorders (OR=.86; 95% CI=.77–.96), internal organ procedures and diagnostics (OR=.87; 95% CI=.78–.97), and serious nutritional compromise (OR=.49; 95% CI=.40–.62) during hospitalization remained independently associated with lower odds of home discharge. Longer hospitalizations and receipt of rehabilitation services while hospitalized acutely were negatively associated, whereas treatment on more bed sections and rehabilitation accreditation of the facility were positively associated with home discharge. Region exerted a statistically significant effect on home discharge.

Conclusions

We found sociological, clinical, and facility-level factors associated with home discharge after hospitalization for acute stroke. Findings document the importance of considering a broad range of characteristics rather than focusing only on a few specific traits during discharge planning.     

Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents

Summary. The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. In the case of severe bleeding in a patient who uses anticoagulant agents or when a patient on anticoagulants needs to undergo an urgent invasive procedure, it may be useful to reverse anticoagulant treatment. Conventional anticoagulants such as vitamin K antagonists may be neutralized by administration of vitamin K or prothrombin complex concentrates, whereas heparin and heparin derivatives can be counteracted by protamine sulphate. The anti‐hemostatic effect of aspirin and other antiplatelet strategies can be corrected by the administration of platelet concentrate and/or desmopressin, if needed. Recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors as well as new antiplatelet agents have been introduced and these drugs show promising results in clinical studies. A limitation of these new agents may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although experimental studies show hopeful results for some of these agents.     

High vs. low doses of low-molecular-weight heparin for the treatment of superficial vein thrombosis of the legs: a double-blind, randomized trial

In contrast with extensive information on the management of deep vein thrombosis of the lower extremities, little is known on the most appropriate treatment of the superficial vein thrombosis (SVT). In a multicenter, prospective, controlled, double-blind, double-dummy clinical trial, 164 consecutive patients with acute SVT of the great saphenous vein were randomized to receive the s.c. administration of either fixed prophylactic doses (2850 a-Xa IU) or body-weight adjusted therapeutic doses of nadroparin once daily for 1 month. The main study outcome was to compare the rate of asymptomatic and symptomatic extension of SVT and/or venous thromboembolic (VTE) complications during a 3-month follow-up period. Of the 81 patients randomized to the prophylactic doses, seven [8.6%; 95% confidence interval (CI), 3.5-17.0] developed SVT progression or VTE complications as compared with six of the 83 (7.2%; 95% CI, 2.8-15.1) allocated to the treatment group (absolute difference, 1.4; 96% CI, -6.9 to 9.7; P = 0.74). No patient in either group developed major bleeding. Our findings suggest that therapeutic doses of low-molecular-weight heparin, administered for 1 month in patients with SVT of the greater saphenous vein do not improve results obtained by prophylactic doses, administered for the same period, over a 3-month follow-up period.     

Mirror therapy enhances lower-extremity motor recovery and motor functioning after stroke: a randomized controlled trial

OBJECTIVE: To evaluate the effects of mirror therapy, using motor imagery training, on lower-extremity motor recovery and motor functioning of patients with subacute stroke. DESIGN: Randomized, controlled, assessor-blinded, 4-week trial, with follow-up at 6 months. SETTING: Rehabilitation education and research hospital. PARTICIPANTS: A total of 40 inpatients with stroke (mean age, 63.5 y), all within 12 months poststroke and without volitional ankle dorsiflexion. INTERVENTIONS: Thirty minutes per day of the mirror therapy program, consisting of nonparetic ankle dorsiflexion movements or sham therapy, in addition to a conventional stroke rehabilitation program, 5 days a week, 2 to 5 hours a day, for 4 weeks. MAIN OUTCOME MEASURES: The Brunnstrom stages of motor recovery, spasticity assessed by the Modified Ashworth Scale (MAS), walking ability (Functional Ambulation Categories [FAC]), and motor functioning (motor items of the FIM instrument). RESULTS: The mean change score and 95% confidence interval (CI) of the Brunnstrom stages (mean, 1.7; 95% CI, 1.2-2.1; vs mean, 0.8; 95% CI, 0.5-1.2; P=.002), as well as the FIM motor score (mean, 21.4; 95% CI, 18.2-24.7; vs mean, 12.5; 95% CI, 9.6-14.8; P=.001) showed significantly more improvement at follow-up in the mirror group compared with the control group. Neither MAS (mean, 0.8; 95% CI, 0.4-1.2; vs mean, 0.3; 95% CI, 0.1-0.7; P=.102) nor FAC (mean, 1.7; 95% CI, 1.2-2.1; vs mean, 1.5; 95% CI, 1.1-1.9; P=.610) showed a significant difference between the groups. CONCLUSIONS: Mirror therapy combined with a conventional stroke rehabilitation program enhances lower-extremity motor recovery and motor functioning in subacute stroke patients.