Recent Research

Urinary test to guide pneumonia treatment, stroke risk after CABG, and more.

Urinary test optimizes treatment of pneumonia

The pneumococcal urinary antigen test can effectively help guide drug selection to treat community-acquired pneumonia (CAP) in the hospital, according to a recent study.

The prospective study included 474 cases in 464 adults who were hospitalized with CAP from February 2007 through January 2008. Blood cultures were performed in 80.6% of patients and pleural fluid was analyzed in 9.9%. Overall, Streptococcus pneumoniae was identified as the causative pathogen in 36.1% of the patients. In 43.8% of those patients, the pathogen was detected exclusively by the urine test. However, 14.6% of patients had CAP caused by a pathogen other than Streptococcus pneumoniae. The sensitivity of the test was 70.5%, but the specificity was 96%, the positive predictive value ranged from 88.8% to 96.5% and positive likelihood ratio ranged from 14.6 to 19.9. The study was published in the Jan. 24 Archives of Internal Medicine.

Based on the results of the test, clinicians reduced the spectrum of antibiotics used in 41 patients, all of whom were cured of pneumonia. The study authors suggested that such optimization might have been possible in all 75 patients diagnosed exclusively by the urine test. It's unfortunate that more physicians didn't use the positive test to guide therapy, agreed a commentary that accompanied the study. The commentary author called for physician education to encourage prescription of narrow-spectrum antibiotics.

The authors of both the study and the commentary concluded that the pneumococcal urinary antigen test is useful for treating hospitalized adults with CAP. When the test is positive, clinicians should use it to optimize antimicrobial therapy by choosing a narrow-spectrum agent. Therefore, the test should be incorporated into clinical guidelines at the same level as, but supplementary to, classic microbiological studies, the study authors concluded. The commentary also noted that urinary antigen tests, along with other rapid tests, should be conducted as soon as possible in patients with suspected pneumonia.

Postoperative stroke risk peaks at 40 hours after CABG

Nearly 60% of strokes in coronary artery bypass grafting (CABG) surgery patients occurred postoperatively rather than intraoperatively, and the risk of postoperative stroke peaked at 40 hours after surgery, a recent study found.

In a prospective study from 1982 through 2009, researchers examined 45,432 consecutive patients at the Cleveland Clinic who underwent isolated primary or reoperative CABG surgery. CABG was performed using off-pump, on-pump with beating heart, on-pump with arrested heart, or on-pump with hypothermic circulatory arrest strategies. The researchers recorded strokes after CABG prospectively and classified them as intraoperative—with neurologic deficit apparent immediately after awakening from anesthesia—or postoperative, meaning the stroke occurred after the patient awoke without neurologic deficit. Stroke was defined as any new focal or global neurologic deficit that lasted more than 24 hours and couldn't be explained by another medical process. Results were published in the Jan. 26 Journal of the American Medical Association.

Among all CABG patients, 1.6% (n=705) had a stroke. Among stroke patients, intraoperative stroke occurred in 40% (n=279) and postoperative stroke in 58% (n=409); timing was indeterminate in 2.4% (n=17). Risk of postoperative stroke peaked at 40 hours after surgery, and by day six had decreased to a constant hazard of 0.055%/day (95% CI, 0.047% to 0.065%). For both types of stroke, risk factors were older age, smaller body surface area, previous stroke, preoperative atrial fibrillation, and on-pump CABG with hypothermic circulatory arrest. New-onset postoperative atrial fibrillation posed no increased risk of stroke, and was in fact associated with a lower risk. Patients with stroke were more likely to die in the hospital (19% vs. 3.7%, P<0.001), have prolonged ventilation (44% vs. 15%, P<0.001), and have renal failure (13% vs 4.3%, P<0.001). They also had longer stays in intensive care (median, 120 vs. 48 hours, P<0.001); longer postoperative lengths of stay (median, 14 days vs. 7 days, P<0.001); and worse survival at one, 10 and 20 years, mostly due to a prolonged early risk of stroke up to about three months.

The timing of postoperative stroke risk reflects a constant “background” risk after surgery due to arteriosclerosis, as well as an unexplained peak risk in the second day after surgery, the authors noted. The peak may be explained, in part, by the inflammatory process and hypercoagulability after surgery; identifying the etiology of this risk could lead to better strategies to prevent it, like more aggressive use of antiplatelet and antithrombotic agents, they wrote. They also noted that the background risk decreased over time, and contributed the most to a downward trend of stroke after CABG that was seen in the last 20 years of the study. Also noteworthy was that the treatment of new-onset postoperative atrial fibrillation with early medical conversion or electrocardioversion, then rate control and anticoagulation if needed, appeared to not only prevent a higher risk of postoperative stroke, but may actually have lowered the risk, they wrote.

Interval between aspirin use and CABG affects transfusions, not mortality

Stopping aspirin less than six days before CABG did not change patients' mortality risk, but it did increase the need for transfusions, according to a recent retrospective study.

For the study, researchers at the Cleveland Clinic categorized more than 4,000 patients who were on aspirin and underwent CABG by how close to surgery they took aspirin. About 2,300 patients discontinued aspirin use six or more days before surgery (early discontinuation) and 1,845 were taking aspirin within five days of surgery (late use). Due to substantial differences between the two groups, the study authors used propensity matching to obtain 1,579 matched pairs of patients. The results showed no difference in in-hospital mortality, myocardial infarction and stroke between the early discontinuation and late use groups (1.7% vs. 1.8%, P=0.80). The study was published in the Feb. 15 Circulation.

The late use group did have more intraoperative transfusions (23% vs. 20%, P=0.03) and postoperative transfusions (30% vs. 26%, P=0.009) than the early discontinuation patients. Patients in the late group also had a trend toward more reoperations, but the difference was not statistically significant (3.4% vs. 2.4%, P=0.10). Some experts would consider the difference in transfusions to be an argument for early discontinuation, the study authors noted, but they concluded that physicians should weigh the risks and benefits for individual patients.

In high-risk patients, the study authors recommended late use of aspirin to reduce the risk of preoperative cardiovascular events. They pointed out that patients who did not undergo planned surgery due to a preoperative illness were not included in the analysis, so any preoperative MIs or strokes resulting from early discontinuation would not have been measured in the analysis.

Current practice and guidelines on aspirin use before CABG vary widely, according to the authors of the study and an accompanying editorial. The American College of Cardiology and American Heart Association call for discontinuation 7 to 10 days before, the Society of Thoracic Surgeons recommends stopping 5 days before elective CABG, and the American Society of Chest Physicians suggests continuing aspirin up to and beyond CABG. The variation is indicative of the lack of definitive evidence on this issue, and the need for a randomized controlled trial to provide such data, the researchers concluded. The authors and the editorialist note that the ongoing Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) study should yield data on the use of antiplatelet and antifibrinolytic therapy given immediately before surgery.

Update released on using dabigatran to manage atrial fibrillation

Several cardiology specialty societies released a focused update on managing patients with atrial fibrillation to include the option of using dabigatran, the first new oral anticoagulant available for clinical use in more than 50 years.

The update contains a recommendation saying dabigatran is a useful alternative to warfarin to prevent stroke and systemic thromboembolism “in patients with paroxysmal to permanent atrial fibrillation and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (<15 mL/min), or advanced liver disease (impaired baseline clotting function).” The recommendation is Class I, meaning the treatment is useful/effective, and the level of evidence is B, meaning it came from a single randomized trial or nonrandomized studies. The update was jointly released by the American College of Cardiology Foundation, the American Heart Association, and the Heart Rhythm Society, and was published online Feb. 14 by the Journal of the American College of Cardiology.

The FDA approved dabigatran on Oct. 19, 2010, at doses of 150 mg twice daily for patients with a creatinine clearance higher than 30 mL/min, and a dose of 75 mg twice daily for patients with a creatinine clearance between 15 and 30 mL/min. There are no dosing recommendations for patients with a creatinine clearance below 15 mL/min or for patients on dialysis.

Approval of the higher dose was based on results of the RE-LY trial, which included more than 18,000 patients with a creatinine clearance of 30 mL/min or greater and a mean score of 2.1 on the CHADS2, a clinical prediction rule for stroke risk in atrial fibrillation patients. The trial compared dabigatran doses of 110 mg twice daily or 150 mg twice daily with open-label warfarin dosed to a target international normalized ratio (INR) of 2 to 3. The 110-mg dose was found to be noninferior, and the 150-mg dose superior, to warfarin for the outcome of stroke or systemic embolism. Results were published Sept. 17, 2009 in the New England Journal of Medicine (NEJM).

Patients who already take warfarin and have excellent INR control “may have little to gain by switching to dabigatran,” the update said, since it involves taking the medication twice a day, and carries a higher risk of nonhemorrhagic side effects. When thinking about the use of dabigatran, clinicians should consider “individual clinical features, including the ability to comply with twice-daily dosing, availability of an anticoagulation management program to sustain routine monitoring of INR, patient preferences, cost, and other factors,” the update said.

Response team and feedback reduce sepsis deaths in ICU

Activating a sepsis response team and using weekly feedback reduce mortality for ICU patients with severe sepsis or septic shock, a study found.

In a 33-month prospective, interventional cohort study at a medical ICU, researchers performed daily screening of patients for severe sepsis or septic shock. Study periods were divided into baseline (screening only), daily auditing with weekly feedback, and sepsis response team activation, with comparisons made among the three periods. The baseline period, from Jan. 1, 2007 to Dec. 28, 2007, involved an educational program for nurses and housestaff on recognizing sepsis, and training on a protocol and order set, among other things. From Dec. 29, 2007 to Sept. 26, 2008, clinicians initiated daily auditing of all sepsis shock/severe sepsis patients in the ICU, in addition to baseline activities. Emergency department and medical ICU clinicians received weekly feedback on compliance with the sepsis resuscitation bundle, and were encouraged to discuss issues with a quality improvement team that met monthly.

From Sept. 27, 2008 to Sept. 30, 2009, a multidisciplinary sepsis response team (SRT) was active. The SRT call was activated 24/7 through an electronic paging system that notified the team when a patient met sepsis criteria. The team included doctors, nurses, respiratory therapists and several other medical staff. Auditing and feedback continued during the SRT period. Outcome measures included compliance with the overall sepsis resuscitation bundle and its individual elements, and hospital mortality. Results were published in February's Critical Care Medicine.

There were 984 episodes of severe sepsis (5.3%, n=52) and septic shock (94.7%, n=932) during the study periods. Compliance with the overall sepsis bundle increased from 12.7% at baseline to 37.7% during the weekly feedback period and 53.7% during the SRT activation period (P<0.001). Mortality was 30.3%, 28.3% and 22% during baseline, feedback and SRT periods, respectively (P=0.029). On multiple logistic regression analysis, the SRT was associated with reduced risk of mortality (odds ratio, 0.657; 95% CI, 0.456 to 0.945; P=0.023). The following conditions were associated with increased risk of death: hepatic cirrhosis, hepatic failure, leukemia, multiple myeloma, transfer from the same hospital ward, do-not-resuscitate status at recognition of severe sepsis/septic shock, and lactate level.

While some have suggested that the sepsis resuscitation bundle and early goal-directed therapy may not benefit patients in facilities with low baseline mortality, the current study suggests otherwise, the authors noted. The results demonstrate that weekly feedback and SRT activation are complementary in improving process of care and outcomes for severe sepsis/septic shock patients, they wrote. Study limitations include generalizability, as it was conducted in a single ICU. Also, researchers may have excluded some patients with severe sepsis due to their inclusion of only patients with hypotension despite fluid resuscitation or elevated lactate levels. Use of before-after comparisons also may have ignored undocumented differences among the study groups and in the patient mix, they noted.

Wireless pulmonary monitoring associated with less hospitalization

A wireless implantable hemodynamic monitoring system was associated with a significant reduction in hospitalizations for heart failure patients, researchers found.

Patients (n=550) from 64 American centers in a single-blind trial were randomly assigned to receive a wireless implantable hemodynamic monitoring system or to a control group receiving standard care for at least six months. Patients had New York Heart Association class III heart failure, irrespective of the left ventricular ejection fraction, and a previous hospital admission for heart failure. Only patients were masked to their assignment group. Results were released online Feb. 10 in The Lancet.

The primary efficacy endpoint was the rate of heart-failure-related hospitalizations at six months. In six months, 83 heart-failure-related hospitalizations were reported in the treatment group (n=270), compared with 120 in the control group (n=280; rate, 0.31 vs. 0.44; hazard ratio [HR], 0.70; 95% CI, 0.60 to 0.84; P<0.0001). During a mean follow-up of 15 months, the treatment group had a 39% reduction in heart-failure-related hospitalization compared with the control group (153 vs. 253; HR, 0.64; 95% CI, 0.55 to 0.75; P<0.0001). Non-heart-failure related hospitalizations were not different between the groups.

The treatment group had a greater reduction in pulmonary artery mean pressure, more days alive outside the hospital, and better quality of life than the control group during six months of follow-up. Survival rates in the treatment and control groups at six months were similar (255 [94%] vs. 260 [93%]; HR, 0.77; 95% CI, 0.40 to 1.51; P=0.45).

Length of stay for heart-failure-related hospitalizations was 2.2 days (SD, 6.8) in the treatment group versus 3.8 days (SD, 11.1) in the control group (P=0.02). The treatment group had a significantly greater number of changes to drugs for heart failure (2,468; mean, 9.1 per patient; SD, 7.4) than did the control group (1,061; 3.8 per patient; SD, 4.5; P<0.0001).

The first primary safety endpoint of the study was device-related or system-related complications (DSRCs). This was defined as adverse events related to the wireless pressure sensor or external electronics that required invasive treatment other than an intramuscular drug administration or a right-heart catheterization. Patients had 98.6% (95% CI, 97.3% to 99.4%) freedom from DSRC.

The second primary safety endpoint was pressure-sensor failure, defined as an inability to obtain readings. No pressure-sensor failures occurred. There were 15 serious adverse events, eight related to DSRC and seven related to the implantation procedure.

AHA issues statement on cerebral venous thrombosis diagnosis, management

The American Heart Association (AHA)/American Stroke Association issued a scientific statement in February on the diagnosis, treatment and management of cerebral venous thrombosis (CVT).

CVT is uncommon, representing 0.5% to 1% of all strokes, and usually affects individuals younger than age 50. Diagnosis and management can be difficult because of the diverse underlying risk factors, and the lack of uniformity in treatment, the statement said. Recommendations for diagnosis and treatment include the following:

  • In patients with suspected CVT, perform routine blood studies comprising complete blood count, chemistry panel, prothrombin time and activated partial thromboplastin time (Class I, Level C evidence).
  • Patients should be screened for potential prothrombotic conditions (including use of contraceptives, underlying inflammatory disease, or infectious process) that may predispose to CVT (Class I, Level C evidence).
  • In patients with headache associated with atypical features, imaging of the cerebral venous system is reasonable to exclude CVT (Class IIa, Level C evidence).
  • Although a plain computed tomography (CT) scan or magnetic resonance imaging (MRI) scan is useful in the initial evaluation of patients with suspected CVT, a negative plain CT or MRI doesn't rule out CVT. If CVT is suspected and either scan is negative, perform a venographic study. The study should also be performed to define the extent of CVT, when CT or MRI suggests the condition (Class I, Level C evidence).
  • Patients with CVT and a suspected bacterial infection should receive appropriate antibiotics and surgical drainage of purulent collections of infectious sources associated with CVT, when appropriate (Class I, Level C evidence).
  • It's reasonable to admit patients with CVT to a stroke unit for treatment and to prevent clinical complications (Class IIa, Level C evidence).
  • For patients with CVT, use initial anticoagulation with adjusted-dose unfractionated heparin or weight-based low-molecular-weight heparin in full anticoagulant doses, followed by vitamin K antagonists, whether or not intracerebral hemorrhage is present (Class IIa, Level C evidence).
  • Patients with CVT and increased intracranial pressure should be monitored for progressive visual loss. If visual loss is observed, they should be treated urgently for increased intracranial pressure (Class I, Level C). In patients with CVT and increased intracranial pressure, it is reasonable to start treatment with acetazolamide. Therapies including lumbar puncture, optic nerve decompression or shunts can be effective if there is progressive visual loss (Class IIa, Level C evidence).
  • Steroids aren't recommended for CVT patients, even in the presence of parenchymal brain lesions on CT/MRI, unless needed for another underlying disease (Class III, Level B evidence). Routine use of antiepileptics also isn't recommended, in the absence of seizures (Class III, Level C evidence).

The recommendations also include evaluation and management of CVT during pregnancy. The statement was published online Feb. 3 by Stroke.