Journal watch: Recent studies of note

Recent studies about predicting surgical outcomes, abdominal CTs for C. diff patients, and other topics.

Perioperative diastolic dysfunction predicts surgery outcomes

Perioperative diastolic dysfunction independently predicts postoperative congestive heart failure (CHF) and prolonged length of stay after major vascular surgery, a recent study found. 0&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=cae91552269908af75546cf967cf4f95

Researchers performed perioperative transesophageal echo (TEE) on 313 patients undergoing elective vascular surgery. Left ventricular diastolic function was assessed with transmitral flow propagation velocity (Vp), with Vp < 45 cm/s defined as abnormal. A left ventricular ejection fraction (LVEF) of < 40% constituted abnormal systolic function. Postoperative adverse outcome was defined as one or more adverse events, including myocardial infarction (MI), CHF, significant arrhythmia, prolonged intubation, renal failure and death. The study was published in the July Journal of Vascular Surgery.

While 8% of patients had isolated systolic dysfunction, 43% had isolated diastolic dysfunction, and 24% had both. Thirty percent of patients experienced at least one adverse outcome in the perioperative period, with CHF being the most common at 20%, and arrhythmia the second most common at 8%. Patients with abnormal diastolic function were twice as likely to have at least one adverse outcome (36% vs. 18%, P=0.002), and a significantly longer length of stay (7 days vs. 5 days, P<0.001), compared with patients with normal diastolic function. This difference was mostly due to increased CHF incidence. Systolic function didn't significantly predict adverse events or length of stay.

Past research has shown that more than 50% of geriatric patients undergoing surgery have preoperative diastolic dysfunction with normal LVEF, the study's authors noted. Until there is specific therapy for diastolic dysfunction, patients likely should continue with anti-ischemic rate control and diuretics, and avoidance of fluid overload. An accurate diagnosis is the first step toward developing a therapeutic strategy, the authors added. Additional studies are needed to determine the benefits of diastolic function assessment for preoperative risk stratification, as well as for goals for therapy.

Abdominal CT helps with prognosis for C. difficile patients

Abdominal computed tomography (CT) provides additional prognostic information for Clostridium difficile patients compared to that which can be obtained through clinical or laboratory means alone, a recent study found.

In their retrospective cohort study of 1,189 adult patients with newly diagnosed C. difficile infection (CDI), researchers found 165 patients who had undergone abdominal CT within 72 hours of diagnosis by positive stool sample. These CT patients were younger, were more likely to have a fever, had a higher peak white blood cell count, and had a higher serum creatinine level than patients who didn't have CT. The study was published online July 10 in Clinical Infectious Diseases.

The two groups didn't differ in outcomes, and there was no difference in CT findings before and after the emergence of the BI/NAP1/027 hypervirulent strain of C. diff. Pleural effusion (adjusted odds ratio [AOR], 2.6; 95% CI, 1.1 to 6.6), colonic wall thickness >15 mm (AOR, 6.0; 95% CI, 1.1 to 33.9), peak white blood cell count ≥ 30 × 109 cells/L (AOR, 4.8; 95% CI, 1.4 to 16.4), albumin level <20 g/L (AOR, 6.9; 95% CI, 2.4 to 20.1), and immunosuppression (AOR, 4.7; 95% CI, 1.5 to 15.3) were independently associated with complicated CDI.

Study weaknesses include an inherent selection bias, in that CT is more likely to be done on patients with more severe disease or atypical presentation. The most important findings were that the presence of pleural effusion, as well as the maximal thickness of the colonic wall, was independently associated with a higher risk of developing complicated CDI, the authors said. Maximal colonic wall thickness must reflect the severity of the inflammatory process in a way that peripheral leukocytosis doesn't entirely capture, they noted. It's not yet known whether the additional information that CT provides can lead to better treatment or outcomes, they added.

Study suggests optimal anticoagulation intensity for some cardiac patients

Anticoagulation in patients with certain cardiac conditions is most effective and least risky at specific international normalized ratios (INRs), according to a recent study.

Dutch researchers examined data from patients with mechanical heart valve prostheses (n=483), atrial fibrillation (n=2,111) and myocardial infarction (MI, n=1,608) who presented to an anticoagulation clinic between 1994 and 1998. The researchers calculated incidence rates of untoward events, defined as major thromboembolism and major hemorrhage, according to intensity of anticoagulation, as measured by INRs. Optimal intensity was defined as “the INR level that provides the lowest overall incidence of untoward events.” The study results appeared in the July 13 Archives of Internal Medicine.

A total of 4,202 patients (7,788 patient-years) and 3,226 hospital admissions were included in the study. Three hundred six hospital admissions were due to untoward events. Rates of untoward events were similar for the three patient groups: 4.3% (95% CI, 3.1% to 5.6%) in patients with mechanical heart valve prostheses, 4.3% (95% CI, 3.7% to 5.1%) for patients with atrial fibrillation and 3.6% (95% CI, 3.0% to 4.4%) for patients with MI. The authors used the medical record to determine patients' INRs on the day of the untoward event in 278 cases and within eight days of the untoward event in 10 cases. INRs were not available in 18 cases. After calculating INR-specific incidence rates, the authors determined that the optimal intensity of anticoagulation was an INR of 2.5 to 2.9 in patients with mechanical heart valve prostheses, an INR of 3.0 to 3.4 in patients with atrial fibrillation, and an INR of 3.5 to 3.9 in patients with MI.

The authors noted that their results should be interpreted with caution because the study included few events and did not consider individual patient characteristics. They also pointed out that vitamin K antagonists and antiplatelet agents are rarely used concomitantly in The Netherlands. Also, their national target ranges at the beginning of the study, which were 3.6 to 4.8 for mechanical heart valve prostheses and 3.0 to 4.0 for atrial fibrillation and MI, changed in 1996 to 3.0 to 4.0 for mechanical heart valve prostheses and MI and 2.5 to 3.5 for atrial fibrillation. However, they concluded that an INR of 3.0 is an appropriate target for patients with mechanical heart prostheses and those with atrial fibrillation, while an INR of 3.5 is appropriate after MI. Future studies should be done to test these ranges and “provide us with a final answer as to which INR level is safest for patients at high risk of arterial thromboembolism,” they wrote.

Low preoperative hemoglobin level predicts post-CABG mortality

A low preoperative hemoglobin level, both as a continuous variable and as a dichotomous variable (“anemic,” defined as a hemoglobin of <13 g/dL in men and <12 g/dL in women, or “not anemic”) is an independent predictor of mortality in patients undergoing coronary artery bypass grafting (CABG), a study has found.

Researchers analyzed data for 10,025 patients who underwent isolated CABG from 1998 through 2007, and classified them into four groups. In the “very low” group, hemoglobin was <12 g/dL for men and <11 g/dL for women; in the “low” group it was ≥12 and <13 g/dL for men and ≥11 and <12 g/dL for women. These latter two groups were considered anemic. In the “normal” group, the hemoglobin level was ≥13 and <14.5 g/dL in men and ≥12 and <13.5 g/dL in women, while the “high normal” group had hemoglobin levels ≥14.5 g/dL in men and ≥13.5 g/dL in women. Follow-up data on mortality were obtained primarily from health insurance companies, with early mortality defined as death within the first 30 postoperative days and late mortality defined as death at 31 or more postoperative days.

On multivariate logistic regression analysis, anemia was found to be an independent risk factor for higher early mortality, while Cox analyses found that both low hemoglobin level and anemia predicted higher late mortality. The annual incidence of death was 7.8 per 100 patient-years in the very low hemoglobin group, 5.3 in the low group, 2.6 in the normal group, and 1.8 in the high-normal group. When compared with a matched general population cohort, patients with the lowest preoperative hemoglobin levels had a worse outcome, and those with the highest levels had a better one. The study appeared in the July 14 Circulation.

It's difficult to determine if the correlation between hemoglobin level and early mortality is linear because of confounders like diabetes, older age, peripheral vascular disease, renal function impairment and low left ventricular ejection fraction, the authors said. Given the study results, a low hemoglobin level should be considered an independent predictor of higher short- and long-term mortality, they added, and future studies may help establish whether treatment of anemia before surgery can improve outcomes.

NIHSS score a poor predictor of proximal occlusion in acute cerebral ischemia

Although a high score on the National Institutes of Health Stroke Scale (NIHSS) correlates with having a proximal arterial occlusion (PO) in patients with acute cerebral ischemia, no score threshold can be safely applied to determine whether such patients should have angiographic imaging, a study found.

In a prospective cohort study, researchers dichotomized 699 acute cerebral ischemia patients by presence of PO, including a subgroup of 177 subjects with middle cerebral artery M1 occlusion. Admission non-enhanced CT scans were obtained, followed by CT angiograms. NIHSS scores were obtained at admission, 24 hours after admission, at discharge, and at six-month follow-up. The study was published in the July 16 online Stroke.

Patients with a PO had a higher median NIHSS score than the overall median (9 vs. 5, P<0.0001). Patients with middle cerebral M1 occlusion had a median NIHSS score of 14. An NIHSS score of ≥ 10 had an 81% positive predictive value for PO, but only 48% sensitivity with a majority of PO patients who presented with lower NIHSS scores. On average, the NIHSS scores of patients found to have PO were just 2.8 points higher than the average for all presenting patients. To detect 90% of patients with PO, all patients with an NIHSS score ≥2 would need to undergo angiographic imaging, the researchers found.

One limitation to the study is that patients who were unable to get intravenous contrast were excluded. Such patients are likely to have had greater comorbidities, and may have influenced the predictive relationship between the NIHSS score and presence of PO in some way, the authors noted. On the whole, however, the results indicate that while there is a need to evaluate acute stroke patients efficiently, physicians wouldn't catch the majority of POs if they tried to increase efficiency by excluding patients with low NIHSS scores from angiographic and perfusion imaging, the authors said.

Higher NIHSS score may predict clinical outcomes after tPA use for ischemic stroke

A higher National Institutes of Health Stroke Scale (NIHSS) score, extensive early CT changes and baseline antiplatelet use are associated with a higher risk of intracerebral hemorrhage after thrombolytic therapy, but only the NIHSS score is associated with clinical outcome, a recent study found.

Researchers studied 965 acute ischemic stroke patients who were treated with intravenous tissue plasminogen activator (tPA) within three hours of symptom onset. The mean time from symptom onset to tPA treatment was 145 ± 33 minutes, and the mean and median NIHSS at enrollment was 14. Post-tPA symptomatic intracerebral hemorrhage was defined as a worsening on the NIHSS score of ≥ 4 points within 36 hours with evidence of hemorrhage on follow-up neuroimaging. Early CT changes were graded using the Alberta Stroke Program Early CT Score (ASPECTS). A good clinical outcome was defined as a modified Rankin scale of 0 to 2 at 90 days. The study was published in the July 16 online Stroke.

Symptomatic intracerebral hemorrhage struck 5.6% of patients, with incidence increased in those with baseline antiplatelet use (single antiplatelet: OR, 2.04, 95% CI, 1.07 to 3.87, P=0.03; double antiplatelet: OR, 9.29, 95% CI, 3.28 to 26.32, P<0.001), higher NIHSS score (OR, 1.09 per point, 95% CI, 1.03 to 1.15 per point, P=0.002), and CT changes (ASPECTS 8 to 9: OR, 2.26, 95% CI, 0.63 to 8.10, P=0.21; ASPECTS ≤7: OR, 5.63, 95% CI, 1.66 to 19.10, P=0.006). A higher NIHSS score was associated with decreased odds of good clinical outcome (OR, 0.82 per point, 95% CI, 0.79 to 0.85 per point, P<0.001), but there was no relationship between clinical outcome and CT changes or baseline antiplatelet use.

The study is limited in that enrolled subjects may not be representative of stroke patients in clinical practice, since exclusion criteria were prior disabling stroke, severe renal disease or multiple comorbidities that limit life expectancy. The finding of an especially increased risk of symptomatic intracerebral hemorrhage with double antiplatelet therapy is novel and requires future confirmation, the authors noted. Since there was no association between prior use of antiplatelet therapy and clinical outcome, the results don't support using this factor to withhold tPA treatment, they concluded.

Postural blood pressure effective, less costly than imaging for diagnosing syncope

Measuring postural blood pressure is often more effective than more expensive imaging and laboratory tests in diagnosing and managing syncope in elderly patients, a recent study found, but it is used in fewer than half of patients admitted for syncope.

Researchers reviewed records of 2,106 consecutive patients age 65 or older who were admitted to one hospital following a syncopal episode. The most frequently obtained tests were electrocardiograms (99% of admissions), telemetry (95%), cardiac enzyme tests (95%) and head computed tomographic scans (63%). However, results from these tests affected diagnosis or management in fewer than 5% of cases while postural blood pressure recording (performed in 38% of patients) had a much higher yield in terms of affecting diagnosis (18% to 26%) and management (25% to 30%) and determining etiology (15% to 21%). The study results appeared in the July 27 Archives of Internal Medicine.

Relatively inexpensive postural blood pressure testing is greatly underused, the researchers commented, potentially leading to missed opportunities to initiate effective treatments, such as medication reduction. They suggested that screening patients with the San Francisco syncope rule, for example, may be helpful in identifying those most likely to benefit from cardiac testing. The San Francisco syncope rule is defined as a history of one or more of the following, according to the study: congestive heart failure, a hematocrit level of less than 30%, an abnormal result on electrocardiography, shortness of breath, or systolic blood pressure below 90 mm Hg.

An accompanying editorial noted that while the study highlights the importance of postural blood pressure testing, it does not discuss whether the changes made as a result of the more expensive tests were lifesaving or only led to mild improvements. In addition, a statement from the American Heart Association and the American College of Cardiology stresses the risk of mortality and recommends an electrocardiogram for every patient with syncope. More clinical trials are needed to inform guidelines, the editorial added.

Antipsychotics associated with hyperglycemia risk in older patients with diabetes

Older patients with diabetes who were prescribed an antipsychotic drug had a significantly increased risk of hospitalization for hyperglycemia, particularly during the initial course of treatment, a recent study reported.

In the nested case-control, population-based study, researchers looked at records of patients age 66 years or older with diabetes who started taking an antipsychotic drug between April 1, 2002 and March 31, 2006 and were followed for up to five years from treatment start until March 31, 2007. Subjects were divided into three groups: insulin-treated, oral hypoglycemic agent only-treated, and no diabetes treatment. Antipsychotic treatment was associated with a higher risk of hyperglycemia compared with remote antipsychotic use in all diabetes treatment groups, with the risk highest among patients treated with atypical and typical agents, especially those just starting treatment. The results appeared in the July 27 Archives of Internal Medicine.

The findings stress the importance of enhanced glycemic monitoring after initiation of antipsychotic therapy in older patients with diabetes, the authors said. Noting the prevalence of diabetes, the widespread use of antipsychotic drugs, and recent warnings regarding higher risk of stroke and death with antipsychotic agents, the authors recommended more careful consideration of the risks and benefits before prescribing them to vulnerable patients.

Further study is needed to determine whether the findings represent a causal effect of antipsychotics, said the authors. For now, physicians should consider other options to manage behavioral symptoms of dementia in older persons with diabetes, and families should be alerted to watch for signs of glycemic decompensation after antipsychotics are initiated, they said.

Look for clinically significant diarrhea before testing for C. diff

As Clostridium difficile infection (CDI) becomes more virulent and frequent, it is critical that physicians relearn two basic criteria for diagnosis: clinically significant diarrhea and the presence of toxigenic C. diff in the stool determined by lab testing, according to an expert commentary in the Aug. 4 Annals of Internal Medicine.

Clinically significant diarrhea, defined as three or more loose stools per day for at least one to two days, is the standard for suspecting CDI but it is not always heeded, the authors said. Studies have shown that asking about the number of loose stools as soon as CDI is suspected identifies those at high risk, they said. The authors cited other studies finding that up to 39% of patients would not need testing if simple diagnostic rules were followed, given that Clostridium difficile colonization can be common.

The authors also noted the following

  • A real-time polymerase chain reaction test to detect the gene for toxin B is the most sensitive and specific test available for detecting toxigenic C. diff in the stool, and results are often available the same day.
  • Repeat testing is not always useful because the stool may contain something that will continue to cause false-negative test results and the probability of disease decreases with each negative test result. Both issues highlight the value of using a high-sensitivity test.

High-dose statin one day before stenting may prevent MI

Administering a single high dose of atorvastatin up to 24 hours before elective percutaneous coronary intervention (PCI) reduces the risk of myocardial infarction (MI), a study concluded.

Researchers randomly assigned 668 statin-naïve patients to 80 mg of atorvastatin or no statin the day before elective PCI. The incidence of periprocedural MI (defined as a CK-MB elevation more than three times the upper limit of normal alone or associated with chest pain or ST-segment or T-wave abnormalities) was 9.5% in the statin group compared with 15.8% in the control group (odds ratio, 0.56; 95% CI, 0.35 to 0.89; P=0.014). The results were published in the Aug. 5 online Journal of the American College of Cardiology.

Previous studies have demonstrated that statins given three to seven days before coronary stent implantation can prevent MI, the authors said. The results of this study suggest that statins' cardioprotective effect occurs more quickly than previously thought and, therefore, there may be no need to postpone PCI in all statin-naïve patients undergoing elective coronary procedures.

The authors noted that the study was not blinded and was not designed to assess the mechanisms of statins' cardioprotective effect. Previous studies suggest that the benefits are related to the so-called pleiotropic effects that modify inflammation responses, endothelial function, plaque stability and thrombus formation. Notably, they said, both the anti-inflammatory and the endothelial effects may occur immediately after a single dose.

Apixaban after knee replacement effective, lowers bleeding risk

Apixaban and enoxaparin had similar efficacy for thromboprophylaxis after knee replacement but apixaban was associated with a lower risk of major bleeding, a recent study concluded.

In the double-blind study, researchers randomly assigned 3,195 patients undergoing total knee replacement to receive 2.5 mg of apixaban orally twice daily or 30 mg of enoxaparin subcutaneously every 12 hours. Medications were started 12 to 24 hours after surgery and continued for 10 to 14 days, after which venography was performed. The rate of the primary efficacy outcome (a composite of asymptomatic and symptomatic deep venous thrombosis, nonfatal pulmonary embolism [PE], and death from any cause during treatment) was similar for both treatments, but the rate of major bleeding and clinically relevant non-major bleeding was higher in the enoxaparin than in the apixaban group (4.3% vs. 2.9%, P=0.03). There was no increased risk of hepatotoxicity or arterial thromboembolism in either group. The study, which was supported by Bristol-Myers Squibb and Pfizer, appeared in the Aug. 6 New England Journal of Medicine.

The rates of symptomatic VTE and related death were low in both groups, although patients treated with apixaban had a higher rate of PE (1.0% vs. 0.4%), possibly due to chance, the authors said. They noted that the primary efficacy outcome was much lower than expected in both groups but that this is consistent with an overall decrease in postoperative thrombosis rates, possibly due to improved anesthetic and surgical techniques and the relatively recent practice of having patients walk sooner after surgery. The statistical criterion for the non-inferiority of apixaban versus enoxaparin was not met since the actual outcome incidence was only about half what was expected.

The authors concluded that specific factor Xa inhibition (apixaban) may have a better benefit-to-risk profile compared with low-molecular-weight heparins (enoxaparin) because of the former's potential to combine effective thromboprophylaxis with a low risk of bleeding.