Recent Research

Pneumonia after stroke, quetiapine for delirium, and more.

New risk score for in-hospital pneumonia after acute ischemic stroke

Researchers have developed a 34-point risk score to predict in-hospital pneumonia after acute ischemic stroke that appears to have better discrimination than older scores.

The researchers used data from the China National Stroke Registry, a nationwide, multicenter, prospective registry of consecutive patients with acute cerebrovascular events. Study patients were at least 18 years old, had been hospitalized with a primary diagnosis of acute ischemic stroke (AIS), and were directly admitted to the hospital from the emergency department or a clinic. Patients were then randomly placed in the derivation (60%) or internal validation (40%) cohorts. For external validation, researchers used the prospective Chinese Intracranial Atherosclerosis Study.

They obtained independent predictors of in-hospital stroke-associated pneumonia (SAP) after AIS by using multivariable logistic regression and β-coefficients to create a point-scoring system. The area under the receiver-operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively. Results were published in the May Stroke.

In the derivation cohort (n=8820) and in the internal (n=5882) and external (n=3037) validation cohorts, the in-hospital SAP rates after AIS were 11.4%, 11.3% and 7.3%, respectively. The 34-point score was developed from independent predictors for SAP, which included age, history of atrial fibrillation, congestive heart failure, chronic obstructive pulmonary disease and current smoking, pre-stroke dependence (modified Rankin Scale >3), National Institutes of Health Stroke Scale score on admission, Glasgow Coma Scale score, dysphagia, Oxfordshire Community Stroke Project subtype, and admission blood glucose.

The AIS-associated pneumonia (APS) score showed good discrimination (area under the receiver-operating characteristic curve) in the internal (0.785; 95% CI, 0.766 to 0.803) and external (0.792; 95% CI, 0.761 to 0.823) validation cohorts. The AIS-APS was well calibrated (Hosmer-Lemeshow test) in the internal (P=0.22) and external (P=0.30) validation cohorts. When compared with three previous scores, the AIS-APS showed significantly better discrimination with regard to in-hospital SAP after AIS (all P<0.0001).

The new score could be used to predict in-hospital SAP on hospital arrival, the authors noted. While prior studies have shown SAP to be a risk factor for morbidity and mortality after stroke, a systematic review of efficacy of early antibiotics prophylaxis after stroke didn't show benefit in outcomes, they noted. That may be due, however, to inclusion in those studies of patients with low risk of developing SAP, they wrote. More research still needs to be done on the effects of such prophylaxis in patients with known SAP risk, they wrote.

Dexmedetomidine associated with improved outcomes after cardiac surgery

Patients who receive dexmedetomidine after cardiac surgery may have lower postoperative rates of mortality as well as complications, according to a study.

Researchers performed a retrospective cohort study at a single medical center to examine whether patients who received dexmedetomidine after coronary artery bypass grafting (CABG) alone or CABG plus valvular or other procedures had better rates of postoperative complications and mortality.

The study's primary outcome measures were mortality and postoperative major adverse cardiocerebral events, including stroke, coma, perioperative myocardial infarction, heart block or cardiac arrest. Secondary outcomes were renal failure, sepsis, delirium, postoperative hours spent on a ventilator, length of hospital stay and 30-day readmission rates. The study results were published in the April 16 Circulation.

Overall, 1,134 patients were included in the study, 568 who received intravenous dexmedetomidine infusion and 566 who did not. Approximately 71% of patients were men, and most (67.6%) were white. Those in the dexmedetomidine group had significantly lower mortality rates in the hospital postsurgery (1.23% vs. 4.59%; adjusted odds ratio, 0.34; P<0.0001), at 30 days (1.76% vs. 5.12%; adjusted odds ratio, 0.39; P<0.0001), and at one year (3.17% vs. 7.95%; adjusted odds ratio, 0.47; P=0.0002). Risk for overall complications (47.18% vs. 54.06%; adjusted odds ratio, 0.80; P=0.0136) and delirium (5.46% vs. 7.42%; adjusted odds ratio, 0.53; P=0.0030) was also lower in the dexmedetomidine group.

The authors noted that their study was limited by its observational cohort design and its use of data from a voluntary database, among other factors. However, they concluded that perioperative use of dexmedetomidine was associated with lower postoperative mortality for up to one year, as well as lower rates of all postoperative complications and delirium in patients undergoing cardiac surgery. They called for additional multicenter randomized trials to confirm their findings.

Higher Framingham scores predict cognitive decline

The Framingham vascular risk scores may be better at predicting cognitive decline in late middle age patients than a score specifically designed to predict dementia in a recent study.

Researchers used data from the Whitehall II study, a longitudinal British cohort study. More than 7,000 study participants, with a mean age of 55.6 years at baseline, were assessed using the Framingham general cardiovascular disease risk score, the Framingham stroke risk score and the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score. To determine the incidence of cognitive decline, participants were given cognitive tests on reasoning, memory, verbal fluency, vocabulary and global cognition at three times over 10 years.

Patients who were at higher risk according to the Framingham scores also showed greater cognitive decline in all the tests except memory. Higher risk according to the CAIDE score was associated with decline in reasoning, vocabulary and global cognitive scores, but the Framingham scores had slightly stronger associations with overall 10-year cognitive decline, the study found. Diabetes, a factor in both Framingham scores, was found to be the biggest independent predictor of cognitive decline. Results were published in Neurology on April 2.

All three risk scores predicted cognitive decline, the study authors concluded. One explanation for the slight difference in accuracy might be the CAIDE score's inclusion of education, a factor that affects the risk of dementia but not the rate of cognitive decline. The Framingham scores also had more risk categories than the CAIDE for certain factors (for example, five systolic blood pressure ranges instead of two), which could make them more sensitive.

In addition to their greater predictive value, the Framingham scores might be more practical for primary prevention of cognitive decline, the authors suggested. A risk evaluation specifically for dementia could induce anxiety in patients, and the addition of another risk score is unlikely to be appealing to busy physicians. The Framingham scores are already used frequently in practice to alert patients to their risk for heart disease and stroke, so “in the future, they could also be told that they may be at higher risk of cognitive decline,” the authors said.

Quetiapine seems safe, effective for treating delirium

The second-generation antipsychotic quetiapine appears to be as safe and effective as other antipsychotics in treating delirium, according to a recent review.

Researchers did a literature search of English-language journal articles published between 1960 and 2012 that involved quetiapine and had treatment of delirium as the focus. They identified eight trials: two double-blind, randomized, placebo-controlled trials; five open-label trials; and one retrospective cohort. Results were published in the April Journal of Hospital Medicine.

One small (n=42) randomized, controlled trial (RCT) found no difference between quetiapine and placebo in total mean delirium scores at individual time points but did find that delirium severity improved 82% faster with quetiapine (P=0.026). The second RCT (n=36) found that the time to first resolution of delirium was shorter with quetiapine versus placebo (1.0 vs. 4.5 days; P=0.001) and that resolution occurred at least once in all quetiapine patients versus 78% of the time in placebo patients (P=0.05). A post-hoc analysis showed quetiapine patients had a significantly longer time to resolution of hyperactivity and agitation. The authors attributed this finding to higher use of as-needed haloperidol in the placebo group and the study design, which self-selected for agitated delirium by requiring as-needed haloperidol use as inclusion criteria. Results of the other six trials also showed significant improvement of delirium from baseline and showed that quetiapine was just as efficacious as haloperidol and amisulpride. All trials found a low incidence of adverse effects with quetiapine.

The authors acknowledged that the studies in the current review “have a limited level of evidence due to their small sample sizes, study designs, and heterogeneous subjects,” and that superiority of a particular antipsychotic can't be established as none of the studies did a head-to-head comparison. They nonetheless concluded that it appears quetiapine may be safe and effective in treating delirium in both general medicine and ICU patients.

Darbepoetin did not improve clinical outcomes for systolic heart failure, anemia

Darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild to moderate anemia, a study found.

Researchers conducted a double-blind trial that randomly assigned 2,278 patients with systolic heart failure and mild to moderate anemia (hemoglobin level, 9.0 to 12.0 g/dL) to receive either darbepoetin to a hemoglobin target of 13 g/dL or placebo.

The primary composite outcome of death from any cause or first hospitalization for worsening heart failure occurred in 576 patients (50.7%) in the darbepoetin group and 565 (49.5%) in the placebo group (hazard ratio [HR] in the darbepoetin group, 1.01; 95% CI, 0.90 to 1.13; P=0.87). Results were similar when adjusted for baseline characteristics (adjusted HR, 1.01; 95% CI, 0.90 to 1.13; P=0.88), in the as-treated analysis (HR, 0.98; 95% CI, 0.86 to 1.13; P=0.82) and across all subgroups examined.

There were 474 deaths (41.7%) in the darbepoetin group and 458 (40.1%) in the placebo group (HR, 1.04; 95% CI, 0.92 to 1.19; P=0.51), for annualized mortality rates of 14.4% and 13.8%, respectively. There were similar rates of death from cardiovascular causes, of first hospitalization for worsening heart failure, and on each component of the composite outcome. Five hundred seventy-two hospitalizations for heart failure (including second and subsequent hospitalizations) occurred in the darbepoetin group and 695 occurred in the placebo group (P=0.06 from a negative binomial model). The study was published in the March 28 New England Journal of Medicine.

The least-squares mean changes from baseline to month 6 in the Overall Summary Score of the Kansas City Cardiomyopathy Questionnaire were 6.68 points (95% CI, 5.35 to 8.01 points) in the darbepoetin group and 4.48 points (95% CI, 3.15 to 5.81 points) in the placebo group (treatment difference, 2.20 points; 95% CI, 0.65 to 3.75 points; P=0.005). An improvement in the Overall Summary Score of 5 points or more at six months was seen in 53% of the darbepoetin group and 48% of the placebo group (P=0.06). Increases from baseline to six months in the Symptom Frequency Score were 6.20 points (95% CI, 4.71 to 7.69 points) in the darbepoetin group and 3.91 points (95% CI, 2.42 to 5.40 points) in the placebo group (P=0.01).

Embolic and thrombotic adverse events were reported in 153 patients (13.5%) in the darbepoetin group and 114 (10.0%) in the placebo group (P=0.01). Septic shock was reported significantly more frequently in the darbepoetin group than in the placebo group, although there was no excess of other serious adverse events related to infection in the darbepoetin group. Cancer-related adverse events did not significantly differ between treatment and control groups, and there was no significant between-group difference in systolic blood pressure during the study. While there were more strokes in the darbepoetin group, the difference was not significant.

The researchers wrote, “[O]ur findings suggest that the hemoglobin level, like other surrogates, is simply a marker of poor prognosis in heart failure rather than a therapeutic target.”

Dabigatran appears at least as safe as warfarin in everyday practice, analysis finds

Dabigatran was at least as safe and efficacious as warfarin in an “everyday clinical practice” population of atrial fibrillation patients, a Danish study found.

Researchers used information from three Danish data sets to identify 4,978 patients treated with dabigatran after Aug. 1, 2011, and a propensity-matched group of 8,936 patients treated with warfarin starting between August 1, 2009 and June 30, 2010, and ending by Dec. 31, 2010. All patients had atrial fibrillation (AF) and were previously untreated with either drug. Patients with mechanical heart valves or previous diagnoses of pulmonary embolism, deep venous thrombosis, or mitral stenosis were excluded. Primary outcomes were stroke, intracranial bleeding and systemic embolism. Median follow-up after incident AF was 10.5 months (interquartile range, 7.9 to 13.4 months).

Rates of stroke and systemic embolism didn't differ significantly between patients treated with dabigatran versus warfarin. Patients who took either the 110-mg or 150-mg dabigatran dose twice a day had lower mortality (propensity-matched, group- stratified hazard ratios [aHR], 0.79 and 0.57, respectively) than those taking warfarin. Also, with both 110-mg and 150-mg dabigatran doses, there was less intracranial bleeding (aHR, 0.24 and 0.08 respectively) and a lower incidence of myocardial infarction (aHR, 0.30 and 0.40, respectively).

Gastrointestinal bleeding was lower with the 110-mg dose of dabigatran (aHR, 0.60) compared to warfarin, but not the 150-mg dose. Pulmonary embolism rates were also lower with both doses of dabigatran than with warfarin. These findings were broadly consistent in a subgroup analysis of dabigatran users at follow-up of at least one year. The analysis was published online March 26 by the Journal of the American College of Cardiology.

The results are the first from a nationwide, post-approval study of dabigatran used in everyday clinical practice, the authors noted. Compared to the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, the Danish study cohort was lower risk and had a lower prevalence of previous myocardial infarction (MI) or risk factors for MI. The study design “cannot account for the possibility that physicians could choose to avoid dabigatran in patients at higher risk of myocardial ischemia,” although results were consistent after risk adjustment, they noted.

“These data reflect ‘real world’ use data from an entire country, and no one is ruled out....This should provide the best conditions for a non-differential comparison between warfarin and dabigatran,” the authors concluded. “The previous concerns about an excess of bleeding events or myocardial infarction amongst dabigatran-treated patients were not evident.”

High-dose statins associated with more admissions for acute kidney injury

High-potency statins were associated with more hospital admissions for acute kidney injury than lower-potency doses, a study found.

Although the effect seemed to be strongest in the first 120 days after initiation of statin treatment, increased risk of admission remained elevated for at least two years, researchers noted.

To quantify an association between acute kidney injury and use of high-potency statins (defined as ≥10 mg of rosuvastatin, ≥20 mg of atorvastatin and ≥40 mg of simvastatin) versus low-potency statins, researchers conducted a retrospective observational analysis including more than two million patients age 40 years or older who were newly treated with statins from January 1997 through April 2008 in the U.S., United Kingdom and Canada. Each person hospitalized for acute kidney injury was matched with 10 controls.

Results appeared online March 19 at BMJ.

Among 2,008,003 patients without chronic kidney disease, there were 4,691 hospitalizations for acute kidney injury within 120 days of treatment. Among 59,636 patients with chronic kidney disease, there were 1,896 hospitalizations. In patients without chronic kidney disease, current users of high-potency statins were 34% more likely to be hospitalized with acute kidney injury within 120 days after starting treatment (fixed-effect rate ratio, 1.34; 95% CI, 1.25 to 1.43) than low-dose statin users. Users of high-potency statins with chronic kidney disease had a 10% increase in admission rate (fixed-effect rate ratio, 1.10; 95% CI, 0.99 to 1.23), a nonsignificant difference compared to low-dose statin users.

Researchers noted that clinicians should consider this potential risk before prescribing high-dose statins when treatment with a low-potency statin is an option. In previous studies of statins, more intensive statin treatment in secondary prevention was associated with a 0.3% reduction in absolute risk in major coronary events per year of treatment. But these previous studies could have overstated statins' efficacies in typical clinical practice, and mostly involved comparisons of a low dose of a statin to its highest possible dose, the authors said.

“In reality, clinicians would not choose between, for example, 10 mg of atorvastatin and 80 mg of atorvastatin,” researchers wrote. “Given what is likely to be a small magnitude of incremental cardiovascular benefit of high potency statins over low potency statins in reality, a pressing question is how to identify patients for whom the risk-benefit balance for high potency statin treatment is unfavorable.”

An editorial noted, “Despite extensive experience with the use of statins over many years, optimization of doses to derive benefit but minimize risk is still evolving. The results of the current study indicate that a randomized controlled trial is needed to compare the adverse effects of high and low potency statins.”

Neurologists offer guidelines on diagnosing sports concussions

Updated recommendations on evaluating and managing sports-related concussions were recently released by the American Academy of Neurology (AAN).

The guideline authors reviewed the literature from 1955 to 2012 to update a 1997 AAN practice parameter and assess risk factors, diagnostic tools, interventions and risk for complications related to concussions. The evidence-based guideline update was published online by Neurology on March 18.

According to the guidelines, the Post-Concussion Symptom Scale and Graded Symptom Checklist are likely to accurately identify sports-related concussions and may be administered by trained personnel, nurses or physicians. The Standardized Assessment of Concussion is also likely to identify concussions in early stages post-injury. Neuropsychological testing could, as well, but requires a neuropsychologist for accurate interpretation. The Balance Error Scoring System identifies concussions with low to moderate diagnostic accuracy, the guidelines said.

CT imaging should not be used to diagnose sports-related concussions but may be used to rule out more serious traumatic brain injury in athletes who have loss of consciousness, post-traumatic amnesia, persistently altered mental status, focal neurological deficits, evidence of skull fracture or signs of clinical deterioration.

Patients who have been diagnosed with a concussion are more likely to suffer post-concussion impairments if they have ongoing clinical symptoms, concussion history or a younger age (high school age or younger concussion patients should be managed more conservatively than older athletes, the guidelines noted). Athletes should be prohibited from returning to play or practice until a licensed health care professional has judged that the concussion has resolved and the athlete is asymptomatic off medication.

Data are insufficient to show that any intervention enhances recovery or diminishes long-term sequelae post- concussion, although, based on research in mild traumatic brain injury, clinicians might provide cognitive restructuring (brief psychological counseling that consists of education, reassurance and reattribution of symptoms) to shorten the duration of subjective symptoms and diminish the risk for chronic post-concussion syndrome, the guidelines said.

An accompanying editorial noted that neurologists have become much more closely involved in maintaining the health and safety of professional athletes in recent years and will play an essential part in responses to the public health problem of sports-related concussions.

Aortic stenosis increases postoperative risks

Patients with aortic stenosis have a higher risk of postoperative myocardial infarction and death 30 days after noncardiac surgery, compared to those without aortic stenosis, a study found.

Researchers aimed to ascertain the validity of recommendations by the American College of Cardiology/American Heart Association that patients with severe symptomatic aortic stenosis (AS) are at elevated risk from elective noncardiac surgeries. The recommendations are based on a few, small observational studies with conflicting results, the researchers said. For their study, they used surgical and echocardiographic databases to identify 244 patients with severe AS and 390 patients with moderate AS. Each patient with AS who underwent noncardiac surgery (NCS) was matched with four control patients. The primary outcome was a composite of 30-day mortality and postoperative myocardial infarction.

The primary outcome was seen in 4.9% of AS patients and 2.1% of control patients (P<0.001). Thirty-day mortality was 2.1% for AS patients and 1.0% in non-AS controls (P=0.036). Postoperative myocardial infarction was more frequent in patients with AS than with controls (3.0% vs. 1.1%; P=0.001). There were no significant differences in postoperative heart failure and stroke between the two groups. Significant predictors of primary outcome in AS patients included high-risk surgery, symptomatic severe AS, coexisting mitral regurgitation and preexisting coronary disease. Results were published in the March Circulation: Cardiovascular Quality and Outcomes.

The study results offer “substantial evidence” for current recommendations by the ACC/AHA, including that patients with severe symptomatic AS should have surgical aortic valve replacement before elective NCS, though “such a recommendation is not available for asymptomatic patients.” Larger-scale studies are needed to see the impact of correcting valvular abnormalities before high- or intermediate-risk NCS, they added. For those patients deemed to be poor surgical candidates, percutaneous transcatheter aortic valve replacement may be a potential therapeutic option before NCS, they wrote.