Recent Research

HIV screening recommendations, perioperative SSRI risks, anticoagulants and endocarditis, and more.


Many younger patients with stroke have cognitive deficit a decade later

As many as half of patients who had a stroke when they were younger than 50 years old appear to have long-term cognitive effects, a recent study found.

Researchers studied 277 consecutive patients aged 18 to 50 years who had a first-ever ischemic stroke and were admitted to a single Dutch academic center from Jan. 1, 1980, to Nov. 1, 2010. Ischemic stroke was defined as focal neurologic deficit persisting longer than 24 hours. Since diagnostic techniques have improved in the last 30 years, all initial diagnoses were reviewed by a panel of experts. A group of 146 controls was recruited among patients' spouses, relatives or social environments; controls had to be at least 18 years old and without history of stroke or transient ischemic attack. Both groups received cognitive assessment sometime between late 2009 and late 2011. Results were published in the June Stroke.

Mean follow-up was 11 years, and the mean age at stroke onset was 40 years. Up to 50% of patients with ischemic stroke had below-average performance or cognitive impairment on testing. Worse cognitive performance was significant on six domains compared with controls: processing speed, working memory, immediate memory, delayed memory, attention and executive functioning (P≤0.0002 for all). In stroke patients, longer follow-up duration was associated with lower immediate memory (P=0.001), delayed memory (P<0.0001) and executive functioning score (P<0.0001). After exclusion of patients with recurrent stroke (n=30), there was no longer a significant relation between follow-up duration and executive functioning. Patients with a left supratentorial infarction had the worst cognitive outcome.

The researchers noted that longer follow-up was associated with worse cognitive functioning and suggested as possible causes incident comorbidity or emergence of neurodegenerative pathology that interacted with the cerebrovascular disease. “Given the importance of cognitive performance for post-stroke quality of life, cognitive functioning should be monitored in clinical practice,” the authors concluded. “This may also yield valuable information for treating rehabilitation services and return to work.”

S. aureus, anticoagulants raise risk of endocarditis complications

In patients with infective endocarditis, four significant risk factors were associated with all neurological complications, while antimicrobial therapy reduced the risk, a recent study found.

The retrospective analysis included data on 1,345 consecutive episodes of left-sided infective endocarditis treated at eight Spanish medical centers. Researchers used Cox regression models to identify variables that predicted neurological complications and associated mortality. Results were published by Circulation on May 6.

Overall, 25% of patients had a neurological complication: 14% had an ischemic event, 6% had encephalopathy/ meningitis, 5% had hemorrhages, and two patients had brain abscesses. Patients faced a significantly higher risk of neurological complication if they had a vegetation of 3 cm or more (hazard ratio [HR] 1.91), Staphylococcus aureus infection (HR, 2.47), or mitral valve involvement (HR, 1.29) or if they received anticoagulant therapy (HR, 1.31). Based on these results, it seems advisable to avoid anticoagulant therapy in patients with these other risk factors, the study authors concluded.

In general, neurological complications were associated with higher mortality risk, but the researchers noted that ischemic stroke and brain hemorrhage were the only complications significantly associated with mortality when assessed individually (HR, 1.63 and 1.73, respectively). Patients with hemorrhage had a higher mortality risk if surgery was performed within four weeks of the hemorrhage (75% vs. 40%). Thus, it may be advisable to delay surgeries in these patients. However, large vegetation size should lead to consideration of early surgery, the authors said, and the risk of postoperative bleeding is low after immediate surgery in patients who have had small ischemic strokes and after a surgical delay of two weeks in patients with moderate to severe strokes.

The authors also noted that the study highlights the critical importance of early appropriate antimicrobial therapy. The embolism rate was much lower in patients who had received a week of appropriate antimicrobial therapy.

Azithromycin not associated with increased cardiovascular risk

Azithromycin was not associated with an increased risk of death from cardiovascular causes in a general population of young and middle-aged adults, a Danish study found.

Researchers conducted a nationwide historical cohort study involving Danish adults in a registry database, ages 18 to 64, from 1997 through 2010. They estimated rate ratios for death from cardiovascular causes, comparing 1,102,050 uses of azithromycin to no use of antibiotic agents (matched in a 1:1 ratio according to propensity score) and 1,102,419 uses of azithromycin to 7,364,292 uses of penicillin V. Results appeared in the May 2 New England Journal of Medicine.

Risk of death from cardiovascular causes was significantly increased with current use of azithromycin compared to no antibiotic use (rate ratio [RR], 2.85; 95% CI, 1.13 to 7.24). There was no significantly increased risk with recent or past use. The risk of noncardiovascular death was also higher with current use of azithromycin compared to no antibiotic (RR, 1.60; 95% CI, 1.00 to 2.54).

However, when compared to penicillin V in an unadjusted analysis, azithromycin was not significantly associated with an increased risk of death from cardiovascular causes during current use (RR, 0.78; 95% CI, 0.47 to 1.28) or recent or past use. In an analysis adjusted for propensity scores, azithromycin was not associated with a significantly increased risk of death from cardiovascular causes during current use (RR, 0.93; 95% CI, 0.56 to 1.55), recent use (RR, 0.75; 95% CI, 0.34 to 1.62) or past use (RR, 0.92; 95% CI, 0.60 to 1.42) compared with penicillin V.

Researchers wrote, “[O]ur findings indicate that the risk of cardiac toxic effects associated with azithromycin may not be generalizable but may rather be limited to high-risk populations. The implications of these findings for clinical decision making are reassuring; they indicate that for the general population of patients seen in office practice, azithromycin can be prescribed without concern about an increased risk of death from cardiovascular causes, whereas the benefits of therapy need to be weighed against the risk of death from cardiovascular causes among patients with a high baseline risk of cardiovascular disease.”

An accompanying editorial from the FDA noted that in March the agency revised the azithromycin product labels to reflect other study results that showed azithromycin can prolong the QT interval.

Chronic pain syndromes appear common after ischemic stroke

Chronic pain syndromes appear to be common in patients who have had an ischemic stroke, according to a recent study.

As part of the PRoFESS (Prevention Regimen for Effectively avoiding Second Stroke) trial, patients who reported chronic pain after their stroke but no history of pain before their stroke were given a standardized chronic pain questionnaire at the next-to-last follow-up visit. Mean follow-up was 2.5 years.

The researchers used multivariable logistic regression to determine risk factors for poststroke pain, pain subtypes, and any relation between poststroke pain and cognitive and functional decline. Cognitive decline was defined as a reduction of three points or more in Mini-Mental State Examination score (range, 0 to 30), and functional decline was defined as an increase of one or more points on the modified Rankin scale score (range, 0 to 5). Study results were published May's Stroke.

Of 15,754 participants, 1,665 (10%) reported having new chronic pain after their stroke. Four hundred thirty-one (2.7%) reported central pain, 238 (1.5%) reported peripheral neuropathic pain, 208 (1.3%) reported pain from spasticity, and 136 (0.9%) reported pain from shoulder subluxation. Eighty-six participants (0.6%) reported having more than one type of pain. More severe stroke, female sex, alcohol intake, statin use, depressive symptoms, diabetes, antithrombotic drugs, and peripheral vascular disease were all found to predict poststroke pain. All types of chronic pain syndrome showed an association with increased disability and dependence, while functional decline appeared to be associated with peripheral neuropathy, spasticity and shoulder subluxation.

The authors noted that they were not able to determine which pain medications participants used during the trial, that the trial excluded patients with intracerebral hemorrhage, and that they measured pain at only one point in time, among other limitations. However, they concluded that chronic pain syndromes appear to be common after ischemic stroke and have a negative effect on cognition and functional dependence. They called for clinical trials to investigate ways of preventing pain syndromes after stroke.

Task Force issues HIV screening recommendations

All adolescents and adults age 15 to 65 should be screened for HIV infection, the U.S. Preventive Services Task Force recently announced.

The Task Force's current recommendation statement, published early online by Annals of Internal Medicine on April 30, expands on its statement from 2005, which strongly recommended HIV screening in all adolescents and adults at increased risk for infection and in all pregnant women. The Task Force continues to strongly recommend screening in these groups but now also includes all adolescents and adults age 15 to 65 who are not known to be at increased HIV risk. Its recommendations for pregnant women include those who present in labor and have not been tested and those whose HIV status is not known.

To develop the current recommendations, the Task Force reviewed evidence on the effectiveness of HIV treatment in HIV-infected patients with CD4 cell counts above 0.200 × 109 cells/L; the effects of screening, counseling and use of antiretroviral therapy on risk behaviors and risk for HIV transmission; and the cardiovascular harms of antiretroviral therapy over the long term. The current recommendations are Grade A recommendations, meaning that the Task Force recommends the service and there is high certainty that the net benefit is substantial.

The authors of an accompanying editorial commented that the Task Force's focus on the timing of antiretroviral therapy initiation and its potential cardiac risk was “surprising.” However, they noted that the Task Force's recommendations are now mostly in agreement with the 2006 guidelines from the CDC, which call for testing all people between 13 and 64 years of age, and that an increasing consensus has emerged on population-based screening for HIV.

Perioperative SSRIs may raise risk of adverse events

Selective serotonin reuptake inhibitors (SSRIs) taken in the perioperative period may increase the risk for adverse events, a recent study suggests.

Researchers retrospectively studied 530,416 adult patients who had major surgery between Jan. 1, 2006, and Dec. 31, 2008, at 375 U.S. hospitals. They used pharmacy data to determine whether patients used SSRIs during the perioperative period and employed multivariable hierarchical models to estimate associations between SSRI use and outcomes. Outcomes included in-hospital death, length of stay, 30-day readmission, bleeding events, transfusion and ventricular arrhythmias.

After adjustment, patients taking SSRIs had higher odds of in-hospital mortality (adjusted odds ratio [AOR], 1.20), bleeding (AOR, 1.09) and 30-day readmission (AOR, 1.22). These patients also were more likely to be obese (17.2% vs. 14.1%; P<0.001), to be depressed (41.0% vs 6.2%; P<0.001), and to have chronic pulmonary disease (22.9% vs. 17.0%; P<0.001). Results were similar in propensity-matched analyses, but the risk of inpatient mortality was attenuated among patients with depression.

In terms of bleeding, transfusion and readmission risk, patients didn't differ based on whether they got SSRIs only postoperatively or during the whole perioperative period. However, patients who took SSRIs only postoperatively had the same mortality risk as those who didn't take SSRIs at all. Results were published online April 29 by JAMA Internal Medicine.

It's not clear whether patient factors or the SSRIs themselves are responsible for the elevated risks among patients taking SSRIs perioperatively, the authors wrote. Nor is it clear whether SSRIs should be held for surgery, and when. “Although holding SSRI therapy at the time of surgery may be an appropriately conservative approach, our data cannot frame a more tailored or nuanced strategy for management in surgical patients receiving SSRIs,” they concluded.

Invited commenters noted the number of patients who would need to be treated with SSRIs to cause a single death or readmission was high (about 1,000), so the risk to patients taking SSRIs and undergoing surgery is small. “Conversely, the cessation of SSRI therapy before surgery may precipitate a discontinuation syndrome, worsen depression, and increase sensitivity to postoperative pain,” they wrote.

Early beta-blockers for noncardiac surgery may improve outcomes

Patients at elevated cardiac risk who continued taking beta- blockers on the day of or day after noncardiac, nonvascular surgery had significantly lower rates of 30-day mortality and cardiac morbidity, according to a study in the April 24 JAMA.

Researchers conducted a retrospective cohort analysis evaluating exposure to beta-blockers on the day of or after major noncardiac surgery in a population-based sample of 136,745 patients who were matched 1:1 on propensity scores (37,805 matched pairs) and treated at 104 VA medical centers from January 2005 through August 2010.

Overall, 55,138 patients (40.3%) were exposed to beta-blockers. There were higher rates of exposure among the 13,863 patients undergoing vascular surgery (66.7%; 95% CI, 65.9% to 67.5%) than among the 122,882 patients undergoing nonvascular surgery (37.4%; 95% CI, 37.1% to 37.6%; P<0.001). Patients with more Revised Cardiac Risk Index factors were more often given beta-blockers: 25.3% (95% CI, 24.9% to 25.6%) of those with no risk factors versus 71.3% (95% CI, 69.5% to 73.2%) of those with four or more risk factors (P<0.001).

Death occurred among 1.1% (95% CI, 1.1% to 1.2%) of patients. Cardiac morbidity, defined as cardiac arrest or Q-wave myocardial infarction, occurred among 0.9% (95% CI, 0.8% to 0.9%) of patients. In the propensity-matched cohort, beta-blocker exposure was associated with lower mortality (relative risk [RR], 0.73; 95% CI, 0.65 to 0.83; P<0.001; number need to treat [NNT], 241; 95% CI, 173 to 397). Conversely, beta-blocker withdrawal within the study period was associated with an approximately two-fold increased risk of mortality.

The association between beta-blocker exposure and lower mortality intensified based on the number of Revised Cardiac Risk Index factors present in patients undergoing nonvascular surgery. Among patients undergoing nonvascular surgery, beta-blocker exposure was also associated with a lower rate of nonfatal Q-wave infarction or cardiac arrest (RR, 0.67; 95% CI, 0.57 to 0.79; P<0.001; NNT=339; 95% CI, 240 to 582).

Researchers noted their findings seem to support use of a cumulative number of Revised Cardiac Risk Index predictors when deciding to start and continue perioperative beta-blockers, but they cautioned about the need for a randomized multi-center trial to provide more information on the topic.

Specialized care for elderly inpatients linked to better outcomes

An interdisciplinary team model of care for older inpatients may reduce adverse events, length of stay and costs, two recent studies suggest.

In a prospective, matched cohort study, researchers at New York's Mount Sinai Hospital examined outcomes from a Mobile Acute Care of the Elderly (MACE) service. The MACE service comprises specialized care for elderly inpatients delivered by an interdisciplinary team, which included a geriatrician-hospitalist. Unlike traditional Acute Care for Elderly (ACE) units, the MACE service isn't located on a physical unit. Study patients were at least 75 years old and admitted for acute illness to the MACE service or a general medical service (usual care). They were matched for age, diagnosis and ability to ambulate independently; there were 173 matched pairs. Results were published online April 22 in JAMA Internal Medicine.

MACE patients were less likely to experience adverse events (adjusted odds ratio, 0.11; P=0.04) and had shorter hospital stays (0.8-day difference; P=0.001) than patients receiving usual care. Patient satisfaction measured with the Care Transition Measure was 7.4 points higher in the MACE group (P=0.001), though patient satisfaction measured with HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) didn't differ between groups. Groups also didn't differ in functional status or in 30-day readmissions rate. The MACE unit may be a viable alternative for hospitals that are unable to set up ACE units due to barriers like costs, staffing and space needs, the authors wrote. However, the higher use of home care services in the ACE group may mediate the reduction in length of stay among these patients.

Researchers in a second, retrospective cohort study used administrative data to analyze costs for 428 ACE versus 390 usual care patients at a single academic center and conduct a subset analysis on the 25 most common diagnosis-related groups (DRGs) shared by the patients. Patients were at least 70 years old. For all DRGs, the mean direct cost per patient was lower with ACE patients ($2,109 vs. $2,480; P=0.009). Adjusted cost ratios showed significant cost savings in ACE units for patients with low or moderate case-mix index scores, although care was cost neutral for patients with high scores. Fewer ACE patients were readmitted within 30 days of discharge, as well (7.9% vs. 12. 8%; P=0.02). Results were published online April 22 in JAMA Internal Medicine.

An editorial for both studies noted that while the MACE study showed improved outcomes in the hospital for MACE patients, posthospital functional abilities in this group weren't different from those receiving usual care. This highlights the need for more seamless care across settings, the editorial said. “Geriatric care tailored to each patient's needs should be available regardless of setting, condition, or provider,” it said. “The time has come to deploy an integrated geriatric model of care.”

Accurate risk prediction exists for CKD patients, but more needed

While high-quality models exist for predicting kidney failure risk in patients with chronic kidney disease (CKD), such models are needed for predicting death and cardiovascular events in this population, a review found.

Researchers performed a MEDLINE search of articles in English published from 1966 to November 2012. Eligible studies were longitudinal cohort studies with at least 100 patients with CKD who were not treated with dialysis and had not had a kidney transplant at baseline, and who had at least one year of follow-up. Eligible studies predicted the outcomes of kidney failure, cardiovascular events or all-cause mortality, and had at least three predictors. Models predicting kidney failure in the setting of acute kidney injury were not included. The researchers extracted data on study design, population characteristics, modeling methods, metrics of model performance, risk of bias, and clinical usefulness.

The researchers found 13 studies that described 23 models—11 for kidney failure, and six each for mortality and cardiovascular (CV) events. Measures of estimated glomerular filtration rate or serum creatinine level were included in 17 models, while measures of proteinuria were included in 15. Only four models met criteria for clinical usefulness, and only three of these had reclassification indices with clinically useful risk categories. The models that predicted CV events and mortality were “generally not parsimonious” nor did they have a decision aid that could be used at the bedside, the researchers wrote. Results were published in the April 16 Annals of Internal Medicine.

The lack of studies predicting the risk for cardiovascular events was “disappointing given the well-recognized increased risk for [CV disease] in patients with CKD, the availability of several medications for cardiovascular risk reduction, and the potential for identifying novel risk–treatment interactions,” the authors noted. In general, the review highlights a need for more validation and clinical testing of models for kidney failure and development of models for all-cause mortality and cardiovascular events in the CKD population, they noted, in order to help guide care.

Continuing statins in severe sepsis may improve mortality

Continuing statins during severe sepsis may improve short-term mortality rates, a recent phase two study found.

Researchers in Australia and New Zealand randomized 250 critically ill adults from 21 ICUs to 20 mg of atorvastatin or placebo daily, to be continued until day 14 of the study or death or discharge, whichever came first. On admission, 77 of the patients (31%) were already taking statins.

The primary outcome was plasma interleukin-6 level, a marker of inflammation, while secondary outcomes included mortality, length of stay and Sequential Organ Failure Assessment (SOFA) score. Patients were followed for at least 90 days. Results were published in the April 1 American Journal of Respiratory and Critical Care Medicine.

In the group of 77 patients already taking statins, those who continued statins had lower mortality at 28 days than those who had discontinued statins because they were randomized to placebo (5% vs. 28%; P=0.01). This difference wasn't statistically significant at 90 days, however (11% vs. 28%; P=0.06). There also was no significant difference in outcomes between the overall atorvastatin or placebo groups in ICU or hospital mortality, 28-day mortality, 90-day mortality, length of stay, adverse effects, hospital discharge, or SOFA score. Plasma interleukin-6 levels were lower at baseline in prior statin users than nonusers (P=0.01) but were similar at study's end.

Previous statin use may be protective against sepsis in the short term, and stopping statins may be harmful for ICU patients already using them, the authors concluded. However, statins may be associated with hepatic toxicity and rhabdomyolysis in critically ill patients taking multiple medications, so clinicians must monitor patients closely if statins are continued, editorialists said.