Recent Research

Scoring systems for pleural effusions, NSAIDS and VTE risk, and more.

MoCA beats MMSE for detecting hypertension-associated cognitive impairment after minor stroke

The Montreal Cognitive Assessment (MoCA) appears to be more sensitive than the Mini-Mental State Examination (MMSE) at detecting hypertension-associated cognitive impairment after minor stroke or transient ischemic attack (TIA), a study found.

British researchers sought to determine whether the MoCA, which in past research found a higher level of cognitive impairment after stroke than the MMSE, is a better marker for underlying cerebrovascular damage related to hypertension. They studied 463 TIA or minor stroke patients who presented at a stroke clinic between April 2008 and January 2012. The patients took the MMSE and MoCA at the beginning and end, respectively, of a 45-minute follow-up appointment 6 months after the incident event.

Blood pressure was measured at the clinic at the initial visit and at one-month followup; researchers also gathered 20 premorbid systolic blood pressure readings from medical records. In addition, patients measured their blood pressures at home from the time of recruitment until one month after, or until their blood pressure was under control. Researchers then used ordinal regression to examine the relationship between MoCA and MMSE scores, blood pressure readings, and presence of hypertensive arteriopathy (determined by creatinine and leukoaraiosis levels, and whether a patient had a stroke vs. TIA). Results were published in the November 2014 Stroke.

Forty-five percent of patients had at least mild cognitive impairment on the MoCA (score of 24 or less) compared to 28% of patients on the MMSE (score of 26 or less; P<0.001). Hypertensive arteriopathy was associated more strongly with cognitive impairment on the MoCA than the MMSE (elevated creatinine odds ratio [OR], 3.99; TIA or stroke OR, 1.53; leukoaraiosis OR, 2.09). Premorbid and home blood pressure measurements also were more strongly associated with cognitive impairment on vascular subdomains of the MoCA than the MMSE (OR/10 mm Hg elevation: visuospatial, 1.29 vs. 1.05; attention, 1.18 vs. 1.07; language, 1.22 vs. 0.91; naming, 1.07 vs. 0.86).

Compared to the MMSE, the MoCA found more hypertension-associated cognitive impairment, due to its greater sensitivity to such impairment in several subdomains, but especially the visuospatial/executive dysfunction subdomain, the researchers noted. The MMSE's poor sensitivity to hypertension-associated cognitive impairment may explain why trials that used the MMSE have found a lack of efficacy of antihypertensives for slowing cognitive impairment, they added. The current results suggest the MoCA may be able to identify a cohort of patients who are at risk of future cognitive decline, and who may benefit from antihypertensives, they said.

Simple CT scoring system helps distinguish between benign, malignant pleural effusions

Researchers have developed a simple CT scoring system for distinguishing between malignant and benign pleural effusions.

Spanish researchers enrolled 343 patients with pleural effusions who received both diagnostic thoracentesis and contrast-enhanced chest CT at their institution between June 2008 and December 2011. All patients had a definite cause for pleural effusion. The researchers compared several chest CT abnormalities between the 228 patients with benign, and 115 with malignant, effusions, using logistic regression analysis to identify independent predictors of malignancy. The accuracy of the scoring system then was evaluated in 2 independent populations. Results were published in the Sept. 25, 2014, CHEST.

CT score factors that predicted malignancy included any pleural lesion (pleural nodularity, thickening, circumferential thickening, or mediastinal pleural involvement) ≥1 cm (5 points); presence of liver metastases, abdominal mass, or lung mass or nodule ≥1 cm (3 points each); and absence of either pleural loculations, pericardial effusions or cardiomegaly (2 points each). A total score of ≥7 (out of 20) yielded an 88% sensitivity, a 94% specificity, and an area-under-the-curve of 0.919 for consideration of a malignant process. A score of <5 would argue against malignancy. In addition, the predictive score would have correctly labeled 69% of 42 patients who had pathologically unconfirmed malignant effusions. The CT scoring system remained robust for the subgroup of patients in whom no diagnosis was obtained after initial thoracentesis—the population for which CT is most often ordered in routine practice, the researchers noted.

Study limitations included that the patient population reflects etiologies of pleural effusions common in Spain, the researchers said. The score should be used as an aid to construct a differential diagnosis of pleural effusions, “which does not preclude obtaining a cytohistologic confirmation of malignancy,” they added. “It may be considered a diagnostic weight to estimate the probability of malignancy, in combination with other clinical findings.” They felt that a prospective validation of this score in large populations is warranted.

NSAIDs may increase risk of VTE

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of venous thromboembolism (VTE), a meta-analysis found.

Researchers conducted a systematic review and meta-analysis of 6 studies (1 cohort and 5 case-control; 21,401 total VTE events) comparing VTE rates among NSAID users and non-users. The pooled risk ratio of VTE in NSAID users versus nonusers was 1.80 (95% CI, 1.28 to 2.52). The VTE risk among selective COX-2 inhibitor users (3 studies) was also significantly elevated compare to nonusers, with a pooled risk ratio of 1.99 (95% CI, 1.44 to 2.75). Results appeared online Sept. 24, 2014, in Rheumatology.

The studies were highly heterogeneous, which researchers said was likely due to differing study designs, definitions of NSAID exposure, and populations. Other differences included:

  • 3 studies included only inpatients, while the other 3 included both ambulatory and hospitalized patients;
  • 1 study included only patients with pulmonary embolism (PE), while the rest included patients with deep vein thrombosis and/or PE;
  • 4 studies used a pharmacology-linked database while 2 used interviews; and
  • Controlling for confounders was widely variable between studies.

The researchers noted that, given the prevalence of NSAID use in the general population, the association with VTE may have important public health implications. “Physicians should be aware of this association and NSAIDs should be prescribed with caution, especially in patients at high baseline risk of VTE,” they wrote.

Systematic review compares new and old anticoagulation options for acute VTE

The benefits and risks of 8 different anticoagulation strategies for patients with venous thromboembolism (VTE), including heparin and new oral anticoagulants, were compared in a large recent analysis.

Researchers used data from 45 trials with 44,989 patients to compare the strategies: vitamin K antagonists combined with unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux; LMWH alone; LMWH with dabigatran or edoxaban; rivaroxaban; or apixaban. Outcomes were recurrent VTE and major bleeding during 3 months of treatment. Only prospective, randomized studies comparing 2 different treatment strategies were included in this network meta-analysis. Results were published in the Sept. 17, 2014, Journal of the American Medical Association.

On the outcome of recurrent VTE, the only strategy that showed substantially different results from the others was UFH with a vitamin K antagonist, which significantly increased risk of VTE recurrence (hazard ratio [HR], 1.42, compared to LMWH-vitamin K antagonist). When the researchers looked at bleeding during treatment, only rivaroxaban and apixaban stood out significantly, both reducing the risk of a bleed compared to LMWH-vitamin K antagonist (HR, 0.55 for rivaroxaban and 0.31 for apixaban).

Based on the results, UFH appears to be the least effective strategy for preventing VTE recurrence, the study authors concluded. This supports current guidelines, they noted, although UFH may still be appropriate for certain patients, such as those with severe renal insufficiency or massive/submassive pulmonary embolism who are potential candidates for thrombolysis or thrombectomy. The study also indicates that rivaroxaban and apixaban may pose the lowest risk of bleeding, which may be helpful information for clinicians, since current guidelines were published prior to the latest evidence on using new oral anticoagulants for acute VTE, the study authors noted.

They cautioned that their analysis included only use of the treatments for acute VTE, not secondary prevention. In addition, the research was limited by the total absence of head-to-head trials comparing the new oral anticoagulants. Costs of the different regimens were also not addressed. The authors called for direct comparison trials, patient-level meta-analyses, or high-quality nonrandomized studies to confirm their findings.

Atypical antipsychotics associated with increased AKI risk

Use of atypical antipsychotics is associated with increased risk for acute kidney injury (AKI), according to a recent study.

Researchers performed a population-based cohort study in Ontario, Canada, from 2003 to 2012 to examine the risk for AKI and other adverse outcomes associated with atypical antipsychotic use versus nonuse. Patients 65 years of age or older who got a new outpatient prescription for an oral atypical antipsychotic drug were matched with patients who didn't get an atypical antipsychotic prescription. The study's primary outcome measure was hospitalization with AKI within 90 days of receiving an atypical antipsychotic prescription. The results appear in the Aug. 19, 2014, Annals of Internal Medicine.

The study included a total of 97,777 drug recipients and 97,777 matched nonrecipients. Mean age was 80.7 years. A total of 23.8% of patients lived in long-term care facilities, and 53.8% had been diagnosed with dementia. Risperidone was the most common atypical antipsychotic prescribed (44,707 patients, 45.7%), followed by quetiapine (34,498 patients, 35.3%) and olanzapine (18,572 patients, 19.0%).

Overall, atypical antipsychotic drug use was associated with higher risk for hospitalization with AKI (1.02% vs. 0.62%; relative risk [RR], 1.73 [95% CI, 1.55 to 1.92]; absolute risk increase, 0.41% [95% CI, 0.33% to 0.49%]) compared with nonuse. The association remained consistent in a subpopulation with available information on serum creatinine levels (5.46% vs. 3.34%; RR, 1.70 [95% CI, 1.22 to 2.38]; absolute risk increase, 2.12% [95% CI, 0.80% to 3.43%]). Associations were also seen between atypical antipsychotic drug use and 90-day risk of hospitalization for hypotension (RR, 1.91 [95% CI, 1.60 to 2.28]), acute urinary retention (RR, 1.98 [95% CI, 1.63 to 2.40]), and 90-day risk of all-cause mortality (RR, 2.39 [95% CI, 2.28 to 2.50]).

The authors noted that their study was observational, included only older adults, and involved only 3 atypical antipsychotic drugs, among other limitations. However, they concluded that new use of atypical antipsychotic drugs is common and is associated with increased AKI risk as well as with additional adverse outcomes, such as hypotension and acute urinary retention, that could explain this association.

“The current available evidence calls for a careful reevaluation of prescribing atypical antipsychotic drugs in older adults, especially for the unapproved indication of managing behavioral symptoms of dementia,” the authors wrote. “The drugs should be used only after other approaches have been exhausted; when prescribed, patients must be warned about potential adverse effects.” The authors suggested that proactive clinical monitoring “seems reasonable,” including serum creatinine testing, blood pressure measurement, and a bladder scan for urinary retention, shortly after the drugs are initiated, along with consideration of the drugs as a potential cause in patients who present with AKI and prompt discontinuation if feasible.

Adding immune-modulating agents to enteral nutrition potentially harmful

Ventilated patients who received enteral nutrition enriched with immune-modulating agents had no fewer infections, and possibly higher mortality, than patients on standard nutrition, a recent study found.

The double-blind multicenter trial randomized 301 European patients who were in intensive care and who were expected to be ventilated and require enteral nutrition for more than 72 hours to standard high-protein enteral nutrition or high-protein enteral nutrition enriched with immune-modulating agents, including omega-3 fatty acids, glutamine, selenium, and vitamins C and E. The trial was conducted from February 2010 through April 2012, and follow-up was 6 months. Results were published in the Aug. 6, 2014, Journal of the American Medical Association.

The 2 groups had similar rates of new infections: 53% (95% CI, 44% to 61%) in the immune-modulated group and 52% (95% CI, 44% to 61%) in the standard group (P=0.96). No significant differences were found on any other endpoints, except that in the subgroup of medical patients (surgical and trauma ICU patients were also included in the overall study), the immune-modulated nutrition was associated with a higher 6-month mortality rate: 54% (95% CI, 40% to 67%) vs. 35% (95% CI, 22% to 49%). When data were adjusted for age and Acute Physiology and Chronic Health Evaluation II score, the immune-modulated group had a 6-month mortality hazard ratio of 1.57 (95% CI, 1.03 to 2.39; P=0.04).

The results confirm other recent findings of no or negative effects of supplementation with glutamine, omega-3 fatty acids, and antioxidants, in contrast to older studies that found benefits, the study authors wrote. They noted that the mortality rate in the standard nutrition group was lower than in some other recent research, which could potentially be explained by the high protein content (1.2 g/kg of body weight per day, day 3) of the standard nutrition. The standard formula also had a balanced amino acid pattern, which recent research has supported.

The study shows that harmful effects may occur with even relatively low dosages of immune-modulating agents administered in enteral feeding, the researchers concluded, calling for a critical appraisal of guidelines on the subject. An accompanying editorial questioned if there may still be a role for immunomodulation or supplementation of individual immunomodulating agents in certain subgroups of critically ill patients, but noted the current evidence should “strongly discourage intensivists from its routine prescription for critically ill patients in clinical practice.”

History of ischemic stroke raises risk of adverse events after noncardiac surgery

A history of ischemic stroke, especially within the previous 9 months, was associated with a higher risk of adverse events after noncardiac surgery, a recent study found.

Danish researchers used national registry data of all elective noncardiac surgeries (n=481,183 surgeries) performed in patients aged 20 years or older in 2005-2011. Using ICD-10 codes, they identified patients with prior ischemic stroke; they didn't include patients with hemorrhagic stroke or transient ischemic attack. Patients whose last stroke occurred more than 5 years before surgery weren't included.

The researchers divided patients into subgroups based on time elapsed between stroke and surgery. The groups were no prior stroke, stroke within less than 3 months, stroke within 3 to less than 6 months, stroke within 6 to less than 12 months, and stroke 12 or more months before surgery. The primary outcomes were all-cause mortality and major adverse cardiovascular events (MACE) up to 30 days after surgery. MACE was a combination of nonfatal acute myocardial infarction, nonfatal ischemic stroke, and cardiovascular death. Results were published online July 16, 2014, by the Journal of the American Medical Association.

Among patients with prior stroke (n=7,137), the crude incidence rate of MACE was 54.4 per 1,000 patients, compared to patients without prior stroke (n=474,046) for whom the MACE incidence rate was 4.1 per 1,000. Regardless of time between ischemic stroke and surgery, a prior ischemic stroke was associated with an adjusted 1.8- and 4.8-fold increased relative risk of 30-day mortality and 30-day MACE, respectively, compared with patients without prior stroke.

There also was a strong time-dependent relationship between previous stroke and adverse postoperative outcome, with patients who had a stroke less than 3 months before surgery at especially high risk. Compared to patients without stroke, odds ratios for MACE were 14.23 for patients with stroke less than 3 months before surgery, 4.65 for stroke 3 to less than 6 months prior, 3.04 for stroke 6 to less than 12 months prior, and 2.47 for stroke 12 months or more prior. In those same subgroups, 30-day mortality risks followed a similar pattern; odds ratios were 3.07, 1.97, 1.45, and 1.46, respectively. Risks for MACE and death were elevated but level after 9 months. MACE risk didn't vary by whether the surgery itself was low-, intermediate- or high-risk.

Studies looking into the optimal timing of surgery in patients with prior stroke are scarce, the authors noted. These results suggest patients should be considered at higher risk of adverse 30-day outcomes after noncardiac surgery until 9 months after stroke, the authors concluded. Given that low- and intermediate-risk surgeries appeared to pose the same risk of MACE as high-risk surgeries, “it seems important to take a history of recent stroke seriously, including in the context of minor surgical procedures,” the authors wrote.

More severe heart failure patients have higher VTE risk

Inpatients with more severe heart failure are at higher short-term risk of venous thromboembolism (VTE) than those with less severe heart failure, an analysis found.

Researchers analyzed data from 2,593 heart failure patients who were part of a larger randomized trial of inpatients who received either rivaroxaban or enoxaparin. The patients had New York Heart Association (NYHA) Class III or IV heart failure. Patients' plasma was drawn at screening, day 10, and day 35 and measured for D-dimer and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations. Patients were stratified into quartiles based on NT-proBNP levels: quartile 1, <765 pg/mL; quartile 2, 767 to 1,904 pg/mL; quartile 3, 1,906 to 5,034 pg/mL; and quartile 4, >5,038 pg/mL.

Up to days 10 and 35, VTE occurred more frequently in heart failure patients with NT-proBNP concentrations in the third and fourth quartiles than in patients in the first and second quartiles. Overall, the trend for an association between VTE risk and NT-proBNP concentration was significant (P=0.01 up to day 10 and P=0.01 up to day 35). D-dimer concentrations in quartiles 3 and 4 of NT-proBNP remained higher than those observed in quartiles 1 and 2.

Multivariable analysis indicated that NT-proBNP level was associated with VTE risk up to day 10 (P=0.017) but not to day 35. It also found that D-dimer (P=0.004) and baseline high-sensitivity C-reactive protein (P=0.05) were associated with VTE risk up to day 35. The association between VTE risk and heart failure severity was seen in the overall group and the enoxaparin subgroup but not the rivaroxaban subgroup. Clinically relevant bleeding was higher in the rivaroxaban group. Results were published in the July 29, 2014, Circulation.

Patients with more severe heart failure, as defined by high NT-proBNP plasma concentration, seem to have higher risk of VTE in the short term, while those with elevated D-dimer levels appear to have higher mid-term VTE risk, the authors concluded. “These findings suggest that NT-proBNP could be used as a simple measure to identify patients with heart failure who are at high risk of thromboembolism and should, therefore, be considered for VTE prophylaxis,” they wrote. “NYHA class had little or no effect on the incidence of VTE, suggesting that NT-proBNP is a better predictor of thromboembolic risk.”

Different factors predict comprehension, adherence to discharge instructions

Elderly patients vary in their comprehension and adherence to post-discharge instructions, with certain factors predicting whether they'll follow different components of the instructions, a recent study found.

The prospective cohort study included 450 patients 65 years of age and older who were discharged from a tertiary care facility. At 5 days post-discharge, comprehension and adherence were assessed by asking the patients about their discharge instructions and comparing their reports to medical charts. The instructions were divided into domains of medications, follow-up appointments, diet, and exercise. Results were published July 12, 2014, by the Journal of General Internal Medicine.

At follow-up, only 5% of patients appeared not to have comprehended their instructions about follow-up appointments, compared to 27% for medications. Of the patients who received exercise instructions (19% of the total), 48% didn't understand or remember them. More than half of the patients were instructed about diet, but only half of those showed comprehension of the instructions.

Older age was associated with slightly higher risk of not understanding or remembering medication (odds ratio [OR], 1.07) and follow-up appointment instructions (OR, 1.08). Men were significantly more likely not to comprehend diet instructions (OR, 1.91; 95% CI, 1.10 to 3.31), and socially isolated patients were less likely to comprehend their exercise instructions (OR, 9.42; 95% CI, 1.50 to 59.11). Lower cognition and education, which were expected to be factors, were not associated with less comprehension in any domain.

After excluding the patients who didn't prove comprehension of the instructions, researchers found that depression was a significant predictor of nonadherence to instructions on both medication (OR, 2.29; 95% CI, 1.02 to 5.10) and diet (OR, 3.30; 95% CI, 1.24 to 8.83). The results show that achieving comprehension is not always sufficient to ensure adherence to instructions, the study authors concluded.