Recent Research

Hyperglycemia and cerebral venous thrombosis outcomes, “opt-out” HIV screening, invasive versus conservative strategy in elderly cardiac patients, and more.


Hyperglycemia predicts worse outcomes in cerebral venous thrombosis

In patients hospitalized with cerebral venous thrombosis, hyperglycemia at admission was a predictor of worse outcomes, a recent European study found.

The retrospective trial included 308 patients treated at hospitals in the Netherlands or Finland between 1998 and 2014 for cerebral venous thrombosis. Patients with known diabetes were excluded. The main outcomes were modified Rankin Scale (mRS) score of 3 to 6 and mortality. Median duration of follow-up was 6 months. Results were published in the February Stroke.

Overall, 21.4% of patients had hyperglycemia (blood glucose level ≥7.8 mmol/L or ≥141 mg/dL) on admission, and 2.6% had severe hyperglycemia (blood glucose level ≥11.1 mmol/L or ≥200 mg/dL). The hyperglycemic patients were more likely to have coma (31.3% vs. 5.0%; P<0.001) and intracerebral hemorrhage (53.0% vs. 32.6%; P=0.002) at presentation. At follow-up, they were also significantly more likely to have an mRS score of 3 to 6 (adjusted odds ratio [OR], 3.10; 95% CI, 1.35 to 7.12) or to have died (adjusted OR, 4.13; 95% CI, 1.41 to 12.09). Severe hyperglycemia was even more strongly associated with these negative outcomes (adjusted ORs, 11.59 [95% CI, 1.74 to 77.30] and 33.36 [95% CI, 3.87 to 287.28], respectively).

This is thought to be the first study to examine associations between admission glucose level and outcomes of cerebral venous thrombosis, the authors noted. The strong association found in the study does not prove a causal relationship, but there are reasons to suspect one, including that hyperglycemia is associated with thrombosis and hypercoagulability and negative outcomes in other conditions. It's also possible that more severe strokes could lead to high glucose concentrations, they said.

If the relationship were causal, lowering glucose levels in these patients could potentially improve outcomes, the authors speculated. That hasn't been studied but should be in a randomized controlled trial, they said, while acknowledging that controlling blood glucose levels in cerebral venous thrombosis could be difficult due to unpredictable nutritional absorption when patients resume oral intake.

Patients more likely to accept ‘opt-out’ HIV screening in ED than other testing offers, study finds

When offering rapid HIV screening to patients in the ED, 1 way of asking seems to produce a higher acceptance rate than others, according to a recent study.

Between June 18, 2011, and June 30, 2013, nonclinical staff at an ED offered HIV screening to patients in 3 ways: opt-in (“You can let me, your nurse, or your doctor know if you'd like a test today”), active choice (“Would you like a test today?”), or opt-out (“You will be tested unless you decline”). Results were published online on Jan. 19 by The BMJ.

Researchers included 4,800 patients in the study, which was conducted in the ED of an urban teaching hospital and regional trauma center. They randomized 33.5% of participants to opt-in, 33.9% to active choice, and 32.6% to opt-out test offers.

Patients accepted 51.6% of all test offers. Opt-out testing had the highest acceptance rate (65.9%), followed by active choice (51.3%) and opt-in (38.0%), an unadjusted difference of 27.9% (95% CI, 24.4% to 31.3%) between the opt-out and opt-in arms. Opt-out testing also yielded 14.6% (95% CI, 11.1% to 18.1%) more acceptances than the active choice option.

Researchers included patients with a wide range of demographics, symptoms, and HIV risk factors. They did not find risk-specific differences in treatment effects, except for high-risk patients in the opt-out arm. Their analysis showed that the opt-out effect was attenuated in high-risk patients (interaction term between opt-out and high risk, −15.5%; 95% CI, −27.8 to −3.1).

The study authors noted limitations to their work, such as how the proportion of patients who accepted testing may vary in other settings. “However, although the test acceptance percentages themselves might vary, we have little reason to expect a different pattern for opt-in versus active choice versus opt-out test schemes,” they wrote. They also noted that study staff was not blinded to treatment assignments, which could introduce bias.

The researchers concluded that active choice testing, which has been considered a form of opt-in testing, is a distinct category and that “simply asking patients if they would like a test increased test acceptance by 13 percentage points.” However, their version of opt-in screening seems “unrealistic” because it is unlikely that clinicians would tell patients that they test for HIV without actually asking if they want to be tested, according to an accompanying editorial.

Nonetheless, opt-out consent appeared to be the best of the 3 approaches in terms of overall acceptance, even in patients who were most at-risk, supporting the use of this kind of consent even in settings that use targeted screening, according to the editorial. The results of this study, the editorialists wrote, “support the notion that ‘the ask’ is a critical piece of the equation and is probably as important as ‘the test.’”

Invasive strategy superior to conservative strategy in elderly with NSTEMI or unstable angina, study finds

Adults 80 years of age and older who have non-ST-elevation myocardial infarction (NSTEMI) or unstable angina may benefit more from invasive than conservative treatment, according to a recent study.

Researchers in Norway conducted an open-label randomized controlled trial in patients admitted to 16 hospitals who were at least 80 years of age and had NSTEMI or unstable angina. Patients were randomly assigned to an invasive strategy, which included early coronary angiography with immediate percutaneous coronary intervention assessment, coronary artery bypass grafting, and optimum medical treatment, or a conservative strategy, which involved optimum medical treatment only. The primary composite outcome of the intention-to-treat analysis was myocardial infarction, need for urgent revascularization, stroke, and death. The study results were published online Jan. 12 by The Lancet.

Patients were recruited between Dec. 10, 2010, and Feb, 21, 2014; median follow-up was 1.53 years. Two hundred twenty-nine patients were assigned to the invasive group (mean age, 84.7 years), and 228 patients were assigned to the conservative group (mean age, 84.9 years). Fifty-five percent of the patients in the invasive group were men versus 44% in the conservative group. Five patients dropped out of the invasive group and 1 dropped out of the conservative group soon after randomization, but all were included in analyses of outcomes and adverse events.

The primary composite outcome occurred in 40.6% of patients in the invasive group versus 61.4% of patients in the conservative group (hazard ratio, 0.53; P=0.0001). The hazard ratios for each component of the primary composite outcome were 0.52 (P=0.0010) for myocardial infarction, 0.19 (P=0.0010) for need for urgent revascularization, 0.60 (P=2.650) for stroke, and 0.89 (P=0.5340) for death from any cause. Major bleeding complication rates were 1.7% and 1.8% in the invasive and conservative groups, respectively, while minor bleeding complication rates were 10.0% and 7.0%.

The authors noted that the open-label nature of their trial might have led to performance and detection bias. However, they concluded that an invasive strategy yielded better outcomes than a conservative strategy for NSTEMI or unstable angina in patients 80 years of age and older, with no difference in bleeding complication rates. They noted that the efficacy of the invasive strategy decreased with increasing age and that they could not determine whether it would be beneficial in patients older than age 90. They concluded that their results support invasive treatment in very elderly patients with NSTEMI and unstable angina who are otherwise clinically stable.

The authors of an accompanying comment said that the current trial “reassures us that invasive management of NSTEMI or unstable angina can be done in clinically stable octogenarians without compromising patient safety” but stressed that clinicians should consider patients' life expectancy, comorbid conditions, bleeding risk, cognitive and functional status, and preferences when deciding on treatment. They called for further analyses that address quality of life, hospital readmissions, and health care costs, as well as additional studies that look at type of revascularization, new antiplatelets, and high-dose statins. Like the study authors, they noted that it is unclear whether the current results should apply to patients over age 90.

Hospital-based physicians may use different nonverbal communication with black vs. white patients, study finds

Hospital-based physicians may use different nonverbal communication but similar verbal communication when speaking with black and white patients about end-of-life care, according to a recent study that examined a small, regional sample of mostly white physicians.

The randomized factorial trial included 33 hospitalists, attending emergency medicine physicians, and intensivists from western Pennsylvania. Their communication was assessed in 2 simulated encounters with prognostically similar, critically and terminally ill black and white older patients with identical treatment preferences who were accompanied by a family member. Results were published in the January Journal of Pain and Symptom Management.

Researchers analyzed audio and video recordings of the encounters and created a measure of communication that gave physicians 1 point or 0 points for the presence or absence of a positive communication behavior (e.g., open body position). They coded verbal emotion-handling and shared decision-making behaviors, as well as nonverbal behaviors, such as eye contact and physical proximity.

The analysis found physicians' nonverbal communication scores to be lower with the black patient than with the white patient (black vs. white: 2.7 vs. 2.9, P=0.014). However, their verbal communication scores did not differ by patient race (black vs. white: 8.4 vs. 8.4, P=0.958). One physician's data were excluded from the analysis because of actor response error during the simulation.

“It is likely that physicians have a greater consciousness of verbal compared with nonverbal behaviors,” the study authors wrote. “...If reflective of actual practice, our findings raise the concern that black patients and their family members may experience fewer positive, rapport-building nonverbal cues and thereby experience lower quality care during this vulnerable decision-making period.”

They noted several limitations of their study, such as potential selection bias for participation, the Hawthorne effect of subjects' behavior being watched, and a possible carryover of learning effects between the first and second case. In addition, the case scenarios were relatively simple, and real clinical decision making often requires more refined communication skills and would likely magnify differences in communication, they noted.

Uptick in sepsis cases may be caused in part by changes in coding, reimbursement, study finds

Two CMS policy changes appear to be associated with the growing number of sepsis cases, according to a recent study.

Researchers analyzed the temporal changes in sepsis incidence and mortality using data from all adult patients hospitalized in California from January 2000 to December 2010. Results of the retrospective cohort study were published online on Jan. 19 by Clinical Infectious Diseases.

The study found that the acute rise in sepsis in California may represent an “up-capture” of the administrative coding of sepsis cases, partly in response to policy changes, which occurred in 2003 with new CMS guidance regarding ICD-9 coding and in 2007 with the introduction of Medical Severity Diagnosis-Related Group (MS-DRG) systems.

Among the 31,431,372 patients in the study, 1,107,541 (3.5%) had a sepsis diagnosis, and 635,780 (57.4%) met criteria for severe sepsis. The annual sepsis hospitalization rate tripled over the 10-year period, from 21.1 to 59.9 cases per 1,000 admissions, with a 2.8- and 2.0-fold increase in severe and non-severe sepsis, respectively. Cases of severe sepsis present on admission increased 3.8-fold over the study period.

Although baseline sepsis rate increases were modest, the researchers noted distinct rate increases after the coding guidance release in 2003 and the introduction of MS-DRG in 2007.

The coding guidance was associated with significant increases in both immediate-level and trend changes in sepsis rates: If baseline trends had continued, the severe sepsis rate in September 2007 would have been 30.6 cases per 1,000 admissions instead of 39.2 cases, the researchers calculated. And the introduction of MS-DRG showed that as of December 2010, compared to a projected rate of 53.5 sepsis cases per 1,000 admissions, the observed rate was 59.9 cases. Without the effect of either policy, the expected severe sepsis rate was projected to be 26.7 cases per 1,000 admissions.

“In our view, these findings do not necessarily represent intentional attempts to improve financial reimbursement, but rather improvements in capture of sepsis in the context of physician training on coding structure and advancing electronic medical records systems,” the study authors wrote.

The authors noted several limitations to their study, such as how they based sepsis on ICD-9 discharge diagnostic coding, with no clinical assessment of sepsis. In addition, the findings are not pertinent to pediatric populations and may not be generalizable to other cohorts.

Studies like this are urgently needed to better characterize the changing epidemiology of sepsis, according to an accompanying editorial. “Only through these efforts can we most effectively target treatment and prevention initiatives appropriately and inform future policies on performance measures,” the editorialist wrote.

ARBs may offer same efficacy, better tolerability than ACE inhibitors

Angiotensin receptor blockers (ARBs) may be as efficacious and safe as angiotensin-converting enzyme (ACE) inhibitors in patients without heart failure, with the added advantage of better tolerability, a meta-analysis found.

Researchers reviewed randomized trials done from January 1980 through April 2015 of ACE inhibitors and ARBs compared with placebo or active controls, then corroborated outcomes with head-to-head trials of ARBs versus ACE inhibitors. Outcomes were all-cause mortality, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, new-onset diabetes, end-stage renal disease, doubling of serum creatinine level, hyperkalemia, and drug withdrawal due to adverse events.

Results appeared in the January Mayo Clinic Proceedings.

The meta-analysis included 106 randomized trials that enrolled 254,301 patients. Compared with placebo, ACE inhibitors but not ARBs reduced the outcomes of all-cause mortality (ACE inhibitors vs. placebo: relative risk [RR], 0.89, 95% CI, 0.80 to 1.00; ARBs vs. placebo: RR, 1.01, 95% CI, 0.96 to 1.06; P=0.04 for the interaction), cardiovascular death (ACE inhibitors vs. placebo: RR, 0.83, 95% CI, 0.70 to 0.99; ARBs vs. placebo: RR, 1.02, 95% CI, 0.92 to 1.14; P=0.05 for the interaction), and myocardial infarction (ACE inhibitors vs. placebo: RR, 0.83, 95% CI, 0.78 to 0.90; ARBs vs. placebo: RR, 0.93, 95% CI, 0.85 to 1.03; P=0.06 for the interaction).

Meta-regression analysis showed that the difference between ACE inhibitors and ARBs compared with placebo was due to a higher placebo event rate in the ACE inhibitor trials for the outcome of all-cause mortality (P=0.001), cardiovascular death (P<0.001), and myocardial infarction (P=0.02). Researchers noted that most of the ACE inhibitor trials were conducted a decade earlier than the ARB trials. Sensitivity analyses restricted to trials published after 2000 revealed similar outcomes with ACE inhibitors versus placebo and ARBs versus placebo (P>0.05 for the interaction). Head-to-head comparison trials of ARBs and ACE inhibitors exhibited no difference in outcomes except for a lower risk of drug withdrawal due to adverse effects with ARBs (RR, 0.72; 95% CI, 0.65 to 0.81).

The researchers noted that treatment of cardiovascular disease changed considerably during the decade between ACE trials, which were conducted before 2000, and ARB trials, which were conducted after 2000, with the majority after 2005. Today, there is more aggressive use of statins and antihypertensives and aggressive cardiovascular risk factor control, including lower rates of smoking in trials conducted after 2000 than in trials conducted before 2000.

“The results of this study have significant clinical implications, in that it widens the choice of RAS [renin-angiotensin system] blockade from an ACE [inhibitor]-first approach to either ACE [inhibitors] or ARBs in patients without heart failure,” the authors wrote. “This is especially important given that most of the ARBs are also generic (and hence reducing cost) and, as a class, are better tolerated than ACE [inhibitors].”

Heart failure may be independent risk factor for VTE

Patients with heart failure in the hospital may be at higher risk for venous thromboembolism (VTE), according to a recent study.

Researchers performed a systematic review and meta-analysis to examine the absolute and relative risks (RRs) for VTE after hospital admission in patients with heart failure. Cohort studies and subgroup analyses of randomized controlled trials that were published between Jan. 1, 1955, and March 31, 2015, were eligible for inclusion if VTE rates or estimates of RRs were reported. The results were published in the January Lancet Haematology.

Seventy-one studies including data from 88 cohorts were included in the study. In 59 cohorts, the overall median rate of symptomatic VTE was 2.48% (interquartile range, 0.84% to 5.61%), with rates of 3.73% (interquartile range, 1.05% to 7.31%) in patients who did not receive thromboprophylaxis and 1.47% (interquartile range, 0.64% to 3.54%) in patients who did. In 21 cohorts, the overall rate for all VTE, both symptomatic and nonsymptomatic, was 11.69% (interquartile range, 6.64% to 17.34%) in 10 cohorts who did not receive prophylaxis and 5.61% (interquartile range, 3.32% to 12.35%) in 11 cohorts who did. In 46 cohorts, the pooled RR for VTE in patients with heart failure in the hospital was 1.51 (interquartile range, 1.36 to 1.68). In analyses by cohort characteristics and types of patients, non-Asian cohorts had much higher rates of VTE without prophylaxis than Asian cohorts, and patients with cancer and heart failure had the highest VTE rates. The authors reported no evidence of publication bias.

The authors could not perform subgroup analyses according to heart failure severity, only a handful of the included studies involved acute heart failure, and most of the analyses had substantial heterogeneity, among other limitations. However, the authors noted that their study has several potential clinical implications, including the possibility of identifying patients at high risk for VTE in the hospital, such as those with both heart failure and cancer and those with heart failure who are having orthopedic surgery.

“With an ageing population, a greater proportion of venous thromboembolism events are occurring in patients with heart failure who have been admitted to hospital,” the authors wrote. “Making physicians more aware of the association between heart failure and venous thromboembolism could help to reduce the incidence of this potentially avoidable and costly disease.”

Thrombocytopenia associated with higher mortality from septic shock

Thrombocytopenia at the onset of septic shock was associated with higher mortality over the following 28 days, a recent study found.

The study included 1,486 patients treated for septic shock in ICUs of French hospitals between November 2009 and September 2011. All patients' platelet counts were measured at least once within the 24 hours after the onset of shock, and if multiple measurements were taken, the lowest one was used. Results were published by Critical Care Medicine on Dec. 14, 2015.

Several factors were found to be associated with thrombocytopenia in the first day: Simplified Acute Physiology Score (SAPS) II ≥56, immunosuppression, age >65 years, cirrhosis, bacteremia, and urinary sepsis. A platelet count ≤100,000 cells/mm3 was independently and significantly associated with increased risk of death by 28 days later, according to multivariate Cox regression analysis. The mortality risk increased with severity of thrombocytopenia: Patients with a count >50,000 cells/mm3 had a hazard ratio for death of 1.65 compared to those with platelets >150,000 cells/mm3 (P<0.0001).

The study authors said they believe this to be the first study to look at thrombocytopenia as a prognostic marker for septic shock but noted that the factors found to be associated with thrombocytopenia are consistent with previous research. The worse outcomes in these patients could be explained by a number of mechanisms, including microvascular thrombotic complications (which can lead to ischemia and multiorgan dysfunction syndrome), increased bleeding, or a decrease in antimicrobial defenses, they speculated.

Whatever the cause, early thrombocytopenia might be useful as a tool in determining septic shock severity and prognosis. “Measuring platelet count is inexpensive and easily feasible for the physician in routine practice, and thus, it could represent an easy ‘alert system’ among patients in septic shock,” the authors wrote. They cautioned that thrombocytopenia should be used in conjunction with other prognostic markers and that the study couldn't measure potential confounding factors.