Recent Research

Urinalysis orders, resistant infections, molecular C. diff testing, and more.

Urinalysis often ordered without indication on admission, study finds

More than half of patients admitted to the general medicine service of a large tertiary care center underwent urinalysis upon admission from the ED, even though most lacked an appropriate clinical indication, according to a recent study.

Results appeared in a research letter published in the October JAMA Internal Medicine.

Of 403 consecutive patients admitted to the general medicine service during 2 study periods in 2014 and 2015, 250 (62.0%; 95% CI, 57.3% to 66.7%) underwent urinalysis upon admission at the discretion of ED or general medicine physicians. Study clinicians assessed each patient within 24 hours for indications for urinalysis, including symptoms of urinary tract infection (UTI) based on guidelines for patients with and without urinary catheters or acute kidney injury. Median age of the patient cohort was 79 years, and 212 (52.6%) were women.

Of 250 tested patients, 211 (84.4%; 95% CI, 79.9% to 88.9%) lacked symptoms of a UTI, and 198 (79.2%; 74.2% to 84.2%) lacked UTI and acute kidney injury. The top 3 most common chief symptoms of these 198 patients were fall or syncope, fever with documented non-urinary cause, and chest pain or dyspnea.

Positive urinalysis results were associated with increased probability of urine culture orders (P<0.001) and antibiotic prescriptions for pyuria or bacteriuria (P<0.001) among asymptomatic patients—often representing low-value care, according to the study's authors—while appropriate urinalysis orders for symptomatic patients were used effectively to exclude UTI and withhold antimicrobial therapy, they said.

After the researchers controlled for other independent variables, only the presence of multiple comorbidities was significantly associated with urinalysis orders without indication (P<0.001; odds ratio, 5.3 [95% CI, 2.5 to 11.0]). “One possible explanation is that patients with complex medical problems are more likely to undergo a broader net of investigations,” the study authors wrote.

One limitation of this study is that the patient cohort comes from a single academic center and may not reflect ordering patterns of other institutions, the authors noted. They also wrote that the use of a guideline-based definition for UTI may have overestimated the proportion of asymptomatic patients, especially among those who could not communicate their symptoms reliably (although dementia was not associated with increased urinalysis orders among patients lacking this UTI definition).

Acinetobacter baumannii infections increasingly resistant to antibiotics

Drug resistance has increased among Acinetobacter baumannii infections in the U.S. over the last decade, a recent study found.

Researchers looked at 39,320 specimens of Acinetobacter baumannii (81.1% respiratory, 18.9% bloodstream) gathered in 2003-2005, 2006-2008, and 2009-2012 in Eurofins' The Surveillance Network. They analyzed the resistance of the bacteria to carbapenems, aminoglycosides, tetracyclines, polymyxins, ampicillin-sulbactam, and trimethoprim-sulfamethoxazole. Results were published by the Journal of Hospital Medicine on Sept. 9.

The highest prevalence of resistance was to doripenem (90.3%), followed by trimethoprim-sulfamethoxazole (55.3%). The lowest rate of resistance was to colistin at 5.3%, although the study authors noted that the rate had “alarmingly” increased from 2.8% in 2006-2008 to 6.9% in 2009-2012. Resistance to carbapenems also more than doubled, from 21.0% in 2003-2005 to 47.9% in 2009-2012. The only drug that saw a decline in resistance was minocycline, which went from 56.5% in 2003-2005 to 30.5% in 2009-2012.

The prevalence of multidrug-resistant Acinetobacter baumannii (which the researchers defined as resistant to at least 3 drug classes) was 21.4% in 2003-2005, 33.7% in 2006-2008, and 35.2% in 2009-2012. Multidrug resistance was most common in nursing homes (46.5%), followed by general hospital wards (29.2%), ICUs (28.7%), and outpatient settings (26.2%). Drug resistance was also found to differ by geographic region, with the highest multidrug resistance in the Mountain and East North Central divisions and the lowest in New England.

The study found lower rates of multidrug resistance than some other analyses, possibly because it omitted fluoroquinolones, the authors said. The finding of lower drug resistance in ICUs than in some other settings is contrary to common assumptions, and the evidence that nursing homes are “a robust reservoir for spread” of resistant bacteria is concerning, the study said.

The reduction in minocycline resistance was the “single encouraging trend” observed in the study. “All of these observations highlight the urgent need to develop novel antibiotics and nontraditional agents, such as antibodies and vaccines,” the authors concluded.

Molecular testing for C. difficile leads to overdiagnosis, increased costs, study finds

Up to half of the patients with positive molecular test results for Clostridium difficile do not experience adverse events without treatment and do not need treatment for C. difficile infection (CDI), according to a recent study.

These molecular tests, while increasingly popular, are not specific for CDI, and when used exclusively, “their sensitivity may lead to overdiagnosis, overtreatment, and increased health care costs,” the study authors wrote. Their results were published online on Sept. 8 by JAMA Internal Medicine.

The researchers analyzed 1,416 hospitalized adults with toxin immunoassay and polymerase chain reaction (PCR) tests. Of these, 1,123 (79.3%) were negative on both, 131 (9.3%) were positive on both, and 162 (11.4%) were immunoassay negative and PCR positive.

Compared with patients who had double positives, the conflicting-result patients had significantly less severe diarrhea, less risk of diarrhea during follow-up, and fewer CDI-related complications or deaths (P<0.001 for each). Their outcomes were similar to those of the patients who were negative on both tests, and virtually all CDI-related complications and deaths occurred in immunoassay-positive patients.

“These findings strongly suggest that most patients with negative toxin test results and C. difficile detected by PCR do not need treatment for CDI,” the study authors wrote. “We suspect that most of these patients were colonized with C. difficile and had another cause of diarrhea.”

An important finding of the study—which is consistent with the literature—is that more of the patients had conflicting results on the tests than positives on both, according to an accompanying editorial.

In hospitals that changed from toxin immunoassays to PCR-based assays for detection, the CDC found that CDI incidence increased by 43% to 67%, which has serious implications, the editorial stated. More positive assays result in costly contact precautions and increase patients' risk for drug-related adverse events and even a higher risk for CDI once treatment ends, the editorialist wrote.

Although the best test to diagnose CDI is unknown, clinicians should be familiar with what assays are used at their facilities and how best to interpret results, according to the editorial. The study authors suggest 2-step testing with a screening test, such as PCR or glutamate dehydrogenase antigen detection, followed by a toxin test to confirm active infection.

The primary limitation of the study was the inability to achieve equivalent risk allocation between groups, they noted. They also could not exclude the possibility that empirical treatment affected outcomes in some conflicting-result patients, although the outcome differences remained when these patients were removed.

CHA2DS2-VASc modestly predicts ischemic stroke, thromboembolism, death in heart failure patients

A common clinical risk score predicted ischemic stroke, thromboembolism, and death among patients with heart failure with or without atrial fibrillation, but only modestly, according to a study.

Danish researchers used registries to examine the CHA2DS2-VASc score (congestive heart failure, hypertension, age 75 years or older [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior heart attack, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) to predict ischemic stroke, thromboembolism, and death within 1 year in patients with a new diagnosis of heart failure with and without afib. The study included 42,987 patients (22% percent with concomitant afib) not receiving anticoagulation who were diagnosed as having new-onset heart failure from 2000 to 2012. CHA2DS2-VASc scores (which are based on 10 possible points, with higher scores indicating higher risk) were stratified by presence of afib at study entry.

Results appeared in the Sept. 8 Journal of the American Medical Association.

Patients with heart failure had a high risk of ischemic stroke, thromboembolism, and death regardless of whether afib was present. However, the CHA2DS2-VASc score was only modestly able to predict these outcomes. Patients without afib had a 3.1% risk of ischemic stroke, 9.9% risk of thromboembolism, and 21.8% risk of death during follow-up. The researchers compared rates of stroke and death for patients with CHA2DS2-VASc scores ranging 1 through 6:

  • ischemic stroke with concomitant afib: 4.5%, 3.7%, 3.2%, 4.3%, 5.6%, and 8.4%;
  • ischemic stroke without concomitant afib: 1.5%, 1.5%, 2.0%, 3.0%, 3.7%, and 7%.
  • all-cause death with concomitant afib: 19.8%, 19.5%, 26.1%, 35.1%, 37.7%, and 45.5%;
  • all-cause death without concomitant afib: 7.6%, 8.3%, 17.8%, 25.6%, 27.9%, and 35.0%.

At high CHA2DS2-VASc scores, the absolute risk of thromboembolism was high regardless of presence of afib, for example, with a score of 4, clot risk was 9.7% for patients without concomitant afib versus 8.2% for those with afib.

The authors wrote, “The poor prognosis of AF [afib] for ischemic stroke and death in patients with HF [heart failure] was evident in our study, but the observation that additional risk factors in patients with HF are particularly significant among those without AF is an important result. Indeed, preventative strategies to reduce ischemic stroke and TE [thromboembolism] risk in this large patient population require further investigation.”

Bleeding on dual antiplatelet therapy after stent implantation predicts mortality risk

About 6% of patients who received dual antiplatelet therapy (DAPT) with drug-eluting stents (DES) had significant bleeding events within 2 years of hospital discharge, according to a recent study that assessed predictors and outcomes of the bleeds.

Researchers conducted a post hoc analysis of 8,582 patients who underwent successful percutaneous coronary intervention with DES as part of the ADAPT-DES study. Between hospital discharge and 2 years later, 6.2% of the patients had clinically relevant bleeding, at a median time since discharge of 300 days. Most (61.7%) of the bleeds were gastrointestinal. Predictors of bleeding included older age, lower baseline hemoglobin, lower platelet reactivity to clopidogrel, and use of chronic oral anticoagulation.

Patients who bled had significantly higher all-cause mortality over the 2 years: 13.0% versus 3.2% (P<0.0001). After adjustment, bleeding was still strongly associated with mortality, even more so than postdischarge myocardial infarction (mortality hazard ratios, 5.03 for bleeding and 1.92 for myocardial infarction). Results were published in the September Journal of the American College of Cardiology.

The results show that postdischarge bleeding is not uncommon in this patient population, occurring in 1 of every 15 patients, with more than half of the events happening more than 300 days after discharge, the study authors concluded. The observed clinical and pharmacological risk factors for bleeding could be used to guide prescribing. “Considering the individual patient's thrombotic and bleeding risk profile to personalize DAPT duration decisions should improve outcomes after DES implantation, although this decision-making process will remain challenging in some cases, and must incorporate patient preferences,” the authors wrote.

The authors also noted that the observed frequency of gastrointestinal bleeds and infrequency of discharge prescriptions for proton-pump inhibitors suggest that “more liberal prophylactic use of these agents during DAPT treatment may improve patient prognosis.” An accompanying comment noted that expert thinking on the use of DAPT after percutaneous coronary intervention has shifted on a pendulum that may be returning to “a more nuanced and individualized approach” and that this study adds valuable data about long-term bleeding risk that had previously been lacking.

Early tracheostomy associated with lower mortality, disparities in treatment

Ventilator-dependent patients who had tracheostomy sooner had lower mortality, according to a recent study, which also identified disparities in which patients receive early tracheostomy.

Researchers pulled data from the University HealthSystem Consortium (UHC) about patients who received tracheostomy after initial intubation from 2007 to 2010. Patients were from 185 different academic medical centers/affiliates, and tracheostomy was performed by 7,585 different clinicians.

Of 49,191 patients who underwent tracheostomy after initial intubation, 42% (n=21,029) received early tracheostomy (within 6 days of intubation) and 58% (n=28,162) received late tracheostomy (more than 10 days after intubation). Results were published online on Aug. 27 by CHEST.

The study found that mortality after tracheostomy was lower for the early cohort compared to the late cohort (14% vs. 21%, P<0.0001). The early cohort had a shorter length of stay in both the ICU (16 days vs. 27 days, P<0.0001) and hospital (25 days vs. 38 days, P<0.0001) compared to the late cohort. Patients in the early cohort also had lower total direct cost and total charges compared to the late cohort ($61,163 vs. $97,292 and $251,333 vs. $400,061, P<0.0001 for both comparisons).

After controlling for clinical factors, the researchers found that women, black patients, Hispanic patients, and Medicaid patients were less likely to receive an early tracheostomy. Patients in the early cohort were more likely than those in the late cohort to be male (63% vs. 57%), to be white (63% vs. 55%), and to have private insurance (35% vs. 26%). They were also more likely to have an admitting diagnosis relating to either trauma (17% vs. 10%) or an acute neurologic event (19% vs. 11%) (P<0.0001 for all comparisons).

One possible reason for these disparities is unconscious clinician bias, the authors noted. It's also possible that women and men (or their proxies) have different cultural preferences on intensity of care in the presence of critical illness, they wrote. And since non-white race has been associated with fewer advance directives and more discord among family members regarding care goals, “inability to arrive at consensus… may explain our finding that non-whites were less likely to undergo early tracheostomy,” the authors wrote.

They also noted limitations of their retrospective study, such as how they could not account for all of the complex factors that clinicians consider for tracheostomy timing and how the administrative data set is subject to coding errors. These findings also may not be generalizable to community hospitals or academic centers that do not participate in the UHC, they noted.

“Despite these potential limitations, this is one of largest studies focusing on tracheostomy timing in the literature and the first to identify the benefits of early tracheostomy across multiple categories of disease and specialties,” they wrote, noting that standardized protocols to determine the timing of tracheostomy for ventilated patients may help correct these disparities.

Postural modification improves effectiveness of Valsalva maneuver

A modification to the Valsalva maneuver significantly increased its effectiveness at stopping supraventricular tachycardia, a recent study found.

The trial included 433 patients who presented with supraventricular tachycardia (excluding atrial fibrillation and flutter) at emergency departments in England in 2013 and 2014. They were randomized to the standard, semi-recumbent Valsalva maneuver or a modified maneuver in which the Valsalva strain was done in a semi-recumbent position, after which the patient was immediately repositioned to be supine with a passive leg raise. Results were published by The Lancet on Aug. 25.

In the standard group, 17% of patients achieved sinus rhythm within 1 minute, compared to 43% of the patients who underwent the modified maneuver (adjusted odds ratio, 3.7; 95% CI, 2.3 to 5.8; P<0.0001). No serious adverse events were recorded. This represents a substantial difference in the number of patients needing other treatments for their supraventricular tachycardia, such as adenosine, which many find unpleasant, the study authors noted.

The modification didn't reduce time spent on the procedure or rate of hospital admission, likely because admission is usually based on concurrent medical conditions. However, it is simple, well tolerated, and free, the authors said. The trial used a manometer to ensure a 40-mm Hg pressure, 15-second strain, but patients could instead be instructed to blow into a 10-mL syringe to move the plunger. The authors noted that the observed success rate is higher than the 31% reported in a previous study of a Trendelenburg Valsalva maneuver, and they called for their modification to become a “routine first treatment.”

An accompanying editorial agreed, noting that the modification could improve identification of the patients who require more aggressive treatment. Not only clinicians but patients could learn to perform the maneuver and possibly avoid a hospital visit entirely, the editorialists wrote, concluding “thus, an attempt by all patients before invasive treatment seems a reasonable part of the standard of care.”

Models show statewide coordination could prevent many resistant infections

A coordinated approach to reducing antibiotic-resistant infections could prevent 619,000 health care-associated infections over the next 5 years, a modeling study calculated.

The CDC used data from the National Healthcare Safety Network and Emerging Infections program to project future rates of health care-associated carbapenem-resistant Enterobacteriaceae (CRE), multidrug-resistant Pseudomonas aeruginosa, invasive methicillin-resistant Staphylococcus aureus (MRSA), and Clostridium difficile. The researchers estimated potential reductions based on published reports of national interventions in other countries. The study was published in the Aug. 7 Morbidity and Mortality Weekly Report.

The study included 2 models of intervention: 1 in which 4 hospitals and 6 nursing homes collaborated and another in which 102 facilities coordinated to prevent these infections. The spread of CRE was simulated under each model and compared to that likely with current infection control. In the coordination models, the facilities shared CRE results with a central authority that targeted preventive activities across their facilities.

The 10-facility coordination resulted in a cumulative 74% reduction in CRE acquisitions over 5 years, while the 102-facility network resulted in a 55% reduction over 15 years, the researchers calculated. This works out to avoidance of an estimated 619,000 health care-associated infections, 37,000 deaths, and $7.7 billion in health care costs (not including intervention costs) over 5 years, they said.

Public health departments are uniquely suited to bring these projections to reality, the authors noted. State-based public health programs could help hospitals share antibiotic resistance data, test accurately for infections, communicate among facilities, and improve infection prevention practices, in addition to responding to infection clusters and strategically targeting resources, the authors said. “The current threat of antibiotic resistance in health care settings suggests that historical independent institution-based efforts to prevent transmission have been inadequate,” they concluded.

Clot recurrence and major bleeds similar with tinzaparin or warfarin, study finds

For cancer patients with venous thromboembolism (VTE), long-term treatment with low-molecular-weight heparin (LMWH) instead of warfarin resulted in similar rates of recurrence and major bleeding, a recent study found.

The open-label, manufacturer-funded study included 900 patients in 164 countries treated between August 2010 and November 2013. They were all adults with active cancer and documented proximal deep venous thrombosis (DVT) or pulmonary embolism, with a life expectancy of at least 6 months and no contraindications to anticoagulation. Half were randomized to the LMWH tinzaparin (175 IU/kg) once daily for 6 months, while the other half received tinzaparin for 5 to 10 days before switching to 6 months of warfarin with a target international normalized ratio between 2 and 3. Results were published in the Aug. 18 Journal of the American Medical Association.

Over 6 months of follow up, tinzaparin was associated with a lower rate of VTE recurrence than warfarin, but the difference was not statistically significant (7.2% vs. 10.5%; hazard ratio, 0.65; 95% CI, 0.41 to 1.03; P=0.07). There were fewer symptomatic DVTs in the tinzaparin group: 12 versus 24 patients (P=0.04). The groups had similar rates of overall mortality (150 patients on tinzaparin vs. 138 on warfarin; P=0.54) and major bleeding (12 patients on tinzaparin vs. 11 on warfarin; P=0.54). The tinzaparin group did have a significantly lower number of clinically relevant nonmajor bleeds: 49 patients versus 69 (hazard ratio, 0.58; 95% CI, 0.40 to 0.84; P=0.004).

The study authors concluded that full-dose tinzaparin did not reduce recurrent VTE, the study's primary endpoint, in patients with active cancer and acute symptomatic VTE in this, the largest known trial to compare efficacy and safety of LMWH and warfarin for this indication. The CLOT trial previously looked at this issue and found benefit with dalteparin compared to warfarin, possibly because it had a higher-risk population, they noted.

The warfarin patients in the current study had a lower than expected rate of VTE, leading the study to be potentially underpowered and the authors to call for future research to assess the efficacy of LMWH in cancer patients at higher clot risk. This study does show, at least, that 6 months of full-dose tinzaparin was safe in a broad oncology population, the authors said. Because the trial was designed before the newer oral anticoagulants came on the market, they were not studied, but guidelines don't currently recommend these drugs for cancer patients, the study authors noted.