Journal watch: Recent studies of note

Recent studies of note.

Use of probiotics helps lower ventilator-associated pneumonia rates

Administering probiotics to critically ill patients appears to help lower the incidence of ventilator-associated pneumonia (VAP), a meta-analysis found.

Photo by Thinkstock
Photo by Thinkstock.

Researchers analyzed five randomized controlled trials that compared administration of probiotics with control (placebo or otherwise) in 689 adult patients undergoing mechanical ventilation, and that reported on VAP incidence. Probiotics were administered alone or with prebiotics. All five studies were published after 2005; the mean sample size of the studies was 159 subjects. The proportion undergoing mechanical ventilation who were trauma patients was 100% in two studies, 20% to 25% in two studies, and less than 10% in one study. The review was published in the March Critical Care Medicine.

Compared with control patients, probiotics patients had lower incidence of VAP (fixed effects model: odds ratio [OR], 0.61; 95% CI, 0.41 to 0.91; random effects model: OR, 0.55; 95% CI, 0.31 to 0.98) and shorter length of ICU stay (fixed effects model: weighted mean difference, −0.99 day; 95% CI, −1.37 to −0.61). Probiotics were also associated with lower colonization of the respiratory tract with Pseudomonas aeruginosa (OR, 0.35; 95% CI, 0.13 to 0.93). Probiotic administration had no effect on ICU mortality, in-hospital mortality, duration of mechanical ventilation and diarrhea. The benefit of probiotics in lowering VAP was retained in subgroup analyses.

The benefit of probiotics on VAP incidence seems to contradict the conclusions of previous reviews, which found no benefit on nosocomial infections, the authors noted. However, the current analysis incorporates studies published since those prior analyses, and focuses on the preventive effects of a different disease, they added. The fact that probiotics patients were less likely to be colonized with Pseudomonas aeruginosa, and that incidence of VAP attributable to this bacterium was found to be lower, may reflect a species-specific effect of probiotics against Pseudomonas, the authors said. However, another cause, such as concurrent antipseudomonal antibiotic therapy, could also explain this effect. Future research is warranted on the issue, they noted.

Patients with superficial vein thrombosis may also have DVT

Many patients who present with superficial venous thrombosis (SVT) also either have or soon develop venous thromboembolism (DVT), a study reported.

The observational French study included 844 consecutive patients who saw a vascular medicine specialist for a symptomatic SVT of the lower limbs that was at least 5 cm on compression ultrasonography. At the first visit, 24.9% of the patients were found to also have a DVT or symptomatic pulmonary embolism. Over three months of follow-up, 10% of the remaining patients developed thromboembolic complications, even though 90% of them received anticoagulants.

Patients who were male, had a history of DVT or pulmonary embolism, had previous cancer, or no varicose veins—risk factors that have been noted by other studies—were at higher risk of complications during follow-up. This study was limited by a premature termination of enrollment with only about half the patients who were originally called for. The results were published in the Feb. 16 Annals of Internal Medicine.

The findings show that SVT is not entirely benign, study authors concluded. Clinicians should consider using compression ultrasonography in SVT patients as well as watching for symptoms of pulmonary embolism (and testing when symptoms are spotted) and following up closely with all of these patients, the researchers said. They also called for more research into the benefits and risks of using systemic anticoagulant therapy for symptomatic relief of SVT and to prevent DVT.

Higher PEEP levels associated with improved survival, but only in ARDS

Higher levels of positive end-expiratory pressure are associated with improved survival in acute lung injury, but only in patients with acute respiratory distress syndrome, according to a study.

Researchers performed a meta-analysis of three trials to determine whether higher or lower positive end-expiratory pressure (PEEP) affected outcomes in patients with acute lung injury or acute respiratory distress syndrome (ARDS) receiving low tidal volume ventilation. Patients with a Pao2:Fio2 of 200 mm Hg or less at baseline were considered to have ARDS. The study results appeared in the March 3 Journal of the American Medical Association.

Data from 2,299 patients were examined. Of these, 1,136 received higher PEEP and 1,163 received lower PEEP. Overall, 374 patients (32.9%) in the higher PEEP group and 409 (35.2%) in the lower PEEP group died (adjusted relative risk [RR], 0.94; 95% CI, 0.86 to 1.04; P=0.25). Among 1,892 patients with ARDS, 324 (34.1%) died in the higher PEEP group while 368 (39.1%) died in the lower PEEP group (adjusted RR, 0.90; 95% CI, 0.81 to 1.00; P=0.049). Among 404 patients without ARDS, 50 (27.2%) died in the higher PEEP group and 44 (19.4%) died in the lower PEEP group (adjusted RR, 1.37; 95% CI, 0.98 to 1.92; P=0.07). Patients receiving higher versus lower PEEP had similar rates of pneumothorax, vasopressor use, and days of breathing unassisted during the study's first 28 days.

The authors acknowledged that their findings in patients with ARDS could have been caused by chance and that their study had low statistical power, among other limitations. However, their conclusion suggests that higher PEEP may be associated with improved outcomes in patients with ARDS. They stressed that clinicians should remember the possible harms of PEEP when treating patients without ARDS, and called for additional meta-analyses of individual-patient data to help determine more definitive guidelines for use.

An accompanying editorial said that the study would be helpful to researchers but less so to clinicians because it did not offer specific treatment recommendations, and that additional meta-analyses may not clarify the remaining clinical questions. “Patients may be better off with a single sufficiently powered and well-designed clinical trial that rigorously tests a specific approach,” the editorialist wrote.

Effects of large ESA and iron doses vary with hematocrit level

More aggressive treatment with erythropoiesis-stimulating agents (ESAs) and iron benefitted dialysis patients with lower hematocrit levels but increased mortality risks in the patients with high hematocrit, a study found.

Researchers used data from the Medicare end-stage renal disease program to analyze the anemia management practices of U.S. dialysis centers. The main outcome was one-year all-cause mortality, and the study found the highest mortality rates in patients with hematocrit below 30% (2.1% monthly mortality) and the lowest (0.7%) in those with hematocrit of 36% or above. The study was published in the March 3 Journal of the American Medical Association.

Among the patients in the under 30% hematocrit group, the lowest mortality rates were seen in dialysis centers that used larger doses of ESAs. Similarly, more use of iron was associated with lower mortality in patients with hematocrit below 33%. However, for patients with hematocrit of 36% or higher, the centers that used ESAs and iron more intensively had higher mortality rates. For ESAs, the association between bigger doses and higher mortality extended to patients with hematocrit between 33% and 35.9%.

The cause of these findings is uncertain, the study authors said. It's unlikely that greater mortality relates directly to higher doses of ESA and iron, since the largest doses were given to the patients with the lowest hematocrit levels. Previous trials have found higher mortality risk associated with targeting of higher hematocrit levels, the authors noted. They concluded that, whatever the cause, greater use of ESAs and iron in patients with higher hematocrit levels is problematic and further research should be conducted to identify optimal treatment algorithms.

Current, validated med lists reduce errors on hospital admission

Presenting a physician-validated medication list upon hospital admission significantly protects against medication errors, a study found.

Researchers at Northwestern Memorial Hospital in Chicago conducted a study for 14 months in 2006-2007. They retrieved the previous days' admissions and obtained from the electronic medical records the physician-obtained medical history, as well as admission medication orders and patient demographics for 651 adult inpatients with 5,701 prescriptions.

The pharmacists then interviewed the patients, checked their prescription bottles, and consulted with pharmacies to reconcile information and compare it with medication orders to identify unexplained history and order discrepancies. Those resulting in order changes were considered errors, and were classified by drug class, type of error and the potential to cause harm had it not been caught. Findings were published in the May issue of the Journal of General Internal Medicine.

Among the group, 35.9% experienced order errors and 85% of them had errors originate in medication histories, almost half of which were omissions. Cardiovascular agents were commonly in error (29.1%). If undetected, 52.4% of order errors could have potentially required increased monitoring or intervention to preclude harm and 11.7% were rated as potentially harmful. Factors significantly associated with errors that could require monitoring or cause harm included age 65 and older (odds ratio [OR], 2.17; 95% CI, 1.09 to 4.30) and number of prescription medications (OR, 1.21; 95% CI, 1.14 to 1.29). Presenting a medication list (OR, 0.35; 95% CI, 0.19 to 0.63) or prescription bottles (OR, 0.55; 95% CI, 0.27 to 1.10) at admission helped.

Attempts to improve the accuracy of medication histories should focus on older patients with a large number of medications, and primary care physicians should help patients and caregivers maintain complete, accurate and understandable medication lists, researchers wrote.

Unexplained discrepancies occurred even though the researchers and the prescribing physician used the same medication lists or bottles. Researchers attributed this to physicians copying lists or prescription labels verbatim without systematically reviewing each medication. This step is important, they said, because labels on prescription bottles may not accurately reflect current regimens, newly prescribed medications or recent changes. A medication reconciliation toolkit is online.

Shock patients have more arrhythmias with dopamine vs. norepinephrine

Dopamine and norepinephrine carry the same overall mortality risk when used to treat shock patients, but dopamine is associated with more arrhythmias, a recent study found.

Photo by Thinkstock
Photo by Thinkstock.

In a multicenter, randomized, blinded trial, researchers assigned 1,679 European patients with shock to either dopamine or norepinephrine in order to restore and maintain blood pressure. A patient was considered to be in shock if the mean arterial pressure was less than 70 mm Hg or the systolic blood pressure was less than 100 mm Hg despite having been administered an adequate amount of fluids, and if there were signs of tissue hypoperfusion. Dosing was administered according to body weight, with doses of dopamine increased or decreased by 2 µg per kilogram per minute and doses of norepinephrine increased or decreased by 0.02 µg per kilogram per minute. If patients were still hypotensive at maximum doses (20 µg per kilogram per minute for dopamine or 0.19 µg per kilogram per minute for norepinephrine), then open-label norepinephrine, epinephrine or vasopressin was added.

Mortality rate at 28 days—the primary outcome—didn't differ significantly between the dopamine (52.5%) and norepinephrine (48.5%) groups (odds ratio [OR] with dopamine, 1.17; 95% CI, 0.97 to 1.42; P =0.10). There was also no difference in mortality at six months, at twelve months, during the hospital stay or during the ICU stay. There were more arrhythmic events among dopamine patients than norepinephrine patients (207 events [24.1%] vs. 102 events [12.4%], P <0.001), including more arrhythmic events that required withdrawal from the study. In predefined subgroup analysis, the 280 patients with cardiogenic shock had a greater mortality risk if they received dopamine versus norepinephrine (P =0.03); this risk difference wasn't present for septic shock and hypovolemic shock subgroups. The study was published in the March 4 New England Journal of Medicine.

Previous, smaller observational studies have suggested dopamine may be harmful to patients with septic shock, yet for the 1,044 septic shock patients in this study, there was no outcome difference based on administration of dopamine versus norepinephrine, the authors noted. The differences in mortality for cardiogenic shock patients and in arrhythmic events for all patients “strongly challenge the current American College of Cardiology American Heart Association guidelines, which recommend dopamine as the first-choice agent to increase arterial pressure among patients who have hypotension as a result of an acute myocardial infarction,” the authors concluded.

Scoring system predicts risk for hospital readmission

A prediction model using patient characteristics can help identify those at risk for early readmission to the hospital, according to a recent study.

Researchers performed a prospective observational cohort study to identify predictors of hospital readmission within 30 days of discharge. The study population involved 10,946 patients, 7,287 in the derivation cohort and 3,659 in the validation cohort, who were discharged from the general medicine service at six academic medical centers. Readmissions were determined from administrative data and from telephone follow-up 30 days after discharge. The authors looked at sociodemographic factors, social support, health condition and health care utilization and used logistic regression to determine which variables were associated with early readmission. The study results appear in the March Journal of General Internal Medicine.

In each cohort, 17.5% of patients were readmitted to the hospital within 30 days. In the derivation cohort, the following factors were associated with early readmission:

  • insurance status,
  • marital status,
  • having a regular physician,
  • Charlson comorbidity score,
  • SF12 physical component score,
  • at least one hospital admission within the past year and
  • a current length of stay longer than two days.

Based on a point system derived from the logistic regression model, the 5% of patients with a risk score of 25 points or higher had a ≥30% risk for readmission in both cohorts. Although marital status and having a regular physician seemed to be unusual predictors of early readmission, the former could result in being discharged home rather than an acute care facility and the latter could indicate the presence of more severe illness, the authors wrote.

The authors noted that their model had only fair discrimination and acknowledged that their results should not be generalized to settings other than academic medical centers, among other limitations. However, they concluded that the factors in this model help identify patients who are at risk for being readmitted to the hospital soon after discharge. “More work is needed to identify additional factors that impact post-discharge health outcomes, optimize the discharge process for all patients, and create interventions tailored to patients' needs in order to prevent potentially avoidable readmissions,” the authors wrote.

Chest radiography not needed in first month after CAP diagnosis

Routine chest radiographs aren't needed in the first month of follow-up after initial diagnosis of mild to moderately severe community-acquired pneumonia (CAP), a recent study suggests.

Researchers studied 119 patients admitted to the hospital for mild to moderately severe CAP, defined as a score of ≤110 on the Pneumonia Severity Index, and with radiological evidence of a new opacity. All patients were initially treated with intravenous amoxicillin, and received a physical examination, routine lab tests and chest radiograph upon admission. Pneumonia-related symptoms were scored using the CAP score, a patient-based questionnaire that aims to capture respiratory symptoms and well-being; patients were also asked to retrospectively evaluate symptoms and general health one month before pneumonia onset (pre-pneumonia score). Patients were followed for a maximum of 28 days. At follow-up visits on day 10 and day 28, researchers performed chest radiography, physical examination, lab analyses and CAP score testing. Radiographs were interpreted by on-call radiologists. The study was published in the March issue of the Journal of General Internal Medicine.

Physician-based clinical cure was defined as continued resolution or improvement of symptoms and clinical signs related to pneumonia without the need for additional or alternative antibiotic therapy, according to the treating physician's opinion. A CAP score equal to or greater than the pre-pneumonia score was taken as proof of a patient-based clinical cure. Multivariable regression analysis was performed to assess parameters associated with delayed radiographic resolution of CAP on days 10 and 28.

At 10-day follow-up, physician-based clinical cure was observed in 93% of patients; patient-based clinical cure (normalized CAP score) was seen in 32% of patients; and radiographic resolution in 30.8% of patients. At 28 days, continued clinical cure was seen in 88.9% of patients; patient-based clinical cure was seen in 41.7% of patients; and 68.4% had complete radiographic resolution. Patients with radiographic resolution at day 10 and day 28 had significantly higher CAP well-being scores at day 10 (62.5 vs. 50.1; P=0.02) and day 28 (71.6 vs. 59.9; P=0.02), compared to patients without radiographic resolution of CAP. At day 10, 57.9% of patients had incomplete radiological response; at day 28, it was 31.6%. About 11% of patients had radiological deterioration during follow-up; all of these patients had at least one clinical or lab sign that suggested clinical failure, such as fever or high respiration rate. Severity of pneumonia on admission was associated with delayed radiological clearance.

Cure of mild to moderately severe CAP as defined by radiography or patient assessment lags behind cure as defined by physician assessment, the authors noted. “Apparently, when patients are considered cured by their physician, they do not feel they are back to baseline,” the authors wrote. Because patients with deterioration of radiographic findings during follow-up had clinical evidence of treatment failure, it appears that monitoring a favorable disease process with routine short-term radiographic follow-up “leads to unnecessary resource use and has no additional value above clinical decisions based on patients' clinical symptoms,” the authors concluded. Follow-up chest radiographs to exclude underlying diseases shouldn't be performed within four weeks of initial diagnosis of mild to moderately severe CAP, they added. While this recommendation is in line with current guidelines, the guideline evidence is “grade D” (ie, expert opinion); this study provides support that the guidelines are appropriate.

Beta-blockers underused before and after cardiac rhythm device procedures

Heart failure patients often don't receive optimal beta-blocker therapy before and after undergoing cardiac rhythm device procedures, according to a recent study.

According to current guidelines, patients considered for cardiac rhythm devices should first receive optimal medical therapy. Researchers speculated that such therapy, particularly beta-blockers, is underused, perhaps because physicians tend to rely on technological rather than medical management of heart failure or are not aware of the impact of beta-blockers in this population. To test their hypothesis, they used a multistate managed care database to examine use of beta-blockers before and after cardiac device procedures in patients with heart failure. The study's primary outcome measures were beta-blocker use before the procedure and changes in beta-blocker use after hospital discharge.

Data from 2,766 managed care beneficiaries were included. Most (approximately 79%) were male; median age was 61 years. Sixty-five percent had hypertension, approximately 36% had diabetes, and approximately 20% had lung disease. Overall, 1,846 patients had implantable cardioverter-defibrillators implanted, revised or replaced; 814 received combined defibrillator-resynchronization devices and 106 received cardiac resynchronization devices. The study results were published in the March Circulation: Cardiovascular Quality and Outcomes.

In the 90 days before a device procedure was performed, patients spent a median of 46 days on beta-blockers, and 925 patients (33.4%) spent no days on beta-blocker therapy. Patients who did not take beta-blockers before receiving a cardiac device were more likely to be elderly and to have fewer outpatient cardiologist visits; they were less likely to have been previously hospitalized for heart failure or acute myocardial infarction. Beta-blocker use was more common in the 180 days after device procedures; the median number of days on beta-blockers was 155, and 83.4% of patients had at least one day prescribed for a beta-blocker.

The authors acknowledged several limitations of their study. For example, they noted, patients could have filled beta-blocker prescriptions without going through their managed care plans, and physicians could have written beta-blocker prescriptions that then went unfilled. However, the authors concluded that beta-blocker use in patients undergoing cardiac device procedures is not optimal, particularly before such procedures are performed. They called for additional studies “to delineate the extent of the problem in the non-managed-care setting, to link underuse with poorer outcomes, and to devise strategies to ensure that optimal medical therapy is provided to patients before device implantation.”