Journal watch: Recent studies of note

Recent studies of note.

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 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.

1996 guidelines better than 2005 set for patients with potentially resistant microorganisms

Older guidelines more accurately predicted whether cases of hospital-acquired pneumonia were drug resistant than updated guidelines, according to a recent study of intensive care patients.

The study, in the April 1 Clinical Infectious Diseases, observed 276 patients who acquired pneumonia while in the intensive care unit. The patients were divided into two groups based on the 2005 guidelines from the American Thoracic Society–Infectious Diseases Society of America, which determined the risk for drug resistance based on time of onset and certain risk factors. The 38 patients in group 1 had early onset of pneumonia and no risk factors. Yet 26% of the patients in the group were found to have potentially drug-resistant microorganisms, resulting in an overall predictive accuracy of 50%.

The 2005 guidelines were better at prediction in the group 2 patients, who had late-onset pneumonia or risk factors, scoring 92%. Overall, the 2005 guidelines successfully predicted causative pathogens in 86% of the patients. When the researchers reclassified patients according to the 1996 American Thoracic Society guidelines, the accuracy was improved, with the etiology accurately predicted in an additional nine patients. The patients were identified based on risk factors that had been eliminated from the 2005 guidelines, including previous prolonged and complicated surgery, chronic alcohol abuse, COPD and solid cancer.

The study also assessed physicians' adherence to guidelines, and found adherence was more common for group 2 patients, possibly indicating that physicians (at least in this hospital) were reluctant to discount previously recommended risk factors, the authors speculated. Adherence to guidelines was associated with better clinical response in the group 2 patients but not in group 1. There was no difference in mortality or length of stay in either group 1 or 2 based on adherence to the guidelines.

The authors also noted that the most common pathogens were the same in patients with early- and late-onset pneumonia. Therefore, rather than the time of onset, identification of risk factors for specific pathogens is crucial in choosing an appropriate empirical treatment. The authors recommended that future guidelines for the treatment of hospital-acquired pneumonia, at least for patients in the ICU, use the risk factors from the 1996 guidelines. Further assessment would be needed to determine whether the findings could be extrapolated to non-ICU patients or ICUs in the rest of the world, they concluded.

Studies examine ABCD2 score for stroke risk prediction

The ABCD2 score is useful for prediction of stroke severity and risk after transient ischemic attack (TIA), according to findings from two studies.

The ABCD2 score, which assesses age (A), blood pressure (B), clinical features (C), symptom duration and diabetes (D2) , was developed to predict stroke risk and determine appropriateness of hospital admission in patients with TIA.

In the first study, researchers in England examined the value of the ABCD2 score for predicting severity of recurrent events in 500 patients who had had TIA. Of these, 11% experienced a recurrent TIA and 10% had recurrent stroke within a week of the initial event, according to face-to-face interviews. The ABCD2 score had a high predictive value for major recurrent stroke and also predicted related variables such as disability and length of stay. However, it was weakly predictive of minor stroke and had an inverse relationship to the risk for recurrent TIA.

In the second study, researchers used data from the North Dublin TIA Study to determine the external validity of the ABCD2 score, carotid stenosis and atrial fibrillation as predictors of early recurrent stroke in 443 patients with confirmed TIA. Carotid stenosis was the best predictor of future events, but the ABCD2 score was useful for predicting recurrent events in patients whose TIA was suspected by nonspecialists. However, in stroke specialist-confirmed TIA cases, the ABCD2 score performed no better than chance alone for predicting stroke at 90 days, largely because some patients experienced recurrent stroke despite having low ABCD2 scores.

The authors of the first study acknowledged that their results were limited by the small number of stroke outcomes studied, among other factors, while the authors of the second study noted “too few” patients had early brain imaging, among other limitations. An accompanying editorial said that both studies emphasize the positive and negative aspects of the ABCD2 score. For example, while it is easy to use and provides information on both diagnosis and prognosis, it does not take brain imaging data or ultrasound data into account.

Nevertheless, “Despite its shortcomings, the ABCD2 score appears to be the best clinical tool available to stratify high-risk TIA patients and may assist in developing admission recommendations in cooperation among neurologists, internists, and emergency department physicians for patients presenting with TIAs,” the editorialists wrote. They stressed, however, that the ABCD2 score should not substitute for individual clinical judgment.

Both studies and the editorial were published in the May issue of Stroke.

Program can help opioid-dependent inpatients transition to outpatient treatment

A program to identify at-risk, opioid-dependent inpatients can successfully engage a sizable number of those patients in outpatient addiction treatment, a study found.

From January 2002 to January 2005, a nurse at Boston Medical Center identified, assessed and enrolled 203 out-of-treatment, opioid-dependent drug users based on their receipt of methadone during hospitalization. Patients transitioned upon discharge to an outpatient interim opioid agonist program that provided 30-day stabilization, followed by 60-day taper. The nurse also provided case management that emphasized HIV risk reduction, health education, medical follow-up and counseling. The study was published in the August Journal of General Internal Medicine.

Of the 203 patients who initially enrolled during hospitalization, 59% received treatment, 26% didn't receive treatment and 16% weren't able to receive treatment due to medical problems, psychiatric issues or incarceration. Among those who enrolled but didn't receive treatment, 46% didn't show at the methadone clinic or left the hospital against medical advice, and 54% didn't show at a long-term opioid treatment program (OTP) clinic for 14 consecutive days or were discharged for behavioral issues.

Thirty-five percent of the 203 patients enrolled in a long-term OTP, while 15% completed methadone taper, 4% entered outpatient or residential substance abuse treatment, and 2% entered an inpatient detoxification facility. Of the 167 patients who became participants at the OTP clinic, 56% obtained discharge prescriptions, 54% attended a primary care appointment, 50% attended two or more group counseling sessions, 17% attended a needle-exchange program, and 16% attended a twelve-step program.

With the provision of interim opioid agonist treatment and a range of treatment intensity options, opioid-dependent inpatients can be linked to appropriate outpatient addiction care and medical care, the authors concluded. The model studied represents a single health care system's experience and thus findings are preliminary, they cautioned. Because there was no comparison group, it wasn't possible to quantify the relative improvement in addiction treatment; still, most participants weren't seeking treatment when they were hospitalized and few would have received treatment had they not enrolled in the study's program, the authors said.

French intervention reduced MRSA infections

A multi-faceted intervention in French hospitals was associated with a decline in rates of methicillin-resistant Staphylococcus aureus (MRSA), a study reported.

The 38 teaching hospitals (acute care, rehab and long-term care) instituted a MRSA-reduction program in 1993. The program included passive and active surveillance, quick notification of cases, barrier precautions, training and feedback. In 2001, a campaign to promote use of alcohol-based hand-rub solutions was added. The observational study calculated MRSA burden in the hospitals by measuring the proportion of S. aureus strains that showed methicillin resistance and the incidence of MRSA cases.

Overall, the hospitals had about a 35% decrease in MRSA burden from 1993 to 2007. Incidence went down from 0.86 to 0.56 per 1,000 hospital days. The MRSA burden decreased most markedly in intensive care units (59% decline), followed by surgical (44%) and medical (32%) wards. Although the ICUs had a steady decline in MRSA burden, the decrease in medical wards was seen only after the launch of the hand sanitizer effort. The use of hand sanitizer increased steadily when averaged for all facilities (from 2 L per 1,000 hospital days to 21 L), but more dramatically (to 26 L) in acute care hospitals.

Because the study was a pragmatic intervention designed to deal with high MRSA rates, observers should be cautious in assuming a causal association between the effort and the MRSA rates, the study authors noted. However, MRSA rates were on the increase at the time of the intervention and other studies have found marked increases in MRSA in other European hospitals during the same time period.

The researchers concluded that an intensive long-term program can result in a sustained reduction of MRSA burden at large institutions with high endemic rates. However, they noted that the studied hospitals' rates remain high in comparison to others in northern Europe and that anti-MRSA efforts need to be maintained and expanded. The study was published in the March 22 Archives of Internal Medicine.

Age-adjusted D-dimer value helps exclude PE in older patients

Using an age-adjusted D-dimer cutoff value increased the proportion of older patients in whom pulmonary embolism could be excluded as a diagnosis, a study found.

In a retrospective, multicenter cohort study in Europe, researchers analyzed data from four studies comprising 5,132 patients with clinically suspected pulmonary embolism (PE). To derive a new D-dimer cutoff value, they used data from two studies to divide patients older than 50 years (the derivation set) into 10-year age groups. They constructed receiver-operating characteristic (ROC) curves of the D-dimer test for each age group to find the best cutoff value, with a sensitivity of 100% and the highest corresponding specificity. Then, the cutoff value was validated with two additional independent data sets. Outcome measures were the proportion of patients in the validation cohorts with a negative D-dimer test, the proportion in whom PE could be excluded, and false-negative rates. The study was published March 30 in BMJ.

For patients older than 50 years, the D-dimer cutoff value was (patient's age × 10) µg/L. The old cutoff value was less than 500 µg/L. When the new value was used, 42% of the patients in the data set with an “unlikely” clinical probability assessment score had PE excluded, compared to 36% with the old value. In the two validation sets, the increase in the proportion of patients with a D-dimer below the new value versus the old value was 5% and 6%. For patients older than 70 years in the three data sets, the absolute increase was 13% to 16%. The failure rates for all ages in the three sets ranged from 0.2% to 0.6%.

The clinical usefulness of the new cutoff value increased significantly with age, the authors noted. Safety wasn't compromised with the new value, as there was no difference in the false-negative rate in the derivation and validation sets, and the 95% upper confidence levels were below 3% for all patients older than 50 years, they said. In addition, the cost-effectiveness of the test in patients older than 80 years probably increases with the new value, as the number needed to test was lower in this group (3.5 vs. 6.6 with the old). This means that for every 35 patients older than 80 years with a low/intermediate or “unlikely” clinical probability of PE, imaging tests can be avoided in 10 patients with the new value, compared to five with the old, the authors said. The new D-dimer cutoff still needs to be validated prospectively before being implemented in practice, they added.

Silent PE occurs in one-third of DVT patients

Silent pulmonary embolism (PE) occurs among one-third of patients with deep vein thrombosis (DVT), and routine screening would offer several advantages and disadvantages, researchers concluded from a systematic review.

Researchers identified 28 published investigations, then stratified them. Tier 1 included 12 studies in which silent PE was diagnosed by a high-probability ventilation-perfusion lung scan using criteria from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria, computed tomography pulmonary angiography, or conventional pulmonary angiography. Tier 2 included 16 studies in which silent PE was diagnosed by ventilation-perfusion lung scans based on unstated or non-PIOPED criteria. Results c&_ct=28&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ed4bae60c4af8cf0bbdf7c13900236a6 appeared in the May American Journal of Medicine.

Among Tier 1 studies, silent PE was detected in 703 of 2,656 patients (27%) with DVT. Among Tier 2 studies, silent PE was detected in 962 of 2,577 patients (37%) with DVT. In total, silent PE was diagnosed in 1,665 of 5,233 DVT patients (32%). Researchers considered this a conservative estimate because many studies used stringent criteria to diagnose PE.

Silent PE is more frequent in patients with proximal DVT than distal. When only those with proximal DVT were considered, the prevalence of silent PE was 600 of 2,269 (26%) in Tier 1 patients and 291 of 538 (54%) in Tier 2 patients. The overall prevalence of silent PE in patients with proximal DVT was 891 of 2,807 (32%).

In five investigations, comparisons were made of the prevalence of silent PE with proximal and distal DVT. In those with proximal DVT, silent PE occurred in 196 of 546 patients (36%) compared with 15 of 113 patients (13%) with distal DVT (P<0.0001). In an investigation of proximal DVT that extended into the pelvic veins, 69 of 139 patients (50%) showed silent PE.


  • Silent PE was associated with aging. Among patients with proximal DVT, silent PE was present in 14% of those aged 40 years or less, 22% of those ages 40 to 70, and 40% of those 70 years or more.
  • Larger perfusion defects occurred more frequently in patients with DVT of the thigh or pelvic veins than in those with distal DVT. Silent emboli may be extensive and involve central pulmonary arteries.
  • Silent PE seemed to increase the risk of recurrent PE. Prevalence was 25 of 488 (5.1%) with silent PE compared to 7 of 1,093 (0.6%) without silent PE.

Routine screening for silent PE among DVT patients would offer a baseline for further imaging studies and a better understanding of a patient's pathophysiology, the authors said. Furthermore, hospitalization would have to be considered if a silent PE was found. Disadvantages include the costs, time and radiation exposure involved.

Arterial and central venous catheters carry similar infection risk

Arterial catheters and central venous catheters carry similar risk for bacterial colonization and catheter-related infection, according to a study.

Infection risk is generally thought to be lower with arterial catheters than with central venous catheters, and guidelines do not recommend that either type of catheter be routinely replaced although supporting data on arterial catheters are lacking. French researchers evaluated data from a previously conducted infection control trial to compare the risk for colonization and catheter-related infection (CRI) in arterial versus central venous catheters. A total of 3,532 catheters and 27,541 catheter-days in seven ICUs were included. The study results appeared in the April Critical Care Medicine.

The authors found that rates of colonization did not differ significantly between arterial catheters and central venous catheters (7.9% vs. 9.6%, respectively), and CRI rates were also similar (0.68% vs. 0.94%). Arterial catheters were associated with a steady increase in daily hazard rate for colonization over time (1.3% on day 5, 2.4% on day 10 and 3.0% on day 15) while with central venous catheters this rate remained stable (1.2% on day 5, 1.6% on day 10 and 1.4% on day 15). The hazard for colonization did not differ by catheter type during the first seven days of catheterization but was higher with arterial catheters after seven days. The researchers identified respiratory failure and femoral insertion as independent risk factors for arterial catheter colonization and trauma or absence of septic shock at ICU admission, femoral or jugular insertion and absence of antibiotic treatment as independent risk factors for central venous catheter colonization.

The authors acknowledged that their study was observational and used catheter colonization as an end point because CRI rates were low. However, they concluded that rates of both catheter colonization and CRI were similar with arterial and central venous catheters, and that infection in both types of catheters should be targeted for prevention in the ICU.

Many stent patients delay taking clopidogrel with adverse results

Patients who delay filling their clopidogrel prescription for even a day after discharge post-implantation of a drug-eluting stent (DES) have a higher risk of death or myocardial infarction (MI).

A retrospective cohort study included 7,402 patients who received a DES at one of three large integrated health centers. According to pharmacy records, 16% of the patients did not fill their prescriptions for clopidogrel on the day of discharge. Patients with any delay in filling clopidogrel had a higher risk of death or MI during follow up (14.2%) compared with patients who filled their prescriptions the day of discharge (7.9%), with a large proportion of the adverse events occurring within the first 30 days after discharge. Patients were less likely to fill the prescription if they were older or had more comorbidities. The study appeared in the May Circulation: Cardiovascular Quality and Outcomes.

Whether patients delayed by one day or more than five had no significant impact on their increased risk, which may be due to the loading dose, patients metabolizing clopidogrel differently or not starting the drug the day they picked it up. The study also found that delay in filling prescriptions for statins did not increase risk, although they could not collect data on compliance with aspirin therapy. The researchers noted that patients who delayed filling the initial prescription were more likely to have gaps between subsequent refills.

The study's results may actually underestimate the degree of the problem, the authors noted, since all patients in the study had prescription drug coverage. The findings highlight the importance of ensuring patients take clopidogrel as prescribed and thereby reduce their risk of stent thrombosis. In order to accomplish this goal, the lead author of the study said that hospitals should ensure that patients receive a follow-up phone call from a pharmacist or nurse soon after discharge, in addition to general efforts to improve the quality of discharge transitions.