News Roundup
New and Noteworthy Information From August 2012

A new tuberculosis multidrug treatment—consisting of the novel drug candidate PA-824, moxifloxacin, and pyrazinamide (PaMZ)—might be more effective than some existing anti-tuberculosis drug therapies, researchers reported in an article published online ahead of print July 23 by the Lancet. In their Phase II trial, they randomized 85 treatment-naïve drug-susceptible patients with uncomplicated pulmonary tuberculosis to one of six treatment regimens: PaMZ, bedaquiline, bedaquiline and pyrazinamide, PA-824 and pyrazinamide, bedaquiline and PA-824, or unmasked standard anti-tuberculosis treatment (control). At 14 days, the early bacterial activity of PaMZ was comparable with that of standard treatment and significantly higher than that of bedaquiline, bedaquiline and pyrazinamide, and bedaquiline and PA-824. It was not higher than that of combined PA-824 and pyrazinamide, however. These results, together with preclinical data, suggest that PaMZ could treat drug-susceptible tuberculosis and some forms of drug-resistant tuberculosis in only four months, according to the researchers.

Tudorza Pressair (aclidinium bromide) was approved by the FDA for the long-term maintenance treatment of bronchospasm associated with COPD. The drug—a dry powder inhaler used twice daily—is a long-acting antimuscarinic agent that improves airflow by helping muscles around the lungs’ large airways to stay relaxed. It was found safe and effective in three randomized, placebo-controlled confirmatory clinical trials including 1,276 COPD patients, ages 40 and older. Potential serious adverse effects include paradoxical bronchospasm, acute narrow-angle glaucoma, and urinary retention, and the most common adverse effects reported include headache, nasopharyngitis, and cough. It should not be used as rescue therapy for acute bronchospasm and is not recommended for patients younger than 18.

Patients with mild or moderate obstructive sleep apnea (OSA) and daytime sleepiness can benefit from continuous positive airway pressure (CPAP), investigators concluded in a study published online ahead of print July 20 by the American Journal of Respiratory and Critical Care Medicine. They randomized 281 OSA patients to eight weeks of active or sham CPAP; at the end of this period, patients in the sham arm received eight weeks of active CPAP. Following the first eight-week intervention, the adjusted mean change in the total score on the Functional Outcomes of Sleep Questionnaire (FOSQ) was 0.89 for the active group and -0.06 for the sham group, indicating an effect size of 0.41. From the beginning to the end of the second eight-week phase, the mean improvement in FOSQ total score was 1.73, indicating an effect size of 0.69.

Rates of community-onset and hospital-onset MRSA among a US military population decreased from 2005 to 2010, according to a report in the July 4 JAMA. The authors performed an observational study of all Department of Defense healthcare insurance beneficiaries from January 2005 through December 2010. Annual incidence rates of community-onset MRSA bacteremia were 1.7 per 100,000 person years in 2005 and 1.2 per 100,000 person-years in 2010. Over the same period, incidence rates of hospital-onset MRSA bacteremia decreased from 0.7 per 100,000 person-years to 0.4 per 100,000 person-years. The proportion of community-onset soft tissue infections due to MRSA peaked at 62% in 2006 and decreased annually to 52% in 2010.

Treatment with drotrecogin alfa (activated; DrotAA) appears to be associated with reduced hospital mortality in patients with septic shock, according to a meta-analysis published online ahead of print July 16 by Lancet Infectious Diseases. The authors analyzed nine controlled trials involving a total of 41,401 patients and 16 single-group studies involving 5,822 patients to determine the drug’s efficacy. They also analyzed 20 studies with 8,245 patients to determine its safety. Patients treated with DrotAA had an 18% reduction in hospital mortality compared with controls—a finding that agreed with the findings from a prominent 2001 trial of DrotAA but differed from the results of a DrotAA study published in May (see “DrotAA Lacks Benefit for Patients With Septic Shock” in the July issue of Pulmonary Reviews). In the current study, DrotAA also was associated with increased rates of bleeding, however.

Hospital volume and surgeon specialty are important determinants of mortality following lung cancer resection, according to a meta-analysis in the July Journal of Thoracic Oncology. The authors analyzed 19 studies published between January 1, 1990 and January 20, 2011. They found that postoperative mortality was significantly lower in high-volume hospitals (odds ratio [OR], 0.71). Surgeon volume was not associated with outcome. In addition, mortality was significantly higher in resections performed by a general surgeon than in those performed by general thoracic surgeons (OR, 0.78) or cardiothoracic surgeons (OR, 0.82). “Evaluation of individual institutions in a national audit program might help elucidate the influence of individual quality-of-care parameters, including hospital volume, on outcome,” the researchers suggested.

Meditation or exercise training may reduce the burden of acute respiratory infection illness (ARI), researchers reported in the July Annals of Family Medicine. Patients ages 50 and older were randomized to eight weeks of training in mindfulness meditation (n = 51), eight weeks of training in moderate-intensity sustained exercise (n = 47), or observational control (n = 51). The meditation, exercise, and control groups had 27, 26, and 40 ARI episodes, respectively, along with 257, 241, and 453 days of illness, respectively. Mean global illness severity scores on the Wisconsin Upper Respiratory Symptom Survey were 144, 248, and 358 in the meditation, exercise, and control groups, respectively; the score was significantly lower in the meditation group than in the control group. Compared with the control group, both the meditation group and the exercise group tended toward shorter illness duration, and the exercise group also tended toward lower global severity.

An investigation of a recent pertussis outbreak in Washington State indicated that immunity from the disease may wane soon after vaccination, the CDC reported in the July 20 Morbidity and Mortality Weekly Report. The authors found 2,520 reported cases of pertussis (37.5 cases per 100,000 residents) from January 1 to June 16, 2012—a 1,300% increase compared with the same period in 2011. High rates of the disease were observed in adolescents aged 13 to 14, although this age group had high rates of vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. “Preliminary national incidence data are consistent with the Washington findings,” the researchers said. Although ongoing research is evaluating Tdap’s duration of protection in adolescents, pertussis vaccination remains the most effective strategy for preventing infection, they added.

In urban children with asthma, missed sleep may contribute to morbidity, researchers reported in the July Annals of Allergy, Asthma, and Immunology. Parents of 147 children ages 6 to 13 were surveyed about their children’s asthma morbidity, missed sleep, and behavior and the parents’ quality of life. Across the sample, reports of missed sleep were associated with more frequent school absences, more activity limitations, and lower quality of life. “The associations between missed sleep and asthma morbidity were stronger for Latino children compared with non-Latino white and African American children,” the researchers noted. “For children with higher anxiety, the associations between missed sleep and asthma morbidity were stronger than for children with lower anxiety.”

A new automated method of reviewing medical records can identify patients with incident lung nodules accurately and efficiently, investigators reported in the August Journal of Thoracic Oncology. They devised an identification method that uses five diagnostic codes, four procedural codes, and a natural language processing algorithm that performs free text searches of radiology transcripts. When the method was used to evaluate medical records of patients in a large community-based health plan from 2006 to 2010, it identified 7,122 unique members as having one or more incident lung nodules. The researchers also compared the natural-language processing algorithm’s findings in a random sample of 116 radiology transcripts with those of an experienced pulmonologist. When the pulmonologist’s findings were used as a reference standard, the algorithm had a sensitivity of 96% specificity of 86% for identifying the presence of lung nodules.

For cystic fibrosis patients, the SPLUNC1 protein and its derivative peptides may offer a means of thinning mucus in the lungs, according to a study published online July 13 by The FASEB Journal. In a previous study, the researchers identified SPLUNC1 as an inhibitor of the epithelial sodium channel (ENaC), which is responsible for Na(+) and fluid absorption across colon, kidney, and airway epithelia. In the current research, they located the ENaC inhibitory domain of SPLUNC1 to the protein’s N terminus and found that G22-A39, a peptide corresponding to this domain, inhibited ENaC activity about as much as full-length SPLUC1. Adding the peptide to cystic fibrosis human bronchial epithelial cultures (HBECs) increased the airway surface liquid height from 4.2 to 7.9 μm, which is comparable to the height in normal HBECs.

A simple algorithm can reliably predict which COPD patients will need supplemental oxygen during air travel, according to research published online ahead of print July 6 by Thorax. The algorithm was constructed using data from 100 patients with COPD referred to hypoxia-altitude simulation test (HAST). It uses sea level pulse oximetry at rest and exercise desaturation to determine whether patients are fit to fly without further assessment, need further evaluation with HAST, or should receive in-flight supplemental oxygen without further evaluation. When the algorithm was tested prospectively on an independent sample of 50 patients with COPD, it had a sensitivity of 100% and a specificity of 80%.

—Jack Baney

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