Literature Roundup: Feburary 2011

Randomized Controlled Trials:       (How do we make this list?)
Patients' Families Unmoved by End-of-Life Care Intervention Bundle
An ambitious, multifaceted intervention at ICUs in 12 hospitals, led by J. Randall Curtis, attempted to change intensivist behavior in approaching end-of-life care with patients and families. However, families of dying patients receiving the intervention reported the same satisfaction with care as controls. There were no differences in ICU length of stay or time to withdrawal of life support. Patients / families were assigned by cluster randomization (each ICU was its own control) to minimize institutional or other biases. (n=2300)  AJRCCM 2011;183:348-355.   

Fidaxomicin cures C.diff infections like vancomycin; prevents more recurrences
Louie et al report results of a phase 3 industry-funded trial of fidaxomicin, a poorly absorbed oral macrolide that's bacteriocidal vs C.difficile. The new drug was equivalent to oral vanco in curing C.diff infections (~90%), and superior at preventing recurrences (~14% vs 24%). It did not prevent recurrences of the more lethal and increasingly prevalent NAP1/BI/027 strain of C.diff. (n=629) NEJM 2011;364:422-431.
Nebulized Gentamicin Helped non-CF Bronchiectasis Patients
12 months of nebulized gentamicin (80 mg bid) markedly reduced symptoms, exacerbations, and bacterial density in people with bronchiectasis from causes other than cystic fibrosis. None of these benefits were sustained after 3 months without therapy, though. (n=65). AJRCCM 2011;183:491-499.

On-site path improves transbronchial needle aspiration (TBNA)?
Patients with on-site evaluation of TBNA samples had fewer sites sampled (1 vs. 2) and general complications (6% vs. 20%), with an equivalent yield compared to patients undergoing usual TBNA (n=168). CHEST 2011;139:395-401.

Lung Transplant Patients with RSV: Inhaled RNA Prevents BO?
In a very small trial (n=24), inhaled RNA (ALN-RSV01) appeared to improve outcomes in lung transplant patients with RSV respiratory infections, by interfering with viral replication. Symptoms were reduced, and at 90 days, incidence of bronchiolitis obliterans syndrome was 6% vs 50% in the control group. AJRCCM 2011;183:531-538
Ciclesonide tests its "me too" claim vs Advair for asthma
Ciclesonide, a new inhaled corticosteroid that seems to cause thrush less often than others, reached for equivalency with salmeterol/fluticasone in mild persistent asthma. Ciclesonide was better than placebo in controlling asthma but Advair users had a longer time to first asthma exacerbation. CHEST 2011;139: online supplement
A Cochrane review on ciclesonide could not establish its equivalence with other ICS at higher doses with certainty, but suggested it's roughly equi-efficacious to fluticasone and other ICS.

Beclomethasone as rescue-therapy-only for childhood asthma
Daily inhaled corticosteroids (ICS) may retard growth in children, who would rather play than take daily inhalers.
 Martinez et al randomized children with mild persistent asthma to four groups, one of which was beclomethasone + albuterol as rescue therapy only (i.e., no daily ICS), for 44 months. They did slightly worse than children taking daily ICS (35% exacerbation rate vs ~30%, and 8.5% treatment failure rate vs 3 - 6%), but grew 1 cm taller over the study period, with no adverse events. (n=843). Lancet 2011;377:650-657.

Once-daily indacaterol as effective as salmeterol bid for COPD
The once-daily beta-agonist was better than placebo and at least as good as twice-daily salmeterol, as measured by the SGRQ, TDI, and FEV1 after 12 weeks. The drug previously matched up well against tiotropium. Indacaterol is available in Europe, but not in the U.S. (n=838). ERJ 2011;37:273-279. 

Notable Journal Articles:
Asthma, down on the farm: The hygiene hypothesis got a boost from Ege et al, who analyzed dust from 16,000 European children's bedrooms and mattresses (stored with clinical/demographic data in two huge repositories, GABRIELA and PARSIFAL), for bacterial DNA or growth on bacterial/fungal culture media. Children living on farms had odds ratios for asthma of 0.49 to 0.76, compared to those with no farm exposure. Farm kids' dust had greater diversity of bacterial DNA and more species of bacteria and fungi in cultures, as well. Authors presume the dust was tracked in from barns, fields, etc. NEJM 2011;364:701-709

Exercise associated with better asthma control: People (n=21) with inadequately controlled asthma in a supervised exercise program for 12 weeks followed by self-motivated exercise for 12 weeks had "clinically significant" 0.5-point lower scores on the Asthma Control Questionnaire, as well as improved aerobic fitness, compared to 16 nonrandomized matched controls. Astonishingly, no serious trial testing exercise in asthma control has ever been done, according to these authors. ERJ 2011;37:318-323.

Pulmonary Vascular Disease
Pulmonary artery pressure measurement by echocardiography: Aduen et al performed simultaneous echocardiograms and right heart catheterizations on 117 patients, concluding echo is more accurate and precise than others previously found. They also promote a method of calculating and reporting mean PA pressure on echo, rather than systolic PA pressure. Right heart catheterization remains indispensable as the gold standard. CHEST 2011;139:347-352

Sleep apnea in CHF may be dangerously underdiagnosed: Using Medicare records from more than 30,000 beneficiaries with CHF, Javaheri et al suggest in this observational epidemiologic study that sleep apnea may be woefully overlooked and undertreated in people with CHF. The 2% of the cohort who were tested and treated for sleep apnea had one-third the 2-year mortality of their risk-matched peers who were never tested, in whom the prevalence of sleep apnea was estimated at 40%.  AJRCCM 2011;183:539-546.

Is polysomnography unnecessary? Chai-Coetzer et al designed and validated a predictive model for diagnosing obstructive sleep apnea without polysomnography in 157 general primary care patients considered at average risk for OSA. Berlin/Epworth questionnaires, snoring, waist size, witnessed apneas and age were fit into an algorithm, followed by home oximetry in a sample of mostly high-Berlin-scoring patients. All patients also underwent home PSG as the internal gold/reference standard. Sensitivity was 88% and specificity 82% in the validation cohort. Thorax 2011;66:213-219.     COMMENTARY by Octavian Ioachimescu, MD, PhD

Lung Cancer
New non-small cell lung cancer classification system: The IASLC, ATS, and ERS got together to better incorporate clinical logic into classification of NSCLC. No more bronchioloalveolar carcinoma (they propose adenocarcinoma in situ or invasive mucinous adenocarcinoma, depending on its size). Large cell carcinoma with neuroendocrine features gets separated out of NSCLC entirely, so it can be treated as small cell. And so on. Giuseppe's digest is easier digested than the whole document. J Thorac Oncol 2011;6:244-285.

Long-term survival after carcinoid resection is excellent: Cao et al report experience with 186 patients with resected bronchopulmonary carcinoid in Australia; median survival was 20 years. Those older than 60 at presentation and/or with higher-grade/atypical tumor histopathology had worse survival. Ann Thorac Surg 2011;91:339-343.

Interstitial Lung Disease
Acute exacerbations of IPF portend grim outcome: Song et al retrospectively reviewed 461 cases of IPF (269 biopsy-proven) in Korea. More than a third of patients were hospitalized for respiratory deteriorations over a 2-year period. About half the deteriorations were attributed to acute exacerbations of IPF, with most of the rest attributed to infections (half the patients had BAL and/or ET aspirates as part of a separate study protocol). In news reports, this is being spun as a surprisingly low number of viral infections causing exacerbations, contradicting dogma. Half of those admitted died in-hospital; 90% of those requiring mechanical ventilation died. ERJ 2011;37:356-363.

Has the biomedical research-industrial complex lost its way? Moses & Martin see an impending crisis of public trust in the entire enterprise. They call for an epic shift in national priorities, policy, and funding of research, envisioning a more collaborative, value-based system-- while acknowledging that such a sea change would take decades. NEJM 2011;364:567-571. FREE FULL TEXT

How industry stole the clinical trials game DeMets & Califf give a historical play-by-play, lament the current state of affairs, and issue a call to arms for academics to leverage the current political climate favoring comparative-effectiveness and translational research, in order to build a new clinical trials edifice that favors the public's health over profits.  JAMA 2011;305:713-714.

Medicare wants health system change; puts $3.5B of GME's funds at risk: MedPAC wants the next generation of MDs to be cost-conscious, evidence-minded, and amenable to standardization of care. To prod GME programs to train young MDs thusly, the influential government advisory body recommends allocating $3.5B of the $9.5B annual GME outlay as at-risk incentive payments. A proposed committee would have 3 years to design metrics for performance by U.S. postgraduate training programs. NEJM 2011;364:693-695.

Topic Reviews: 

Long-term oxygen therapy: Christopher KL & Porte P, CHEST 2011;139:430-440
Transtracheal oxygen therapy: Christopher KL, Schwartz MD

Optimal duration of anticoagulation after VTE: Goldhaber SZ, Circulation 2011;123:664-667. FREE FULL TEXT

Inspiratory muscle training in COPD: Gosselink R, ERJ 2011;37:416-425.
Long-term complications of critical care: Desai SV, Crit Care Med 2011;39:371-379.

Pulmonary Complications of Lung Transplantation: Ahmad, CHEST 2011;139:402-411.

ARDS and multi-organ failure: Curr Opin Crit Care 2011;17:1-6.