Literature Roundup: April 2011

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Featured Commentary 
This Month :

In 1998, Cheryl Misak, PhD survived ARDS with multi-organ failure in the ICU. Today, she's Provost of the 
University of Toronto. She tells us what it was like to be a patient in the ICU -- and to struggle through her arduous 

In a shocking retrospective look at Medicare data, 72.5% of those undergoing mechanical ventilation (MV) died within 
one year of that hospitalization; many more were disabled. Lead author Amber Barnato, MD, MPH, MS explains the Blue Journal study.

Author and IDSA Fellow Brad Spellberg, MD gives his take on two contradictory articles on MRSA prevention out this month, and the Infectious Diseases Society of America's fresh policy paper on how we can best fight the growing threat of antibiotic resistance.

A small single-center study showed daily respiratory workouts might help the chronically vented. Gerald Staton, MD muses on what it could mean for his LTAC and yours.

Randomized Controlled Trials :           (How do we make this list?)

Dalteparin vs. unfractionated heparin for ICU DVT prophylaxis (PROTECT trial)Dalteparin is a low-molecular weight heparin that, unlike enoxaparin, is safe for people with renal failure. Among 3,746 ICU patients in 6 countries, followed until hospital discharge, there was no difference in the rate of proximal deep venous thrombosis (5.1% vs 5.8%, 1' endpoint) between once-daily dalteparin and twice-daily UFH, as detected by twice-weekly ultrasounds. There were less pulmonary emboli in the dalteparin group (2' endpoint; 1.3% vs. 2.3%, p=0.01; number needed to treat with dalteparin to prevent one PE = 100). Each LWMH may have unique properties and efficacies in different patient populations, and this trial does not answer the question of dalteparin's performance compared to other LMWHs, nor against q8' UFH. (n=3,746). NEJM 2011;364:1305-1314.

Observations: Fully 80-90% of DVTs were clinically silent; i.e., detected only because of surveillance ultrasonography. Patients were much more prone to clots while in the ICU than on the medical floor. Of the 205 proximal DVTs, 182 occurred in the ICU, 23 on the ward; of 67 PEs, 47 occurred in the ICU. Only 13 of the 67 patients with a PE (19%) had a simultaneous proximal DVT. HIT was rare: less than 0.5% among all patients.

MRSA & VRE in the ICU: Heightened surveillance and barrier precautions didn't reduce transmission (STAR*ICU trial)Huskins et al cluster-randomized 18 ICUs to an intervention of surveillance cultures with contact precautions for positive patients, or a control of no cultures and universal precautions (gloves). The intervention ICUs used contact precautions more frequently (51% vs. 38%), but had the same MRSA/VRE colonization/infection rates, the primary endpoint (40 vs 35%, p=0.35). Clinician compliance was higher in the intervention group, but only fair with gloves (72-82%), gowns (77%) and hand hygiene (62-69%). (n=9,100) NEJM 2011;364:1407-1418. 

Wait, yes they did? ... at VAs nationwide, thanks to an MRSA bundle: After implementing an "MRSA bundle" in 2007 including nasal surveillance, contact precautions for positive patients, hand hygiene, and culture-indoctrination of employees, MRSA infections among all VA hospital ICUs fell from 1.64 to 0.62 per 1000 patient-days (a 62% reduction, p<0.001). MRSA infections on the wards fell from 0.47 to 0.26 per 1000 patient-days (45% reduction, p<0.001). Put that gown back on, please. (n=8,318,675 patient-days) NEJM 2011;364:1419-1430.

Educational intervention improved asthma control in adolescents: Adolescents randomized to the ASMA school-based intervention (education and self-assessment tools for kids & their providers) had better control of their asthma on multiple hard and soft outcome measures, compared to kids getting usual care, Bruzzese et al report. (n=345). AJRCCM 2011;183:998-1006.

Preloading with Chantix improved quit rates: Varenicline is to be started one week prior to the smoking quit date. Hajek et al randomized patients to take Chantix or placebo as a run-in for 3 weeks prior to that. All patients took varenicline for 1 week prior and 3 months after quitting. Those who were "preloaded" had 12-week abstinence rates of 47%, vs. 21%, p=0.005. Arch Int Med 2011;171:770-777.

Antimicrobial "locking" of dialysis catheters prevented bloodstream infections: Maki et al randomized 407 patients at 25 dialysis units to have their catheters "locked" for up to 6 months with either heparin, or "C-MB-P solution" (citric acid, methylene blue, and propylparaben). The patients getting the antimicrobial potion had a 0.29 relative risk for bloodstream infection (BSI) without loss of catheter patency. (n=407) Crit Care Med 2011;39:613-620.
Biggest losers shed 22 pounds in Qnexa weight loss drug trial: Fen-phen died in court, but phenteramine was cleared of all serious charges. Gadde et al report phase III results for Qnexa (by Vivus), a phenteramine-topiramate combination. Over 56 weeks, takers of a double-dose of study drug lost 10 kg; single-dose, 8 kg; and placebo, 1.4 kg. There were plenty of side effects (dry mouth and paresthesias 20%; dysgeusia, insomnia, dizziness, depression & anxiety-related adverse events each in 7% or more at the high dose). (n=2,487). Lancet 2011;377:1341-1352.

Fixed-dose drug combination non-inferior to loose pills for tuberculosis: Four-drug therapy (RIPE) requires high patient commitment and imposes logistical demands on health systems in developing countries. Lienhardt et al report that a fixed-drug combination (FDC) of rifampin, isoniazid, pyrazinamide, and ethambutol was noninferior in producing negative cultures at 18 months compared to taking the drugs separately (both arms ~94% cure rate) in Africa, Asia and Latin America. Adverse events were roughly equal, but could be addressed more discriminately in the conventional group (i.e., stop one drug rather than all four at once). Patients in the FDC group took at most 3 or 4 pills a day, compared to the usual 9 to 16. (n=1,585). JAMA 2011;305:1415-1423.

Acute lung injury not improved by recombinant surfactant protein C product: Those patients with severe acute lung injury due to pneumonia or aspiration who received the rSP-C surfactant product did no better on important outcomes (28-day survival, need for ventilation, organ-failure-free days) than those receiving usual care, report Spragg et al. (n=843). AJRCCM 2011;183:1055-1061.

Pramipexole for restless legs syndrome: Patients taking pramipexole for 6 months had a 14-point fall in their IRLS score, and 59% "responded" (had at least a 50% fall in their score). But time worked well, too: placebo patients had an 11-point decline in scores and 43% responded. So 1 in 6 responded to pramipexole, practically speaking (they don't say this, though). Augmentation also occurred more in the pramipexole group (9%), and rose with time on the drug, report Hogl et al. (n=331). Sleep Medicine 2011;12:351-360.

Notable Journal Articles:


Educational intervention improved asthma control in adolescents: A randomized trial (see above).

Radiographic emphysema correlated with low bone mineral density: COPD's systemic inflammatory effects are postulated to negatively impact bone turnover. After looking at CT scans, PFTs, and steroid history in 190 current and former smokers, Bon et al found visual emphysema on chest CT was highly correlated with osteopenia/osteoporosis, with an odds ratio of 2.55 that was independent of airflow limitation, age, sex, inhaled/oral steroid use, and current smoking status. AJRCCM 2011;183:885-890.
COPD in never-smokers: BOLD unravels some of the mystery. Never-smokers make up >25% of the people with COPD in some studies. Who are these people? The BOLD study gathered data from 14 countries (in the U.S., Europe, Turkey, China, South Africa, Philippines and Australia), including spirometry and questionnaires on environmental exposures and symptoms from 10,000 people. Of the 4,291 never-smokers, 4% had ATS-defined COPD (5.6% by GOLD). Impressively, these never-smokers comprised 20% of the moderate-to-severe (GOLD II+) COPD cases, and 81% of them were undiagnosed. More than two-thirds were women.
They had a 72% rate of respiratory symptoms (compared to 44% for never-smokers without COPD), and they were more likely to report 10 years of exposure to indoor fires (22% vs 15%) and/or organic dusts in the workplace (19% vs 10%) than unobstructed never-smokers. COPD rates in never-smokers were highest in Australia (7.5%) and Poland (9%), and lowest in the U.S. (3.5%). A collective of drug companies are funding this ongoing study that could guide public health efforts (and drug marketing). CHEST 2011;139:752-763.

Natural history of nonspecific pulmonary function tests: Iyer et al re-checked PFTs on 1,284 people with nonspecific results (low FEV1 or FVC but normal TLC and FEV1/FVC ratio), at a median of 3 years after the abnormal test. 64% continued to have the nonspecific result; 16% had restriction; 15% had obstruction; 2% had a mixed pattern; 3% were normal. They recommend changing the current guidelines that label these people as having obstruction. CHEST 2011;139:878-886.

Cardiovascular Disease

AHA Scientific Statement on Management of VTE Badness: A 44-page guideline from the American Heart Association on the management of massive & submassive pulmonary embolism; proximal deep venous thrombosis, and chronic thromboembolic pulmonary hypertension. Circulation 2011;123:1788-1830. FREE FULL TEXT

Oral contraceptives with drospirenone increase risk of nonfatal DVT/PE: Drospirenone is the new progesterone analog in heavily marketed new oral contraceptive pills (Yaz, Yasmin, Angelique). Using a large insurance claims database, Jick et al identified 186 cases of DVT or PE in women aged 15-44 taking oral contraceptives and compared them to controls. Those taking drospirenone-containing OCPs had a nonfatal DVT/PE incidence of 30 per 100,000 person-years, compared to 12.5 for those taking levonorgestrel-containing agents. BMJ 2011;342:d2151. FREE FULL TEXT

Upper limit of normal for pulmonary artery pressure = 40 for endurance athletes? Pulmonary hypertension is often "diagnosed" with a tricuspid regurgitant jet velocity > 2.5 m/s on echocardiogram. Bossone et al found that 76 of 615 (12%) trained athletes (strength or endurance) exceeded this number, and suggest the upper limit of normal should be 40 mm Hg in endurance athletes. CHEST 2011;139:788-794.

Dabigatran, a new oral thrombin inhibitor : Hankey GJ, Circulation 2011;123:1436-1450. REVIEW

Post cardiac arrest syndrome: Review of therapies: Stub D, Circulation 2011;123:1428-1435. REVIEW

Pressors and inotropes in circulatory shock: Hollenberg SM, AJRCCM 2011;183:847-855. REVIEW

Venous thromboembolism, long term management of: Bauer K, JAMA 2011;305:1336-1345. REVIEW

Tako-tsubo cardiomyopathy, natural history of: Parodi G et al, CHEST 2011;139:887-892. REVIEW

  Critical Care

Five-year outcomes after ARDS: In the longest longitudinal study of ARDS yet, Herridge et al followed 109 young survivors of severe ARDS (medians: age 44; Lung Injury Score 3.7 out of 4) in Canada for 5 years, enrolling 1998-2001. Twelve died in the first year. At 5 years, the survivors remained below their pre-ARDS exercise tolerance; they had low six-minute walk distances (median, 76% predicted); were one standard deviation below the mean in self-reported quality of life on SF-36, and had a 5-year 50% incidence of depression or anxiety. On the up side, they had near normal PFTs and the vast majority had returned to work and were functioning "normally" despite their lingering symptoms, medical problems and cosmesis concerns. Follow up was >85%. NEJM 2011;364:1293-1304.

Death and disability the overwhelming norm for Medicare beneficiaries undergoing mechanical ventilation: In this shocking retrospective look at robust Medicare data (54,771 person-years) by Barnato et al, 72.5% of the 534 beneficiaries undergoing mechanical ventilation (MV) died within one year of that hospitalization. An additional 12.5% of survivors were in nursing homes the following year. Survivors of MV had a slightly higher disability burden than those surviving hospitalizations without MV, with both being about 15-25% disabled the following year. The patients were a mean ~76 years old. These surprising findings deserve more than a blurb, so we asked Amber Barnato, the lead author, to tell us more. AJRCCM 2011;183:1037-1043.

Survivor after critical illness tells it like it is: In 1998, Dr. Cheryl Misak survived organ failure in the ICU; this month, she shares her story of a long and difficult recovery from debility. Although highly educated and motivated, and in top pre-admission physical shape, her struggle was formidable. Twelve years later, are we doing any better at adequately informing and preparing patients like Dr. Misak of the intensity and diversity of challenges to come, and providing the support they need? AJRCCM 2011;183:845-846.  

Code status & patient expectations -- reality disconnect: Interviewing 100 patients or their surrogates in the ICU, 85% of whom were "full code," Gehlbach et al found 16% of patients' code status in the chart did not correlate with their expressed preferences during the interview (10 wanted less care, 6 wanted more). Respondents' average prediction for their survival should they have a cardiac arrest: 72%. Only 4% could identify the 3 components of CPR (intubation, compressions, shocks). After learning of the evidence-based estimates of likelihood of survival and neurologic outcome, only about 10% (8 patients) felt less eager to get full-bore CPR than they were before. CHEST 2011;139:802-809.

Among Spain’s healthy elderly 12 months post-ICU, the half that survived lived well: Sacanella et al prospectively observed 230 generally healthy, cognitively intact, highly functional & independently living Spaniards 65 years or older (mean age 75) after urgent admission to a single MICU. About half received mechanical ventilation (54%). Seventy died in-hospital; 48 died within a year, for a one-year survival of 49%. But among the 112 survivors, ~70-80% returned to near-premorbid scores on autonomy and quality of life measures. Mechanical ventilation, older age, and lower premorbid functional status predicted lower one-year survival. Critical Care 2011;15:R105.     FULL FREE TEXT

Transfusing freshest RBC associated with better ICU survival:  In a 5-week prospective observational study in 47 Australian & New Zealand ICUs, Pettila et al (the ANZICS group) followed 757 RBC-transfused patients. Those in the quartile receiving the youngest RBCs (mean age 7.7 days) had an absolute 8% lower mortality than the other 3 quartiles (13% vs 21%, CI 2.2-14.0), who were transfused 23-day old RBCs, on average. This was before adjusting for any covariates. After adjusting for what they could, the odds ratio for death in the “freshest RBC” quartile was ~0.5 (this was presented as an OR of 2.0 in the 3 “old RBC” quartiles, which sounds scarier). Critical Care 2011;15:R116   FULL FREE TEXT

A 2009 review in Transfusion could not establish an association between age of transfused RBCs and survival, from 24 studies that were too heterogeneous to combine into a meta-analysis.

Fresh frozen plasma transfusion practices: anarchy in the UK:   Stanworth et al previously showed that 30% of ICU patients have prothrombin time prolongation at some point. Here, they examined FFP transfusion In an 8-week-long prospective observational study in 29 ICUs in the UK. Fully 31% of FFP units were given to patients with INR < 1.5. About half the FFP units went to patients believed to be bleeding (although not massively so), and 36% as pre-procedure prophylaxis. Given that some of the trauma literature advocates high FFP:RBC transfusion ratios, this isn't entirely indefensible; authors rightly suggest better guidelines should be issued on FFP use. Critical Care 2011;15:R108
Vitamin D deficiency associated with mortality in critically ill: Looking retrospectively at 2,399 ICU patients with preadmission vitamin D measurements on file, those with vitamin D deficiency had an odds ratio of ~1.7 for 30, 90, and 365-day mortality after ICU admission, after multivariate analysis. Braun et al, Crit Care Med 2011;39:671-677.

ICU decedents' families depressed, traumatized: 20% of U.S. deaths now occur during or soon after an ICU stay -- but the families live on, often with upsetting memories, depression, and anxiety. Kross et al re-heat data from the IPACC palliative care study in Washington, surveying family members of ICU decedents, showing they had a 14% prevalence of PTSD symptoms and 18% of depression. (However, only 13% of eligible patients had a family member who responded to the survey, increasing the likelihood of response bias.) Younger age of the deceased patient and family presence at the time of death were associated with higher rates of symptoms. Comfort-care extubation was linked to lower family symptoms. Authors suggest that families should be offered the option of not being present at the time of a family member's death in the ICU.  CHEST 2011;139:795-801.

Heads of beds in ICU? Use your own head, guideline critiquers say:  A systematic review of 3 trials (n=337) by the Bed Head Elevation Study Group (not to be confused with the Bedhead photo group) found no good evidence that head-of-bed (HOB) elevation to 45’ helps or harms in any way (pneumonia, decubiti, mortality, VTE, or hemodynamic instability). Nevertheless, a consensus panel of 22 experts agrees with previous recommendations in the Institute for Health Care Improvement’s ventilator bundle: elevate the HOB to 30’ if there is no good reason not to. There is some evidence that the ventilator bundle in toto may reduce the rate of ventilator-associated pneumonia. Critical Care 2011;15:R111     FULL FREE TEXT

Infectious Disease

New MTB/RIF test looks good for TB diagnosis: The MTB/RIF test is a rapid nucleic acid amplification test for TB. In a rollout in developing countries on 6,648 patients, the test was 90% sensitive for active TB, vs. 67% for smear microscopy (sputum culture was the gold standard). In smear-negative, culture-positive TB, the test was 77% sensitive and 99% specific. It also accurately detects rifampin resistance. Lancet 2011;377:1495-1505. 

Creepy ... MRSA's "MIC creep" to vancomycin portends worse outcomes: Overt vancomycin resistance in MRSA is still unusual, but ID docs are worried about the bug's rising minimum inhibitory concentrations in some regions, with MICs > 1 mcg/mL associated with worse outcomes. Kullar et al retrospectively looked at Detroit's Henry Ford Hospital's 5-year micro data in 320 patients with MRSA bacteremia, reporting a 52% rate of vancomycin treatment failure. Vanco MIC > 1 had an odds ratio of 1.5 for treatment failure. They suggest targeting high troughs of 15-20 mg/mL and/or the more complex pharmacokinetic calculation, the 24-hour-area-under-the-curve-to-MIC (24-hr AUC/MIC) > 421. Clin Infect Dis 2011;52:975-981.
Predicing vancomycin failure in MRSA bacteremia: Death, long hospital stays, and treatment failures are more likely when vancomycin is used for MRSA bacteremia with minimum inhibitory concentrations (MIC) > 1 mcg/mL. Lubin et al propose a clinical prediction rule to predict relative vancomycin resistance, based on a retrospective analysis of 272 patients with MRSA bacteremia at Tufts. Oversimplifying slightly: Having less than two risk factors (age > 50; prior receipt of vanco; prior MRSA bacteremia; chronic liver disease, or a nontunneled venous catheter) had a 91% negative predictive value for having an MRSA strain with MIC > 1 (relative vancomycin resistance). Having 2 or more factors had a positive predictive value of only 30%, though. There was no prospective validation cohort. Clin Infect Dis 2011;52:997-1002.

Computer model says vanco near useless, toxic for MRSA with MIC > 1.9: Patel et al ran 9,999 computer simulations using various vancomycin doses and MICs. When the MIC was 2.0 or greater, 2 g IV q12 hours failed to achieve target drug levels 57% of the time, with 35% predicted nephrotoxicity.'s also true that multiple vancomycin models have been published, which are each internally valid using their own study data, but yielding widely inconsistent results when given the same inputs. Clin Infect Dis 2011;52:969-974.

Interferon-gamma release assays in the diagnosis of latent tuberculosis infection: Herrera V, Clin Infect Dis 2011;52:1031-1037. REVIEW
Latent tuberculosis infection in the U.S.: Horsburgh CR, NEJM 2011;364:1441-1448. REVIEW

Molecular diagnosis of respiratory tract infection in COPD exacerbations: Sethi S, Clin Infect Dis 2011;52 (supplement 4):S290-294. REVIEW
Mucormycosis: clinical presentations and management: Sun H, Lancet Infect Dis 2011;11:301-311. REVIEW

Pseudomonas pneumonia: Epidemiology, clinical diagnosis, source: Fujitani S et al, CHEST 2011;139:909-919. REVIEW
Viral community-acquired pneumonia: Ruuskanen O, Lancet 2011;377:1264-1275. REVIEW

Antimicrobial "locking" of dialysis catheters prevented bloodstream infections: a randomized trial (see above).

Fixed-dose drug combination non-inferior to loose pills for tuberculosis: a randomized trial (see above).

SPECIAL ISSUE: Preventing Infections in Intensive Care Units, Sem Resp Crit Care Med April 2011.

Lung Cancer, Pleural Disease, Interventional Pulmonology

Outcomes after tunneled pleural catheters for malignant effusions: In a retrospective review of 418 tunneled pleural catheters placed over 2 years, 91% of patients did not require any other drainage procedure. Spontaneous pleurodesis occurred in one-quarter, in whom the catheter was taken out at a median 44 days. More patients with catheters placed in the operating room achieved pleurodesis (36%). Complication rate overall was ~5%. J Thorac Onc 2011;6:762-767.
Smells like victory! Diesel fumes implicated as likely cause of lung cancer: After pooling a staggering amount of data on lifetime work histories and tobacco exposure from 13,304 cases and 16,282 controls in 11 previous studies (the SYNERGY project), Olsson et al conclude that yes, breathing diesel exhaust probably causes lung cancer. But the highest-exposure quartile's odds ratio was only 1.3, compared to the unexposed people. See you at the monster truck rally. AJRCCM 2011;183:941-948. 

Percent positive of sampled lymph nodes predicts prognosis in N1 NSCLC: Survival varies widely among people with N1 non-small cell lung cancer. Examining SEER data on 1,682 patients age > 65, who had a median 8 lymph nodes resected between 1992 and 2005, Wisnivesky et al observe that the ratio of positive-to-negative sampled lymph nodes independently predicted survival. Having more than 50% positive LNs foretold a median survival of 21 months; with <= 15% positive LNs, 47 months; and in-between, 37 months (p<0.0001). The relationship persisted after multivariate analysis. Thorax 2011;66:287-293.

Finding PET-CT's place in mediastinal staging of NSCLC: Establishing mediastinal spread of non-small cell lung cancer (N2-3 disease) precludes surgery and worsens prognosis; whether PET-CT imaging can improve overall accuracy or safely prevent mediastinoscopies is still unknown. Fischer et al re-heat the data from their 2009 NEJM randomized trial in Denmark, with EUS-FNA and mediastinoscopy on 189 NSCLC patients, in which they concluded that the half who first got PET-CTs had fewer futile thoracotomies. Here, they report: 1) PET-CT improved diagnostic accuracy, mainly in peripheral tumors, with the gold standard of consensus N staging; 2) Size of lymph nodes on imaging was extremely important: For mediastinal LNs >=10 mm, PET had a 15% false-negative rate, but for normal-sized LNs, the rate was only 4%. They recommend A) PET-CT for all new diagnoses of NSCLC; B) straight-to-resection for people with normal-sized mediastinal LNs that are PET-negative; C) enlarged LNs need invasive sampling regardless of PET uptake, as do PET-positive LNs. Accuracy of mediastinal sampling techniques (mediastinoscopy / EUS / EBUS FNA) vary by local availability and expertise. Thorax 2011;66:294-300.

Combining PET and volume-doubling time could improve lung nodule management: 
Ashraf et al selected people with lung nodules from the Danish Lung Cancer Screening Trial, referring them for PET. Having a suspicious PET scan, or a volume-doubling time (VDT) of < 1 year, each separately had a sensitivity of 71% and a specificity of 91% for lung cancer. Combining PET data with VDT improved sensitivity to 90% with a specificity of 82%. Nodules with discordant PET/VDT were malignant 57% of the time (n=8 of 14). Gold standard was stability after 2 years (negative) or pathology (positive); 54 nodules were analyzed. The VDTs were performed by cool software analyzing nodules on scans at least 3 months apart. Thorax 2011;66:315-319.

Does CT-guided needle biopsy seed the pleura with cancer? A retrospective look at 447 patients with stage I non-small cell lung cancer by Inoue et al suggests yes, but without affecting survival. When cancer recurred in those initially diagnosed by CT-guided needle biopsy, pleural dissemination was more likely (8 of 13 recurrences). However, 5-year disease free survival was 89% in the CT-biopsy group and 85.5% in those diagnosed by bronchoscopic / open biopsy. Ann Thorac Surg 2011;91:1066-1071.

Lung Transplantation 
More lungs, please! Ex-vivo perfusion might convert bad donor lungs to good: Lungs from brain-dead or deceased donors are considered unusable 85% of the time, worsening waiting-list times and death rates. At a single Toronto center, Cypel et al perfused damaged donor lungs ex-vivo (EVLP; here's how) for 4 hours, and if their numbers were good (PaO2/FiO2 > 349; less than 15% worsening in compliance, pulmonary vascular resistance and peak inspiratory pressure), transplanted the lungs. Of 23 high-risk donor lung sets, 20 passed that test and were grafted. Primary graft dysfunction at 72 hours was 15% in the EVLP group (none severe), vs. 30% in the standard care group (9% severe). There were no severe adverse events. One-year survival was 80% (EVLP) vs 83.6% (control), p=0.54.   NEJM 2011;364:1431-1440.

Elevated mesenchymal cells in BAL predicts post-lung transplant BOS: In 173 patients free of bronchiolitis obliterans syndrome at least 6 months post-transplant, having 10 or more colony-forming units of mesenchymal cells in bronchoalveolar lavage fluid carried a >5.0 hazard ratio for subsequently developing BOS. The relation persisted after multivariate analysis, report Badri et al. AJRCCM 2011;183:1062-1070.

During lung transplant for IPF, high pulmonary artery pressure predicted graft failure: Fang et al prospectively observed 126 patients undergoing lung transplant at 9 U.S. centers. PA pressure was obtained invasively in the OR just after transplant. Those who developed grade 3 primary graft dysfunction at 72 hours (1' endpoint) had mPAP of 38.5 mm Hg, compared to 29.6 for those who did not; the relationship persisted after multivariate analysis. Cardiopulmonary bypass attenuated the relationship. Mortality rates were higher in the high mPAP group but didn't achieve significance. CHEST 2011;139:182-187.

Mechanical Ventilation & Chronic Critical Illness 
Most Taiwanese chronic critically ill live ~2-6 months on the vent: Analyzing 50,481 victims of prolonged mechanical ventilation in Taiwan 1997-2007, Hung et al report outcomes were frankly terrible, with median survival of about 4 months. Those with a primary indication of neurologic damage fared significantly better. Those with a PMV indication of COPD, younger than 85, had 6-18 months median survival. Authors take the additional steps of incorporating actuarial life expectancy data for comparison and all but explicitly suggesting a QALY cost analysis for prolonged mechanical ventilation as an intervention in the elderly.  Critical Care 2011;15:R107.     FULL FREE TEXT

Outpatient Pulmonary Medicine

Preloading with Chantix improved quit rates: a randomized trial (see above).
Policy, Public Health & Medical Education

Pro/con editorial on comparative-effectiveness research: Dr. C.Goss takes the pro, Dr. J.Krishnan the con in this spirited Blue Journal soundoff. Both seem to agree that "comparative effectiveness research" is today so broad and undefined as to be either meaningless or all-encompassing, depending on your general attitude. (But maybe that's to be expected for a potential paradigm shift?)

The slow death of empathy: Remember when you were a third year medical student? Me neither. But that's when you first started to build that tough & isolating carapace to protect you from all the overwhelming emotions flying through the hospital, & you, this essay suggests. A seasoned clinical educator and a third-year med student have a conversation about our shared indoctrination that's evocative, eloquent, and touching (the conversation, not the indoctrination). NEJM 2011;364:1190-1193  FREE FULL TEXT

How to lose friends and humiliate people: Psychiatrist Aaron Lazare from U-Mass has been writing and thinking about humiliation in medical education and practice for years. This engrossing article exposes the destructiveness and persistence of this toxic emotion that (he argues) is sadly endemic in our profession. CHEST 2011;139:746-751. 

Sleep disordered breathing plus daytime somnolence associated with early death in elderly: Gooneratne et al selected 289 people over 65 (nondemented, nondepressed), half of whom had excessive daytime sleepiness (EDS). All got polysomnograms and were followed for a mean of 14 years. Those with EDS and sleep disordered breathing (SDB) had a hazard ratio for mortality of 2.7, that fell to 2.3 after adjusting for covariates. People with EDS or SDB in isolation had no increased mortality risk. Sleep 2011;34:435-442.

CPAP adherence after home sleep testing was equal to in-lab PSG: Lettieri et al prospectively observed 210 patients with obstructive sleep apnea, who were diagnosed & titrated in-lab or at home. Those who were diagnosed and titrated at home and managed through their primary care clinic had equivalent adherence with CPAP therapy (~70% of nights; ~4.5 hrs/night; regular use ~52%) to those diagnosed and titrated in-lab and followed by sleep experts. CHEST 2011;139:849-854.
Sleep medicine, a 3,000-year history: Kirsch DB, CHEST 2011;139:939-946. REVIEW

Pramipexole for restless legs syndrome: A randomized trial (see above). 

Review Articles:

Acute liver failure: Larsen FS, Curr Opin Crit Care 2011;17:160-164.

Acute-on-chronic liver failure, concept, natural history, prognosis: Olson JC, Curr Opin Crit Care 2011;17:165-169.

Cryptogenic and secondary organizing pneumonia: Drakopanagiotakis F et al, CHEST 2011;139:893-900.

Dabigatran, a new oral thrombin inhibitor : Hankey GJ, Circulation 2011;123:1436-1450.

Delirium in the ICU, management of: Schiemann A, Curr Opin Crit Care 2011;17:131-140.

Intracerebral hemorrhage, acute management of: Flower O, Curr Opin Crit Care 2011;17:106-114.
Latent tuberculosis infection in the U.S.: Horsburgh CR, NEJM 2011;364:1441-1448.

Molecular diagnosis of respiratory tract infection in COPD exacerbations: Sethi S, Clin Infect Dis 2011;52 (supplement 4):S290-294.
Mucormycosis: clinical presentations and management: Sun H, Lancet Infect Dis 2011;11:301-311.
Post cardiac arrest syndrome: Review of therapies: Stub D, Circulation 2011;123:1428-1435.

Pressors and inotropes in circulatory shock: Hollenberg SM, AJRCCM 2011;183:847-855.

Probiotics and lung diseases: Forsythe P, CHEST 2011;139:901-908.

Pseudomonas pneumonia: Epidemiology, clinical diagnosis, source: Fujitani S et al, CHEST 2011;139:909-919.

Sleep medicine, a 3,000-year history: Kirsch DB, CHEST 2011;139:939-946.

Status epilepticus, refractory, treatment of: Holtkamp M, Curr Opin Crit Care 2011;17:94-100.

Subarachnoid hemorrhage, critical care of: Wartenburg KE, Curr Opin Crit Care 2011;17:85-93.
Tako-tsubo cardiomyopathy, natural history of: Parodi G et al, CHEST 2011;139:887-892. 

Venous thromboembolism, long term management of:
Bauer K, JAMA 2011;305:1336-1345.

Viral community-acquired pneumonia: Ruuskanen O, Lancet 2011;377:1264-1275.

Special Issues:

Serious Infections in Intensive Care Units: 100+ pages, 12 articles reflecting the state of the art on managing infections and antibotic usage in the ICU. Sem Resp Crit Care Med, April 2011.

Workshop on molecular diagnostics for respiratory tract infections:  Procalcitonin shows promise as a biomarker for differentiating bacterial from viral pneumonias, and to assess response to therapy. Rapid PCR for MRSA in sputum may become available after further development & testing. Molecular tests for S. pneumonia in respiratory secretions currently are uninterpretable in practice, due to technical limitations. Clin Infect Dis 2011;52 (supplement 4).

Combating antimicrobial resistance; Policy recommendations to save lives: Clin Infect Dis 2011;52 (supplement 5). 

Candida urinary tract infections: Clin Infect Dis 2011;52 (supplement 6).