J. Lance Lichtor, M.D., Editor
PARTNER Trial Investigators: Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011; 364: 2187–98
Transcatheter aortic-valve implantation: At what price? N Engl J Med 2011; 364:2256–8
Although transcatheter aortic-valve replacement may reduce complications for high- risk patients with aortic stenosis, it is unclear whether it is superior in patients who are still surgical candidates. A multicenter, randomized study compared the outcomes of high-risk patients (n = 699) with severe aortic stenosis treated with either transcatheter aortic-valve replacement with a balloon-expandable bovine pericardial valve or surgical replacement. The rates of death for any cause at 30 days (P = 0.07) and 100 days (P = 0.44) were similar between groups. Major vascular complications were significantly higher in patients who received transcatheter replacement (11.0%vs. 3.2%; P < 0.001). However, major bleeding (9.3%vs. 19.5%; P < 0.001) and new-onset atrial fibrillation (8.6%vs. 16.0%; P = 0.006) were significantly higher after surgical replacement. Major stroke occurred more frequently (3.8%vs. 2.1%), although not significantly, in the transcatheter replacement group.
This is the first multicenter randomized study to show equivalent death rates between patients with aortic stenosis after either transcatheter aortic-valve replacement or surgical replacement. The accompanying editorial suggests that although noninferiority was demonstrated, transcatheter aortic-valve replacement procedures may still lead to serious complications and that further analysis is warranted.
Association of operative time of day with outcomes after thoracic organ transplant. JAMA 2011; 305:2193–9
Surgical complications are among the most common causes of preventable morbidity and mortality. Nighttime care and subsequent staff fatigue may contribute to complications. A retrospective cohort study of the United Network for Organ Sharing (UNOS) database was conducted to evaluate the effect of time of day of surgery and outcomes for thoracic organ transplants. Records from 27,118 patients were included and approximately half underwent transplant surgery (heart or lung) during the day. Survival rates were similar regardless of whether the procedure took place during the day (from 7 AM to 7 PM) or night (from 7 PM to 7 AM). Other outcomes, including length of stay, cardiac reoperation, and new onset dialysis, were also similar regardless of when the procedures were performed.
In this retrospective cohort study, mortality was similar whether heart or lung transplants were performed during the day or night. The typical confines of a retrospective study may complicate the interpretation of these results.
Survival among high-risk patients after bariatric surgery. JAMA 2011; 305:2419–26
The rate of obesity surgeries has been rapidly increasing; however, there is limited evidence of the long-term outcomes. A retrospective cohort study of predominantly older male patients (n = 850) with a high obesity-related mortality rate undergoing bariatric surgery in the Veterans Affairs system was conducted. The mean age was 49.5 yr and the mean body mass index was 47.4. Crude mortality rates were decreased in the bariatric surgery group. Unadjusted (hazard ratio = 0.64) and covariate adjusted (hazard ratio = 0.80) Cox regression analysis favored bariatric surgery. However, in a smaller group of 1,694 propensity-matched patients there was no difference between groups (hazard ratio = 0.94).
In this retrospective analysis of patients undergoing bariatric surgery versus usual care in the Veterans Affairs medical system, covariate adjusted mortality was significantly lower compared with nonsurgical controls after a mean follow-up of 6.7 yr. However, in 1,694 propensity matched patients, no difference was observed. Patients who underwent some laparoscopic banding procedures were not included in this study; thus, the long-term benefit of less invasive bariatric surgery was not determined.
Paid malpractice claims for adverse events in inpatient and outpatient settings. JAMA 2011; 305:2427–31
Malpractice risk in ambulatory settings: An increasing and underrecognized problem. JAMA 2011; 305:2464–5
Increased focus has been on patient safety in recent years. Because there are almost 30 times more outpatient visits than hospital visits each year, a retrospective analysis was performed. Malpractice claims paid in outpatient and inpatient settings were evaluated using data from the National Practitioner Data Bank. The number of paid claims was similar between inpatient and outpatient settings (47.6%vs. 43.1%, respectively). The most common reasons for claims were diagnostic in the outpatient setting (45.9%) and surgical in the inpatient setting (34.1%). Anesthesia had the lowest claim rates; however, anesthesia claims were higher in the inpatient setting compared with outpatient setting (4.2%vs. 1.8%).
In this study, malpractice damage awards from 2005 to 2009 were analyzed. Malpractice claims declined slightly, although the decline was greater in hospitals. Thirty percent of anesthesia-related claims occurred in outpatient settings. Although malpractice claims are a crude measure, patient safety initiatives should be focused on both inpatient and outpatient settings.
Incidence and risk factors of venous thromboembolism in colorectal surgery: Does laparoscopy impart an advantage? Arch Surg 2011; 146:739–43
Patients undergoing colorectal surgery are at risk for developing postoperative thromboembolic complications such as venous thromboembolism (VTE). This retrospective analysis of the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database compared the incidences of VTE after laparoscopic colorectal and open colorectal procedures over a 4-yr period. Of 149,304 elective colorectal surgeries, 5.3% were performed laparoscopically. The incidence of VTE was significantly higher in patients who underwent open procedures compared with laparoscopy (1.44%vs. 0.8%, P < 0.001). The highest incidence of VTE was found in patients with inflammatory bowel disease (1.4%), cancer (1.3%), and diverticulitis (0.9%). Multivariate regression analysis identified a significantly increased risk of VTE in patients undergoing open compared with laparoscopic procedures (odds ratio = 1.8).
This retrospective study of the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database found a lower rate of VTE rate after laparoscopic procedures compared with open procedures and identified inflammatory bowel disease, malignancy, obesity, or congestive heart failure as risk factors for VTE. These findings may help identify patients for whom VTE prophylaxis is most beneficial.
Critical Care Medicine
Jean Mantz, M.D., Ph.D., Editor
Detection of blast-related traumatic brain injury in US military personnel. N Engl J Med 2011; 364:2091–100
Because of the ongoing wars, the rate of blast-related traumatic brain injury in US military personnel is increasing. However, the exact clinical markers to identify mild injury are not fully known. In this study, military personnel with a clinical diagnosis of mild, uncomplicated traumatic brain injury (n = 63) or control subjects (n = 21) underwent advanced magnetic resonance imaging with diffusion tensor imaging (DTI) to assess axonal injuries. DTI demonstrated abnormalities consistent with traumatic axonal injury in several brain regions. Abnormalities were identified using DTI even in the absence of evidence using conventional magnetic resonance imaging. Conventional magnetic resonance imaging only detected abnormalities consistent with traumatic brain injury in one patient. Overall, 18 of 63 patients (29%) with traumatic brain injury had abnormalities on DTI that were consistent with multifocal traumatic axonal injury including anisotropy reductions in 2 or more brain regions.
This study, using advanced imaging techniques, showed that abnormalities associated with traumatic brain injury were found more often using DTI scanning than with conventional magnetic resonance imaging. Advanced magnetic resonance imaging techniques such as DTI may be useful to better understand the relationship between neuroanatomic findings and clinical outcome, particularly cognitive impairment. However, mild traumatic brain injury remains primarily a clinical diagnosis.
Pathophysiology of early trauma-induced coagulopathy: Emerging evidence for hemodilution and coagulation factor depletion. J Trauma 2011; 70:1401–7
Early trauma-induced coagulopathy is a primary event contributing to mortality in trauma patients. A prospective case-control study was performed to further elucidate the pathophysiology of early trauma-induced coagulopathy in patients (n = 91) presenting to a Level 1 trauma center. Compared with matched controls, patients with early trauma-induced coagulopathy had decreases in factors V and VII, antithrombin, and protein C activities. Thrombin and fibrin generation increased in both groups. Patients with early trauma-induced coagulopathy had a significantly longer hospital length of stay, erythrocyte transfusions, and a higher mortality rate (P < 0.01 for each).
In this case-control study of severe trauma patients, hemodilution led to a lower hematocrit and lower coagulation factor activities, primarily factor VII. It is noteworthy that thrombin and fibrin generation were preserved, indicating patients still have a balanced hemostatic response. These results suggest that a resuscitation strategy combining limited amount of crystalloids and supplying coagulation factors may be promising at the early stage of severe trauma.
Nicotine replacement therapy in critically ill patients: A prospective observational cohort study. Crit Care Med 2011; 39:1635–40
Forced nicotine withdrawal for hospitalized critically ill patients may complicate illness and recovery. This prospective observational cohort study is the first to assess the safety of nicotine replacement therapy for active smokers (n = 330) admitted to a medical intensive care unit. Patients who received replacement therapy (n = 174) had similar baseline characteristics compared with patients who did not receive nicotine therapy (n = 156). There was no significant difference in the unadjusted all-cause mortality between groups (7.8%vs. 6.3% in the treated and untreated groups, respectively). Hospital length of stay, mechanical ventilator-free days, and Sequential Organ Failure Assessment scores were also similar between groups. Adjusted propensity scores were also similar.
Nicotine replacement therapy can treat symptoms of nicotine withdrawal. Although the benefit of nicotine replacement therapy in critically ill active smokers remains to be proven, this cohort study supports the safety of this strategy. Improved outcomes and benefits are yet to be determined.
Diagnostic use of serum procalcitonin levels in pulmonary aspiration syndromes. Crit Care Med 2011; 39:1251–6
In the absence of a reliable marker, it is difficult to differentiate bacterial aspiration infections from chemical pneumonitis in critically ill patients. A prospective observational study was conducted to assess the predictive accuracy of serum procalcitonin in patients (n = 65) admitted to the intensive care unit with pulmonary aspiration. No differences in median serum concentrations of procalcitonin were observed between patients with positive or negative bronchoalveolar lavage cultures at any time point measured. In patients with a decreased procalcitonin level on day 1 compared with day 3, duration of mechanical ventilation (6.7 vs. 11.1 day, P = 0.03) and antibiotic therapy (8.2 vs. 12.8, P < 0.001) were shorter.
The use of procalcitonin as a specific diagnostic marker of infection in critically ill patients remains controversial. This cohort study confirms and extends the poor diagnostic value of serum procalcitonin levels in discriminating bacterial aspiration pneumonia from aspiration pneumonitis based on the culture of bronchoalveolar lavage. Serial measurements of procalcitonin serum levels may exhibit some prognostic value.
Early versus late parenteral nutrition in critically ill adults. N Engl J Med 2011; 365:506–17
The appropriate timing and route of administration of artificial nutrition in critically ill patients remain unclear, and therefore guidelines differ between countries. Early initiation (within 48 h) of parenteral nutrition was compared with late initiation (after day 8) in a randomized, multicenter trial of patients in the intensive care unit. Patients in the late-initiation group (n = 2,328) were more likely to be discharged alive earlier (hazard ratio = 1.06) and had fewer intensive care unit infections (22.8%vs. 26.2%; P = 0.008) compared with the early-initiation group (n = 2,312). The proportion of patients on mechanical ventilation for more than 2 days was also smaller in the late-initiation group.
This large prospective, randomized, controlled trial clearly establishes that late parenteral nutrition (more than 8 days after intensive care unit admission) together with tight glycemic control improves outcomes in comparison with early nutrition (within 48 h from admission). These results suggest that early parenteral nutrition in critically ill patients at risk for malnutrition should not be considered at the early phase of their illness.
Timothy J. Brennan, Ph.D., M.D., Editor
Efficacy and safety of tanezumab in the treatment of chronic low back pain. Pain 2011; doi: 10.1016/j.pain.2011.05.003
Blocking the effects of NGF as a route to safe and effective pain relief: Fact or fancy? Pain 2011; doi: 10.1016/j.pain.2011.06.015
Current treatments for chronic low back pain, such as nonsteroidal antiinflammatory drugs and opioids, result in approximately 30,000 deaths annually because of adverse events. This randomized, placebo-controlled study assessed the safety and efficacy of an intravenous antibody directed against nerve growth factor, tanezumab, in patients with chronic low back pain. Patients received either 200 μg/kg tanezumab plus oral placebo (n = 88), intravenous placebo plus oral naproxen 500 mg twice a day (n = 88), or intravenous placebo plus oral placebo (n = 41). The mean change in average lower back pain intensity at week 6 was significantly greater with tanezumab versus naproxen (P = 0.004) and versus placebo (P < 0.001). The proportion of people reporting ≥30% or ≥50% reduction in average low back pain at week 6 was significantly greater for patients treated with tanezumab (P = 0.013 and P = 0.002, respectively). Consistent improvement was sustained from week 4 through week 12 (P < 0.05 for all). Adverse events associated with tanezumab included abnormal peripheral sensation, were generally mild, and resolved before study completion. Nine patients discontinued treatment because of adverse events.
Nerve growth factor has been shown to be effective for the treatment of degenerative osteoarthritis. However, adverse events were noted in some patients. In this study, an antibody directed against nerve growth factor therapy was superior to both naproxen and placebo, not only for pain, but also for disability metrics. Trials in antibody therapy directed against nerve growth factor are currently on hold due to serious adverse events in the osteoarthritis population.