Treatment for Premature Infants May Have Long-Term Benefits on Cognition


Treating premature infants with erythropoietin or darbepoetin may improve their neurodevelopmental outcomes at 18-22 months of age. Image: JAMA, ©AMA

Treatment of premature infants with red blood cell–stimulating agents such as erythropoietin or darbepoetin in the early weeks of life may have long-term benefits on cognitive outcomes and brain development, according to a study released today in Pediatrics.

Erythropoietin and darbepoetin, which help stimulate the bone marrow to produce more red blood cells, are used in both children and adults to treat certain types of chronic anemia (low red blood cell counts). However, early studies in both animals and humans have suggested that these agents also may act on nerve cells in the brain and have positive effects on brain development and cognition. Such effects could be particularly helpful for premature infants, in whom incomplete brain development often results in future complications, such as cerebral palsy or developmental delay.

Researchers from the University of New Mexico in Albuquerque randomly assigned more than 100 premature, very low-birth-weight infants (500 to 1250 grams at birth) to receive injections of erythropoietin, darbepoetin, or placebo from birth to what would have been 35 weeks gestation. When the infants were evaluated for cognitive outcomes at age 18 to 22 months (by individuals who didn’t know whether the infants received one of the drugs or placebo), scores on cognitive testing were significantly higher among infants in both the erythropoietin and darbepoetin groups compared with the placebo group.

The authors found no difference in weight, head circumference, hearing impairment, or visual impairment among the 3 groups. However, 5 of the 24 children in the placebo group had a diagnosis of cerebral palsy vs none of the 56 children in the erythropoietin or darbepoetin groups.

The study did not include enough patients to determine if there was a difference between erythropoietin and darbepoetin. Previous studies looking at erythropoietin and cognitive outcomes have had mixed results, but this is the first randomized trial involving darbepoetin, which the authors suggest may be more advantageous because darbepoetin treatment only requires a once-weekly injection compared with erythropoietin, which requires 3 injections per week.

Expediting Medicaid Coverage for Prison Inmates

Prison system policies can help inmates benefit from Medicaid coverage (mediaphotos/

Prison system policies can help inmates benefit from Medicaid coverage (mediaphotos/

As many state Medicaid programs expand through the Affordable Care Act (ACA), a new survey indicates that some state prisons could improve prisoners’ health care and lower state spending by revising policies on prisoner enrollment in the state-federal health plan.

The survey, published online today in the American Journal of Public Health, evaluated Medicaid policies from December 2011 to August 2012 at 42 state prison systems. According to the results, 66.7% of the prisons terminated enrollment and 21.4% suspended inmates from Medicaid when they were incarcerated. However, two-thirds of these prisons also helped prisoners reenroll when they were discharged.

“Enrollment improves access to basic health services, including substance use and mental health services, and can in turn benefit the health of the communities and families to which prisoners return,” lead author Josiah Rich, MD, MPH, said in a statement.

Rich and his colleagues questioned the policies to terminate coverage during incarceration as ACA provisions roll out. States with expanded Medicaid programs will cover all adults, regardless of whether they’re disabled or have dependents, up to 138% of the federal poverty level. Broader eligibility means more prisoners likely will be covered. But if their coverage is terminated, prisons can’t benefit from a 1997 federal law that allows Medicaid to cover inpatient care that inmates receive outside of the prison system, as long as they’re Medicaid eligible.

“Although the proportion of prisoners who require inpatient, community care is likely modest, their health care costs may be relatively high,” the investigators wrote. If inmates’ Medicaid coverage is terminated, state corrections departments miss out on federal reimbursement dollars. Officials in only 15 state prison systems submitted Medicaid applications to obtain reimbursement for inmates who weren’t enrolled and received inpatient care away from the prison.

Also, broader eligibility means more released prisoners may be covered. But the survey showed that prisoners whose coverage was suspended weren’t automatically reenrolled, and they faced similar challenges as prisoners whose coverage was terminated and had to reenroll: timing release dates to match effective coverage dates, coordination among state agencies, excessive paperwork, and following through the enrollment process. Even so, coverage usually resumed within a month of release, according to the findings.

The investigators found that two-thirds of the prison systems with termination or suspension systems offered some type of assistance to enroll or reenroll in Medicaid. However, they noted, “the lack of assistance in the remaining [systems] should be addressed, as this constitutes a basic function of discharge planning.”

Pulmonologists Release “Top 5 List” of Common Things Done for Diagnosing, Treating Lung Disease That Physicians and Patients Should Question

Choosing Wisely campaign releases top 5 list of things physicians and patients should question in pulmonary medicine. Image: logoboom/

The Choosing Wisely campaign releases list of top 5 things physicians and patients should question in pulmonary medicine. Image: logoboom/

This decade of US health care is all about choosing wisely: that is, choosing the best interventions to use (and not to use) when diagnosing and treating patients through a careful weighing of the costs, risks, and benefits of each intervention.

The Choosing Wisely campaign, a nationwide initiative developed by the American Board of Internal Medicine (ABIM) Foundation, encourages doctors and patients to do just that when faced with the myriad tests, procedures, and treatments that are readily available in this current era of medicine. Since 2011, Choosing Wisely has published “top 5 lists” of common practices that both physicians and patients should question in terms of their true medical necessity for more than 40 subspecialties of medicine.

Pulmonologists announced their opinions about the wisest choices in pulmonary medicine at CHEST 2013, the annual meeting of the American College of Chest Physicians held in Chicago this past week.

They unveiled the top 5 list for adult pulmonary medicine, which includes the following 5 recommendations:

  • Do not perform computed tomography (CT) scans to evaluate indeterminate lung nodules at more frequent intervals or for a longer period of time than recommended by established guidelines.
  • Do not routinely offer advanced vasoactive agents (which allow for improved blood flow through the lungs) that are only approved for treatment of pulmonary arterial hypertension (a specific type of high blood pressure in the lung circulation) to patients with other types of pulmonary hypertension.
  • Do not renew a prescription of supplemental home oxygen for patients recently discharged after hospitalization for an acute illness without assessing whether there is an ongoing need for home oxygen.
  • Do not perform CT angiography to evaluate for a pulmonary embolism (blood clot in the lung) in patients with a low clinical probability of this problem.
  • Do not perform CT screening for lung cancer in patients at low risk for lung cancer.

Scott Halpern, MD, PhD, of the University of Pennsylvania, who led the session, noted that the United States spent $2.87 trillion on health care in 2012, and of that, critical care spending accounted for $103 billion. Given the steady increase of this number out of proportion with the increase in US gross domestic product, the ABIM Foundation added a clause reflecting concerns about costs to its charter of professionalism for physicians in 2002, stating that “physicians are required to provide health care that is based on the wise and cost-effective management of limited clinical resources.… The physician’s professional responsibility for appropriate allocation of resources requires scrupulous avoidance of superfluous tests and procedures.”

This idea that cost-conscious and cost-effective medicine is an ethical responsibility of physicians on par with other Hippocratic commitments laid the foundation for the ABIM Foundation’s launch of the Choosing Wisely campaign in 2011. Each top 5 list is developed through an extensive and careful review of evidence of effectiveness, cost, relevance, and potential to change practice by members of the professional societies of each medical specialty.

The list for pulmonary medicine was developed by the American College of Chest Physicians and the American Thoracic Society. A full manuscript discussing the evidence supporting the recommendations is slated for publication in the journal CHEST in upcoming months.

The CHEST 2013 session also featured a preliminary glimpse of the upcoming top 5 list for adult critical care medicine, developed by the American College of Chest Physicians, the American Thoracic Society, the Society of Critical Care Medicine, and, importantly, the American Association of Critical-Care Nurses, making it the only list to date that includes input from a nonphysician society. Seven potential topics were addressed, 5 of which will ultimately make the final list, which will be published in conjunction with its presentation at the Society of Critical Care Medicine meeting in January 2014.

These current 7 items of importance in critical care medicine include:

  • The appropriate use of routine lab tests
  • The appropriate use of broad-spectrum antimicrobial agents
  • The optimal level and duration of sedation for patients receiving mechanical ventilation
  • The optimal threshold for blood transfusion
  • The optimal timing of initiation of intravenous nutrition
  • The optimal timing of central venous catheter and arterial line insertion
  • The optimal approach to discussing life-sustaining vs comfort care measures for end-of-life care in the intensive care unit

The Choosing Wisely top 5 lists are intended to stimulate conversation between physicians and patients; they should not be viewed as a rigid set of guidelines or rules that must be followed, cautioned Halpern.

Study Suggests Treatment Strategy for Respiratory Distress Syndrome in Very Preterm Infants

New research suggests a slight advantage to using nasal continuous positive airway pressure over mechanical ventilation by intubation in treating very preterm infants for respiratory distress syndrome. (Image: herjua/

New research suggests a slight advantage to using nasal continuous positive airway pressure over mechanical ventilation by intubation in treating very preterm infants for respiratory distress syndrome. (Image: herjua/

A study published Thursday in BMJ provides some guidance to neonatologists treating lung issues in very preterm infants.

Nearly all infants born before 28 weeks of pregnancy develop respiratory distress syndrome resulting from the lungs’ structural immaturity and their inability to make enough surfactant, a substance that coats the inside of the lungs, keeping air sacs open and allowing oxygen and carbon dioxide exchange. Left untreated, respiratory distress syndrome can lead to brain and other organ damage and even death. Most infants who show signs of the syndrome are quickly moved to a neonatal intensive care unit for around-the-clock care, which includes surfactant replacement therapy and breathing support through mechanical ventilation.

But breathing support—either by intubation or from a nasal continuous positive airway pressure (CPAP) machine—makes these infants susceptible to bronchopulmonary dysplasia, a chronic lung disorder characterized by inflammation and scarring in the lungs. This increases the risk for frequent hospital readmissions in the first 2 years after birth and even into adolescence for persistent respiratory symptoms and lung function abnormalities.

The BMJ study, by researchers from Austria and Canada, found nasal CPAP to be slightly better than intubation for reducing the risk of bronchopulmonary dysplasia. The authors concluded that 1 additional infant could survive to 36 weeks without bronchopulmonary dysplasia for every 25 babies treated with nasal CPAP rather than being intubated. They based this conclusion on a meta-analysis of 4 randomized controlled trials involving 2782 preterm infants needing respiratory support.

The authors offered some caveats to their findings, noting that surfactant administration varied among the trials and that the infants ranged in gestational age from 24 to 29 weeks at enrollment, which left out those born even earlier, who are a high-risk group with high mortality. The authors said that future trials should investigate different levels of nasal CPAP and different strategies and thresholds for administering surfactant.

Delirium Implicated in Long-term Cognitive Problems After ICU Stay

Delirium is an independent risk factor for cognitive deficits after an intensive care unit stay. (Image: kondyukandrey/

Delirium is an independent risk factor for cognitive deficits after an intensive care unit stay, according to a new study. (Image: kondyukandrey/

Critically ill patients hospitalized in intensive care units (ICU) may develop cognitive deficits similar to mild Alzheimer disease that sometimes last as long as a year, according to a new study. The research also linked a longer period of delirium while hospitalized with more severe cognitive problems.

A study team led by researchers at Vanderbilt University Medical Center and Saint Thomas Hospital in Nashville, Tennessee, evaluated 821 adults admitted to medical or surgical ICUs with respiratory failure or shock between 2007 and 2010. About 6% of the patients had cognitive impairments when admitted. Delirium developed in 74% during their hospital stay and lasted a median of 4 days, the investigators reported today in the New England Journal of Medicine.

About 31% of the patients died within 3 months of being discharged; another 7% of the original group died within 12 months. At each follow-up, about three-fourths of surviving patients underwent cognitive testing.

Results showed that at 3 months, 40% of all the patients had cognitive deficits more severe than those typically seen in patients with moderate traumatic brain injury (TBI), and 26% had impairments similar to mild Alzheimer disease. At 12 months, 34% had impairments similar to moderate TBI and 24% had deficits comparable with mild Alzheimer disease.

Age wasn’t linked with developing cognitive impairment. The patients’ median age was 61 years, but even some in their 40s had deficits comparable with moderate TBI or mild Alzheimer disease. Having a coexisting illness when admitted wasn’t linked with cognitive impairment, and neither was sedative use. However, higher doses of benzodiazepines were linked at the 3-month follow-up with lower test scores for executive function, which is the ability to organize information and regulate behavior.

Longer duration of delirium—acute malfunctioning in the brain that often occurs during critical illness—was shown to be an independent risk factor for worse cognitive functioning 1 year after being discharged.

“Most of the medical profession doesn’t even know this is happening,” senior author Wes Ely, MD, MPH, professor of medicine at Vanderbilt, said in a statement. Ely noted that some levels of cognitive impairment may be preventable with careful delirium monitoring; efforts to shorten the duration of delirium; and earlier attempts to wean patients from sedatives and help them sit, stand, or walk.

“Even after the patient leaves the hospital, we think that cognitive rehabilitation might be helpful,” Ely added. “We have some preliminary data supporting this.”

Antibiotic Tygacil Gets FDA Boxed Warning About Increased Death Risk

Because of an increased risk of death, tigecycline (Tygacil), an antibacterial drug, should only be used when alternative treatments are not suitable, said the US Food and Drug Administration. (Image: ntmw/

Because of an increased risk of death, tigecycline (Tygacil), an antibacterial drug, should only be used when alternative treatments are not suitable, said the US Food and Drug Administration. (Image: ntmw/

The US Food and Drug Administration (FDA) approved today a new boxed warning, the strongest warning given to a drug, for intravenous tigecycline (Tygacil; Pfizer), a tetracycline-class antibacterial drug. Tigecycline, first approved in 2005, is used for treating complicated skin infections, complicated intra-abdominal infections, and community-acquired bacterial pneumonia in adults.

In 2010, the FDA issued a drug safety communication showing, in a meta-analysis of 13 trials, an increased risk of death among patients receiving tigecycline compared with other antibacterial drugs (4.0% vs 3.0% with an adjusted risk difference of 0.6%). The increased risk was greatest in patients with ventilator-associated pneumonia, a use for which the FDA has not approved the drug. Increased risk of death was also seen in patients with complicated skin infections, complicated intra-abdominal infections, and diabetic foot infections—another complication for which the drug has not been approved.

After the 2010 communication, the FDA analyzed data from 10 clinical trials involving tigecycline and only agency-approved uses. Again, analysis showed a higher risk of death among patients receiving tigecycline compared with other antibacterial drugs (2.5% vs 1.8% with an adjusted risk difference of 0.6%). These deaths, in general, resulted from worsening infections, complications of infection, or other underlying medical conditions, but the FDA said the cause of this mortality risk difference has not been established.

The FDA wrote that health care professionals should reserve tigecycline for use in situations when alternative treatments are not suitable. In the prescribing label, the FDA said tigecycline should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. Such bacteria include Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Klebsiella pneumoniae, and Legionella pneumophila.

Author Insights: Do-Not-Resuscitate Orders May Influence Overall Care for Pediatric Patients

 Amy Sanderson, MD, a pediatric intensivist at Boston Children’s Hospital, and her colleagues found that having a do-not-resuscitate order for a pediatric patient may in some cases lead to more compassionate care or change the patient’s overall care in some way. Image: Boston Children’s Hospital

Amy Sanderson, MD, a pediatric intensivist at Boston Children’s Hospital, and her colleagues found that having a do-not-resuscitate order for a pediatric patient may in some cases lead to more compassionate care or change the patient’s overall care in some way. Image: Boston Children’s Hospital

Do-not-resuscitate (DNR) orders for a pediatric patient with a serious illness may influence that child’s overall care, for better or worse, according to results of a survey published today in JAMA Pediatrics.

Discussions that lead up to a DNR order can help patients or their proxies become better informed about the options for care in the event of a cardiac arrest. Such orders give physicians crucial information about the preferred course of action, but there is some evidence that having a DNR for an adult patient may also influence the care the patient receives outside of the circumstances of a cardiac arrest.

To investigate whether this holds true for pediatric patients, a team of researchers from Boston recently conducted a survey of pediatric nurses and physicians to gather more information about possible effects of a DNR on pediatric care.

The investigators surveyed 107 physicians and 159 nurses at Boston Children’s Hospital and the Dana-Farber Children’s Hospital Cancer Center. They found that 66.7% of the respondents believe the DNR only limits care in the case of a cardiac arrest, while 33.1% believed a DNR suggested limitations for other nonresuscitation-related treatments. Two-thirds of the surveyed clinicians said that DNR orders have broader effects on patient care. Of those who believe patient care changes more globally after a DNR, 11.2% said such changes only occur when a cardiac arrest has happened; 36.7% said there is an increased emphasis on patient comfort; and 52.1% reported changes in nonresuscitation-related care, such as reduced testing or withdrawal of treatments.

Lead author Amy Sanderson, MD, a pediatric intensivist at Boston Children’s Hospital, discussed the findings with news@JAMA.

news@JAMA: Some patients may worry about having a DNR for fear that physicians will “give up.” Does your study give us a sense of whether those fears are justified?

Dr Sanderson: We did ask clinicians whether they thought that having a DNR meant giving up on a patient, and the vast majority of physicians thought that was not the case at all.

news@JAMA: In what ways did clinicians report that having a DNR changes patient care?

Dr Sanderson: The majority of clinicians thought it changed patient care if a cardiopulmonary arrest happens, and that is what a DNR is intended to do. Some other physicians thought having a DNR leads to an increase in attention to patient comfort.

news@JAMA: When do you think is the optimal timing for these discussions?

Dr Sanderson: It’s a hard question to answer; it’s probably different for every patient. Physicians in the survey thought that, on the whole, it happens a little later than is ideal.

news@JAMA: You found that parent-related factors were often cited for delaying the discussion of a DNR or other care preferences. What were these factors?

Dr Sanderson: The top 3 barriers mentioned were unrealistic parent expectations of the patient’s condition or prognosis, a lack of parent readiness to discuss a DNR, and a difference between parents’ and clinicians’ understanding of the prognosis.

news@JAMA: How do you think communication and care surrounding DNR can be improved?

Dr Sanderson: When discussing a DNR, it should happen in the context of a discussion about the overall goals of care for the patient. When DNRs are discussed in isolation, there may be inappropriate assumptions by clinicians about what the parent or patient would like.