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Prenatal Exposure to Antiepileptic Drugs May Be Associated With a Higher Risk of Impaired Fine Motor Skills in 6-month-olds—But Not Because of Breastfeeding
At age 6 months, infants of mothers using antiepileptic drugs (AEDs) (n = 223) had a higher risk of impaired fine motor skills (11.5%), compared with a reference group of children of parents without epilepsy (4.8%), especially when the infants were exposed to multiple AEDs, according to a study published in the November 2013 issue of JAMA Neurology. However, because breastfeeding in women using AEDs was not associated with any harmful effects on child development at ages 6 to 36 months—and was even found to protect against low weight during the postnatal period—the study’s authors concluded that women with epilepsy should be encouraged to breastfeed their children regardless of antiepileptic medication use.
The study was part of the prospective Norwegian Mother and Child Cohort Study (MoBa) in which women in Norway, recruited at 13 to 17 weeks of pregnancy, reported on their child’s development at 6 months (n = 78,744), 18 months (n = 61,351), and 36 months (n = 44,147) using validated screening tools and also provided detailed information on breastfeeding during the first year. For the substudy examining the developmental effects of prenatal exposure to AEDs, all 974 children of mothers or fathers with validated epilepsy in the MoBa cohort at 6 months formed the epilepsy group, while the remaining 77,770 children of parents without epilepsy served as the reference group. Exposure to AEDs by mothers during pregnancy and by fathers within 6 months prior to conception was also validated.
Significantly different results were seen for children of women who used AEDs compared with children of women who did not use the drugs and to children of men with epilepsy—two subgroups found to have normal development at 6 months. For example, children of mothers using multiple AEDs had the highest risk for impaired motor skills (25.0%, vs 4.8% for the reference group) while also having impaired social skills (22.5% vs 10.2%, respectively).
By contrast, continuous breastfeeding during the first 6 months was associated with a tendency toward improved outcome for all the developmental domains measured regardless of maternal AED treatment. At 18 months, while children in the drug-exposed group had an increased risk of impaired development compared with the reference group, the risks tended to be elevated particularly in children whose breastfeeding had been discontinued. At 36 months, prenatal AED was associated with adverse development regardless of breastfeeding status during the first year.
—Fred Balzac
Velby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy. JAMA Neurol. 2013;70(11):1367-1374.
At age 6 months, infants of mothers using antiepileptic drugs (AEDs) (n = 223) had a higher risk of impaired fine motor skills (11.5%), compared with a reference group of children of parents without epilepsy (4.8%), especially when the infants were exposed to multiple AEDs, according to a study published in the November 2013 issue of JAMA Neurology. However, because breastfeeding in women using AEDs was not associated with any harmful effects on child development at ages 6 to 36 months—and was even found to protect against low weight during the postnatal period—the study’s authors concluded that women with epilepsy should be encouraged to breastfeed their children regardless of antiepileptic medication use.
The study was part of the prospective Norwegian Mother and Child Cohort Study (MoBa) in which women in Norway, recruited at 13 to 17 weeks of pregnancy, reported on their child’s development at 6 months (n = 78,744), 18 months (n = 61,351), and 36 months (n = 44,147) using validated screening tools and also provided detailed information on breastfeeding during the first year. For the substudy examining the developmental effects of prenatal exposure to AEDs, all 974 children of mothers or fathers with validated epilepsy in the MoBa cohort at 6 months formed the epilepsy group, while the remaining 77,770 children of parents without epilepsy served as the reference group. Exposure to AEDs by mothers during pregnancy and by fathers within 6 months prior to conception was also validated.
Significantly different results were seen for children of women who used AEDs compared with children of women who did not use the drugs and to children of men with epilepsy—two subgroups found to have normal development at 6 months. For example, children of mothers using multiple AEDs had the highest risk for impaired motor skills (25.0%, vs 4.8% for the reference group) while also having impaired social skills (22.5% vs 10.2%, respectively).
By contrast, continuous breastfeeding during the first 6 months was associated with a tendency toward improved outcome for all the developmental domains measured regardless of maternal AED treatment. At 18 months, while children in the drug-exposed group had an increased risk of impaired development compared with the reference group, the risks tended to be elevated particularly in children whose breastfeeding had been discontinued. At 36 months, prenatal AED was associated with adverse development regardless of breastfeeding status during the first year.
—Fred Balzac
At age 6 months, infants of mothers using antiepileptic drugs (AEDs) (n = 223) had a higher risk of impaired fine motor skills (11.5%), compared with a reference group of children of parents without epilepsy (4.8%), especially when the infants were exposed to multiple AEDs, according to a study published in the November 2013 issue of JAMA Neurology. However, because breastfeeding in women using AEDs was not associated with any harmful effects on child development at ages 6 to 36 months—and was even found to protect against low weight during the postnatal period—the study’s authors concluded that women with epilepsy should be encouraged to breastfeed their children regardless of antiepileptic medication use.
The study was part of the prospective Norwegian Mother and Child Cohort Study (MoBa) in which women in Norway, recruited at 13 to 17 weeks of pregnancy, reported on their child’s development at 6 months (n = 78,744), 18 months (n = 61,351), and 36 months (n = 44,147) using validated screening tools and also provided detailed information on breastfeeding during the first year. For the substudy examining the developmental effects of prenatal exposure to AEDs, all 974 children of mothers or fathers with validated epilepsy in the MoBa cohort at 6 months formed the epilepsy group, while the remaining 77,770 children of parents without epilepsy served as the reference group. Exposure to AEDs by mothers during pregnancy and by fathers within 6 months prior to conception was also validated.
Significantly different results were seen for children of women who used AEDs compared with children of women who did not use the drugs and to children of men with epilepsy—two subgroups found to have normal development at 6 months. For example, children of mothers using multiple AEDs had the highest risk for impaired motor skills (25.0%, vs 4.8% for the reference group) while also having impaired social skills (22.5% vs 10.2%, respectively).
By contrast, continuous breastfeeding during the first 6 months was associated with a tendency toward improved outcome for all the developmental domains measured regardless of maternal AED treatment. At 18 months, while children in the drug-exposed group had an increased risk of impaired development compared with the reference group, the risks tended to be elevated particularly in children whose breastfeeding had been discontinued. At 36 months, prenatal AED was associated with adverse development regardless of breastfeeding status during the first year.
—Fred Balzac
Velby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy. JAMA Neurol. 2013;70(11):1367-1374.
Velby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy. JAMA Neurol. 2013;70(11):1367-1374.
A Significant Proportion of Patients With Juvenile Myoclonic Epilepsy May Be Able to Remain Seizure-Free
In a retrospective cohort study analyzing seizure outcome in 66 patients with juvenile myoclonic epilepsy (JME) followed for a mean of nearly 45 years, investigators in Berlin, Germany, found that seizure remission occurred in 59.1% of patients, with 16.7% of all patients remaining seizure-free off antiepileptic drugs (AEDs) for at least five years before the last study contact. The results of the study, published in the December 10, 2013, issue of Neurology, suggest that treatment response and long-term remission in JME are more favorable than previously thought possible.
In addition, in identifying occurrence of absence seizures at the onset of JME as a significant predictor for poor outcome, the study points to a potentially different JME subtype—one that is indicative of a worse outcome.
Among its main findings, the study showed that, of the 39 patients who had a five-year terminal remission, 28 (71.8%) were still taking AEDs and 11 (28.2%) had been completely off medication for at least the past five years. Of the clinical variables assessed as potential predictors of seizure outcome in patients with (n = 39) and without (n = 27) remission, only additional manifestation of absence seizures at onset of JME was significantly associated with lack of five-year terminal remission.
The investigators also found, among all patients with remission, a significantly younger age at last seizure in patients who had achieved remission without AED therapy (mean age, 29.3 ± 9.3 years) versus those who had achieved remission and were currently receiving AED therapy—ie, patients with “controlled epilepsy” (39.8 ± 15 years).
Encompassing the largest cohort and longest follow-up period examining evolution of seizures in JME, as far as its authors could determine, this study demonstrated that seizures could be controlled in the majority of cases, with a significant proportion of patients off AED therapy—supporting, as lead author Philine Senf, MD, wrote, “the results of previous work showing that lifelong treatment in patients with JME may no longer apply as a general prognostic guideline.”
In an accompanying commentary, Norman K. So, MB, of the Cleveland Clinic, observed that “a proportion [of JME] remains resistant to treatment despite the advent of more and newer drugs” and that “Predictors of seizure persistence have been hard to come by,” suggesting that the identification of additional absence seizures as a predictor of unfavorable outcome is an important aspect of the “reappraisal” of JME that this study provides.
—Fred Balzac
Senf P, Schmitz B, Holtkamp M, Janz D. Prognosis of juvenile myoclonic epilepsy 45 years after onset: seizure outcome and predictors. Neurology. 2013;81(24):2128-2133.
So NK. Comment: a reappraisal of juvenile myoclonic epilepsy. Neurology. 2013;8(24):2132.
In a retrospective cohort study analyzing seizure outcome in 66 patients with juvenile myoclonic epilepsy (JME) followed for a mean of nearly 45 years, investigators in Berlin, Germany, found that seizure remission occurred in 59.1% of patients, with 16.7% of all patients remaining seizure-free off antiepileptic drugs (AEDs) for at least five years before the last study contact. The results of the study, published in the December 10, 2013, issue of Neurology, suggest that treatment response and long-term remission in JME are more favorable than previously thought possible.
In addition, in identifying occurrence of absence seizures at the onset of JME as a significant predictor for poor outcome, the study points to a potentially different JME subtype—one that is indicative of a worse outcome.
Among its main findings, the study showed that, of the 39 patients who had a five-year terminal remission, 28 (71.8%) were still taking AEDs and 11 (28.2%) had been completely off medication for at least the past five years. Of the clinical variables assessed as potential predictors of seizure outcome in patients with (n = 39) and without (n = 27) remission, only additional manifestation of absence seizures at onset of JME was significantly associated with lack of five-year terminal remission.
The investigators also found, among all patients with remission, a significantly younger age at last seizure in patients who had achieved remission without AED therapy (mean age, 29.3 ± 9.3 years) versus those who had achieved remission and were currently receiving AED therapy—ie, patients with “controlled epilepsy” (39.8 ± 15 years).
Encompassing the largest cohort and longest follow-up period examining evolution of seizures in JME, as far as its authors could determine, this study demonstrated that seizures could be controlled in the majority of cases, with a significant proportion of patients off AED therapy—supporting, as lead author Philine Senf, MD, wrote, “the results of previous work showing that lifelong treatment in patients with JME may no longer apply as a general prognostic guideline.”
In an accompanying commentary, Norman K. So, MB, of the Cleveland Clinic, observed that “a proportion [of JME] remains resistant to treatment despite the advent of more and newer drugs” and that “Predictors of seizure persistence have been hard to come by,” suggesting that the identification of additional absence seizures as a predictor of unfavorable outcome is an important aspect of the “reappraisal” of JME that this study provides.
—Fred Balzac
In a retrospective cohort study analyzing seizure outcome in 66 patients with juvenile myoclonic epilepsy (JME) followed for a mean of nearly 45 years, investigators in Berlin, Germany, found that seizure remission occurred in 59.1% of patients, with 16.7% of all patients remaining seizure-free off antiepileptic drugs (AEDs) for at least five years before the last study contact. The results of the study, published in the December 10, 2013, issue of Neurology, suggest that treatment response and long-term remission in JME are more favorable than previously thought possible.
In addition, in identifying occurrence of absence seizures at the onset of JME as a significant predictor for poor outcome, the study points to a potentially different JME subtype—one that is indicative of a worse outcome.
Among its main findings, the study showed that, of the 39 patients who had a five-year terminal remission, 28 (71.8%) were still taking AEDs and 11 (28.2%) had been completely off medication for at least the past five years. Of the clinical variables assessed as potential predictors of seizure outcome in patients with (n = 39) and without (n = 27) remission, only additional manifestation of absence seizures at onset of JME was significantly associated with lack of five-year terminal remission.
The investigators also found, among all patients with remission, a significantly younger age at last seizure in patients who had achieved remission without AED therapy (mean age, 29.3 ± 9.3 years) versus those who had achieved remission and were currently receiving AED therapy—ie, patients with “controlled epilepsy” (39.8 ± 15 years).
Encompassing the largest cohort and longest follow-up period examining evolution of seizures in JME, as far as its authors could determine, this study demonstrated that seizures could be controlled in the majority of cases, with a significant proportion of patients off AED therapy—supporting, as lead author Philine Senf, MD, wrote, “the results of previous work showing that lifelong treatment in patients with JME may no longer apply as a general prognostic guideline.”
In an accompanying commentary, Norman K. So, MB, of the Cleveland Clinic, observed that “a proportion [of JME] remains resistant to treatment despite the advent of more and newer drugs” and that “Predictors of seizure persistence have been hard to come by,” suggesting that the identification of additional absence seizures as a predictor of unfavorable outcome is an important aspect of the “reappraisal” of JME that this study provides.
—Fred Balzac
Senf P, Schmitz B, Holtkamp M, Janz D. Prognosis of juvenile myoclonic epilepsy 45 years after onset: seizure outcome and predictors. Neurology. 2013;81(24):2128-2133.
So NK. Comment: a reappraisal of juvenile myoclonic epilepsy. Neurology. 2013;8(24):2132.
Senf P, Schmitz B, Holtkamp M, Janz D. Prognosis of juvenile myoclonic epilepsy 45 years after onset: seizure outcome and predictors. Neurology. 2013;81(24):2128-2133.
So NK. Comment: a reappraisal of juvenile myoclonic epilepsy. Neurology. 2013;8(24):2132.
Reviews of Research on Haloperidol and ICU Delirium, Proton Pump Inhibitors, Thrombolytics and Stroke
In This Edition
Literature At A Glance
A guide to this month’s studies
- Intravenous haloperidol does not prevent ICU delirium
- Predicting delirium risk in hospitalized adults
- Oral PPIs as effective as IV PPIs in peptic ulcer bleeding
- Probiotic benefit questioned in the elderly
- Colchicine and NSAID better than NSAID alone for acute pericarditis
- Improvement needed in patient understanding at hospital discharge
- Effectiveness of a multihospital effort to reduce rehospitalization
- Hospitals profit from preventing surgical site infections
- Prothrombin complex concentrate safer than fresh frozen plasma in rapidly reversing INR
- Hospital-acquired anemia associated with higher mortality, increased LOS
- Thrombolytics and stroke: the faster the better
Intravenous Haloperidol Does Not Prevent ICU Delirium
Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?
Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.
Study design: Randomized, double-blinded, placebo-controlled trial.
Setting: Single, adult ICU in England.
Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.
This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.
Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.
Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.
Predicting Delirium Risk in Hospitalized Adults
Clinical question: Can a simple tool be developed and used for predicting delirium in hospitalized adults?
Background: Delirium is a common condition that results in higher mortality, longer length of stays, and higher probability of discharge to nursing home. Current delirium prediction tools are complicated, or restricted to surgical or critically ill patients.
Study design: Prospective cohort study, with separate derivation and validation cohorts.
Setting: Two academic hospitals and a VA hospital in San Francisco.
Synopsis: Investigators enrolled 374 hospitalized patients who were more than 50 years of age and not delirious at time of admission (209 patients in the derivation and 165 in the validation). The authors identified four predictors of delirium: Age >80; failure to spell “World” backwards; disOrientation to place; and higher nurse-rated iLlness severity (AWOL). The authors found that rates of delirium increased with increasing number of predictors (with zero predictors, 2% developed delirium; one predictor, 4%; two predictors, 14%; three predictors, 20%; four predictors, 64%).
These predictors are similar to other previously identified risk factors, as well as to prediction tools that are in use for surgical patients. However, this tool is quick and can be completed by nursing staff, so it may have a role to play in helping triage patients to units more specialized in preventing delirium.
Bottom line: The AWOL prediction tool is simple to use, broadly applicable, and adds another tool to the literature to determine delirium risk.
Citation: Douglas VC, Hessler CS, Dhaliwal G, et al. The AWOL tool: derivation and validation of a delirium prediction rule. J Hosp Med. 2013;8(9);493-499.
Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding
Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?
Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.
Study design: Meta-analysis of prospective, randomized control trials.
Setting: OVID database search in June 2012.
Synopsis: A literature search identified six prospective, randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56-1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).
Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.
Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.
Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.
Probiotic Benefit Questioned in the Elderly
Clinical question: Do probiotics prevent antibiotic-associated diarrhea (AAD) in patients 65 and older?
Background: Individual studies using different protocols to assess the efficacy of probiotics in preventing AAD, including Clostridium difficile-associated diarrhea (CDAD), suggest a decreased incidence of AAD when taking probiotics. Meta-analysis of this data also suggests that probiotics are effective in prevention of AAD; however, these results are undermined by the high heterogeneity of the studies included.
Study Design: Randomized, double-blind, placebo-controlled trial.
Setting: Multicenter trial in the United Kingdom.
Synopsis: Nearly 3,000 patients ages 65 years and older who had received one or more antibiotics within seven days were randomized to receive placebo or high-dose probiotics for 21 days. After recruitment, the patients were assessed for AAD up to eight weeks and CDAD up to 12 weeks. Results did not demonstrate a reduction of AAD or CDAD in patients taking probiotics. AAD occurred in 10.8% of patients taking the probiotic and 10.4% of patients taking placebo (95% confidence interval 0.83-1.32). CDAD occurred in 0.8% of patients taking the probiotic and 1.2% of patients taking placebo (95% confidence interval 0.34-1.47).
Based on the results of this double-blind, placebo-controlled trial, there is insufficient evidence to support initiation of probiotics for the prevention of AAD and CDAD in patients 65 years and older. Future studies utilizing standardized protocols against specific antibiotics, along with improved understanding of the underlying mechanisms of AAD prevention, are needed.
Bottom line: High-dose probiotics (lactobacillus acidophilus and bifidobacterium bifidum) do not prevent AAD in elderly patients.
Citation: Allen S, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249-1257.
Colchicine and NSAID Better than NSAID Alone for Acute Pericarditis
Clinical question: Is colchicine safe, effective, and able to prevent recurrence in acute pericarditis?
Background: Colchicine is effective for the treatment of recurrent pericarditis. More recent open-label trials have established its role in acute pericarditis when combined with conventional NSAID therapy. However, a definitive randomized control trial has not been performed to establish colchicine’s role in acute pericarditis.
Study design: Double-blinded, randomized, controlled trial.
Setting: Multicenter in Northern Italy.
Synopsis: Investigators randomized 240 patients to receive either colchicine or placebo in addition to standard therapy of either aspirin or ibuprofen. Incessant or recurrent pericarditis occurred in 16.7% of patients treated with colchicine versus 37.5% in patients receiving placebo (RR 0.56; 95% CI 0.30-0.72; P<0.001). The number needed to treat to prevent one episode of incessant or recurrent pericarditis was four. Colchicine therapy also reduced the frequency of symptom persistence at 72 hours, number of recurrences per patient, rate of hospitalization, and the rate of readmission within one week.
It should be noted that the study excluded the following groups: patients with an elevated troponin, elevated transaminases (>1.5 upper limit of normal), and serum creatinine >2.5.
Bottom line: In addition to conventional therapy, colchicine reduces incessant or recurrent pericarditis in patients with a first episode of acute pericarditis.
Citation: Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.
Improvement Needed in Patient Understanding at Hospital Discharge
Clinical question: How well do older patients with heart failure, pneumonia, or acute coronary syndrome understand their diagnosis and post-discharge follow-up plans compared with medical record data?
Background: As hospitals across the country work on preventing 30-day readmissions, more attention has been given to assessing the quality of discharge processes; few evaluations have been conducted from a patient-centered perspective.
Study Design: Prospective, observational cohort study.
Setting: An urban, academic medical center.
Synopsis: This study evaluated the quality of the discharge process among 377 hospitalized patients >65 years old. Medical record data were compared with patient responses during a telephone interview within one week of discharge. By medical records, every patient received discharge instructions that in 97% of cases included discharge diagnosis, activity instructions, follow-up physician information, and warning signs. The authors determined that discharge diagnosis was not written in lay terms 26% of the time. By patient report, 90% expressed that they understood their discharge diagnosis, yet only around 60% fully understood their diagnosis as it was written in the medical record. Although about half of patients reported having a follow-up appointment upon discharge, only about a third of patients had a documented follow-up appointment in the medical record.
Bottom line: Multiple discrepancies were identified between medical record review and patients’ understanding of their discharge diagnosis and plans. Improvements in discharge processes (such as making follow-up appointments) and in patient education (such as increased use of layperson language) are needed.
Citation: Horwitz LI, Moriarty JP, Chen C, et al. Quality of discharge practices and patient understanding at an academic medical center [published online ahead of print August 19, 2013]. JAMA Intern Med.
Effectiveness of a Multihospital Effort to Reduce Rehospitalization
Clinical question: Does Project BOOST reduce 30-day rehospitalization for hospitals participating in a quality improvement collaborative?
Background: With the advent of penalties for hospitals with excessive 30-day readmissions among Medicare beneficiaries, hospitals nationwide are attempting to reduce 30-day readmission rates. Few interventions aimed at reducing 30-day hospital readmissions have been effective, and successful interventions have limited generalizability.
Study design: Semi-controlled, pre-post study.
Setting: Volunteer sample of acute care pilot units within a nationally representative sample of 11 academic and non-academic hospitals.
Synopsis: The 11 hospitals enrolled in this quality improvement collaborative planned and implemented Project BOOST tools over 12 months with support from an external quality improvement mentor. Each hospital tailored the BOOST tools that they implemented based on a needs assessment. Reporting of clinical outcome data was voluntary; administrative sources at each hospital provided these data. Although 30 hospitals participated in this collaborative, only 11 hospitals reported data for this analysis.
Average 30-day rehospitalization rates among BOOST units fell from pre- to post-implementation (14.7% to 12.7%, P=0.010); 30-day rehospitalization rates among control units did not change during this same time period (14.1% to 14.0%, respectively, P=0.831).
Bottom line: Although the 11 hospitals in this collaborative found reduced 30-day readmissions in association with BOOST implementation, this finding may be biased due to voluntary reporting of data and improvements at one hospital driving the overall effect of the intervention. More rigorous evaluation of Project BOOST is needed.
Citation: Hansen LO, Greewald JL, Budnitz T, et al. Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization. J Hosp Med. 2013;8(8):421-427.
Hospitals Profit from Preventing Surgical Site Infections
Clinical question: Does quality improvement, in this case preventing surgical site infections (SSIs), necessarily lead to improvement in hospital profit?
Background: It’s clear that preventing SSIs benefits patients and saves money for health insurance providers, but it’s unclear what financial impact SSIs have on hospitals and how best to calculate it. This quantification is needed for cost-benefit analyses of interventions designed to prevent SSIs.
Study design: Retrospective study.
Setting: Four Johns Hopkins-affiliated, tertiary care hospitals.
Synopsis: This retrospective study included all patients admitted to or having certain surgical procedures at four Johns Hopkins-affiliated hospitals between Jan. 1, 2007, and Dec. 31, 2010. Patients were first stratified by complexity, and then those who had a SSI (618) were compared to those without SSIs (399,627 admissions and 25,849 surgeries) for differences in daily hospital charges, length of stay, 30-day readmission rates, and hospital profit.
Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.
The authors propose equations to determine the change in hospital profit due to a single SSI and calculated that preventing one SSI led to an increase in hospital profit between $4,147 and $22,239. These numbers haven’t included the cost of a SSI prevention program, and the limitations in applying these numbers to all hospitals include widely varying hospital costs and differing ability to fill empty beds.
Bottom line: In these four tertiary care hospitals, each SSI prevented could increase hospital profit by thousands of dollars, as well as significantly decrease length of stay and 30-day readmission rates.
Citation: Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital management perspective. JAMA Surg. 2013;148(10):907-914.
Prothrombin Complex Concentrate Is Safer than Fresh Frozen Plasma in Rapidly Reversing INR
Clinical question: Is prothrombin complex concentrate (PCC) safer and more effective than fresh frozen plasma (FFP) in reversing international normalized ratio (INR)?
Background: In Canada, PCC has become the standard of care over FFP for reversal of critical INR due to decreased time of administration, faster preparation, lack of allergic reactions, and small volume. Few studies compare these two products in their adverse effects, time to INR reversal, length of stay, and blood transfusion requirements.
Study design: Retrospective cohort study.
Setting: Two tertiary care EDs in Canada.
Synopsis: Health records of adult patients with an INR ≥1.8 who received FFP over a two-year period prior to PCC introduction (n=149) were compared to those who received PCC in the two years after PCC introduction (n=165). Total serious adverse events, which include mortality, myocardial infarction, and heart failure, were higher in the FFP group (19.5% versus 9.7%, P=0.0164). Heart failure exacerbations, time to reversal of INR, and units of blood transfused were increased in the FFP group. There was no difference in thromboembolic events or in length of stay.
Due to this study’s retrospective nature, there were issues with documentation of INR measurements, so true rapidity of INR reversal is unknown. In the United States, the FDA only recently approved PCC for use, so availability might be limited.
Bottom line: Prothrombin complex concentrate is an effective and fast alternative to FFP for reversal of critical INR levels.
Citation: Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-364.
Hospital-Acquired Anemia Associated with Higher Mortality, Increased LOS
Clinical question: What is the prevalence of hospital-acquired anemia (HAA), and does it lead to increased mortality and resource utilization?
Background: HAA is a multifactorial care-based problem that occurs as a result of hemodilution, phlebotomy, blood loss from procedures, and impaired erythropoiesis. In the general hospital population, very little is known about HAA prevalence or whether HAA is associated with increased mortality, greater length of stay (LOS), or higher costs.
Study design: Retrospective cohort study.
Setting: Large academic health system in Ohio.
Synopsis: Using administrative data and electronic health record data, an analysis of 188,447 hospitalizations showed that HAA prevalence was 74%. Worsening HAA was correlated to an increase in mortality, so that the odds ratio of mortality with moderate anemia (Hgb between >9 and ≤11) was 1.51 (95% confidence interval 1.33-1.71, P<0.001) and severe anemia (Hgb ≤9) was 3.28 (95% confidence interval 2.90-3.72, P<0.001). Increased degree of HAA was correlated to increasing LOS (up to 1.88 extra days for patients with severe anemia) and higher hospital costs.
Because this is a retrospective observational study, no true causal relationship can be discerned from this study. However, the body of evidence linking iatrogenic causes of anemia to negative outcomes is compelling. Hospitalists should attempt to limit blood loss through judicious use of phlebotomy and procedures in their patients, so as to avoid anemia and subsequent unnecessary transfusions.
Bottom line: Hospital-acquired anemia is associated with higher mortality, LOS, and hospital costs in all hospitalized patients.
Citation: Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512.
Thrombolytics and Stroke: The Faster the Better
Clinical question: Does time from ischemic stroke onset to treatment with intravenous thrombolysis make a difference?
Background: Previous studies have shown that “time is brain.” Quicker treatment with intravenous thrombolysis improves outcomes. Multicenter comparison of very early treatment (i.e., <90 minutes) to a later onset to treatment has not been done.
Study design: Observational study.
Setting: Patient information from 1998 to 2012 from 10 European stroke centers.
Synopsis: A total of 6,856 patients were included, of which 19% received thrombolysis in <90 minutes. None of the patients received endovascular treatment for stroke. Modified Rankin score, a functional assessment, was used to determine outcome. A score of 0 or 1, an “excellent” outcome, was seen more often in patients with a moderate severity stroke (NIH stroke scale of 7-12) who received thrombolysis in <90 minutes, but not in other groups. Thrombolysis in <90 minutes was associated with fewer intracerebral hemorrhages (ICH), but symptomatic ICH was not statistically significantly different. Mortality at three months was not different in the two time groups.
Limitations to this study included an unknown presumed cause of stroke in more than a quarter of patients. Deviations from acute stroke protocols are not described. This study adds to the body of literature supporting the early use of intravenous thrombolysis in eligible acute stroke patients.
Bottom line: Expedient treatment with intravenous thrombolysis should occur in acute stroke patients.
Citation: Strbian D, Ringleb P, Michel P, et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly? Stroke. 2013;44(10):2913-2916.
In This Edition
Literature At A Glance
A guide to this month’s studies
- Intravenous haloperidol does not prevent ICU delirium
- Predicting delirium risk in hospitalized adults
- Oral PPIs as effective as IV PPIs in peptic ulcer bleeding
- Probiotic benefit questioned in the elderly
- Colchicine and NSAID better than NSAID alone for acute pericarditis
- Improvement needed in patient understanding at hospital discharge
- Effectiveness of a multihospital effort to reduce rehospitalization
- Hospitals profit from preventing surgical site infections
- Prothrombin complex concentrate safer than fresh frozen plasma in rapidly reversing INR
- Hospital-acquired anemia associated with higher mortality, increased LOS
- Thrombolytics and stroke: the faster the better
Intravenous Haloperidol Does Not Prevent ICU Delirium
Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?
Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.
Study design: Randomized, double-blinded, placebo-controlled trial.
Setting: Single, adult ICU in England.
Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.
This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.
Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.
Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.
Predicting Delirium Risk in Hospitalized Adults
Clinical question: Can a simple tool be developed and used for predicting delirium in hospitalized adults?
Background: Delirium is a common condition that results in higher mortality, longer length of stays, and higher probability of discharge to nursing home. Current delirium prediction tools are complicated, or restricted to surgical or critically ill patients.
Study design: Prospective cohort study, with separate derivation and validation cohorts.
Setting: Two academic hospitals and a VA hospital in San Francisco.
Synopsis: Investigators enrolled 374 hospitalized patients who were more than 50 years of age and not delirious at time of admission (209 patients in the derivation and 165 in the validation). The authors identified four predictors of delirium: Age >80; failure to spell “World” backwards; disOrientation to place; and higher nurse-rated iLlness severity (AWOL). The authors found that rates of delirium increased with increasing number of predictors (with zero predictors, 2% developed delirium; one predictor, 4%; two predictors, 14%; three predictors, 20%; four predictors, 64%).
These predictors are similar to other previously identified risk factors, as well as to prediction tools that are in use for surgical patients. However, this tool is quick and can be completed by nursing staff, so it may have a role to play in helping triage patients to units more specialized in preventing delirium.
Bottom line: The AWOL prediction tool is simple to use, broadly applicable, and adds another tool to the literature to determine delirium risk.
Citation: Douglas VC, Hessler CS, Dhaliwal G, et al. The AWOL tool: derivation and validation of a delirium prediction rule. J Hosp Med. 2013;8(9);493-499.
Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding
Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?
Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.
Study design: Meta-analysis of prospective, randomized control trials.
Setting: OVID database search in June 2012.
Synopsis: A literature search identified six prospective, randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56-1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).
Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.
Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.
Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.
Probiotic Benefit Questioned in the Elderly
Clinical question: Do probiotics prevent antibiotic-associated diarrhea (AAD) in patients 65 and older?
Background: Individual studies using different protocols to assess the efficacy of probiotics in preventing AAD, including Clostridium difficile-associated diarrhea (CDAD), suggest a decreased incidence of AAD when taking probiotics. Meta-analysis of this data also suggests that probiotics are effective in prevention of AAD; however, these results are undermined by the high heterogeneity of the studies included.
Study Design: Randomized, double-blind, placebo-controlled trial.
Setting: Multicenter trial in the United Kingdom.
Synopsis: Nearly 3,000 patients ages 65 years and older who had received one or more antibiotics within seven days were randomized to receive placebo or high-dose probiotics for 21 days. After recruitment, the patients were assessed for AAD up to eight weeks and CDAD up to 12 weeks. Results did not demonstrate a reduction of AAD or CDAD in patients taking probiotics. AAD occurred in 10.8% of patients taking the probiotic and 10.4% of patients taking placebo (95% confidence interval 0.83-1.32). CDAD occurred in 0.8% of patients taking the probiotic and 1.2% of patients taking placebo (95% confidence interval 0.34-1.47).
Based on the results of this double-blind, placebo-controlled trial, there is insufficient evidence to support initiation of probiotics for the prevention of AAD and CDAD in patients 65 years and older. Future studies utilizing standardized protocols against specific antibiotics, along with improved understanding of the underlying mechanisms of AAD prevention, are needed.
Bottom line: High-dose probiotics (lactobacillus acidophilus and bifidobacterium bifidum) do not prevent AAD in elderly patients.
Citation: Allen S, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249-1257.
Colchicine and NSAID Better than NSAID Alone for Acute Pericarditis
Clinical question: Is colchicine safe, effective, and able to prevent recurrence in acute pericarditis?
Background: Colchicine is effective for the treatment of recurrent pericarditis. More recent open-label trials have established its role in acute pericarditis when combined with conventional NSAID therapy. However, a definitive randomized control trial has not been performed to establish colchicine’s role in acute pericarditis.
Study design: Double-blinded, randomized, controlled trial.
Setting: Multicenter in Northern Italy.
Synopsis: Investigators randomized 240 patients to receive either colchicine or placebo in addition to standard therapy of either aspirin or ibuprofen. Incessant or recurrent pericarditis occurred in 16.7% of patients treated with colchicine versus 37.5% in patients receiving placebo (RR 0.56; 95% CI 0.30-0.72; P<0.001). The number needed to treat to prevent one episode of incessant or recurrent pericarditis was four. Colchicine therapy also reduced the frequency of symptom persistence at 72 hours, number of recurrences per patient, rate of hospitalization, and the rate of readmission within one week.
It should be noted that the study excluded the following groups: patients with an elevated troponin, elevated transaminases (>1.5 upper limit of normal), and serum creatinine >2.5.
Bottom line: In addition to conventional therapy, colchicine reduces incessant or recurrent pericarditis in patients with a first episode of acute pericarditis.
Citation: Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.
Improvement Needed in Patient Understanding at Hospital Discharge
Clinical question: How well do older patients with heart failure, pneumonia, or acute coronary syndrome understand their diagnosis and post-discharge follow-up plans compared with medical record data?
Background: As hospitals across the country work on preventing 30-day readmissions, more attention has been given to assessing the quality of discharge processes; few evaluations have been conducted from a patient-centered perspective.
Study Design: Prospective, observational cohort study.
Setting: An urban, academic medical center.
Synopsis: This study evaluated the quality of the discharge process among 377 hospitalized patients >65 years old. Medical record data were compared with patient responses during a telephone interview within one week of discharge. By medical records, every patient received discharge instructions that in 97% of cases included discharge diagnosis, activity instructions, follow-up physician information, and warning signs. The authors determined that discharge diagnosis was not written in lay terms 26% of the time. By patient report, 90% expressed that they understood their discharge diagnosis, yet only around 60% fully understood their diagnosis as it was written in the medical record. Although about half of patients reported having a follow-up appointment upon discharge, only about a third of patients had a documented follow-up appointment in the medical record.
Bottom line: Multiple discrepancies were identified between medical record review and patients’ understanding of their discharge diagnosis and plans. Improvements in discharge processes (such as making follow-up appointments) and in patient education (such as increased use of layperson language) are needed.
Citation: Horwitz LI, Moriarty JP, Chen C, et al. Quality of discharge practices and patient understanding at an academic medical center [published online ahead of print August 19, 2013]. JAMA Intern Med.
Effectiveness of a Multihospital Effort to Reduce Rehospitalization
Clinical question: Does Project BOOST reduce 30-day rehospitalization for hospitals participating in a quality improvement collaborative?
Background: With the advent of penalties for hospitals with excessive 30-day readmissions among Medicare beneficiaries, hospitals nationwide are attempting to reduce 30-day readmission rates. Few interventions aimed at reducing 30-day hospital readmissions have been effective, and successful interventions have limited generalizability.
Study design: Semi-controlled, pre-post study.
Setting: Volunteer sample of acute care pilot units within a nationally representative sample of 11 academic and non-academic hospitals.
Synopsis: The 11 hospitals enrolled in this quality improvement collaborative planned and implemented Project BOOST tools over 12 months with support from an external quality improvement mentor. Each hospital tailored the BOOST tools that they implemented based on a needs assessment. Reporting of clinical outcome data was voluntary; administrative sources at each hospital provided these data. Although 30 hospitals participated in this collaborative, only 11 hospitals reported data for this analysis.
Average 30-day rehospitalization rates among BOOST units fell from pre- to post-implementation (14.7% to 12.7%, P=0.010); 30-day rehospitalization rates among control units did not change during this same time period (14.1% to 14.0%, respectively, P=0.831).
Bottom line: Although the 11 hospitals in this collaborative found reduced 30-day readmissions in association with BOOST implementation, this finding may be biased due to voluntary reporting of data and improvements at one hospital driving the overall effect of the intervention. More rigorous evaluation of Project BOOST is needed.
Citation: Hansen LO, Greewald JL, Budnitz T, et al. Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization. J Hosp Med. 2013;8(8):421-427.
Hospitals Profit from Preventing Surgical Site Infections
Clinical question: Does quality improvement, in this case preventing surgical site infections (SSIs), necessarily lead to improvement in hospital profit?
Background: It’s clear that preventing SSIs benefits patients and saves money for health insurance providers, but it’s unclear what financial impact SSIs have on hospitals and how best to calculate it. This quantification is needed for cost-benefit analyses of interventions designed to prevent SSIs.
Study design: Retrospective study.
Setting: Four Johns Hopkins-affiliated, tertiary care hospitals.
Synopsis: This retrospective study included all patients admitted to or having certain surgical procedures at four Johns Hopkins-affiliated hospitals between Jan. 1, 2007, and Dec. 31, 2010. Patients were first stratified by complexity, and then those who had a SSI (618) were compared to those without SSIs (399,627 admissions and 25,849 surgeries) for differences in daily hospital charges, length of stay, 30-day readmission rates, and hospital profit.
Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.
The authors propose equations to determine the change in hospital profit due to a single SSI and calculated that preventing one SSI led to an increase in hospital profit between $4,147 and $22,239. These numbers haven’t included the cost of a SSI prevention program, and the limitations in applying these numbers to all hospitals include widely varying hospital costs and differing ability to fill empty beds.
Bottom line: In these four tertiary care hospitals, each SSI prevented could increase hospital profit by thousands of dollars, as well as significantly decrease length of stay and 30-day readmission rates.
Citation: Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital management perspective. JAMA Surg. 2013;148(10):907-914.
Prothrombin Complex Concentrate Is Safer than Fresh Frozen Plasma in Rapidly Reversing INR
Clinical question: Is prothrombin complex concentrate (PCC) safer and more effective than fresh frozen plasma (FFP) in reversing international normalized ratio (INR)?
Background: In Canada, PCC has become the standard of care over FFP for reversal of critical INR due to decreased time of administration, faster preparation, lack of allergic reactions, and small volume. Few studies compare these two products in their adverse effects, time to INR reversal, length of stay, and blood transfusion requirements.
Study design: Retrospective cohort study.
Setting: Two tertiary care EDs in Canada.
Synopsis: Health records of adult patients with an INR ≥1.8 who received FFP over a two-year period prior to PCC introduction (n=149) were compared to those who received PCC in the two years after PCC introduction (n=165). Total serious adverse events, which include mortality, myocardial infarction, and heart failure, were higher in the FFP group (19.5% versus 9.7%, P=0.0164). Heart failure exacerbations, time to reversal of INR, and units of blood transfused were increased in the FFP group. There was no difference in thromboembolic events or in length of stay.
Due to this study’s retrospective nature, there were issues with documentation of INR measurements, so true rapidity of INR reversal is unknown. In the United States, the FDA only recently approved PCC for use, so availability might be limited.
Bottom line: Prothrombin complex concentrate is an effective and fast alternative to FFP for reversal of critical INR levels.
Citation: Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-364.
Hospital-Acquired Anemia Associated with Higher Mortality, Increased LOS
Clinical question: What is the prevalence of hospital-acquired anemia (HAA), and does it lead to increased mortality and resource utilization?
Background: HAA is a multifactorial care-based problem that occurs as a result of hemodilution, phlebotomy, blood loss from procedures, and impaired erythropoiesis. In the general hospital population, very little is known about HAA prevalence or whether HAA is associated with increased mortality, greater length of stay (LOS), or higher costs.
Study design: Retrospective cohort study.
Setting: Large academic health system in Ohio.
Synopsis: Using administrative data and electronic health record data, an analysis of 188,447 hospitalizations showed that HAA prevalence was 74%. Worsening HAA was correlated to an increase in mortality, so that the odds ratio of mortality with moderate anemia (Hgb between >9 and ≤11) was 1.51 (95% confidence interval 1.33-1.71, P<0.001) and severe anemia (Hgb ≤9) was 3.28 (95% confidence interval 2.90-3.72, P<0.001). Increased degree of HAA was correlated to increasing LOS (up to 1.88 extra days for patients with severe anemia) and higher hospital costs.
Because this is a retrospective observational study, no true causal relationship can be discerned from this study. However, the body of evidence linking iatrogenic causes of anemia to negative outcomes is compelling. Hospitalists should attempt to limit blood loss through judicious use of phlebotomy and procedures in their patients, so as to avoid anemia and subsequent unnecessary transfusions.
Bottom line: Hospital-acquired anemia is associated with higher mortality, LOS, and hospital costs in all hospitalized patients.
Citation: Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512.
Thrombolytics and Stroke: The Faster the Better
Clinical question: Does time from ischemic stroke onset to treatment with intravenous thrombolysis make a difference?
Background: Previous studies have shown that “time is brain.” Quicker treatment with intravenous thrombolysis improves outcomes. Multicenter comparison of very early treatment (i.e., <90 minutes) to a later onset to treatment has not been done.
Study design: Observational study.
Setting: Patient information from 1998 to 2012 from 10 European stroke centers.
Synopsis: A total of 6,856 patients were included, of which 19% received thrombolysis in <90 minutes. None of the patients received endovascular treatment for stroke. Modified Rankin score, a functional assessment, was used to determine outcome. A score of 0 or 1, an “excellent” outcome, was seen more often in patients with a moderate severity stroke (NIH stroke scale of 7-12) who received thrombolysis in <90 minutes, but not in other groups. Thrombolysis in <90 minutes was associated with fewer intracerebral hemorrhages (ICH), but symptomatic ICH was not statistically significantly different. Mortality at three months was not different in the two time groups.
Limitations to this study included an unknown presumed cause of stroke in more than a quarter of patients. Deviations from acute stroke protocols are not described. This study adds to the body of literature supporting the early use of intravenous thrombolysis in eligible acute stroke patients.
Bottom line: Expedient treatment with intravenous thrombolysis should occur in acute stroke patients.
Citation: Strbian D, Ringleb P, Michel P, et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly? Stroke. 2013;44(10):2913-2916.
In This Edition
Literature At A Glance
A guide to this month’s studies
- Intravenous haloperidol does not prevent ICU delirium
- Predicting delirium risk in hospitalized adults
- Oral PPIs as effective as IV PPIs in peptic ulcer bleeding
- Probiotic benefit questioned in the elderly
- Colchicine and NSAID better than NSAID alone for acute pericarditis
- Improvement needed in patient understanding at hospital discharge
- Effectiveness of a multihospital effort to reduce rehospitalization
- Hospitals profit from preventing surgical site infections
- Prothrombin complex concentrate safer than fresh frozen plasma in rapidly reversing INR
- Hospital-acquired anemia associated with higher mortality, increased LOS
- Thrombolytics and stroke: the faster the better
Intravenous Haloperidol Does Not Prevent ICU Delirium
Clinical question: Can haloperidol reduce delirium in critically ill patients if initiated early in ICU stay?
Background: Prior studies suggest antipsychotics reduce intensity and duration of delirium in hospitalized patients. Evidence is mixed for preventing delirium. A trial of risperidone demonstrated delirium rate reduction in coronary artery bypass grafting (CABG) patients, but another trial of haloperidol in hip surgery patients failed to prevent onset of delirium. There is little evidence on antipsychotics in ICU delirium.
Study design: Randomized, double-blinded, placebo-controlled trial.
Setting: Single, adult ICU in England.
Synopsis: The study randomized 142 critically ill patients to receive 2.5 mg of intravenous haloperidol versus placebo every eight hours for up to 14 days. There was no significant difference between groups in the total time spent free of delirium or coma. Limitations include the use of open-label haloperidol in 21% of the placebo group patients. More sedation but less agitation was seen with the use of haloperidol, which also prolonged QTc. No severe adverse effects were observed.
This study supports the idea that scheduled antipsychotics should not be used to reduce ICU delirium. Addressing modifiable risk factors and using dexmedetomidine rather than lorazepam for sedation in the ICU continue to be first-line strategies to lower delirium rates.
Bottom line: Prophylactic haloperidol should not be used to prevent ICU delirium.
Citation: Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. Lancet Respir Med. 2013;1(7):515-523.
Predicting Delirium Risk in Hospitalized Adults
Clinical question: Can a simple tool be developed and used for predicting delirium in hospitalized adults?
Background: Delirium is a common condition that results in higher mortality, longer length of stays, and higher probability of discharge to nursing home. Current delirium prediction tools are complicated, or restricted to surgical or critically ill patients.
Study design: Prospective cohort study, with separate derivation and validation cohorts.
Setting: Two academic hospitals and a VA hospital in San Francisco.
Synopsis: Investigators enrolled 374 hospitalized patients who were more than 50 years of age and not delirious at time of admission (209 patients in the derivation and 165 in the validation). The authors identified four predictors of delirium: Age >80; failure to spell “World” backwards; disOrientation to place; and higher nurse-rated iLlness severity (AWOL). The authors found that rates of delirium increased with increasing number of predictors (with zero predictors, 2% developed delirium; one predictor, 4%; two predictors, 14%; three predictors, 20%; four predictors, 64%).
These predictors are similar to other previously identified risk factors, as well as to prediction tools that are in use for surgical patients. However, this tool is quick and can be completed by nursing staff, so it may have a role to play in helping triage patients to units more specialized in preventing delirium.
Bottom line: The AWOL prediction tool is simple to use, broadly applicable, and adds another tool to the literature to determine delirium risk.
Citation: Douglas VC, Hessler CS, Dhaliwal G, et al. The AWOL tool: derivation and validation of a delirium prediction rule. J Hosp Med. 2013;8(9);493-499.
Oral Proton Pump Inhibitors (PPIs) as Effective as IV PPIs in Peptic Ulcer Bleeding
Clinical question: In patients with peptic ulcer bleeding, are oral PPIs of equal benefit to intravenous PPIs?
Background: PPI therapy has been shown in several studies to reduce re-bleeding risk in patients when used adjunctively for peptic ulcer bleeding. In spite of this data, there is still uncertainty about the optimal dose and route of administration.
Study design: Meta-analysis of prospective, randomized control trials.
Setting: OVID database search in June 2012.
Synopsis: A literature search identified six prospective, randomized control trials. Overall, 615 patients were included across the six trials. No significant difference in risk of re-bleeding was discovered between the two groups (8.6% oral vs. 9.3% IV, RR: 0.92, 95% CI: 0.56-1.5). Length of hospital stay was statistically significantly lower for oral PPIs (-0.74 day, 95% CI: -1.10 to -0.39 day).
Because these findings are based on a meta-analysis of studies with notable flaws—including lack of blinding—it is difficult to draw any definitive conclusions from this data. Hospitalists should use care before changing their practice patterns, given the risk of bias and need for further study.
Bottom line: Oral PPIs may reduce hospital length of stay without an increased risk of re-bleeding; however, further study with a well-powered, double-blind, randomized control trial is necessary.
Citation: Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38(7):721-728.
Probiotic Benefit Questioned in the Elderly
Clinical question: Do probiotics prevent antibiotic-associated diarrhea (AAD) in patients 65 and older?
Background: Individual studies using different protocols to assess the efficacy of probiotics in preventing AAD, including Clostridium difficile-associated diarrhea (CDAD), suggest a decreased incidence of AAD when taking probiotics. Meta-analysis of this data also suggests that probiotics are effective in prevention of AAD; however, these results are undermined by the high heterogeneity of the studies included.
Study Design: Randomized, double-blind, placebo-controlled trial.
Setting: Multicenter trial in the United Kingdom.
Synopsis: Nearly 3,000 patients ages 65 years and older who had received one or more antibiotics within seven days were randomized to receive placebo or high-dose probiotics for 21 days. After recruitment, the patients were assessed for AAD up to eight weeks and CDAD up to 12 weeks. Results did not demonstrate a reduction of AAD or CDAD in patients taking probiotics. AAD occurred in 10.8% of patients taking the probiotic and 10.4% of patients taking placebo (95% confidence interval 0.83-1.32). CDAD occurred in 0.8% of patients taking the probiotic and 1.2% of patients taking placebo (95% confidence interval 0.34-1.47).
Based on the results of this double-blind, placebo-controlled trial, there is insufficient evidence to support initiation of probiotics for the prevention of AAD and CDAD in patients 65 years and older. Future studies utilizing standardized protocols against specific antibiotics, along with improved understanding of the underlying mechanisms of AAD prevention, are needed.
Bottom line: High-dose probiotics (lactobacillus acidophilus and bifidobacterium bifidum) do not prevent AAD in elderly patients.
Citation: Allen S, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249-1257.
Colchicine and NSAID Better than NSAID Alone for Acute Pericarditis
Clinical question: Is colchicine safe, effective, and able to prevent recurrence in acute pericarditis?
Background: Colchicine is effective for the treatment of recurrent pericarditis. More recent open-label trials have established its role in acute pericarditis when combined with conventional NSAID therapy. However, a definitive randomized control trial has not been performed to establish colchicine’s role in acute pericarditis.
Study design: Double-blinded, randomized, controlled trial.
Setting: Multicenter in Northern Italy.
Synopsis: Investigators randomized 240 patients to receive either colchicine or placebo in addition to standard therapy of either aspirin or ibuprofen. Incessant or recurrent pericarditis occurred in 16.7% of patients treated with colchicine versus 37.5% in patients receiving placebo (RR 0.56; 95% CI 0.30-0.72; P<0.001). The number needed to treat to prevent one episode of incessant or recurrent pericarditis was four. Colchicine therapy also reduced the frequency of symptom persistence at 72 hours, number of recurrences per patient, rate of hospitalization, and the rate of readmission within one week.
It should be noted that the study excluded the following groups: patients with an elevated troponin, elevated transaminases (>1.5 upper limit of normal), and serum creatinine >2.5.
Bottom line: In addition to conventional therapy, colchicine reduces incessant or recurrent pericarditis in patients with a first episode of acute pericarditis.
Citation: Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528.
Improvement Needed in Patient Understanding at Hospital Discharge
Clinical question: How well do older patients with heart failure, pneumonia, or acute coronary syndrome understand their diagnosis and post-discharge follow-up plans compared with medical record data?
Background: As hospitals across the country work on preventing 30-day readmissions, more attention has been given to assessing the quality of discharge processes; few evaluations have been conducted from a patient-centered perspective.
Study Design: Prospective, observational cohort study.
Setting: An urban, academic medical center.
Synopsis: This study evaluated the quality of the discharge process among 377 hospitalized patients >65 years old. Medical record data were compared with patient responses during a telephone interview within one week of discharge. By medical records, every patient received discharge instructions that in 97% of cases included discharge diagnosis, activity instructions, follow-up physician information, and warning signs. The authors determined that discharge diagnosis was not written in lay terms 26% of the time. By patient report, 90% expressed that they understood their discharge diagnosis, yet only around 60% fully understood their diagnosis as it was written in the medical record. Although about half of patients reported having a follow-up appointment upon discharge, only about a third of patients had a documented follow-up appointment in the medical record.
Bottom line: Multiple discrepancies were identified between medical record review and patients’ understanding of their discharge diagnosis and plans. Improvements in discharge processes (such as making follow-up appointments) and in patient education (such as increased use of layperson language) are needed.
Citation: Horwitz LI, Moriarty JP, Chen C, et al. Quality of discharge practices and patient understanding at an academic medical center [published online ahead of print August 19, 2013]. JAMA Intern Med.
Effectiveness of a Multihospital Effort to Reduce Rehospitalization
Clinical question: Does Project BOOST reduce 30-day rehospitalization for hospitals participating in a quality improvement collaborative?
Background: With the advent of penalties for hospitals with excessive 30-day readmissions among Medicare beneficiaries, hospitals nationwide are attempting to reduce 30-day readmission rates. Few interventions aimed at reducing 30-day hospital readmissions have been effective, and successful interventions have limited generalizability.
Study design: Semi-controlled, pre-post study.
Setting: Volunteer sample of acute care pilot units within a nationally representative sample of 11 academic and non-academic hospitals.
Synopsis: The 11 hospitals enrolled in this quality improvement collaborative planned and implemented Project BOOST tools over 12 months with support from an external quality improvement mentor. Each hospital tailored the BOOST tools that they implemented based on a needs assessment. Reporting of clinical outcome data was voluntary; administrative sources at each hospital provided these data. Although 30 hospitals participated in this collaborative, only 11 hospitals reported data for this analysis.
Average 30-day rehospitalization rates among BOOST units fell from pre- to post-implementation (14.7% to 12.7%, P=0.010); 30-day rehospitalization rates among control units did not change during this same time period (14.1% to 14.0%, respectively, P=0.831).
Bottom line: Although the 11 hospitals in this collaborative found reduced 30-day readmissions in association with BOOST implementation, this finding may be biased due to voluntary reporting of data and improvements at one hospital driving the overall effect of the intervention. More rigorous evaluation of Project BOOST is needed.
Citation: Hansen LO, Greewald JL, Budnitz T, et al. Project BOOST: Effectiveness of a multihospital effort to reduce rehospitalization. J Hosp Med. 2013;8(8):421-427.
Hospitals Profit from Preventing Surgical Site Infections
Clinical question: Does quality improvement, in this case preventing surgical site infections (SSIs), necessarily lead to improvement in hospital profit?
Background: It’s clear that preventing SSIs benefits patients and saves money for health insurance providers, but it’s unclear what financial impact SSIs have on hospitals and how best to calculate it. This quantification is needed for cost-benefit analyses of interventions designed to prevent SSIs.
Study design: Retrospective study.
Setting: Four Johns Hopkins-affiliated, tertiary care hospitals.
Synopsis: This retrospective study included all patients admitted to or having certain surgical procedures at four Johns Hopkins-affiliated hospitals between Jan. 1, 2007, and Dec. 31, 2010. Patients were first stratified by complexity, and then those who had a SSI (618) were compared to those without SSIs (399,627 admissions and 25,849 surgeries) for differences in daily hospital charges, length of stay, 30-day readmission rates, and hospital profit.
Although daily charges were essentially the same between the groups, patients with SSIs had almost double the mean length of stay than patients without SSIs. SSI patients also had a drastically higher 30-day readmission rate.
The authors propose equations to determine the change in hospital profit due to a single SSI and calculated that preventing one SSI led to an increase in hospital profit between $4,147 and $22,239. These numbers haven’t included the cost of a SSI prevention program, and the limitations in applying these numbers to all hospitals include widely varying hospital costs and differing ability to fill empty beds.
Bottom line: In these four tertiary care hospitals, each SSI prevented could increase hospital profit by thousands of dollars, as well as significantly decrease length of stay and 30-day readmission rates.
Citation: Shepard J, Ward W, Milstone A, et al. Financial impact of surgical site infections on hospitals: the hospital management perspective. JAMA Surg. 2013;148(10):907-914.
Prothrombin Complex Concentrate Is Safer than Fresh Frozen Plasma in Rapidly Reversing INR
Clinical question: Is prothrombin complex concentrate (PCC) safer and more effective than fresh frozen plasma (FFP) in reversing international normalized ratio (INR)?
Background: In Canada, PCC has become the standard of care over FFP for reversal of critical INR due to decreased time of administration, faster preparation, lack of allergic reactions, and small volume. Few studies compare these two products in their adverse effects, time to INR reversal, length of stay, and blood transfusion requirements.
Study design: Retrospective cohort study.
Setting: Two tertiary care EDs in Canada.
Synopsis: Health records of adult patients with an INR ≥1.8 who received FFP over a two-year period prior to PCC introduction (n=149) were compared to those who received PCC in the two years after PCC introduction (n=165). Total serious adverse events, which include mortality, myocardial infarction, and heart failure, were higher in the FFP group (19.5% versus 9.7%, P=0.0164). Heart failure exacerbations, time to reversal of INR, and units of blood transfused were increased in the FFP group. There was no difference in thromboembolic events or in length of stay.
Due to this study’s retrospective nature, there were issues with documentation of INR measurements, so true rapidity of INR reversal is unknown. In the United States, the FDA only recently approved PCC for use, so availability might be limited.
Bottom line: Prothrombin complex concentrate is an effective and fast alternative to FFP for reversal of critical INR levels.
Citation: Hickey M, Gatien M, Taljaard M, Aujnarain A, Giulivi A, Perry JJ. Outcomes of urgent warfarin reversal with frozen plasma versus prothombin complex concentrate in the emergency department. Circulation. 2013;128(4):360-364.
Hospital-Acquired Anemia Associated with Higher Mortality, Increased LOS
Clinical question: What is the prevalence of hospital-acquired anemia (HAA), and does it lead to increased mortality and resource utilization?
Background: HAA is a multifactorial care-based problem that occurs as a result of hemodilution, phlebotomy, blood loss from procedures, and impaired erythropoiesis. In the general hospital population, very little is known about HAA prevalence or whether HAA is associated with increased mortality, greater length of stay (LOS), or higher costs.
Study design: Retrospective cohort study.
Setting: Large academic health system in Ohio.
Synopsis: Using administrative data and electronic health record data, an analysis of 188,447 hospitalizations showed that HAA prevalence was 74%. Worsening HAA was correlated to an increase in mortality, so that the odds ratio of mortality with moderate anemia (Hgb between >9 and ≤11) was 1.51 (95% confidence interval 1.33-1.71, P<0.001) and severe anemia (Hgb ≤9) was 3.28 (95% confidence interval 2.90-3.72, P<0.001). Increased degree of HAA was correlated to increasing LOS (up to 1.88 extra days for patients with severe anemia) and higher hospital costs.
Because this is a retrospective observational study, no true causal relationship can be discerned from this study. However, the body of evidence linking iatrogenic causes of anemia to negative outcomes is compelling. Hospitalists should attempt to limit blood loss through judicious use of phlebotomy and procedures in their patients, so as to avoid anemia and subsequent unnecessary transfusions.
Bottom line: Hospital-acquired anemia is associated with higher mortality, LOS, and hospital costs in all hospitalized patients.
Citation: Koch CG, Li L, Sun Z, et al. Hospital-acquired anemia: prevalence, outcomes, and healthcare implications. J Hosp Med. 2013;8(9):506-512.
Thrombolytics and Stroke: The Faster the Better
Clinical question: Does time from ischemic stroke onset to treatment with intravenous thrombolysis make a difference?
Background: Previous studies have shown that “time is brain.” Quicker treatment with intravenous thrombolysis improves outcomes. Multicenter comparison of very early treatment (i.e., <90 minutes) to a later onset to treatment has not been done.
Study design: Observational study.
Setting: Patient information from 1998 to 2012 from 10 European stroke centers.
Synopsis: A total of 6,856 patients were included, of which 19% received thrombolysis in <90 minutes. None of the patients received endovascular treatment for stroke. Modified Rankin score, a functional assessment, was used to determine outcome. A score of 0 or 1, an “excellent” outcome, was seen more often in patients with a moderate severity stroke (NIH stroke scale of 7-12) who received thrombolysis in <90 minutes, but not in other groups. Thrombolysis in <90 minutes was associated with fewer intracerebral hemorrhages (ICH), but symptomatic ICH was not statistically significantly different. Mortality at three months was not different in the two time groups.
Limitations to this study included an unknown presumed cause of stroke in more than a quarter of patients. Deviations from acute stroke protocols are not described. This study adds to the body of literature supporting the early use of intravenous thrombolysis in eligible acute stroke patients.
Bottom line: Expedient treatment with intravenous thrombolysis should occur in acute stroke patients.
Citation: Strbian D, Ringleb P, Michel P, et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly? Stroke. 2013;44(10):2913-2916.
In Las Vegas, HM 14 Can Include Whole Family
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Task Force Identifies Requirements for Diagnosing Psychogenic Seizures
In areas where video EEG (vEEG) is not available, clinicians can use a staged approach to diagnosing psychogenic nonepileptic seizures (PNES) that incorporates medical histories, eyewitness accounts, and video recordings of seizure activity, according to a task force of the International League Against Epilepsy. Their report was published in the November issue of Epilepsia.
Most patients with recurrent seizures are presumed to have epilepsy and are treated with antiepileptic drugs (AEDs), but AEDs could exacerbate PNES. Therefore, early and accurate recognition of PNES is “of paramount importance,” said W. Curt LaFrance, Jr., MD, Assistant Professor of Psychiatry and Neurology at Brown University in Providence, Rhode Island, and leader of the task force. Diagnosis is complicated by the fact that epilepsy is a recognized risk factor for the development of PNES.
The task force’s report aims “to provide greater clarity about the process and certainty of the diagnosis of PNES, with the intent to improve the care for people with epilepsy and nonepileptic seizures,” said the investigators. “The ability to diagnose PNES when vEEG is not available may open opportunities to lower and middle income countries where monitoring is not available.”
The authors reviewed the medical literature to evaluate approaches to diagnosing PNES, including taking a history; EEG; ambulatory EEG; vEEG or monitoring; neurophysiologic, neurohumoral, neuroimaging, and neuropsychologic testing; hypnosis; and conversation analysis.
The combination of vEEG with history taken from patients and witnesses is the diagnostic standard, “however, vEEG is not available in some locations, and in some patients, events cannot be recorded,” said the task force.
The group proposed the following four categories of certainty for PNES diagnosis and their respective requirements:
• Documented PNES relies on clinical history plus a vEEG recording of habitual events.
• Clinically established PNES is defined by a clinical history, clinician witness, and ambulatory EEG recording of habitual event or events without video. This diagnosis would be appropriate if a clinician witness observed a seizure and documented the exam findings typically found in PNES, such as resisted eye-opening, or if a clinician could review a non-EEG event by video or in person.
• Probable PNES is determined by a clinical history, a clinician review of video recording or live events, and a normal interictal EEG. This diagnosis would be appropriate if a clinician could review a home or cell phone video recording of seizure activity or witness it in person.
• Possible PNES relies on clinical history from the patient or witness and a normal interictal EEG. At minimum, a patient’s history and description of events and an eyewitness description could help identify possible PNES, but without the clinician “observing the ictus on video or in person, an alternative diagnosis of epilepsy would have to be considered very carefully,” said the investigators.
—Karen Blum
IMNG Medical News
Suggested Reading
Cervenka MC, Lesser R, Tran TT, et al. Does the teddy bear sign predict psychogenic nonepileptic seizures? Epilepsy Behav. 2013;28(2):217-220.
Lafrance WC Jr, Baker GA, Duncan R, et al. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: A staged approach: A report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia. 2013;54(11):2005-2018.
Thomas AA, Preston J, Scott RC, Bujarski KA. Diagnosis of probable psychogenic nonepileptic seizures in the outpatient clinic: Does gender matter? Epilepsy Behav. 2013;29(2):295-297.
In areas where video EEG (vEEG) is not available, clinicians can use a staged approach to diagnosing psychogenic nonepileptic seizures (PNES) that incorporates medical histories, eyewitness accounts, and video recordings of seizure activity, according to a task force of the International League Against Epilepsy. Their report was published in the November issue of Epilepsia.
Most patients with recurrent seizures are presumed to have epilepsy and are treated with antiepileptic drugs (AEDs), but AEDs could exacerbate PNES. Therefore, early and accurate recognition of PNES is “of paramount importance,” said W. Curt LaFrance, Jr., MD, Assistant Professor of Psychiatry and Neurology at Brown University in Providence, Rhode Island, and leader of the task force. Diagnosis is complicated by the fact that epilepsy is a recognized risk factor for the development of PNES.
The task force’s report aims “to provide greater clarity about the process and certainty of the diagnosis of PNES, with the intent to improve the care for people with epilepsy and nonepileptic seizures,” said the investigators. “The ability to diagnose PNES when vEEG is not available may open opportunities to lower and middle income countries where monitoring is not available.”
The authors reviewed the medical literature to evaluate approaches to diagnosing PNES, including taking a history; EEG; ambulatory EEG; vEEG or monitoring; neurophysiologic, neurohumoral, neuroimaging, and neuropsychologic testing; hypnosis; and conversation analysis.
The combination of vEEG with history taken from patients and witnesses is the diagnostic standard, “however, vEEG is not available in some locations, and in some patients, events cannot be recorded,” said the task force.
The group proposed the following four categories of certainty for PNES diagnosis and their respective requirements:
• Documented PNES relies on clinical history plus a vEEG recording of habitual events.
• Clinically established PNES is defined by a clinical history, clinician witness, and ambulatory EEG recording of habitual event or events without video. This diagnosis would be appropriate if a clinician witness observed a seizure and documented the exam findings typically found in PNES, such as resisted eye-opening, or if a clinician could review a non-EEG event by video or in person.
• Probable PNES is determined by a clinical history, a clinician review of video recording or live events, and a normal interictal EEG. This diagnosis would be appropriate if a clinician could review a home or cell phone video recording of seizure activity or witness it in person.
• Possible PNES relies on clinical history from the patient or witness and a normal interictal EEG. At minimum, a patient’s history and description of events and an eyewitness description could help identify possible PNES, but without the clinician “observing the ictus on video or in person, an alternative diagnosis of epilepsy would have to be considered very carefully,” said the investigators.
—Karen Blum
IMNG Medical News
In areas where video EEG (vEEG) is not available, clinicians can use a staged approach to diagnosing psychogenic nonepileptic seizures (PNES) that incorporates medical histories, eyewitness accounts, and video recordings of seizure activity, according to a task force of the International League Against Epilepsy. Their report was published in the November issue of Epilepsia.
Most patients with recurrent seizures are presumed to have epilepsy and are treated with antiepileptic drugs (AEDs), but AEDs could exacerbate PNES. Therefore, early and accurate recognition of PNES is “of paramount importance,” said W. Curt LaFrance, Jr., MD, Assistant Professor of Psychiatry and Neurology at Brown University in Providence, Rhode Island, and leader of the task force. Diagnosis is complicated by the fact that epilepsy is a recognized risk factor for the development of PNES.
The task force’s report aims “to provide greater clarity about the process and certainty of the diagnosis of PNES, with the intent to improve the care for people with epilepsy and nonepileptic seizures,” said the investigators. “The ability to diagnose PNES when vEEG is not available may open opportunities to lower and middle income countries where monitoring is not available.”
The authors reviewed the medical literature to evaluate approaches to diagnosing PNES, including taking a history; EEG; ambulatory EEG; vEEG or monitoring; neurophysiologic, neurohumoral, neuroimaging, and neuropsychologic testing; hypnosis; and conversation analysis.
The combination of vEEG with history taken from patients and witnesses is the diagnostic standard, “however, vEEG is not available in some locations, and in some patients, events cannot be recorded,” said the task force.
The group proposed the following four categories of certainty for PNES diagnosis and their respective requirements:
• Documented PNES relies on clinical history plus a vEEG recording of habitual events.
• Clinically established PNES is defined by a clinical history, clinician witness, and ambulatory EEG recording of habitual event or events without video. This diagnosis would be appropriate if a clinician witness observed a seizure and documented the exam findings typically found in PNES, such as resisted eye-opening, or if a clinician could review a non-EEG event by video or in person.
• Probable PNES is determined by a clinical history, a clinician review of video recording or live events, and a normal interictal EEG. This diagnosis would be appropriate if a clinician could review a home or cell phone video recording of seizure activity or witness it in person.
• Possible PNES relies on clinical history from the patient or witness and a normal interictal EEG. At minimum, a patient’s history and description of events and an eyewitness description could help identify possible PNES, but without the clinician “observing the ictus on video or in person, an alternative diagnosis of epilepsy would have to be considered very carefully,” said the investigators.
—Karen Blum
IMNG Medical News
Suggested Reading
Cervenka MC, Lesser R, Tran TT, et al. Does the teddy bear sign predict psychogenic nonepileptic seizures? Epilepsy Behav. 2013;28(2):217-220.
Lafrance WC Jr, Baker GA, Duncan R, et al. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: A staged approach: A report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia. 2013;54(11):2005-2018.
Thomas AA, Preston J, Scott RC, Bujarski KA. Diagnosis of probable psychogenic nonepileptic seizures in the outpatient clinic: Does gender matter? Epilepsy Behav. 2013;29(2):295-297.
Suggested Reading
Cervenka MC, Lesser R, Tran TT, et al. Does the teddy bear sign predict psychogenic nonepileptic seizures? Epilepsy Behav. 2013;28(2):217-220.
Lafrance WC Jr, Baker GA, Duncan R, et al. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: A staged approach: A report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia. 2013;54(11):2005-2018.
Thomas AA, Preston J, Scott RC, Bujarski KA. Diagnosis of probable psychogenic nonepileptic seizures in the outpatient clinic: Does gender matter? Epilepsy Behav. 2013;29(2):295-297.
ICU May Increase Risk for Dementia-Like Illness
Patients who are admitted to a medical or surgical intensive care unit (ICU) have a high risk for long-term cognitive impairment, according to a study in the October 3 New England Journal of Medicine.
At 12 months postdischarge, 24% of ICU patients had a score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) that was similar to that for patients with mild Alzheimer’s disease, while 34% had an RBANS score comparable to that of patients with moderate traumatic brain injury (TBI), reported Pratik P. Pandharipande, MD, Professor in the Department of Anesthesiology, Division of Critical Care, Vanderbilt University School of Medicine in Nashville, and colleagues. The researchers also found that a longer period of delirium in the hospital was associated with worse global cognition and executive function scores at three and 12 months.
Dr. Pandharipande’s group included 821 ICU patients with respiratory failure or shock (cardiogenic or septic). These patients were evaluated for delirium, and their global cognition and executive function was assessed with the RBANS and the Trail Making Test, Part B, at three and 12 months after discharge. Fifty-one participants (6%) had cognitive impairment at baseline, and 606 patients (74%) developed delirium (median duration of four days) during their hospital stay.
At three months after discharge, 252 patients (31%) had died, and an additional 59 patients died within the 12-month follow-up. A total of 448 surviving patients underwent cognitive testing after discharge at three months, and 382 surviving patients were tested at 12 months postdischarge.
Participants had a mean RBANS score of 79 at three months and 80 at 12 months. At three months, 40% of patients had a global cognition score that was 1.5 SD below the age-adjusted population mean, which was a similar score to that of patients with moderate TBI. In addition, 26% had a score that was 2 SD below the population mean, which was a score similar to that of patients with mild Alzheimer’s disease. The cognitive deficits continued in both older and younger patients throughout the 12-month follow-up. “A longer duration of delirium was independently associated with worse global cognition at three and 12 months and worse executive function at three and 12 months,” stated Dr. Pandharipande. “Use of sedative or analgesic medications was not consistently associated with cognitive impairment at three and 12 months.
“The significant association between benzodiazepines and executive function at three months should be interpreted cautiously, owing to multiple testing and the nonsignificant associations between benzodiazepines and global cognition scores at 12 months,” Dr. Pandharipande said. “However, the lack of a consistent association should not be taken to suggest that large doses of sedatives are safe, given studies showing that oversedation is associated with adverse outcomes.”
Because delirium is linked to long-term cognitive impairment, the researchers suggested that interventions aimed at reducing delirium may lessen the degree of brain injury that is associated with critical illness.
“Although the judicious use of sedative agents and routine monitoring for delirium—recommended components of care for all patients in the ICU—are increasingly applied, only a few interventions (eg, early mobilization and sleep protocols) have been shown to reduce the risk of delirium among patients in the ICU, and it is not known whether any preventive or treatment strategies can reduce the risk of long-term cognitive impairment after critical illness,” Dr. Pandharipande said.
—Colby Stong
Editor
Suggested Reading
Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.
Patients who are admitted to a medical or surgical intensive care unit (ICU) have a high risk for long-term cognitive impairment, according to a study in the October 3 New England Journal of Medicine.
At 12 months postdischarge, 24% of ICU patients had a score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) that was similar to that for patients with mild Alzheimer’s disease, while 34% had an RBANS score comparable to that of patients with moderate traumatic brain injury (TBI), reported Pratik P. Pandharipande, MD, Professor in the Department of Anesthesiology, Division of Critical Care, Vanderbilt University School of Medicine in Nashville, and colleagues. The researchers also found that a longer period of delirium in the hospital was associated with worse global cognition and executive function scores at three and 12 months.
Dr. Pandharipande’s group included 821 ICU patients with respiratory failure or shock (cardiogenic or septic). These patients were evaluated for delirium, and their global cognition and executive function was assessed with the RBANS and the Trail Making Test, Part B, at three and 12 months after discharge. Fifty-one participants (6%) had cognitive impairment at baseline, and 606 patients (74%) developed delirium (median duration of four days) during their hospital stay.
At three months after discharge, 252 patients (31%) had died, and an additional 59 patients died within the 12-month follow-up. A total of 448 surviving patients underwent cognitive testing after discharge at three months, and 382 surviving patients were tested at 12 months postdischarge.
Participants had a mean RBANS score of 79 at three months and 80 at 12 months. At three months, 40% of patients had a global cognition score that was 1.5 SD below the age-adjusted population mean, which was a similar score to that of patients with moderate TBI. In addition, 26% had a score that was 2 SD below the population mean, which was a score similar to that of patients with mild Alzheimer’s disease. The cognitive deficits continued in both older and younger patients throughout the 12-month follow-up. “A longer duration of delirium was independently associated with worse global cognition at three and 12 months and worse executive function at three and 12 months,” stated Dr. Pandharipande. “Use of sedative or analgesic medications was not consistently associated with cognitive impairment at three and 12 months.
“The significant association between benzodiazepines and executive function at three months should be interpreted cautiously, owing to multiple testing and the nonsignificant associations between benzodiazepines and global cognition scores at 12 months,” Dr. Pandharipande said. “However, the lack of a consistent association should not be taken to suggest that large doses of sedatives are safe, given studies showing that oversedation is associated with adverse outcomes.”
Because delirium is linked to long-term cognitive impairment, the researchers suggested that interventions aimed at reducing delirium may lessen the degree of brain injury that is associated with critical illness.
“Although the judicious use of sedative agents and routine monitoring for delirium—recommended components of care for all patients in the ICU—are increasingly applied, only a few interventions (eg, early mobilization and sleep protocols) have been shown to reduce the risk of delirium among patients in the ICU, and it is not known whether any preventive or treatment strategies can reduce the risk of long-term cognitive impairment after critical illness,” Dr. Pandharipande said.
—Colby Stong
Editor
Patients who are admitted to a medical or surgical intensive care unit (ICU) have a high risk for long-term cognitive impairment, according to a study in the October 3 New England Journal of Medicine.
At 12 months postdischarge, 24% of ICU patients had a score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) that was similar to that for patients with mild Alzheimer’s disease, while 34% had an RBANS score comparable to that of patients with moderate traumatic brain injury (TBI), reported Pratik P. Pandharipande, MD, Professor in the Department of Anesthesiology, Division of Critical Care, Vanderbilt University School of Medicine in Nashville, and colleagues. The researchers also found that a longer period of delirium in the hospital was associated with worse global cognition and executive function scores at three and 12 months.
Dr. Pandharipande’s group included 821 ICU patients with respiratory failure or shock (cardiogenic or septic). These patients were evaluated for delirium, and their global cognition and executive function was assessed with the RBANS and the Trail Making Test, Part B, at three and 12 months after discharge. Fifty-one participants (6%) had cognitive impairment at baseline, and 606 patients (74%) developed delirium (median duration of four days) during their hospital stay.
At three months after discharge, 252 patients (31%) had died, and an additional 59 patients died within the 12-month follow-up. A total of 448 surviving patients underwent cognitive testing after discharge at three months, and 382 surviving patients were tested at 12 months postdischarge.
Participants had a mean RBANS score of 79 at three months and 80 at 12 months. At three months, 40% of patients had a global cognition score that was 1.5 SD below the age-adjusted population mean, which was a similar score to that of patients with moderate TBI. In addition, 26% had a score that was 2 SD below the population mean, which was a score similar to that of patients with mild Alzheimer’s disease. The cognitive deficits continued in both older and younger patients throughout the 12-month follow-up. “A longer duration of delirium was independently associated with worse global cognition at three and 12 months and worse executive function at three and 12 months,” stated Dr. Pandharipande. “Use of sedative or analgesic medications was not consistently associated with cognitive impairment at three and 12 months.
“The significant association between benzodiazepines and executive function at three months should be interpreted cautiously, owing to multiple testing and the nonsignificant associations between benzodiazepines and global cognition scores at 12 months,” Dr. Pandharipande said. “However, the lack of a consistent association should not be taken to suggest that large doses of sedatives are safe, given studies showing that oversedation is associated with adverse outcomes.”
Because delirium is linked to long-term cognitive impairment, the researchers suggested that interventions aimed at reducing delirium may lessen the degree of brain injury that is associated with critical illness.
“Although the judicious use of sedative agents and routine monitoring for delirium—recommended components of care for all patients in the ICU—are increasingly applied, only a few interventions (eg, early mobilization and sleep protocols) have been shown to reduce the risk of delirium among patients in the ICU, and it is not known whether any preventive or treatment strategies can reduce the risk of long-term cognitive impairment after critical illness,” Dr. Pandharipande said.
—Colby Stong
Editor
Suggested Reading
Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.
Suggested Reading
Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.
The First Attack of Multiple Sclerosis May Target Gray Matter
Gray matter, rather than myelin, may be involved in the earliest stages of multiple sclerosis (MS), according to research published September 3 in PLOS One. Gray matter components (eg, axons, neurons, and synapses) may distinguish the CSF proteome of a patient with a true first attack of MS from those of healthy controls and patients with established relapsing-remitting MS.
Nogo receptor was markedly elevated in the CSF of patients with a true first attack of MS, compared with patients with established relapsing-remitting MS and controls, said Steven E. Schutzer, MD, Professor of Medicine at Rutgers University New Jersey Medical School in Newark. Patients with a first attack of MS also had a significant increase of contactin-2/TAG-1, an axonal glycoprotein, in their CSF. Contactin-2/TAG-1 has been reported as an autoimmune target in MS.
Researchers Analyzed CSF From Three Patient Groups
Previous imaging studies have suggested that gray matter changes, and not white matter changes, occur early and predict the development of MS. Other data have conflicted with this idea, however. To determine whether gray matter is involved in early MS, Dr. Schutzer and colleagues collected CSF from three groups of patients. The first group included nine patients with clinically isolated syndrome (CIS) who eventually met diagnostic criteria for MS. The second group included 12 patients with established diagnoses of relapsing-remitting MS according to the McDonald criteria. The third group included six control subjects with no apparent CNS disease.
For the purpose of comparison, the investigators used previously published protein lists generated from two groups of persons with other neurologic diseases and more than 200 healthy controls. The researchers also analyzed a separate group of 10 patients with CIS to compare them with the CIS patients in the study. Dr. Schutzer and colleagues performed protein separation and fractionation on the CSF samples and analyzed them with direct liquid chromatography–mass spectrometry.
Quantities of 20 Proteins Differed Among the Groups
The researchers found 20 proteins that were present in significantly different quantities in patients with CIS, patients with established relapsing-remitting MS, and controls. Nine of these proteins were significantly increased in patients with first-attack CIS, compared with the other two groups. Five proteins were significantly decreased in patients with first-attack CIS, compared with the other groups. The remaining proteins were increased in patients with CIS, compared with patients with relapsing-remitting MS, but decreased compared with controls. Fifteen of the 20 proteins were associated with gray matter.
“There is an increasing literature on the importance of gray matter, neuronal, and axonal involvement in MS, even at very early time points,” said Dr. Schutzer. “Our findings support this [hypothesis] and indicate that axonal, neuronal, and synaptic involvement may be required for the initial presentation of MS. It is interesting in this disease, which is characterized by demyelination as it progresses, that gray matter components may be diagnostically more useful than myelin components at the earliest stages,” he added.
—Erik Greb
Senior Associate Editor
Suggested Reading
Schutzer SE, Angel TE, Liu T, et al. Gray matter is targeted in first-attack multiple sclerosis. PLoS One. 2013;8(9):e66117.
Brink BP, Veerhuis R, Breij EC, et al. The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions. J Neuropathol Exp Neurol. 2005;64(2):147-155.
Huizinga R, Gerritsen W, Heijmans N, Amor S. Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments. Neurobiol Dis. 2008;32(3):461-470.
Gray matter, rather than myelin, may be involved in the earliest stages of multiple sclerosis (MS), according to research published September 3 in PLOS One. Gray matter components (eg, axons, neurons, and synapses) may distinguish the CSF proteome of a patient with a true first attack of MS from those of healthy controls and patients with established relapsing-remitting MS.
Nogo receptor was markedly elevated in the CSF of patients with a true first attack of MS, compared with patients with established relapsing-remitting MS and controls, said Steven E. Schutzer, MD, Professor of Medicine at Rutgers University New Jersey Medical School in Newark. Patients with a first attack of MS also had a significant increase of contactin-2/TAG-1, an axonal glycoprotein, in their CSF. Contactin-2/TAG-1 has been reported as an autoimmune target in MS.
Researchers Analyzed CSF From Three Patient Groups
Previous imaging studies have suggested that gray matter changes, and not white matter changes, occur early and predict the development of MS. Other data have conflicted with this idea, however. To determine whether gray matter is involved in early MS, Dr. Schutzer and colleagues collected CSF from three groups of patients. The first group included nine patients with clinically isolated syndrome (CIS) who eventually met diagnostic criteria for MS. The second group included 12 patients with established diagnoses of relapsing-remitting MS according to the McDonald criteria. The third group included six control subjects with no apparent CNS disease.
For the purpose of comparison, the investigators used previously published protein lists generated from two groups of persons with other neurologic diseases and more than 200 healthy controls. The researchers also analyzed a separate group of 10 patients with CIS to compare them with the CIS patients in the study. Dr. Schutzer and colleagues performed protein separation and fractionation on the CSF samples and analyzed them with direct liquid chromatography–mass spectrometry.
Quantities of 20 Proteins Differed Among the Groups
The researchers found 20 proteins that were present in significantly different quantities in patients with CIS, patients with established relapsing-remitting MS, and controls. Nine of these proteins were significantly increased in patients with first-attack CIS, compared with the other two groups. Five proteins were significantly decreased in patients with first-attack CIS, compared with the other groups. The remaining proteins were increased in patients with CIS, compared with patients with relapsing-remitting MS, but decreased compared with controls. Fifteen of the 20 proteins were associated with gray matter.
“There is an increasing literature on the importance of gray matter, neuronal, and axonal involvement in MS, even at very early time points,” said Dr. Schutzer. “Our findings support this [hypothesis] and indicate that axonal, neuronal, and synaptic involvement may be required for the initial presentation of MS. It is interesting in this disease, which is characterized by demyelination as it progresses, that gray matter components may be diagnostically more useful than myelin components at the earliest stages,” he added.
—Erik Greb
Senior Associate Editor
Gray matter, rather than myelin, may be involved in the earliest stages of multiple sclerosis (MS), according to research published September 3 in PLOS One. Gray matter components (eg, axons, neurons, and synapses) may distinguish the CSF proteome of a patient with a true first attack of MS from those of healthy controls and patients with established relapsing-remitting MS.
Nogo receptor was markedly elevated in the CSF of patients with a true first attack of MS, compared with patients with established relapsing-remitting MS and controls, said Steven E. Schutzer, MD, Professor of Medicine at Rutgers University New Jersey Medical School in Newark. Patients with a first attack of MS also had a significant increase of contactin-2/TAG-1, an axonal glycoprotein, in their CSF. Contactin-2/TAG-1 has been reported as an autoimmune target in MS.
Researchers Analyzed CSF From Three Patient Groups
Previous imaging studies have suggested that gray matter changes, and not white matter changes, occur early and predict the development of MS. Other data have conflicted with this idea, however. To determine whether gray matter is involved in early MS, Dr. Schutzer and colleagues collected CSF from three groups of patients. The first group included nine patients with clinically isolated syndrome (CIS) who eventually met diagnostic criteria for MS. The second group included 12 patients with established diagnoses of relapsing-remitting MS according to the McDonald criteria. The third group included six control subjects with no apparent CNS disease.
For the purpose of comparison, the investigators used previously published protein lists generated from two groups of persons with other neurologic diseases and more than 200 healthy controls. The researchers also analyzed a separate group of 10 patients with CIS to compare them with the CIS patients in the study. Dr. Schutzer and colleagues performed protein separation and fractionation on the CSF samples and analyzed them with direct liquid chromatography–mass spectrometry.
Quantities of 20 Proteins Differed Among the Groups
The researchers found 20 proteins that were present in significantly different quantities in patients with CIS, patients with established relapsing-remitting MS, and controls. Nine of these proteins were significantly increased in patients with first-attack CIS, compared with the other two groups. Five proteins were significantly decreased in patients with first-attack CIS, compared with the other groups. The remaining proteins were increased in patients with CIS, compared with patients with relapsing-remitting MS, but decreased compared with controls. Fifteen of the 20 proteins were associated with gray matter.
“There is an increasing literature on the importance of gray matter, neuronal, and axonal involvement in MS, even at very early time points,” said Dr. Schutzer. “Our findings support this [hypothesis] and indicate that axonal, neuronal, and synaptic involvement may be required for the initial presentation of MS. It is interesting in this disease, which is characterized by demyelination as it progresses, that gray matter components may be diagnostically more useful than myelin components at the earliest stages,” he added.
—Erik Greb
Senior Associate Editor
Suggested Reading
Schutzer SE, Angel TE, Liu T, et al. Gray matter is targeted in first-attack multiple sclerosis. PLoS One. 2013;8(9):e66117.
Brink BP, Veerhuis R, Breij EC, et al. The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions. J Neuropathol Exp Neurol. 2005;64(2):147-155.
Huizinga R, Gerritsen W, Heijmans N, Amor S. Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments. Neurobiol Dis. 2008;32(3):461-470.
Suggested Reading
Schutzer SE, Angel TE, Liu T, et al. Gray matter is targeted in first-attack multiple sclerosis. PLoS One. 2013;8(9):e66117.
Brink BP, Veerhuis R, Breij EC, et al. The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions. J Neuropathol Exp Neurol. 2005;64(2):147-155.
Huizinga R, Gerritsen W, Heijmans N, Amor S. Axonal loss and gray matter pathology as a direct result of autoimmunity to neurofilaments. Neurobiol Dis. 2008;32(3):461-470.
COMMENTARY—The Principal Site of MS-Related Tissue Injury Remains Unclear
In a small but well-designed study, Schutzer et al used high-resolution mass spectrometry to compare CSF proteins in patients with clinically isolated syndrome (CIS) who eventually developed multiple sclerosis (MS), patients with established relapsing-remitting MS, and controls with no obvious neurologic disease. CSF proteins from patients with CIS were differentially enriched for gray matter components (eg, axons, neurons, and synapses), compared with other groups.
The prominence of gray matter CSF proteins early in MS evolution is not surprising. Sophisticated MRI techniques have allowed investigators to describe gray matter lesions as an early phenomenon in MS, and these lesions may even be more prominent than white matter lesions. Cerebral gray matter is active metabolically; it has greater blood flow, oxygen consumption, and tissue volume than white matter. Axonal pathology is an early and common finding in MS, even in apparently normal white matter, possibly because of immune-mediated inflammatory damage and associated Wallerian degeneration. In addition, gray matter MS pathology can be seen adjacent to meningeal inflammation, and oligodendrocytes and myelinated axons are present in gray matter. These findings are consistent with diffusion of CSF-reactive lymphocytes or their products into cerebral gray matter, and a similar mechanism may occur in white matter across the blood–brain barrier.
However, the concept that CSF gray matter proteins are more enriched in patients with CIS than in those with established MS comes as somewhat of a surprise. While patients with CIS have had only one clinically documented event, there are usually multiple brain lesions that are clinically silent but detected on MRI. These can be considered subclinical relapses because the lesions occur in less eloquent areas or are less destructive. Thus, one does not usually know with certainty when MS actually starts. In this regard, it would be interesting to obtain information on gray matter proteins after a second spinal tap in patients with CIS who later develop definite MS.
Lastly, although gray matter may be affected early in MS, there is insufficient evidence as to whether or not a gray matter protein is an autoimmune trigger in MS.
—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz Professor
of Neurology and Neurosciences
Rutgers, The State University of New Jersey, Newark
In a small but well-designed study, Schutzer et al used high-resolution mass spectrometry to compare CSF proteins in patients with clinically isolated syndrome (CIS) who eventually developed multiple sclerosis (MS), patients with established relapsing-remitting MS, and controls with no obvious neurologic disease. CSF proteins from patients with CIS were differentially enriched for gray matter components (eg, axons, neurons, and synapses), compared with other groups.
The prominence of gray matter CSF proteins early in MS evolution is not surprising. Sophisticated MRI techniques have allowed investigators to describe gray matter lesions as an early phenomenon in MS, and these lesions may even be more prominent than white matter lesions. Cerebral gray matter is active metabolically; it has greater blood flow, oxygen consumption, and tissue volume than white matter. Axonal pathology is an early and common finding in MS, even in apparently normal white matter, possibly because of immune-mediated inflammatory damage and associated Wallerian degeneration. In addition, gray matter MS pathology can be seen adjacent to meningeal inflammation, and oligodendrocytes and myelinated axons are present in gray matter. These findings are consistent with diffusion of CSF-reactive lymphocytes or their products into cerebral gray matter, and a similar mechanism may occur in white matter across the blood–brain barrier.
However, the concept that CSF gray matter proteins are more enriched in patients with CIS than in those with established MS comes as somewhat of a surprise. While patients with CIS have had only one clinically documented event, there are usually multiple brain lesions that are clinically silent but detected on MRI. These can be considered subclinical relapses because the lesions occur in less eloquent areas or are less destructive. Thus, one does not usually know with certainty when MS actually starts. In this regard, it would be interesting to obtain information on gray matter proteins after a second spinal tap in patients with CIS who later develop definite MS.
Lastly, although gray matter may be affected early in MS, there is insufficient evidence as to whether or not a gray matter protein is an autoimmune trigger in MS.
—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz Professor
of Neurology and Neurosciences
Rutgers, The State University of New Jersey, Newark
In a small but well-designed study, Schutzer et al used high-resolution mass spectrometry to compare CSF proteins in patients with clinically isolated syndrome (CIS) who eventually developed multiple sclerosis (MS), patients with established relapsing-remitting MS, and controls with no obvious neurologic disease. CSF proteins from patients with CIS were differentially enriched for gray matter components (eg, axons, neurons, and synapses), compared with other groups.
The prominence of gray matter CSF proteins early in MS evolution is not surprising. Sophisticated MRI techniques have allowed investigators to describe gray matter lesions as an early phenomenon in MS, and these lesions may even be more prominent than white matter lesions. Cerebral gray matter is active metabolically; it has greater blood flow, oxygen consumption, and tissue volume than white matter. Axonal pathology is an early and common finding in MS, even in apparently normal white matter, possibly because of immune-mediated inflammatory damage and associated Wallerian degeneration. In addition, gray matter MS pathology can be seen adjacent to meningeal inflammation, and oligodendrocytes and myelinated axons are present in gray matter. These findings are consistent with diffusion of CSF-reactive lymphocytes or their products into cerebral gray matter, and a similar mechanism may occur in white matter across the blood–brain barrier.
However, the concept that CSF gray matter proteins are more enriched in patients with CIS than in those with established MS comes as somewhat of a surprise. While patients with CIS have had only one clinically documented event, there are usually multiple brain lesions that are clinically silent but detected on MRI. These can be considered subclinical relapses because the lesions occur in less eloquent areas or are less destructive. Thus, one does not usually know with certainty when MS actually starts. In this regard, it would be interesting to obtain information on gray matter proteins after a second spinal tap in patients with CIS who later develop definite MS.
Lastly, although gray matter may be affected early in MS, there is insufficient evidence as to whether or not a gray matter protein is an autoimmune trigger in MS.
—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz Professor
of Neurology and Neurosciences
Rutgers, The State University of New Jersey, Newark
Observation-Status Patients Are Clinically Heterogeneous, Costly to Hospitals
Clinical question: What are the characteristics of a large cohort of patients under observation status?
Background: The use of observation hospital services has increased significantly. The Centers for Medicare and Medicaid Services (CMS) defines observation status as a “well-defined set of specific, clinically appropriate services,” usually lasting <24 hours and exceeding 48 hours in “only rare and exceptional cases.”
Study design: Retrospective descriptive study.
Setting: University of Wisconsin Hospital and Clinics, a 566-bed tertiary academic medical center.
Synopsis: A total of 43,853 hospitalizations were reviewed during the study period. Of those, 4578 (10.4%) were observation. The mean observation LOS was 33.3 hours, which included 16.5% of patients with LOS >48 hours. Although chest pain was the top observation diagnosis, 1141 distinct observation diagnosis codes were found.
These findings illustrate a significant disparity between the CMS definition for observation stay and the description of observation patients in this cohort, despite using CMS-endorsed InterQual criteria to determine status. While the cost per encounter for observation care was less than inpatient care, reimbursement was insufficient to cover those reduced costs. Ultimately, the net loss of revenue per observation encounter was $331, compared to a net gain in revenue per inpatient encounter of $2,163. This operating loss for hospitals is coupled with the fact that some of this cost is being transferred to patients.
Bottom line: Definitions and reimbursement models for observation status warrant continued research and discussion in the context of our evolving healthcare climate.
Citation: Sheehy AM, Graf B, Gangireddy S, et al. Hospitalized but not admitted: characteristics of patients with “observation status” at an academic medical center [published online ahead of print July 8, 2013]. JAMA Intern Med.
Clinical question: What are the characteristics of a large cohort of patients under observation status?
Background: The use of observation hospital services has increased significantly. The Centers for Medicare and Medicaid Services (CMS) defines observation status as a “well-defined set of specific, clinically appropriate services,” usually lasting <24 hours and exceeding 48 hours in “only rare and exceptional cases.”
Study design: Retrospective descriptive study.
Setting: University of Wisconsin Hospital and Clinics, a 566-bed tertiary academic medical center.
Synopsis: A total of 43,853 hospitalizations were reviewed during the study period. Of those, 4578 (10.4%) were observation. The mean observation LOS was 33.3 hours, which included 16.5% of patients with LOS >48 hours. Although chest pain was the top observation diagnosis, 1141 distinct observation diagnosis codes were found.
These findings illustrate a significant disparity between the CMS definition for observation stay and the description of observation patients in this cohort, despite using CMS-endorsed InterQual criteria to determine status. While the cost per encounter for observation care was less than inpatient care, reimbursement was insufficient to cover those reduced costs. Ultimately, the net loss of revenue per observation encounter was $331, compared to a net gain in revenue per inpatient encounter of $2,163. This operating loss for hospitals is coupled with the fact that some of this cost is being transferred to patients.
Bottom line: Definitions and reimbursement models for observation status warrant continued research and discussion in the context of our evolving healthcare climate.
Citation: Sheehy AM, Graf B, Gangireddy S, et al. Hospitalized but not admitted: characteristics of patients with “observation status” at an academic medical center [published online ahead of print July 8, 2013]. JAMA Intern Med.
Clinical question: What are the characteristics of a large cohort of patients under observation status?
Background: The use of observation hospital services has increased significantly. The Centers for Medicare and Medicaid Services (CMS) defines observation status as a “well-defined set of specific, clinically appropriate services,” usually lasting <24 hours and exceeding 48 hours in “only rare and exceptional cases.”
Study design: Retrospective descriptive study.
Setting: University of Wisconsin Hospital and Clinics, a 566-bed tertiary academic medical center.
Synopsis: A total of 43,853 hospitalizations were reviewed during the study period. Of those, 4578 (10.4%) were observation. The mean observation LOS was 33.3 hours, which included 16.5% of patients with LOS >48 hours. Although chest pain was the top observation diagnosis, 1141 distinct observation diagnosis codes were found.
These findings illustrate a significant disparity between the CMS definition for observation stay and the description of observation patients in this cohort, despite using CMS-endorsed InterQual criteria to determine status. While the cost per encounter for observation care was less than inpatient care, reimbursement was insufficient to cover those reduced costs. Ultimately, the net loss of revenue per observation encounter was $331, compared to a net gain in revenue per inpatient encounter of $2,163. This operating loss for hospitals is coupled with the fact that some of this cost is being transferred to patients.
Bottom line: Definitions and reimbursement models for observation status warrant continued research and discussion in the context of our evolving healthcare climate.
Citation: Sheehy AM, Graf B, Gangireddy S, et al. Hospitalized but not admitted: characteristics of patients with “observation status” at an academic medical center [published online ahead of print July 8, 2013]. JAMA Intern Med.
Early Surgery Might Not Provide Survival Benefit in All Patients with Prosthetic Valve Endocarditis
Clinical question: Is early surgery associated with better survival in patients with prosthetic valve endocarditis (PVE)?
Background: PVE occurs in 3% to 6% of patients within five years of valve implantation. Consensus guidelines, based on expert opinion, recommend surgical intervention with debridement and valve replacement in PVE, especially for patients with complications that are unlikely to be successfully treated with medical therapy, such as valve dysfunction, heart failure, and cardiac abscesses. Studies comparing survival with medical therapy versus surgery have reported conflicting results.
Study Design: Multi-center, prospective, cohort study.
Setting: International, multi-center cohort of patients from tertiary care hospitals.
Synopsis: The International Collaboration on Endocarditis—Prospective Cohort Study (ICE-PCS) cohort consisted of 1025 patients with PVE, 490 of whom underwent early surgery and 535 of whom received medical therapy alone.
Unadjusted initial analysis showed early surgery was associated with lower mortality; however, this survival benefit was not evident after the data was adjusted for treatment selection bias and survivor bias for in-hospital mortality and one-year mortality. The hazard ratios were 0.9 (95% CI 0.76 -1.07) and 1.04 (95% CI 0.89 -1.23), respectively.
Subgroup analysis indicated that early surgery in patients with high-risk features was associated with fewer poor outcomes compared to medical therapy: 28% versus 50% (P=.007)
Bottom line: Early surgery may not be associated with mortality benefits for PVE. High-risk patients, however, still might benefit from early surgery.
Citation: Lalani T, Chu VH, Park LP, et al. In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis. JAMA Intern Med. 2013:173:1495-1504.
Clinical question: Is early surgery associated with better survival in patients with prosthetic valve endocarditis (PVE)?
Background: PVE occurs in 3% to 6% of patients within five years of valve implantation. Consensus guidelines, based on expert opinion, recommend surgical intervention with debridement and valve replacement in PVE, especially for patients with complications that are unlikely to be successfully treated with medical therapy, such as valve dysfunction, heart failure, and cardiac abscesses. Studies comparing survival with medical therapy versus surgery have reported conflicting results.
Study Design: Multi-center, prospective, cohort study.
Setting: International, multi-center cohort of patients from tertiary care hospitals.
Synopsis: The International Collaboration on Endocarditis—Prospective Cohort Study (ICE-PCS) cohort consisted of 1025 patients with PVE, 490 of whom underwent early surgery and 535 of whom received medical therapy alone.
Unadjusted initial analysis showed early surgery was associated with lower mortality; however, this survival benefit was not evident after the data was adjusted for treatment selection bias and survivor bias for in-hospital mortality and one-year mortality. The hazard ratios were 0.9 (95% CI 0.76 -1.07) and 1.04 (95% CI 0.89 -1.23), respectively.
Subgroup analysis indicated that early surgery in patients with high-risk features was associated with fewer poor outcomes compared to medical therapy: 28% versus 50% (P=.007)
Bottom line: Early surgery may not be associated with mortality benefits for PVE. High-risk patients, however, still might benefit from early surgery.
Citation: Lalani T, Chu VH, Park LP, et al. In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis. JAMA Intern Med. 2013:173:1495-1504.
Clinical question: Is early surgery associated with better survival in patients with prosthetic valve endocarditis (PVE)?
Background: PVE occurs in 3% to 6% of patients within five years of valve implantation. Consensus guidelines, based on expert opinion, recommend surgical intervention with debridement and valve replacement in PVE, especially for patients with complications that are unlikely to be successfully treated with medical therapy, such as valve dysfunction, heart failure, and cardiac abscesses. Studies comparing survival with medical therapy versus surgery have reported conflicting results.
Study Design: Multi-center, prospective, cohort study.
Setting: International, multi-center cohort of patients from tertiary care hospitals.
Synopsis: The International Collaboration on Endocarditis—Prospective Cohort Study (ICE-PCS) cohort consisted of 1025 patients with PVE, 490 of whom underwent early surgery and 535 of whom received medical therapy alone.
Unadjusted initial analysis showed early surgery was associated with lower mortality; however, this survival benefit was not evident after the data was adjusted for treatment selection bias and survivor bias for in-hospital mortality and one-year mortality. The hazard ratios were 0.9 (95% CI 0.76 -1.07) and 1.04 (95% CI 0.89 -1.23), respectively.
Subgroup analysis indicated that early surgery in patients with high-risk features was associated with fewer poor outcomes compared to medical therapy: 28% versus 50% (P=.007)
Bottom line: Early surgery may not be associated with mortality benefits for PVE. High-risk patients, however, still might benefit from early surgery.
Citation: Lalani T, Chu VH, Park LP, et al. In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis. JAMA Intern Med. 2013:173:1495-1504.