Associations between knee extensor power and functional performance in patients after total knee arthroplasty and normal controls without knee pain.

PURPOSE/BACKGROUND: Deficits in functional abilities persist after total knee arthroplasty (TKA), while static measures of knee extensor strength (e.g. isometric contractions) are related to functional performance, little is known about the associations between functional ability and dynamic knee extensor strength (e.g. power). With the growing rate of these procedures, in a progressively younger and more active cohort, a better understanding of the functional importance of dynamic strength (muscle power) is needed. The purpose of this study was to examine the associations between functional performance and peak knee extensor power (isokinetic and isotonic measures) from patients after unilateral TKA. DESIGN: Cross-sectional, controlled laboratory study, with correlation and regression analyses. SETTING: Institutional clinic and research laboratory. PARTICIPANTS: Patients 6 months after TKA (N=24, 12 men and women), most of whom were mildly to very active. A normal control group without knee pain (CON; N=22, 10 men and 12 women) was also assessed for comparison. MAIN OUTCOME MEASURES: Static and dynamic strength measures were assessed during normalized voluntary isometric contractions (NMVIC), isokinetic contractions at three velocities (60, 90, and 120 deg/s), and isotonic contractions against three body weight normalized resistances (20, 30 and 40% BW). Functional performance was assessed using the timed up-and-go (TUG), stair climbing test (SCT), and 6- minute walk (6MW). Analyses of the relationships between functional performance measures and peak knee extensor NMVIC and power were performed. Regression analyses predicting functional performance from power were also performed after controlling for NMVIC. RESULTS: Peak power across isokinetic velocities, isotonic resistances, and NMVICs were correlated with the functional performance measures for the TKA group. Unlike the TKA group, functional performance was not significantly associated with peak power across all isokinetic velocities and isotonic resistances (e.g no significant associations between peak isotonic power and 6MW distance). In the TKA group, inclusion of the isotonic power against 30% BW, after controlling for NMVIC, improved the predictability of all three functional performance tests; TUG (p= 0.022), SCT (p=0.006), and 6MW (p=0.001). CONCLUSIONS: Measurements of knee extensor power may be a useful tool for clinicians when assessing and setting milestones during rehabilitation. LEVEL OF EVIDENCE: Prospective cohort study, level II.

Online support for employed informal caregivers: psychosocial outcomes.

The overall objectives of this project were to evaluate whether psychosocial outcomes in employed family caregivers of people with chronic disease, who participate in online support, differ from nonactive participants and whether psychosocial outcomes differ based on the format of online group support. A randomized longitudinal design comparing two types of online support groups and nonactive participants, on the basis of three principal measures, was utilized. Eighty-six self-reported family caregivers of people with chronic disease, who spoke English and had Internet access, took part in the study. Subjects were randomly assigned to professionally facilitated/psychoeducational or moderated/peer-directed online support groups for a period of 12 weeks. The setting was a password-protected Web page housed on a university server. Independent variables were type of online support groups and level of participation; the dependent variables were depressive symptoms, caregiver burden, and caregiver quality of life. There were significant differences in depressive symptoms and quality of life among nonactive participants and either of the two intervention groups, but not between the two intervention groups. Results suggest that professionally facilitated/psychoeducational and moderated/peer-directed online support groups help reduce depressive symptoms and improve quality of life for those who actively participate and that both types of online support groups provided similar benefits. Men and minorities should be targeted in future caregiver research.

A comparative study of two nebulizers in the emergency department: breath-actuated nebulizer and handheld nebulizer.

INTRODUCTION: The breath-actuated nebulizer (BAN) and the handheld nebulizer (HHN) are 2 nebulizers used in the ED of Cooper University Hospital. The purpose of this study was to compare the nebulizers to identify which device resulted in a resolution of symptoms with fewer treatments. The primary hypothesis was that adult ED patients with a chief complaint of wheezing and dyspnea who were given nebulized treatments via the BAN would require less nebulizer treatments than those patients given nebulized treatments via HHN. In addition, the secondary purposes of the study was to determine if the BAN would have significantly higher peak expiratory flow measurements, lower Modified Borg Score, overall decreased respiratory rate, and lower heart rates compared to subjects receiving nebulized treatments via HHN. METHODS: A single-site, prospective, randomized, comparative design study was conducted in the ED between March 2010 and February 2011. Fifty-four subjects presenting with dyspnea and wheezing and an Emergency Severity Index of 3 or 4 were enrolled and randomly assigned to 1 of 2 groups (BAN or HHN). Subjects were administered 1 to 3 nebulizer treatments (#1 ipratropium bromide and albuterol sulfate, #2 ipratropium bromide and albuterol sulfate, #3 albuterol sulfate), which was consistent with the ED Advanced Nursing Guideline for Wheezing. Nebulizer treatments were discontinued if a patient's dyspnea or wheezing resolved. IRB approval was obtained prior to study commencement. RESULTS: There was no significant difference found between the HHN and BAN in respect to number of treatments, respiratory rate, peak flow measurements, and Modified Borg scores in the 54 subjects. There was a difference of 7 points in pulse rate between the pre- and post-second BAN treatment (n = 51, P = 0.01). Subjects in the BAN group who completed all 3 treatments (n = 18) had a total treatment time that was on average of 10 minutes longer than those in the HHN group. CONCLUSIONS: This study demonstrated no clinical difference between the BAN and HHN in terms of respiratory rate, peak flow, perception of dyspnea, and number of treatments. It is possible that the longer treatment times account for the elevated pulse rate. The data suggests that the higher cost and the longer treatment time do not justify the use of the BAN in this setting. We recommend that these devices be tested with a larger sample size to further test the differences between these 2 devices.

The NT-ProBNP Test in Subjects with End-Stage Renal Disease on Hemodialysis Presenting with Acute Dyspnea: Is Knowing Worth the Cost?

Background. The NT-ProBNP/BNP test has been validated as a marker for determining the etiology of acute dyspnea. In the setting of end-stage renal disease on hemodialysis (ESRD on HD), the utility of the NT-ProBNP/BNP test has not been validated. This study examines the clinical utility of the NT-ProBNP test in the setting of ESRD on HD patients presenting with acute dyspnea. Methods. A retrospective case series of 250 subjects were admitted to Cooper University Hospital, 07/2010-03/2011, with ESRD and HD presenting with dyspnea. The incidences of echocardiography, cardiology consultation, and NT-ProBNP elevated and normal were examined. Correlation coefficients were calculated for NT-ProBNP with age (years), estimated dry weight (kg), amount of fluid removed (L), and ejection fraction (EF in %) among other echocardiography parameters. Results. Of the total sample 235 patients had NT-ProBNP levels performed. Cardiology consults were placed in 68.8% and 58% who underwent echocardiography. Of those for whom an echocardiography was performed estimated mean EFs of 54.6%, 50.8%, and 61.7% were observed among the NT-ProBNP elevated group, normal group, and no NT-ProBNP group, respectively. No differences were detected in all other echocardiography measurements. No correlation was observed between NT-ProBNP and age (r = 0.05), baseline EDW (r = -0.09), amount of fluid removed (r = 0.07), or EF (r = 0.02). Conclusion. In the setting of ESRD on HD, the NT-ProBNP test has no clinical utility in determining the etiology of acute dyspnea. This can be demonstrated through echocardiographic and therapeutic parameters measured in this study.

Prevalence and impact of anemia in hospitalized patients.

OBJECTIVE: The prevalence of anemia is increasing in the general population similarly to other comorbidities and is associated with high mortality in a variety of settings. Most studies, however, have analyzed older adults or specific comorbidities, and the independent impact of anemia on outcomes in a general population of hospitalized patients has not been clearly defined. METHODS: Retrospective analysis of a medical records database of all consecutive patient discharges (aged 18 years or older) admitted to our institution from January 1, 1999 through December 31, 2008. RESULTS: A total of 179,516 admissions were included. Of these, 18,589 patients were diagnosed as having anemia (10.4%). There were 123,586 patients younger than 65 years. The prevalence of anemia among all of the discharges was characterized by a significant linear increase across the 10-year time frame, from 8.7% (1999) to 12.8% (2008), as was the average number of comorbidities. Over time, anemic patients were characterized by increasing comorbidity. Anemia was significantly associated with mortality (6.5% vs 2.5%; P < 0.001, odds ratio 2.68). This association remained significant after additional adjustment for demographic characteristics and comorbidities. The risk of mortality was significantly higher in patients younger than 65 years than it was in patients older than 65 (odds ratio 3.2 vs 2.1, respectively). CONCLUSIONS: The prevalence of anemia increased during a 10-year time frame, as did the average number of associated comorbid conditions. With adjustment for time, demographic factors, and additional comorbidities, anemia remained independently associated with mortality. This association was stronger in younger patients.

A Curriculum to Improve Residents' End-of-Life Communication and Pain Management Skills During Pediatrics Intensive Care Rotation: Pilot Study.

BACKGROUND: Research suggests pediatrics practitioners lack confidence and skills in the end-of-life (EOL) care. OBJECTIVE: This pilot study explored the impact of a curriculum designed to prepare future pediatricians to manage pain and provide comfort for children and infants with life-threatening conditions and to be more confident and competent in their EOL discussions with families. METHODS: Participants included 8 postgraduate year (PGY)-2 residents in the study group and 9 PGY-3 residents in a control group. The EOL curriculum included 4, 1-hour sessions consisting of didactic lectures, videos, and small-group, interactive discussions. Topics included discussing EOL with families, withdrawal of care, and pain assessment and management. Curriculum evaluation used an objective structured clinical examination (OSCE), self-assessment confidence and competency questionnaire, and a follow-up survey 18 months after the intervention. RESULTS: The OSCE showed no statistically significant differences between PGY-2 versus PGY-3 residents in discussing EOL issues with family (mean  =  48.3 [PGY-2] versus 41.0 [PGY-3]), managing withdrawal of care (mean  =  20.9 [PGY-2] versus 18.91 [PGY-3]), and managing adolescent pain (mean  =  30.97 [PGY-2] versus 29.27 [PGY-3]). The self-assessment confidence and competency scores improved significantly after the intervention for both PGY-2 residents (0.62 versus 0.86, P < .01) and PGY-3 residents (0.61 versus 0.85, P < .01). CONCLUSIONS: An EOL curriculum for PGY-2 pediatrics residents delivered during the intensive care unit rotation is feasible and may be effective. Residents reported the curriculum was useful in their practice.

Therapeutic hypothermia and vasopressor dependency after cardiac arrest.

OBJECTIVE: Clinical trials of therapeutic hypothermia (TH) after cardiac arrest excluded patients with persistent hemodynamic instability after return of spontaneous circulation (ROSC), and thus equipoise may exist regarding use of TH in these patients. Our objective was to determine if TH is associated with worsening hemodynamic instability among patients who are vasopressor-dependent after ROSC. METHODS: We performed a prospective observational study in vasopressor-dependent post-cardiac arrest patients. Inclusion criteria were age >17, non-trauma cardiac arrest, comatose after ROSC, and persistent vasopressor dependence. The decision to initiate TH (33-34 ° C) was made by the treating physician. We measured cumulative vasopressor index (CVI) and mean arterial pressure (MAP) every 15 min during the first 6h after ROSC. The outcome measures were change in CVI (primary outcome) and MAP (secondary outcome) over time. We graphed median CVI and MAP over time for the treated and not treated cohorts, and used propensity adjusted repeated measures mixed models to test for an association between TH induction and change in CVI or MAP over time. RESULTS: Seventy-five post-cardiac arrest patients were included (35 treated; 40 not treated). We observed no major differences in CVI or MAP over time between the treated and not treated cohorts. In the mixed models we found no statistically significant association between TH induction and changes in CVI or MAP. CONCLUSION: In patients with vasopressor-dependency after cardiac arrest, the induction of hypothermia was not associated with a decrease in mean arterial pressure or increase in vasopressor requirement.

Increased prevalence of temporary cardiac pacing in people with epilepsy.

INTRODUCTION: Even though ictal tachyarrhythmias are more common, ictal brady-asystole is more likely to be fatal, and yet is potentially preventable with pacemaker (PM) implantation. We sought to quantify the degree of association of PM placement in people with and without epilepsy, including neurological and cardiovascular cohorts. METHODS: Retrospective cross-sectional analysis of the National Hospital Discharge database using International Classification of Diseases Clinical Modification (ICD-9-CM) codes. We identified people with and without epilepsy between 1990 and 2006. The epilepsy cohort was compared to patients without epilepsy and other cardiovascular and central nervous system (CNS) disease cohorts. RESULTS: People with epilepsy had higher odds of temporary PM (TPM; OR 1.6) than patients without epilepsy, especially amongst males (OR 2.0), young- (OR 4.6) and middle-aged (OR 4.3) patients. The epilepsy cohort had significantly higher odds of TPM than demyelinating disease (OR 7.9) and migraine (OR 9.1) cohorts. Compared to stroke, people with epilepsy had higher odds of TPM in the male (OR 1.6) and middle-age (OR 2.4) subgroups. No significant association was seen with permanent PM (PPM). CONCLUSIONS: Our study demonstrates the high likelihood of TPM placement in epilepsy patients as compared to cohorts without epilepsy. Significant associations were seen especially in males and young- and middle-aged patients. Since demyelinating and migraine cohorts are somewhat similar to epilepsy patients in age and sex characteristics, the higher odds of TPM in epilepsy patients may be related to the disease mechanism causing brady-asystole; however this requires further study.

Removal of industry-sponsored formula sample packs from the hospital: does it make a difference?

BACKGROUND: Most US hospitals distribute industry-sponsored formula sample packs. No research has examined outcomes associated with sample pack removal as part of a hospital intervention to eliminate sample distribution postpartum. OBJECTIVE: To examine prospectively hospital-based and breastfeeding outcomes associated with removal of industry-sponsored formula sample packs from the hospital. METHODS: We enrolled mothers postpartum at Cooper University Hospital, an urban New Jersey hospital, in 2009-2010. For the first 6 months, all women received industry-sponsored formula samples packs (control group); for the next 6 months, all postpartum women received hospital-sponsored bags with no formula at source (intervention group). Research assistants blinded to the design called subjects weekly for 10 weeks to determine feeding practices. RESULTS: We enrolled 527 breastfeeding women (284 control; 243 intervention). At 10 weeks postpartum, 82% of control and 36% of intervention women (P < .001) reported receiving formula in the "diaper discharge bag." Kaplan-Meyer curves for any breastfeeding showed the intervention was associated with increased breastfeeding (P = .03); however, exclusive breastfeeding was not significantly different between intervention and controls (P = .46). In post hoc analysis, receiving no take-home formula in bottles from the hospital was associated with increased exclusive breastfeeding in control (P = .02) and intervention (P = .03) groups at 10 weeks. CONCLUSION: Although the hospital-branded replacement contained no formula at source, many women reported receiving bottles of formula from the hospital. Change in practice to remove industry-sponsored formula sample packs was associated with increased breastfeeding over 10 weeks, but the intervention may have had a greater impact had it not been contaminated.

Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced, nonsquamous nonsmall cell lung cancer.

BACKGROUND: The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer. METHODS: Previously untreated patients with advanced, nonsquamous nonsmall cell lung cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 received bevacizumab 15 mg/kg, pemetrexed 500 mg/m(2) and carboplatin at an area under the concentration-time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression. RESULTS: In total, 43 patients (40 who were evaluable for response) were entered on the study. Treatment-related grade 3/4 toxicities were low and included febrile neutropenia (2%), neutropenia (28%), anemia (18%), thrombocytopenia (11%), hypertension (7%), epistaxis (5%), venous thrombosis (8%), dyspnea (7%), rectovaginal fistula (2.3%), infusion reaction (2%), and cerebrovascular event (2%). One patient died from complications of venous thromboembolism and cerebrovascular accident after Cycle 2. Minimal clinically significant toxicity occurred during maintenance bevacizumab. Two complete responses (5%) were observed, and 17 patients (42%) had a partial response. Fifteen patients (38%) displayed disease stability. The overall disease control rate was 85%. At a median follow-up of 15.8 months, the median progression-free survival was 7.1 months (95% confidence interval, 5.9-8.3 months), and the median overall survival was 17.1 months (95% confidence interval, 8.8-25.5 months). CONCLUSIONS: Combined bevacizumab, pemetrexed, and carboplatin followed by maintenance bevacizumab was well tolerated and displayed remarkable activity in patients with previously untreated, advanced, nonsquamous nonsmall cell lung cancer.

Betamethasone dosing interval: 12 or 24 hours apart? A randomized, noninferiority open trial.

OBJECTIVE: We sought to determine whether the incidence of neonatal respiratory distress syndrome (RDS) is similar with 12- vs 24-hour dosing interval of betamethasone. STUDY DESIGN: This was a prospective, randomized, open, noninferiority trial. Mothers (n = 228) with a singleton or multiple pregnancies (fetuses = 260), between gestational age of 23-34 weeks, at risk for preterm delivery, received standard 2 doses of betamethasone either 12 or 24 hours apart in 2:1 ratio, respectively. RESULTS: Incidence of RDS was similar in the 2 cohorts (36.5% vs 37.3%; P = not significant). Women unable to receive the complete course of corticosteroids with the 24-hour interval can be reduced by half with the 12-hour interval. However, increased incidence of necrotizing enterocolitis was seen with 12-hour dosing (6.2% vs 0%; P = .03). CONCLUSION: The 12-hour dosing interval is equivalent to the 24-hour dosing interval for prevention of RDS in neonates of mothers delivering prematurely. A larger multicenter study is needed to confirm our findings.

The impact of hospitalists on length of stay and costs: systematic review and meta-analysis.

BACKGROUND: Hospital medicine has undergone remarkable growth since its creation. Most (but not all) of the published literature demonstrates better outcomes for patients cared for by hospitalists. PURPOSE: We performed a systematic review and meta-analysis to estimate the magnitude of the impact of hospitalists on length of stay (LOS) and cost. DATA SOURCES: Medline/PubMed. STUDY SELECTION: Articles published through February 2011 comparing outcomes (LOS and/or cost) of hospitalists with others. DATA EXTRACTION: Two reviewers independently searched for abstracted information. We also contacted individual authors to provide us with missing data. DATA SYNTHESIS: We used a random-effects model. RESULTS: A total of 502 abstracts were initially identified and 17 studies of 137,561 patients were included in the final analysis. LOS was significantly shorter in the hospitalist group compared with the non-hospitalist group, with a mean difference of -0.44 days (95% confidence interval [CI] -0.68 to -0.20, P < .001). In studies that compared a (non-resident) hospitalist service with a (non-resident) non-hospitalist service, LOS was also significantly shorter in the hospitalist group (mean difference -0.69 days [95% CI -0.93 to -0.46, P < .001]). Cost was not found to be significantly different (11 studies). There was significant heterogeneity between studies and we found no evidence of publication bias. CONCLUSIONS: Despite its limitations, our analysis supports the conclusion that hospitalists significantly reduce LOS without increasing costs. These findings can be used to define and measure expectations of performance for hospital medicine groups.

The fallacy of the BUN:creatinine ratio in critically ill patients.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) is common in critically ill patients and is associated with a high mortality rate. Pre-renal azotemia, suggested by a high blood urea nitrogen to serum creatinine (BUN:Cr) ratio (BCR), has traditionally been associated with a better prognosis than other forms of AKI. Whether this pertains to critically ill patients is unknown. METHODS: We conducted a retrospective observational study of two cohorts of critically ill patients admitted to a single center: a derivation cohort, in which AKI was diagnosed, and a larger validation cohort. We analyzed associations between BCR and clinical outcomes: mortality and renal replacement therapy (RRT). RESULTS: Patients in the derivation cohort (N = 1010) with BCR >20 were older, predominantly female and white, and more severely ill. A BCR >20 was significantly associated with increased mortality and a lower likelihood of RRT in all patients, patients with AKI and patients at risk for AKI. Patients in the validation cohort (N = 10 228) with a BCR >20 were older, predominantly female and white, and more severely ill. A BCR >20 was associated with increased mortality and a lower likelihood of RRT in all patients and in those at risk for AKI, BUN correlated with age and severity of illness. CONCLUSIONS: A BCR >20 is associated with increased mortality in critically ill patients. It is also associated with a lower likelihood of RRT, perhaps because of misinterpretation of the BCR. Clinicians should not use a BCR >20 to classify AKI in critically ill patients.

Does the urgency of endoscopic retrograde cholangiopancreatography (ercp)/percutaneous biliary drainage (pbd) impact mortality and disease related complications in ascending cholangitis? (deim-i study).

BACKGROUND: The Tokyo Guidelines have greatly impacted the management of ascending cholangitis. Though ERCP is the favored modality for biliary decompression, no evidence exists for the timing of ERCP. The DEIM-I study set out to determine if the time from patient presentation to biliary decompression impacted in hospital all cause mortality in ascending cholangitis. METHOD: DEIM-I cohort study was a single-blinded and consisted of 250 subjects with moderate to severe ascending cholangitis who underwent ERCP/PBD. Subjects were randomized into quartiles based upon time from presentation until ERCP/PBD. The primary outcome utilized logistic regression to estimate relative risk (RR) of all cause, in hospital mortality with time to procedure as the predictive covariate. Secondary outcomes were analyzed using multivariate logistic regression and included; multiple organ failure (MOF), sepsis, systemic inflammatory response syndrome (SIRS), surgical incidence, hospital readmission and length of stay (LOS). RESULTS: The risk for hospital mortality was significantly less when biliary drainage was performed within 11 h, compared to >42 h (RR 0.34, 95%CI 0.12 to 0.99, p=0.049). Hospital readmission was lower in subjects who underwent biliary decompression less than 11 h, when compared to those greater than 22 h. Subjects who underwent biliary decompression within 21 h had significant higher risk for surgery compared to those 22-42 h. CONCLUSION: The relative risk of all cause in hospital mortality was lower in subjects who underwent biliary decompression in under 11 h compared to greater than 42 h.

Relationship between supranormal oxygen tension and outcome after resuscitation from cardiac arrest.

BACKGROUND: Laboratory and recent clinical data suggest that hyperoxemia after resuscitation from cardiac arrest is harmful; however, it remains unclear if the risk of adverse outcome is a threshold effect at a specific supranormal oxygen tension, or is a dose-dependent association. We aimed to define the relationship between supranormal oxygen tension and outcome in postresuscitation patients. METHODS AND RESULTS: This was a multicenter cohort study using the Project IMPACT database (intensive care units at 120 US hospitals). Inclusion criteria were age >17 years, nontrauma, cardiopulmonary resuscitation preceding intensive care unit arrival, and postresuscitation arterial blood gas obtained. We excluded patients with hypoxia or severe oxygenation impairment. We defined the exposure by the highest partial pressure of arterial oxygen (PaO(2)) over the first 24 hours in the ICU. The primary outcome measure was in-hospital mortality. We tested the association between PaO(2) (continuous variable) and mortality using multivariable logistic regression adjusted for patient-oriented covariates and potential hospital effects. Of 4459 patients, 54% died. The median postresuscitation PaO(2) was 231 (interquartile range 149 to 349) mm Hg. Over ascending ranges of oxygen tension, we found significant linear trends of increasing in-hospital mortality and decreasing survival as functionally independent. On multivariable analysis, a 100 mm Hg increase in PaO(2) was associated with a 24% increase in mortality risk (odds ratio 1.24 [95% confidence interval 1.18 to 1.31]. We observed no evidence supporting a single threshold for harm from supranormal oxygen tension. CONCLUSION: In this large sample of postresuscitation patients, we found a dose-dependent association between supranormal oxygen tension and risk of in-hospital death.

Down-regulation of OPA1 in patients with primary open angle glaucoma.

PURPOSE: Heterozygous optic atrophy type1 (OPA1) mutations are responsible for dominant optic atrophy, and the down regulation of OPA1 expression in patients with Leber hereditary optic neuropathy may imply that Opa1 protein levels in mitochondria play a role in other spontaneous optic neuropathies as well. Mitochondrial and metabolic abnormalities may put the optic nerve at risk in primary open angle glaucoma (POAG), and this preliminary study was designed to investigate whether altered OPA1 expression might be present in the progressive optic neuropathy of POAG. METHODS: Patients were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure ≥ 21 mmHg in at least one eye before treatment, normal-appearing anterior chamber angles bilaterally on gonioscopy, and optic nerve injury characteristic of POAG. RNA was extracted from leukocytes and converted to cDNA by reverse transcriptase enzyme, and real time PCR was used to assess expression levels of OPA1 and the ß-globulin (HBB) housekeeping gene. The ratio of OPA1 expression to HBB expression (OPA1/HBB) for POAG patients was compared to that of controls and to clinical characteristics of POAG patients. RESULTS: Forty-three POAG patients and 27 controls were completely phenotyped with a full ophthalmologic examination and static perimetry. Mean age (POAG 67.9 years; controls 61.8 years) and sex (POAG 26 males/17 females; controls 11/16) were similar for the two groups. Mean OPA1/HBB of POAG patients (1.16, SD 0.26) was 18% lower than controls (1.41, SD 0.50), and this difference was statistically significant (p≤0.021). OPA1 expression differed between the groups (p≤0.037), but HBB expression did not differ (p≤0.24). OPA1/HBB was not correlated with any clinical feature of POAG patients. CONCLUSIONS: Transcriptional analysis of peripheral blood leucocytes is a limited model system for studying the consequences of mitochondrial abnormalities in the optic nerve. Nevertheless, OPA1 is known to affect mitochondrial stability and has now been implicated in several spontaneous optic neuropathies. Decreased OPA1 expression in POAG patients is another indication that mitochondrial function, and possibly mitochondrially-induced apoptosis, may play a role in the development of POAG.

Residency curriculum improves breastfeeding care.

OBJECTIVES: Multiple studies have revealed inadequacies in breastfeeding education during residency, and results of recent studies have confirmed that attitudes of practicing pediatricians toward breastfeeding are deteriorating. In this we study evaluated whether a residency curriculum improved physician knowledge, practice patterns, and confidence in providing breastfeeding care and whether implementation of this curriculum was associated with increased breastfeeding rates in patients. SUBJECTS AND METHODS: A prospective cohort of 417 residents was enrolled in a controlled trial of a novel curriculum developed by the American Academy of Pediatrics in conjunction with experts from the American College of Obstetricians and Gynecologists, American Academy of Family Physicians, and Association of Pediatric Program Directors. Six intervention residency programs implemented the curriculum, whereas 7 control programs did not. Residents completed pretests and posttests before and after implementation. Breastfeeding rates were derived from randomly selected medical charts in hospitals and clinics at which residents trained. RESULTS: Trained residents were more likely to show improvements in knowledge (odds ratio [OR]: 2.8 [95% confidence interval (CI): 1.5-5.0]), practice patterns related to breastfeeding (OR: 2.2 [95% CI: 1.3-3.7]), and confidence (OR: 2.4 [95% CI: 1.4-4.1]) than residents at control sites. Infants at the institutions in which the curriculum was implemented were more likely to breastfeed exclusively 6 months after intervention (OR: 4.1 [95% CI: 1.8-9.7]). CONCLUSIONS: A targeted breastfeeding curriculum for residents in pediatrics, family medicine, and obstetrics and gynecology improves knowledge, practice patterns, and confidence in breastfeeding management in residents and increases exclusive breastfeeding in their patients. Implementation of this curriculum may similarly benefit other institutions.

Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality.

CONTEXT: Laboratory investigations suggest that exposure to hyperoxia after resuscitation from cardiac arrest may worsen anoxic brain injury; however, clinical data are lacking. OBJECTIVE: To test the hypothesis that postresuscitation hyperoxia is associated with increased mortality. DESIGN, SETTING, AND PATIENTS: Multicenter cohort study using the Project IMPACT critical care database of intensive care units (ICUs) at 120 US hospitals between 2001 and 2005. Patient inclusion criteria were age older than 17 years, nontraumatic cardiac arrest, cardiopulmonary resuscitation within 24 hours prior to ICU arrival, and arterial blood gas analysis performed within 24 hours following ICU arrival. Patients were divided into 3 groups defined a priori based on PaO(2) on the first arterial blood gas values obtained in the ICU. Hyperoxia was defined as PaO(2) of 300 mm Hg or greater; hypoxia, PaO(2) of less than 60 mm Hg (or ratio of PaO(2) to fraction of inspired oxygen <300); and normoxia, not classified as hyperoxia or hypoxia. MAIN OUTCOME MEASURE: In-hospital mortality. RESULTS: Of 6326 patients, 1156 had hyperoxia (18%), 3999 had hypoxia (63%), and 1171 had normoxia (19%). The hyperoxia group had significantly higher in-hospital mortality (732/1156 [63%; 95% confidence interval {CI}, 60%-66%]) compared with the normoxia group (532/1171 [45%; 95% CI, 43%-48%]; proportion difference, 18% [95% CI, 14%-22%]) and the hypoxia group (2297/3999 [57%; 95% CI, 56%-59%]; proportion difference, 6% [95% CI, 3%-9%]). In a model controlling for potential confounders (eg, age, preadmission functional status, comorbid conditions, vital signs, and other physiological indices), hyperoxia exposure had an odds ratio for death of 1.8 (95% CI, 1.5-2.2). CONCLUSION: Among patients admitted to the ICU following resuscitation from cardiac arrest, arterial hyperoxia was independently associated with increased in-hospital mortality compared with either hypoxia or normoxia.

Significance of arterial hypotension after resuscitation from cardiac arrest.

OBJECTIVE: Expert guidelines advocate hemodynamic optimization after return of spontaneous circulation (ROSC) from cardiac arrest despite a lack of empirical data on prevalence of post-ROSC hemodynamic abnormalities and their relationship with outcome. Our objective was to determine whether post-ROSC arterial hypotension predicts outcome among postcardiac arrest patients who survive to intensive care unit admission. DESIGN: Cohort study utilizing the Project IMPACT database (intensive care unit admissions from 120 U.S. hospitals) from 2001-2005. SETTING: One hundred twenty intensive care units. PATIENTS: Inclusion criteria were: 1) age > or =18 yrs; 2) nontrauma; and 3) received cardiopulmonary resuscitation before intensive care unit arrival. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Subjects were divided into two groups: 1) Hypotension Present--one or more documented systolic blood pressure <90 mm Hg within 1 hr of intensive care unit arrival; or 2) Hypotension Absent--all systolic blood pressure > or =90 mm Hg. The primary outcome was in-hospital mortality. The secondary outcome was functional status at hospital discharge among survivors. A total of 8736 subjects met the inclusion criteria. Overall mortality was 50%. Post-ROSC hypotension was present in 47% and was associated with significantly higher rates of mortality (65% vs. 37%) and diminished discharge functional status among survivors (49% vs. 38%), p < .001 for both. On multivariable analysis, post-ROSC hypotension had an odds ratio for death of 2.7 (95% confidence interval, 2.5-3.0). CONCLUSIONS: Half of postcardiac arrest patients who survive to intensive care unit admission die in the hospital. Post-ROSC hypotension is common, is a predictor of in-hospital death, and is associated with diminished functional status among survivors. These associations indicate that arterial hypotension after ROSC may represent a potentially treatable target to improve outcomes from cardiac arrest.

Hypofractionated stereotactic radiotherapy for the treatment of brain metastases.

BACKGROUND: This retrospective review evaluated the efficacy and toxicity profiles of various dose fractionations using hypofractionated stereotactic radiotherapy (HSRT) in the treatment of brain metastases. METHODS: Between 2004 and 2007, 36 patients with 66 brain metastases were treated with HSRT. Nine of these subjects were excluded because of the absence of post-treatment magnetic resonance imaging scans, resulting in 27 patients with a total of 52 lesions. Of these 52 lesions, 45 lesions were treated with whole-brain radiotherapy plus a HSRT boost and 7 lesions were treated with HSRT as the primary treatment. The median prescribed dose was 25 grays (Gy) (range, 20 Gy-36 Gy) with a median of 5 fractions (range, 4 fractions-6 fractions) to a median 85% isodose line (range, 50%-100%). The median follow-up interval was 6.6 months (range, 0.9 months-26.8 months). RESULTS: The median overall survival time was 10.8 months, and 66.7% of patients died of disease progression. After HSRT treatment of 52 brain lesions, 13 lesions demonstrated complete responses, 12 lesions demonstrated partial responses, 22 lesions demonstrated stable disease, and 5 lesions demonstrated progressive disease. Actuarial local tumor control rates at 6 months and 1 year were 93.9% and 68.2%, respectively. Maximum tumor dimension, concurrent chemotherapy, and a tumor volume <1 cc were found to be statistically significant factors for local tumor control. One patient had a grade 3 toxicity (according to National Cancer Institute Common Terminology Criteria for Adverse Events). CONCLUSIONS: HSRT provides a high level of tumor control with minimal toxicity comparable to single-fraction stereotactic radiosurgery (SRS). The results of the current study warrant a prospective randomized study comparing single-fraction SRS with HSRT in this patient population.