Non-invasive perfusion MR imaging of the human brain via breath-holding.

Dynamic susceptibility contrast (DSC) MRI plays a pivotal role in the accurate diagnosis and prognosis of several neurovascular diseases, but is limited by its reliance on gadolinium, an intravascularly injected chelated metal. Here, we determined the feasibility of measuring perfusion using a DSC analysis of breath-hold-induced gradient-echo-MRI signal changes. We acquired data at both 3 T and 7 T from ten healthy participants who engaged in eight consecutive breath-holds. By pairing a novel arterial input function strategy with a standard DSC MRI analysis, we measured the cerebral blood volume, flow, and transit delay, and found values to agree with those documented in the literature using gadolinium. We also observed voxel-wise agreement between breath-hold and arterial spin labeling measures of cerebral blood flow. Breath-holding resulted in significantly higher contrast-to-noise (6.2 at 3 T vs. 8.5 at 7 T) and gray matter-to-white matter contrast at higher field strength. Finally, using a simulation framework to assess the effect of dynamic vasodilation on perfusion estimation, we found global perfusion underestimation of 20-40%. For the first time, we have assessed the feasibility of and limitations associated with using breath-holds for perfusion estimation with DSC. We hope that the methods and results presented in this study will help pave the way toward contrast-free perfusion imaging, in both basic and clinical research.

Cooling in neonatal hypoxic-ischemic encephalopathy: practices and opinions on minimum standards in the state of California.

OBJECTIVE: Although hospitals increasingly offer therapeutic hypothermia (TH), there is variable implementation of related services. We assessed current practices and opinions regarding what services should be required of centers providing TH in California. STUDY DESIGN: We surveyed neonatal intensive care unit physicians statewide regarding practices and opinions about services related to TH. RESULTS: Of the 50 participating centers (47% response rate), 66% offer TH. Most TH centers reported using: an evidence-based protocol (92%), neurology consultation (92%), amplitude-integrated electroencephalography (aEEG) or EEG (88%), magnetic resonance imagings (MRIs) interpreted by pediatric neuroradiologists (71%) and developmental follow-up (93%). TH centers reported treating a median of 11 patients annually (interquartile range (IQR) 4 to 24). Respondents considered it 'critical' that TH centers offer: aEEG monitoring (70%), MRI (69%), occupational and physical therapy (67%) and developmental follow-up (94%). Over 70% thought TH centers should treat a minimum volume annually (median=10, IQR 5 to 12). CONCLUSION: Physicians across practice settings in California endorsed minimum standards for TH centers to promote quality of care.

Low utilization of prenatal and pre-implantation genetic diagnosis in Huntington disease - risk discounting in preventive genetics.

Huntington disease (HD) is a late-onset, fatal neurodegenerative disorder caused by a (CAG) triplet repeat expansion in the Huntingtin gene that enlarges during male meiosis. In 1996 in this journal, one of us (J. D. S.) presented a methodology to perform pre-implantation genetic diagnosis in families at-risk for HD without revealing the genetic status of the at-risk parent. Despite the introduction of accurate prenatal and pre-implantation genetic testing which can prevent transmission of the abnormal HD gene in the family permanently, utilization of these options is extremely low. In this article, we examine the decision-making process regarding genetic testing in families with HD and discuss the possible reasons for the low uptake among this group.

Accounting for variation in length of NICU stay for extremely low birth weight infants.

OBJECTIVE: To develop a length of stay (LOS) model for extremely low birth weight (ELBW) infants. STUDY DESIGN: We included infants from the California Perinatal Quality Care Collaborative with birth weight 401 to 1000 g who were discharged to home. Exclusion criteria were congenital anomalies, surgery and death. LOS was defined as days from admission to discharge. As patients who died or were transferred to lower level of care were excluded, we assessed correlation of hospital mortality rates and transfers to risk-adjusted LOS. RESULTS: There were 2012 infants with median LOS 79 days (range 23 to 219). Lower birth weight, lack of antenatal steroids and lower Apgar score were associated with longer LOS. There was negligible correlation between risk-adjusted LOS and hospital mortality rates (r=0.0207) and transfer-out rates (r=0.121). CONCLUSION: Particularly because ELBW infants have extended hospital stays, identification of unbiased and informative risk-adjusted LOS for these infants is an important step in benchmarking best practice and improving efficiency in care.

[Phantom studies using a high-resolution CT for ex-vivo imaging of degradable magnesium implants and simulated peri-implant bone formation in rabbit tibiae]. / Phantomuntersuchungen an einem hochauflösenden CT zur Ex-vivo-Darstellung von degradierbaren Magnesiumimplantaten und simulierten periimplantären Knochenschichten in Kaninchentibiae.

PURPOSE: Evaluation of the suitability of the high-resolution CT XtremeCT for ex vivo imaging of degradable magnesium implants with simulated peri-implant bone formation in rabbit tibiae and development of a method for calibrating the mass concentration of a magnesium alloy in an implant volume. MATERIALS AND METHODS: Using specially designed phantoms, degradable magnesium implants of the alloys LAE442, ZEK100, AX30 and MgCa 0.8 %, without coating and with peri-implant bone formation simulated by a coating, as well as rabbit tibiae were scanned. CT numbers and the contrast-to-noise-ratio (CNR) of the studied materials were determined. The visual distinction between implant and coating was evaluated. To calibrate the implant density, exemplary LAE442 pins with different mass concentrations were scanned using a specially constructed phantom. Subsequently, CT numbers corresponding to the appropriate mass concentration were determined. RESULTS: The implants, coating and substantia corticalis showed a similar density. Visual distinction between coating and implant was strongly dependent on the respective magnesium alloy and chosen scan parameter. A CNR of at least 0.2 was required for a distinction between implant and coating. For the mass concentration, a high CT number linearity (R2=0.99) throughout the measuring range (1811-1273 mg/cm3 LAE442) was found. CONCLUSION: As expected, the XtremeCT is primarily suitable for the imaging of bone tissue and implants. Good visual distinction of peri-implant bone formation on magnesium implants in an ex vivo phantom model ranges from possible to difficult depending on the bone density and alloy composition.

Initiating delivery room stabilization/resuscitation in very low birth weight (VLBW) infants with an FiO(2) less than 100% is feasible.

BACKGROUND: Oxygen exposure during delivery room (DR) resuscitation, even when brief, is potentially toxic. A practice plan (PP) was introduced for very low birth weight (VLBW) infants < or = 1500 g as follows: initial FiO(2) from 0.21 to 1.0 using blenders, oxygen guided by oximetry to maintain saturation between 85% to 95% from birth. OBJECTIVE: To determine whether the initiating FiO(2) could be safely lowered, and by doing so whether the number of infants with a PaO(2) >80 mm Hg could be minimized on admission, as well as lowering oxygen requirement at 24 h. METHODS: In all, 53 infants admitted between June 2006 and June 2007 were evaluated and compared with 47 infants from 2004 managed with 100 % oxygen (historical comparison group (HC)). RESULT: Stabilization/Resuscitation included intubation (n=28) and continuous positive airway pressure (CPAP) (n=25); no cardiopulmonary resuscitation (CPR). The heart rate increased rapidly in all cases. The initiating FiO(2) decreased from 0.42 to 0.28 over 12 months (P=0.00005); 14 (26%) were resuscitated with room air. Correspondingly, the pH increased from 7.24 to 7.30 (P=0.002) and PCO(2) decreased from 53 to 41 (P=0.001). A comparison of infants during the PP with the HC revealed that 36/53 versus 21/47 had an initial PaO(2) <80 mm Hg (P=0.02); the median PaO(2), that is, 64 versus 86 and saturation, that is, 95% versus 99% on admission were significantly lower. The median FiO(2) at 24 h was 0.25 versus 0.40. CONCLUSION: DR resuscitation of VLBW infants can be initiated with less oxygen even with room air without concomitant overt morbidity. This change was associated with more infants with an initial PaO(2) <80 mm Hg and lower saturation values on admission as well as a lower FiO(2) requirement at 24 h.

Development of a statewide collaborative to decrease NICU central line-associated bloodstream infections.

OBJECTIVE: To characterize hospital-acquired bloodstream infection rates among New York State's 19 regional referral NICUs (at regional perinatal centers; RPCs) and develop strategies to promote best practices to reduce central line-associated bloodstream infections (CLABSIs). STUDY DESIGN: During 2006 and 2007, RPC NICUs reported bloodstream infections, patient-days and central line-days to the Department of Health, and shared their results. Aiming to improve, participants created a central line-care bundle based on visiting a potentially best performing NICU and reviewing the literature. RESULT: All 19 RPCs participated in this quality initiative, contributing 218,096 patient-days and 56,911 central line-days of observation. Individual RPC nosocomial sepsis infection (NI) rates ranged from 1.0 to 5.8 NIs per 1000 patient-days (2006), and CLABSI rates ranged from 2.6 to 15.1 CLABSIs per 1000 central line-days (2007). A six-fold rate variation among RPC NICUs was observed. Participants unanimously approved a level-1 evidence-based central line-care bundle. CONCLUSION: Individual RPC rates and consequent morbidity and resource use attributable to these infections were substantial and varied greatly. No center was without infections. It is hoped that the cooperation and accountability exhibited by the RPCs will result in a major network for characterizing performance and improving outcomes.

How to interpret your dot: decoding the message of clinical performance indicators.

Comparative performance reports continue to proliferate, so it is increasingly important that healthcare workers can interpret the graphically displayed results correctly. This article acquaints readers with key concepts for thinking clearly and critically about such displays: (1) articulating the question a display answers, along with reflecting on questions the display might appear to, but does not, answer; (2) establishing that provider comparisons are made fairly, ever mindful of methodological assumptions and limitations; (3) accounting for systematic differences among performers that are unexplained by specified predictors, that is, random effect methods that yield 'shrunken' estimates; (4) understanding funnel plots used to summarize complex analyses and how one may vary the interrogative focus so that 'outlier' values most likely signal extraordinary performance. Finally, these concepts are given broader context in a view of the ultimate aim of the evaluative enterprise.

Studying determinants of length of hospital stay.

Clinicians are accustomed to focusing on individual patients. However, when studying how long their patients stay in the hospital, the focus must widen. Length of stay summarizes the performance of the entire, exceedingly complex, NICU system. Ordinary statistical methods for modeling patient outcomes assume that what happens to one patient is unrelated to what happens to another. However, patients in the same NICU are exposed to similar hospital practices, so patient outcomes may be correlated. Length of stay data must be analyzed by methods that account for possibly correlated outcomes. In addition, to improve patient care and outcomes, predictive models must include determinants clinicians can influence. Such variables describe care process exposures, available beds, demand for beds, and staffing levels.

Battery powered BION FES network.

The Alfred Mann Foundation is completing development of a coordinated network of BION microstimulator/sensor (hereinafter implant) that has broad stimulating, sensing and communication capabilities. The network consists of a master control unit (MCU) in communication with a group of BION implants. Each implant is powered by a custom lithium-ion rechargeable 10 mW-hr battery. The charging, discharging, safety, stimulating, sensing, and communication circuits are designed to be highly efficient to minimize energy use and maximize battery life and time between charges. The stimulator can be programmed to deliver pulses in any value in the following range: 5 microA to 20 mA in 3.3% constant current steps, 7 micros to 2000 micros in 7 micros pulse width steps, and 1 to 4000 Hz in frequency. The preamp voltage sensor covers the range 10 microV to 1.0 V with bandpass filtering and several forms of data analysis. The implant also contains sensors that can read out pressure, temperature, DC magnetic field, and distance (via a low frequency magnetic field) up to 20 cm between any two BION implants. The MCU contains a microprocessor, user interface, two-way communication system, and a rechargeable battery. The MCU can command and interrogate in excess of 800 BlON implants every 10 ms, i.e., 100 times a second.

Neuropsychiatric thalamocortical dysrhythmia: surgical implications.

Clearly, more clinical experience must be amassed to define in detail the possibilities of this surgical approach in disabling neuropsychiatric disorders. We propose, however, that the evidence for benign and efficient surgical intervention against the neuropsychiatric TCD syndrome is already compelling. The potential appearance of strong postoperative reactive manifestations requires a close association between surgery and psychotherapy, with the latter providing support for the integration of the new situation as well as the resolution of old unresolved issues.

Second-generation microstimulator.

The first-generation injectable microstimulator was glass encased with an external tantalum capacitor electrode. This second-generation device uses a hermetically sealed ceramic case with platinum electrodes. Zener diodes protect the electronics from defibrillation shocks and from electrostatic discharge. The capacitor is sealed inside the case so that it cannot be inadvertently damaged by surgical instruments. This microstimulator, referred to as BION, is the main component of a 255-channel wireless stimulating system. BION devices have been implanted in rats for periods of up to 5 months. Results show benign tissue reactions resulting in identical encapsulation around BION and controls. Stimulation threshold levels did not change significantly over time and ranged between 0.81 to 1.35 mA for all the animals at a 60 micros pulse width. All of the tests performed to date indicate that the BION is safe and effective for long-term human implant. We have elected to develop BION applications by seeking collaboration with the research community through our BION Technology Partnership.

State level estimates of the incidence and economic burden of head injuries stemming from non-universal use of bicycle helmets.

OBJECTIVE: To develop national and state level estimates for preventable bicycle related head injuries (BRHIs) and associated direct and indirect health costs from the failure to use bicycle helmets. METHODS: Information on the effectiveness and prevalence of use of bicycle helmets was combined to estimate the avoidable fraction, that is, the proportion of BRHIs that could be prevented through the use of bicycle helmets. The avoidable fraction multiplied by the expected number of BRHIs gives an estimate of the number of preventable cases. Direct and indirect health costs are estimated from a social perspective for the number of preventable BRHIs to assess potential cost savings that would be achieved if all riders wore helmets. RESULTS: Approximately 107,000 BRHIs could have been prevented in 1997 in the United States. These preventable injuries and deaths represent an estimated $81 million in direct and $2.3 billion in indirect health costs. Estimates range from 200 preventable BRHIs and $3 million in health costs in Wyoming (population 480,000) to 13,700 preventable BRHIs and $320 million in health costs in California (population 32.3 million). CONCLUSIONS: A number of successful approaches to increasing bicycle helmet use exist, including mandatory use laws and community based programs. The limited use of these strategies may be related to the fact that too little information is available to state agencies about the public health and economic burden of these preventable injuries. In conjunction with information on program costs, our estimates can assist state planners in better quantifying the number of preventable BRHIs and the costs and benefits of helmet promotion programs.

Myeloid dendritic cells stimulate both Th1 and Th2 immune responses depending on the nature of the antigen.

It has been shown that different types of pathogens induce different immune responses. Recovery from intracellular bacterial and viral infection is dependent on the secretion of Th1 cytokines, such as interferon-gamma (IFN-gamma), and on the generation of cytotoxic T cells. In contrast, responses to some parasitic invaders are of the Th2 type, characterized by secretion of interleukin-4 (IL-4). At present, it is not clear what directs this choice, and the most prevalent hypotheses are based on the dendritic cells (DC). In this work, we studied the immune responses generated in mice to a number of antigens, both replicating and nonreplicating, using bone marrow-derived DC as vehicles for immunization. We demonstrate that DC infected with influenza virus prime for a pure Th1 response in vivo devoid of IL-4 induction. This immune response correlates with the induction of DC maturation by the virus. In contrast, nonreplicating antigens, such as fetal bovine serum (FBS), beta-galactosidase, or inactivated influenza virus, do not mature the DC and prime for responses characterized by the secretion of large amounts of IL-4. These data support the hypothesis that myeloid DC are capable of eliciting both types of responses depending on the nature of the antigen.

"Thinking upstream" to evaluate and to improve the daily work of the newborn intensive care unit.

One may divide patient care problem-solving approaches into two categories: (1) "Ready, aim, fire" and (2) "Ready, fire, aim." The present paper invites the reader to think about these distinctions and to identify which of these categories might apply to the reader's daily work experience. Espousing the first of these categories, and anchored in the notions of systems thinking, this paper offers the reader a framework to better understand and implement the daily work of the newborn intensive care unit. This knowledge and competence may be achieved by "thinking upstream," connecting "downstream" outcomes with "upstream" work process steps. The central elements that govern and inform the process of "thinking upstream" are articulated here in actionable terms.

Pregnancy rates in sequential in vitro fertilization cycles by oocyte donors(1).

OBJECTIVE: To evaluate the clinical outcome of in vitro fertilization (IVF) treatment cycles from individual oocyte donors who underwent multiple sequential donations. METHODS: We reviewed clinical outcome data from sequential anonymous oocyte donation cycles using donors who underwent multiple IVF stimulations. Donors were grouped by the interval between cycles and the cycle number (rank). The primary outcome measure was delivery rate by individual donor per retrieval from the combined derivative fresh and frozen embryo transfers. RESULTS: Duration and amount of gonadotropin therapy and the fertilization rates did not correlate significantly with the interval between cycles or cycle rank. Cumulative delivered pregnancy rates for cycles 1-6 were 51.5%, 54.6%, 50.5%, 51.5%, 51.1%, and 57.6%, respectively. Delivered pregnancy rates did not vary by interval between cycles. CONCLUSION: Young healthy presumed or proven fertile women can reliably donate oocytes for at least six cycles with the expectation of consistently high pregnancy rates.

Early-stage breast cancer treatment among medically underserved women diagnosed in a national screening program, 1992-1995.

BACKGROUND: Little research has been conducted on the breast cancer treatment of low income, underserved women. This study was designed to describe initial treatment of breast cancer among low-income women diagnosed through federally funded screening programs in Detroit, Michigan, and the states of New Mexico and California; and to compare the treatment received by program women with early-stage breast cancer with that of all women diagnosed in those regions. METHODS: Data from the three screening programs were linked with cancer registry data from the corresponding geographic areas. All women diagnosed between 1992 and 1995 through the state-based screening programs and all women contemporaneously diagnosed with breast cancer in the three regions were studied. Descriptive analyses were done of the proportion of women with breast cancer receiving treatment; the proportion of early-stage breast cancer (stage I or II) cases treated with breast-conserving surgery, and the proportion treated with mastectomy; and among women with breast-conserving surgery, the proportion receiving radiation therapy. Logistic regression models controlled for age and stage at diagnosis, race or ethnicity and geographic region. RESULTS: Less than 2% of program women diagnosed with breast cancer received no treatment. More than two of five women with early-stage breast cancer underwent breast-conserving surgery, with 72% of these women receiving radiation therapy. Multivariate regression analysis revealed that women with stage IIA or IIB breast cancer had lower odds of undergoing breast-conserving surgery than women with stage I (0.51 [95% CI = 0.30-0.87] and 0.36 [95% CI = 0.19-0.70], respectively). Women over age 65 and those with incompletely staged cancer had the lowest odds for receiving radiation therapy after breast-conserving surgery (0.29 [95% CI = 0.09-0.99] and 0.14 [95% CI = 0.03-0.72], respectively). Women diagnosed through the screening programs had odds of undergoing breast-conserving surgery similar to those of all women in the regions (1.11 [95% CI= 0.89-1.39]). CONCLUSIONS: Treatment patterns for women diagnosed with early-stage breast cancer through three state-based screening programs appear to have been similar to those reported in the literature. In addition, their treatment appears to have been similar to that of other women during the same time period.