The RSNA Image Sharing Network.

In the era of health information exchanges, there are trade-offs to consider when sharing a patient's medical record among all providers that a patient might choose. Exchange among in-network partners on the same electronic medical records (EMR) and other integrated information systems is trivial. The patient identifier is common, as are the relevant departmental systems, to all providers. Difficulties arise when patient records including images (and reports) must be shared among different networks and even with the patients themselves. The National Institutes of Health (NIH) challenged Radiological Society of North America (RSNA) to develop a transport method that could supersede the need for physical media (for patients or other providers), replace point-to-point private networks among providers, and enable image exchange on an ad hoc basis between arbitrary health networks without long legal delays. In concert with the evolving US health care paradigm, patient engagement was to be fundamental. With Integrating Healthcare Enterprise's (IHE's) help, the challenge has been met with an operational system.

A phase l study of three different dosing schedules of the oral aurora kinase inhibitor MSC1992371A in patients with solid tumors.

Aurora kinase inhibitors (AKIs) are a class of antimitotic, small-molecule anticancer agents. MSC1992371A is an AKI being evaluated for the treatment of patients with solid tumors. This phase I, open-label, dose-escalation study determined the maximum tolerated dose (MTD) of MSC1992371A in different dosing schedules in patients with locally advanced or metastatic solid tumors. MSC1992371A was administered on days 1 and 8 (schedule 1) or on days 1, 2, and 3 (schedule 2) of a 21-day cycle. The study was expanded with a third schedule (study drug on days 1-3 and 8-10). Adverse events were monitored throughout the study. Antitumor efficacy, drug pharmacokinetics, and pharmacodynamics were evaluated. Ninety-two patients were enrolled. MSC1992371A was dosed over eight levels in schedules 1 and 2, and the MTD was determined as 74 mg/m(2) per cycle for both schedules and as 60 mg/m(2) in schedule 3, albeit only in three patients due to discontinuation of the study. Overall, the most common grade 3 or 4 treatment-emergent adverse events were neutropenia, febrile neutropenia, thrombocytopenia, anemia, and fatigue. The most frequent dose-limiting toxicity over all schedules was neutropenia. MSC1992371A plasma concentrations tended to increase with increasing dose levels. Although no complete or partial responses were seen, stable disease ≥3 months was observed in 11 patients. Analysis for markers of target modulation and pharmacodynamics effects was unsuccessful. MSC1992371A was generally well tolerated in patients, with mainly transient hematologic toxicities apparent at an MTD of 60-74 mg/m(2)/21-day cycle, independent of dosing frequency.

Identifying a standard set of outcome parameters for the evaluation of orthogeriatric co-management for hip fractures.

BACKGROUND AND PURPOSE: Osteoporotic fractures are an increasing problem in the world due to the ageing of the population. Different models of orthogeriatric co-management are currently in use worldwide. These models differ for instance by the health-care professional who has the responsibility for care in the acute and early rehabilitation phases. There is no international consensus regarding the best model of care and which outcome parameters should be used to evaluate these models. The goal of this project was to identify which outcome parameters and assessment tools should be used to measure and compare outcome changes that can be made by the implementation of orthogeriatric co-management models and to develop recommendations about how and when these outcome parameters should be measured. It was not the purpose of this study to describe items that might have an impact on the outcome but cannot be influenced such as age, co-morbidities and cognitive impairment at admission. METHODS: Based on a review of the literature on existing orthogeriatric co-management evaluation studies, 14 outcome parameters were evaluated and discussed in a 2-day meeting with panellists. These panellists were selected based on research and/or clinical expertise in hip fracture management and a common interest in measuring outcome in hip fracture care. RESULTS: We defined 12 objective and subjective outcome parameters and how they should be measured: mortality, length of stay, time to surgery, complications, re-admission rate, mobility, quality of life, pain, activities of daily living, medication use, place of residence and costs. We could not recommend an appropriate tool to measure patients' satisfaction and falls. We defined the time points at which these outcome parameters should be collected to be at admission and discharge, 30 days, 90 days and 1 year after admission. CONCLUSION: Twelve objective and patient-reported outcome parameters were selected to form a standard set for the measurement of influenceable outcome of patients treated in different models of orthogeriatric co-managed care.

Open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of intravenously administered CNF1010 (17-(allylamino)-17-demethoxygeldanamycin [17-AAG]) in patients with solid tumors.

BACKGROUND: 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin that binds to and inhibits the Hsp90 family of molecular chaperones leading to the proteasomal degradation of client proteins critical in malignant cell proliferation and survival. We have undertaken a Phase 1 trial of CNF1010, an oil-in-water nanoemulsion of 17-AAG. METHODS: Patients with advanced solid tumors and adequate organ functions received CNF1010 by 1-h intravenous (IV) infusion, twice a week, 3 out of 4 weeks. Doses were escalated sequentially in single-patient (6 and 12 mg/m(2)/day) and three-to-six-patient (≥25 mg/m(2)/day) cohorts according to a modified Fibonacci's schema. Plasma pharmacokinetic (PK) profiles and biomarkers, including Hsp70 in PBMCs, HER-2 extracellular domain, and IGFBP2 in plasma, were performed. RESULTS: Thirty-five patients were treated at doses ranging from 6 to 225 mg/m(2). A total of 10 DLTs in nine patients (2 events of fatigue, 83 and 175 mg/m(2); shock, abdominal pain, ALT increased, increased transaminases, and pain in extremity at 175 mg/m(2); extremity pain, atrial fibrillation, and metabolic encephalopathy at 225 mg/m(2)) were noted. The PK profile of 17-AAG after the first dose appeared to be linear up to 175 mg/m(2), with a dose-proportional increase in C max and AUC0-inf. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects of CNF1010 at doses >83 mg/m(2). CONCLUSION: The maximum tolerated dose was not formally established. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects. The CNF1010 clinical program is no longer being pursued due to the toxicity profile of the drug and the development of second-generation Hsp90 molecules.

Regional grey matter shrinks in hypertensive individuals despite successful lowering of blood pressure.

The aim of the study was to determine whether the reduction in brain grey matter volume associated with hypertension persisted or was remediated among hypertensive patients newly treated over the course of a year. A total of 41 hypertensive patients were assessed over the course of a 1-year successful anti-hypertensive treatment. Brain areas identified previously in cross-sectional studies differing in volume between hypertensive and normotensive individuals were examined with a semi-automated measurement technique (automated labelling pathway). Volumes of grey matter regions were computed at baseline after a year of treatment and compared with archival data from normotensive individuals. Reductions in regional grey matter volume over the follow-up period were observed despite successful treatment of blood pressure (BP). The comparison group of older, but normotensive, individuals showed no significant changes over a year in the regions tested in the treated hypertensive group. These novel results suggest that essential hypertension is associated with regional grey matter shrinkage, and successful reduction of BP may not completely counter that trend.

A phase I study evaluating the effect of CDHP as a component of S-1 on the pharmacokinetics of 5-fluorouracil.

UNLABELLED: The purpose of this study was to investigate the effect of gimeracil (CDHP), a reversible dihydropyrimidine dehydrogenase (DPD) inhibitor, on the pharmacokinetics of 5-fluorouracil (5-FU) and other related metabolites by comparing the pharmacokinetic (PK) profile of S-1 (tegafur [FT] + CDHP + oteracil potassium [Oxo]) to that of FT alone. PATIENTS AND METHODS: Patients with advanced solid tumors received single oral doses of S-1 (50 mg) and FT (800 mg) on days 1 and 8 in a randomized crossover fashion. Plasma samples were collected on days 1, 2, 3, 8, 9 and 10. Single-dose PK parameters were determined for FT, 5-FU and α-fluoro-ß-alanine (FBAL). Following the single-dose crossover period, patients entered an extension phase and received treatment with S-1 b.i.d. for 14 days followed by a 7-day rest, repeated every 3 weeks. RESULTS: A total of 12 patients were enrolled; median age was 59 years and mean body surface area was 1.94 m(2). Following S-1 administration, 5-FU exposure was significantly greater (approximately 3-fold) compared to FT alone (p ≤ 0.0007 for AUC0-inf, AUC0-last, and C(max) of 5-FU) despite the 16-fold higher dose of FT administered alone compared to S-1, while plasma concentrations of FT and FBAL were significantly lower with S-1 (p < 0.0001 for all comparisons). Following both single- and multiple-dose administration of S-1, the average maximum DPD inhibition was observed at 4 h post-dose. The extent of inhibition was similar following single and multiple dosing. Following single- and multiple-dose administration of S-1, plasma concentrations of uracil returned to baseline levels within approximately 48 h of dosing, indicating reversibility of DPD inhibition by CDHP. CONCLUSION: Despite the differences in the FT dose administered, exposure to 5-FU was significantly greater following S-1 administration compared to FT administration. Conversely, exposure to FT and FBAL were significantly less following S-1 administration compared to FT administration. Thus, the DPD inhibitory action of CDHP contributes to a decrease in 5-FU catabolism and to significantly higher blood levels of 5-FU compared to FT alone.

Co-managed care for fragility hip fractures (Rochester model).

Hip fractures in older adults are a common event with a high risk of morbidity and mortality. Patients who sustain a hip fracture often present with multiple co-morbid conditions that can benefit from co-management by orthopedic surgeons and geriatricians. This manuscript describes a co-managed model of care for patients with hip fractures. This model of care will be explained, and the benefits and results will be described. Retrospective review of the care of all native non-pathological hip fracture patients aged 60 years and older admitted between April 2005 and March 2009 to a 261-bed community teaching hospital. The outcome measures include patient characteristics, length of stay, mortality, 30-day readmission, re-operation, and costs of care. Seven hundred fifty-eight patients were identified with an average age of 84.8 (SD 8.4); 77.8% of the patients were female, 94.7% Caucasian, and 37.3% from nursing homes, and the mean Charlson score is 2.9 (SD 2.1). The length of stay was 4.3 days, 30-day readmission rate was 10.4%, 17-month re-operation rate was 1.9%, and costs of care to the system were $15,188. The 1-year mortality rate was 21.2%. This model of care resulted in improvements in all measures studied. Previous studies have shown reduction in in-hospital complications. Additional studies are needed to show if this model of care can be translated to other systems or to other surgical conditions. Wide application of this model care could substantially improve the quality of care and cost of caring for frail elders with hip fractures.

Clinical, ethical and legal considerations in the treatment of newborns with non-ketotic hyperglycinaemia.

Non-ketotic hyperglycinaemia (NKH) is a devastating neurometabolic disorder leading, in its classical form, to early death or severe disability and poor quality of life in survivors. Affected neonates may need ventilatory support during a short period of respiratory depression. The transient dependence on ventilation dictates urgency in decision-making regarding withdrawal of therapy. The occurrence of patients with apparent transient forms of the disease, albeit rare, adds uncertainty to the prediction of clinical outcome and dictates that the current practice of withholding or withdrawing therapy in these neonates be reviewed. Both bioethics and law take the view that treatment decisions should be based on the best interests of the patient. The medical-ethics approach is based on the principles of non-maleficence, beneficence, autonomy and justice. The law relating to withholding or withdrawing life-sustaining treatment is complex and varies between jurisdictions. Physicians treating newborns with NKH need to provide families with accurate and complete information regarding the disease and the relative probability of possible outcomes of the neonatal presentation and to explore the extent to which family members are willing to take part in the decision making process. Cultural and religious attitudes, which may potentially clash with bioethical and juridical principles, need to be considered.

Imaging of the thymus.

Technologic advances in imaging, particularly CT and MR imaging, have revolutionized the ability to noninvasively image the thymus. Increasing knowledge of the normal and pathologic states of the thymus has been accompanied by an increasing ability to depict morphologic alterations in this gland with fine spatial resolution and can even provide functional information. This article discusses the role of various imaging modalities in identifying suspected thymic disease, which historically required surgery to visualize. The role of imaging is best understood with an appreciation of the embryology, anatomy, and pathology of the thymus.

Pulmonary artery and aortic sarcomas: cross-sectional imaging.

Sarcomas of the major arteries are rare tumors often misdiagnosed due to nonspecific symptomatology. The authors present three cases of pulmonary artery and aortic sarcomas that were initially believed to be more common diseases. Modern imaging techniques including helical computed tomography (CT) and magnetic resonance imaging (MRI) are increasing the frequency of premortem diagnosis of these entities and aided surgical planning.

The role of respiratory care practitioners in a changing healthcare system: emerging areas of clinical practice.

OBJECTIVE: To evaluate shifts in respiratory care practice in the context of changing healthcare system and market dynamics. STUDY DESIGN: Telephone survey, structured interview, and case studies. METHODS: We conducted a telephone survey of 471 respiratory care practitioners (RCPs), drawn from the membership database of the American Association for Respiratory Care. We also interviewed 10 employers of RCPs and conducted 2 in-depth case studies to supplement our survey results. We used several statistical techniques to analyze our data, including calculation of population-weighted descriptive statistics and multivariate regression models. RESULTS: Changes in the healthcare system have prompted RCPs to broaden their practice settings, skills, and responsibilities. Respiratory care practitioners are taking part in managed care-related activities, such as cost control and disease management. We found that the need for certain skills and responsibilities varies by practice setting. In our interviews, employers considered RCPs cost effective providers for certain services. CONCLUSIONS: The practice of respiratory care is evolving to meet the changing needs of the healthcare system. A key challenge is to ensure appropriate growth and development of the respiratory care profession, as well as the delivery of appropriate services under new care management settings and processes.

Acute evaluation of a preformed single-pass VDD/DDD pacing lead.

The clinical utility of single lead, atrial synchronous, ventricular pacing (VDD), for patients with normal sinus function and heart block is well established. Atrial stimulation, unavailable in VDD systems presents a significant disadvantage. DDD pacing systems however, require the introduction and positioning of two separate leads. The acute human study discussed evaluated a modified version of a commercially available VDD lead with a preshaped lobe, capable of both sensing and pacing the right atrium. "P" waves and atrial stimulation thresholds were determined in five patients. The mean P-wave was 2.5 +/- 1 millivolts. Atrial stimulation in the unipolar configuration was 1.6 +/- 0.5 volts and 1.7 +/- 0.9 volts in the bipolar configuration. These acute stimulation thresholds and sensing amplitudes were comparable to conventional DDD pacing systems. Therefore, single-lead DDD pacing may be feasible and warrants further study.

Outcomes and effectiveness research in the private sector.

Private-sector health care organizations increasingly tout the use of outcomes and effectiveness research in activities ranging from pharmaceutical research to insurance coverage determinations. The rapid development of this research raises important questions about the role of the Agency for Health Care Policy and Research (AHCPR) as the producer, funder, and champion of outcomes and effectiveness research. To address this issue, we reviewed the activities of pharmaceutical companies, insurers, managed care organizations, health information technology companies, and other private-sector actors in outcomes and effectiveness research. We found that it is being used in a focused way to promote business goals and other organizational objectives, particularly in the pharmaceutical, insurance, and managed care industries. We also found significant gaps in its application to important public health issues and virtually no overlap with prior federal activities in this area.

Pneumothorax and pneumomediastinum after laparoscopic surgery.

Pneumothorax, pneumomediastinum, pneumopericardium, and subcutaneous emphysema have been described as complications of laparoscopy. This study evaluates the incidence and significance of these extra alveolar collections of air. We found that pneumomediastinum with or without pneumothorax was not associated with significant morbidity and is more likely after laparoscopic fundoplication than other laparoscopic surgeries. The presence of pneumomediastinum after fundoplication is a normal finding. However, pneumothorax has clinical significance and should be considered pathological.

Health information systems and the role of state government.

State government entities have created a range of innovative electronic information systems to support their diverse and evolving roles in the health care system. Primary goals of these initiatives include improvement of traditional public health programs, meaningful oversight of providers, simplification of administrative procedures, and support of state purchasing decisions. We establish a taxonomy of state efforts, describing primary capabilities to (1) provide meaningful data to state decisionmakers; (2) disseminate information to purchasers and consumers; (3) coordinate and improve government services; (4) establish mechanisms for electronic transactions; and (5) support telemedicine services. Reductions in the costs of technology and use of the Internet have dramatically increased state capabilities in recent years. Both the successes and failures of existing programs offer important lessons for states that are initiating new electronic communication initiatives.

The anatomy of online information for physicians.

Online medical networked information (OMNI) is one of the newest and fastest growing types of information sources for physicians. The authors present an organizational framework for understanding the range of available OMNI sources and discuss the practical applications, strengths and limitations of online resources. Physicians can now gain access on line to a wealth of information relating to many aspects of clinical medicine and can consult interactively with colleagues on clinical and research questions. The limitations of networked online resources include lack of access, difficulty in navigating online systems and the potential for fraudulent use. Net-worked online systems are growing in popularity and may become integral to medical practice as barriers to efficient use are overcome.

Detection of hepatocellular carcinoma in cirrhotic patients: sensitivity of CT and ultrasonography.

Patients with cirrhosis are at increased risk for the development of hepatocellular carcinoma. The heterogeneous hepatic parenchyma produced by cirrhosis makes detection of hepatomas more difficult. The purpose of this study was to determine the sensitivities of CT and ultrasonography for detecting hepatomas in cirrhotic patients. A retrospective analysis was performed of 733 patients who underwent liver transplantation at our institution. A study population of 21 patients was selected who met our inclusion criteria. The inclusion criteria required a pathologic diagnosis of hepatocellular carcinoma, pathologic evidence of cirrhosis, and contrast-enhanced CT and sonographic examinations performed within 1 week of each other. The sensitivities of CT and ultrasonography were determined by comparing the imaging findings with pathology findings from serially sectioned total hepatectomy specimens. A total of 40 hepatomas were detected pathologically in the 21 patients in our study population. CT identified 12 of 21 patients with hepatomas and detected 18 of 40 individual lesions (patient detection sensitivity = 57%, lesion detection sensitivity = 45%). Ultrasonography identified 14 of 21 patients with hepatomas and detected 21 of 40 individual lesions (patient detection sensitivity = 67%, lesion detection sensitivity = 51%). Combining the findings of CT and ultrasonography allowed identification of 17 of 21 patients with hepatomas and detection of 24 of 40 individual lesions (patient detection sensitivity = 80%, lesion detection sensitivity = 60%). We conclude that CT and ultrasonography have a low sensitivity for the detection of hepatocellular carcinoma in patients with cirrhosis.