Evaluation of factors associated with interhospital transfers to pediatric and adult tertiary level of care: A study of acute neurological disease cases.

INTRODUCTION: Patient referrals to tertiary level of care neurological services are often potentially avoidable and result in inferior clinical outcomes. To decrease transfer burden, stakeholders should acquire a comprehensive perception of specialty referral process dynamics. We identified associations between patient sociodemographic data, disease category and hospital characteristics and avoidable transfers, and differentiated factors underscoring informed decision making as essential care management aspects. MATERIALS AND METHODS: We completed a retrospective observational study. The inclusion criteria were pediatric and adult patients with neurological diagnosis referred to our tertiary care hospital. The primary outcome was potentially avoidable transfers, which included patients discharged after 24 hours from admission without requiring neurosurgery, neuro-intervention, or specialized diagnostic methodologies and consult in non-neurologic specialties during their hospital stay. Variables included demographics, disease category, health insurance and referring hospital characteristics. RESULTS: Patient referrals resulted in 1615 potentially avoidable transfers. A direct correlation between increasing referral trends and unwarranted transfers was observed for dementia, spondylosis and trauma conversely, migraine, neuro-ophthalmic disease and seizure disorders showed an increase in unwarranted transfers with decreasing referral trends. The age group over 90 years (OR, 3.71), seizure disorders (OR, 4.16), migraine (OR, 12.50) and neuro-ophthalmic disease (OR, 25.31) significantly associated with higher probability of avoidable transfers. Disparities between pediatric and adult transfer cases were identified for discrete diagnoses. Hospital teaching status but not hospital size showed significant associations with potentially avoidable transfers. CONCLUSIONS: Neurological dysfunctions with overlapping clinical symptomatology in ageing patients have higher probability of unwarranted transfers. In pediatric patients, disease categories with complex symptomatology requiring sophisticated workup show greater likelihood of unwarranted transfers. Future transfer avoidance recommendations include implementation of measures that assist astute disorder assessment at the referring hospital such as specialized diagnostic modalities and teleconsultation. Additional moderators include after-hours specialty expertise provision and advanced directives education.

Applying physical science techniques and CERN technology to an unsolved problem in radiation treatment for cancer: the multidisciplinary 'VoxTox' research programme.

The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose.

Cost-effectiveness of stereotactic radiosurgery with and without whole-brain radiotherapy for the treatment of newly diagnosed brain metastases.

OBJECT: Stereotactic radiosurgery (SRS) alone is increasingly used in patients with newly diagnosed brain metastases. Stereotactic radiosurgery used together with whole-brain radiotherapy (WBRT) reduces intracranial failure rates, but this combination also causes greater neurocognitive toxicity and does not improve survival. Critics of SRS alone contend that deferring WBRT results in an increased need for salvage therapy and in higher costs. The authors compared the cost-effectiveness of treatment with SRS alone, SRS and WBRT (SRS+WBRT), and surgery followed by SRS (S+SRS) at the authors' institution. METHODS: The authors retrospectively reviewed the medical records of 289 patients in whom brain metastases were newly diagnosed and who were treated between May 2001 and December 2007. Overall survival curves were plotted using the Kaplan-Meier method. Multivariate proportional hazards analysis (MVA) was used to identify factors associated with overall survival. Survival data were complete for 96.2% of patients, and comprehensive data on the resource use for imaging, hospitalizations, and salvage therapies were available from the medical records. Treatment costs included the cost of initial and all salvage therapies for brain metastases, hospitalizations, management of complications, and imaging. They were computed on the basis of the 2007 Medicare fee schedule from a payer perspective. Average treatment cost and average cost per month of median survival were compared. Sensitivity analysis was performed to examine the impact of variations in key cost variables. RESULTS: No significant differences in overall survival were observed among patients treated with SRS alone, SRS+WBRT, or S+SRS with respective median survival of 9.8, 7.4, and 10.6 months. The MVA detected a significant association of overall survival with female sex, Karnofsky Performance Scale (KPS) score, primary tumor control, absence of extracranial metastases, and number of brain metastases. Salvage therapy was required in 43% of SRS-alone and 26% of SRS+WBRT patients (p < 0.009). Despite an increased need for salvage therapy, the average cost per month of median survival was $2412 per month for SRS alone, $3220 per month for SRS+WBRT, and $4360 per month for S+SRS (p < 0.03). Compared with SRS+WBRT, SRS alone had an average incremental cost savings of $110 per patient. Sensitivity analysis confirmed that the average treatment cost of SRS alone remained less than or was comparable to SRS+WBRT over a wide range of costs and treatment efficacies. CONCLUSIONS: Despite an increased need for salvage therapy, patients with newly diagnosed brain metastases treated with SRS alone have similar overall survival and receive more cost-effective care than those treated with SRS+WBRT. Compared with SRS+WBRT, initial management with SRS alone does not result in a higher average cost.

Recurrence-free chronic subdural hematomas: a retrospective analysis of the instillation of tissue plasminogen activator in addition to twist drill or burr hole drainage in the treatment of chronic subdural hematomas.

OBJECTIVE: To evaluate whether increasing the volume drained from chronic subdural hematomas (SDHs) via either twist drill drainage (TDD) or burr hole drainage (BHD) followed by instillation of tissue plasminogen activator (tPA) is more efficacious than simple drainage alone. METHODS: Patients admitted over the course of 42 months (2007-2010) to a single institution for treatment of chronic SDH were retrospectively evaluated. RESULTS: There were 139 patients treated for chronic SDH; 54 patients were treated with BHD alone, 3 were treated with tPA after BHD, 85 were treated with TDD alone, and 12 were treated with tPA after TDD. Follow-up examinations were performed 1 month after treatment in 13 of 15 patients treated with tPA and 93 of 124 patients treated without tPA. Patients treated with tPA had a significantly lower rate of recurrence than patients treated without tPA (P=0.041). Patients treated with BHD had a recurrence rate of 11.8%, whereas patients treated with BHD and tPA had 0% recurrence. Patients treated with TDD had a recurrence rate of 30%, whereas patients treated with TDD and tPA had 0% recurrence. Without tPA, BHD was found to be a significantly better treatment than TDD (P=0.016). Mean drainage for TDD with tPA was 427.33 mL. There were no complications related to the administration of tPA. CONCLUSIONS: This study adds another therapeutic option for patients with chronic SDH requiring treatment. In this retrospective study, the addition of tPA increased the volume of hematoma drained and significantly reduced the incidence of recurrence requiring further intervention regardless of cranial access route. No complications occurred related directly or indirectly to the administration of tPA. Further study of this technique is warranted.

Cauda equina syndrome (CES) from lumbar disc herniations.

STUDY DESIGN: A retrospective review was performed to determine the outcomes of patients with cauda equina syndrome (CES) from a herniated lumbar disc at our institutions. OBJECTIVE: CES from lumbar herniated discs is considered the only absolute indication for surgery. It is considered a neurosurgical emergency with the outcome related to how quickly it is diagnosed and treated. The results of recovery of bladder function are felt by many authors to be related to early diagnosis and surgical intervention. Most authors recommend a wide decompressive laminectomy when surgery is performed. We reviewed our cases to determine if they conformed to these assumptions. SUMMARY OF BACKGROUND DATA: Although many articles regarding the outcome of CES from herniated lumbar discs suggest that early surgery is superior to surgery that is delayed, others have demonstrated no correlation between time-to-surgery and chances for recovery of neurologic and bladder function. METHODS: A retrospective review of all patients with lumbar herniated discs and CES from the years 1985 to 2004 was carried out. There were 31 patients, 28 of whom had bladder incontinence or retention requiring catheterization. Six patients were operated within 24 hours, 8 between 24 and 48 hours, and 17 after 48 hours (range: 60 h to 2 wk). Average follow-up was 5 years. RESULTS: Twenty-seven of these patients regained continence not requiring catheterization. There was no correlation between the time-to-surgery and recovery of bladder function. There was also no correlation between the time-to-surgery and recovery of motor and sensory function. The majority of patients underwent unilateral hemilaminotomy or bilateral hemilaminotomies; decompressive laminectomy was reserved for patients with underlying spinal stenosis or posteriorly herniated fragments. All of the patients were relieved of their radicular pain. CONCLUSIONS: In our series of patients with CES and bladder incontinence or retention, over 90% regained continence. Recovery of function was not related to the time to surgical intervention. The majority of the patients were adequately treated without the need for a complete laminectomy.

Successful endovascular treatment of a ruptured mycotic intracavernous carotid artery aneurysm in an AIDS patient.

INTRODUCTION: As the medical treatment for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) continues to advance, the HIV-related aneurysms may pose a clinical problem of increasing magnitude. The authors report on a successfully treated ruptured mycotic intracavernous carotid artery aneurysm case in an AIDS patient. METHODS: This 41-year-old AIDS patient presented with severe epistaxis. His head CT revealed acute blood in the left sphenoid sinus with bony erosion of the lateral wall (Fig. 1). The cerebral angiogram demonstrated a quite irregularly shaped intracavernous carotid artery aneurysm with proximal arterial stenosis (Fig. 2). RESULTS: After balloon test occlusion, this aneurysm was trapped endovascularly with detachable balloons (Fig. 3). The blood culture was positive for Aspergillus. The patient died 2 years later from other AIDS-related causes. CONCLUSION: The cerebral aneurysms in HIV/AIDS patients can be generally categorized into two groups: the mycotic aneurysms from bacterial or fungal infections and the HIV-associated aneurysms as a distinct entity. To plan appropriate interventions, a high degree of clinical suspicion must be exercised to promptly recognize the mycotic nature of many HIV-related aneurysms.

Cytogenetic, spectral karyotyping, fluorescence in situ hybridization, and comparative genomic hybridization characterization of two new secondary leukemia cell lines with 5q deletions, and MYC and MLL amplification.

Cytogenetic studies of patients with therapy-induced acute myeloid leukemia (t-AML) have demonstrated whole chromosome loss or q-arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML-1 and SAML-2, from two patients who developed t-AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML-1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter-->1p22::5q31-->5qter), der(5)(5pter-->5q22::1p22-->1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML-2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G-banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t-AML.

The variant hepatocyte nuclear factor 1 activates the P1 promoter of the human alpha-folate receptor gene in ovarian carcinoma.

The alpha folate receptor (alpha FR) is a membrane glycoprotein that binds folates, and mediates their uptake and that of antifolate drugs. alpha FR is absent on ovarian surface epithelium (OSE) but is detectable during early transforming events in this epithelium, with increasing expression levels in association with tumor progression. Analysis of transcriptional regulation of the alpha FR gene have revealed two promoter regions, P1 and P4, flanking exons 1 and 4, respectively, and a requirement for three SP1 sites and an INR element for optimal P4 activity. Here, we focused on the P1 transcription regulation in ovarian carcinoma cells. RNase protection assay indicated that the 5'-untranslated region is heterogeneous because of different start sites and alternative splicing of exon 3. A core region of the P1 promoter was sufficient for maximal promoter activity in ovarian carcinoma cell lines but not in OSE cells or in alpha FR-nonexpressing cell lines. Deletion and mutation analysis of this core promoter identified a cis-regulatory element at position +27 to +33 of the untranslated exon 1, which is responsible for maximum P1 activity. This element formed an abundant DNA-protein complex with nuclear proteins from ovarian cancer cells but not from other cell lines or OSE cells. Competition experiments and supershift assays demonstrated binding of the P1 cis-regulatory element by a transcription factor involved in embryonic development, the variant hepatocyte nuclear factor-1 (vHNF1). Analysis of RNA from various cell lines and surgical specimens confirmed that vHNF1 is expressed in ovarian carcinomas. Thus, vHNF1 regulates tissue-specific transcription in ovarian carcinoma.

Sorting and function of the human folate receptor is independent of the caveolin expression in Fisher rat thyroid epithelial cells.

Caveolae are small, flask-shaped, non-clathrin coated invaginations of the plasma membrane of many mammalian cells. Caveolae have a coat that includes caveolin. They have been implicated in numerous cellular processes, including potocytosis. Since the human folate receptor (hFR) and other glycosyl-phosphatidylinositol GPI)-tailed proteins have been co-localized to caveolae, we studied the caveolin role in the hFR function by transfecting hFR and/or caveolin cDNA into Fisher rat thyroid epithelial (FRT) cells that normally do not express detectable levels of either protein. We isolated and characterized stable clones as follows: they express (1) high levels of caveolin alone, (2) hFR and caveolin, or (3) hFR alone. We discovered that hFR is correctly processed, sorted, and anchored by a GPI tail to the plasma membrane in FRT cells. No difference in the total folic acid binding or cell surface folic acid binding activity were found between the FRT cells that were transfected with hFR, or cells that were transfected with hFR and caveolin. The hFR that was expressed on the cell surface of clones that were transfected with hFR was also sensitive to phosphatidylinositol-specific phospholipase C (PI-PLC) release, and incorporated radiolabeled ethanolamine that supports the attachment of a GPI-tail on hFR. We conclude that the processing, sorting, and function of hFR is independent on the caveolin expression in FRT cells.