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Background Patients with sickle cell disease (SCD) experience a broad range of mental health disorders placing them at risk for more complicated hospitalizations for pain. The current study examined the impact of mental health disorders on admission rates and hospital length of stay (LOS) for vaso-occlusive pain events (VOE) in pediatric patients with SCD. Procedure Patients (5–18 years old) with a primary discharge diagnosis of SCD with crisis were acquired through the Pediatric Health Information System and categorized by history of mental health disorders (mood disorder, anxiety disorder, disruptive behavior disorder, and substance use disorder). Using a retrospective cohort design, hospital admission rates for VOE were examined as the primary outcome and LOS as a secondary outcome. Results A total of 5,825 patients accounted for 23,561 admissions for SCD with crisis with approximately 8% of the patients having a mental health diagnosis. Longer LOS was found among patients with a history of any mental health diagnosis (P

High-grade gliomas remain one of the most fatal tumors with median survivals ranging from 3–5 years for WHO (World Health Organizaiton) grade III anaplastic astrocytoma and 12–14 months for WHO grade IV glioblastoma.1 Until recently, few treatment options were available for patients once standard chemoradiation therapy with temozolomide had failed. With the identification of multiple signaling pathways and growth factors essential for tumor angiogenesis, several new anti-angiogenic drugs have been developed. One of these, bevacizumab, is a recombinant humanized monoclonal IgG1 antibody that binds to human vascular endothelial growth factor (VEGF) and inhibits angiogenesis.2 Bevacizumab received accelerated FDA approval for the treatment of recurrent glioblastoma on May 5, 2009, and has since become the standard of care for treatment of high-grade glioma. Patients with recurrent high-grade glioma treated with bevacizumab have demonstrated an excellent radiographic response rate and improved clinical outcome when compared with historical data.3 In 2 of the early prospective phase II clinical trials,4,5 the rate of progression-free survival (PFS) at 6 months was 29%–42.6% compared with the 15% historical control rates. However, a statistically significant increase in overall survival (OS) was not demonstrated. In these trials, the traditional approach for assessing response, the MacDonald Criteria,6 were used. The MacDonald criteria are based on the 2-dimensional measurement of enhancing tumor on MRI or CT. In later studies using a modified MacDonald criteria that included fluid-attenuated inversion recovery (FLAIR) imaging, increases in both PFS and OS were reported.3 Subsequently, the RANO (Response Assessment in Neuro-Oncology) criteria were published in 2010 as an update to the MacDonald criteria.7 The RANO criteria newly incorporates FLAIR imaging to assess the degree of peritumoral edema and is therefore the standard approach used by many institutions for assessing disease progression and treatment response in glioblastoma. Though these assessment criteria are considered standard, it is becoming increasingly clear that these anatomic measures of tumor response to bevacizumab are often unreliable. Contrast-agent enhancement and FLAIR hyperintensities on imaging primarily reflect the breakdown of the blood-brain-barrier. Bevacizumab acts as a powerful corticosteroid decreasing the permeability of the blood-brain-barrier.8 Thus, rapid decreases in the degree of contrast enhancement and FLAIR hyperintensity may not necessarily reflect true changes in tumor biology or cellular burden. As such, measures derived from standard imaging may neither be able to predict OS reliably nor be an accurate representation of PFS. The antivascular permeability effect of VEGF inhibition likely accounts for the high initial radiographic response rate, with profound reductions in enhancement on MRI being observed as soon as 24 hours after the first dose of bevacizumab.5,9 Yet, as demonstrated in a recent study,5 this is clearly too early for an equally profound cellular antitumor effect since rapid subsequent progression developed in nearly half of the initial responders. Still, patients do derive clinical benefit from treatment as manifested by decreased cerebral edema, improved neurological symptoms, and decreased requirement for corticosteroids. In addition, some bevacizumab-mediated antumor effect likely occurs in at least a subpopulation of patients because nearly half of the initial radiographic responders were progression free for more than 6 months. Consequently, biomarkers that more directly measure the biologic effects of these agents are vital for better stratification into various treatment arms, as well as the improvement of research pursuing new therapies and strategies for high-grade tumors. Relative cerebral blood volume (rCBV) imaging, which is derived from dynamic susceptibility contrast (DSC) MRI, has the potential to serve as a predictive biomarker of response. With DSC-MRI, T2 or T2*-weighted images are acquired with high temporal resolution during the bolus adminstration of a gadolinium (Gd) contrast agent.10 The resulting rCBV image maps have demonstrated the ability to predict tumor grade11–16 and survival17 and to distinguish posttreatment radiation effects from recurrent tumor.18–20 In preliminary studies the, potential of rCBV to predict response to anti-angiogenic therapy more reliably than standard MRI has been demonstrated.21 Though DSC-MRI has shown great promise for the evaluation of brain tumors, its role as a prognostic measure for response to bevacizumab has not been fully evaluated. Consequently, the goal of this study is to investigate the utility of rCBV, or more specifically standardized rCBV (stdRCBV), to predict the overall survival (OS) and progression free survival (PFS) in response to bevacizumab in comparison with FLAIR-hyperintense and contrast-agent enhancing tumor volumes.

In order to determine the prevalence of psychoactive substance use in three specialty groupings, 1,624 questionnaires were sent to physicians in medicine, surgery and anaesthesia; all had trained at the same academic institution. A response rate of 57.8% was achieved. Comparison of prevalence of impairment rates showed no differences between Surgery (14.4%), Medicine (19.9%) and Anaesthesia (16.8%). Substance abuse was clearly associated with a family history of abuse; 32.1% of the abusers had a family history of such abuse compared with 11.7% of the non-abusers. Increased stress at various career stages did not appear to increase substance abuse; problem areas during medical life times were similar for each specialty. Substances most frequently used were marijuana (54.7%), amphetamines (32.9%); and benzodiazepines (25.1%). Seventy-three used psychoactive drugs which were non-prescribed. Drug counselling programmes were judged inadequate by most. Use of alcohol and drugs by faculty members was reported by a number of respondents.

Autoantibodies associated with the subepidermal blistering disorders bullous pemphigoid and herpes gestationis react with a 180-kD transmembrane hemidesmosomal protein, designated BP180. The BP180 ectodomain is composed of a series of interrupted collagen triple helical domains. Located on one of the noncollagenous extracellular segments of this protein is an immunodominant epitope, designated MCW-1, recognized by patient autoantibodies. In this investigation we have developed an enzyme-linked immunosorbent assay system to detect antibody reactivity against the MCW-1 epitope with the use of a bacterial fusion protein containing the BP180 autoantibody-reactive site. The following sera were assayed for reactivity with this recombinant protein: bullous pemphigoid (n = 62), herpes gestationis (n = 28), endemic pemphigus foliaceus (n = 17), lupus erythematosus (n = 15), and normal human sera (n = 22). This enzyme-linked immunosorbent assay-based protocol was shown to be highly specific (98.3%) in detecting autoantibody activity in bullous pemphigoid and herpes gestationis patients. Fifty-three percent of bullous pemphigoid sera and 71% of herpes gestations sera, but none of the control sera, yielded positive results in this assay. Of the patient sera that were known to react with full-length BP180, almost all showed reactivity with the MCW-1 antigenic site of this protein. Autoantibodies detected in this assay were predominantly of the immunoglobulin G class. The results presented here lend support to the hypothesis that this well-defined antigen/antibody system may be relevant in pathogenesis.

Insulin secretion, clearance dynamics, and their relationship to peripheral plasma insulin and glucose levels were monitored during three 12-h periods of overnight rest, intake of three meals, and continuous enteral feeding of mixed nutrients. The low-frequency ultradian and the high-frequency insulin secretion pulsatility characteristics during the steady-states of overnight rest and continuous enteral feeding were also examined. In abdominally obese subjects, the insulin secretion rate was consistently higher than normal by 2.3-fold. Peripheral plasma insulin levels were increased by 3.4-fold during the overnight period and by 4- to 5-fold during the two fed states. Endogenous insulin clearance was significantly reduced during feeding. Both low- and high-frequency insulin secretory pulsatilities were detected in the abdominally obese subjects. Pulse periods were within the normal range. Pulse maxima, nadirs, and absolute amplitudes were increased concomitant with the increase in insulin secretion. Ultradian relative pulse amplitudes, however, were blunted. A significantly higher pulse-to-pulse variability was observed in the abdominally obese subjects compared with normal subjects. Furthermore, a significantly higher level of interindividual variability in the nutrient-stimulated insulin secretion and in the ultradian pulse characteristics was observed. Thus in abdominal obesity, the increase in pancreatic insulin output is limited and the secretory pulsatilities are aberrant, suggesting a defect in the insulin secretory process. Diminished insulin clearance contributes to the degree of peripheral hyperinsulinemia compensating for the insulin resistance characteristic of this form of obesity.

Summary: The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 μmol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaineand BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.

purpose: The efficacy of the automatic implantable cardioverter defibrillator (AICD) was compared in elderly patients and younger patients with life-threatening ventricular tachyarrhythmias. Clinical characteristics, surgical complications, and long-term survival rates were compared between the two age groups. patients and methods: A retrospective study was conducted of 54 elderly patients (greater than 65 years) and 79 younger patients (less than 65 years) who had had AICDs implanted for recurrent symptomatic ventricular tachycardia and/or ventricular fibrillation. results: In 85% of elderly patients and 78% of younger patients, coronary artery disease was the underlying disease (NS). The mean left ventricular ejection fraction was 31.4 ± 14.3% in the elderly patients and 35.7 ± 17.6% in the younger patients (NS). Concomitant myocardial revascularization was performed in 37% of elderly patients and 29% of younger patients (NS); however, only 4% of elderly patients had concomitant left ventricular resection or cryoablation, compared with 15% of younger patients (p conclusion: It is concluded that AICD is a very effective treatment for life-threatening ventricular tachyarrhythmias, and this benefit applies to elderly patients as well as younger patients.

Changes in intellectual function during the course of treatment for acute lymphocytic leukemia were studied. Twenty-four children had baseline psychological evaluations and annual reevaluations for 3-6 years postdiagnosis. Treatment in all patients included combination chemotherapy, 2,400 cGy prophylactic cranial irradiation, and intrathecal methotrexate. Central Nervous System (CNS) relapse occurred in eight of these children. It was then treated with 3,000 cGy cranial plus 1,800 cGy spinal irradiation. Patients who remained in continuous complete remission showed no decline in global intelligence quotient (IQ). Patients who experienced CNS relapse had a mean decline of 16 IQ points by 3 years postdiagnosis and the long-term survivors displayed a mean loss of 25 IQ points 5-6 years postdiagnosis. Three of the five long-term survivors of CNS relapse function within the retarded range of mental ability and require special education. The other two have learning problems and display poor academic performance relative to same-age peers. There was no association noted between age at diagnosis and ultimate loss of IQ points. This prospective study suggests that children who receive a second course of cranial irradiation for treatment of CNS relapse are at high risk for significant and progressive intellectual loss.

Substantial geographic and hospital-based variations have been documented in the use of breast-conserving surgery (BCS) in 1986. The authors studied the patterns of adoption of this procedure from 1986 to 1990. National Medicare inpatient claims were used to study women aged 65 to 79 who underwent an operation for local or regional breast cancer in 1986 (38,679 patients) or 1990 (43,083 patients). Breast-conserving surgery was used for 5,509 (14.1%) of the Medicare patients in 1986 and 6,476 (15.0%) in 1990. The only region with an increase in BCS use from 1986 to 1990 was New England. Many hospitals had low volumes of operations, with a median of six to seven patients annually. Ten percent of the hospitals performed 55% of the conservative operations. Large hospitals, urban hospitals, and those with higher patient volumes or a cancer center were somewhat more likely to have increased use of BCS by 1990. Despite the substantial evidence supporting BCS as an alternative to mastectomy, the overall use of BCS in Medicare inpatients increased minimally from 1986 to 1990. Many patients are treated in hospitals with little experience with BCS. Hospitals using more BCS in 1986 were somewhat more likely to increase the use of BCS by 1990.

It is feasible to apply prehospital 12-lead electrocardiography to most stable prehospital chest pain patients. Prehospital diagnostic accuracy is improved compared with single-lead telemetry.One-hundred sixty-six stable adult patients who sought paramedic evaluation for a chief complaint of nontraumatic chest pain.One-hundred fifty-one prehospital 12-lead ECGs of diagnostic quality were obtained by paramedics on 166 adult patients presenting with nontraumatic chest pain. Paramedics and base station physicians were blinded to the information on acquired prehospital 12-lead ECGs and treated patients according to current standard of care-clinical diagnosis and single-lead telemetry. Final hospital diagnoses were classified into three groups: acute myocardial infarction (24); suspected angina or ischemia (61); and nonischemic chest pain (66). Paramedics and base station physicians' clinical diagnoses and prehospital and emergency department ECGs were similarly classified and compared. Prehospital and ED 12-lead ECGs were read retrospectively by two cardiologists.Paramedics achieved a high success rate (98.7%) in obtaining diagnostic quality prehospital 12-lead ECGs in 94.6% of eligible prehospital patients. For patients with acute myocardial infarction, prehospital ECG alone had significantly higher specificity than did the paramedic clinical diagnosis (99.2% vs 70.9%; P less than .001), and significantly higher positive predictive value (92.9% vs 32.7%; P less than .001). For patients with angina, combining the paramedic clinical diagnosis and the prehospital ECG significantly improved sensitivity (90.2% vs 62.3%; P less than .001) and increased negative predictive value (88.9% vs 71.3%; P less than .02) compared with paramedic clinical diagnosis alone. There was a high concordance between prehospital and ED ECG diagnosis (99.3% for acute myocardial infarction and 92.8% for angina). Furthermore, ten patients whose prehospital ECGs demonstrated ischemia and who had final hospital diagnoses of angina or acute myocardial infarction were mistriaged by paramedics and/or received no base station physician-directed therapy.It is feasible to apply prehospital 12-lead electrocardiography to most stable prehospital chest pain patients. Prehospital 12-lead ECGs have the potential to significantly increase the diagnostic accuracy in chest pain patients, approach congruity with ED 12-lead ECG diagnoses, and may allow for consideration of altering and improving prehospital and hospital-based management in this patient population.

The ability of surgery and radiotherapy to control advanced squamous cell carcinoma of the head and neck has reached its maximal potential. We initiated a randomized, prospective, stratified study of adjuvant chemotherapy. Patients with stage II disease of the pyriform sinus and stage II and IV disease of the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, and paranasal sinuses were eligible. Patients were randomized to receive either standard therapy alone or two courses of 5-fluorouracil (B-CMF) chemotherapy prior to and two courses after the completion of standard therapy. Standard therapy consisted of preoperative irradiation followed by radical surgery. Of 133 patients with advanced disease, 83 were included in the study--43 in the chemotherapy group and 40 in the control group. Rates of residual and recurrent disease, as well as distant metastases, were similar for the two groups. The survival rates of patients without persistent disease at the end of treatment showed no significant difference for the two groups. The study has been discontinued because statistical analysis indicated that the addition of more patients would not materially increase the statistical significance of the study.

The recognition of an association between coronary heart disease (CHD) and coronary prone behavior (CPB) has raised the question of whether behavior may directly affect coronary atherosclerosis. The relationship of coronary occlusion measured by arteriography and angina pectoris to questionnaire responses selected as consistent with the attitudes and behavior of CPB were examined retrospectively in 2215 employed male patients. Nonbehavioral factors such as serum cholesterol and triglycerides were highly related to occlusion but not to angina. By comparison, most subjective attitudes and some quantitative behaviors consistent with CPB were overrepresented in angina but not in occlusion. Certain neurotic behaviors were also disproportionately represented in angina but not in occlusion. These results indicate that attitudinal and behavioral aspects of CPB contribute to angina pectoris and perhaps indirectly to atherosclerosis. This association was greatest in patients older than 50 years, but comparable to some standard risk factors in younger patients also.

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.

We examined the relation of carcinoembryonic antigen levels to time, site and extent of recurrence in 358 patients with colorectal cancer. The recurrence rate was higher in patients with Dukes' B and Dukes' C lesions who had preoperative levels higher than 5 ng per milliliter. There was a linear inverse correlation between preoperative levels and estimated mean time to recurrence in patients with Dukes' B and C lesions, ranging from 30 months for a level of 2 to 9.8 months for a level of 70 ng per milliliter. In patients with Dukes' C lesions the median time to recurrence was 13 months if preoperative levels were higher than 5 ng per milliliter, and 28 months if they were lower. Preoperative carcinoembryonic antigen levels in patients with resectable Dukes' B and C cancer provided an additional criterion for allocating these patients to groups at high or low risk for recurrence.

This study was undertaken to clarify the relationship between coronary artery occlusion (CAO) and coronary-prone behavior attitudes (CPBA) in a large coronary arteriography population. A group of 2451 male patients responded to a questionnaire prior to coronary arteriography. Ten questions from the questionnaire, selected to form a scale measuring CPBA, were found to be reliably associated with standard measures of Type A behavior. No differences in CPBA were found when the group was divided into mild, moderate, and severe CAO, but angina pectoris (AP) tended to increase from mild to severe CAO. Multiple regression analysis confirmed that CPBA were independently associated with AP but were not associated with CAO. These findings suggest that angina pectoris is an important intervening variable between CPBA and CAO and that the relationship of AP in a population should be carefully considered before conclusions are drawn as to the relationship between CPBA and CAO.

Conventional radiography is the standard method of objectively identifying sacroiliitis. Single views of the sacroiliac joints can be unequivocally interpreted in 70-80% of patients with low back pain. A series of views usually correctly resolves the ambiguity in the remaining 20-30% of patients (67% correct). Computed tomography will be helpful in the few patients in whom a series of views produces equivocal interpretation.