Utilization of a MAB for BRAF(V600E) detection in papillary thyroid carcinoma.

Identification of BRAF(V600E) in thyroid neoplasia may be useful because it is specific for malignancy, connotes a worse prognosis, and is the target of novel therapies currently under investigation. Sanger sequencing is the 'gold standard' for mutation detection but is subject to sampling error and requires resources beyond many diagnostic pathology laboratories. In this study, we compared immunohistochemistry (IHC) using a BRAF(V600E) mutation-specific MAB to Sanger sequencing on DNA from formalin-fixed paraffin-embedded tissue, in a well-characterized cohort of 101 papillary thyroid carcinoma (PTC) patients. For all cases, an IHC result was available; however, five cases failed Sanger sequencing. Of the 96 cases with molecular data, 68 (71%) were BRAF(V600E) positive by IHC and 59 (61%) were BRAF(V600E) positive by sequencing. Eleven cases were discordant. One case was negative by IHC and initially positive by sequencing. Repeat sequencing of that sample and sequencing of a macrodissected sample were negative for BRAF(V600E). Of ten cases positive by IHC but negative by sequencing on whole sections, repeat sequencing on macrodissected tissue confirmed the IHC result in seven cases (suggesting that these were false negatives of sequencing on whole sections). In three cases, repeat sequencing on recut tissue remained negative (including using massive parallel sequencing), but these cases demonstrated relatively low neoplastic cellularity. We conclude that IHC for BRAF(V600E) is more sensitive and specific than Sanger sequencing in the routine diagnostic setting and may represent the new gold standard for detection of BRAF(V600E) mutation in PTC.

Myofascial pain response to topical lidocaine patch therapy: case report.

This is a case from a preliminary open trial to assess the efficacy of topically applied lidocaine patches as an alternative to trigger point injections for myofascial pain. We describe one case in this report that had a dramatic response to the lidocaine patch. Her pain relief increased, pain intensity decreased, and functional capacity increased. Her pain intensity and relief was measured by the Brief Pain Inventory-Short Form (BPI-SF). A quality of life measure was also included in the BPI-SF. While this was a dramatic response to this patient, it is only one case from an open-trial. The response to other patients has varied. The true clinical utility cannot be obtained from this one report, but only after the data have been analyzed from this initial trial. If the data are promising, a randomized, double-blind, crossover trial is planned.

Geographic variation in the treatment of acute myocardial infarction: the Cooperative Cardiovascular Project.

CONTEXT: Quality indicators for the treatment of acute myocardial infarction include pharmacologic therapy, reperfusion, and smoking cessation advice, but these therapies may not be administered to all patients who could benefit from them. OBJECTIVE: To assess geographic variation in adherence to quality indicators for treatment of acute myocardial infarction. DESIGN: Inception cohort using data from the Health Care Financing Administration Cooperative Cardiovascular Project. SETTING: Acute care hospitals in the United States. PATIENTS: A total of 186800 Medicare beneficiaries hospitalized for treatment of confirmed acute myocardial infarction from February 1994 through July 1995. MAIN OUTCOME MEASURES: Adherence to quality indicators for pharmacologic therapy, reperfusion, and smoking cessation advice for patients judged to be ideal candidates for these therapies. The mean rates of adherence to these quality indicators for the entire United States were determined, and the 20th and 80th percentiles of the age- and sex-adjusted rates for each of 306 hospital referral regions were contrasted (mean rate [20th-80th percentiles]). RESULTS: Aspirin was used frequently both during hospitalization (86.2% [82.6%-90.1%]) and at discharge (77.8% [72.5% -83.9%]). Calcium channel blockers were withheld from most patients with impaired left ventricular function (81.9% [73.6%-90.8%]). Lower rates were seen in the use of angiotensin-converting enzyme inhibitors at discharge (59.3% [49.2%-69.2%]); reperfusion, using thrombolytic therapy or coronary angioplasty (67.2% [59.8%-75.1%]); prescription of beta-blockers at discharge (49.5% [35.8%-61.5%]); and for smoking cessation advice (41.9% [32.8%-51.3%]). CONCLUSIONS: Substantial geographic variation exists in the treatment of patients with acute myocardial infarction, and these gaps between knowledge and practice have important consequences. Therapies with proven benefit for AMI are underused despite strong evidence that their use will result in better patient outcomes.

Cooperative Cardiovascular Project (CCP) quality improvement in Maine, New Hampshire, and Vermont.

The Cooperative Cardiovascular Project (CCP) is a nationwide quality improvement project (quality indicator measurement, feedback, remeasurement) in Medicare acute myocardial infarction (AMI) patients sponsored by the Health Care Financing Administration (HCFA). In Maine, New Hampshire, and Vermont, 3,472 baseline records were abstracted from 76 hospitals from January 1994 to February 1995. After feedback, 2,270 remeasurements were collected from October 1996 to May 1997. At remeasurement, performance improved significantly for "ideal" candidates (defined by the CCP) on five quality indicators--aspirin during hospitalization 88% to 93% (p < .001), thrombolytic timing 60% to 69% (p < .01), discharge aspirin 83% to 90% (p < .001), discharge beta-blockers 69% to 82% (p < .01), and calcium channel blocker avoidance 83% to 93% (p < .05). Reperfusion, angiotensin converting enzyme inhibitors, and smoking cessation advice did not improve significantly. This study demonstrates that evidence-based indicators, nationally designed data collection, and locally based interventions can significantly improve AMI care.

Effects of anesthetic technique on myocardial wall motion abnormalities during abdominal aortic surgery.

OBJECTIVE: To assess the impact of regional supplemented general anesthesia (RSGEN) on regional myocardial function during abdominal aortic surgery (AAS). DESIGN: Prospective randomized study. SETTING: Single academic medical center. PARTICIPANTS: Seventy-three patients scheduled for infrarenal aortic aneursymectomy. INTERVENTIONS: Patients received standardized intraoperative anesthetic management consisting of either general anesthesia (GA; n = 37) or general anesthesia supplemented by epidural anesthesia (RSGEN; n = 36). MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements and transesophageal echocardiograms (TEE) were obtained at eight intraoperative times. The electrocardiogram (ECG) was continuously recorded using Holter monitoring. Of the 56 patients with interpretable TEE recordings, 8 of 30 (27%) GA patients and 7 of 26 (27%) RSGEN patients developed new segmental wall motion abnormalities (SWMAs). There was no treatment effect on either the incidence (p = 0.23) or the intensity (p = 0.34) of SWMAs. Cross-clamping of the aorta was associated with the onset of new SWMAs (odds ratio, 8.2; 95% CI, 1.1 to 64; p = 0.04). Among the 63 patients with interpretable Holter recordings, 9 of 34 (26%) GA patients and 9 of 29 (31%) RSGEN patients exhibited intraoperative ischemia. There was no treatment effect on the incidence (p = 0.22) or intensity (p = 0.67) of ECG ischemia. CONCLUSION: Despite providing modest hemodynamic depression, RSGEN did not reduce the incidence or intensity of either regional myocardial dysfunction or ECG ischemia. New SWMAs were temporally associated with cross-clamping of the aorta and tended to resolve with unclamping.

Use of the laryngeal mask airway in managing a patient with a large anterior mediastinal mass: a case report.

This is a case presentation of a patient with a large anterior mediastinal mass in whom the airway was maintained with a laryngeal mask airway. The patient was otherwise managed in the "classic" fashion with spontaneous respiration via a light general anesthetic. In reviewing many of the potential pitfalls of anesthesia in this class of patients, the laryngeal mask airway was found to be both a valuable and viable option for airway management.

A validation of the functional independence measurement and its performance among rehabilitation inpatients.

The Functional Independence Measurement (FIM) is a new functional status instrument for use among rehabilitation inpatients, but its validity and reliability have been only partially established. Because of its rapid dissemination, we sought further evidence concerning the FIM's internal consistency, responsiveness over time, and construct validity. We examined Uniform Data System (UDS) data on 11,102 general rehabilitation inpatients from the Pacific Northwest. Mean age was 65 and 51% were male. The most common diagnoses were stroke (52%), orthopedic conditions (10%), and brain injury (10%). Internal consistency of the FIM was calculated using Cronbach's alpha. To assess FIM responsiveness, we examined differences between admission and discharge FIM scores. For construct validation purposes, we hypothesized that the FIM would vary with age, comorbidity, discharge destination, and impairment severity. Comorbidity was quantified with the Charlson Comorbidity Index. The FIM had a high overall internal consistency (discharge FIM alpha = .93). The FIM registered significant functional gains during rehabilitation (33% FIM score improvement, p < .001), as do many other functional status indicators. The greatest and least functional improvements were observed for traumatic brain injury and low back pain (53% and 8% FIM score improvement, respectively). The FIM discriminates patients on the basis of age, comorbidity, and discharge destination. Severity differences could be distinguished among spinal cord injury and stroke patients. We conclude that the FIM has high internal consistency and adequate discriminative capabilities for rehabilitation patients. It is a good indicator of burden of care, and demonstrates some responsiveness, but its capacity to measure change over time needs further examination and comparison with competing scales.

Prophylactic nitroglycerin infusion during noncardiac surgery does not reduce perioperative ischemia.

We evaluated the impact of prophylactic nitroglycerin on the incidence of perioperative myocardial ischemia in patients with known or suspected coronary artery disease who undergo noncardiac surgery. Our goals were to better define the role of nitroglycerin in the management of high-risk patients and to explore the mechanisms of perioperative myocardial ischemia. Patients were assigned randomly to either a control group (n = 23) or to receive 0.9 micrograms.kg-1.min-1 of intravenous nitroglycerin (n = 22). The diagnosis of myocardial ischemia was based on a review of Holter electrocardiogram (ECG) recordings. There was no difference in the incidence of ischemia between groups. Seven control patients (30%) and seven nitroglycerin patients (32%) exhibited ECG evidence of ischemia. The preponderance of myocardial ischemia occurred during emergence from anesthesia (of the 14 patients exhibiting ischemia, 12 did so at emergence). There was an acute increase in heart rate at the onset of ischemia in all patients exhibiting ischemia with 14 of 18 episodes associated with an increase of 20% or greater. The heart rate associated with the onset of ischemia was greater in the nitroglycerin-treated patients than in the control group. We also found that the occurrence of myocardial ischemia on a preoperative Holter recording was strongly predictive of the subsequent occurrence of perioperative ischemia. In conclusion, the addition of nitroglycerin to standard anesthetic management of these high-risk patients does not measurably reduce perioperative ischemia.

Distance education and adult learning.

PIP: It is argued that interaction plays a crucial role in any humane distance education program that aims to be widely effective. Thus far, nonformal education has been neglected in the development of distance education. The argument for expansion of nonformal education is 2-fold: much of the world's population has been deprived of formal educational opportunities as children, and, as adults their educational needs are practical, immediate, and life-related rather than certificate-oriented; and the ability to reach most adults with traditional class-based adult education is strictly limited, particularly in the developing world where the need is greatest. The advantages of distance education include economy, the ability to enter into students' homes, and the flexibility of time and place. There also are some problems. A large number of the educationally deprived also are illiterate, so print, the central component of distance education, is of limited direct individual use. Additionally, nonformal education often teaches practical skills for immediate application, but distance education methods have notorious difficulty teaching practical subjects. Consequently, if distance education is to be used, it should be used in group learning situations. 3 examples of nonformal educational programs that have used distance education in this way are cited as excellent illustrations. The program in Zambia has been in existence for several years. The Pakistan program has grown from a small research project into a university program. The Ghana program remains in the planning stage. In all 3 examples, the target audiences are educationally-deprived rural populations in developing countries. The subject matter in all 3 is of vital concern to their livelihood and well-being. The aim of each program is to reach large numbers of people scattered across wide areas with limited financial and personal resources. Different combinations of media and different organizational and materials development approaches are used, but all combine distance-learning media and group interaction. All use media and packaged learning materials to enable people in remote areas to organize and lead groups of illiterate and neoliterate adults to learn and study together. The subjects they study and the group-learning methods being used lead to group decisions and group actions.^ieng