Practice makes perfect: the critical role of mixed practice in the acquisition of ECG interpretation skills

Purpose. To examine the effect of instructional format on medical students' learning of ECG diagnosis. Method. Two experiments employed different learning and practice methods. In the first, students were randomly allocated to one of two instructional approaches, one organized around features (e.g., QRS voltage) and the other around diagnostic categories (e.g., bundle branch blocks), followed by a practice phase. In the second experiment, the instruction was standardized, and students were randomly allocated to one of two practice phases, either contrastive where examples from various categories are mixed together, or non-contrastive where all the examples in a single category are practiced in a single block.Results. In the first experiment, there was no significant differences in students' diagnostic accuracy on novel ECG examples. In the second experiment, students exposed to the contrastive approach in the practice phase had superior diagnostic accuracy (46%) compared to 30% accuracy for the non-contrastive session, p < 0.05).Conclusion. These experiments highlight two important features in the design of instructional materials. First, learning around the features of the problem (analogous to problem – based learning) may have no advantages over learning the category. Second, the design and organization of deliberate practice can result in significant learning gain.This revised version was published online in October 2005 with corrections to the Cover Date.     

A novel erythromycin, 6-desmethyl erythromycin D,made by substituting an acyltransferase domain of the erythromycin polyketide synthase

The acyltransferase (AT) domain in module 4 of the erythromycin polyketide synthase (PKS) was substituted with an AT domain from the rapamycin PKS module 2 in order to alter the substrate specificity from methylmalonyl-CoA to malonyl-CoA. The resulting strain produced 6-desmethyl erythromycin D as the predominant product. This AT domain swap completes the library of malonyl-CoA AT swaps on the erythromycin PKS and reinforces PKS engineering as a robust and generic tool.     

Synthesis and evaluation of imidazole acetic acid inhibitors of activated thrombin-activatable fibrinolysis inhibitor as novel antithrombotics

Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis, and inhibitors of this enzyme have potential use in antithrombotic and thrombolytic therapy. Appropriately substituted imidazole acetic acids such as 10j were found to be potent inhibitors of activated TAFI and selective versus the related carboxypeptidases CPA, CPN, and CPM but not CPB. Further, 10j accelerated clot lysis in vitro and was shown to be efficacious in a primate model of thrombosis.     

Current status and future of relapsed primary central nervous system lymphoma (PCNSL)

The treatment of primary central nervous system lymphoma (PCNSL) has centered around high-dose methotrexate and radiotherapy (RT). Methotrexate administered intra-arterially (IA) with blood-brain barrier disruption (BBBD) and without RT, has been a highly effective treatment with a 5 year survival of 42% without cognitive loss. The purpose of this analysis is to determine responses for patients with relapsed PCNSL treated with second line IA carboplatin-based chemotherapy with BBBD. Between February 1991 and April 2000, 37 relapsed PCNSL patients, most who failed front line therapy with methotrexate based chemotherapy, were treated at Oregon Health & Science University (OHSU) and Hadassah Hebrew University Hospital (HHUH) with IA carboplatin-based chemotherapy with BBBD. Nine patients had prior RT. The mean age was 57.5 years, and all but 1 patient were treated within 8 months after relapse. The median time for survival from first IA carboplatin/BBBD treatment was 6.8 months;however, 7 out of 37 patients survived > or = 27 months. Nine patients had radiographic complete response (CR), 4 patients had radiographic partial response (PR), 12 had stable disease (SD), 10 had progressive disease (PD), and 2 were non-evaluable. The median time to failure for patients with CR and PR was 9.1 months. One long-term survivor is alive at 91.0 months from first carboplatin/BBBD treatment. In conclusion, we show that relapsed PCNSL has shown sensitivity to second line IA carboplatin-based chemotherapy with BBBD. We have developed a new protocol using i.v. rituximab prior to BBBD with IA carboplatin, i.v. cyclophosphamide and i.v. etoposide phosphate. The long-term program goal is to consolidate dose-intensive chemotherapy with monoclonal antibody directed radiation. Because patients with recurrent PCNSL commonly continue to relapse even after obtaining a complete response to enhanced chemotherapy treatment, patients w ho complete or fail the above carboplatin/BBBD treatment regimen will be offered consolidation with radioimmunotherapy using zevalin (Ibritumomab tiuxetan), IDEC-2B8 conjugated with yttrium-90 (90Y).     

Two year prognosis of sarcoidosis: the ACCESS experience

A cohort of 215 sarcoidosis patients from the ACCESS study underwent a clinical evaluation at study enrollment and two years later. Approximately 80% of subjects had an improved or stable FVC, FEV1, chest radiograph determined by Scadding stage, and dyspnea scale. African-Americans had less improvement in FVC than Caucasians (p = 0.04). Patients with erythema nodosum at presentation were more likely to have improvement in the chest radiograph at two-year follow-up (p = 0.007). Patients with a lower annual family income were more likely to worsen with respect to dyspnea (p = 0.01) and more likely to have new organ involvement at two-year follow-up (p = 0.045). The development of new organ involvement over the two year follow-up period was more common in African-Americans compared to Caucasians (p = 0.002) and more likely in those with extrapulmonary involvement at study entry (p = 0.003). There was an excellent concordance between changes in FVC and FEV1 over the two-year period. However, changes in FVC alone were inadequate to describe the change in pulmonary status of the patients, as changes in chest radiographic findings or the level of dyspnea did often but not always move in the same direction as FVC. In conclusion, data from this heterogeneous United States sarcoidosis population indicate that sarcoidosis tends to improve or remain stable over two years in the majority of patients. Several factors associated with improved or worse outcome over two years were identified.     

Uterine adenosarcoma with sarcomatous overgrowth versus uterine carcinosarcoma: comparison of treatment and survival

OBJECTIVE: Uterine adenosarcoma with sarcomatous overgrowth (ASSO) is a rare variant of uterine sarcoma first described in 1989. This clinicopathologic study was undertaken to compare the treatment and survival of uterine adenosarcoma with sarcomatous overgrowth to that of uterine carcinosarcomas. METHODS: A review of uterine sarcomas diagnosed at Washington Hospital Center from January 1988 to December 1998 was performed. Records were reviewed for demographic data, surgical staging, primary and adjuvant therapy, metastatic site, disease recurrence, and survival. All pathology was reviewed and diagnosis confirmed. Statistical analysis included chi(2) test and Student's t test. Kaplan-Meier survival curves were plotted to estimate the median and 5-year survival times. The log-rank test was used to compare survival times. A P value <0.05 was considered significant. RESULTS: Sixty patients were diagnosed with uterine sarcoma at Washington Hospital Center. Of these, 33 (55%) were uterine carcinosarcomas, 11 (18%) ASSOs, 6 (10%) adenosarcomas, and 10 (17%) leiomyosarcomas. Of the patients diagnosed with uterine ASSO, 3 (27%) were stage I, 3 (27%) stage II, 1 (9%) stage III, and 4 (36%) stage IV. All 11 patients with uterine ASSO underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and tumor debulking. Postoperative adjuvant therapy included chemotherapy (n = 4), radiation (n = 4), combination radiation and chemotherapy (n = 1), and no adjuvant therapy (n = 2). The overall median survival time of patients with uterine ASSO was 13 months. Nine of eleven patients are dead of disease, and two patients (both with stage I) are alive without evidence of disease at 18 and 19 months. Thirty-three patients with carcinosarcoma were identified, with follow-up available on 29 patients. Of these, 10 (34%) were stage I, 6 (22%) stage II, 3 (10%) stage III, and 10 (34%) stage IV. Twenty-seven of the twenty-nine patients diagnosed with carcinosarcoma underwent surgical therapy to include total abdominal hysterectomy, bilateral salpingo-oophorectomy, staging and tumor debulking. Two patients died prior to treatment. Postoperative adjuvant therapy included chemotherapy (n = 9), radiation (n = 13), combination (n = 1), and no further therapy (n = 4). Twenty of the twenty-nine patients are dead of disease; there were nine surviving patients at the time of this report (stage I-5, stage II-3, stage III-1). The median survival of these patients was 31 months, with an overall 5-year survival of 22%. Comparison of the Kaplan-Meier survival curves using the log-rank test suggests a worse prognosis for uterine ASSO. However, this did not reach statistical significance (P = 0.0522). CONCLUSIONS: Patients diagnosed with uterine ASSO have a poor prognosis similar to that of carcinosarcoma. Management should include complete surgical staging. Additional therapy in the form of radiation, chemotherapy, or both has been reported; however, the superiority of one modality could not be determined from our data.     

Speed of sound measurements in mandibular and phalangeal bone during growth

The micromechanical and elastic properties of bone, its structural maturity and, indirectly, mineral density are important factors for the planning and assessment of orthodontic and/or jaw orthopaedic treatment. This clinical study was undertaken to evaluate age-related changes in the anterior mandibular body. The speed of sound (SOS) has demonstrated age dependency in various peripheral bones and has been proposed as an alternative method for investigating bone parameters without the use of radiation. The ultrasound transmission velocity was measured in 184 healthy subjects (93 females, 91 males; mean age 17.6±13.7 years). According to the statistical analysis, the data did not reveal any gender- related differences, but were significantly age-dependent. Different kinetics were established between the maturity of the phalanx and the anterior mandible. Further clinical investigations of age-dependent structural changes in bone maturation parameters may provide information that should be taken into account for early functional jaw orthopaedic treatment. Received: 31 January 2000 / Accepted: 15 May 2000     

Effects of afternoon "siesta" naps on sleep, alertness, performance, and circadian rhythms in the elderly

STUDY OBJECTIVES: To determine the effects of a 90-minute afternoon nap regimen on nocturnal sleep, circadian rhythms, and evening alertness and performance levels in the healthy elderly. DESIGN AND SETTING: Nine healthy elderly subjects (4m, 5f, age range 74y-87y) each experienced both nap and no-nap conditions in two studies each lasting 17 days (14 at home, 3 in the laboratory). In the nap condition a 90-minute nap was enforced between 13:30 and 15:00 every day, in the no-nap condition daytime napping was prohibited, and activity encouraged in the 13:30-15:00 interval. The order of the two conditions was counterbalanced. PARTICIPANTS: N/A INTERVENTIONS: N/A MEASUREMENTS: Diary measures, pencil and paper alertness tests, and wrist actigraphy were used at home. In the 72 hour laboratory studies, these measures were augmented by polysomnographic sleep recording, continuous rectal temperature measurement, a daily evening single trial of a Multiple Sleep Latency Test (MSLT), and computerized tests of mood, activation and performance efficiency. RESULTS: By the second week in the "at home" study, an average of 58 minutes of sleep was reported per siesta nap; in the laboratory, polysomnography confirmed an average of 57 minutes of sleep per nap. When nap and no-nap conditions were compared, mixed effects on nocturnal sleep were observed. Diary measures indicated no significant difference in nocturnal sleep duration, but a significant increase (of 38 mins.) in 24-hour Total Sleep Time (TST) when nocturnal sleeps and naps were added together (p<0.025). The laboratory study revealed a decrease of 2.4% in nocturnal sleep efficiency in the nap condition (p<0.025), a reduction of nocturnal Total Sleep Time (TST) by 48 mins. in the nap condition (p<0.001) which resulted primarily from significantly earlier waketimes (p<0.005), but no reliable effects on Wake After Sleep Onset (WASO), delta sleep measures, or percent stages 1 & 2. Unlike the diary study, the laboratory study yielded no overall increase in 24-hour TST consequent upon the siesta nap regimen. The only measure of evening alertness or performance to show an improvement was sleep latency in a single-trial evening MSLT (nap: 15.6 mins., no nap: 11.5 mins., p<0.005). No significant change in circadian rhythm parameters was observed. CONCLUSIONS: Healthy seniors were able to adopt a napping regimen involving a 90-minute siesta nap each day between 13:30 and 15:00, achieving about one hour of actual sleep per nap. There were some negative consequences for nocturnal sleep in terms of reduced sleep efficiency and earlier waketimes, but also some positive consequences for objective evening performance and (in the diary study) 24-hour sleep totals. Subjective alertness measures and performance measures showed no reliable effects and circadian phase parameters appeared unchanged.