Influence of PBL with open-book tests on knowledge retention measured with progress tests.

The influence of problem-based learning (PBL) and open-book tests on long-term knowledge retention is unclear and subject of discussion. Hypotheses were that PBL as well as open-book tests positively affect long-term knowledge retention. Four progress test results of fifth and sixth-year medical students (n = 1,648) of three medical schools were analyzed. Two schools had PBL driven curricula, and the third one had a traditional curriculum (TC). One of the PBL schools (PBLob) used a combination of open-book (assessing backup knowledge) and closed-book tests (assessing core knowledge); the other two schools (TC and PBLcb) only used closed-book tests. The items of the progress tests were divided into core and backup knowledge. T tests (with Bonferroni correction) were used to analyze differences between curricula. PBL students performed significantly better than TC students on core knowledge (average effect size (av ES) = 0.37-0.74) and PBL students tested with open-book tests scored somewhat higher than PBL students tested without such tests (av ES = 0.23-0.30). Concerning backup knowledge, no differences were found between the scores of the three curricula. Students of the two PBL curricula showed a substantially better long-term knowledge retention than TC students. PBLob students performed somewhat better on core knowledge than PBLcb students. These outcomes suggest that a problem-based instructional approach in particular can stimulate long-term knowledge retention. Distinguishing knowledge into core and backup knowledge and using open-book tests alongside closed-book tests could enhance long-term core knowledge retention.

Directing students to profound open-book test preparation: the relationship between deep learning and open-book test time.

BACKGROUND: Considering the growing amount of medical knowledge and the focus of medical education on acquiring competences, using open-book tests seems inevitable. A possible disadvantage of these tests is that students underestimate test preparation. AIMS: We examined whether students who used a deep learning approach needed less open-book test time, and how students performed on open-book questions asked in a closed-book setting. METHOD: Second- (N = 491) and third-year students (N = 325) prepared half of the subject matter to be tested closed-book and half to be tested open-book. In agreement with the Board of Examiners, some questions in the closed-book test concerned open-book subject matter, and vice versa. Data were gathered about test time, deep learning and preparation time. Repeated measurement analysis, t-tests and partial correlations were used to analyse the data. RESULTS: We found a negative relationship between deep learning and open-book test time for second-year students. Students scored the lowest on closed-book questions about open-book subject matter. CONCLUSIONS: Reduction of the available test time might force students to prepare longer and deeper for open-book tests. Further research is needed to identify variables that influence open-book test time and to determine how restrictive this time should be.

Learning strategies during clerkships and their effects on clinical performance.

BACKGROUND: Previous research revealed relationships between learning strategies and knowledge acquisition. During clerkships, however, students' focus widens beyond mere knowledge acquisition as they further develop overall competence. This shift in focus can influence learning strategy use. AIM: We explored which learning strategies were used during clerkships and their relationship to clinical performance. METHODS: Participants were 113 (78%) clerks at the university hospital or one of six affiliated hospitals. Learning strategies were assessed using the 'Approaches to Learning at Work Questionnaire' (deep, surface-rational and surface-disorganised learning). Clinical performance was calculated by taking the mean of clinical assessment marks. The relationship between learning strategies and clinical performance was explored using regression analysis. RESULTS: Most students (89%) did not clearly prefer a single learning strategy. No relationship was found between learning strategies and clinical performance. DISCUSSION: Since overall competence comprises integration of knowledge, skills and professional behaviour, we assume that students without a clear preference use more than one learning strategy. Finding no relationship between learning strategies and clinical performance reflects the complexity of clinical learning. Depending on circumstances it may be important to obtain relevant information quickly (surface-rational) or understand material thoroughly (deep). In future research we will examine when and why students use different learning strategies.

The Lambert-Eaton myasthenic syndrome 1988-2008: a clinical picture in 97 patients.

BACKGROUND: Neuromuscular symptoms in patients with Lambert-Eaton myasthenic syndrome (LEMS) and a small cell lung cancer (SCLC) develop more rapidly than in LEMS patients without a SCLC. We studied how this clinical information, which is readily available at the first consultation, can be used to predict the presence of SCLC. PATIENTS AND METHODS: In our study we included 52 LEMS patients with SCLC and 45 non-tumor patients (NT-LEMS). We interviewed patients using a structured checklist and reviewed their clinical records. We compared frequency and onset of symptoms during the course of LEMS. RESULTS: In the first six months, over half the SCLC-LEMS patients had developed seven separate symptoms, while NT-LEMS patients developed only two symptoms. Proximal leg weakness and dry mouth were early symptoms in both groups. Rapid involvement of proximal arm muscles (p=0.0001), distal arm muscles (p=0.0037), distal leg muscles (p=0.0002), dysartria (p=0.0091) and the presence of erectile dysfunction (p=0.007) were found significantly more often in SCLC-LEMS patients in both cohorts. Cerebellar symptoms, although present in 9% of LEMS patients, were almost exclusively related to SCLC-LEMS. CONCLUSION: A rapidly progressive course of disease from onset in LEMS patients should raise a high suspicion of SCLC. Special attention should be paid to involvement of upper extremities, involvement of distal arm and distal leg muscles, to erectile dysfunction and probably ataxia in order to discriminate between SCLC-LEMS and NT-LEMS.

Open-book tests to complement assessment-programmes: analysis of open and closed-book tests.

Today's health sciences educational programmes have to deal with a growing and changing amount of knowledge. It is becoming increasingly important for students to be able to use and manage knowledge. We suggest incorporating open-book tests in assessment programmes to meet these changes. This view on the use of open-book tests is discussed and the influence on test quality is examined. To cope with the growing amount of medical knowledge, we have divided the body of knowledge into core knowledge, which students must know without need for references, and backup knowledge, which students need to understand and use properly with the help of references if so desired. As a result, all tests consist of a subtest for reproduction and understanding of core knowledge (a closed-book test) and a subtest for the ability to understand and manage backup knowledge (an open-book test). Statistical data from 14 such double-subtest exams for first and second-year students were analyzed for two cohorts (N = 435 and N = 449) with multilevel analysis, in accordance with generalizability theory. The reliability of the open and closed-book sections of the separate tests varied between 0.712 and 0.850. The open-book items reduce reliability somewhat. The estimated disattenuated correlation was 0.960 and 0.937 for cohorts 1 and 2 respectively. It is concluded that the use of open-book items with closed-book items slightly decreases test reliability but the overall index is acceptable. In addition, open and closed-book sections are strongly positively related. Therefore, open-book tests could be helpful in complementing today's assessment programmes.

[Two patients with mitochondrial respiratory chain disease]. / Twee patiënten met een mitochondriale myopathie.

A 23-year-old woman and a 13-year-old boy were diagnosed with mitochondrial respiratory chain disease. The woman had muscle pain, fatigue and bilateral ophthalmoplegia--symptoms consistent with Kearns-Sayre syndrome. The boy had aspecific symptoms; eventually, reduced activity of complex 1 was found to be the cause of the mitochondrial respiratory chain disease in the boy and his mother, who had suffered from unexplained fatigue and muscle pain for 15 years. Mitochondrial diseases often involve several organ systems. Diagnosis can be difficult, because laboratory tests such as serum and urinary lactate and creatine kinase have low sensitivity and specificity. Biochemical assessment of muscle biopsy can reveal reduced oxidation ATP synthesis and sometimes specific abnormalities in individual protein complexes. DNA analysis may be helpful in demonstrating mitochondrial or nuclear mutations or deletions. The goal of treatment is to increase mitochondrial ATP production, improve clinical symptoms and enhance stamina. Replacement of the following substances (also referred to as cofactors) may be attempted: co-enzyme Q10, antioxidants (lipoic acid, vitamins C and E), riboflavin, thiamine, creatine and carnitine. Evidence regarding the optimal treatment approach is lacking; one usually has to rely on observing effects in the individual patient.

Grey scales uncover similar attentional effects in homonymous hemianopia and visual hemi-neglect.

Multi-component models of visual hemi-neglect have postulated that visual hemi-neglect is characterised by various attentional deficits. A grey scales task has been developed to quantify the early, automatic, (perhaps obligatory) ipsilesional orienting of visual attention, frequently assumed as the first of these attentional deficits. Explanations for this attentional imbalance are up until now mainly formulated in terms of right hemisphere activation. This lateral attentional bias has also been demonstrated in controls, in whom it is expressed as a leftward perceptual asymmetry. We reproduced previous literature findings on a grey scales task, considering controls and neglect patients. Three patients with neglect showed an extreme ipsilesional lateral bias. This bias did not change during or after cognitive rehabilitation. Additionally, we presented this grey scale task to 32 patients with left- and right-sided homonymous hemianopia (HP). HP is the loss of sight in one visual hemi-field. The HH patients had no clinical signs of impaired lateralised attention. Results revealed that HH patients showed a similar ipsilesional bias, albeit to a lesser degree than in neglect. Left-sided HH patients presented a quantitatively similar, but qualitatively opposite bias than the right-sided HH patients. We suggest that sensory effects can be an alternative source of attentional imbalance, which can interact with the previously proposed (right) hemispheric effects. This suggests that the perceptual asymmetry in the grey scales task is not necessarily an indicator of impaired right hemisphere attention. It rather suggests a pattern of functional cerebral asymmetry, which can also be caused by asymmetric sensory input.

Azathioprine in myasthenia gravis: observations in 41 patients and a review of literature.

We report azathioprine treatment of 41 patients with myasthenia gravis, with a follow-up of more than 3 yr. The data show that azathioprine is effective in controlling the disease, both as a single drug as well as in combination with prednisone. In addition it may be steroid sparing. Older patients derived more benefit from the medicament. Side-effects could be managed fairly well, except for one patient who developed a non-Hodgkin lymphoma. Data from this study do not support the supposition that the therapeutic effect of azathioprine is dependent on macrocytosis. Fluctuations of serum levels of antibodies to the acetylcholine receptor were simultaneous with clinical changes and thus were not of predictive volume for the clinical course.

HLA type is not indicative for the effect of thymectomy in myasthenia gravis.

The frequency of HLA types in a selected group of 40 patients with myasthenia gravis in relation to the effect of thymectomy and also to gender, and thymus histology was studied. As generally described we found a significant increase in the frequency of HLA-A1, HLA-B8, HLA-DR3 and HLA-DQ2 in the total group. There were no further differences between subgroups of patients, which demonstrates that HLA type is not indicative for the effect of thymectomy in myasthenia gravis.

Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients.

Myasthenia gravis (MG) susceptibility is partially determined by allelic heterogeneity of immune-modulatory genes. IgG receptors (FcgammaR) link the humoral and cellular branches of the immune system, and regulate immune responses and inflammation. Three FcgammaR subclasses (FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb) exhibit functional polymorphisms, which affect efficiency of FcgammaR-mediated functions. FcgammaRIIa genotypes, but not FcgammaRIIIa and FcgammaRIIIb genotypes, were differentially distributed among 107 MG patients as compared to 239 healthy controls (Pz.Lt;0.01), with a relative increase of the FcgammaRIIa-R/R131 genotype (Odds ratio 2.4, 95% confidence interval 1.4-3.9). These data suggest that the FcgammaRIIa-R/R131 genotype is a marker for susceptibility to MG.

HLA class I and II in Lambert-Eaton myasthenic syndrome without associated tumor.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder, in which antibodies against voltage-gated calcium channels located at nerve terminals cause muscle weakness and autonomic dysfunction. In approximately half of the patients the autoimmune process is initiated by a tumor. In the other half of patients no tumor is found and the etiology is unknown. The aims of this study were to investigate the strength of HLA-associations with nontumor LEMS (NT-LEMS) and to study the relation of HLA-haplotypes with age at onset of LEMS and other clinical features. Therefore, typing of HLA class I and II was performed in 19 patients with NT-LEMS, who were clinically evaluated. NT-LEMS was significantly associated with alleles of both HLA-class I (i.e. HLA-B8) as well as -class II (i.e. HLA-DR3 and -DQ2). HLA-B8+ patients had significantly younger age at onset of LEMS and tended to be female. This study shows that HLA-class I haplotype is associated with a distinct phenotype in NT-LEMS.

Myasthenia gravis: diagnosis and follow-up of 100 consecutive patients.

One hundred consecutive patients with myasthenia gravis (MG) referred between 1985 and 1989 were analysed for epidemiological characteristics, evolution of early signs, delay in diagnosis, yield of diagnostic tests and effects of treatment. The female to male ratio was 1.6:1.0. Sixteen patients had a thymoma. Ocular MG occurred in 14. Associated autoimmune diseases were found in 15 patients. In 34% of the women and 10% of the men the diagnosis was delayed for more than 2 years. In the first 3 months progression was more rapid in men than in women. Anti-acetylcholine receptor antibodies were found in 94% of the patients with generalized MG and in 29% of the ocular patients. The neostigmine or the edrophonium test was positive in 84% of the generalized and in 60% of the ocular patients. Electromyography was diagnostic in 71% of the generalized and in 42% of the ocular patients tested. Thymectomy was performed in 56 patients (12 with thymomas). Fifty-one per cent were treated with one or more immunosuppressive drugs, at any time. After a mean follow-up of 9.6 years after onset remissions had occurred in 43%, considerable improvement in 25%, moderate improvement in 20% and 12% remained unchanged. There were no deaths due to MG. Thirty-six per cent remained dependent on immunosuppressive drugs. Medication-free remission was most frequent (35%) in the early-onset (< 50 years) group. Side-effects of pyridostigmine were noted in 34% of 99 patients, of prednisone in 65% of 49 patients, and of azathioprine in 54% of 28 patients, but these necessitated stopping the drug in only 1%, 10% and 14% respectively.

Antibodies to skeletal muscle in myasthenia gravis. Part 3. Relation with clinical course and therapy.

Fluctuations of anti skeletal muscle antibodies (AMA) were studied in relation to clinical changes and fluctuations in anti acetylcholine receptor antibodies (a-AChR). Forty-two patients with generalized myasthenia gravis were studied in clinical and serological follow-up during several years under various conditions. Results from this study demonstrate that AMA fluctuate in strong relation to a-AChR, clinical course and immunosuppressive therapy. Thymomectomy resulted in an increase or de novo appearance of AMA in 10 of the 12 patients who did not receive immunosuppressive medication.

Antibodies to skeletal muscle in myasthenia gravis. Part 2. Prevalence in non-thymoma patients.

Anti-skeletal muscle antibodies (AMA) were measured in 340 non-thymoma patients with myasthenia gravis (MG) by both an ELISA with citric acid muscle extract and by immunofluorescence assay. Three a-AChR negative but AMA-positive patients were found. The occurrence of AMA was related to the age at onset in patients with an onset of MG beyond 40 years and with duration of disease in patients with an earlier onset of MG. This stresses the heterogeneity of late onset and early onset MG. Serial measurements in individual patients revealed no evidence for a thymic role in the generation of AMA. There was no difference in specificity of AMA in early and late onset patients. The presence of AMA in CT-negative patients is not necessarily suggestive of a radiological shortcoming in the detection of thymoma since in 16 AMA-positive patients from our series no thymoma was found at operation or obduction.

Antibodies to skeletal muscle in myasthenia gravis. Part 1. Diagnostic value for the detection of thymoma.

The role of anti-muscle antibodies (AMA) in the diagnosis of thymoma in patients with myasthenia gravis (MG) is evaluated. We compared ELISA and Western blot assay for antibodies to citric acid muscle extract (a-CAE) with an immunofluorescence assay (IF). Sera from 234 selected MG patients and 123 controls were tested. There was no essential difference between ELISA and IF. Western blot was superior in young onset patients but less useful in patients with an onset beyond the age of 40 years. Unusually high post-test probabilities were found by our patient selection criteria which seem most realistic for clinical practice. Western blot revealed no differences in specificity of AMA in thymoma and non-thymoma patients irrespective of age at onset of disease.

What's in a smile?: Quantification of the vertical smile of patients with myasthenia gravis.

Many patients with myasthenia gravis who experience bulbar symptoms show a vertical smile, which may have a considerable, and often underestimated, impact on social life. Peri-oral muscle function can be quantified by calculating lip-length and snout indices, which indicate the degree to which a person is capable of smiling and of pursing the lips, respectively. In the present study patients with bulbar myasthenia gravis were compared to patients with ocular myasthenia gravis, patients now in remission (but previously suffering from bulbar myasthenia gravis), and healthy subjects. The lip-length and snout indices of patients with bulbar myasthenia gravis were significantly lower than those of the other groups. The facial impairments were no longer detectable in patients with bulbar myasthenia gravis in remission and no subclinical impairments in lip-length and snout indices were found in the ocular myasthenia gravis group. These findings were consistent with the patients' reports of impairment of smiling and other oral functions. The patients suffering from a vertical smile or other oral impairments were well aware of their condition, most probably because of the social consequences of being unable to smile. The indices could be of importance in the longitudinal evaluation of therapy in individual patients and in pharmacotherapeutical research. We found a low correlation between the lip-length and snout indices, which reflects the capricious pattern of involvement of separate muscles in myasthenia gravis. Therefore both indices deserve special attention if they are used for monitoring myasthenic symptoms.

Masticatory performance in patients with myasthenia gravis.

Masticatory muscle electromyograms (EMGs) were recorded while patients with bulbar myasthenia gravis chewed artificial food and compared with those of patients with ocular myasthenia gravis, patients in clinical remission who had previously suffered from bulbar myasthenia gravis and healthy individuals. Masticatory performance and EMGs were significantly smaller in the bulbar group. There were no indications of subclinical masticatory muscle weakness in patients with bulbar myasthenia gravis in remission and in patients with ocular myasthenia gravis. Patients with bulbar myasthenia gravis barely compensated for muscular weakness by chewing at a higher percentage of their maximal EMG. These quantitative findings, when combined with subjective reports of masticatory muscle weakness, show that a need to support the jaw is characteristic of patients with bulbar myasthenia gravis who produce low EMG activity.

Myasthenia gravis on the Dutch antilles: an epidemiological study.

We carried out an epidemiological study on the prevalence and annual incidence of myasthenia gravis on tropical islands Curaçao and Aruba in the period 1980-1995. Twenty-one patients (seven men and 14 women) were identified. The point prevalence increased from 29 per million in 1980 to about 70 per million in 1990-1995; the annual incidence over the total period was 4.7 per million. The female:male ratio was 2:1; purely ocular cases (2/21) comprised 9.5% and thymomas (4/21), 19%. These data are in accordance with most other epidemiological studies in non-tropical areas. No other studies on myasthenia gravis in tropical areas have been reported.