Withdrawal of antiepileptic drugs in patients with low grade and anaplastic glioma after long-term seizure freedom: a prospective observational study.

BACKGROUND: When glioma patients experience long-term seizure freedom the question arises whether antiepileptic drugs (AEDs) should be continued. As no prospective studies exist on seizure recurrence in glioma patients after AED withdrawal, we evaluated the decision-making process to withdraw AEDs in glioma patients, and seizure outcome after withdrawal. METHODS: Patients with a histologically confirmed low grade or anaplastic glioma were included. Eligible patients were seizure free ≥ 1 year from the date of last antitumor treatment, or ≥ 2 years since the last seizure when seizures occurred after the end of the last antitumor treatment. Patients and neuro-oncologists made a shared decision on the preferred AED treatment (i.e. AED withdrawal or continuation). Primary outcomes were: (1) outcome of the shared decision-making process and (2) rate of seizure recurrence. RESULTS: Eighty-three patients fulfilled all eligibility criteria. However, in 12/83 (14%) patients, the neuro-oncologist had serious objections to AED withdrawal. Therefore, 71/83 (86%) patients were analyzed; In 46/71 (65%) patients it was decided to withdraw AED treatment. In the withdrawal group, 26% (12/46) had seizure recurrence during follow-up. Seven of these 12 patients (58%) had tumor progression, of which three within 3 months after seizure recurrence. In the AED continuation group, 8% (2/25) of patients had seizure recurrence of which one had tumor progression. CONCLUSION: In 65% of patients a shared decision was made to withdraw AEDs, of which 26% had seizure recurrence. AED withdrawal should only be considered in carefully selected patients with a presumed low risk of tumor progression.

Assessment of the anterior loop of the inferior alveolar nerve using reformatted computed tomography: a retrospective study.

The anterior loop of the inferior alveolar nerve (IAN) is an important landmark in the anterior mandible that must be considered during the placement of dental implants. We measured the length and prevalence of loops of the IAN in 188 consecutive, dentate patients using reformatted computed tomography (CT). A total of 158/188 (84%) had at least one anterior loop; 111/188 (59%) had bilateral loops. The mean (SD) length of the loops in the third quadrant was 1.4 (0.7)mm; 95% CI 1.3 to 1.6; (range 0.3 - 4.0mm). The mean (SD) length of the loops in the fourth quadrant was 1.5 (0.9)mm; 95% CI 1.4 to 1.6; range 0.3 - 5.5mm. In total 42/188 (22%) had loops that were longer than 2mm in quadrants three and four. CT images that have been reformatted with specialised software may be useful to identify loops in the IAN, particularly when recent cone-beam CT images are not freely available. The prevalence of these loops is high while their length varies, which makes meticulous assessment necessary before the placement of implants.

Students' perceptions of vertical and horizontal integration in a discipline-based dental school.

INTRODUCTION: Integration is a key concern in discipline-based undergraduate dental curricula. Therefore, this study compared feedback on integration from students who participated in different instructional designs in a Comprehensive Patient Care course. METHODS: The study was conducted at the University of Pretoria (2009-2011). Third-year cohorts (Cohorts A, B and C) participated in pre-clinical case-based learning, whilst fourth-year cohorts (Cohorts D and E) received didactic teaching in Comprehensive Patient Care. Cohorts A, D and E practised clinical Comprehensive Patient Care in a discipline-based clinic. Cohort B conducted their Comprehensive Patient Care patient examinations in a dedicated facility supervised by dedicated faculty responsible to teach integration. Students had to indicate on visual analogue scales whether the way they were taught at the school helped them to integrate knowledge from the same (horizontal integration) and preceding (vertical integration) year of study. The end-points of the scales were defined as 'definitely' and 'not at all'. Analysis of variance (ANOVA) was employed to measure the differences between cohorts according to the year of study. RESULTS: Third-year case-based learning cohorts rated the horizontal integration close to 80/100 and vertical integration ranging from 64 to 71/100. In year four, Cohort B rated vertical and horizontal integration 9-15% higher (ANOVA, P < 0.05) than Cohorts A and D. In year five, Cohort A rated vertical and horizontal integration 11-18% higher (ANOVA, P < 0.05) than Cohorts D and E. CONCLUSION: Pre-clinical case-based learning and Comprehensive Patient Care supervised by dedicated faculty were associated with more favourable perceptions about integration in the discipline-based undergraduate dental curriculum.

Developing students' clinical reasoning skills: correlates of perceived relevance of two teaching and learning approaches.

INTRODUCTION: 'Relevance' is a key concept in adult learning. Hence, this study sought to examine students' perceptions of relevance of the teaching and learning in relation to different instructional designs employed in a Comprehensive Patient Care (CPC) course that aims to develop integrated clinical reasoning skills. METHODS: Third to fifth year students (2009-2011) were asked to anonymously rate the relevance of the instructional design (RELID) they participated in by means of visual analogue scales at the School of Dentistry, University of Pretoria. They were also asked to rate their perceptions of the alignment between teaching and learning and outcomes (ATLO), assessments' contribution to learning (ACL), course organisation (CO) and teacher competence (TC). RELID served as the outcome measure in stepwise linear regression analyses. ATLO, ACL, CO, TC and the instructional design (case-based learning (CBL = 1) and the combination of discipline-based and lecture-based teaching in CPC (DB-LBT = 0)) served as the co-variables for each of the years of study. RESULTS: The analyses showed positive correlations between RELID and ATLO and between RELID and ACL for all the years of study. RELID was associated with TC in year three and four and CO was associated with RELID in year four and five. CBL outperformed DB-LBT in terms of perceived relevance of the teaching and learning. CONCLUSION: The results suggest that students' perceptions of the relevance of the instructional design may be enhanced when outcomes, teaching, learning and assessment are constructively aligned during the development of clinical reasoning skills.

Socio-demographic and academic correlates of clinical reasoning in a dental school in South Africa.

INTRODUCTION: There are no empirical studies that describe factors that may influence the development of integrated clinical reasoning skills in dental education. Hence, this study examines the association between outcomes of clinical reasoning in relation with differences in instructional design and student factors. MATERIALS AND METHODS: Progress test scores, including diagnostic and treatment planning scores, of fourth and fifth year dental students (2009-2011) at the University of Pretoria, South Africa served as the outcome measures in stepwise linear regression analyses. These scores were correlated with the instructional design (lecture-based teaching and learning (LBTL = 0) or case-based teaching and learning (CBTL = 1), students' grades in Oral Biology, indicators of socio-economic status (SES) and gender. RESULTS: CBTL showed an independent association with progress test scores. Oral Biology scores correlated with diagnostic component scores. Diagnostic component scores correlated with treatment planning scores in the fourth year of study but not in the fifth year of study. 'SES' correlated with progress test scores in year five only, while gender showed no correlation. CONCLUSION: The empirical evidence gathered in this study provides support for scaffolded inductive teaching and learning methods to develop clinical reasoning skills. Knowledge in Oral Biology and reading skills may be important attributes to develop to ensure that students are able to reason accurately in a clinical setting.

Prognostic value of the S100B protein in newly diagnosed and recurrent glioma patients: a serial analysis.

The S100B protein is associated with brain damage and a breached blood-brain barrier. A previous pilot study showed that high serum levels of S100B are associated with shorter survival in glioma patients. The aim of our study was to assess the prognostic value in terms of survival and longitudinal dynamics of serum S100B for patients with newly diagnosed and recurrent glioma. We obtained blood samples from patients with newly diagnosed and recurrent glioma before the start (baseline) and at fixed time-points during temozolomide chemotherapy. S100B-data were dichotomized according to the upper limit of the reference value of 0.1 µg/L. Overall survival (OS) was estimated with Kaplan-Meier curves and groups were compared with the log rank analysis. To correct for potential confounders a Cox regression analysis was used. We included 86 patients with newly-diagnosed and 27 patients with recurrent glioma. Most patients in both groups had baseline serum levels within normal limits. In the newly diagnosed patients we found no significant difference in OS between the group of patients with S100B levels >0.1 µg/L at baseline compared to those with <0.1 µg/L. In the patients with recurrent glioma we found a significantly shorter OS for patients with raised levels. In both groups, S100B values did not change significantly throughout the course of the disease. Serum S100B levels do not seem to have prognostic value in newly diagnosed glioma patients. In recurrent glioma patients S100B might be of value in terms of prognostication of survival.

Developing integrated clinical reasoning competencies in dental students using scaffolded case-based learning - empirical evidence.

INTRODUCTION: This study provides empirical evidence of the development of integrated clinical reasoning in the discipline-based School of Dentistry, University of Pretoria, South Africa. Students were exposed to case-based learning in comprehensive patient care (CPC) in the preclinical year of study, scaffolded by means of the four-component instructional design model for complex learning. METHODS: Progress test scores of third- to fifth-year dental students, who received case-based teaching and learning in the third year (2009-2011), were compared to the scores of preceding fourth- and fifth-year cohorts. These fourth- and fifth-year cohorts received content-based teaching concurrently with their clinical training in CPC. The progress test consisted of a complex case study and 32 MCQs on tracer conditions. Students had to gather the necessary information and had to make diagnostic and treatment-planning decisions. RESULTS: Preclinical students who participated in the case-based teaching and learning achieved similar scores compared to final-year students who received lecture-based teaching and learning. Final-year students who participated in the case-based learning made three more correct clinical decisions per student, compared to those who received content-based teaching. Students struggled more with treatment-planning than with diagnostic decisions. CONCLUSION: The scaffolded case-based learning appears to contribute to accurate clinical decisions when compared to lecture-based teaching. It is suggested that the development of integrated reasoning competencies starts as early as possible in a dental curriculum, perhaps even in the preclinical year of study. Treatment-planning should receive particular attention.

Developing clinical reasoning in the classroom - analysis of the 4C/ID-model.

OBJECTIVES: The purpose of this study is to provide a theoretical rationale for the implementation of the four-component instructional design model for complex learning (4C/ID-model) at the University of Pretoria with the aim of systematically developing the clinical reasoning of undergraduate dental students in a classroom setting. METHODS: Recent literature provides a rationale for the use of the 4C/ID-model to teach clinical reasoning in terms of four strategic teaching and learning needs: (i) the need for authenticity in the learning process; (ii) the need to manage cognitive load during the learning process; (iii) the need for repeated practice; (iv) a need for valid assessment, feedback and reflection. RESULTS AND DISCUSSION: The literature review indicated that the 4C/ID-model makes provision for teaching and learning in an authentic context and proposes systematically structured methods that could be practically applied to manage cognitive load during repetitive exercises. The model also makes provision for cognitive feedback following assessment in order to eliminate misconceptions about content and to develop the cognitive strategies of the learner. CONCLUSIONS: On the basis of the literature review above, it is recommended that the 4C/ID-model be considered as a basis for classroom teaching and learning to develop competence in clinical reasoning in undergraduate dental students, even at pre-clinical level. The model may also have an application in medical education.

Symptoms and medication management in the end of life phase of high-grade glioma patients.

During the end of life (EOL) phase of high-grade glioma (HGG) patients, care is primarily aimed at reducing symptom burden while maintaining quality of life as long as possible. In this study, we evaluated the prevalence of symptoms and medication management in HGG patients during the EOL phase. We analyzed disease-specific symptoms, general EOL symptoms, symptom frequency, and medication use at 3 months and 1 week before death in a cohort of 178 HGG patients, based on questionnaires completed by physicians responsible for EOL care. In addition, information on patient's perceived quality of care (QOC) was derived from 87 questionnaires completed by patient's relatives. Somnolence, focal neurological deficits and cognitive disturbances were the most prevalent symptoms during the EOL phase. Overall, disease-specific symptoms occurred more often than general EOL symptoms at both 3 months and 1 week before death. Somnolence and/or dysphagia were present in 81 % of patients whose medication was withdrawn and 96 % of patients in whom antiepileptic drugs (AEDs) were withdrawn. One week before death, 65.9 % of patients with high symptom frequency experienced good QOC, compared to 87.5 % of patients with low symptom frequency (p = 0.032). Disease-specific symptoms are the main concern in EOL care for HGG patients. Somnolence and dysphagia may hamper the regular oral administration of drugs, and particularly AEDs, during the EOL phase. High symptom frequency at 1 week before death negatively affects patient's perceived QOC.

End of life care in high-grade glioma patients in three European countries: a comparative study.

Exploring cross-national differences is useful to evaluate whether different patterns of end of life (EOL) care meet patient's specific needs. This study aimed to (1) compare EOL care processes for high-grade glioma (HGG) patients in three European countries, (2) explore differences in perceived quality of care (QOC), and (3) identify aspects of good QOC in the EOL phase. We analyzed 207 questionnaires from relatives of deceased HGG patients, using a similar retrospective study design in three countries [The Netherlands (n = 83), Austria (n = 72) and the UK (n = 52)], and examined four subthemes: (1) organization of EOL care, (2) treatment preferences, (3) experiences with EOL care, (4) perceived QOC. Three months before death 75 % of patients were at home. In all countries, on average, 50 % were transferred to a hospital at least once and received effective symptom treatment during the last 3 months. In The Netherlands, Austria and UK, respectively, patients most often died at home (60 %), in a hospital (41 %) or hospice (41 %) (p < 0.001). Advance directives were present in 46 % of Dutch, 36 % of British and 6 % of Austrian patients (p < 0.001). Fifty-three percent of patients experienced good QOC, irrespective of country. Dying at the preferred place, satisfaction with information provided and effective symptom treatment were independently associated with good QOC. There are various cross-national differences in organization and experiences with EOL care for HGG, but patient's perceived QOC is similar in the three countries. As symptom treatment was considered effective in only half of HGG patients, and independently predicted good QOC, this particularly needs further improvement in all countries.

Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma: a prospective longitudinal study.

Following tumor resection, the majority of high-grade glioma (HGG) patients are treated with a combined modality regimen of radiotherapy and temozolomide. As a result of the tumor itself or as treatment-related neurotoxic side-effects, these patients may experience cognitive deficits. Additionally, radiological abnormalities expressed as white matter hyperintensities (WMH) and cerebral atrophy (CA) can develop. In this study, these functional and morphological parameters are evaluated, and their relation is investigated. After surgery, HGG patients underwent chemo-irradiation for six weeks, followed by six cycles of temozolomide. Assessments were performed before chemo-irradiation, post-concomitantly, after the third and sixth adjuvant cycle, and 3 and 7 months after treatment. Degree of WMH and CA was scored on MRI. Patients' neuropsychological performance was compared to healthy matched controls, yielding six cognitive domain z-scores. Development or progression of pre-existing WMH and CA during follow-up was observed in 36 and 45 % of the patients (n = 39) respectively. Cognitive functioning remained stable or improved in 70 % of the patients and deteriorated in 30 % of the patients (n = 33). Of the cognitive decliners, 80 % had tumor progression within 4 months thereafter. No clear association between cognitive functioning and WMH or CA was found. Central neurotoxic effects of combined modality treatment in HGG patients expressed by radiological abnormalities are encountered in approximately 40 % of patients. However, functional impact as indexed by cognitive functioning was found to be limited. Furthermore, development or progression of pre-existing WMH and CA does not consistently result in functional impairment as measured by cognitive tests.

Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin.

BACKGROUND: The different perception and assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) between healthcare providers and patients has not yet been fully addressed, although these two approaches might eventually lead to inconsistent, possibly conflicting interpretation, especially regarding sensory impairment. PATIENTS AND METHODS: A cohort of 281 subjects with stable CIPN was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC v. 2.0) sensory scale, the clinical Total Neuropathy Score (TNSc©), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (mISS) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). RESULTS: Patients' probability estimates showed that the EORTC QLQ-CIPN20 sensory score was overall more highly related to the NCI-CTC sensory score. However, the vibration perception item of the TNSc had a higher probability to be scored 0 for EORTC QLQ-CIPN20 scores lower than 35, as vibration score 2 for EORTC QLQ-CIPN20 scores between 35 and 50 and as grade 3 or 4 for EORTC QLQ-CIPN20 scores higher than 50. The linear models showed a significant trend between each mISS item and increasing EORTC QLQ-CIPN20 sensory scores. CONCLUSION: None of the clinical items had a perfect relationship with patients' perception, and most of the discrepancies stood in the intermediate levels of CIPN severity. Our data indicate that to achieve a comprehensive knowledge of CIPN including a reliable assessment of both the severity and the quality of CIPN-related sensory impairment, clinical and PRO measures should be always combined.

Rasch-built Overall Disability Scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS).

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary R-ODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS: After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION: Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

Childhood brain tumours due to germline bi-allelic mismatch repair gene mutations.

Childhood brain tumours may be due to germline bi-allelic mismatch repair (MMR) gene mutations in MLH1, MSH2, MSH6 or PMS2. These mutations can also lead to colorectal neoplasia and haematological malignancies. Here, we review this syndrome and present siblings with early-onset rectal adenoma and papillary glioneural brain tumour, respectively, due to novel germline bi-allelic PMS2 mutations. Identification of MMR protein defects can lead to early diagnosis of this condition. In addition, assays for these defects may help to classify brain tumours for research protocols aimed at targeted therapies.

An analysis of complaints against oral health professionals charged with misconduct at the HPCSA: 2004-2009.

AIM: This study investigates the nature, frequency, and outcome of complaints relating to misconduct laid against oral healthcare professionals (OHPs), charged with misconduct in South Africa. METHODS: Records of the Health Professions Council of South Africa (2004-2009) were analysed and classified using the ethical rules as a reference. "Clinically-related complaints" and "fraud" were added as extra categories. The nature and outcome of the complaints and the penalties were quantified, and the detailed nature of the complaints was qualitatively reported. RESULTS: Two percent of the registered dentists and 5.5% of the registered dental therapists were charged with misconduct. Clinically related complaints (59%) and fraud (29%) were most prevalent amongst the accused dentists. Fraud (46%), clinically related complaints (19%), advertising (15%), infection control (8%), and creating expectations that could not be met (8%) were the most common complaints against dental therapists. CONCLUSIONS: Substandard dental treatment and fraud were the main reasons for patient dissatisfaction that led to OHPs being charged with misconduct. Both these undesirable practices may be financially motivated. OHPs should take cognisance of these statistics and should adjust their professional approach accordingly in order to reflect acceptable ethical behaviour.

Clinical correlates of oral malodour in a population of patients attending a preventive clinic in Pretoria, South Africa.

AIM: This study investigates the occurrence of oral malodour in an adult dental clinic population in Pretoria, South Africa, and the clinical parameters associated with the condition. METHODS: Data collected from new patients (n=896), examined by oral hygiene students under supervision of instructors, between January - October 2004, were retrospectively analysed. Subjects self-reported their medical history and smoking status. Caries experience, plaque index, pocket depths, bleeding on probing (BOP), tongue coating status, and oral hygiene practises were recorded. Malodour was diagnosed using the halimeter (> or = 120ppb) and an organoleptic measurement (0-5 point scale) of > or = 3. Data analysis included chi-square, t-tests and logistical regression. RESULTS: 15.1% presented with organoleptically-determined malodour and 20.9% presented with malodour detected by the use of the halimeter. Irrespective of the diagnostic tool used, tongue coating, increased plaque levels and BOP were associated with an increased likelihood for oral malodour, while regular flossing reduced the likelihood of presenting with the condition. Periodontitis was associated with oral malodour when applying organoleptic ratings, but not with the halimeter. CONCLUSIONS: Oral malodour prevalence corresponds with values reported in developed countries. Interdental flossing was the most effective self-care practise associated with a reduced likelihood of presenting with malodour. Halimeter performance should be further investigated in relation to varying degrees of severity of periodontal disease.