Implementation of at-line capillary zone electrophoresis for fast and reliable determination of adenovirus concentrations in vaccine manufacturing.

A CZE method was validated and implemented for fast and accurate in-process determination of adenovirus concentrations of downstream process samples obtained during manufacturing of adenovirus vector-based vaccines. An analytical-quality-by-design approach was embraced for method development, method implementation, and method maintenance. CZE provided separation of adenovirus particles from sample matrix components, such as cell debris, residual DNA and proteins. The intermediate precision of the virus particle concentration was 6.9% RSD and the relative bias was 2.3%. In comparison, the CZE method is intended to replace a quantitative polymerase chain reaction method which requires three replicates in three analytical runs to achieve an intermediate precision of 8.1% RSD. Given that, in addition, the time from sampling till reporting results of the CZE method was less than 2 h, whereas quantitative polymerase chain reaction requires 3 days, it follows that the CZE method enables faster processing times in downstream processing.

Exploring mechanisms of change in cognitive therapy and interpersonal psychotherapy for adult depression.

The present study explored the temporal relationships between change in five candidate causal mechanisms and change in depressive symptoms in a randomized comparison of individual Cognitive Therapy (CT) and Interpersonal Psychotherapy (IPT) for adult depression. Furthermore, hypotheses concerning the mediation of change in these treatments were tested. Patients were 151 depressed adult outpatients treated with either CT (n = 76) or IPT (n = 75). Depression severity was assessed with the BDI-II. Candidate mediators included both therapy-specific as well as common factors. Measures were taken multiple times over the course of treatment (baseline, mid-, and post-treatment). Pearson's correlations and Latent-Difference-Score models were used to examine the direct and indirect relationships between (change in) the candidate mediators and (subsequent) (change in) depression. Patients showed improvement on all measures. No differential effects in pre- to post-treatment changes were observed between the two conditions. However, change in interpersonal functioning occurred more rapidly in IPT. Only little empirical support for the respective theoretical models of change in CT and IPT was found. Future studies should pay special attention to the timing of assessments and within-patient variance.

Pneumonia, Intake Problems, and Survival Among Nursing Home Residents With Variable Stages of Dementia in the Netherlands: Results From a Prospective Observational Study.

OBJECTIVES: We explored how pneumonia and intake problems affect survival in nursing home residents in variable stages of dementia. METHODS: In a longitudinal observational study (372 residents) with up to 3.5 years of follow-up, we examined relationships between dementia severity, the development of pneumonia, intake problems, and mortality using joint modeling, Cox models, and mediation analyses. Dementia severity was measured semiannually with the Bedford Alzheimer Nursing Severity-Scale (BANS-S). RESULTS: The median BANS-S score at baseline was 13 (range, 7 to 28). Pneumonia occurred in 103 (28%) and intake problems in 126 (34%) of 367 residents with complete registration of pneumonia and intake problems. Compared with dementia severity, incident pneumonia and, even more so, incident intake problems were more strongly associated with mortality risk. Pneumonia and intake problems both mediated the relationship between more severe dementia and mortality. DISCUSSION: Developing pneumonia and intake problems affects survival, and this is not limited to advanced dementia. The occurrence of pneumonia and intake problems are important signals to consider a palliative care approach in nursing home residents with dementia, and an active focus on advance care planning is needed. Future studies should investigate whether this is also relevant for patients in primary care.

Improving comfort in people with dementia and pneumonia: a cluster randomized trial.

BACKGROUND: Pneumonia in people with dementia has been associated with severe discomfort. We sought to assess the effectiveness of a practice guideline for optimal symptom relief for nursing home residents with dementia and pneumonia. METHODS: A single-blind, multicenter, cluster randomized controlled trial was conducted in 32 Dutch nursing homes. Outcomes were assessed on the patient level. The main outcome measures were discomfort and symptoms: discomfort (DS-DAT: Discomfort Scale-Dementia of Alzheimer Type), (lack of) comfort (EOLD-CAD: End Of Life in Dementia-Comfort Assessment in Dying), pain (PAINAD: Pain Assessment in Advanced Dementia), and respiratory distress (RDOS: Respiratory Distress Observation Scale). Outcomes were scheduled daily from diagnosis until 10 days later and a final time between 13-15 days from diagnosis by trained observers who were blinded to the intervention and the residents' condition and treatment. In a pre-intervention phase, usual care was provided to all homes. In the intervention phase, matched clusters of homes were randomized to either the control (n = 16) or intervention condition (n = 16). RESULTS: Between 1 January 2012 and 1 May 2015, 464 episodes of pneumonia were included. Outcomes were obtained for 399 episodes in 367 residents. Longitudinal multilevel linear regression analyses were performed on log-transformed outcomes, so coefficients should be interpreted as a ratio, and a coefficient of 1 means no difference. The practice guideline in the intervention phase did not reduce the level of discomfort and symptoms: DS-DAT: 1.11 (95 % CI 0.93-1.31), EOLD-CAD: 1.01 (95 % CI 0.98-1.05), PAINAD: 1.04 (95 % CI 0.93-1.15), RDOS: 1.11 (95 % CI 0.90-1.24). However, in both the intervention and control groups, lack of comfort and respiratory distress gradually decreased during the entire 3.5 years of data collection, and were lower in the intervention phase compared to the pre-intervention phase: DS-DAT: 0.93 (95 % CI 0.85-1.01), EOLD-CAD: 0.98 (95 % CI 0.97-1.00), PAINAD: 0.96 (95 % CI 0.91-1.01), RDOS: 0.92 (95 % CI 0.87-0.98). CONCLUSIONS: When compared to usual care, the practice guideline for optimal symptom relief did not relieve discomfort and symptoms in nursing home residents with dementia and pneumonia. However, discomfort and symptoms decreased gradually throughout the data collection in both the intervention homes and the control homes. An intervention that focuses on creating awareness may be more effective than a physician practice guideline. TRIAL REGISTRATION: The Netherlands National Trial Register (ID number NTR5071 . Registered 10 March 2015).

Mediators of Exercise Effects on HRQoL in Cancer Survivors after Chemotherapy.

PURPOSE: We investigated the hypothesis that combined resistance and endurance exercise improves cardiorespiratory fitness and muscle strength, thereby reducing fatigue and improving global quality of life (QoL) and physical function among cancer survivors who completed curative treatment including chemotherapy. METHODS: Cancer survivors were assigned to a 12-wk exercise intervention (n = 186) or a wait list control group (n = 91). Data were collected at baseline and after 12 wk. Path analyses using follow-up values adjusted for baseline values, age, and gender were conducted to test if the exercise effects on global QoL and physical function (European Organization Research and Treatment of Cancer Quality of Life questionnaire-Core 30) were mediated by changes in cardiorespiratory fitness (peak V˙O2), hand-grip strength, lower body muscle function (30-s chair stand test), and fatigue (Multidimensional Fatigue Inventory). RESULTS: Compared with the wait list control, exercise increased cardiorespiratory fitness (ß = 1.8; 95% confidence interval (CI), 1.0-2.6 mL·kg·min) and reduced general (ß = -1.0; 95% CI, -1.8 to -0.2) and physical fatigue (ß = -1.5; 95% CI, -2.3 to -0.6). The exercise effect on physical fatigue was mediated by change in cardiorespiratory fitness (ß = -0.2; 95% CI, -0.4 to -0.1). Higher hand-grip strength was significantly associated with lower physical fatigue and better lower body muscle function with lower physical and general fatigue. Lower general fatigue and physical fatigue were significantly associated with higher global QoL (ß = -1.6; 95% CI, -2.2 to -1.1; and ß = -1.7; 95% CI, -2.3 to -1.1, respectively) and physical function (ß = -1.0; 95% CI, -1.3 to -0.7; and ß = -1.2; 95% CI, -1.6 to -0.9, respectively). The models explained 44%-61% of the variance in global QoL and physical function. CONCLUSION: Beneficial effects of exercise on global QoL and physical function in cancer survivors were mediated by increased cardiorespiratory fitness and subsequent reductions in fatigue.

Intra-Rater, Inter-Rater and Test-Retest Reliability of an Instrumented Timed Up and Go (iTUG) Test in Patients with Parkinson's Disease.

BACKGROUND: The "Timed Up and Go" (TUG) is a widely used measure of physical functioning in older people and in neurological populations, including Parkinson's Disease. When using an inertial sensor measurement system (instrumented TUG [iTUG]), the individual components of the iTUG and the trunk kinematics can be measured separately, which may provide relevant additional information. OBJECTIVE: The aim of this study was to determine intra-rater, inter-rater and test-retest reliability of the iTUG in patients with Parkinson's Disease. METHODS: Twenty eight PD patients, aged 50 years or older, were included. For the iTUG the DynaPort Hybrid (McRoberts, The Hague, The Netherlands) was worn at the lower back. The device measured acceleration and angular velocity in three directions at a rate of 100 samples/s. Patients performed the iTUG five times on two consecutive days. Repeated measurements by the same rater on the same day were used to calculate intra-rater reliability. Repeated measurements by different raters on the same day were used to calculate intra-rater and inter-rater reliability. Repeated measurements by the same rater on different days were used to calculate test-retest reliability. RESULTS: Nineteen ICC values (15%) were ≥ 0.9 which is considered as excellent reliability. Sixty four ICC values (49%) were ≥ 0.70 and < 0.90 which is considered as good reliability. Thirty one ICC values (24%) were ≥ 0.50 and < 0.70, indicating moderate reliability. Sixteen ICC values (12%) were ≥ 0.30 and < 0.50 indicating poor reliability. Two ICT values (2%) were < 0.30 indicating very poor reliability. CONCLUSIONS: In conclusion, in patients with Parkinson's disease the intra-rater, inter-rater, and test-retest reliability of the individual components of the instrumented TUG (iTUG) was excellent to good for total duration and for turning durations, and good to low for the sub durations and for the kinematics of the SiSt and StSi. The results of this fully automated analysis of instrumented TUG movements demonstrate that several reliable TUG parameters can be identified that provide a basis for a more precise, quantitative use of the TUG test, in clinical practice.

Evaluation of the Multiple Sclerosis Walking Scale-12 (MSWS-12) in a Dutch sample: Application of item response theory.

BACKGROUND: The Multiple Sclerosis Walking Scale-12 (MSWS-12) measures walking ability from the patients' perspective. We examined the quality of the MSWS-12 using an item response theory model, the graded response model (GRM). METHODS: A total of 625 unique Dutch multiple sclerosis (MS) patients were included. After testing for unidimensionality, monotonicity, and absence of local dependence, a GRM was fit and item characteristics were assessed. Differential item functioning (DIF) for the variables gender, age, duration of MS, type of MS and severity of MS, reliability, total test information, and standard error of the trait level (θ) were investigated. RESULTS: Confirmatory factor analysis showed a unidimensional structure of the 12 items of the scale, explaining 88% of the variance. Item 2 did not fit into the GRM model. Reliability was 0.93. Items 8 and 9 (of the 11 and 12 item version respectively) showed DIF on the variable severity, based on the Expanded Disability Status Scale (EDSS). However, the EDSS is strongly related to the content of both items. CONCLUSION: Our results confirm the good quality of the MSWS-12. The trait level (θ) scores and item parameters of both the 12- and 11-item versions were highly comparable, although we do not suggest to change the content of the MSWS-12.

Development of a Risk Stratification Model for Delayed Inpatient Recovery of Physical Activities in Patients Undergoing Total Hip Replacement.

STUDY DESIGN: Prospective cohort design using data derived from usual care. BACKGROUND: It is important that patients are able to function independently as soon as possible after total hip replacement. However, the speed of regaining activities differs significantly. OBJECTIVES: To develop a risk stratification model (RSM) to predict delayed inpatient recovery of physical activities in people who underwent total hip replacement surgery. METHODS: This study was performed in 2 routine orthopaedic settings: Diakonessenhuis Hospital (setting A) and Nij Smellinghe Hospital (setting B). Preoperative screening was performed for all consecutive patients. In-hospital recovery of activities was assessed with the Modified Iowa Level of Assistance Scale. Delayed inpatient recovery of activities was defined as greater than 5 days. The RSM, developed using logistic regression analysis and bootstrapping, was based on data from setting A (n = 154). External validation was performed on the data set from setting B (n = 271). RESULTS: Twenty-one percent of the patients in setting A had a delayed recovery of activities during their hospital stay. Multivariable logistic regression modeling yielded a preliminary RSM that included the following factors: male sex (odds ratio [OR] = 0.8; 95% confidence interval [CI]: 0.2, 2.6), 70 or more years of age (OR = 1.2; 95% CI: 0.4, 3.4), body mass index of 25 kg/m(2) or greater (OR = 2.2; 95% CI: 0.7, 7.4), an American Society of Anesthesiologists score of 3 (OR = 1.2; 95% CI: 0.3, 4.4), a Charnley score of B or C (OR = 6.1; 95% CI: 2.2, 17.4), and a timed up-and-go score of 12.5 seconds or greater (OR = 3.1; 95% CI: 1.1, 9.0). The area under the receiver operating characteristic (ROC) curve was 0.82 (95% CI: 0.74, 0.90) and the Hosmer-Lemeshow test score was 3.57 (P>.05). External validation yielded an area under the ROC curve of 0.71 (95% CI: 0.61, 0.81). CONCLUSION: We demonstrated that the risk for delayed recovery of activities during the hospital stay can be predicted by using preoperative data. Level of Evidence Prognosis, level 1b.

Motivation of medical students: selection by motivation or motivation by selection.

BACKGROUND: Medical schools try to implement selection procedures that will allow them to select the most motivated students for their programs. Though there is a general feeling that selection stimulates student motivation, conclusive evidence for this is lacking. The current study aims to use the perspective of Self-determination Theory (SDT) of motivation as a lens to examine how medical students' motivation differs in relation to different selection procedures. The hypotheses were that 1) selected students report higher strength and autonomous motivation than non-selected students, and 2) recently selected students report higher strength and autonomous motivation than non-selected students and students who were selected longer ago. METHODS: First- (Y1) and fourth-year (Y4) medical students in the six-year regular programme and first-year students in the four-year graduate entry programme (GE) completed questionnaires measuring motivation strength and type (autonomous-AM, controlled-CM). Scores were compared between students admitted based on selection, lottery or top pre-university GPA (top GPA) using ANCOVAs. Selected students' answers on open-ended questions were analysed using inductive thematic analysis to identify reasons for changes in motivation. RESULTS: The response rate was 61.4 % (n = 357). Selected students (Y1, Y4 and GE) reported a significantly higher strength of motivation than non-selected students (Y1 and Y4 lottery and top GPA) (p < 0.01). Recently selected students (Y1 and GE) reported significantly higher strength (p < 0.01) and higher AM (p < 0.01) and CM (p < 0.05) than non-selected students (lottery and top GPA) and Y4 students who were selected three years ago. Students described that being selected enhanced their motivation as they felt autonomous, competent and that they belonged to a special group. These reported reasons are in alignment with the basic psychological needs described by Self-Determination Theory as important in enhancing autonomous motivation. CONCLUSIONS: A comprehensive selection procedure, compared to less demanding admission procedures, does not seem to yield a student population which stands out in terms of autonomous motivation. The current findings indicate that selection might temporarily enhance students' motivation. The mechanism through which this occurs seems to be through feelings of autonomy, competence and relatedness inspired by selection.

The identification of cognitive subtypes in Alzheimer's disease dementia using latent class analysis.

OBJECTIVE: Alzheimer's disease (AD) is a heterogeneous disorder with complex underlying neuropathology that is still not completely understood. For better understanding of this heterogeneity, we aimed to identify cognitive subtypes using latent class analysis (LCA) in a large sample of patients with AD dementia. In addition, we explored the relationship between the identified cognitive subtypes, and their demographical and neurobiological characteristics. METHODS: We performed LCA based on neuropsychological test results of 938 consecutive probable patients with AD dementia using Mini-Mental State Examination as the covariate. Subsequently, we performed multinomial logistic regression analysis with cluster membership as dependent variable and dichotomised demographics, APOE genotype, cerebrospinal fluid biomarkers and MRI characteristics as independent variables. RESULTS: LCA revealed eight clusters characterised by distinct cognitive profile and disease severity. Memory-impaired clusters-mild-memory (MILD-MEM) and moderate-memory (MOD-MEM)-included 43% of patients. Memory-spared clusters mild-visuospatial-language (MILD-VILA), mild-executive (MILD-EXE) and moderate-visuospatial (MOD-VISP) -included 29% of patients. Memory-indifferent clusters mild-diffuse (MILD-DIFF), moderate-language (MOD-LAN) and severe-diffuse (SEV-DIFF) -included 28% of patients. Cognitive clusters were associated with distinct demographical and neurobiological characteristics. In particular, the memory-spared MOD-VISP cluster was associated with younger age, APOE e4 negative genotype and prominent atrophy of the posterior cortex. CONCLUSIONS: Using LCA, we identified eight distinct cognitive subtypes in a large sample of patients with AD dementia. Cognitive clusters were associated with distinct demographical and neurobiological characteristics.

Factors Related to Rejection of Care and Behaviors Directed towards Others: A Longitudinal Study in Nursing Home Residents with Dementia.

AIMS: The aim of this study was to analyze factors related to rejection of care and behaviors directed towards others in nursing home residents with dementia. METHODS: The relationship of lack of understanding, depression, psychosis and pain with rejection of care and behaviors directed towards others was explored using four assessments from the Minimum Data Set (MDS) within a period of 15 months on 1,101 residents with dementia in Dutch nursing homes. Presence of depressive symptoms was ascertained using a validated MDS scale, and presence of lack of understanding, rejection of care, psychosis and pain through the individual MDS items. A structural equation modeling approach and latent growth models were used to investigate the longitudinal relationship between changes in rejection of care and physical or verbal behaviors directed towards others, and changes in lack of understanding, pain, depression and psychotic symptoms. RESULTS: Changes in lack of understanding predicted changes in rejection of care, and there was also a relationship between changes in depression and rejection of care. Changes of behaviors directed towards others were related to changes in lack of understanding and depression. Pain and behaviors directed towards others were unrelated, and psychosis was rather stable throughout. A mediation model suggested that the relationship of lack of understanding with behaviors directed towards others was mediated by rejection of care. CONCLUSION: These results indicate that lack of understanding and depression are important factors in development of rejection of care and behaviors directed towards others. The relationship between lack of understanding and behaviors directed towards others is mediated by rejection of care. Improvement in communication between residents and caregivers, and perhaps also effective treatment of depression may prevent or ameliorate these behaviors directed towards others.

Going into surgery: Risk factors for hypertrophic scarring.

The aim of this study was to examine the association between possible risk factors for excessive scarring and the formation of hypertrophic scars (HTS). Hypertrophic skin scarring remains a difficult problem in medicine and can cause considerable morbidity. Nevertheless, few extensive prospective studies have been conducted which assess risk factors in relation to HTS formation. Therefore, a prospective observational study was performed. Patients who had elective cardiothoracic surgery were followed for the duration of 1 year and information was collected about a variety of possible risk factors in these patients. The associations between the risk factors and the development of HTSs were investigated. Body mass index, ethnic background, and scar related factors are positively associated with HTS formation. Antihypertensive therapeutics and factors influencing erythropoiesis are negatively associated with HTS formation.

From admission to death: prevalence and course of pain, agitation, and shortness of breath, and treatment of these symptoms in nursing home residents with dementia.

OBJECTIVES: Burdensome symptoms frequently develop as part of the dementia trajectory and influence quality of life. We explore the course of symptoms and their treatment during nursing home stay to help target adequate symptom management. DESIGN: Data were collected as part of the Dutch End of Life in Dementia study, a longitudinal observational study with up to 3.5 years of follow-up. Physicians performed assessments at baseline, semiannually, and shortly after death of pain, agitation, shortness of breath, and treatment provided for these symptoms. SETTING: Long-term care facilities (28) in the Netherlands. PARTICIPANTS: Newly admitted nursing home residents (372) in variable stages of dementia. MEASUREMENTS: We described prevalence and course of symptoms, and treatment provided for these symptoms. We used generalized estimating equations to evaluate the longitudinal change in symptoms and their treatment, and the associations between the symptoms of pain and agitation, as well as between stage of dementia and symptoms. RESULTS: Pain was common (varying from 47% to 68% across the semiannual assessments) and frequently persistent (36%-41% of all residents); it increased to 78% in the last week of life. Agitation was the most common symptom (57%-71%), and also frequently persistent (39%-53%), yet it decreased to 35% in the last week of life. Shortness of breath was less common (16%-26%), but it increased to 52% at the end of life. Pain was not significantly associated with agitation. Advanced dementia was associated with more pain only. Treatment changed in particular at the end of life. Pain was treated mostly with acetaminophen (34%-52%), and at the end of life with parenteral opioids (44%). Agitation was mostly treated nonpharmacologically (78%-92%), and at the end of life anxiolytics were the most frequently prescribed treatment (62%). Overall, aerosolized bronchodilators were the most frequently prescribed treatment for shortness of breath (29%-67%), but at the end of life, this was morphine (69%). CONCLUSION: Pain and agitation were common and frequently persisted in residents with dementia during nursing home stay, but symptom management intensified only at the end of life. Symptom control may be suboptimal from admission, and a stronger focus on symptom control is needed at an earlier stage than the end of life.

Intralesional cryotherapy for treatment of keloid scars: a prospective study.

BACKGROUND: Intralesional cryotherapy is a novel treatment for keloid scars in which the scar is frozen from inside. Published results are promising, but the treatment has only been tested in a Caucasian patient population. Therefore, the authors evaluated intralesional cryotherapy in a patient population including different Fitzpatrick skin types (I through VI). METHODS: This prospective multicenter study with a 1-year follow-up included 27 patients with 29 keloid scars. Intralesional cryotherapy was administered with a disposable liquid nitrogen-based device called CryoShape. Scar assessment was performed using the Patient and Observer Scar Assessment Scale and four objective devices to determine scar color, scar elasticity, scar volume, and patient skin type. RESULTS: Keloid scars showed an average volume decrease of 63 percent (range, 16 to 100 percent) after 12 months, compared with baseline (p < 0.01). Recurrence was seen in seven keloids (24 percent) and hypopigmentation recovered in 69 percent of all keloid scars within 12 months. Scar assessment with the Patient and Observer Scar Assessment Scale showed an overall improvement according to both doctors and patients. In addition, complaints of pain and itching were reduced. When analyzing the results per Fitzpatrick skin type, African American patients showed a higher incidence of persistent hypopigmentation (p = 0.02). CONCLUSIONS: Intralesional cryotherapy for the treatment of keloid scars shows favorable results in terms of reduction of volume and complaints of pain and pruritus. However, no complete eradication was obtained in some cases and recurring scars were seen. In addition, persistent hypopigmentation proved a problem in non-Caucasian patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Joint modeling of longitudinal health-related quality of life data and survival.

PURPOSE: In cancer research, outcome measures may co-vary. Treatment and treatment related impairment of health-related quality of life (HRQoL) may affect survival. When these effects are analyzed separately, bias may arise. Therefore, we investigated the combined effect of treatment and longitudinally measured HRQoL on survival. METHODS: Patients with anaplastic oligodendrogliomas (n = 288) who were randomized (EORTC 26951) to radiotherapy (RT) alone or RT plus procarbazine, lomustine, and vincristine (PCV) chemotherapy were analyzed. HRQoL [appetite loss (AP)] was assessed with the EORTC QLQ-C30. We compared survival results from different analysis strategies: Cox model with treatment only [model 1 (M1)] or with treatment and time-dependent AP score [model 2 (M2)] and the joint model combining longitudinal AP score and survival [model 3 (M3)]. RESULTS: The estimated hazard ratio (HR) for RT plus PCV was 0.76 (95 % CI 0.58-1.00) for M1, 0.72 (0.55-0.96) for M2, and 0.69 (0.52-0.92) for M3. This corresponds to a lower risk of death of 24 % in M1, 28 % in M2, and 31 % in M3, for patients treated with RT plus PCV chemotherapy. AP resulted in an increased risk of death, with estimated HR of 1.06 (1.01-1.12) for M2 and 1.13 (1.03-1.23) for M3: Every 10-point increase of AP resulted in a 13 % increased risk of death in M3 as compared to 6 % in M2. CONCLUSION: Part of the survival benefit of treatment with RT plus PCV chemotherapy can be masked by the negative effect that this treatment has on patients' HRQoL. In our study, up to 7 % of the theoretical treatment efficacy was lost when AP was not adjusted through joint modeling.

Modeling the World Health Organization Disability Assessment Schedule II using non-parametric item response models.

The World Health Organization Disability Assessment Schedule II (WHO-DAS II) is a multidimensional instrument developed for measuring disability. It comprises six domains (getting around, self-care, getting along with others, life activities and participation in society). The main purpose of this paper is the evaluation of the psychometric properties for each domain of the WHO-DAS II with parametric and non-parametric Item Response Theory (IRT) models. A secondary objective is to assess whether the WHO-DAS II items within each domain form a hierarchy of invariantly ordered severity indicators of disability. A sample of 352 patients with a schizophrenia spectrum disorder is used in this study. The 36 items WHO-DAS II was administered during the consultation. Partial Credit and Mokken scale models are used to study the psychometric properties of the questionnaire. The psychometric properties of the WHO-DAS II scale are satisfactory for all the domains. However, we identify a few items that do not discriminate satisfactorily between different levels of disability and cannot be invariantly ordered in the scale. In conclusion the WHO-DAS II can be used to assess overall disability in patients with schizophrenia, but some domains are too general to assess functionality in these patients because they contain items that are not applicable to this pathology.

Five teacher profiles in student-centred curricula based on their conceptions of learning and teaching.

BACKGROUND: Teachers' conceptions of learning and teaching are partly unconscious. However, they are critical for the delivery of education and affect students' learning outcomes. Lasting changes in teaching behaviour can only be realized if conceptions of teachers have been changed accordingly. Previously we constructed a questionnaire named COLT to measure conceptions. In the present study, we investigated if different teacher profiles could be assessed which are based on the teachers' conceptions. These teacher profiles might have implications for individual teachers, for faculty development activities and for institutes. Our research questions were: (1) Can we identify teacher profiles based on the COLT? (2) If so, how are these teacher profiles associated with other teacher characteristics? METHODS: The COLT questionnaire was sent electronically to all teachers in the first three years of the undergraduate curriculum of Medicine in two medical schools in the Netherlands with student-centred education. The COLT (18 items, 5 point Likert scales) comprises three scales: 'teacher centredness', 'appreciation of active learning' and 'orientation to professional practice'. We also collected personal information about the participants and their occupational characteristics. Teacher profiles were studied using a K-means cluster analysis and calculating Chi squares. RESULTS: The response rate was 49.4% (N = 319/646). A five-cluster solution fitted the data best, resulting in five teacher profiles based on their conceptions as measured by the COLT. We named the teacher profiles: Transmitters (most traditional), Organizers, Intermediates, Facilitators and Conceptual Change Agents (most modern). The teacher profiles differed from each other in personal and occupational characteristics. CONCLUSIONS: Based on teachers' conceptions of learning and teaching, five teacher profiles were found in student-centred education. We offered suggestions how insight into these teacher profiles might be useful for individual teachers, for faculty development activities and for institutes and departments, especially if involved in a curriculum reform towards student-centred education.

When do people with dementia die peacefully? An analysis of data collected prospectively in long-term care settings.

BACKGROUND: Little is known about dying peacefully with dementia in long-term care facilities. Dying peacefully may be influenced by characteristics of the palliative care provided and characteristics of the long-term care setting. If so, dying peacefully may serve as a quality indicator for palliative care in dementia. AIM: This study aims to describe whether residents with dementia in Dutch long-term care facilities die peacefully and to assess which characteristics of the resident, the palliative care provided and the facilities are associated with dying peacefully. DESIGN AND SETTING: We analysed existing data from the Dutch End of Life in Dementia study, collected between January 2007 and July 2010 in 34 long-term care facilities in the Netherlands. We used descriptive statistics and Generalised Estimating Equation models. RESULTS: The sample consisted of 233 residents with dementia. Family members indicated that the resident died peacefully in 56% of cases. This percentage ranged from 17% to 80% across facilities. Residents were more likely to die peacefully if they had an optimistic attitude, if family found that there were enough nurses available and if residents died in facilities with a moderate (versus no) perceived influence of religious affiliation on end-of-life decision-making policies. CONCLUSIONS: Only half of the residents with dementia in Dutch long-term care facilities die peacefully, as perceived by relatives. In addition to residents' optimistic attitude, facility characteristics are associated with dying peacefully, which suggests that 'the percentage of relatives who indicate that the patient died peacefully' can function as a quality indicator.