Ancillary investigations to diagnose parkinsonism: a prospective clinical study.

Various ancillary investigations can assist clinicians in the differential diagnosis of patients with parkinsonism. It is unknown which test offers greatest diagnostic value in clinical practice. We included 156 consecutive patients with parkinsonism, but with an initially uncertain diagnosis. At baseline, all patients underwent extensive clinical testing and the following ancillary investigations: brain magnetic resonance imaging (MRI); (123)I-iodobenzamide single photon-emission computed tomography (IBZM-SPECT); analysis of cerebrospinal fluid (CSF); and anal sphincter electromyography (EMG). The final diagnosis was established after 3-year follow-up by two movement disorder specialists, according to international consensus criteria. We determined the diagnostic value by comparing the baseline clinical parameters and ancillary studies with the final diagnosis. Out of a potential 138 parameters, univariate analysis identified 35 parameters that discriminated Parkinson's disease (PD, n = 62) and atypical parkinsonism (AP, n = 94), with AUC of 0.55-0.81. Stepwise logistic regression showed that the combination of tandem gait, axial UPDRS subscore, slow saccadic eye movements and dysphagia yielded an AUC of 0.93, adjusted for optimism. The combination of tandem gait and axial UDPRS subscore yielded an AUC of 0.90. None of the ancillary investigations alone or in combination with clinical testing improved this clinically based diagnostic accuracy, not even in a subgroup of patients with the greatest diagnostic uncertainty at baseline. Our study demonstrates that a comprehensive set of clinical tests provides good accuracy to differentiate PD from AP. Our results also suggest that routine MRI, IBZM-SPECT, CSF analysis and anal sphincter EMG do not improve this diagnostic accuracy. Future work should evaluate the possible diagnostic value of more advanced diagnostic tests.

Doxorubicin/cyclophosphamide with concurrent versus sequential docetaxel as neoadjuvant treatment in patients with breast cancer.

BACKGROUND: This study was designed to determine whether delivering neo-adjuvant chemotherapy at a higher dose in a shorter period of time improves outcome of breast cancer patients. PATIENTS AND METHODS: Women with newly diagnosed breast cancer were randomly assigned to neoadjuvant chemotherapy of four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (AC 60/600 - T 100 mg/m(2)) or six cycles of TAC (75/50/500 mg/m(2)) every 3 weeks. The primary endpoint was the pathologic complete response (pCR) rate, defined as no invasive tumour present in the breast. RESULTS: In total, 201 patients were included. Baseline characteristics were well balanced. AC-T resulted in pCR in 21% and TAC in 16% of patients (odds ratio 1.44 (95% confidence interval (CI) 0.67-3.10). AC-T without primary granulocyte-colony stimulating factor (G-CSF) prophylaxis was associated with more febrile neutropenia compared to TAC with primary G-CSF prophylaxis (23% versus 9%), and with more grade 3/4 sensory neuropathy (5% versus 0%). CONCLUSIONS: With a higher cumulative dose for the concurrent arm, no differences were observed between the two treatment arms with respect to pCR rate. The differential toxicity profile could partly be explained by different use of primary G-CSF prophylaxis.

Health status one year after TransInguinal PrePeritoneal inguinal hernia repair and Lichtenstein's method: an analysis alongside a randomized clinical study.

BACKGROUND: The Lichtenstein technique is the treatment of first choice according to guidelines for primary inguinal hernia treatment. Postoperative chronic pain has been reported as complication in 15-40 % after Lichtenstein's repair. The postoperative effects on health status after open preperitoneal hernia repair have hardly been examined. Development of an open technique that combines the safe anterior approach of the Lichtenstein with the 'promising' preperitoneal soft mesh position was done; the transinguinal preperitoneal (TIPP) mesh repair. A double-blind prospective randomized controlled trial (TULIP trial, ISRCTN93798494) was conducted to compare different outcome parameters after TIPP or Lichtenstein, one parameter is topic of evaluation in this paper; the health status after TIPP and Lichtenstein for inguinal hernia repair. METHODS: The study protocol has been published. It was hypothesized that the health status of inguinal hernia patients would be better after the TIPP repair compared with the Lichtenstein technique. The size of this study was based on chronic pain as primary outcome measure. Three hundred and two patients were randomized. Patients and the outcome assessors were blinded. Follow-up was scheduled after 14 days, 3 months, and 1 year. The three dimensions of possible errors were warranted. RESULTS: With regard to health status, significant differences were found in the dimensions 'physical pain' [difference: 6.1 (95 % CI 2.3-9.9, p = 0.002)] and 'physical functioning' [difference: 3.5 (95 % CI 0.5-6.7, p = 0.023)], favoring the TIPP patients after 1 year. CONCLUSION: In conclusion, the SF-36 'physical function' and 'physical pain' dimensions after TIPP show significant better patient outcomes at 1 year compared with the Lichtenstein patients in this trial. These differences are in line with reported significant differences in less patients with postoperative chronic pain after TIPP compared with Lichtenstein at 1 year.

First trial reactions and habituation rates over successive balance perturbations in Parkinson's disease.

BACKGROUND: Balance control in Parkinson's disease is often studied using dynamic posturography, typically with serial identical balance perturbations. Because subjects can learn from the first trial, the magnitude of balance reactions rapidly habituates during subsequent trials. Changes in this habituation rate might yield a clinically useful marker. We studied balance reactions in Parkinson's disease using posturography, specifically focusing on the responses to the first, fully unpractised balance disturbance, and on the subsequent habituation rates. METHODS: Eight Parkinson patients and eight age- and gender-matched controls received eight consecutive toe-up rotations of a support-surface. Balance reactions were measured with a motion analysis system and converted to centre of mass displacements (primary outcome). RESULTS: Mean centre of mass displacement during the first trial was 51% greater in patients than controls (P=0.019), due to excessive trunk flexion and greater ankle plantar-flexion. However, habituated trials were comparable in both groups. Patients also habituated slower: controls were fully habituated at trial 2, whereas habituation in patients required up to five trials (P=0.004). The number of near-falls during the first trial was significantly correlated with centre of mass displacement during the first trial and with habituation rate. CONCLUSIONS: Higher first trial reactions and a slow habituation rate discriminated Parkinson's patients from controls, but habituated trials did not. Further work should demonstrate whether this also applies to clinical balance tests, such as the pull test, and whether repeated delivery of such tests offers better diagnostic value for evaluating fall risks in parkinsonian patients.

Relevant impact of central pathology review on nodal classification in individual breast cancer patients.

BACKGROUND: In the MIRROR study, pN0(i + ) and pN1mi were associated with reduced 5-year disease-free survival (DFS) compared with pN0. Nodal status (N-status) was assessed after central pathology review and restaging according to the sixth AJCC classification. We addressed the impact of pathology review. PATIENTS AND METHODS: Early favorable primary breast cancer patients, classified pN0, pN0(i + ), or pN1(mi) by local pathologists after sentinel node procedure, were included. We assessed the impact of pathology review on N-status (n = 2842) and 5-year DFS for those without adjuvant therapy (n = 1712). RESULTS: In all, 22% of the 1082 original pN0 patients was upstaged. Of the 623 original pN0(i + ) patients, 1% was downstaged, 26% was upstaged. Of 1137 patients staged pN1mi, 15% was downstaged, 11% upstaged. Originally, 5-year DFS was 85% for pN0, 74% for pN0(i + ), and 73% for pN1mi; HR 1.70 [95% confidence interval (CI) 1.27-2.27] and HR 1.57 (95% CI 1.16-2.13), respectively, compared with pN0. By review staging, 5-year DFS was 86% for pN0, 77% for pN0(i + ), 77% for pN1mi, and 74% for pN1 + . CONCLUSION: Pathology review changed the N-classification in 24%, mainly upstaging, with potentially clinical relevance for individual patients. The association of isolated tumor cells and micrometastases with outcome remained unchanged. Quality control should include nodal breast cancer staging.

Cost-effectiveness of adjuvant systemic therapy in low-risk breast cancer patients with nodal isolated tumor cells or micrometastases.

BACKGROUND: The cost-effectiveness of adjuvant systemic therapy in patients with low-risk breast cancer and nodal isolated tumor cells or micrometastases is unknown. PATIENTS AND METHODS: A cost-effectiveness analysis of adjuvant systemic therapy was carried out using the costs per 1% event prevented after 5 years of follow-up as incremental cost-effectiveness ratio (ICER). Secondary objective was to establish when adjuvant systemic therapy becomes cost saving. Patients included in the MIRROR study with isolated tumor cells or micrometastases who had a complete 5-year follow-up and who either did or did not receive systemic therapy were eligible. Sensitivity analyses were carried out. RESULTS: In the no adjuvant therapy cohort (N = 366), 24.9% of patients had an event within 5 years versus 16.8% of patients in the adjuvant therapy cohort (N = 483) (P < 0.01). The ICER was €363 per 1% event prevented. Beyond 18 years after diagnosis, the extrapolated mean cumulative costs per patient in the no adjuvant therapy cohort exceeded those of the adjuvant therapy cohort. CONCLUSIONS: In this population of breast cancer patients with isolated tumor cells or micrometastases, €36 300 had to be invested to prevent one event in 5 years of follow-up. Adjuvant systemic therapy was cost saving beyond 18 years after diagnosis.

Pseudo cluster randomization: balancing the disadvantages of cluster and individual randomization.

While designing a trial to evaluate a complex intervention, one may be confronted with the dilemma that randomization at the level of the individual patient risks contamination bias, whereas cluster randomization risks incomparability of study arms and recruitment problems. Literature provides only few solutions to this dilemma and these are not always feasible. As an alternative solution for this dilemma, we developed a new two-stage randomization method called pseudo cluster randomization. In the first stage, the clusters (e.g., recruiting physicians) are randomized into two groups: one group of clusters in which the majority of the participants (e.g., 80%) will receive the experimental treatment; one group of clusters in which the majority will receive the control condition. Following this, the second stage of the randomization involves randomly assigning participants within clusters in the proportions determined by the first stage. This has important advantages. Compared with cluster randomization the potential occurrence of baseline incomparability of treatment arms and poor recruitment is reduced, because the physicians who recruit the participants are unable to know in advance which treatment condition the next participant they recruit will be assigned to. Limiting the exposure of half of the physicians to the innovative intervention lowers risk of contamination bias. When this type of contamination bias is present, pseudo cluster randomization can be more efficient than individual or cluster randomization in that smaller number of study participants is needed to achieve a predefined power.

GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study.

BACKGROUND: Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of 1.5 µg/L for GFAP and 1.13 µg/L for S100B from a previous study. METHODS: In 79 patients with TBI (Glasgow Coma Scale score [GCS] ≤12), serum, taken at hospital admission, was analyzed for GFAP and S100B. Data collected included injury mechanism, age, gender, mass lesion on CT, GCS, pupillary reactions, Injury Severity Score (ISS), presence of hypoxia, and hypotension. Outcome was assessed, using the Glasgow Outcome Scale Extended (dichotomized in death vs alive and unfavorable vs favorable), 6 months post injury. RESULTS: In patients who died compared to alive patients, median serum levels were increased: GFAP 33.4-fold and S100B 2.1-fold. In unfavorable compared to favorable outcome, GFAP was increased 19.8-fold and S100B 2.1-fold. Univariate logistic regression analysis revealed that mass lesion, GFAP, absent pupils, age, and ISS, but not GCS, hypotension, or hypoxia, predicted death and unfavorable outcome. Multivariable analysis showed that models containing mass lesion, pupils, GFAP, and S100B were the strongest in predicting death and unfavorable outcome. S100B was the strongest single predictor of unfavorable outcome with 100% discrimination. CONCLUSION: This study confirms that GFAP and S100B levels in serum are adjuncts to the assessment of brain damage after TBI and may enhance prognostication when combined with clinical variables.

Side of symptom onset affects motor dysfunction in Parkinson's disease.

The healthy brain appears to have an asymmetric dopamine distribution, with higher levels of dopamine in the left than in the right striatum. Here, we test the hypothesis that this neurochemical asymmetry renders the right striatum relatively more vulnerable to the effects of dopaminergic denervation in Parkinson's disease (PD). Using the pegboard dexterity test, we compared motor performance of both hands between healthy subjects (n=48), PD patients with predominantly right-hemispheric dopamine depletion (PD-RIGHT; n=83) and PD patients with more severe left-hemispheric dopamine depletion (PD-LEFT; n=103). All subjects were right-handed. After adjusting for hand-dominance effects, we found that PD-RIGHT patients exhibited a 55% larger difference between right and left dexterity scores than PD-LEFT patients. This effect could be attributed to greater motor dysfunction of the more-affected hand in PD-RIGHT patients, while the less-affected hand performed similarly in both groups. We conclude that the side of symptom onset affects motor dysfunction in PD, and suggest that the non-dominant right hemisphere may be more susceptible to dopaminergic denervation than the dominant left hemisphere.

The development of a screening instrument to select patients at risk of residual complaints after lumbar disc surgery.

AIM: A considerable number of patients who undergo surgery for a lumbosacral radicular syndrome (LRS) continue to experience disability, pain, and loss of work capacity. The goal of the study is to develop a brief screening instrument to identify these patients at risk of residual complaints. METHODS: In a prospective study of 277 patients, the predictors for the outcomes disability, pain, and loss of work capacity were investigated. The best predictive model was constructed using a stepwise selection procedure (forward selection), which calculates the discriminative power of the model. Based on the relationship between regression coefficients, a clinical prediction rule was derived that predicted the probability of residual complaints after surgery for LRS. RESULTS: At 6 month follow-up 141 patients (51%) had residual complaints. The discriminative power of the instrument was .78 (AUC). The "Nijmegen Outcome of Lumbar Disc surgery Screening-instrument" (NOLDS) was based on the variables "lower education level", "younger age", "pain 3 days postoperatively", "passive pain coping", and "fear of movement/(re)injury". CONCLUSION: The results of the study are promising, showing that a brief clinical screening instrument can be used to identify patients at risk of residual complaints at 6 months after surgery for LRS. The early identification of patients at risk having residual complaints may make it possible to start tailored treatment early in the rehabilitation process.

Dynamic posturography in Parkinson's disease: diagnostic utility of the "first trial effect".

Previous dynamic posturography studies demonstrated clear abnormalities in balance responses in Parkinson's disease (PD) patients compared to controls at the group level, but its clinical value in the diagnostic process and fall risk estimation in individual patients leaves for improvement. Therefore, we investigated whether a new approach, focusing on the balance responses to the very first and fully unpractised trial rather than a pooled mean response to a series of balance perturbations, could further improve the diagnostic utility of dynamic posturography. Following the first trial, subjects were exposed to repeated balance perturbations, which also permitted us to investigate the training responses. Fourteen patients with PD and 18 age-matched controls were enrolled, who received a series of multidirectional postural perturbations, induced by support surface rotations. We measured trunk and upper arm kinematics and electromyographic responses, and evaluated group differences at three levels: the postural response to the very first backward perturbation; pooled first and habituated postural responses; and habituation rates. Analysis of the first trial responses yielded similar results as evaluation of the mean response over trials: forward flexion of the trunk induced by backward perturbations was decreased in patients, accompanied by increased muscle responses present. Moreover, trunk movement and muscle activity were equally present in both groups-suggesting a preserved training response in PD patients. Early masseter activity in both groups might be indicative of a startle-like component to the balance response. In terms of diagnostic utility, focusing on the first trial response or habituation rate is no better than analysis of pooled responses to a series of perturbations. The apparently preserved training response in PD patients suggests that balance reactions in PD can be improved by repeated exposure, and this may have implications for future exercise studies. Early masseter activity warrants further studies to evaluate a potential startle component in the pathophysiology of balance disorders.

Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases.

BACKGROUND: The prognostic relevance of isolated tumor cells and micrometastases in lymph nodes from patients with breast cancer has become a major issue since the introduction of the sentinel lymph node procedure. We conducted a systematic review of this issue. METHODS: Studies published from January 1, 1977, until August 11, 2008, were identified by use of MEDLINE, EMBASE, and the Cochrane Library. A total of 58 studies (total number of patients = 297,533) were included and divided into three categories according to the method for pathological assessment of the lymph nodes: cohort studies with single-section pathological examination of axillary lymph nodes (n = 285,638 patients), occult metastases studies with retrospective examination of negative lymph nodes by step sectioning and/or immunohistochemistry (n = 7740 patients), and sentinel lymph node biopsy studies with intensified work-up of the sentinel but not of the nonsentinel lymph nodes (n = 4155 patients). We used random-effects meta-analyses to calculate pooled estimates of the relative risks (RRs) of 5- and 10-year disease recurrence and death and the multivariably corrected pooled hazard ratio (HR) of overall survival of the cohort studies. RESULTS: In the cohort studies, the presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes was associated with poorer overall survival (pooled HR of death = 1.44, 95% confidence interval [CI] = 1.29 to 1.62). In the occult metastases studies, the presence (vs the absence) of occult metastases was associated with poorer 5-year disease-free survival (pooled RR = 1.55, 95% CI = 1.32 to 1.82) and overall survival (pooled RR = 1.45, 95% CI = 1.11 to 1.88), although these endpoints were not consistently assessed in multivariable analyses. Sentinel lymph node biopsy studies were limited by small patient groups and short follow-up. CONCLUSION: The presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes detected on single-section examination was associated with poorer disease-free and overall survival.

Prevalence and definition of drooling in Parkinson's disease: a systematic review.

Drooling (saliva loss) is a frequently reported symptom in patients with Parkinson's disease (PD), but an accurate estimate of the prevalence of drooling is lacking. The aim of this study was to systematically review the prevalence of drooling in published research papers. A systematic PubMed and CINAHL search was done, including studies published until January 2009. Eight studies were found, presenting prevalence rates of drooling based on responses of PD patients to questionnaires. The statistical heterogeneity was highly significant (P < 0.0001), with prevalence rates ranging from 32 to 74%. The pooled prevalence estimate with random effect analysis was of 56% (95% CI 44-67) for PD patients and 14% (95% CI 3-25) for healthy controls; the pooled relative risk (RR) with random effect analysis was 5.5 (95% CI 2.1-14.4). All studies reported data of community dwelling idiopathic PD patients, with a mean age around 65 years and mild PD in 50-60% of the cases. Heterogeneity was mainly caused by differences in definition or frequency of drooling. The highest prevalence rates included nocturnal drooling where others noted only diurnal drooling. Analysis of the data of two studies showed that drooling is reported frequently by 22-26% of the patients. Prevalence rates were lower in milder PD patients. The summarized findings demonstrate that drooling can be present in half of all PD patients. In about a quarter of PD patients, drooling appears to be a frequently occurring problem. We recommend to report drooling in future studies with more detailed consideration of severity, frequency and nocturnal versus diurnal complaints.

Clinimetric analyses of the Modified Parkinson Activity Scale.

OBJECTIVE: The Parkinson Activity Scale (PAS) is designed for functional assessment in Parkinson's disease (PD), but the scale has - in its current form - several drawbacks. The objectives of the present study are to (a) introduce a Modified PAS, with unambiguous scoring options and without ceiling effect; (b) evaluate the inter-rater agreement, using physiotherapists with and without PD-specific expertise; and (c) examine the concurrent validity with the VAS-Global Functioning and the UPDRS-III. METHODS: The Modified PAS was developed based on the results of a recent pilot feasibility study [Keus SHJ, Bloem BR, van Hilten JJ, Ashburn A, Munneke M. Effectiveness of physiotherapy in Parkinson's disease: The feasibility of a randomised controlled trial. Parkinsonism Relat Disord 2007; 13(2):115-21.]. To evaluate inter-rater agreement, the Modified PAS was scored by a large number of raters (n=13) in 15 patients (Hoehn and Yahr stage 2-4), thus yielding a high number of observations (n=195) and creating adequate power. To ascertain broad applicability of the results, both physiotherapists with and without PD-specific expertise participated. RESULTS: The interquartile range of the Modified PAS total scores was 40-51, within a possible range of 0 (optimal performance) to 56 (worst performance), suggesting lack of ceiling effect. The precision of these scores was 2.6 points, with an inter-rater error of 1.3 and a patient-induced error of 2.3. There were no differences between experts and non-experts. Correlation to Global Functioning (0.79) and UPDRS-III (0.64) was good. CONCLUSION: The Modified PAS showed no ceiling effect, good concurrent validity, good inter-rater agreement and no differences between experts and non-experts.

Effect of subthalamic nucleus deep brain stimulation on axial motor control and protective arm responses in Parkinson's disease.

Stereotactic surgical interventions for Parkinson's disease (PD) can considerably improve appendicular motor signs, but their effect on axial motor signs--especially balance control under optimal drug therapy--remains unclear. Here, we investigated the effect of bilateral subthalamic nucleus (STN) stimulation on levodopa-resistant axial and appendicular postural impairment in PD. Fourteen patients (11 with young-onset PD) and 18 age-matched controls were included. Patients were tested after intake of a suprathreshold levodopa dose, ensuring optimal response to drug therapy, and with stimulators both turned on and off. Balance control was assessed using multidirectional dynamic posturography. Outcome measures included full body kinematics and surface electromyography of paraspinal and deltoid muscles. Patients with stimulators turned off showed early decreased trunk roll with a loss of directional dependency, followed by increased and abnormally directed--i.e. destabilizing--trunk roll. Pelvis pitch motion showed decreased directional dependency in these patients. The abnormal trunk motion was not corrected by STN stimulation, but directional dependency of both trunk and pelvis motion partially improved, along with a general decrease in muscle activity. Even with stimulators off, protective arm movements were similar in the optimally treated patients and controls, indicating that these appendicular signs respond better to dopaminergic treatment than axial motor control. Our findings indicate that instability in PD results from a reduced flexibility of the trunk and pelvis that is largely resistant to STN stimulation combined with optimal drug treatment. These postural abnormalities are therefore likely associated with non-dopaminergic pathology. In contrast, protective arm movements did appear to be levodopa-responsive. Future studies should focus on identifying subgroups of optimal responders, particularly patients with levodopa-induced dyskinesias.

Clinical validation of the non-invasive cardiac output monitor USCOM-1A in critically ill patients.

BACKGROUND AND OBJECTIVE: Cardiac output is frequently monitored to maintain and improve cardiac function with the primary goal of adequate tissue perfusion. The pulmonary artery catheter is considered to be the gold standard although several non-invasive devices are being introduced and gaining attention. To evaluate the accuracy of the ultrasonic cardiac output monitor (USCOM)-1A (Pty Ltd, Coffs Harbour, NSW, Australia), a non-invasive cardiac output device including its capability to differentiate between different shock states in haemodynamically unstable ICU patients was used in this single-centre, prospective, observational study. METHODS: Cardiac output was measured with a pulmonary artery catheter and transcutaneously via a suprasternal approach with the USCOM-1A by continuous-wave Doppler ultrasound in 25 adult patients in a mixed medical and surgical ICU in a major teaching hospital in the Netherlands. RESULTS: A total of 1315 USCOM-1A cardiac output measurements were performed. In order to reduce time-variability, the mean of five consecutive USCOM-1A measurements was calculated. Total 263 values were compared with 263 thermodilution cardiac output measurements performed with a pulmonary artery catheter. Data were analysed for systematic error, precision and correlation. Systematic and random errors were found. On average USCOM-1A values were 12% lower than thermodilution measurements (systematic error), while the random error was 17% (coefficient of variation). The error comprised an inter-operator variability of 3%, an inter-patient variability of 11% and residual variability of 15%. The correlation coefficient of the calculated cardiac index with the USCOM-1A and the pulmonary artery catheter was r = 0.8024 and 0.6438, respectively. Temperature and gender did not influence correlations. The learning curve for USCOM-1A skill acquisition was steep. CONCLUSIONS: The correlation between the two techniques was acceptable, although relevant systematic and variable errors were detected. USCOM-1A provided adequate data to distinguish non-invasively different shock types in ICU patients.

Pseudo cluster randomization performed well when used in practice.

OBJECTIVE: In the Dutch EASYcare Study, pseudo cluster randomization (PCR) randomized clinicians in two groups (H and L) with a high or a low proportion of the patients of the clinician randomized to intervention or to control arm accordingly. We used PCR because cluster randomization risked selection bias and individual randomization risked contamination. We evaluated the performance of PCR. STUDY DESIGN AND SETTING: Clinicians were asked about treatment arm preferences, recruitment behavior, possible contaminating behavior, and what they thought the allocation ratio was. We compared patients' baseline characteristics and clinicians' recruitment rates. RESULTS: The groups were comparable at baseline. Clinicians favored the intervention arm (Visual Analogue Scale 14.5 [SD 15.6]; 0-100; 0=strongly favoring intervention arm, 100=strongly favoring usual care arm) and 58% said they would have recruited fewer patients had every participant been allocated to the control group. Sixty five percent of clinicians used intervention elements in control patients. Sixty seven percent of clinicians estimated that a 50:50 allocation ratio was used. CONCLUSION: The assumptions underlying PCR largely applied in this study. PCR performed satisfactorily without signs of unblinding or selection bias.

Can an EASYcare based dementia training programme improve diagnostic assessment and management of dementia by general practitioners and primary care nurses? The design of a randomised controlled trial.

BACKGROUND: Early diagnosis of dementia benefits both patient and caregiver. Nevertheless, dementia in primary care is currently under-diagnosed. Some educational interventions developed to improve dementia diagnosis and management were successful in increasing the number of dementia diagnoses and in changing attitudes and knowledge of health care staff. However, none of these interventions focussed on collaboration between GPs and nurses in dementia care. We developed an EASYcare-based Dementia Training Program (DTP) aimed at stimulating collaboration in dementia primary care. We expect this program to increase the number of cognitive assessments and dementia diagnoses and to improve attitudes and knowledge of GPs and nurses. METHODS: The DTP is a complex educational intervention that consists of two workshops, a coaching program, access to an internet forum, and a Computerized Clinical Decision Support System on dementia diagnostics. One hundred duos of GPs and nurses will be recruited, from which 2/3 will be allocated to the intervention group and 1/3 to the control group. The effects of implementation of the DTP will be studied in a cluster-randomised controlled trial. Primary outcomes will be the number of cognitive assessments and dementia diagnoses in a period of 9 months following workshop participation. Secondary outcomes are measured on GP and nurse level: adherence to national guidelines for dementia, attitude, confidence and knowledge regarding dementia diagnosis and management; on patient level: number of emergency calls, visits and consultations and patient satisfaction; and on caregiver level: informal caregiver burden and satisfaction. Data will be collected from GPs' electronic medical records, self-registration forms and questionnaires. Statistical analysis will be performed using the MANOVA-method. Also, exploratory analyses will be performed, in order to gain insight into barriers and facilitators for implementation and the possible causal relations between the rate of success of the intervention components and the outcomes. DISCUSSION: We developed multifaceted dementia training programme. Novelties in this programme are the training in fixed collaborative duos and the inclusion of an individual coaching program. The intervention is designed according to international guidelines and educational standards. Exploratory analysis will reveal its successful elements. Selection bias and contamination may be threats to the reliability of future results of this trial. Nevertheless, the results of this trial may provide useful information for policy makers and developers of continuing medical education. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00459784.

Early prediction of favourable recovery 6 months after mild traumatic brain injury.

BACKGROUND: Predicting outcome after mild traumatic brain injury (MTBI) is notoriously difficult. Although it is recognised that milder head injuries do not necessarily mean better outcomes, less is known about the factors that do enable early identification of patients who are likely to recover well. OBJECTIVE: To develop and internally validate two prediction rules for identifying patients who have the highest chance for good 6 month recovery. METHODS: A prospective cohort study was conducted among patients with MTBI admitted to the emergency department. Apart from MTBI severity indices, a range of pre-, peri- and early post-injury variables were considered as potential predictors, including emotional and physical functioning. Logistic regression modelling was used to predict the absence of postconcussional symptoms (PCS) and full return to work (RTW). RESULTS: At follow-up, 64% of the 201 participating patients reported full recovery. Based on our prediction rules, patients without premorbid physical problems, low levels of PCS and post-traumatic stress early after injury had a 90% chance of remaining free of PCS. Patients with over 11 years of education, without nausea or vomiting on admission, with no additional extracranial injuries and only low levels of pain early after injury had a 90% chance of full RTW. The discriminative ability of the prediction models was satisfactory, with an area under the curve >0.70 after correction for optimism. CONCLUSIONS: Early identification of patients with MTBI who are likely to have good 6 month recovery was feasible on the basis of relatively simple prognostic models. A score chart was derived from the models to facilitate clinical application.