Patient room lighting influences on sleep, appraisal and mood in hospitalized people.

Irregular 24 h light/dark cycles with night-time light exposure and a low amplitude are disruptive for sleep, mood and circadian rhythms. Nevertheless such lighting conditions are quite common in medical care facilities. A controlled clinical trial among 196 cardiology ward patients (mean age 66.5 ± 13.1 years SD) investigated how a patient room lighting intervention affects sleep, appraisal and mood across hospitalization. Patients were either assigned to a standardly-lit room or to a room with an interventional lighting system offering a dynamic 24 h light/dark cycle with low nocturnal light exposure and 2 h of bright light (1750 lux) during daytime. Measures included wrist actigraphy and questionnaires assessing alertness, sleep quality, anxiety, depression and lighting appraisal. The median length of hospitalization was 5 days in both study arms. Subjective scores on sleep, alertness, anxiety and depression did not differ between arms. Lighting appraisal in intervention rooms was better as compared to standardly-lit rooms, both in patients (P < 0.001) and staff (P < 0.005). Actigraphic sleep duration of patients improved by 5.9 min (95% CI: 0.6-11.2; P = 0.03 intervention × time effect) per hospitalization day with interventional lighting instead of standard lighting. After 5 days of hospitalization, sleep duration in the lighting intervention rooms increased by 29 min, or a relative 7.3%, as compared to standardly-lit rooms. A 24 h lighting system with enhanced daytime brightness and restricted nocturnal light exposure can improve some aspects of appraisal and objective sleep in hospital patients. More clinical research is needed to establish the best lighting strategy to promote healing and wellbeing within healthcare settings.

Observational skills assessment score: reliability in measuring amount and quality of use of the affected hand in unilateral cerebral palsy.

BACKGROUND: The Observational Skills Assessment Score (OSAS) measures amount and quality of use of the affected hand in children with unilateral Cerebral Palsy (CP) in bimanual activities and could therefore be a valuable addition to existing assessment tools. The OSAS consists of tasks that are age appropriate and require use of the affected hand. METHODS: To measure the agreement and reliability of the OSAS a convenience sample of two groups of 16 children with unilateral spastic CP (2.5-6 and 12-16 years old), performed age specific bimanual tasks in 2 measurement sessions. Three experienced raters took part in testing and 8 in scoring. Intra class correlation (ICC) values for intra- and inter-rater reliability, and the mean and standard deviation of the differences between measurements were calculated. For test-retest reliability beside ICC scores, Smallest Detectable Differences (SDDs) were calculated in 16 older and 10 younger children. RESULTS: Generally, there seems to be good agreement between repeated measurements of the OSAS, as indicated by the small SDDs on most scales for quality of movement, compared to the range of their scales. This indicates potentially good sensitivity to change if used for patient evaluation purposes. The exceptions were the 'quality of reach' score for all tasks, and all quality scores for the stacking blocks task for the young children. As used in the present study, the OSAS has good discriminative capacity within patient populations as indicated by the high ICCs for most quality scores. Measuring the amount of use does not seem to be useful for either discrimination or evaluation. CONCLUSION: In general, the OSAS seems to be a reliable tool for assessing the quality of use of the affected hand in bimanual activities in younger and older children with unilateral CP. Some modifications may improve its usefulness and efficiency.

The impact of delirium on the prediction of in-hospital mortality in intensive care patients.

INTRODUCTION: Predictive models, such as acute physiology and chronic health evaluation II (APACHE-II), are widely used in intensive care units (ICUs) to estimate mortality. Although the presence of delirium is associated with a higher mortality in ICU patients, delirium is not part of the APACHE-II model. The aim of the current study was to evaluate whether delirium, present within 24 hours after ICU admission, improves the predictive value of the APACHE-II score. METHODS: In a prospective cohort study 2116 adult patients admitted between February 2008 and February 2009 were screened for delirium with the confusion assessment method-ICU (CAM-ICU). Exclusion criteria were sustained coma and unable to understand Dutch. Logistic regression analysis was used to estimate the predicted probabilities in the model with and without delirium. Calibration plots and the Hosmer-Lemeshow test (HL-test) were used to assess calibration. The discriminatory power of the models was analyzed by the area under the receiver operating characteristics curve (AUC) and AUCs were compared using the Z-test. RESULTS: 1740 patients met the inclusion criteria, of which 332 (19%) were delirious at the time of ICU admission or within 24 hours after admission. Delirium was associated with in-hospital mortality in unadjusted models, odds ratio (OR): 3.22 (95% confidence interval [CI]: 2.23 - 4.66). The OR between the APACHE-II and in-hospital mortality was 1.15 (95% CI 1.12 - 1.19) per point. The predictive accuracy of the APACHE-II did not improve after adding delirium, both in the total group as well as in the subgroup without cardiac surgery patients. The AUC of the APACHE model without delirium was 0.77 (0.73 - 0.81) and 0.78 (0.74 - 0.82) when delirium was added to the model. The z-value was 0.92 indicating no improvement in discriminative power, and the HL-test and calibration plots indicated no improvement in calibration. CONCLUSIONS: Although delirium is a significant predictor of mortality in ICU patients, adding delirium as an additional variable to the APACHE-II model does not result in an improvement in its predictive estimates.

Prediction of peak pressure from clinical and radiological measurements in patients with diabetes.

BACKGROUND: Various structural and functional factors of foot function have been associated with high local plantar pressures. The therapist focuses on these features which are thought to be responsible for plantar ulceration in patients with diabetes. Risk assessment of the diabetic foot would be made easier if locally elevated plantar pressure could be indicated with a minimum set of clinical measures. METHODS: Ninety three patients were evaluated through vascular, orthopaedic, neurological and radiological assessment. A pressure platform was used to quantify the barefoot peak pressure for six forefoot regions: big toe (BT) and metatarsals one (MT-1) to five (MT-5). Stepwise regression modelling was performed to determine which set of the clinical and radiological measures explained most variability in local barefoot plantar peak pressure in each of the six forefoot regions. Comprehensive models were computed with independent variables from the clinical and radiological measurements. The difference between the actual plantar pressure and the predicted value was examined through Bland-Altman analysis. RESULTS: Forefoot pressures were significant higher in patients with neuropathy, compared to patients without neuropathy for the whole forefoot, the MT-1 region and the MT-5 region (respectively 138 kPa, 173 kPa and 88 kPa higher: mean difference). The clinical models explained up to 39 percent of the variance in local peak pressures. Callus formation and toe deformity were identified as relevant clinical predictors for all forefoot regions. Regression models with radiological variables explained about 26 percent of the variance in local peak pressures. For most regions the combination of clinical and radiological variables resulted in a higher explained variance. The Bland and Altman analysis showed a major discrepancy between the predicted and the actual peak pressure values. CONCLUSION: At best, clinical and radiological measurements could only explain about 34 percent of the variance in local barefoot peak pressure in this population of diabetic patients. The prediction models constructed with linear regression are not useful in clinical practice because of considerable underestimation of high plantar pressure values. Identification of elevated plantar pressure without equipment for quantification of plantar pressure is inadequate. The use of quantitative plantar pressure measurement for diabetic foot screening is therefore advocated.

Long-term effectiveness and costs of a brief self-management intervention in women with pregnancy-related low back pain after delivery.

BACKGROUND: Pregnancy-related low back pain is considered an important health problem and potentially leads to long-lasting pain and disability. Investigators draw particular attention to biomedical factors but there is growing evidence that psychosocial and social factors might be important. It prompted us to start a large cohort study (n = 7526) during pregnancy until one year after delivery and a nested randomized controlled intervention study in the Netherlands. METHODS: A randomized controlled trial (n = 126) nested within a cohort study, of brief self-management techniques versus usual care for treatment of women with persisting non-specific pregnancy-related low back pain three weeks after delivery. Women in the intervention group were referred to a participating physiotherapist. Women in the usual care group were free to choose physiotherapy, guidance by a general practitioner or no treatment. Follow up took place at 3 months, 6 months and one year after delivery.Outcomes included change in limitations in activities (RDQ), pain (VAS), severity of main complaints (MC), global feeling of recovery (GPE), impact on participation and autonomy (IPA), pain-related fear (TSK), SF-36, EuroQol and a cost diary. For the outcome measures, series of mixed models were considered. For the outcome variable global perceived effect (GPE) a logistic regression analysis is performed. RESULTS: Intention-to-treat outcomes showed a statistical significant better estimated regression coefficient RDQ -1.6 {-2.9;-0.5} associated with treatment, as well as better IPA subscale autonomy in self-care -1.0 {-1.9;-0.03} and TSK -2.4 {-3.8;-1.1} but were not clinical relevant over time. Average total costs in the intervention group were much lower than in usual care, primarily due to differences in utilization of sick leave but not statistically significant. CONCLUSION: Brief self-management techniques applied in the first 3 months after delivery may be a more viable first-line approach but further research is needed to draw inference on costs and to determine whether no care is a better option in the long term. TRIAL REGISTRATION: [ISRCTN08477490].

Daily-life activities and in-shoe forefoot plantar pressure in patients with diabetes.

OBJECTIVE: To assess differences regarding in-shoe forefoot plantar pressure (PP) in patients with diabetes during various daily-life activities. RESEARCH DESIGN AND METHODS: In-shoe PP was measured in 93 patients during: level walking, ramp and stair walking, turning in different settings and while performing the Up & Go test. Separate PPs were determined for the big toe and metatarsal (mt) regions one to five. RESULTS: Across all activities, similar PPs were measured in the big toe and mt-1 to mt-3 region. Lower PPs were measured in mt-4 and mt-5 region. PPs during level walking were mostly higher when compared to the other activities (p

Testing the proficiency to distinguish locations with elevated plantar pressure within and between professional groups of foot therapists.

BACKGROUND: Identification of locations with elevated plantar pressures is important in daily foot care for patients with rheumatoid arthritis, metatarsalgia and diabetes. The purpose of the present study was to evaluate the proficiency of podiatrists, pedorthists and orthotists, to distinguish locations with elevated plantar pressure in patients with metatarsalgia. METHODS: Ten podiatrists, ten pedorthists and ten orthotists working in The Netherlands were asked to identify locations with excessively high plantar pressure in three patients with forefoot complaints. Therapists were instructed to examine the patients according to the methods used in their everyday clinical practice. Regions could be marked through hatching an illustration of a plantar aspect. A pressure sensitive platform was used to quantify the dynamic bare foot plantar pressures and was considered as 'Gold Standard' (GS). A pressure higher than 700 kPa was used as cut-off criterion for categorizing peak pressure into elevated or non-elevated pressure. This was done for both patient's feet and six separate forefoot regions: big toe and metatarsal one to five. Data were analysed by a mixed-model ANOVA and Generalizability Theory. RESULTS: The proportions elevated/non-elevated pressure regions, based on clinical ratings of the therapists, show important discrepancies with the criterion values obtained through quantitative plantar pressure measurement. In general, plantar pressures in the big toe region were underrated and those in the metatarsal regions were overrated. The estimated method agreement on clinical judgement of plantar pressures with the GS was below an acceptable level: i.e. all intraclass correlation coefficient's equal or smaller than .60. The inter-observer agreement for each discipline demonstrated worrisome results: all below .18. The estimated mutual agreements showed that there was virtually no mutual agreement between the professional groups studied. CONCLUSION: Identification of elevated plantar pressure through clinical evaluation is difficult, insufficient and may be potentially harmful. The process of clinical plantar pressure screening has to be re-evaluated. The results of this study point towards the merit of quantitative plantar pressure measurement for clinical practice.

Effectiveness of a tailor-made intervention for pregnancy-related pelvic girdle and/or low back pain after delivery: short-term results of a randomized clinical trial [ISRCTN08477490].

BACKGROUND: For the moment, scientific evaluation of programs on treatment of pregnancy-related pelvic girdle and/or low back pain after delivery is hardly available with only one study with a positive result, suggesting uncertainty about the optimal approach. Investigators draw particular attention to biomedical factors but there is growing evidence that biopsychosocial factors appear to be even more important as a basis of an intervention program. METHODS: We studied the effectiveness of a tailor-made program with respect to biopsychosocial factors (intervention group) in women with pregnancy-related pelvic girdle and/ or low back pain versus usual care based on a pain contingent basis (control group) shortly after delivery in a randomized controlled trial. Women with severe complaints shortly after delivery were selected from a longitudinal prospective cohort study (n = 7526), aimed at pregnancy-related pelvic girdle and/or low back pain in the Netherlands. A concealed block randomization was performed after collecting baseline data. Researchers were blinded to treatment assignment. Outcomes were evaluated within the domains of the biopsychosocial approach. Primary outcome concerned limitations in activities (RDQ). Follow-up measurements were performed 12 weeks after delivery. RESULTS: Since May 2001 until July 2003, 869 women out of the cohort made a request for treatment by a physiotherapist, 10 days after delivery. Because of a quick recovery in two weeks time, we included only 126 women three weeks after delivery. There was a statistically significant and clinically relevant difference in improvement on the primary outcome (RDQ) between the two groups in favor of the experimental intervention. CONCLUSION: The results favored the hypotheses. Women's worries about their condition were major targets in the experimental intervention. The prognosis after delivery, especially in de first weeks, turned out to be favorable.

Casting methods and plantar pressure: effects of custom-made foot orthoses on dynamic plantar pressure distribution.

Foot orthoses are widely used to treat various foot problems. A literature search revealed no publications on differences in plantar pressure distribution resulting from casting methods for foot orthoses. Four casting methods were used for construction of orthoses. Two foam box techniques were used: accommodative full weightbearing method (A) and functional semiweightbearing method (B). Also, two suspension plaster casting techniques were used: accommodative casting (C) and functional subtalar joint neutral position (Root) method (D). Their effects on contact area, plantar pressure, and walking convenience were evaluated. All orthoses increased the total contact area (mean, 17.4%) compared with shoes without orthoses. Differences in contact areas between orthoses for total plantar surface were statistically significant. Peak pressures for the total plantar surface were lower with orthoses than without orthoses (mean, 22.8%). Among orthoses, only the difference between orthoses A and B was statistically significant. Differences between orthoses for the forefoot were small and not statistically significant. The gait lines of the shoe without an insole and of the accommodative orthoses are more medially located than those of functional orthoses. Walking convenience in the shoe was better rated than that with orthoses. There were no differences in perception of walking convenience between orthoses A, B, and C. Orthosis D had the lowest convenience rating. The four casting methods resulted in differences between orthoses with respect to contact areas and walking convenience but only slight differences in peak pressures.

Members of research ethics committees accepted a modification of the randomized consent design.

BACKGROUND AND OBJECTIVE: The use of randomized consent designs has been subject of methodologic and ethical controversy. In most Western countries, research ethics committees make the decision as to whether a randomized consent design can be applied. The purpose of the study is to assess to what extent a randomized consent design and a modification of this design is accepted by research ethics committees, in terms of ethics, health law, and methodology. METHODS: A postal survey was conducted among members of research ethics committees in the United Kingdom, and in The Netherlands, with professional competence in ethics, (health) law, methodology, or clinical practice. RESULTS: In both the UK and in The Netherlands, the modified randomized consent design appears to be statistically significantly more acceptable than the randomized consent design, with respect to ethical and judicial aspects. The overall rejection rate of the randomized consent design was 66% in the UK and 59% in The Netherlands. However, the modified randomized consent design was rejected by 47 and 41% in the two countries, respectively. CONCLUSION: the modified randomized consent design appears to be more acceptable than the randomized consent design. To increase consistency in the way research ethics committees handle study protocols, a discussion about the use of randomized consent designs appears necessary.

Comparison of foot orthoses made by podiatrists, pedorthists and orthotists regarding plantar pressure reduction in The Netherlands.

BACKGROUND: There is a need for evidence of clinical effectiveness of foot orthosis therapy. This study evaluated the effect of foot orthoses made by ten podiatrists, ten pedorthists and eleven orthotists on plantar pressure and walking convenience for three patients with metatarsalgia. Aims were to assess differences and variability between and within the disciplines. The relationship between the importance of pressure reduction and the effect on peak pressure was also evaluated. METHODS: Each therapist examined all three patients and was asked to rate the 'importance of pressure reduction' through a visual analogue scale. The orthoses were evaluated twice in two sessions while the patient walked on a treadmill. Plantar pressures were recorded with an in-sole measuring system. Patients scored walking convenience per orthosis. The effects of the orthoses on peak pressure reduction were calculated for the whole plantar surface of the forefoot and six regions: big toe and metatarsal one to five. RESULTS: Within each discipline there was an extensive variation in construction of the orthoses and achieved peak pressure reductions. Pedorthists and orthotists achieved greater maximal peak pressure reductions calculated over the whole forefoot than podiatrists: 960, 1020 and 750 kPa, respectively (p < .001). This was also true for the effect in the regions with the highest baseline peak pressures and walking convenience rated by patients A and B. There was a weak relationship between the 'importance of pressure reduction' and the achieved pressure reduction for orthotists, but no relationship for podiatrists and pedorthotists. CONCLUSION: The large variation for various aspects of foot orthoses therapy raises questions about a consistent use of concepts for pressures management within the professional groups.

Effects of botulinum toxin A and/or bimanual task-oriented therapy on upper extremity impairments in unilateral Cerebral Palsy: an explorative study.

OBJECTIVE: This study reports on the effects of botulinum toxin A (BoNT-A) injections in the upper extremity (UE) of children with unilateral Cerebral Palsy (uCP) combined with bimanual task oriented therapy (BITT) or either treatment modality performed separately on UE range of motion (ROM), spasticity and (functional) strength. METHODS: Thirty-five children, mean age 7.14 years (SD 2.63) of whom 11 had a Manual Ability Classification Score (MACS) I, 15 MACS II and 9 MACS III, participated. The trial started with four study groups: BoNT-A-only (n = 5), BITT-only (n = 11), BoNT-A + BITT (n = 13), and control (n = 6). Twenty-two children were randomized and, due to recruitment problems 13 children received their parents' preferred treatment: BoNT-A + BITT or BITT-only. Three comparisons were analysed: BITT (BoNT-A + BITT and BITT-only; n = 24) versus no BITT (BoNT-A-only and control; n = 11), BoNT-A (BoNT-A-only and BoNT-A + BITT; n = 18) versus no BoNT-A (BITT-only and control; n = 17), and the additional effect of BoNT-A (BoNT-A + BITT versus BITT-only). RESULTS: BoNT-A significantly decreased key grip strength and finger flexion tone, had a clinically relevant (additional) positive effect on active thumb abduction and supination and a significantly negative effect on unilateral functional strength. BITT + BoNT-A significantly increased active supination. BITT reduced elbow flexor tone and BITT-only resulted in more improvement than BoNT-A + BITT in functional unimanual and, to a lesser extent, in bimanual grip strength. CONCLUSIONS: In comparison with BoNT-A + BITT, BITT-only gives more improvement on functional grip strength and, therefore, could possibly increase bimanual performance. In this case, the (additional) role of BoNT-A may be an increase in active supination and thumb abduction.

The balanced incomplete block design is not suitable for the evaluation of complex interventions.

OBJECTIVES: In quality of care research, the balanced incomplete block (BIB) design is regularly claimed to have been used when evaluating complex interventions. In this article, we reflect on the appropriateness of using this design for evaluating complex interventions. STUDY DESIGN AND SETTING: Literature study using PubMed and handbooks. RESULTS: After studying various articles on health services research that claim to have applied the BIB and the original methodological literature on this design, it became clear that the applied method is in fact not a BIB design. CONCLUSION: We conclude that the use of this design is not suited for evaluating complex interventions. We stress that, to prevent improper use of terms, more attention should be paid to proper referencing of the original methodological literature.

Index event bias-a numerical example.

Studies of determinants of recurrent disease often give unexpected results. In particular, well-established risk factors may seem not to have much influence on the recurrence risk. Recently, it has been argued that such paradoxical findings may be because of the bias caused by the selection of patients based on the occurrence of an earlier episode of the disease. This bias was referred to as index event bias. Here, we give a theoretical quantitative example of index event bias, showing that, as a result of selection of patients on the basis of previous disease: (1) risk factors become inversely associated when they are not in the unselected population, and (2) the crude association between the risk factor of interest and disease becomes biased toward the null.

Randomised trial comparing bone remodelling around two uncemented stems using modified Gruen zones.

For assessment of bone remodelling around total hip arthroplasty using dual-emission X-ray absorptiometry (DEXA), a variety of different systems to identify regions of interest (ROI) have been used, making comparisons between stem designs difficult. The Gruen zones are now widely used for this purpose. We present the results of a randomised clinical trial comparing 2 uncemented stem designs with proximal coating, using a modification of the Gruen zones to allow improved representation of the effect of the implant on bone mineral density (BMD) over time. DEXA-data were used in a randomised trial with 2 years follow up, comparing the uncemented Symax(TM) (n=25) and Omnifit(®) (n=24) stems. The effect on BMD was determined using the 'standard' adapted Gruen zones, and a modification which studied an equal length and position for zones 1 and 7 around both stems, assuring that the same regions in terms of cancellous and cortical bone were compared. The 'modified' regions of interest give lower BMD values around the Omnifit(®) than using the 'standard' Gruen zones (3.6 % in zone 7, p<0.05). The difference with the Symax(TM) BMD values, which had been concealed using the standard Gruen zones, became statistically significant in favour of the Symax(TM) implant. This adaptation can detect a statistically significant difference in bone preservation in zone 7 between stems that would otherwise not have been revealed. We recommend the use of 'modified' Gruen zones for more valid comparison of remodelling caused by different implant designs.

Predictive validity of the Glasgow Blatchford Bleeding Score in an unselected emergency department population in continental Europe.

BACKGROUND AND AIM: Glasgow Blatchford Bleeding Score stratifies patients presenting with acute upper gastrointestinal haemorrhage at the emergency department according to the likelihood of the need for treatment. The objective of this study was to validate the Glasgow Blatchford Bleeding Score for use in an emergency department in the Netherlands. Furthermore, we assessed its clinical usefulness for safe discharge of low-risk acute upper gastrointestinal haemorrhage patients and compared its test validity to that of other scoring systems. METHODS: This multicentre historic cohort study was conducted in two hospitals in the Netherlands. All 478 patients presenting with a suspicion of acute upper gastrointestinal haemorrhage at our emergency departments during a 1-year period were included. For each patient we calculated Glasgow Blatchford Bleeding Score and other commonly used scores. Test validity was assessed using the receiver operated characteristics curve analysis; calibration plots were used to assess the probability of the need for treatment of different levels of the scores. RESULTS: Glasgow Blatchford Bleeding Score had a good discriminative ability in predicting the need for treatment, receiver operated characteristics curve analysis showed an area under the curve of 0.879. Counting a score of 2 or less as low risk (negative), 104 patients (21.7%) were classified as low-risk, with a negative predictive value of 98.1%. These results were superior to those of the other scoring systems. CONCLUSION: Patients presenting at an emergency department in continental Europe with acute upper gastrointestinal haemorrhage and a Glasgow Blatchford Bleeding Score of 2 or less can be safely discharged. The Glasgow Blatchford Bleeding Score performed better than the other commonly used scoring systems.

Monitoring response to antiangiogenic therapy in non-small cell lung cancer using imaging markers derived from PET and dynamic contrast-enhanced MRI.

UNLABELLED: With antiangiogenic agents, tumor shrinkage may be absent, despite survival benefit. The present study assessed the predictive value of molecular imaging for the identification of survival benefit during antiangiogenic treatment with bevacizumab and erlotinib in patients with advanced non-small cell lung cancer. METHODS: Patients were evaluated using an imaging protocol including CT, 18F-FDG PET, H2(15)O PET, and dynamic contrast-enhanced MRI to derive measurements on tumor size, glucose metabolism, perfusion, and microvascular permeability. The percentage change in imaging parameters after 3 wk of treatment as compared with baseline was calculated and correlated with progression-free survival (PFS). RESULTS: Forty-four patients were included, and 40 underwent CT and 18F-FDG PET at both time points. Complete datasets, containing all imaging modalities, were available for 14 patients. Bevacizumab and erlotinib treatment resulted in decreased metabolism, perfusion, and tumor size. A decrease in standardized uptake value or tumor perfusion of more than 20% at week 3 was associated with longer PFS (9.7 vs. 2.8 mo, P=0.01, and 12.5 vs. 2.9 mo, P=0.009, respectively). Whole-tumor Ktrans (the endothelial transfer constant) was not associated with PFS, but patients with an increase of more than 15% in the SD of tumor Ktrans values-that is, an increase in regions with low or high Ktrans values-after 3 wk had shorter PFS (2.3 vs. 7.0 mo, P=0.008). A partial response, according to the response evaluation criteria in solid tumors (RECIST), at week 3 was also associated with prolonged PFS (4.6 vs. 2.9 mo, P=0.017). However, 40% of patients with a partial response as their best RECIST response still had stable disease at week 3. In these cases tumor perfusion was already decreased and Ktrans heterogeneity showed no increase, indicating that the latter parameters seem to be more discriminative than RECIST at the 3-wk time point. CONCLUSION: PET and dynamic contrast-enhanced MRI were able to identify patients who benefit from bevacizumab and erlotinib treatment. Molecular imaging seems to allow earlier response evaluation than CT.

Extending the range of treadmill testing for patients with intermittent claudication.

PURPOSE: There is a need to evaluate patients with peripheral arterial disease (PAD) with a limited or extended walking distance. We aimed to enable an estimation of walking distance as measured on a frequently used "standard" graded (3.2 km·h(-1), 2% increase per 2 min) protocol for walking distances measured on protocols with a lower or higher workload. METHODS: Patients with PAD and an absolute claudication distance (ACD) of <500 or between 1000 and 1600 m as measured with the "standard" protocol were included. Four graded study treadmill protocols, two with lower and two with higher workload than the "standard" protocol, were developed. Two study protocols (low or high) and the "standard" protocol were repeated in random order. Quality was determined with the intraclass correlation coefficient and the coefficient of variation. Orthogonal regression analysis was used to predict walking distances on the standard protocol on the basis of the study protocols. RESULTS: Forty-three patients with an ACD <500 m and 23 patients with an ACD between 1000 and 1600 m were included. Because feasibility from the protocols with 2.0 km·h(-1) and 2% increase every 2 min and 4.4 km·h(-1) and 2% increase every minute was highest, they were calibrated against the "standard" protocol, and reliability was comparable with the "standard" protocol. The coefficient of variation between the prediction of walking distance on the "standard" protocol on the basis of the new protocols and the measured distances were in the same range (22%-25%) as the variation measured performing the same treadmill test twice. CONCLUSIONS: An accurate estimate of walking distance as measured on a "standard" treadmill protocol can be derived from a protocol with a lower or higher workload.

Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI).

BACKGROUND: The aims of this study were to show 1) the effect of changing from computed tomography (CT) to magnetic resonance imaging (MRI) on the prevalence of detected brain metastases (BM) in patients with newly diagnosed small cell lung cancer (SCLC); 2) the difference in survival between patients with single and multiple BM; and 3) the effect of the change in patient labeling on eligibility for prophylactic brain irradiation. METHODS: From 1980 to 2004, 481 consecutive patients with SCLC were enrolled. Brain imaging was routinely performed after diagnosis of SCLC. At the start of 1991, MRI replaced CT in almost all patients. All patients were regularly examined by a neurologist. RESULTS: The prevalence of detected BM was 10% in the CT era and 24% in the MRI era. In the CT era, all detected BM were symptomatic, whereas in the MRI era, 11% were asymptomatic. In both periods, patients labeled as single BM survived longer than those labeled as multiple BM. For patients labeled as single BM or multiple BM, survival was longer in the MRI era than in the CT era. The proportion of patients who were eligible for prophylactic cranial irradiation was lower in the MRI era. CONCLUSIONS: The estimated prevalence of BM increases when MRI is used instead of CT. Patients with a detected single BM survive longer than patients with multiple BM. The apparently increased survival in the MRI era can be attributed to the "Will Rogers phenomenon". The use of MRI makes fewer patients eligible for prophylactic cranial irradiation.

Response of asymptomatic brain metastases from small-cell lung cancer to systemic first-line chemotherapy.

PURPOSE: The purpose of this study was to investigate the radiologic response of asymptomatic brain metastases (BM) from small-cell lung cancer (SCLC) to first-line systemic chemotherapy. PATIENTS AND METHODS: From 1990 to 2003, 181 consecutive patients with SCLC were enrolled onto this study. Patients were examined by a neurologist on a regular basis. Magnetic resonance imaging (MRI) of the brain was performed routinely before (at diagnosis of SCLC) and after first-line systemic chemotherapy. Patients were treated with combination chemotherapy consisting of cyclophosphamide, doxorubicin, and etoposide. Clinically manifest BM were treated with whole-brain radiotherapy (WBRT). The response rate (RR) of BM was assessed by changes in the size or the number of enhanced lesions on MRI using standard criteria. RESULTS: Synchronous asymptomatic BM were found in 24 SCLC patients (13%). In six (27%) of the 22 assessable patients, the asymptomatic BM responded to systemic chemotherapy. A systemic response was found in 16 patients (73%). All patients became symptomatic during follow-up. The symptom-free survival did not differ between cranial responders and cranial nonresponders. CONCLUSION: The RR of asymptomatic BM from SCLC to systemic chemotherapy is 27% and evidently lower than the systemic RR. Future studies should focus on the possible beneficial effect of WBRT for patients with asymptomatic synchronous BM.