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Background: This study was designed to evaluate the association between structural hospital characteristics and failure-to-rescue (FTR) after colorectal cancer surgery. A growing body of evidence suggests a large hospital variation concerning mortality rates in patients with a severe complication (FTR) in colorectal cancer surgery. Which structural hospital factors are associated with better FTR rates remains largely unclear., Methods: All patients undergoing colorectal cancer surgery from 2009 through 2011 in 92 Dutch hospitals were analysed. Univariate and multivariate logistic regression models, including casemix, hospital volume, teaching status, and different levels of intensive care unit (ICU) facilities, were used to analyse risk-adjusted FTR rates., Results: A total of 25,591 patients from 92 hospitals were included. The FTR rate ranged between 0 and 39 %. In univariate analysis, high hospital volume (>200 vs. ≤200 patients/year), teaching status (academic vs. teaching vs. nonteaching hospitals) and high level of ICU facilities (highest level 3 vs. lowest level 1) were associated with lower FTR rates. Only the higher levels of ICU facilities (2 or 3 compared with level 1) were independently associated with lower failure-to-rescue rates (odds ratio 0.72; 95 % confidence interval 0.65-0.88) in multivariate analysis., Discussion: Hospital type and annual hospital volume were not independently associated with FTR rates in colorectal cancer surgery. Instead, the lowest level of ICU facilities was independently associated with higher rates. This suggests that a more advanced ICU may be an important factor that contributes to better failure-to-rescue rates, although individual hospitals perform well with lower ICU levels.

Introduction: When comparing mortality rates between hospitals to explore hospital performance, there is an important role for adjustment for differences in case-mix. Identifying outcome measures that are less influenced by differences in case-mix may be valuable. The main goal of this study was to explore whether hospital differences in anastomotic leakage (AL) and postoperative mortality are due to differences in case-mix or to differences in treatment factors., Methods: Data of the Dutch Surgical Colorectal Audit were used. Case-mix factors and treatment-related factors were identified from the literature and their association with AL and mortality were analysed with logistic regression. Hospital differences in observed AL and mortality rates, and adjusted rates based on the logistic regression models were shown. The reduction in hospital variance after adjustment was analysed with Levene's test for equality of variances., Results: 17 of 22 case-mix factors and 4 of 11 treatment factors related to AL derived from the literature were available in the database. Variation in observed AL rates between hospitals was large with a maximum rate of 17%. This variation could not be attributed to differences in case-mix but more to differences in treatment factors. Hospital variation in observed mortality rates was significantly reduced after adjustment for differences in case-mix., Conclusions: Hospital variation in AL is relatively independent of differences in case-mix. In contrast to 'postoperative mortality' the observed AL rates of hospitals evaluated in our study were only slightly affected after adjustment for case-mix factors. Therefore, AL rates may be suitable as an outcome indicator for measurement of surgical quality of care.

Background: Postoperative mortality is frequently used in hospital comparisons as marker for quality of care. Differences in mortality between hospitals may be explained by varying complication rates. A possible modifying factor may be the ability to let patients with a serious complication survive, referred to as failure to rescue (FTR). The purpose of this study was to evaluate how hospital performance on postoperative mortality is related to severe complications or to FTR and to explore the value of FTR in quality improvement programs., Methods: All patients operated for colorectal cancer from 2009 to 2011, registered in the Dutch Surgical Colorectal Audit, were included. Logistic regression models were used to obtain adjusted mortality, complication, and FTR rates. Hospitals were grouped into 5 quintiles according to adjusted mortality. Outcomes were compared between quintiles., Results: A total of 24,667 patients were included. Severe complications ranged from 19 % in the lowest to 25 % in the highest mortality quintile (odds ratio 1.5, 95 % confidence interval 1.37-1.67). Risk-adjusted FTR rates showed a marked difference between the quintiles, ranging from 9 % to 26 % (odds ratio 3.0, 95 % confidence interval 2.29-3.98). There was significant variability in FTR rates. Seven hospitals had significantly lower FTR rates than average., Conclusions: High-mortality hospitals had slightly higher rates of severe complications than low-mortality hospitals. However, FTR was three times higher in high-mortality hospitals than in low-mortality hospitals. In quality improvement projects, feedback to hospitals of FTR rates, along with complication rates, may illustrate shortcomings (prevention or management of complications) per hospital, which may be an important step in reducing mortality.

Purpose: Evaluation of risk factors for survival in patients surgically treated for symptomatic spinal epidural metastases (SEM)., Methods: One hundred and six patients who were surgically treated for symptomatic SEM in a 10-year period in two cooperatively working hospitals were retrospectively studied for nine risk factors: age, gender, site of the primary tumor, location of the symptomatic spinal metastasis, functional and neurologic status, the presence of visceral metastases and the presence of other spinal and extraspinal bone metastases. Analysis was performed using the Kaplan-Meier method, univariate log-rank tests and Cox-regression models., Results: Overall median survival was 10.7 months (0.2-107.5 months). Overall 30-day complication rate was 33 %. Multivariate Cox-regression analysis showed that fast growing primary tumors (HR 3.1, 95 % CI 1.6-6.2, p = 0.001), the presence of visceral metastases (HR 1.7, 95 % CI 1.0-2.9, p = 0.033) and a low performance status (HR 2.7, 95 % CI 1.1-6.6, p = 0.025) negatively influenced the survival., Conclusion: Primary tumor type, presence of visceral metastases and performance status are significant predictors for survival after surgery for symptomatic SEM and should be evaluated before deciding on the extent of treatment. More accurate prediction models are needed to select the best treatment option for the individual patient.

In this multicenter retrospective study, the long-term outcomes of 878 adults with AML and refractory anemia with excess blasts (RAEB) with BM blasts <10% who underwent transplantation with an HLA-identical sibling donor between 1998 and 2004 were analyzed according to four regimens of conditioning intensity: reduced-intensity conditioning (RIC) (either intermediate RIC (IntermRIC) or non-myeloablative (NMA) RIC), and myeloablative conditioning (MC) in 718 patients (either conventional MC or hyperintense MC. In multivariate cox analysis, patients undergoing NMA transplantation had lower non-relapse mortality risk in the first 100 days after transplantation (P<0.01), but a higher risk beyond day +100 (P=0.02), as well as higher relapse incidence in the first 12 months (P<0.01), but the risk was similar in all groups beyond 12 months. The probabilities of PFS and OS up to 7 years were significantly lower only in the NMA subgroup (P0.01 for both). The 7-year OS was 53%, 29%, 56% and 51%, respectively. Our data suggest that prospective studies comparing RIC regimens (especially IntermRIC) with MC are appropriate in patients with AML and RAEB who are in a non-advanced disease status.

The purpose of this study is to know the views of people about their illness, i.e., illness perceptions, determine coping strategies, and outcome. Previous research suggests a higher prevalence and a different perception of musculoskeletal complaints between musicians and nonmusicians. The aim of this study is to compare illness perceptions related to musculoskeletal complaints between musicians and nonmusicians. In this cross-sectional study, students from three music academies (n = 345) and one university medical center (n = 2,870) in the Netherlands received an electronic questionnaire concerning questions on sociodemographic characteristics, use of musical instruments, occurrence and characteristics of musculoskeletal complaints in the past year, and the Brief Illness Perception Questionnaire (B-IPQ). Baseline and B-IPQ scores were compared between the samples by means of t tests, chi-square tests, and regression models to adjust for differences in sociodemographic characteristics. Eighty-three music academy students and 494 medical students completed the questionnaire (response rates, 25.5 and 17.6 %, respectively). Seventy-four (89 %) persons in the musician group and 382 (78 %) persons in the nonmusician group reported occurrence of musculoskeletal complaints during the last 12 months. Adjusted for sociodemographic characteristics, the B-IPQ scores of the domains consequences (my illness is a serious condition), concern (I am extremely concerned about my illness), and emotions (my illness makes me scared) were significantly higher among musicians, whereas personal control (there is little I can do to improve my illness), identity (number of symptoms patient sees as part of illness) were not significantly different. Music academy students had a significant more positive score on treatment control. Music academy students report more negative perceptions of their musculoskeletal complaints compared to medical students. Although some selection bias is present, this is supposed to have a minor effect on the outcomes of this study. Addressing illness perceptions in musicians with musculoskeletal complaints could have beneficial effects on physical and functional outcomes.

Objective: To compare the effectiveness of two educational courses aiming to improve adherence to recommendations in a Dutch physiotherapy practice guideline for hip and knee OA., Methods: Physiotherapists (PTs) from three regions in The Netherlands were invited to participate in a study comparing an interactive workshop (IW) with conventional education (CE). Participants were randomly assigned to one of the two courses. Satisfaction with the course (scale 0-10), knowledge (score range 0-76) and guideline adherence (score range 0-72) were measured at baseline, immediately after the educational course and 3 months after that. Data were analysed using a linear mixed model., Results: In total, 203 (10%) PTs participated in the IW (n = 108) and the CE (n = 95). There were no differences between groups at baseline. Satisfaction was significantly higher in the IW than in the CE group [mean scores (S.D.) 7.5 (1.1) and 6.7 (1.6), respectively (P < 0.001)]. A significantly greater improvement in adherence was seen over time in the IW group compared with the CE group (F = 3.763, P = 0.024), whereas the difference in improvement of knowledge was not significant (F = 1.283, P = 0.278)., Conclusion: An IW led to greater satisfaction and was more effective in improving adherence to recommendations in a PT guideline on hip and knee OA than CE, whereas the increase in knowledge did not differ significantly.

Background: Research comparing the frequency of musculoskeletal complaints between musicians and non-musicians is scarce. The aim of this study was to compare the prevalence of musculoskeletal complaints between musicians and non-musicians., Methods: A cross-sectional study in 3215 students from three music academies (n = 345) and one medical school (n = 2870) in The Netherlands was performed, using an electronic questionnaire. The questionnaire included socio-demographic characteristics, use of music instruments and the occurrence of musculoskeletal complaints in six body regions. Questions were related to musculoskeletal complaints over the last twelve months and at the time of the questionnaire. Chi-square, t-tests and Kruskal-Wallis tests were used for comparison between the two groups. The association between musculoskeletal complaints and possible predictors was analyzed using a logistic and Poisson regression., Results: Eighty-seven music academy students and 503 medical students returned the questionnaire, of which respectively eighty-three and 494 were included in the study. Seventy-four music academy students (89.2%) reported one or more musculoskeletal complaints during the last twelve months, compared to 384 (77.9%) medical students (p = 0.019). Moreover 52 music academy students (62.7%) and 211 medical students (42.7%) reported current musculoskeletal complaints (p = 0.001). The odds ratio (OR) for the development of musculoskeletal complaints during the last twelve months in music academy students versus medical students is 2.33 (95% CI 1.61-3.05, p = 0.022). The OR at the time of the questionnaire is 2.25 (95% CI 1.77-2.73, p = 0.001). The total number of complaints have been modeled by employing a Poisson regression; the results show that non-musicians have on average less complaints than musicians (p = 0.01). The adjusted means are 2.90 (95% CI 2.18-3.63) and 1.83 (95% CI 1.63-2.04) respectively for musicians and non-musicians. Regarding the localization of complaints, music academy students reported more complaints concerning the right hand, wrists, left elbow, shoulders, neck, jaw and mouth in contrast to medical students., Conclusions: Musculoskeletal complaints are significantly more common among musicians compared to non-musicians, mainly due to a higher number of upper extremity complaints.

Introduction: Considerable evidence suggests that patients with more advantaged Socio-Economic Positions undergo Total Hip and Knee Replacement (THR/TKR) more often, despite having a lower need. We questioned whether more disadvantaged Socio-Economic Position is associated with an lower improvement in Health-Related Quality of Life (HRQoL) and a lower patient satisfaction after THR/TKR., Methods: Patients who underwent primary THR/TKR in one academic and three community hospitals between 2005 and 2009, were eligible for inclusion. The highest completed levels of schooling were aggregated to index social class. We compared the improvement in HRQoL and postoperative satisfaction with surgery (measured using the Short-Form 36 (SF36) and an 11-point numeric rating scale of satisfaction) between the aggregated groups of highest completed levels of schooling, using linear mixed model analysis, with center as a random effect and potential confounders (i.e. age, gender, Body Mass Index and Charnley's comorbidity classification) as fixed effects., Results: 586 THR patients and 400 TKR patients (40% of all eligible patients) agreed to participate and completed all questionnaires sufficiently. We found no differences in HRQoL improvement in any dimension of the SF36 in THR patients. Patients with a higher completed level of schooling had a larger improvement in role-physical (9.38 points, 95%-CI:0.34-18.4), a larger improvement in general health (3.67 points, 95%-CI:0.56-6.79) and a smaller improvement in mental health (3.60 points, 95%-CI:0.82-6.38) after TKR. Postoperative patient satisfaction did not differ between different highest completed level of schooling groups., Discussion: Completed level of schooling has no effect on the improvement in HRQoL and patient satisfaction in a Dutch THR population and a small effect in a similar TKR population. Undertreatment of patients with more disadvantaged Socio-Economic Position cannot be justified, given the similar improvement in HRQoL and postoperative level of satisfaction with surgery between the social groups examined.

Osteosarcomas of hands or feet are rare, and seemingly these cases differ in presentation and behavior compared to those in usual locations. The clinico-pathological presentation of patients with osteosarcomas of the hand or foot was studied and compared with published cases. Forty osteosarcomas were identified among 4,221 cases, representing 0.95 % of all osteosarcomas. Thirty of these were well documented. Mean age at diagnosis was 43 years (hands) and 36 years (feet) and male-female ratio was 1.2:1 and 2.0:1, respectively. In the hand, 62 % of the osteosarcomas presented in the metacarpals and 23 % in the phalanges, and only two cases occurred in the carpal bones. Distribution in the foot was tarsal bones 56 %, metatarsal bones 33 %, and phalanges 11 %.Of the cases in the hand 54 % were of high grade and of those in the foot 71 %. Survival of osteosarcomas of the hand or foot was 81 %. Only patients with high-grade osteosarcoma died of the disease. Histological grade was the only significant variable related to survival. High-grade osteosarcoma of the hand or feet should be treated similar to those in conventional sites. Osteosarcomas of hands or feet are rare and in a relative high proportion are of low grade. Survival in high-grade cases is comparable to that in conventional sites.

Introduction: Although Total Hip and Knee Replacements (THR/TKR) improve Health-Related Quality of Life (HRQoL) at the group level, up to 30% of patients are dissatisfied after surgery due to unfulfilled expectations. We aimed to assess whether the pre-operative radiographic severity of osteoarthritis (OA) is related to the improvement in HRQoL after THR or TKR, both at the population and individual level., Methods: In this multi-center observational cohort study, HRQoL of OA patients requiring THR or TKR was measured 2 weeks before surgery and at 2-5 years follow-up, using the Short-Form 36 (SF36). Additionally, we measured patient satisfaction on a 11-point Numeric Rating Scale (NRSS). The radiographic severity of OA was classified according to Kellgren and Lawrence (KL) by an independent experienced musculoskeletal radiologist, blinded for the outcome. We compared the mean improvement and probability of a relevant improvement (defined as a patients change score ≥ Minimal Clinically Important Difference) between patients with mild OA (KL Grade 0-2) and severe OA (KL Grade 3+4), whilst adjusting for confounders., Results: Severe OA patients improved more and had a higher probability of a relevant improvement in physical functioning after both THR and TKR. For TKR patients with severe OA, larger improvements were found in General Health, Vitality and the Physical Component Summary Scale. The mean NRSS was also higher in severe OA TKR patients., Discussion: Patients with severe OA have a better prognosis after THR and TKR than patients with mild OA. These findings might help to prevent dissatisfaction after THR and TKR by means of patient selection or expectation management.

Background and Purpose: The association between excessive early migration of acetabular cups and late aseptic revision has been scantily reported. We therefore performed 2 parallel systematic reviews and meta-analyses to determine the association between early migration of acetabular cups and late aseptic revision., Methods: One review covered early migration data from radiostereometric analysis (RSA) studies, while the other focused on revision rates for aseptic loosening from long-term survival studies. Thresholds for acceptable and unacceptable migration were classified according the Swedish Hip Arthroplasty Register and the Australian National Joint Replacement Registry: < 5% revision at 10 years., Results: Following an elaborate literature search, 26 studies (involving 700 cups) were included in the RSA review and 49 studies (involving 38,013 cups) were included in the survival review. For every mm increase in 2-year proximal migration, there was a 10% increase in revision rate, which remained after correction for age, sex, diagnosis, hospital type, continent, and study quality. Consequently, proximal migration of up to 0.2 mm was considered acceptable and proximal migration of 1.0 mm or more was considered unacceptable. Cups with proximal migration of between 0.2 and 1.0 mm were considered to be at risk of having revision rates higher than 5% at 10 years., Interpretation: There was a clinically relevant association between early migration of acetabular cups and late revision due to loosening. The proposed migration thresholds can be implemented in a phased evidence-based introduction, since they allow early detection of high-risk cups while exposing a small number of patients.

Purpose: We performed two parallel systematic reviews and meta-analyses to determine the association between early migration of tibial components and late aseptic revision., Methods: One review comprised early migration data from radiostereometric analysis (RSA) studies, while the other focused on revision rates for aseptic loosening from long-term survival studies. Thresholds for acceptable and unacceptable migration were determined according to that of several national joint registries: < 5% revision at 10 years., Results: Following an elaborate literature search, 50 studies (involving 847 total knee prostheses (TKPs)) were included in the RSA review and 56 studies (20,599 TKPs) were included in the survival review. The results showed that for every mm increase in migration there was an 8% increase in revision rate, which remained after correction for age, sex, diagnosis, hospital type, continent, and study quality. Consequently, migration up to 0.5 mm was considered acceptable during the first postoperative year, while migration of 1.6 mm or more was unacceptable. TKPs with migration of between 0.5 and 1.6 mm were considered to be at risk of having revision rates higher than 5% at 10 years., Interpretation: There was a clinically relevant association between early migration of TKPs and late revision for loosening. The proposed migration thresholds can be implemented in a phased, evidence-based introduction of new types of knee prostheses, since they allow early detection of high-risk TKPs while exposing only a small number of patients.

Objectives: The Kaplan-Meier estimation is widely used in orthopedics to calculate the probability of revision surgery. Using data from a long-term follow-up study, we aimed to assess the amount of bias introduced by the Kaplan-Meier estimator in a competing risk setting., Methods: We describe both the Kaplan-Meier estimator and the competing risk model, and explain why the competing risk model is a more appropriate approach to estimate the probability of revision surgery when patients die in a hip revision surgery cohort. In our study, a total of 62 acetabular revisions were performed. After a mean of 25 years, no patients were lost to follow-up, 13 patients had undergone revision surgery and 33 patients died of causes unrelated to their hip., Results: The Kaplan-Meier estimator overestimates the probability of revision surgery in our example by 3%, 11%, 28%, 32% and 60% at five, ten, 15, 20 and 25 years, respectively. As the cumulative incidence of the competing event increases over time, as does the amount of bias., Conclusions: Ignoring competing risks leads to biased estimations of the probability of revision surgery. In order to guide choosing the appropriate statistical analysis in future clinical studies, we propose a flowchart.

Purpose: To systematically review published studies comparing Quality of Life (QoL), functional ability and/or physical activity between different surgical interventions due to a malignant bone tumour of the leg., Methods: A systematic literature search, covering the years 2000-2010 was performed using the PubMed, Embase, Web of science and Cochrane databases. Studies were included if they described and statistically compared QoL, functional ability and/or physical activity of at least two surgical interventions for lower extremity bone cancer. In addition, the methodological quality of the selected studies was evaluated by using a 24-point scale. Where appropriate, a qualitative analysis or meta-analysis was performed., Results: The search strategy resulted in a list of 246 citations. Based on titles and abstracts 50 full-text articles were selected, of which 13 articles describing 12 studies, were finally included. Overall, the methodological quality of the studies was moderate. Studies were heterogeneous with respect to their categorisation of surgical interventions, average age of patients and average duration of follow-up. Overall, results regarding differences between ablative and limb-sparing surgery varied largely. Meta-analysis was considered to be not appropriate due to clinical heterogeneity, methodological differences and flaws., Conclusion: Twelve studies comparing the outcomes of QoL, functional ability and physical activity between limb-sparing and ablative surgery groups were identified, with an overall moderate methodological quality. Their largely varying outcomes suggest that no general conclusions on the advantage of either limb-sparing or ablative surgery in patients with malignant bone tumours of the lower extremity can be drawn., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: We aimed first to summarise minimal clinically important differences (MCIDs) after total hip (THR) or knee replacement (TKR) in health-related quality of life (HRQoL), measured using the Short-Form 36 (SF-36). Secondly, we aimed to improve the precision of MCID estimates by means of meta-analysis., Methods: We conducted a systematic review of English and non-English articles using MEDLINE, the Cochrane Controlled Trials Register (1960-2011), EMBASE (1991-2011), Web of Science, Academic Search Premier and Science Direct. Bibliographies of included studies were searched in order to find additional studies. Search terms included MCID or minimal clinically important change, THR or TKR and Short-Form 36. We included longitudinal studies that estimated MCID of SF-36 after THR or TKR., Results: THREE STUDIES MET OUR INCLUSION CRITERIA, DESCRIBING A DISTINCT STUDY POPULATION: primary THR, primary TKR and revision THR. No synthesis of study results can be given., Conclusions: Although we found MCIDs in HRQoL after THR or TKR have limited precision and are not validated using external criteria, these are still the best known estimates of MCIDs in HRQoL after THR and TKR to date. We therefore advise these MCIDs to be used as absolute thresholds, but with caution.

Background and Purpose: In contrast to early migration, the long-term migration of hydroxyapatite- (HA-) coated tibial components in TKA has been scantily reported. This randomized controlled trial investigated the long-term migration measured by radiostereometric analysis (RSA) of HA-coated, uncoated, and cemented tibial components in TKA., Patients and Methods: 68 knees were randomized to HA-coated (n = 24), uncoated (n = 20), and cemented (n = 24) components. All knees were prospectively followed for 11-16 years, or until death or revision. RSA was used to evaluate migration at yearly intervals. Clinical and radiographic evaluation was according to the Knee Society system. A generalized linear mixed model (GLMM, adjusted for age, sex, diagnosis, revisions, and BMI) was used to take into account the repeated-measurement design., Results: The present study involved 742 RSA analyses. The mean migration at 10 years was 1.66 mm for HA, 2.25 mm for uncoated and 0.79 mm for the cemented group (p < 0.001). The reduction of migration by HA as compared to uncoated components was most pronounced for subsidence and external rotation. 3 tibial components were revised for aseptic loosening (2 uncoated and 1 cemented), 3 for septic loosening (2 uncoated and 1 cemented), and 1 for instability (HA-coated). 2 of these cases were revised for secondary loosening after a period of stability: 1 case of osteolysis and 1 case of late infection. There were no statistically significant differences between the fixation groups regarding clinical or radiographic scores., Interpretation: HA reduces migration of uncemented tibial components. This beneficial effect lasts for more than 10 years. Cemented components showed the lowest migration. Longitudinal follow-up of TKA with RSA allows early detection of secondary loosening.

Studies on the effectiveness of information provision for patients with arthritis through the Internet are scarce. This study aimed to describe rheumatoid arthritis (RA) patients' knowledge and information needs before and after launching a website providing information on regional health care services for patients with rheumatic conditions. The intervention consisted of a weekly updated website comprising practical information on regional health care services for patients with arthritis. In addition, patients were offered information leaflets and an information meeting. Before (T1) and 24 months after (T2) the website was launched, a random sample of 400 RA patients filled in a questionnaire regarding knowledge and information need (scores 0-18) about accessibility and contents of 18 regional health care services. Two hundred and fifty-one patients returned the questionnaire (response rate 63%) at T1 and 200 patients (50%) at T2, respectively, with 160 paired observations (112 females (70%), mean age 60.4 years (SD 9.9)). The total score for insufficient knowledge about contents decreased from 9.3 (SD 4.9) to 8.5 (SD 4.8; p = 0.03) and for accessibility from 8.6 (SD 4.7) to 8.4 (SD 4.9; p = 0.59). Total score for information need about contents decreased from 4.2 (SD 4.5) to 1.9 (SD 2.9; p < 0.01) and for accessibility from 3.6 (SD 4.5) to 1.4 (SD 2.4; p < 0.01) (paired t-tests).After the administration of a website comprising practical health care information, RA patients' information need and to a lesser extent their perception of having insufficient knowledge on relevant regional health care services decreased significantly. The results of this descriptive study suggest that the use of the Internet to inform patients may be effective, although controlled studies are required to evaluate and optimize web-delivered information.

Objective: To measure patient-perceived knowledge and information need regarding regional health care services and their determinants among 400 patients with rheumatoid arthritis (RA) and to identify the preferred method of information provision., Methods: Postal survey on knowledge and information need (content and accessibility) of 18 regional health care services and preferences for the mode of delivery of information. Logistic regression analyses determined which factors were associated with insufficient knowledge and information need., Results: Two-hundred and thirty-seven (94%) patients reported insufficient knowledge about the contents and 235 (94%) about the accessibility of at least one health care services, whereas 172 patients (69%) reported an information need about the content and 154 (61%) on the accessibility. Age was significantly associated with knowledge whereas both age and physical functioning were significantly associated with information need. Seventy-nine percent of the patients mentioned written information, 21% the Internet and 12% personal contact with a professional as a preferred method of information delivery., Conclusion: Many RA patients reported a lack of knowledge or information need concerning the contents and accessibility of regional health care services., Practice Implications: Active strategies to provide practical information about health care services are needed for RA patients., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aim: Since the introduction of chemotherapy, survival in localised high-grade osteosarcoma has improved considerably. However, there is still no worldwide consensus on a standard chemotherapy approach. In this systematic review evidence for effectiveness of each single drug and the role of response guided salvage treatment of adjuvant chemotherapy are addressed, whereas in a meta-analysis the number of drugs in current protocols is considered., Methods: A systematic literature search for clinical studies in localised high-grade osteosarcoma was undertaken, including both randomised and non-randomised trials. Historical clinical studies from the pre-chemotherapy era were included for comparison purposes., Results: Nine historical studies showed a long-term survival of 16% after only local treatment. Fifty single agent phase II studies showed high response rates for adriamycin (A, 43%), ifosfamide (Ifo, 33%), methotrexate (M, 32%), cisplatin (P, 26%) but only 4% for etposide (E). In 19 neo-adjuvant studies the mean 5-year event free survival (EFS) was 48% for 2-drug regimens and 58% for ⩾3 drug regimens, with a 5-year overall survival (OAS) of 62% and 70%, respectively. Meta-analysis showed that ⩾3 drug regimens including methotrexate plus adriamycin plus cisplatin (plus ifosfamide) (MAP(Ifo)) had significant better outcome (EFS: HR=0.701 (95% confidence interval [95% CI]: 0.615-0.799); OAS: HR=0.792 (95% CI: 0.677-0.926) than 2-drug regimens, but there was no significant difference between MAP and MAPIfo (or plus etoposide). Salvage of poor responders by changing drugs, or intensifying treatment postoperatively has not proven to be useful in this analysis., Conclusion: Meta-analysis in patients with localised high-grade osteosarcoma shows that 3-drug regimens, for example MAP are the most efficacious drug regimens., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In recent years, multi-state models have been studied widely in survival analysis. Despite their clear advantages, their use in biomedical and other applications has been rather limited so far. An important reason for this is the lack of flexible and user-friendly software for multi-state models. This paper introduces a package in R, called 'mstate', for each of the steps of the analysis of multi-state models. It can be applied to non- and semi-parametric models. The package contains functions to facilitate data preparation and flexible estimation of different types of covariate effects in the context of Cox regression models, functions to estimate patient-specific transition intensities, dynamic prediction probabilities and their associated standard errors (both Greenwood and Aalen-type). Competing risks models can also be analyzed by means of mstate, as they are a special type of multi-state models. The package is available from the R homepage http://cran.r-project.org. We give a self-contained account of the underlying mathematical theory, including a new asymptotic result for the cumulative hazard function and new recursive formulas for the calculation of the estimated standard errors of the estimated transition probabilities, and we illustrate the use of the key functions of the mstate package by the analysis of a reversible multi-state model describing survival of liver cirrhosis patients., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Diagnostic tests play an important role in clinical practice. The objective of a diagnostic test accuracy study is to compare an experimental diagnostic test with a reference standard. The majority of these studies dichotomize test results into two categories: negative and positive. But often the underlying test results may be categorized into more than two, ordered, categories. This article concerns the situation where multiple studies have evaluated the same diagnostic test with the same multiple thresholds in a population of non-diseased and diseased individuals. Recently, bivariate meta-analysis has been proposed for the pooling of sensitivity and specificity, which are likely to be negatively correlated within studies. These ideas have been extended to the situation of diagnostic tests with multiple thresholds, leading to a multinomial model with multivariate normal between-study variation. This approach is efficient, but computer-intensive and its convergence is highly dependent on starting values. Moreover, monotonicity of the sensitivities/specificities for increasing thresholds is not guaranteed. Here, we propose a Poisson-correlated gamma frailty model, previously applied to a seemingly quite different situation, meta-analysis of paired survival curves. Since the approach is based on hazards, it guarantees monotonicity of the sensitivities/specificities for increasing thresholds. The approach is less efficient than the multinomial/normal approach. On the other hand, the Poisson-correlated gamma frailty model makes no assumptions on the relationship between sensitivity and specificity, gives consistent results, appears to be quite robust against different between-study variation models, and is computationally very fast and reliable with regard to the overall sensitivities/specificities.

The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin-Frankfurt-Münster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9 followed the Total Therapy approach; cranial irradiation was replaced by medium-dose methotrexate infusions and prolonged triple intrathecal therapy; dexamethasone was used instead of prednisone. Studies ALL-7 and ALL-8 had a BFM backbone, including more intensive remission induction, early reinduction and maintenance therapy without vincristine and prednisone pulses. The 5-year event-free survival and overall survival increased from 65.4 to 80.6% (P<0.001) and from 78.7 to 86.4% (P=0.07) in ALL-7 and ALL-9, respectively. In ALL-7 and ALL-8 National Cancer Institute (NCI) high-risk criteria, male gender, T-lineage ALL and high white blood cells (WBCs) predict poor outcome. In ALL-9 NCI criteria, gender, WBC >100 x 109/l, and T-lineage ALL have prognostic impact. We conclude that the chemotherapy-only approach in children with ALL in Total Therapy-based strategies and BFM-backbone treatment does not jeopardize survival and preserves cognitive functioning. This experience is implemented in the current DCOG-ALL-10 study using a BFM backbone and minimal residual disease-based stratification.

We address the problem of meta-analysis of pairs of survival curves under heterogeneity. Starting point for the meta-analysis is a set of studies, each comparing the same two treatments, containing information about multiple survival outcomes. Under heterogeneity, we model the number of events using an extension of the Poisson correlated gamma-frailty model with serial within-arm and positive between-arm correlations. The parameters of the models are estimated following a two-stage estimation procedure. In the first stage the underlying hazards and between-study variance are estimated using the marginals, while a second stage is used to estimate both within-arm and between-arm correlations. The methodology is illustrated with an observational study on breast cancer.

We describe a new multivariate gamma distribution and discuss its implication in a Poisson-correlated gamma-frailty model. This model is introduced to account for between-subjects correlation occurring in longitudinal count data. For likelihood-based inference involving distributions in which high-dimensional dependencies are present, it may be useful to approximate likelihoods based on the univariate or bivariate marginal distributions. The merit of composite likelihood is to reduce the computational complexity of the full likelihood. A 2-stage composite-likelihood procedure is developed for estimating the model parameters. The suggested method is applied to a meta-analysis study for survival curves.

In this paper we address two issues arising in multi-state models with covariates. The first issue deals with how to obtain parsimony in the modeling of the effect of covariates. The standard way of incorporating covariates in multi-state models is by considering the transitions as separate building blocks, and modeling the effect of covariates for each transition separately, usually through a proportional hazards model for the transition hazard. This typically leads to a large number of regression coefficients to be estimated, and there is a real danger of over-fitting, especially when transitions with few events are present. We extend the reduced-rank ideas, proposed earlier in the context of competing risks, to multi-state models, in order to deal with this issue. The second issue addressed in this paper was motivated by the wish to obtain standard errors of the regression coefficients of the reduced-rank model. We propose a model-based resampling technique, based on repeatedly sampling trajectories through the multi-state model. The same ideas are also used for the estimation of prediction probabilities in general multi-state models and associated standard errors. We use data from the European Group for Blood and Marrow Transplantation to illustrate our techniques.

Standard survival data measure the time span from some time origin until the occurrence of one type of event. If several types of events occur, a model describing progression to each of these competing risks is needed. Multi-state models generalize competing risks models by also describing transitions to intermediate events. Methods to analyze such models have been developed over the last two decades. Fortunately, most of the analyzes can be performed within the standard statistical packages, but may require some extra effort with respect to data preparation and programming. This tutorial aims to review statistical methods for the analysis of competing risks and multi-state models. Although some conceptual issues are covered, the emphasis is on practical issues like data preparation, estimation of the effect of covariates, and estimation of cumulative incidence functions and state and transition probabilities. Examples of analysis with standard software are shown., (Copyright 2006 John Wiley & Sons, Ltd.)

Competing events concerning individual subjects are of interest in many medical studies. For example, leukemia-free patients surviving a bone marrow transplant are at risk of developing acute or chronic graft-versus-host disease, or they might develop infections. In this situation, competing risks models provide a natural framework to describe the disease. When incorporating covariates influencing the transition intensities, an obvious approach is to use Cox's proportional hazards model for each of the transitions separately. A practical problem then is how to deal with the abundance of regression parameters. Our objective is to describe the competing risks model in fewer parameters, both in order to avoid imprecise estimation in transitions with rare events and in order to facilitate interpretation of these estimates. Suppose that the regression parameters are gathered into a p x K matrix B, with p and K as the number of covariates and transitions, respectively. We propose the use of reduced rank models, where B is required to be of lower rank R, smaller than both p and K. One way to achieve this is to write B = AGamma(intercal) with A and Gamma matrices of dimensions p x R and K x R, respectively. We shall outline an algorithm to obtain estimates and their standard errors in a reduced rank proportional hazards model for competing risks and illustrate the approach on a competing risks model applied to 8966 leukemia patients from the European Group for Blood and Marrow Transplantation.

Background: Cardiopulmonary bypass (CPB) is associated with postoperative myocardial stunning, hypothermia, formation of microemboli, and systemic inflammatory response syndrome, all of which may prolong recovery from coronary artery bypass grafting (CABG) surgery. This study sought to compare outcomes in patients undergoing CABG off pump versus on pump., Methods: Outcomes, including mortality and several morbidities, were reviewed in 1,623 on-pump patients and 683 off-pump patients. Morbidities assessed included postoperative bleeding, incidence of multiorgan dysfunction, and neurologic complications. Chi-square and t-test analysis were used to determine statistical significance., Results: Mortality was 42% lower in the off-pump group than the on-pump group. Both critical care and total hospital length of stay were significantly shorter in the off-pump group. The incidence of postoperative bleeding requiring transfusion or a return to the operating room was reduced by 29% in the off-pump group and the incidence of multiorgan dysfunction was reduced by 31%. The off-pump patients also presented a significantly lower incidence of cerebral vascular accidents and seizures than on-pump patients., Conclusions: We conclude that there is an association between improved patient outcome and off-pump CABG surgery. The outcomes of this study show a statistically significant decrease in mortality, critical care length of stay, total hospital stay, incidence of bleeding requiring transfusion or return to the operating room, amount of blood transfused, incidence of multiorgan dysfunction, cerebral vascular accidents, and seizures in off-pump patients when compared with on-pump patients. Such results support the use of myocardial revascularization off pump as an alternative to CABG surgery on pump. CABG surgery off pump may allow a better postoperative clinical course in patients who are candidates for the procedure.

Study Objectives: To characterize acute changes in the dynamic, passive mechanical properties of the lungs and chest wall, elastance (E) and resistance (R), caused by lung volume reduction surgery (LVRS)., Design: Prospective data collection., Patients: Nine anesthetized/paralyzed patients with severe emphysema., Interventions: Bilateral LVRS., Measurements and Results: From measurements of airway and esophageal pressures and flow during mechanical ventilation throughout the physiologic range of breathing frequency (f) and tidal volume (VT), E and R of the total respiratory system (Ers and Rrs), lungs (EL and RL), and chest wall (Ecw and Rcw) immediately before and after LVRS were calculated. After surgery, Ers, EL, Rrs, and RL were all greatly increased at each combination off and VT (p<0.05). Ecw and Rcw showed no consistent changes (p>0.05). The increases in EL were greatest in those patients with the lowest residual volumes, highest FEV1 values, and highest maximum voluntary ventilations measured 3 months preoperatively (p<0.05); the increases in RL were greatest in those patients with the lowest preoperative residual volumes (p<0.05). The largest increases in RL were in those patients with the largest decreases in residual volume and total lung capacity, measured 3 months postoperatively, caused by LVRS (p<0.05)., Conclusion: Acute effects of LVRS are large increases in lung elastic tension and resistance; these increases need to be considered in immediate postoperative care, and can be predicted roughly from results of preoperative pulmonary function tests.

Malignant pleural and pericardial effusions are debilitating complications of metastatic malignancy. Improper management may lead to multiple hospital admissions and loss of quality of life for patients with a short life expectancy. The majority of malignant pleural effusions are diagnosed and controlled by thoracentesis and sclerosis. Those with pericardial malignancy are best diagnosed and treated with pericardiocentesis and pericardial window. Strategies for the management of more difficult cases are also discussed in this article.

A new technique for pericardial resection is described using thoracoscopy. With the advent of newer videolaparoscopic techniques allowing better visualization and the use of new endoscopic staplers, a whole spectrum of surgical procedures can now be performed through the thoracoscope.

Preoperative staging in esophageal cancer is usually done by noninvasive tests. Currently, in the staging of lung cancer, when lymph nodes are identified preoperatively by CT or MRI to be greater than 1 cm, surgical staging using mediastinoscopy, Chamberlain procedures, or thoracoscopy are employed. We describe herein the use of thoracoscopy in routine preoperative staging of esophageal cancer. With the advent of newer laparoscopic techniques currently available, thoracoscopy plays an increasing role in the management of intrathoracic disease. Staging thoracoscopy as a routine preoperative invasive staging test appears to be a good diagnostic test.

Diffuse interstitial lung disease and pulmonary fibrosis occurred after the use of vindesine and radiation therapy in a patient with squamous cell carcinoma of the lung. Clinical improvement occurred after the drug was discontinued and corticosteroid therapy was initiated. Review of the literature reveals no previously reported cases of pulmonary toxicity due to vindesine when used alone or in combination with other therapeutic modalities.