Cost-effectiveness of manual therapy versus physiotherapy in patients with sub-acute and chronic neck pain: a randomised controlled trial.

PURPOSE: To evaluate the cost-effectiveness of manual therapy according to the Utrecht School (MTU) in comparison with physiotherapy (PT) in sub-acute and chronic non-specific neck pain patients from a societal perspective. METHODS: An economic evaluation was conducted alongside a 52-week randomized controlled trial, in which 90 patients were randomized to the MTU group and 91 to the PT group. Clinical outcomes included perceived recovery (yes/no), functional status (continuous and yes/no), and quality-adjusted life-years (QALYs). Costs were measured from a societal perspective using self-reported questionnaires. Missing data were imputed using multiple imputation. To estimate statistical uncertainty, bootstrapping techniques were used. RESULTS: After 52 weeks, there were no significant between-group differences in clinical outcomes. During follow-up, intervention costs (ß:€-32; 95 %CI: -54 to -10) and healthcare costs (ß:€-126; 95 %CI: -235 to -32) were significantly lower in the MTU group than in the PT group, whereas unpaid productivity costs were significantly higher (ß:€186; 95 %CI:19-557). Societal costs did not significantly differ between groups (ß:€-96; 95 %CI:-1975-2022). For QALYs and functional status (yes/no), the maximum probability of MTU being cost-effective in comparison with PT was low (≤0.54). For perceived recovery (yes/no) and functional status (continuous), a large amount of money must be paid per additional unit of effect to reach a reasonable probability of cost-effectiveness. CONCLUSIONS: From a societal perspective, MTU was not cost-effective in comparison with PT in patients with sub-acute and chronic non-specific neck pain for perceived recovery, functional status, and QALYs. As no clear total societal cost and effect differences were found between MTU and PT, the decision about what intervention to administer, reimburse, and/or implement can be based on the preferences of the patient and the decision-maker at hand. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00713843.

Blockade of BCL-2 proteins efficiently induces apoptosis in progenitor cells of high-risk myelodysplastic syndromes patients.

Deregulated apoptosis is an identifying feature of myelodysplastic syndromes (MDS). Whereas apoptosis is increased in the bone marrow (BM) of low-risk MDS patients, progression to high-risk MDS correlates with an acquired resistance to apoptosis and an aberrant expression of BCL-2 proteins. To overcome the acquired apoptotic resistance in high-risk MDS, we investigated the induction of apoptosis by inhibition of pro-survival BCL-2 proteins using the BCL-2/-XL/-W inhibitor ABT-737 or the BCL-2-selective inhibitor ABT-199. We characterized a cohort of 124 primary human BM samples from MDS/secondary acute myeloid leukemia (sAML) patients and 57 healthy, age-matched controls. Inhibition of anti-apoptotic BCL-2 proteins was specifically toxic for BM cells from high-risk MDS and sAML patients, whereas low-risk MDS or healthy controls remained unaffected. Notably, ABT-737 or ABT-199 treatment was capable of targeting the MDS stem/progenitor compartment in high-risk MDS/sAML samples as shown by the reduction in CD34(+) cells and the decreased colony-forming capacity. Elevated expression of MCL-1 conveyed resistance against both compounds. Protection by stromal cells only partially inhibited induction of apoptosis. Collectively, our data show that the apoptotic resistance observed in high-risk MDS/sAML cells can be overcome by the ABT-737 or ABT-199 treatment and implies that BH3 mimetics might delay disease progression in higher-risk MDS or sAML patients.

Cks1 is a critical regulator of hematopoietic stem cell quiescence and cycling, operating upstream of Cdk inhibitors.

Cyclin-dependent kinase subunit 1 (Cks1) is a critical rate-limiting component of the Skp1-Cullin1-Skp2 (SCF(Skp2)) ubiquitin ligase that controls cell cycle inhibitor abundance. Cyclin-dependent kinase (Cdk) inhibitors (CKIs) regulate hematopoietic stem cell (HSC) self-renewal, regeneration after cytotoxic stress and tumor cell proliferation. We thus studied the role of Cks1 in HSC and in a prototypic stem cell disorder, chronic myeloid leukemia (CML). Cks1 transcript was highly expressed in Lin-Sca-1+Kit+ (LSK) HSC, and the loss resulted in accumulation of the SCF(Skp2)/Cks1 substrates p21, p27, p57 and p130 particularly in CD150+ LSK cells. This accumulation correlated with decreased proliferation and accumulation of Cks1(-/-) HSC, slower regeneration after stress and prolonged HSC quiescence. At the hematopoietic progenitor (HPC) level, loss of Cks1 sensitized towards apoptosis. In CML, Cks1 expression was increased, and treatment with the Abl kinase inhibitor, imatinib, reduced Cks1 expression. Also, we found that Cks1 is critical for Bcr-Abl-induced cytokine-independent clonogenic activity. In conclusion, our study presents a novel function of Cks1 in maintaining HSC/HPC homeostasis and shows that Cks1 is a possible target in therapies aimed at the SCF(Skp2)/Cks1 complex that controls CKI abundance and cancer cell proliferation.

Therapeutic targeting of naturally presented myeloperoxidase-derived HLA peptide ligands on myeloid leukemia cells by TCR-transgenic T cells.

T cells have been proven to be therapeutically effective in patients with relapsed leukemias, although target antigens on leukemic cells as well as T-cell receptors (TCRs), potentially recognizing those antigens, are mostly unknown. We have applied an immunopeptidomic approach and isolated human leukocyte antigen (HLA) ligands from primary leukemia cells. We identified a number of ligands derived from different genes that are restrictedly expressed in the hematopoietic system. We exemplarily selected myeloperoxidase (MPO) as a potential target and isolated a high-avidity TCR with specificity for a HLA-B*07:02-(HLA-B7)-restricted epitope of MPO in the single HLA-mismatched setting. T cells transgenic for this TCR demonstrated high peptide and antigen specificity as well as leukemia reactivity in vitro and in vivo. In contrast, no significant on- and off-target toxicity could be observed. In conclusion, we here demonstrate, exemplarily for MPO, that leukemia-derived HLA ligands can be selected for specific effector tool development to redirect T cells to be used for graft manipulation or adoptive T-cell therapies in diverse transplant settings. This approach can be extended to other HLA ligands and HLA molecules in order to provide better treatment options for this life-threatening disease.

Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1.

Chronic lymphocytic leukemia (CLL) has a high prevalence in western countries and remains incurable to date. Here, we provide evidence that the multikinase inhibitor sorafenib induces apoptosis in primary CLL cells. This strong pro-apoptotic effect is not restricted to any subgroup of patients, based on Binet stage and the expression of ZAP70 or CD38. Mechanistically, sorafenib-induced cell death is preceded by a rapid downregulation of Mcl-1 through the inhibition of protein translation. Subsequently, the cell intrinsic apoptotic pathway is activated, indicated by destabilization of the mitochondrial membrane potential and activation of caspase-3 and -9. In contrast to sorafenib, the monoclonal vascular epidermal growth factor (VEGF)-antibody bevacizumab failed to induce apoptosis in CLL cells, suggesting that sorafenib induces cell death irrespectively of VEGF signalling. Notably, although sorafenib inhibits phosphorylation of the Scr-kinase Lck, knock-down of Lck did not induce apoptosis in CLL cells. Of note, the pro-apoptotic effect of sorafenib is not restricted to cell-cycle arrested cells, but is also maintained in proliferating CLL cells. In addition, we provide evidence that sorafenib can overcome drug resistance in CLL cells protected by microenvironmental signals from stromal cells. Conclusively, sorafenib is highly active in CLL and may compose a new therapeutic option for patients who relapse after immunochemotherapy.

Speech pathology interventions in patients with neuromuscular diseases: a systematic review.

PURPOSE: A systematic review was conducted to summarize and evaluate the literature on the effectiveness of speech pathology interventions in adults with neuromuscular diseases. METHOD: Databases searched included the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE, PsycINFO and PubMed. A total of 1,772 articles were independently screened on title and abstract by 2 reviewers. RESULTS: No randomized controlled trials or clinical controlled trials were found. Four other designs were included. Only one study on oculopharyngeal muscle dystrophy (OPMD) appeared to have sufficient methodological quality. There is evidence indicating that correction of head position in patients with OPMD improves swallowing efficiency (level III evidence). CONCLUSION: Despite 1,772 studies, there is only evidence of level III regarding the effectiveness of speech pathology interventions in patients with OPMD. Recommendations for future research are given.

Quality indicators indicate good adherence to the clinical practice guideline on "Osteoarthritis of the hip and knee" and few prognostic factors influence outcome indicators: a prospective cohort study.

BACKGROUND: Evaluation with quality indicators of adherence to the clinical practice guideline on "Osteoarthritis of the hip and knee" and of treatment outcomes. AIM: Furthermore to determine prognostic factors for outcome indicators. DESIGN: Prospective cohort study. POPULATION: Twenty-seven well informed physical therapists recorded patient and treatment characteristics of 103 community-dwelling patients referred by a general practitioner diagnosed with osteoarthritis of hip or knee. METHODS: With selected process and outcome indicators adherences to the guideline and treatment outcomes were assessed. Prognostic factors were calculated for Algofunctional Index (AI) and Visual Analogue Scale (VAS) for pain (decreases of ≤25% indicating "poor outcome"), number of sessions (>12) and duration of treatment (>6 weeks), using multivariate logistic regression models. RESULTS: Process indicators showed that information & advice was given to 95% of the patients and functions and activities were exercised in 97% respectively 87%. Aftercare was arranged for 46% of the patients, that was clearly lower than the benchmark of 90%. Outcome indicators VAS-pain and AI decreased by 45% and 36%, respectively. The combination ">12 months" duration of complaints and age ≥65" was associated with a "poor outcome" on AI (OR 2.53; 95% CI 1.01-6.38). Co-morbidity (OR 2.8; 95% CI 1.17-6.88), and "VAS-pain at baseline ≥51 mm" (OR 3.1; 95% CI 1.34-7.23) were associated with a higher number of treatment sessions. CONCLUSION AND CLINICAL REHABILITATION IMPACT: and Quality indicators showed that a group of well-informed physical therapists could to a large extent adhere to key recommendations of the guideline and that clinically relevant improvements were obtained in terms of pain and physical functioning. Prognostic factors for poorer outcome on outcome indicators were comorbidity, a higher pain score at baseline and the combination ">12 months' duration of complaints and age ≥65".

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.

Dose-finding and pharmacokinetic study of orally administered indibulin (D-24851) to patients with advanced solid tumors.

Indibulin (ZIO-301/D-24851) is an orally applied small molecule with antitumor activity based upon destabilization of microtubule polymerization. The purpose of this phase I study was to determine the maximum tolerated dose (MTD) as well as the dose limiting toxicity (DLT), the pharmacokinetics, safety and tolerability of orally administered indibulin as capsule formulation in patients with advanced solid tumors. Patients received a single dose of indibulin. Seven dose-levels were evaluated: 100 mg, 150 mg, 250 mg, 350 mg and 600 mg once daily (QD), 450 mg and 600 mg twice daily (BID). After a washout period, patients received indibulin at the pre-defined daily dose for 14 days every 3 weeks (multiple dose part). A total of 28 patients entered the study. Indibulin administered as capsules was generally well tolerated. The MTD was not reached. There was a disproportionate increase of the area under the plasma concentration-time curve (AUC) with dose, with declining AUC corrected for dose starting at the 250 mg dose-level. There was no significant difference in AUC of indibulin after multiple dosing (day 1-14) compared to single administration (day-4). Inter-patient variability in AUC (102% CV) was high. A plateau in drug exposure was observed prior to reaching the MTD. Continued dose-escalation was unlikely to yield any increase in exposure of indibulin. The formulation needs optimization to increase the systemic exposure upon oral administration.

Optimizing referral of patients with neuromuscular disorders to allied health care.

BACKGROUND AND PURPOSE: To report the predictive validity of the perceived limitations in activities and need questionnaire (PLAN-Q), a screening instrument to support neurologists to select patients with neuromuscular disorders (NMD) for referral for a one-off consultation by occupational therapist (OT), physical therapist (PT) and speech therapist (ST). METHODS: In a cross-sectional validation study, 102 patients with various NMD participated. Patients received a one-off consultation by an expert OT, PT and ST and filled out the PLAN-Q. Therapists rated the appropriateness of the one-off consultations based on need, available treatment and patient's motivation. Receiver Operation Characteristic analysis and multivariate logistic regression analysis were used to obtain a PLAN-Q based prediction model for the appropriateness of the one-off consultations. RESULTS: Probability for a one-off OT consultation increased from 64% to 78% (95% CI: 69-85%). Prior test probability for a one-off ST consultation increased from 44% to 61% (95% CI: 48-73%). Prior test probability for one-off PT consultation could not be increased. CONCLUSION: Screening patients with NMD using the PLAN-Q may assist neurologists in selecting the appropriate patients for a one-off consultation by OT and ST. Unlike our expectations the screening did not guide referral for a one-off consultation by PT.

Quality indicators for physiotherapy in Parkinson's disease.

AIM: The aim of this study was to develop quality indicators for physiotherapy in Parkinson's disease (PD) according to international criteria. METHODS: Indicators were based on an evidence-based guideline for physiotherapy in PD. Guideline recommendations were transformed into indicators and rated for their relevance by an expert panel. Relevant indicators were incorporated into a questionnaire termed ''Quality Indicators for Physiotherapy in PD'' (QIP-PD). The QIP-PD was piloted among 105 physiotherapists. The adjusted version was evaluated in 46 physiotherapists with specific expertise in PD and in 795 general physiotherapists. The following clinimetric aspects of the QIP-PD were tested: completeness of answers, response distribution, internal consistency, and discriminative power. The reliability of the QIP-PD was evaluated by interviews among a randomly selected cohort of 32 PD experts and 32 general physiotherapists. RESULTS: The expert panel selected 16 indicators, which were transformed into an adjusted 17-item QIP-PD. The adjusted QIP-PD was completed by 41 expert physiotherapists and 286 general physiotherapists. Comple-teness of item scores ranged from 95-98%. Six items were excluded from the final analyses as they showed ceiling effect among both groups, or lacked discriminative power. The total QIP-PD score for the 11 items was significantly higher for expert physiotherapists (35.1+/-4.2) compared to general physiotherapists (22.2+/-7.7; P=0.01). Internal consistency was good (Crohnbach's alpha 0.84). QIP-PD scores of therapists and interviewers (correlated using Intraclass Correlations Coefficients) ranged from 0.63 to 0.75. CONCLUSIONS: The QIP-PD is a relevant, feasible, valid, discriminative and reliable instrument to measure adherence to guidelines for physiotherapy in PD. In addition, the results underscore that quality improvement interventions for physiotherapy in PD are needed, as guideline adherence is suboptimal in physiotherapists without specific PD expertise.

Bioequivalence study of a new oral topotecan formulation, relative to the current topotecan formulation, in patients with advanced solid tumors.

OBJECTIVE: The aims of this study were to investigate the bioequivalence of a new oral topotecan formulation (i.e., proposed commercial formulation) relative to the current oral formulation (formulation used in previous clinical trials), the effect of food on the absorption and disposition of the new oral topotecan and its safety and tolerability in patients with advanced solid tumors. PATIENTS AND METHODS: This was a multi-center, pharmacological Phase I, multiple-dose, randomized, open-label, cross-over bioequivalence study. In the bioequivalence part, 85 patients were randomized to receive either a 4 mg (4 x 1 mg) dose of the new or current formulation on Days 1 or 8. In the food-effect part, 23 patients received a 4 mg (4 x 1 mg) dose of the new formulation in a fasted and fed state. Total topotecan and topotecan lactone were determined and pharmacokinetic data were analyzed by non-compartmental method. RESULTS: Bioequivalence was demonstrated as the 90% confidence intervals of the ratio of the new to current formulation for both the area under the plasma concentration-time curve (AUC) and the maximal drug concentration (Cmax) for topotecan lactone were contained within the 0.8 - 1.25 boundary. The AUC and Cmax were similar in the fed and fasted state whilst food delayed the tmax for topotecan lactone and total topotecan. Safety data were collected on all subjects enrolled (n = 108) and were consistent with observations from previous studies of oral topotecan. All subjects experienced at least one adverse event, the majority of which were graded as mild to moderate in severity. CONCLUSION: The new oral topotecan formulation demonstrated bioequivalence to the current formulation and demonstrated it can be administered to patients with solid tumors in the fed or fasted state with similar systemic exposure.

Influence of behaviour and risk factors on motor performance in preterm infants at age 2 to 3 years.

The aim of this cross-sectional study was to determine the influence of test-taking behaviour and risk factors for delayed motor performance in 437 preterm infants (244 males, 193 females; < or = 32 weeks of gestation) at the corrected age of 2 to 3 years (mean 29mo [SD 3.3]). Other mean (SD) sample demographics were: postmenstrual age 29(+5) weeks (1(+5)), range 25(+0)-32(+0); birthweight 1213.7g (331.7), range 468-2350; and days in the neonatal intensive care unit 21.1 (21.3), range 1-165. Children (n=23) with a severe disability were excluded. We assessed motor performance and behaviour during testing with the Motor Scale and the Behaviour Rating Scale (BRS) of the Bayley Scales of Infant Development, 2nd edition (BSID-II). Risk factors were tested against delayed motor performance as the dependent variable in binary logistic regression analysis. Median score on the Motor Scale in terms of the BSID-II Psychomotor Developmental Index (PDI) was 86. 'Delayed' motor performance was observed in 46.5% of the children tested, and behaviour was 'not-optimal' in 31.4%. The Motor Scale and BRS scores were significantly correlated (r(s)=0.62, p<0.01). Risk factors for delayed motor performance were: neonatal convulsions (odds ratio [OR] 4.5; 95% confidence interval [CI] 1.6-12.9), low maternal educational level (OR 3.3; 95% CI 1.7-6.5), male sex (OR 2.8; 95% CI 1.8-4.3), and chronic lung disease (OR 2.1; 95% CI 1.1- 4.1). We conclude that preterm infants are at high risk of delayed motor performance and non-optimal test-taking behaviour.

A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon alpha/beta.

Type I interferon (IFN) is shown to control the reversible quiescence of a primitive human bone marrow mesenchymal stem cell (MSC) subpopulation. A 24 h pre-treatment of Stro1+/GlycoA- or CD45-/GlycoA- subpopulations with a monoclonal antibody (mAb) against the IFNAR1 chain of the human type I IFN receptor (64G12), or with a polyclonal anti-IFNalpha antibody, resulted in a marked increase in the number of very large colonies (CFU-F >3000 cells) obtained in the presence of low, but necessary, concentrations of bFGF. Over a 2-month culture period, this short activation promoted a faster and greater amplification of mesenchymal progenitors for adipocytes and osteoblasts. Activation correlated with inhibition of STAT1 and STAT2 phosphorylation and of STAT1 nuclear translocation. A non-neutralizing anti-IFNAR1 mAb was ineffective. We demonstrate that control and activated MSCs express ST3GAL3, a sialyltransferase necessary to produce the embryonic antigens SSEA-3 and -4. Interestingly, activated MSC progeny expressed SSEA-3 and -4 at a higher level than control cultures, but this was not correlated with a significant expression of other embryonic markers. As MSCs represent an essential tool in tissue regeneration, the use of 64G12, which rapidly recruits a higher number of primitive cells, might increase amplification safety for cell therapy.

Construct validity of instruments measuring impairments in body structures and function in rheumatic disorders: which constructs are selected for validation? A systematic review.

PURPOSE: This paper focuses on the construct validity of instruments measuring impairments in body structures and function in rheumatic disorders. The objective is: 1) to make an inventory of constructs, based on the domains of the International Classification of Functioning, Disabilities and Health problems (ICF), against which instruments measuring impairments in body structures and function were validated; 2) to analyse whether validation against a similar construct resulted in higher correlation coefficients than validation against a dissimilar construct. METHODS: In a systematic review papers were identified in which instruments measuring impairments in body structures and function for patients with rheumatic disorders were validated. The instruments identified were assessed on their methodological properties and the constructs against which they were validated. Subsequently, pooled (interclass) correlations of similar constructs and dissimilar constructs against which was validated were compared. An instrument was decided to have good construct validity, if the correlation coefficient was 0.50 or higher, and the measurement instrument in question is validated against similar constructs. RESULTS: In total 216 papers were identified analysing the validity of 42 different instruments. Only 16% of these instruments were validated against instruments that represent the most similar construct. In general, estimates of construct validity were lower when validated against dissimilar constructs, except for instruments measuring impairments in mental functions. CONCLUSION: There is a trend that validation against a similar construct yields higher correlation coefficients than validation against a dissimilar construct. If an instrument measuring impairments is validated against the most similar construct, and a criterion of r > 0.50 is applied, only 10 out of the 42 identified instruments turned out to be valid.

[The STEMMAT-project as part of health initiative BayernAktiv: adult stem cells from umbilical cord and cord blood as alternative to embryonic stem cell research]. / Das STEMMAT-Projekt als Teil der Gesundheitsinitiative BayernAktiv: Adulte Stammzellen aus Nabelschnur und -blut als Alternative zur embryonalen Stammzellforschung.

Adult stem cells from umbilical cord and cord blood are an interesting alternative to embryonic stem cells because such research is commonly recognized as ethical undisputed and many aspects are still insufficiently investigated. In the context of the STEMMAT research project (STEM = Stem Cell and MAT = Material) different aspects of stem cells from umbilical cord and cord blood are investigated, to improve basic science understanding and potentially leading someday to a clinical application.

Effect on the process of care of an active strategy to implement clinical guidelines on physiotherapy for low back pain: a cluster randomised controlled trial.

OBJECTIVES: To evaluate the effect on the process of care of an active strategy to implement clinical guidelines on physiotherapy for low back pain. DESIGN: A cluster randomised controlled trial comparing an active strategy with standard dissemination. SETTING: Primary care physiotherapy practices. PARTICIPANTS: 113 physiotherapists were randomly allocated to receive the guidelines by mail (control group) or to receive an additional active strategy (intervention group) which consisted of a multifaceted programme including education, discussion, role playing, feedback, and reminders. MAIN OUTCOME MEASURES: Adherence to the guidelines was measured by means of individual patients' forms recording the treatment completed by the physiotherapist. The forms were assessed using an algorithm based on the number of treatment sessions, treatment goals, interventions, and patient education. RESULTS: Physiotherapists in the intervention group more often correctly limited the number of treatment sessions for patients with a normal course of back pain (OR 2.39; 95% CI 1.12 to 5.12), more often set functional treatment goals (OR 1.99; 95% CI 1.06 to 3.72), more often used mainly active interventions (OR 2.79; 95% CI 1.19 to 6.55), and more often gave adequate patient education (OR 3.59; 95% CI 1.35 to 9.55). They also adhered more to all four criteria (OR 2.05; 95% CI 1.15 to 3.65). CONCLUSIONS: The active strategy moderately improved adherence to the guidelines. Active strategies are recommended to implement the clinical guidelines on physiotherapy for low back pain.

Which are the best instruments for measuring disabilities in gait and gait-related activities in patients with rheumatic disorders.

OBJECTIVES: Our first objective was to make an inventory of available instruments for the assessment of disabilities in gait and related activities in patients with rheumatic disorders. Our second aim was to investigate which of these instruments have acceptable methodological quality with regard to reliability and validity. Our third aim was to investigate the assumption that the evaluation of convergent construct validity results in stronger correlations when validated against a more similar construct. MATERIALS: A computer-aided literature search (1982-2001) of several databases was performed to identify studies focusing on the clinimetric properties of instruments to assess impairments in function in patients with rheumatic disorders. Data on intra-rater reliability, inter-rater reliability and convergent construct validity were extracted in a standardized manner and compared to a priori defined criteria. RESULTS: In total 78 instruments were eligible. Intra-observer reliability was investigated for 28 instruments and only 7 demonstrated good reliability as well as good validity. Surprisingly, the convergent construct validation against a similar construct resulted often in lower correlations than validation against a less similar construct. CONCLUSION: Based on the available information, the Rheumatoid Arthritis Quality of Life Scale and the Health Assessment Questionnaire seem to be the best instruments for assessing disabilities in gait and related activities in patients with rheumatic disorders.

Psychometric properties of the Tampa Scale for kinesiophobia and the fear-avoidance beliefs questionnaire in acute low back pain.

The transition from acute to chronic low back pain (LBP) is influenced by many interacting factors. Pain-related fear, as measured by the Tampa Scale for Kinesiophobia (TSK) and the Fear-Avoidance Beliefs Questionnaire (FABQ), is one of these factors. The objectives of this study were to investigate, in a population with acute LBP, the reliability of TSK and FABQ through evaluation of the internal consistency, the test-retest reliability, and the concurrent validity between TSK and FABQ. One hundred and Seventy-Six patients suffering LBP for no longer than 4 weeks completed a Visual Analogue Scale for pain (VAS), the TSK, the FABQ, and a socio-demographic questionnaire. Each patient completed the VAS, TSK, and FABQ twice within 24 h. Internal consistency of TSK and FABQ scores range from alpha=0.70 to 0.83. Test-retest reliability ranges from r(s)=0.64 to 0.80 (P<0.01). Concurrent validity is moderate, ranging from r(s) =0.33 to 0.59 (P<0.01). It may be concluded that in a population with acute LBP, both the TSK and the FABQ are reliable measures of pain-related fear. In the clinical setting they may provide the practitioner a means of identifying pain-related fear in a patient with acute LBP.

Stromal cells from murine embryonic aorta-gonad-mesonephros region, liver and gut mesentery expand human umbilical cord blood-derived CAFC(week6) in extended long-term cultures.

The first definitive long-term repopulating hematopoietic stem cells (HSCs) emerge from and undergo rapid expansion in the embryonic aorta-gonad-mesonephros (AGM) region. To investigate the presumptive unique characteristics of the embryonic hematopoietic microenvironment and its surrounding tissues, we have generated stromal clones from subdissected day 10 and day 11 AGMs, embryonic livers (ELs) and gut mesentery. We here examine the ability of 19 of these clones to sustain extended long-term cultures (LTCs) of human CD34(+) umbilical cord blood (UCB) cells in vitro. The presence of in vitro repopulating cells was assessed by sustained production of progenitor cells (extended LTC-CFC) and cobblestone area-forming cells (CAFC). The embryonic stromal clones differed greatly in their support for human HSCs. Out of eight clones tested in the absence of exogenous cytokines, only one (EL-derived) clone was able to provide maintenance of HSCs. Addition of either Tpo or Flt3-L + Tpo improved the long-term support of about 50% of the tested clones. Cultures on four out of 19 clones, ie the EL-derived clone mentioned, two urogenital-ridge (UG)-derived clones and one gastrointestinal (GI)-derived clone, allowed a continuous expansion of primitive CAFC and CFU-GM with over several hundred-fold more CAFC(week6) produced in the 12th week of culture. This expansion was considerably higher than that found with the FBMD-1 cell line, which is appreciated by many investigators for its support of human HSCs, under comparable conditions. This stromal cell panel derived from the embryonic regions may be a powerful tool in dissecting the factors mediating stromal support for maintenance and expansion of HSCs.