Validation of the French Version of the "Patterns of Activity Measure" in Patients with Chronic Musculoskeletal Pain.

Background. The "Patterns of Activity Measure" (POAM-P) is a self-administered questionnaire that assesses "avoidance", "pacing" and "overdoing" activity patterns in chronic pain patients. Objectives. To adapt the POAM-P to French ("POAM-P/F") and test its validity and reliability in Chronic Musculo-Skeletal Pain patients (CMSP). Methods. We followed the recommended procedure for translation of questionnaires. Five hundred and ninety five inpatients, admitted to a tertiary rehab center in the French-speaking part of Switzerland for chronic pain after orthopedic trauma, were included (sex ratio M/F = 4.36, mean age 43 ± 12). Face, content and criterion validities, internal consistency and reliability were assessed. Data included: TAMPA Scale for Kinesiophobia (TSK), Chronic Pain Coping Inventory (CPCI), Pain Catastrophizing Scale (PCS), Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS). Results. Face and content validities were checked during the translation process. Correlations between POAM-P/F-avoidance and TSK, POAM-P/F-pacing and CPCI-pacing, POAM-P/F-overdoing and CPCI-task persistence were highly significant (r > 0.3, p < 10(-2)). The three subscales demonstrated excellent homogeneity (Cronbach's alpha coefficients > 0.8) and test-retest reliability (Intraclass Correlation Coefficients > 0.8). They correlated very differently with the other scales. Discussion and Conclusion. The three POAM-P/F subscales clearly assess different behaviors in CMSP. The POAM-P/F is a suitable questionnaire for classifying French speaking CMSP into avoiders, pacers or overdoers

Are patients with hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorder so different?

Diagnosing hypermobile Ehlers-Danlos syndrome (hEDS) remains challenging, despite new 2017 criteria. Patients not fulfilling these criteria are considered to have hypermobile spectrum disorder (HSD). Our first aim was to evaluate whether patients hEDS were more severely affected and had higher prevalence of extra-articular manifestations than HSD. Second aim was to compare their outcome after coordinated physical therapy. Patients fulfilling hEDS/HSD criteria were included in this real-life prospective cohort (November 2017/April 2019). They completed a 16-item Clinical Severity Score (CSS-16). We recorded bone involvement, neuropathic pain (DN4) and symptoms of mast cell disorders (MCAS) as extra-articular manifestations. After a standardized initial evaluation (T0), all patients were offered the same coordinated physical therapy, were followed-up at 6 months (T1) and at least 1 year later (T2), and were asked whether or not their condition had subjectively improved at T2. We included 97 patients (61 hEDS, 36 HSD). Median age was 40 (range 18-73); 92.7% were females. Three items from CSS-16 (pain, motricity problems, and bleeding) were significantly more severe with hEDS than HSD. Bone fragility, neuropathic pain and MCAS were equally prevalent. At T2 (20 months [range 18-26]) 54% of patients reported improvement (no difference between groups). On multivariable analysis, only family history of hypermobility predicted (favorable) outcome (p = 0.01). hEDS and HDS patients showed similar disease severity score except for pain, motricity problems and bleeding, and similar spectrum of extra-articular manifestations. Long-term improvement was observed in > 50% of patients in both groups. These results add weight to a clinical pragmatic proposition to consider hEDS/HSD as a single entity that requires the same treatments

Feasibility of a prehabilitation program before major abdominal surgery: a pilot prospective study.

To assess the feasibility of a prehabilitation program and its effects on physical performance and outcomes after major abdominal surgery. In this prospective pilot study, patients underwent prehabilitation involving three training sessions per week for 3 weeks preoperatively. The feasibility of delivering the intervention was assessed based on recruitment and adherence to the program. Its impacts on fitness (oxygen uptake (VO <sub>2</sub> )) and physical performance (Timed Up and Go Test, 6-Minute Walk Test) were evaluated. From May 2017 to January 2020, 980 patients were identified and 44 (4.5%) were invited to participate. The main obstacles to patient recruitment were insufficient time (<3 weeks) prior to scheduled surgery (n = 276, 28%) and screening failure (n = 312, 32%). Of the 44 patients, 24 (55%) declined to participate, and 20 (23%) were included. Of these, six (30%) were not adherent to the program. Among the remaining 14 patients, VO <sub>2</sub> at ventilatory threshold significantly increased from 9.7 to 10.9 mL/min/kg. No significant difference in physical performance was observed before and after prehabilitation. Although prehabilitation seemed to have positive effects on exercise capacity, logistic and patient-related difficulties were encountered. The program is not feasible in its current form for all-comers

"Minimal clinically important difference" estimates of 6 commonly-used performance tests in patients with chronic musculoskeletal pain completing a work-related multidisciplinary rehabilitation program.

Functional tests are widely used to measure performance in patients with chronic musculoskeletal pain. Our objective was to determine the Minimal Clinically Important Differences (MCID) for the 6-min walk test (6MWT), the Steep Ramp Test (SRT), the 1-min stair climbing test (1MSCT), the sit-to-stand test (STS), the Jamar dynamometer test (JAM) and the lumbar Progressive Isoinertial Lifting Evaluation (PILE) in chronic musculoskeletal pain patients. A single-center prospective observational study was conducted in a rehabilitation center. Patients with upper-limb, lower-limb or neck/back lesions were included over a period of 21 months. We used the anchor-based method as a reference method, supplemented by the distribution-based and opinion-based approaches, to determine the MCIDs. 838 chronic musculoskeletal pain patients were included. The estimation method and thelesion location had a significant influence on the results. MCIDs were estimated at +75m and +60m for the 6MWT (lower-limb and neck/back lesions, respectively), +18 steps for the 1MSCT (lower-limb and neck/back lesions) and +6kg for the JAM (upper limb lesions). The anchor-based method could not provide valid estimations for the three other scales, but distribution and opinion-based methods provided rough values of MCIDs for the SRT (+39w to +61w), the STS (-5 sec to -7 sec) and the PILE (+4kg to +7kg). The above MCID estimations for the 6MWT, 1MSCT and JAM can be used in chronic musculoskeletal pain patients participating in vocational multidisciplinary rehabilitation programs or in therapeutic trials. The use of specific anchors might give better estimations of MCIDs for the three other scales in future research

Transcultural adaptation and validation of a French version of the Prosthetic Limb Users Survey of Mobility 12-item Short-Form (PLUS-M/FC-12) in active amputees.

The PLUS-M 12-item Short-Form is a self-questionnaire that assesses the perceived capacity of lower limb amputees (LLAs) to perform a number of daily-life activities. Its psychometric properties are excellent (intraclass correlation coefficient [ICC]>0.9, fast administration and scoring, normative data available), and it can be used in clinical practice or for research purposes. We aimed to develop a French version of this questionnaire and to assess its psychometric properties. We followed international recommendations for translation and cross-cultural validation of questionnaires. In total, 52 LLAs (age 53±16, 40 males, 28/12/12 transtibial/Gritti-Stokes/transfemoral, 20/28/4 ischemic/traumatic/other) participated. Criterion and construct validities were assessed with the Pearson correlation coefficient (PCC) between the PLUS-M 12-item Short-Form and other constructs (Prosthetic-Profile-of-the-Amputee-Locomotor Capabilities Index, Activities-specific Balance Confidence scale, 2-min walking test and Timed Up and Go test), internal consistency with the Cronbach α and reliability with the ICC in 46 individuals who completed the questionnaire twice in a 7-day interval. The mean (SD) PLUS-M 12-item Short-Form T-score was 56.1 (7.8; range 40.3 to 71.4). Construct and criterion validity, internal consistency and reliability ranged from low to excellent (r=0.43 to 0.84, P<10 <sup>-2</sup> to 0.002; Cronbach α=0.90, ICC=0.89 [0.81-0.94]). We found no floor or ceiling effect. The French version of the PLUS-M 12-item Short-Form has good to excellent psychometric properties, comparable to those of the original version. Its use could definitely be proposed for both clinical and research purposes, once its validation is completed by assessing other psychometric qualities, especially sensitivity to change

Diagnostic yield and cost analysis of electrocardiographic screening in Swiss paediatric athletes

OBJECTIVES Athletes performing sports on high level are at increased risk for sudden cardiac death. This includes paediatric athletes, even though data on screening strategies in this age group remain scarce. This study aimed to assess electrocardiogram interpretation criteria in paediatric athletes and to evaluate the cost of screening. METHODS National, multicentre, retrospective, observational study on 891 athletes of paediatric age (<18 years) evaluated by history, physical examination and 12-lead electrocardiogram. The primary outcome measure was abnormal electrocardiogram findings according to the International Recommendations for Electrographic Interpretation in Athletes. The secondary outcome measure was cost of screening. RESULTS 19 athletes (2.1%) presented abnormal electrocardiogram findings requiring further investigations, mainly abnormal T-wave inversion. These 19 athletes were predominantly males, performing endurance sports with a mean volume of 10 weekly hours for a mean duration of 6 years of training. Further investigations did not identify any relevant pathology. All athletes were cleared for competition with regular follow-up. Total costs of the screening were 108,860 USD (122 USD per athlete). CONCLUSIONS Our study using the International Recommendations for Electrographic Interpretation in Athletes identified a low count of abnormal findings in paediatric athletes, yet raising substantially the cost of screening. Hence, the utility of electrocardiogram-inclusive screening of paediatric athletes remains to be elucidated by longitudinal data

Phase I study of MLN8237—investigational Aurora A kinase inhibitor—in relapsed/refractory multiple myeloma, Non-Hodgkin lymphoma and chronic lymphocytic leukemia

Purpose Amplification or over-expression of the mitotic Aurora A kinase (AAK) has been reported in several heme-lymphatic malignancies. MLN8237 (alisertib) is a novel inhibitor of AAK that is being developed for the treatment of advanced malignancies. The objectives of this phase I study were to establish the safety, tolerability, and pharmacokinetic profiles of escalating doses of MLN8237 in patients with relapsed or refractory heme-lymphatic malignancies. Methods Sequential cohorts of patients received MLN8237 orally as either a powder-in-capsule (PIC) or enteric-coated tablet (ECT) formulation. Patients received MLN8237 PIC 25–90 mg for 14 or 21 consecutive days plus 14 or 7 days’ rest, respectively, or MLN8237 ECT, at a starting dose of 40 mg/day once-daily (QD) for 14 days plus 14 days’ rest, all in 28-day cycles. Subsequent cohorts received MLN8237 ECT 30–50 mg twice-daily (BID) for 7 days plus 14 days’ rest in 21-day cycles. Results Fifty-eight patients were enrolled (PIC n = 28, ECT n = 30). The most frequent grade ≥3 drug-related toxicities were neutropenia (45 %), thrombocytopenia (28 %), anemia (19 %), and leukopenia (19 %). The maximum tolerated dose on the ECT 7-day schedule was 50 mg BID. The terminal half-life of MLN8237 was approximately 19 h. Six (13 %) patients achieved partial responses and 13 (28 %) stable disease. Conclusion The recommended phase II dose of MLN8237 ECT is 50 mg BID for 7 days in 21-day cycles, which is currently being evaluated as a single agent in phase II/III trials in patients with peripheral T-cell lymphoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10637-013-0050-9) contains supplementary material, which is available to authorized users

After the sunset: the residual effect of temporary legislation

The difference between permanent legislation and temporary legislation is the default rule of termination: permanent legislation governs perpetually, while temporary legislation governs for a limited time. Recent literature on legislative timing rules considers the effect of temporary legislation to stop at the moment of expiration. When the law expires, so does its regulatory effect. This article extends that literature by examining the effect of temporary legislation beyond its expiration. We show that in addition to affecting compliance behavior which depends on statutory enforcement, temporary legislation also affects compliance behavior which does not depend on statutory enforcement, and more generally, organizational behavior after a sunset. When temporary legislation expires therefore, it can continue to administer regulatory and other effects. We specify the conditions for this process and give the optimal legislative response

Mean-Field Limits Beyond Ordinary Differential Equations

16th International School on Formal Methods for the Design of Computer, Communication, and Software Systems, SFM 2016, Bertinoro, Italy, June 20-24, 2016, Advanced LecturesInternational audienceWe study the limiting behaviour of stochastic models of populations of interacting agents, as the number of agents goes to infinity. Classical mean-field results have established that this limiting behaviour is described by an ordinary differential equation (ODE) under two conditions: (1) that the dynamics is smooth; and (2) that the population is composed of a finite number of homogeneous sub-populations, each containing a large number of agents. This paper reviews recent work showing what happens if these conditions do not hold. In these cases, it is still possible to exhibit a limiting regime at the price of replacing the ODE by a more complex dynamical system. In the case of non-smooth or uncertain dynamics, the limiting regime is given by a differential inclusion. In the case of multiple population scales, the ODE is replaced by a stochastic hybrid automaton

Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity.

This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape