Moving fluoroscopy-based analysis of THA kinematics during unrestricted activities of daily living.

Introduction: Knowledge of the accurate in-vivo kinematics of total hip arthroplasty (THA) during activities of daily living can potentially improve the in-vitro or computational wear and impingement prediction of hip implants. Fluoroscopy- based techniques provide more accurate kinematics compared to skin marker-based motion capture, which is affected by the soft tissue artefact. To date, stationary fluoroscopic machines allowed the measurement of only restricted movements, or only a portion of the whole motion cycle. Methods: In this study, a moving fluoroscopic robot was used to measure the hip joint motion of 15 THA subjects during whole cycles of unrestricted activities of daily living, i.e., overground gait, stair descent, chair rise and putting on socks. Results: The retrieved hip joint motions differed from the standard patterns applied for wear testing, demonstrating that current pre-clinical wear testing procedures do not reflect the experienced in-vivo daily motions of THA. Discussion: The measured patient-specific kinematics may be used as input to in vitro and computational simulations, in order to investigate how individual motion patterns affect the predicted wear or impingement.

Medial unicompartmental knee arthroplasty in ACL-deficient knees is a viable treatment option: in vivo kinematic evaluation using a moving fluoroscope.

PURPOSE: Unicompartmental knee arthroplasty (UKA), resulting in similar kinematics to native knees, is functionally superior to total knee arthroplasty (TKA). However, ACL deficiency is generally considered to be a contraindication. The main purpose of this study was to investigate if UKA in ACL-deficient knees would result in similar kinematics to conventional UKA with an intact ACL. METHODS: Ten conventional UKA patients were compared to eight ACL-deficient patients with a reduced tibial slope to compensate for instability, resulting from the deficient ACL. Knee kinematics was evaluated with a moving fluoroscope, tracking the knee joint during daily activities. In a standing position (baseline), posterior shift of the femur was observed for ACL-deficient UKA patients, compared to conventional UKA patients. RESULTS: A significant posterior femoral shift in the ACL-deficient group was observed during the first 25% (near extension) of deep knee bend, while there was no difference in kinematic waveforms for all other activities. No significant range of motion differences across different activities between the two UKA groups were detected, except for an increase of medial AP translation in the ACL-deficient group, during deep knee bend and stair descent. CONCLUSION: Despite the posterior femoral shift due to ACL deficiency, both UKA groups showed similar kinematic waveforms, indicating that posterior tibial slope reduction can partially compensate for ACL function. This supported our hypothesis that fixed bearing UKA can be a viable treatment option for selected ACL-deficient patients, allowing patient-specific kinematics. While anteroposterior laxity can be compensated, rotational stability was a prerequisite for this approach. LEVEL OF EVIDENCE: III.

Effect of Combination l-Citrulline and Metformin Treatment on Motor Function in Patients With Duchenne Muscular Dystrophy: A Randomized Clinical Trial.

Importance: Nitric oxide precursors, such as the amino acid l-arginine and the biguanide antidiabetic drug metformin, have been associated with metabolism and muscle function in patients with Duchenne muscular dystrophy (DMD). The treatment of DMD remains an unmet medical need. Objective: To evaluate the benefits and harms of a combination of l-citrulline and metformin treatment among patients with DMD. Design, Setting, and Participants: A single-center randomized double-blind placebo-controlled parallel-group clinical trial was conducted between December 12, 2013, and March 30, 2016, at the University Children's Hospital Basel in Switzerland. A total of 47 ambulant male patients aged 6.5 to 10 years with genetically confirmed DMD were recruited locally and from the patient registries of Switzerland, Germany, Austria, and France. Data were analyzed from April 6, 2016, to September 5, 2019. Interventions: Patients in the treatment group received 2500 mg of l-citrulline and 250 mg of metformin (combination therapy) 3 times a day for 26 weeks compared with patients in the control group, who received placebo. Main Outcomes and Measures: The primary end point was the change in transfer and standing posture, as assessed by the first dimension of the Motor Function Measure, version 32, from baseline to week 26. Secondary end points included assessments of timed function, quantitative muscle force, biomarkers for muscle necrosis, and adverse events. The 2 prespecified subgroups comprised patients who were able to walk 350 m or more in 6 minutes (stable subgroup) and patients who were not able to walk 350 m in 6 minutes (unstable subgroup) at baseline. Results: Among 49 ambulant male children with DMD who were screened for eligibility, 47 patients with a mean (SD) age of 8.2 (1.1) years were randomized to a treatment group receiving combination therapy (n = 23) or a control group receiving placebo (n = 24), and 45 patients completed the study. No significant differences between groups were found in the results of timed function and muscle force tests for overall, proximal and axial, and distal motor function. Among patients receiving combination therapy, the Motor Function Measure first dimension subscore decrease was 5.5% greater than that of patients receiving placebo (95% CI, -1.0% to 12.1%; P = .09). The administration of combination therapy had significantly favorable effects on the first dimension subscore decrease among the 29 patients in the stable subgroup (6.7%; 95% CI, 0.9%-12.6%; P = .03) but not among the 15 patients in the unstable subgroup (3.9%; 95% CI, -13.2% to 20.9%; P = .63). Overall, the treatment was well tolerated with only mild adverse effects. Conclusions and Relevance: Treatment with combination therapy was not associated with an overall reduction in motor function decline among ambulant patients with DMD; however, a reduction in motor function decline was observed among the stable subgroup of patients treated with combination therapy. The statistically nonsignificant difference of distal motor function in favor of combination therapy and the reduced degeneration of muscle tissue appear to support the treatment concept, but the study may have lacked sufficient statistical power. Further research exploring this treatment option with a greater number of patients is warranted. Trial Registration: ClinicalTrials.gov identifier: NCT01995032.

The reproducibility of psychiatric evaluations of work disability: two reliability and agreement studies.

BACKGROUND: Expert psychiatrists conducting work disability evaluations often disagree on work capacity (WC) when assessing the same patient. More structured and standardised evaluations focusing on function could improve agreement. The RELY studies aimed to establish the inter-rater reproducibility (reliability and agreement) of 'functional evaluations' in patients with mental disorders applying for disability benefits and to compare the effect of limited versus intensive expert training on reproducibility. METHODS: We performed two multi-centre reproducibility studies on standardised functional WC evaluation (RELY 1 and 2). Trained psychiatrists interviewed 30 and 40 patients respectively and determined WC using the Instrument for Functional Assessment in Psychiatry (IFAP). Three psychiatrists per patient estimated WC from videotaped evaluations. We analysed reliability (intraclass correlation coefficients [ICC]) and agreement ('standard error of measurement' [SEM] and proportions of comparisons within prespecified limits) between expert evaluations of WC. Our primary outcome was WC in alternative work (WCalternative.work), 100-0%. Secondary outcomes were WC in last job (WClast.job), 100-0%; patients' perceived fairness of the evaluation, 10-0, higher is better; usefulness to psychiatrists. RESULTS: Inter-rater reliability for WCalternative.work was fair in RELY 1 (ICC 0.43; 95%CI 0.22-0.60) and RELY 2 (ICC 0.44; 0.25-0.59). Agreement was low in both studies, the 'standard error of measurement' for WCalternative.work was 24.6 percentage points (20.9-28.4) and 19.4 (16.9-22.0) respectively. Using a 'maximum acceptable difference' of 25 percentage points WCalternative.work between two experts, 61.6% of comparisons in RELY 1, and 73.6% of comparisons in RELY 2 fell within these limits. Post-hoc secondary analysis for RELY 2 versus RELY 1 showed a significant change in SEMalternative.work (- 5.2 percentage points WCalternative.work [95%CI - 9.7 to - 0.6]), and in the proportions on the differences ≤ 25 percentage points WCalternative.work between two experts (p = 0.008). Patients perceived the functional evaluation as fair (RELY 1: mean 8.0; RELY 2: 9.4), psychiatrists as useful. CONCLUSIONS: Evidence from non-randomised studies suggests that intensive training in functional evaluation may increase agreement on WC between experts, but fell short to reach stakeholders' expectations. It did not alter reliability. Isolated efforts in training psychiatrists may not suffice to reach the expected level of agreement. A societal discussion about achievable goals and readiness to consider procedural changes in WC evaluations may deserve considerations.

Is ACL deficiency always a contraindication for medial UKA? Kinematic and kinetic analysis of implanted and contralateral knees.

BACKGROUND: Prevalence of knee osteoarthritis increases because life expectancy continues to rise with an active patient population. Hence, the concept of unicompartmental knee arthroplasty (UKA) has regained popularity as a treatment option for unicompartmental knee osteoarthritis. Anterior cruciate ligament (ACL) deficiency is widely considered as a contraindication for UKA, however, there are conflicting reports. If otherwise indicated, some surgeons consider UKA for ACL-deficient patients using a modified surgical technique, with a reduction of posterior tibial slope. RESEARCH QUESTION: The purpose of this study was to evaluate outcomes in UKA patients with ACL deficiency in comparison to a conventional UKA group (intact ACL) by the measurement of knee kinematics and kinetics. METHODS: Ten patients with conventional UKA and an intact ACL and eight patients with an ACL-deficient UKA and a reduced posterior tibial slope relative to the native knee were recruited. Three-dimensional joint kinematics of the knee were measured, using skin markers and an infrared optical motion capture system. Ground reaction forces (GRF) were measured with force plates in all three directions. Level walking, ramp descent and stair descent were analyzed, comparing implanted and contralateral native knees and the two UKA groups. RESULTS: No significant differences in kinetics and kinematics were observed between conventional UKA and ACL-deficient UKA groups for any of the activities. However, some asymmetries in GRF between the implanted and contralateral side were present for the ACL-deficient group, during level walking (unloading rate) and stair descent (stance time). SIGNIFICANCE: Promising outcomes of the ACL-deficient UKA group suggest that ACL deficiency may not always be a contraindication. Therefore, ACL-deficient UKA could be an alternative treatment option to total knee arthroplasty for an appropriate surgeon selected patient population.

Cadaver-Specific Models for Finite-Element Analysis of Iliopsoas Impingement in Dual-Mobility Hip Implants.

BACKGROUND: Joint dislocation is a major cause of failure in total hip arthroplasty. Dual-mobility implants provide a femoral head diameter that can match the native hip size for greater stability against dislocation. However, such large heads are prone to impingement against surrounding soft tissues. To address this concern, the concept of an anatomically contoured dual-mobility implant was evaluated using cadaver-specific finite-element analysis (FEA). METHODS: The stiffness of 10 iliopsoas tendons was measured and also 3D bone models, contact pressure, and iliopsoas tendon stress were evaluated for 2 implant designs according to a previous cadaveric experiment. The iliopsoas interaction with an anatomically contoured and conventional dual-mobility implant was analyzed throughout hip flexion. RESULTS: The tensile test of cadaveric iliopsoas tendons revealed an average linear stiffness of 339.4 N/mm, which was used as an input for the FEA. Tendon-liner contact pressure and tendon von Mises stress decreased with increasing hip flexion for both implants. Average contact pressure and von Mises stresses were lower in the anatomically contoured design compared with the conventional implant across all specimens and hip flexion angles. CONCLUSIONS: This study was built upon a previous cadaver study showing reduced tenting of the iliopsoas tendon for an anatomically contoured design compared with a conventional dual-mobility implant. The present cadaver-specific FEA study found reduced tendon-liner contact pressure and tendon stresses with contoured dual-mobility liners. Anatomical contoured design may be a solution to avoid anterior soft-tissue impingement when using hip prostheses with large femoral heads.

Web-Based Stress Management for Newly Diagnosed Patients With Cancer (STREAM): A Randomized, Wait-List Controlled Intervention Study.

Purpose Being diagnosed with cancer causes major psychological distress; however, a majority of patients lack psychological support during this critical period. Internet interventions help patients overcome many barriers to seeking face-to-face support and may thus close this gap. We assessed feasibility and efficacy of Web-based stress management (STREAM [Stress-Aktiv-Mindern]) for newly diagnosed patients with cancer. Patients and Methods In a randomized controlled trial, patients with cancer who had started first-line treatment within the previous 12 weeks were randomly assigned to a therapist-guided Web-based intervention or a wait-list (control), stratified according to distress level (≥ 5 v < 5 on scale of 0 to 10). Primary efficacy end point was quality of life after the intervention (Functional Assessment of Chronic Illness Therapy-Fatigue). Secondary end points included distress (Distress Thermometer) and anxiety or depression (Hospital Anxiety and Depression Scale). Treatment effect was assessed with analyses of covariance, adjusted for baseline distress. Results A total of 222 of 229 screened patients applied online for participation. Between September 2014 and November 2016, 129 newly diagnosed patients with cancer, including 92 women treated for breast cancer, were randomly assigned to the intervention (n = 65) or control (n = 64) group. Adherence was good, with 80.0% of patients using ≥ six of eight modules. Psychologists spent 13.3 minutes per week (interquartile range, 9.5-17.9 minutes per week) per patient for online guidance. After the intervention, quality of life was significantly higher (Functional Assessment of Chronic Illness Therapy-Fatigue: mean, 8.59 points; 95% CI, 2.45 to 14.73 points; P = .007) and distress significantly lower (Distress Thermometer: mean, -0.85; 95% CI, -1.60 to -0.10; P = .03) in the intervention group as compared with the control. Changes in anxiety or depression were not significant in the intention-to-treat population (Hospital Anxiety and Depression Scale: mean, -1.28; 95% CI, -3.02 to 0.45; P = .15). Quality of life increased in the control group with the delayed intervention. Conclusion The Web-based stress management program STREAM is feasible and effective in improving quality of life.

Camera-based measurement of respiratory rates is reliable.

OBJECTIVES: Respiratory rate (RR) is one of the most important vital signs used to detect whether a patient is in critical condition. It is part of many risk scores and its measurement is essential for triage of patients in emergency departments. It is often not recorded as measurement is cumbersome and time-consuming. We intended to evaluate the accuracy of camera-based measurements as an alternative measurement to the current practice of manual counting. MATERIALS AND METHODS: We monitored the RR of healthy male volunteers with a camera-based prototype application and simultaneously by manual counting and by capnography, which was considered the gold standard. The four assessors were mutually blinded. We simulated normoventilation, hypoventilation and hyperventilation as well as deep, normal and superficial breathing depths to assess potential clinical settings. The volunteers were assessed while being undressed, wearing a T-shirt or a winter coat. RESULTS: In total, 20 volunteers were included. The results of camera-based measurements of RRs and capnography were in close agreement throughout all clothing styles and respiratory patterns (Pearson's correlation coefficient, r=0.90-1.00, except for one scenario, in which the volunteer breathed slowly dressed in a winter coat r=0.84). In the winter-coat scenarios, the camera-based prototype application was superior to human counters. CONCLUSION: In our pilot study, we found that camera-based measurements delivered accurate and reliable results. Future studies need to show that camera-based measurements are a secure alternative for measuring RRs in clinical settings as well.

ACL substitution may improve kinematics of PCL-retaining total knee arthroplasty.

PURPOSE: One of the key factors responsible for altered kinematics and joint stability following contemporary total knee arthroplasty (TKA) is resection of the anterior cruciate ligament (ACL). However, ACL retention can present several technical challenges, and in some cases may not be viable due to an absent or nonfunctional ACL. Therefore, the goal of this research was to investigate whether substitution of the ACL through an anterior post mechanism could improve kinematic deficits of contemporary posterior cruciate ligament (PCL) retaining implants. METHODS: Kinematic analysis of different implant types was done using KneeSIM, a previously established dynamic simulation tool. Walking, stair-ascent, chair-sit, and deep knee bend were simulated for an ACL-substituting (PCL-retaining) design, a bi-cruciate-retaining and ACL-sacrificing (PCL-retaining) implant, as well as the native knee. The motion of the femoral condyles relative to the tibia was recorded for kinematic comparisons. RESULTS: The ACL-substituting and ACL-retaining implants provided similar kinematic improvements over the ACL-sacrificing implant, by reducing posterior femoral shift in extension and preventing paradoxical anterior sliding. During all simulated activities, the ACL-sacrificing implant showed between 7 and 8 mm of posterior shift in extension in contrast to the ACL-retaining implant and the ACL-substituting design, which showed overall kinematic trends similar to the native knee. CONCLUSION: The absence of ACL function has been linked to abnormal kinematics and joint stability in patients with contemporary TKA. ACL-substituting implants could be a valuable treatment option capable of overcoming the limitations of contemporary TKA, particularly when retaining the native ACL is not feasible or is challenging.

Timed function tests, motor function measure, and quantitative thigh muscle MRI in ambulant children with Duchenne muscular dystrophy: A cross-sectional analysis.

The development of new therapeutic agents for the treatment of Duchenne muscular dystrophy has put a focus on defining outcome measures most sensitive to capture treatment effects. This cross-sectional analysis investigates the relation between validated clinical assessments such as the 6-minute walk test, motor function measure and quantitative muscle MRI of thigh muscles in ambulant Duchenne muscular dystrophy patients, aged 6.5 to 10.8 years (mean 8.2, SD 1.1). Quantitative muscle MRI included the mean fat fraction using a 2-point Dixon technique, and transverse relaxation time (T2) measurements. All clinical assessments were highly significantly inter-correlated with p < 0.001. The strongest correlation with the motor function measure and its D1-subscore was shown by the 6-minute walk test. Clinical assessments showed no correlation with age. Importantly, quantitative muscle MRI values significantly correlated with all clinical assessments with the extensors showing the strongest correlation. In contrast to the clinical assessments, quantitative muscle MRI values were highly significantly correlated with age. In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration.

Determining 3D Kinematics of the Hip Using Video Fluoroscopy: Guidelines for Balancing Radiation Dose and Registration Accuracy.

BACKGROUND: Video fluoroscopy is a technique currently used to retrieve the in vivo three-dimensional kinematics of human joints during activities of daily living. Minimization of the radiation dose absorbed by the subject during the measurement is a priority and has not been thoroughly addressed so far. This issue is critical for the motion analysis of the hip joint, because of the proximity of the gonads. The aims of this study were to determine the x-ray voltage and the irradiation angle that minimize the effective dose and to achieve the best compromise between delivered dose and accuracy in motion retrieval. METHODS: Effective dose for a fluoroscopic study of the hip was estimated by means of Monte Carlo simulations and dosimetry measurements. Accuracy in pose retrieval for the different viewing angles was evaluated by registration of simulated radiographs of a hip prosthesis during a prescribed virtual motion. RESULTS: Absorbed dose can be minimized to about one-sixth of the maximum estimated values by irradiating at the optimal angle of 45° from the posterior side and by operating at 80 kV. At this angle, accuracy in retrieval of internal-external rotation is poorer compared with the other viewing angles. CONCLUSION: The irradiation angle that minimizes the delivered dose does not necessarily correspond to the optimal angle for the accuracy in pose retrieval, for all rotations. For some applications, single-plane fluoroscopy may be a valid lower dose alternative to the dual-plane methods, despite their better accuracy.

Return-to-work coordination programmes for improving return to work in workers on sick leave.

BACKGROUND: To limit long-term sick leave and associated consequences, insurers, healthcare providers and employers provide programmes to facilitate disabled people's return to work. These programmes include a variety of coordinated and individualised interventions. Despite the increasing popularity of such programmes, their benefits remain uncertain. We conducted a systematic review to determine the long-term effectiveness of return-to-work coordination programmes compared to usual practice in workers at risk for long-term disability. OBJECTIVES: To assess the effects of return-to-work coordination programmes versus usual practice for workers on sick leave or disability. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11), MEDLINE, Embase, CINAHL and PsycINFO up to 1 November 2016. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled workers absent from work for at least four weeks and randomly assigned them to return-to-work coordination programmes or usual practice. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-text articles for study eligibility; extracted data; and assessed risk of bias from eligible trials. We contacted authors for additional data where required. We conducted random-effects meta-analyses and used the GRADE approach to rate the quality of the evidence. MAIN RESULTS: We identified 14 studies from nine countries that enrolled 12,568 workers. Eleven studies focused on musculoskeletal problems, two on mental health and one on both. Most studies (11 of 14) followed workers 12 months or longer. Risk of bias was low in 10 and high in 4 studies, but findings were not sensitive to their exclusion.We found no benefits for return-to-work coordination programmes on return-to-work outcomes.For short-term follow-up of six months, we found no effect on time to return to work (hazard ratio (HR) 1.32, 95% confidence interval (CI) 0.93 to 1.88, low-quality evidence), cumulative sickness absence (mean difference (MD) -16.18 work days per year, 95% CI -32.42 to 0.06, moderate-quality evidence), the proportion of participants at work at end of the follow-up (risk ratio (RR) 1.06, 95% CI 0.86 to 1.30, low-quality evidence) or on the proportion of participants who had ever returned to work, that is, regardless of whether they had remained at work until last follow-up (RR 0.87, 95% CI 0.63 to 1.19, very low-quality evidence).For long-term follow-up of 12 months, we found no effect on time to return to work (HR 1.25, 95% CI 0.95 to 1.66, low-quality evidence), cumulative sickness absence (MD -14.84 work days per year, 95% CI -38.56 to 8.88, low-quality evidence), the proportion of participants at work at end of the follow-up (RR 1.06, 95% CI 0.99 to 1.15, low-quality evidence) or on the proportion of participants who had ever returned to work (RR 1.03, 95% CI 0.97 to 1.09, moderate-quality evidence).For very long-term follow-up of longer than 12 months, we found no effect on time to return to work (HR 0.93, 95% CI 0.74 to 1.17, low-quality evidence), cumulative sickness absence (MD 7.00 work days per year, 95% CI -15.17 to 29.17, moderate-quality evidence), the proportion of participants at work at end of the follow-up (RR 0.94, 95% CI 0.82 to 1.07, low-quality evidence) or on the proportion of participants who had ever returned to work (RR 0.95, 95% CI 0.88 to 1.02, low-quality evidence).We found only small benefits for return-to-work coordination programmes on patient-reported outcomes. All differences were below the minimal clinically important difference (MID). AUTHORS' CONCLUSIONS: Offering return-to-work coordination programmes for workers on sick leave for at least four weeks results in no benefits when compared to usual practice. We found no significant differences for the outcomes time to return to work, cumulative sickness absence, the proportion of participants at work at end of the follow-up or the proportion of participants who had ever returned to work at short-term, long-term or very long-term follow-up. For patient-reported outcomes, we found only marginal effects below the MID. The quality of the evidence ranged from very low to moderate across all outcomes.

Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial.

BACKGROUND: Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the acute illness. L-citrulline is known to change muscular metabolism synthesis by raising nitric oxide (NO) levels and increasing protein synthesis. This investigator-initiated, randomised, placebo-controlled, double-blind, trial aims to demonstrate that L-citrulline positively influences muscle function and increases muscular energy production in patients with PPS. METHODS/DESIGN: Thirty ambulant PPS patients will be recruited in Switzerland. Patients will be randomly allocated to one of the two arms of the study (placebo:verum 1:1). After a 24-week run-in phase to observe natural disease history and progression, participants will be treated either with L-citrulline or placebo for 24 weeks. The primary endpoint is change in the 6-min Walking Distance Test. Secondary endpoints will include motor function measure, quantitative muscle force, quantitative muscle magnetic resonance imaging and magnetic resonance spectroscopy and serum biomarker laboratory analysis DISCUSSION: The aim of this phase IIa trial is to determine if treatment with L-citrulline shows a positive effect on clinical function and paraclinical biomarkers in PPS. If treatment with L-citrulline shows positive effects, this might represent a cost-efficient symptomatic therapy for PPS patients. TRIAL REGISTRATION: ClinicalTrial.gov, ID: NCT02801071 . Registered on 6 June 2016.

Personalized Prescription Feedback Using Routinely Collected Data to Reduce Antibiotic Use in Primary Care: A Randomized Clinical Trial.

Importance: Feedback interventions using routinely collected health data might reduce antibiotic use nationwide without requiring the substantial resources and structural efforts of other antibiotic stewardship programs. Objective: To determine if quarterly antibiotic prescription feedback over 2 years reduces antibiotic use when implemented in a complex health care system. Design, Setting, and Participants: Pragmatic randomized trial using routinely collected claims data on 2900 primary care physicians with the highest antibiotic prescription rates in Switzerland. Interventions: Physicians were randomized to quarterly updated personalized antibiotic prescription feedback over 2 years (n = 1450) or usual care (n = 1450). Feedback was provided both by mail and online from October 2013 to October 2015 and was supported by an initial 1-time provision of evidence-based guidelines. Main Outcomes and Measures: The primary outcome was the prescribed defined daily doses (DDD) of any antibiotic to any patient per 100 consultations in the first year analyzed by intention-to-treat. We further analyzed prescriptions of specific antibiotics, age groups, and sex for the first and second year to investigate persistency of effects over time. Results: The 2900 physicians had 10 660 124 consultations over 2 years of follow-up, prescribed 1 175 780 packages of antibiotics with 10 290 182 DDD. Physicians receiving feedback prescribed the same amount of antibiotics to all patients in the first year (between-group difference, 0.81%; 95% CI, -2.56% to 4.30%; P = .64) and second year (between-group difference, -1.73%; 95% CI, -5.07% to 1.72%; P = .32) compared with the control group. Prescribing to children aged 6 to 18 years was -8.61% lower in the feedback than in the control group in the first year (95% CI, -14.87% to -1.90%; P = .01). This difference diminished in the second year (between-group difference, -4.10%; 95% CI, -10.78% to 3.07%; P = .25). Physicians receiving feedback prescribed fewer antibiotics to adults aged 19 to 65 years in the second year (between-group difference, -4.59%; 95% CI, -7.91% to -1.16%; P < .01). Prescribing to other patient groups or of specific antibiotic types was not significantly different between groups. Conclusions and Relevance: This nationwide antibiotic stewardship program with routine feedback on antibiotic prescribing was not associated with a change of antibiotic use. In older children, adolescents, and younger adults less antibiotics were prescribed, but not consistently over the entire intervention period. Trial Registration: clinicaltrials.gov Identifier: NCT01773824.

Personalized prescription feedback to reduce antibiotic overuse in primary care: rationale and design of a nationwide pragmatic randomized trial.

BACKGROUND: Antimicrobial resistance has become a serious worldwide public health problem and is associated with antibiotic overuses. Whether personalized prescription feedback to high antibiotic prescribers using routinely collected data can lower antibiotic use in the long run is unknown. METHODS: We describe the design and rationale of a nationwide pragmatic randomized controlled trial enrolling 2900 primary care physicians in Switzerland with high antibiotic prescription rates based on national reimbursement claims data. About 1450 physicians receive quarterly postal and online antibiotic prescription feedback over 24 months allowing a comparison of the individual prescription rates with peers. Initially, they also receive evidence based treatment guidelines. The 1450 physicians in the control group receive no information. The primary outcome is the amount of antibiotics prescribed over a one year-period, measured as defined daily doses per 100 consultations. Other outcomes include the amount of antibiotics prescribed to specific age groups (<6, 6 to 18, 19 to 65, >65 years), to male and female patients, in addition to prescriptions of specific antibiotic groups. Further analyses address disease-specific quality indicators for outpatient antibiotic prescriptions, the acceptance of the intervention, and the impact on costs. DISCUSSION: This trial investigates whether continuous personalized prescription feedback on a health system level using routinely collected health data reduces antibiotic overuse. The feasibility and applicability of a web-based interface for communication with primary care physicians is further assessed. TRIAL REGISTRATION: ClinTrials.gov NCT01773824 (Date registered: August 24, 2012).

Treatment with L-citrulline and metformin in Duchenne muscular dystrophy: study protocol for a single-centre, randomised, placebo-controlled trial.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that affects 1 in 3500-6000 male births. Despite broad research aiming to improve muscle function as well as heart and brain function, sufficient therapeutic efficacy has not yet been achieved and current therapeutic management is still supportive. In a recent pilot trial, oral treatment with L-arginine and metformin showed consistent changes of muscular metabolism both in vitro and in vivo by raising NO levels and expression of mitochondrial proteins in the skeletal muscle tissue of patients with DMD. This randomised, double-blind, placebo-controlled trial aims to demonstrate the superiority of L-citrulline and metformin therapy over placebo in DMD patients with regard to the Motor Function Measure (MFM) D1 subscore (primary endpoint) as well as additional clinical and subclinical tests. METHODS/DESIGN: A total of 40-50 ambulant patients with DMD will be recruited at the outpatient department of the University of Basel Children's Hospital (Switzerland), as well as from the DMD patient registries of Switzerland, Germany and Austria. Patients will be randomly allocated to one of the two arms of the study and will receive either a combination of L-citrulline and metformin or placebo for 26 weeks. Co-medication with glucocorticoids is allowed. The primary endpoint is the change of the MFM D1 subscore from baseline to week 26 under L-citrulline and metformin therapy. Secondary endpoints will include the motor function measure (MFM) and its items and subscores, the 6-minute walking test, timed function tests and quantitative muscle testing. Furthermore, quantitative muscle MRI assessment to evaluate the muscle fat fraction as well as safety and biomarker laboratory analyses from blood will be included. For comparison, muscle metabolism and mitochondrial function will be analysed in 10-20 healthy age-matched male children. DISCUSSION: The aim of this study is to test if a 6-month treatment of a combination of L-citrulline and metformin is more effective than placebo in preventing loss of motor function and muscle degeneration in DMD. The MFM D1 subscore is used as a clinical outcome measure and a quantitative muscle MRI assessment as the surrogate outcome measure of fatty muscle degeneration. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01995032 . Registered on 20 November 2013.

Use of a structured functional evaluation process for independent medical evaluations of claimants presenting with disabling mental illness: rationale and design for a multi-center reliability study.

BACKGROUND: Work capacity evaluations by independent medical experts are widely used to inform insurers whether injured or ill workers are capable of engaging in competitive employment. In many countries, evaluation processes lack a clearly structured approach, standardized instruments, and an explicit focus on claimants' functional abilities. Evaluation of subjective complaints, such as mental illness, present additional challenges in the determination of work capacity. We have therefore developed a process for functional evaluation of claimants with mental disorders which complements usual psychiatric evaluation. Here we report the design of a study to measure the reliability of our approach in determining work capacity among patients with mental illness applying for disability benefits. METHODS/DESIGN: We will conduct a multi-center reliability study, in which 20 psychiatrists trained in our functional evaluation process will assess 30 claimants presenting with mental illness for eligibility to receive disability benefits [Reliability of Functional Evaluation in Psychiatry, RELY-study]. The functional evaluation process entails a five-step structured interview and a reporting instrument (Instrument of Functional Assessment in Psychiatry [IFAP]) to document the severity of work-related functional limitations. We will videotape all evaluations which will be viewed by three psychiatrists who will independently rate claimants' functional limitations. Our primary outcome measure is the evaluation of claimant's work capacity as a percentage (0 to 100 %), and our secondary outcomes are the 12 mental functions and 13 functional capacities assessed by the IFAP-instrument. Inter-rater reliability of four psychiatric experts will be explored using multilevel models to estimate the intraclass correlation coefficient (ICC). Additional analyses include subgroups according to mental disorder, the typicality of claimants, and claimant perceived fairness of the assessment process. DISCUSSION: We hypothesize that a structured functional approach will show moderate reliability (ICC ≥ 0.6) of psychiatric evaluation of work capacity. Enrollment of actual claimants with mental disorders referred for evaluation by disability/accident insurers will increase the external validity of our findings. Finding moderate levels of reliability, we will continue with a randomized trial to test the reliability of a structured functional approach versus evaluation-as-usual.

Analysis of Dual Mobility Liner Rim Damage Using Retrieved Components and Cadaver Models.

BACKGROUND: The objective of this study was to assess the retentive rim of retrieved dual mobility liners for visible evidence of deformation from femoral neck contact and to use cadaver models to determine if anterior soft tissue impingement could contribute to such deformation. METHODS: Fifteen surgically retrieved polyethylene liners were assessed for evidence of rim deformation. The average time in vivo was 31.4 months, and all patients were revised for reasons other than intraprosthetic dislocation. Liner interaction with the iliopsoas was studied visually and with fluoroscopy in cadaver specimens using a dual mobility system different than the retrieval study. For fluoroscopic visualization, a metal wire was sutured to the iliopsoas and wires were also embedded into grooves on the outer surface of the liner and the inner head. RESULTS: All retrievals showed evidence of femoral neck contact. The cadaver experiments showed that liner motion was impeded by impingement with the iliopsoas tendon in low flexion angles. When observing the hip during maximum hyperextension, 0°, 15°, and 30° of flexion, there was noticeable tenting of the iliopsoas caused by impingement with the liner. CONCLUSION: Liner rim deformation resulting from contact with the femoral neck likely begins during early in vivo function. The presence of deformation is indicative of a mechanism inhibiting mobility of the liner. The cadaver studies showed that liner motion could be impeded because of its impingement with the iliopsoas. Such soft tissue impingement may be one mechanism by which liner motion is routinely inhibited, which can result in load transfer from the neck to the rim.

Reducing the distal profile of dual mobility liners can mitigate soft-tissue impingement and liner entrapment without affecting mechanical performance.

Soft-tissue impingement with dual mobility liners can cause anterior hip pain and intra-prosthetic dislocation. The hypothesis of this study was that reducing liner profile below the equator (contoured design) can mitigate soft-tissue impingement without compromising inner-head pull-out resistance and hip joint stability. The interaction of conventional and contoured liners with anterior soft tissues was evaluated in cadaver specimens via visual observation and fluoroscopic imaging. Resistance to inner-head pull-out was evaluated via finite element analyses, and hip joint stability was evaluated by rigid-body mechanics simulation of dislocation in two modes (A, B). Cadaveric experiments showed that distal portion of conventional liners impinge on anterior hip capsule and cause iliopsoas tenting at low flexion angles (≤30°). During hip extension, the rotation imparted to the liner from posterior engagement with femoral neck was impeded by anterior soft-tissue impingement. The iliopsoas tenting was significantly reduced with contoured liners (p ≤ 0.04). Additionally, the contoured and conventional liners had identical inner-head pull-out resistance (901 N vs. 909 N), jump distance (9.4 mm mode-A, 11.7 mm mode-B) and impingement-free range of motion (47° mode-A, 29° mode-B). Thus, soft-tissue impingement with conventional dual mobility liners may be mitigated by reducing liner profile below the equator, without affecting mechanical performance. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:889-897, 2016.

Regaining Native Knee Kinematics Following Joint Arthroplasty: A Novel Biomimetic Design with ACL and PCL Preservation.

Lack of ACL and non-anatomic articular surfaces in contemporary total knee implants result in kinematic abnormalities. We hypothesized that such abnormalities may be addressed with a biomimetic bi-cruciate retaining (BCR) design having anatomical articular surfaces. We used dynamic computer simulations to compare kinematics among the biomimetic BCR, a contemporary BCR and cruciate-retaining implant for activities of daily living. During simulated deep knee bend, chair-sit and walking, the biomimetic BCR implant showed activity dependent kinematics similar to healthy knees in vivo. Restoring native knee geometry together with ACL preservation provided these kinematic improvements over contemporary ACL-preserving and ACL-sacrificing implants. Further clinical studies are required to determine if such biomimetic implants can result in more normal feeling knees and improve quality of life for active patients.