Erenumab versus topiramate for the prevention of migraine - a randomised, double-blind, active-controlled phase 4 trial.

BACKGROUND: We compared the tolerability and efficacy of erenumab, a monoclonal antibody binding to the calcitonin gene-related peptide receptor, to topiramate for migraine prophylaxis in adults. METHODS: HER-MES was a 24-week, randomised, double-blind, double-dummy, controlled trial conducted in 82 sites in Germany. Patients with ≥4 migraine days per month and naïve to study drugs were randomly assigned (1:1) to either subcutaneous erenumab (70 or 140 mg/month) plus topiramate placebo (erenumab group) or oral topiramate at the individual dose with optimal efficacy (50-100 mg/day) plus erenumab placebo (topiramate group).The primary endpoint was medication discontinuation due to an adverse event during the double-blind phase. The proportion of patients that achieved ≥50% reduction from baseline in monthly migraine days during the last 3 months of the double-blind phase was a secondary endpoint. RESULTS: Seven hundred and seventy-seven patients were randomised (from 22 February 2019 to 29 July, 2020) and 95.1% completed the study. In the erenumab group, 10.6% discontinued medication due to adverse events compared to 38.9% in the topiramate group (odds ratio, 0.19; 95% confidence interval 0.13-0.27; p < 0.001). Significantly more patients achieved a ≥50% reduction in monthly migraine days from baseline with erenumab (55.4% vs. 31.2%; odds ratio 2.76; 95% confidence interval 2.06-3.71; p < 0.001). No new safety signals occurred. CONCLUSIONS: Erenumab demonstrated a favourable tolerability and efficacy profile compared to topiramate.Trial registration: ClinicalTrials.gov NCT03828539, URL: https://clinicaltrials.gov/ct2/show/NCT03828539.

Erenumab versus topiramate: post hoc efficacy analysis from the HER-MES study.

OBJECTIVE: HER-MES was the first head-to-head, phase 4 trial to assess the tolerability and effectiveness of erenumab against standard of care treatment (topiramate). This post hoc analysis compared the efficacy of erenumab with topiramate in patients who completed the trial on study medication. METHODS: Post hoc sensitivity analysis was performed using the full analysis set. Outcomes assessed included the proportion of patients with a ≥50% reduction in monthly migraine days (MMD) from baseline (50% responder rate), over the last 3 months (months 4, 5, and 6) of the double-blind treatment phase (DBTP), the 50% responder rate during the first month of the DBTP, and change from baseline in MMD during the DBTP. Multiple imputation was done for efficacy values of patients who discontinued study treatment. RESULTS: Patients (N = 777) were randomly assigned (1:1) to either 70 or 140 mg/month erenumab (N = 389) or 50-100 mg/day topiramate (N = 388). Of these, 334 patients (85.9%) receiving erenumab, and 231 patients (59.5%) receiving topiramate completed the DBTP on study medication. Patients on study medication until the end of the DBTP received a mean dose of 119 mg/month for erenumab and 92 mg/day for topiramate. At month 1, a significantly greater proportion of patients receiving erenumab (39.2%) reported ≥50% reduction in MMD from baseline compared with those receiving topiramate (24.0%; p < 0.001). In the last 3 months, a significantly larger proportion of patients receiving erenumab (60.3%) achieved ≥50% reduction in MMD from baseline compared with those receiving topiramate (43.3%; p < 0.001). Patients receiving erenumab demonstrated significantly greater reductions in MMD during the last 3 months from baseline versus those receiving topiramate (- 6.13 vs - 4.90; 95% CI: - 1.87 to - 0.61; p < 0.001). CONCLUSIONS: This post hoc analysis demonstrated significantly superior efficacy of erenumab versus topiramate in achieving a ≥50% reduction in MMD with an early onset of efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03828539 .

24-Months Cluster-Randomized Intervention Trial of a Targeted Fall Prevention Program in a Primary Care Setting.

BACKGROUND: Falls and fall-related injuries are common in community-dwelling older persons. Longitudinal data on effective fall prevention programs are rare. OBJECTIVE: Therefore, we evaluated a 4-months multi-component exercise fall prevention program in a primary care setting on long-term effects over 24 months on falls and concomitant injuries in older community-dwelling persons with high risk of falling. DESIGN AND SETTING: In the Prevention of Falls (PreFalls) study, forty general practitioners in Germany were cluster-randomized (1:1) into an intervention group (IG) or control group (CG). Three hundred seventy-eight independently living people with high risk of falling (78.1 ± 5.9 years, 75% women) were assigned to IG (n = 222) or CG (n = 156). INTERVENTION AND MEASUREMENTS: Patients in IG took part in a 4-months multi-component exercise program comprising strength and balance exercises (28 sessions); patients in CG received no intervention. Primary outcome measure was number of falls over 24 months, analyzed by a patient-level, linear mixed Poisson model. Secondary endpoints were number of fall-related injuries, changes in physical function, fear of falling, and mortality. RESULTS: After 24 months, the IG demonstrated significantly fewer falls (IRR = 0.63, p = 0.021), injurious falls (IRR = 0.69, p = 0.034), and less fear of falling (p = 0.005). The mortality rate was 5.0% in IG and 10.3% in CG (HR = 0.51, 95% CI: 0.24 to 1.12; p = 0.094). CONCLUSIONS: In older community-dwelling persons with high risk of falling, a short-term multi-component exercise intervention reduced falls and injurious falls, as well as fear of falling over 24 months.

Effects of behavioural exercise therapy on the effectiveness of multidisciplinary rehabilitation for chronic non-specific low back pain: a randomised controlled trial.

BACKGROUND: The long-term effects of behavioural medical rehabilitation (BMR), as a type of multidisciplinary rehabilitation, in the treatment of chronic non-specific low back pain (CLBP) have been shown. However, the specific effects of behavioural exercise therapy (BET) compared to standard exercise therapy (SET) within BMR are not well understood. The aim of the study was to assess the effectiveness of BMR + BET compared to BMR + SET in individuals with CLBP in a two-armed, pre-registered, multicentre, parallel, randomised controlled trial (RCT). METHODS: A total of 351 adults with CLBP in two rehabilitation centres were online randomised based on an 'urn randomisation' algorithm to either BMR + SET (n = 175) or BMR + BET (n = 176). Participants in both study groups were non-blinded and received BMR, consisting of an multidisciplinary admission, a psychosocial assessment, multidisciplinary case management, psychological treatment, health education and social counselling. The intervention group (BMR + BET) received a manualised, biopsychosocial BET within BMR. The aim of BET was to develop self-management strategies in coping with CLBP. The control group (BMR + SET) received biomedical SET within BMR with the aim to improve mainly physical fitness. Therapists in both study groups were not blinded. The BMR lasted on average 27 days, and both exercise programmes had a mean duration of 26 h. The primary outcome was functional ability at 12 months. Secondary outcomes were e.g. pain, avoidance-endurance, pain management and physical activity. The analysis was by intention-to-treat, blinded to the study group, and used a linear mixed model. RESULTS: There were no between-group differences observed in function at the end of the BMR (mean difference, 0.08; 95% CI - 2.82 to 2.99; p = 0.955), at 6 months (mean difference, - 1.80; 95% CI; - 5.57 to 1.97; p = 0.349) and at 12 months (mean difference, - 1.33; 95% CI - 5.57 to 2.92; p = 0.540). Both study groups improved in the primary outcome and most secondary outcomes at 12 months with small to medium effect sizes. CONCLUSION: BMR + BET was not more effective in improving function and other secondary outcomes in individuals with CLBP compared to BMR + SET. TRIAL REGISTRATION: Current controlled trials NCT01666639 , 16/08/2012.

Internet-Supported Physical Exercise Training for Persons with Multiple Sclerosis-A Randomised, Controlled Study.

Physical exercise is effective in improving functional outcomes in persons with multiple sclerosis (pwMS). We evaluated the feasibility and effectiveness of internet-based exercise training (e-training) for pwMS on health-related quality of life (HrQoL). Secondary outcomes were muscle strength, aerobic capacity, lung function, physical activity, and fatigue. This is a randomised, controlled trial with a wait-list control group. Data were collected at baseline, after three and six months, and analysed using a hybrid linear model. One-hundred twenty-six pwMS participated in the home-based aerobic (1×/week) and strength training (2×/week) intervention that was supervised and documented via an internet-platform. The intervention group received e-training for six months, and the control group received e-training after a three months waiting period. Significant differences between the groups were only observed for muscle strength (knee flexion (effect size ES = 0.3, p = 0.003), knee extension (ES = 0.24, p = 0.015)), peak expiratory flow (ES = 0.2, p = 0.039), and sports activity (ES = 0.33, p = 0.001) after three months. E-training had no effect on HrQoL but did on muscle strength, lung function, and physical activity. It is a promising and feasible approach to facilitate large-scale, yet individual, training support.

Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity.

Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36), and Beck Depression Inventory (BDI). We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL). Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

Effects of behavioural exercise therapy on the effectiveness of a multidisciplinary rehabilitation for chronic non-specific low back pain: study protocol for a randomised controlled trial.

BACKGROUND: In Germany, a multidisciplinary rehabilitation named "behavioural medical rehabilitation" (BMR) is available for treatment of chronic low back pain (clbp). A central component of BMR is standard exercise therapy (SET), which is directed mainly to improve physical fitness. There is a need to address psychosocial factors within SET and therefore to improve behavior change with a focus on the development of self-management skills in dealing with clbp. Furthermore, short-term effectiveness of BMR with a SET has been proven, but the impact of a behavioural exercise therapy (BET) for improvement of the long-term effectiveness of BMR is unclear. METHODS/DESIGN: To compare the effectiveness of two exercise programs with different approaches within BMR on the effects of BMR a prospective randomized controlled trial (RCT) in two rehabilitation centres will be performed. 214 patients aged 18-65 with clbp will be, based on an "urn randomisation"-algorithm, randomly assigned to a BMR with SET (function-oriented, n=107) and BMR with BET (behaviour-oriented, n=107). Both exercise programs have a mean duration of 26 hours in three weeks and are delivered by a limited number of not-blinded study therapists in closed groups with six to twelve patients who will be masked regarding study group. The main differences of BET lie in its detailed manualised program with a theory-based, goal-orientated combination of exercise, education and behavioural elements, active participation of patients and consideration of their individual preferences and previous experiences with exercise. The primary outcome is functional ability assessed with the Hannover Functional Ability Questionnaire directly before and after the rehabilitation program, as well as a six and twelve-month follow-up. DISCUSSION: This RCT is designed to explore the effects of BET on the effectiveness of a BMR compared to a BMR with SET in the management of patients with clbp. Methodological challenges arise from conducting a RCT within routine health care as well as from ensuring high treatment integrity. Findings of this study might contribute to a better understanding of the mechanism of action of BMR and the special effects of BET and may be used to improve the quality of these interventions in routine care, therefore reducing the burden to patients with disabling clbp. TRIAL REGISTRATION: Current controlled trials NCT01666639.

Combined telemonitoring and telecoaching for heart failure improves outcome.

Telemedicine has been shown to improve the outcome of heart failure (HF) patients in addition to medical and device therapy. We investigate the effectiveness of a comprehensive telehealth programme in patients with recent hospitalisation for HF on subsequent HF hospitalisations and mortality compared to usual care in a real-world setting. The telehealth programme consists of daily remote telemonitoring of HF signs/symptoms and regular individualised telecoaching sessions. Between January 2018 and September 2020, 119,715 patients of a German health insurer were hospitalised for HF and were eligible for participation in the programme. Finally, 6065 HF patients at high risk for re-hospitalisation were enroled. Participants were retrospectively compared to a propensity score matched usual care group (n = 6065). Median follow-up was 442 days (IQR 309-681). Data from the health insurer was used to evaluate outcomes. After one year, the number of hospitalisations for HF (17.9 vs. 21.8 per 100 patient years, p < 0.001), all-cause hospitalisations (129.0 vs. 133.2 per 100 patient years, p = 0.015), and the respective days spent in hospital (2.0 vs. 2.6 days per year, p < 0.001, and 12.0 vs. 13.4, p < 0.001, respectively) were significantly lower in the telehealth than in the usual care group. Moreover, participation in the telehealth programme was related to a significant reduction in all-cause mortality compared to usual care (5.8 vs. 11.0 %, p < 0.001). In a real-life setting of ambulatory HF patients at high risk for re-hospitalisation, participation in a comprehensive telehealth programme was related to a reduction of HF hospitalisations and all-cause mortality compared to usual care.

Residual effects of muscle strength and muscle power training and detraining on physical function in community-dwelling prefrail older adults: a randomized controlled trial.

BACKGROUND: Although resistance exercise interventions have been shown to be beneficial in prefrail or frail older adults it remains unclear whether there are residual effects when the training is followed by a period of detraining. The aim of this study was to establish the sustainability of a muscle power or muscle strength training effect in prefrail older adults following training and detraining. METHODS: 69 prefrail community-dwelling older adults, aged 65-94 years were randomly assigned into three groups: muscle strength training (ST), muscle power training (PT) or controls. The exercise interventions were performed for 60 minutes, twice a week over 12 weeks. Physical function (Short Physical Performance Battery=SPPB), muscle power (sit-to-stand transfer=STS), self-reported function (SF-LLFDI) and appendicular lean mass (aLM) were measured at baseline and at 12, 24 and 36 weeks after the start of the intervention. RESULTS: For the SPPB, significant intervention effects were found at 12 weeks in both exercise groups (ST: p = 0.0047; PT: p = 0.0043). There were no statistically significant effects at 24 and 36 weeks. In the ST group, the SPPB declined continuously after stop of exercising whereas the PT group and controls remained unchanged. No effects were found for muscle power, SF-LLFDI and aLM. CONCLUSIONS: The results showed that both intervention types are equally effective at 12 weeks but did not result in statistically significant residual effects when the training is followed by a period of detraining. The unchanged SPPB score at 24 and 36 weeks in the PT group indicates that muscle power training might be more beneficial than muscle strength training. However, more research is needed on the residual effects of both interventions. Taken the drop-out rates (PT: 33%, ST: 21%) into account, muscle power training should also be used more carefully in prefrail older adults. TRIAL REGISTRATION: This trial has been registered with clinicaltrials.gov (NCT00783159)

Effects of localized and general fatigue on static and dynamic postural control in male team handball athletes.

In team sports, sensorimotor impairments resulting from previous injuries or muscular fatigue have been suggested to be factors contributing to an increased injury risk. Although it has been widely shown that physical fatigue affects static postural sway, it is still questionable as to what extent these adaptations are relevant for dynamic, sports-related situations. The objective of this study was to determine the effects of whole-body and localized fatigue on postural control in stable and unstable conditions. Nineteen male team handball players were assessed in 2 sessions separated by 1 week. Treadmill running and single-leg step-up exercises were used to induce physical fatigue. The main outcome measures were center of pressure (COP) sway velocity during a single-leg stance on a force plate and maximum reach distances of the star excursion balance test (SEBT). The COP sway velocity increased significantly (p < 0.05) after general (+47%) and localized fatigue (+10%). No fatigue effects were found for the SEBT. There were no significant correlations between COP sway velocity and SEBT mean reach in any condition. The results showed that although fatigue affects static postural control, sensorimotor mechanisms responsible for regaining dynamic balance in healthy athletes seem to remain predominantly intact. Thus, our data indicate that the exclusive use of static postural sway measures might not be sufficient to allow conclusive statements regarding sensorimotor control in the noninjured athlete population.

A bio-psycho-social exercise program (RÜCKGEWINN) for chronic low back pain in rehabilitation aftercare--study protocol for a randomised controlled trial.

BACKGROUND: There is strong, internationally confirmed evidence for the short-term effectiveness of multimodal interdisciplinary specific treatment programs for chronic back pain. However, the verification of long-term sustainability of achieved effects is missing so far. For long-term improvement of pain and functional ability high intervention intensity or high volume seems to be necessary (> 100 therapy hours). Especially in chronic back pain rehabilitation, purposefully refined aftercare treatments offer the possibility to intensify positive effects or to increase their sustainability. However, quality assured goal-conscious specific aftercare programs for the rehabilitation of chronic back pain are absent. METHODS/DESIGN: This study aims to examine the efficacy of a specially developed bio-psycho-social chronic back pain specific aftercare intervention (RÜCKGEWINN) in comparison to the current usual aftercare (IRENA) and a control group that is given an educational booklet addressing pain-conditioned functional ability and back pain episodes. Overall rehabilitation effects as well as predictors for compliance to the aftercare programs are analysed. Therefore, a multicenter prospective 3-armed randomised controlled trial is conducted. 456 participants will be consecutively enrolled in inpatient and outpatient rehabilitation and assigned to either one of the three study arms. Outcomes are measured before and after rehabilitation. Aftercare programs are assessed at ten month follow up after dismissal form rehabilitation. DISCUSSION: Special methodological and logistic challenges are to be mastered in this trial, which accrue from the interconnection of aftercare interventions to their residential district and the fact that the proportion of patients who take part in aftercare programs is low. The usability of the aftercare program is based on the transference into the routine care and is also reinforced by developed manuals with structured contents, media and material for organisation assistance as well as training manuals for therapists in the aftercare.

A multicenter controlled study for dementia prevention through physical, cognitive and social activities - GESTALT-kompakt.

Prevention of dementia is a public health priority. Physical activity (PA) can reduce the risk of dementia, but the majority of people remain sedentary. We conducted a multicenter controlled study with older adults (60+ years). We hypothesized that an evidence-based PA intervention - GEhen, Spielen und Tanzen Als Lebenslange Tätigkeiten - kompakt [walking, playing and dancing as lifelong activities-compact] (GESTALT-kompakt) - would lead to significantly larger improvements in PA levels (step counts/Fitbit Zip™), cognitive functions (DemTect) and social activities (Social Activity Log), compared to an active control group. Data were collected at baseline and after 3 and 12 months. The intervention group received a 12-week (1/week) multimodal and multicomponent PA program, which combined PA with cognitive and social activities. The control group received either regular gymnastics or cognitive training (1/week). A mixed linear model was chosen for analysis. A total of 87 older individuals were recruited in the GESTALT-kompakt study (68 females, average age =76.0 years, SD ±9.2, range 52-95 years). Marginally significant differences were observed in the intervention group (n=57) in comparison to the control group (n=30), regarding improvements in PA (difference of mean changes =866.4 steps, p=0.055) after 3 months. However, their PA decreased to the baseline score value after 12 months (-866.0 steps, p=0.061). GESTALT-kompakt did not cause significant differences in cognitive functioning (-0.8620, p=0.074) and social activities (-0.2428, p=0.288) in comparison to the control intervention from T0 to T1. Sixteen (24.2%) study participants who finished T2 reported a negative life event during the follow-up period, which severely influenced their PA behavior. GESTALT-kompakt might be effective in increasing PA in the short term, but did not have a long-term impact on the PA levels, cognitive functions or social activities of the participants. We recommend PA programs with longer duration to change behavior in the long term.

Image quality, diagnostic accuracy, and potential for radiation dose reduction in thoracoabdominal CT, using Sinogram Affirmed Iterative Reconstruction (SAFIRE) technique in a longitudinal study.

OBJECTIVE: To step-wise evaluate image quality of sinogram-affirmed iterative reconstruction (SAFIRE) in reduced-dose (RD) thoracoabdominal computed tomography (CT) compared to full-dose (FD) and RD filtered back projection (FBP) in a longitudinal study. MATERIALS AND METHODS: 122 patients were included in this prospective study. 49 patients (14 men: mean age ± SD, 56±0.4 years; 35 women: 58±1.3 years) completed FD, RD1 (80%-dose) and RD2 (60%-dose) thoracoabdominal CT. Each CT dataset was reconstructed with FBP and SAFIRE. For quantitative image analysis image noise was measured in defined tissue regions. Qualitative image evaluation was performed according to the European Guidelines on Quality criteria for CT. Additionally artifacts, lesion conspicuity, and edge sharpness were assessed. RESULTS: Compared to FD-FBP noise in soft tissue increased by 12% in RD1-FBP and 27% in RD2-FBP reconstructions, whereas SAFIRE lead to a decrease of 28% (RD1) and 17% (RD2), respectively (all p <0.001). Visually sharp reproduction, lesion conspicuity, edge sharpness of pathologic findings, and overall image quality did not differ statistically significant between FD-FBP and RD-SAFIRE datasets. Image quality decreased in RD1- and RD2-FBP compared to FD-FBP, reaching statistically significance in RD2 datasets (p <0.001). In RD1- and RD2-FBP (p <0.001) streak artifacts were noted. CONCLUSION: Using SAFIRE the reference mAs in thoracoabdominal CT can be reduced by at least 30% in clinical routine without loss of image quality or diagnostic information.

Fall Prevention in a Primary Care Setting.

BACKGROUND: Falls and fall-related injuries are common in community-dwelling elderly people. Effective multifactorial fall prevention programs in the primary care setting may be a promising approach to reduce the incidence rate of falls. METHODS: In a cluster randomized trial in 33 general practices 378 people living independently and at high risk of falling (65 to 94 years old; 285 women) were allocated to either a 16 week exercise-based fall prevention program including muscle strengthening and challenging balance training exercises, combined with a 12 week home-based exercise program (222 participants), or to usual care (156 participants). The main outcome was number of falls over a period of 12 months. Secondary outcomes were the number of fall-related injuries, physical function (Timed-Up-and-Go-Test, TUG, Chair-Stand-Test, CST, modified Romberg Test), and fear of falling. RESULTS: In the intervention group (n=222 patients in 17 general practices) 291 falls occurred, compared to 367 falls in the usual care group (n=156 patients in 16 general practices). We observed a lower incidence rate for falls in the intervention group (incidence rate ratio/IRR: 0.54; 95% confidence interval (CI): [0.35; 0.84], p=0.007) and for fall-related injuries (IRR: 0.66; [0.42; 0.94], p=0.033). Additionally, patients in the intervention group showed significant improvements in secondary endpoints (TUG: -2.39 s, [-3.91; -0.87], p=0.014; mRomberg: 1.70 s, [0.35; 3.04], p=0.037; fear of falling: -2.28 points, [-3.87; -0.69], p=0.022) compared to usual care. CONCLUSION: A complex falls prevention program in a primary care setting was effective in reducing falls and fall-related injuries in community dwelling older adults at risk.

Long-term effects of interprofessional biopsychosocial rehabilitation for adults with chronic non-specific low back pain: a multicentre, quasi-experimental study.

BACKGROUND: Improvement of the long-term effectiveness of multidisciplinary ortho-paedic rehabilitation (MOR) in the management of chronic non-specific low back pain (CLBP) remains a central issue for health care in Germany. We developed an interprofessional and interdisciplinary, biopsychosocial rehabilitation concept named "PASTOR" to promote self-management in adults with CLBP and compared its effectiveness with the current model of MOR. METHODS: A multicentre quasi-experimental study with three measurement time points was implemented. 680 adults aged 18 to 65 with CLBP were assed for eligibil-ity in three inpatient rehabilitation centres in Germany. At first the effects of the MOR, with a total extent of 48 hours (control group), were assessed. Thereafter, PASTOR was implemented and evaluated in the same centres (intervention group). It consisted of six interprofessional modules, which were provided on 12 days in fixed groups, with a total extent of 48 hours. Participants were assessed with self-report measures at baseline, discharge, and 12 months for functional ability (primary outcome) using the Hannover Functional Ability Questionnaire (FFbH-R) and vari-ous secondary outcomes (e.g. pain, health status, physical activity, pain coping, pain-related cognitions). RESULTS: In total 536 participants were consecutively assigned to PASTOR (n=266) or MOR (n=270). At 12 months, complete data of 368 participants was available. The adjusted between-group difference in the FFbH-R at 12 months was 6.58 (95% CI 3.38 to 9.78) using complete data and 3.56 (95% CI 0.45 to 6.67) using available da-ta, corresponding to significant small-to-medium effect sizes of d=0.42 (p<0.001) and d=0.10 (p=0.025) in favour of PASTOR. Further improvements in secondary out-comes were also observed in favour of PASTOR. CONCLUSION: The interprofessional and interdisciplinary, biopsychosocial rehabilita-tion program PASTOR shows some improvements of the long-term effectiveness of inpatient rehabilitation in the management of adults with CLBP. Further insights into mechanisms of action of complex intervention programs are required. TRIAL REGISTRATION: ClinicalTrials.gov NCT02056951.

Fatigue-induced alterations of static and dynamic postural control in athletes with a history of ankle sprain.

CONTEXT: Sensorimotor control is impaired after ankle injury and in fatigued conditions. However, little is known about fatigue-induced alterations of postural control in athletes who have experienced an ankle sprain in the past. OBJECTIVE: To investigate the effect of fatiguing exercise on static and dynamic balance abilities in athletes who have successfully returned to preinjury levels of sport activity after an ankle sprain. DESIGN: Cohort study. SETTING: University sport science research laboratory. PATIENTS OR OTHER PARTICIPANTS: 30 active athletes, 14 with a previous severe ankle sprain (return to sport activity 6-36 months before study entry; no residual symptoms or subjective instability) and 16 uninjured controls. INTERVENTION(S): Fatiguing treadmill running in 2 experimental sessions to assess dependent measures. MAIN OUTCOME MEASURE(S): Center-of-pressure sway velocity in single-legged stance and time to stabilization (TTS) after a unilateral jump-landing task (session 1) and maximum reach distance in the Star Excursion Balance Test (SEBT) (session 2) were assessed before and immediately after a fatiguing treadmill exercise. A 2-factorial linear mixed model was specified for each of the main outcomes, and effect sizes (ESs) were calculated as Cohen d. RESULTS: In the unfatigued condition, between-groups differences existed only for the anterior-posterior TTS (P = .05, ES = 0.39). Group-by-fatigue interactions were found for mean SEBT (P = .03, ES = 0.43) and anterior-posterior TTS (P = .02, ES = 0.48). Prefatigue versus postfatigue SEBT and TTS differences were greater in previously injured athletes, whereas static sway velocity increased similarly in both groups. CONCLUSIONS: Fatiguing running significantly affected static and dynamic postural control in participants with a history of ankle sprain. Fatigue-induced alterations of dynamic postural control were greater in athletes with a previous ankle sprain. Thus, even after successful return to competition, ongoing deficits in sensorimotor control may contribute to the enhanced ankle reinjury risk.

Effects of fatiguing treadmill running on sensorimotor control in athletes with and without functional ankle instability.

BACKGROUND: Sensorimotor control is permanently impaired following functional ankle instability and temporarily decreased following fatigue. Little is known on potential interactions between both conditions. The purpose was to investigate the effect of fatiguing exercise on sensorimotor control in athletes with and without (coper, controls) functional ankle instability. METHODS: 19 individuals with functional ankle instability, 19 ankle sprain copers, and 19 non-injured controls participated in this cohort study. Maximum reach distance in the star excursion balance test, unilateral jump landing stabilization time, center of pressure sway velocity in single-leg-stance, and passive ankle joint position sense were assessed before and immediately after fatiguing treadmill running. A three factorial linear mixed model was specified for each outcome to evaluate the effects of group, exhausting exercise (fatigue) and their interactions (group by fatigue). Effect sizes were calculated as Cohen's d. FINDINGS: Maximum reach distance in the star excursion balance test, jump stabilization time and sway velocity, but not joint position sense, were negatively affected by fatigue in all groups. Effect sizes were moderate, ranging from 0.27 to 0.68. No significant group by fatigue interactions were found except for one measure. Copers showed significantly larger prefatigue to postfatigue reductions in anterior reach direction (P≤0.001; d=-0.55) compared to the ankle instability (P=0.007) and control group (P=0.052). INTERPRETATION: Fatiguing exercise negatively affected postural control but not proprioception. Ankle status did not appear to have an effect on fatigue-induced sensorimotor control impairments.

Effects of a complex intervention on fall risk in the general practitioner setting: a cluster randomized controlled trial.

PURPOSE: To study the feasibility of first, reaching functionally declined, but still independent older persons at risk of falls through their general practitioner (GP) and second, to reduce their physiological and psychological fall risk factors with a complex exercise intervention. We investigated the effects of a 16-week exercise intervention on physiological (function, strength, and balance) and psychological (fear of falling) outcomes in community-dwelling older persons in comparison with usual care. In addition, we obtained data on adherence of the participants to the exercise program. METHODS: Tests on physical and psychological fall risk were conducted at study inclusion, and after the 16-week intervention period in the GP office setting. The 16-week intervention included progressive and challenging balance, gait, and strength exercise as well as changes to behavioral aspects. To account for the hierarchical structure in the chosen study design, with patients nested in GPs and measurements nested in patients, a three-level linear mixed effects model was determined for analysis. RESULTS: In total, 33 GPs recruited 378 participants (75.4% females). The mean age of the participants was 78.1 years (standard deviation 5.9 years). Patients in the intervention group showed an improvement in the Timed-Up-and-Go-test (TUG) that was 1.5 seconds greater than that showed by the control group, equivalent to a small to moderate effect. For balance, a relative improvement of 0.8 seconds was accomplished, and anxiety about falls was reduced by 3.7 points in the Falls Efficacy Scale-International (FES-I), in the intervention group relative to control group. In total, 76.6% (N = 170) of the intervention group participated in more than 75% the supervised group sessions. CONCLUSION: The strategy to address older persons at high risk of falling in the GP setting with a complex exercise intervention was successful. In functionally declined, community-dwelling, older persons a complex intervention for reducing fall risks was effective compared with usual care.

High-pitch thoracic CT with simultaneous assessment of coronary arteries: effect of heart rate and heart rate variability on image quality and diagnostic accuracy.

OBJECTIVES: The aim of this study was to evaluate the mean heart rate and heart rate variability (HRV) required for diagnostic imaging of the coronary arteries simultaneously with thoracic computed tomography for noncardiac purposes, applying a high-pitch spiral image acquisition protocol for computed tomography angiography (CTA) using a dual-source system. BACKGROUND: For the primary prevention of coronary heart disease, screening methods to identify currently asymptomatic people who are at high risk for developing coronary heart disease are essential. Coronary CTA can rule out coronary artery stenoses with high negative predictive value. METHODS: High-pitch thoracic computed tomography was performed in 111 consecutive patients (mean age 60.2 ± 11.5 years; range 37 to 81 years) using a dual-source system (2 × 128 0.6-mm sections, 38.4-mm collimation width, 0.28-s rotation time). Data acquisition was prospectively electrocardiographically triggered at 60% of the R-R interval using a pitch of 3.2. Image quality was evaluated using a 3-point scale (1=excellent, 2=moderate, 3=poor). RESULTS: Close interobserver agreement for image quality scores of 1,998 evaluated coronary segments was found (κ=0.93). Image quality was of diagnostic value in 828 of 1,739 segments (47.6%). In 29 of 111 patients (26%), diagnostic image quality was observed for all segments. Average heart rate and HRV were significantly (p<0.001) higher in patients with at least 1 nondiagnostic coronary segment compared with those without. All patients with mean heart rates <64 beats/min and HRV <13 beats/min had diagnostic image quality in all coronary segments. Effective radiation dose for thoracic CTA was 1.9 ± 0.66 mSv. The mean scan time was 0.9 ± 0.1 s. CONCLUSIONS: Simultaneous evaluation of coronary arteries in high-pitch dual-source CTA of the thorax for noncardiac purposes is consistently diagnostic in patients with low heart rates and HRV, whereas most patients not receiving beta-blockers had at least 1 segment that was not diagnostic because of heart rate and HRV. Beta blockers are recommended if there are no contraindications and coronary interpretation is anticipated.