Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients.

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.

Willingness of Patients with Breast Cancer in the Adjuvant and Metastatic Setting to Use Electronic Surveys (ePRO) Depends on Sociodemographic Factors, Health-related Quality of Life, Disease Status and Computer Skills.

Introduction: Because of the often unfavorable prognosis, particularly for patients with metastases, health-related quality of life is extremely important for breast cancer patients. In recent years, data on patient-relevant endpoints is being increasingly collected electronically; however, knowledge on the acceptance and practicability of, and barriers to, this form of data collection remains limited. Material and Methods: A questionnaire was completed by 96 patients to determine to what extent existing computer skills, disease status, health-related quality of life and sociodemographic factors affect patients' potential willingness to use electronics methods of data collection (ePRO). Results: 52 of 96 (55 %) patients reported a priori that they could envisage using ePRO. Patients who a priori preferred a paper-based survey (pPRO) tended to be older (ePRO 53 years vs. pPRO 62 years; p = 0.0014) and typically had lower levels of education (p = 0.0002), were in poorer health (p = 0.0327) and had fewer computer skills (p = 0.0003). Conclusion: Barriers to the prospective use of ePRO were identified in older patients and patients with a lower quality of life. Given the appropriate conditions with regard to age, education and current health status, opportunities to participate should be provided to encourage patients' willingness to take part and ensure the validity of survey results. Focusing on ease of use of ePRO applications and making applications more patient-oriented and straightforward appears to be the way forward.

Disseminated tumor cells from the bone marrow of patients with nonmetastatic primary breast cancer are predictive of locoregional relapse.

BACKGROUND: Disseminated tumor cells (DTCs) are detectable in the bone marrow (BM) of patients with primary breast cancer (PBC) and predictive of an impaired prognosis. This large trial aimed to analyze the impact of DTC detection on locoregional relapse (LR). PATIENTS AND METHODS: Patients with nonmetastatic PBC were eligible for this analysis. BM aspiration (BMA1) was carried out during primary surgery and DTCs were detected by using immunocytochemistry (A45-B/B3 antibody against pancytokeratin) and morphological criteria. At the time of LR, a subgroup of patients with nonmetastatic and operable LR received a secondary BM aspiration (BMA2). RESULTS: A total of 3072 patients were included into the analysis. Of these, 732 (24%) presented with DTCs at BMA1. One hundred thirty-nine patients experienced LR and 48 of these (35%) were initially DTC positive. DTC detection was significantly associated with an increased risk of LR in univariate (P = 0.002) and multivariate analysis (P = 0.009) with a hazard ratio of 1.65 (95% confidence interval 1.13-2.40). Of the patients with LR, 55 patients were available for BMA2 and 17 of these (32%) were DTC positive. DTC detection at the time of LR was indicative of impaired overall survival (univariate analysis, P = 0.037). CONCLUSIONS: DTC detection in patients with PBC is associated with an increased risk of LR, indicating that tumor cells may have the ability to recirculate from the BM to the site of the primary tumor. The impaired prognosis associated with DTC detection at the time of LR may help to identify patients that are in need for additional or more aggressive treatment.

Clinical characteristics, pathological reevaluation, surgical management and adjuvant therapy of patients with endometrial stromal tumors.

PURPOSE: To review a single-center experience over a 27-year period in the management of endometrial stromal sarcoma (ESS) and undifferentiated endometrial sarcoma (UES) for insight into clinical characteristics, pathological diagnosis, surgical practice, adjuvant therapy and clinical outcome. MATERIALS AND METHODS: This was a retrospective study of women with histologically proven ESS and UES who were treated at the Department of Obstetrics and Gynecology, University of Tuebingen, Germany, between 1983 and 2010. Available tumor tissue, as well as inpatient and ambulatory records were reviewed; follow-up and survival data were ascertained. RESULTS: The study sample comprised ten patients with ESS and seven patients with UES. Primary surgical treatment consisted of total hysterectomy in nine patients (90.0 %) with ESS and six patients (85.7 %) with UES; one patient (10.0 %) with ESS and one patient (14.3 %) with UES underwent debulking surgery. All patients (100 %) from the ESS group and six patients (85.7 %) from the UES group underwent bilateral salpingo-oophorectomy. Seven women (70.0 %) with ESS and six women (85.7 %) with UES underwent lymphadenectomy. Median DFS was 83.8 months (95 % CI 80.6-87.0) and median OS was 232.6 (95 % CI 49.3-415.9) for patients with ESS; median DFS was 12.9 months (95 % CI 0-284.1) and median OS was 17.6 (95 % CI 0-37.0) for patients with UES. There was no significant difference in DFS between patients with ESS as compared with patients with UES. However, patients with ESS had a significantly better OS when compared to patients with UES (p = 0.011). CONCLUSION: ESS and UES are very rare uterine neoplasms. Surgery consisting of total hysterectomy with or without bilateral salpingo-oophorectomy is the most important treatment-element in patients with ESS or UES.

Placing the perceptual-cognitive approach in perspective.

Although some features of the "psychological approach" are compelling, its immediate impact as a theoretical framework appears to be limited by somewhat ambiguous key constructs and the lack of appropriate placement vis-a-vis extant conceptual views.

Bilateral facilitation of motor control in chronic hemiplegia.

The present study addressed the efficacy of concurrently moving both arms, with and without a load added to the uninvolved arm, in facilitating the quality of movement of the involved side in individuals with moderate, chronic hemiplegia. Six hemiplegic cerebrovascular accident (CVA) subjects with left-hemisphere lesions participated in the study. The four males and two females ranged from 46 to 77 years of age and 30-96 months post-CVA. All subjects scored at least 70% on the Fugl-Meyer test of motor function. The task was to perform discrete unilateral and bilateral elbow extensions in the horizontal plane. The movements were 45 degrees in amplitude and were to terminate in a 10 degrees target zone that was indicated by an illustration of a coffee mug. The instructions were to move toward the mug as smoothly as possible in a movement time (MT) determined to be 20% longer than their minimal MT for that distance. The primary dependent variable was the percentage of continuous vs. discontinuous trajectories observed in each condition, based on whether or not a transient hesitation or reversal was observed. Phase of peak velocity was also quantified as a general indication of the symmetry of the velocity profile. Three of the six subjects exhibited a greater percentage of continuous movements of the involved arm in the nonloaded bilateral condition than the unimanual condition. Five subjects benefited when the uninvolved arm was inertially loaded in the bilateral condition when compared with unimanual performance. Only the oldest subject failed to exhibit facilitation. Peak velocity phase tended to normalize toward symmetry in the bilateral conditions. These findings are consistent with prior evidence that the control of the involved arm improves during bimanual performance for some hemiplegic subjects. It further suggests loading the uninvolved arm may benefit some subjects with respect to unimanual performance, with age perhaps playing a role in determining efficacy.

Generation of bimanual trajectories of disparate eccentricity: levels of interference and spontaneous changes over practice.

The authors examined intermanual interactions of 2 hands that were required to concurrently follow trajectories that differed in eccentricity. Ten healthy participants attempted to learn to trace 2 figures, a circle and an ellipse, with bilaterally isochronous (1:1) timing demands. Initial unimanual trials were followed by bilateral practice comprising 750 movement cycles. Two objectives were addressed: The authors' primary aim was to determine if kinematic interlimb interference is evident independent of spatial and temporal interference and to observe the potential practice-related changes in the nature of that interference. That test was afforded by participants' natural tendency to draw a circle with a relatively constant tangential velocity and an ellipse with a systematically varying velocity. A second aim was to observe the nature of spontaneous changes in the performance of each individual effector, and in the relationship between effectors, across practice. Those objectives were specifically addressed in a context in which augmented feedback was not available to direct the learners' attention to a particular feature of performance. The results suggested that interlimb assimilation of spatial features is the primary source of interference for that task and that apparent effects at the kinematic level are the secondary, indirect product of spatial coupling. Those results were found across blocks of practice. With respect to nondirected performance changes, substantially less improvement was evident in the performance of each individual effector than in the reduction of interlimb interference. Specifically, no practice-related changes in temporal variability or velocity bias, and minimal changes in trajectory smoothness, were evident in individual limbs. Conversely, significant reductions were observed in the variability of relative phase between limbs and in the magnitude of interlimb phase lag.

Hierarchical control of different elbow-wrist coordination patterns.

The present paper focused on the role of mechanical factors arising from the multijoint structure of the musculoskeletal system and their use in the control of different patterns of cyclical elbow-wrist movements. Across five levels of cycling frequency (from 0.45 Hz up to 3.05 Hz), three movement patterns were analyzed: (1) unidirectional, including rotations at the elbow and wrist in the same direction; (2) bidirectional, with rotation at the joints in opposite directions, and (3) free-wrist pattern, which is characterized by alternating flexions and extensions at the elbow with the wrist relaxed. Angular position of both joints and electromyographic activity of biceps, triceps, the wrist flexor, and the wrist extensor were recorded. It was demonstrated that control at the elbow was principally different from control at the wrist. Elbow control in all three patterns was similar to that typically observed during single-joint movements: elbow accelerations-decelerations resulted from alternating activity of the elbow flexor and extensor and were largely independent of wrist motion at all frequency plateaus. The elbow muscles were responsible not only for the elbow movement, but also for the generation of interactive torques that played an important role in wrist control. There were two types of interactive torques exerted at the wrist: inertial torque arising from elbow motion and restraining torque arising from physical limits imposed on wrist rotation. These interactive torques were the primary source of wrist motion, whereas the main function of wrist-muscle activity was to intervene with the interactive effects and to adjust the wrist movement to comply with the required coordination pattern. The unidirectional pattern was more in agreement with interactive effects than the bidirectional pattern, thus causing their differential difficulty at moderate cycle frequencies. When cycling frequency was further increased, both the unidirectional and bidirectional movements lost their individual features and acquired features of the free-wrist pattern. The deterioration of the controlled patterns at high cycling frequencies suggests a crucial role for proprioceptive information in wrist control. These results are supportive of a hierarchical organization of control with respect to elbow-wrist coordination, during which the functions of control at the elbow and wrist are principally different: the elbow muscles generate movement of the whole linkage and the wrist muscles produce corrections of the movement necessary to fulfill the task.

Exploring interlimb constraints during bimanual graphic performance: effects of muscle grouping and direction.

Past studies on bimanual coordination have revealed a general preference to move the limbs in a symmetrical fashion, also denoted as the in-phase mode. Its counterpart, the asymmetrical or anti-phase mode, is performed with lower degrees of accuracy and stability. This ubiquitous tendency to activate the homologous muscle groups is referred to as the muscle grouping constraint (egocentric constraint). The present study confirmed the generalizability of this constraint across various coordination patterns, performed in the horizontal plane. In addition, evidence was generated that movement direction in extrinsic space also constrains bimanual coordination (allocentric constraint). Overall, the present observations suggest that direction is an important movement parameter that is encoded in the central nervous system and that is subject to interactions between the neural specifications of both limbs.

Coping with systematic bias during bilateral movement.

The present studies examined the nature of kinematic interlimb interference during bilateral elbow movements of 1:1, 2:1 and 3:1 frequency ratios and the manner in which subjects cope with coordination bias. Analysis of movement trajectories in the first experiment indicated progressively greater angular velocity assimilation across 2:1 and 3:1 conditions. The desired temporal relationship was maintained by slowing or pausing the low-frequency movement at peak extension while the high-frequency arm produced intervening cycles. An increase in amplitude was also evident for concurrent, homologous cycles. Movement smoothness was emphasized and additional practice was provided in a second experiment. This resulted in dissociated peak angular velocity between limbs and eliminated hesitations and amplitude effects. Bias was still evident, however, as an intermittent approach toward a 1:1 ratio within each cycle. This systematic tendency was somewhat greater at the lower of two absolute frequency combinations but was not influenced by the role of each arm in producing the higher or lower frequency movement. The findings from the first experiment suggest that subjects initially accommodate interlimb kinematic assimilation, while producing the intended timing ratio, by intermittently slowing or pausing the lower-frequency movement. This attenuates the need for bilaterally-disparate movement parameters and provides additional time for organizing residual kinematic differences, perhaps reducing "transient coupling." Evidence from the second experiment indicates that subtle relative motion preferences are still evident following sufficient practice to perform the movements smoothly. The within-cycle locations of the points of greatest interlimb bias for the 2:1 rhythms were positively displaced from those previously observed for 1:1 oscillations. The persistent coordination tendencies noted in both experiments perhaps reflect an assimilation/compensation cycle and constitute one potential source of the systematic error that often emerges during the acquisition of complex skills.

The organization of patterns of multilimb coordination as revealed through reaction time measures.

Simple visual reaction time (RT) during the performance of sagittal movements of the upper and/or lower limbs was investigated. Experiment 1 demonstrated that RTs increased when more limbs were to be moved simultaneously. This effect was more apparent for the upper than for the lower limbs. Experiment 2 allowed a separation of RT into premotor time (PMT) and motor time (MOT) components through analysis of electromyographic activity, and showed that these longer response delays were associated with increased PMTs. This suggests that the time required for the central organization of movements increased as more limbs were to be controlled simultaneously. Compared to single-limb performance conditions, the increases in RT were much larger in the upper limbs (up to 16%) than in the lower limbs (up to 5%) when limb segments were added. During single-limb conditions, RTs in the upper limbs tended to be smaller than in the lower limbs, in accordance with efferent nerve conduction time estimates. Conversely, the lower limb(s) was (were) initiated before the upper limb(s) when both effector types were moved simultaneously. This pattern of activation is reminiscent of the organization of postural control during upright standing, where goal-directed arm activity is preceded by (bilateral) leg activity to anticipate for the upcoming postural destabilization. Finally, hemifield manipulations in experiment 2 revealed faster RTs and PMTs for stimuli presented in the right visual field in comparison with the left field. This advantage was evident for ipsilateral as well as contralateral responses and supports the pre-eminence of the left hemisphere in the complex organization of gross motor responses.

Acquiring bimanual skills: contrasting forms of information feedback for interlimb decoupling.

The present experiments addressed the learner's capability to perform different upper-limb actions simultaneously with the help of various sources of information feedback. An elbow flexion movement was made in the left limb together with a flexion-extension-flexion movement in the right limb. Interlimb interactions were assessed at the structural as well as the metrical level of movement specification during acquisition and retention. Despite a strong initial tendency for the limbs to be synchronized, findings revealed that Ss became gradually more successful in interlimb decoupling as a result of practice with augmented feedback. However, detailed knowledge of movement kinematics was no more effective than global outcome information for interlimb decoupling, indicating that knowledge of results may have more potential for acquiring multiple degree-of-freedom tasks than previously believed. Finally, the data support the general notion that learning new coordination tasks involves the suppression of preexisting preferred coordination tendencies, which is often a prerequisite for building new coordination modes.

Potentiating ballistic limb movements through voluntary production of the stretch-shorten cycle.

The purpose of this study was to examine the effect of learning to produce voluntarily a basic biomechanical mechanism, the stretch-shorten cycle (SSC), on the acceleration of a ballistic arm movement. The task required an elbow flexion at maximal effort performed with the forearm resting upon a horizontal manipulandum. Subjects in three groups received either no augmented feedback, feedback concerning the velocity of the flexion, or a combination of feedback on velocity and feedback related to the rate of stretch of the SSC during 80 training trials. The training trials were preceded by a pretest and followed by a posttest without feedback. Analyses showed that the subjects receiving feedback concerning the SSC exhibited earlier and greater peak angular acceleration than the other groups. These findings provide evidence that acquiring the control of relevant, basic mechanisms like the SSC may be useful in facilitating tasks requiring limb movements of maximal effort.

Adaptive tuning of interlimb attraction to facilitate bimanual decoupling.

Motor skills that require limbs to concurrently produce different spatiotemporal patterns are often quite difficult to learn. This article outlines a general strategy for training subjects to perform skills that require such disparate limb movements. The strategy is based on the notion that certain preferred movement patterns naturally emerge through the dynamics of the perceptual-motor system, even when quite different movements are intended. The training strategy proposes that the acquisition of relative motion patterns that diverge from preferred patterns can be facilitated by initially "tuning" system dynamics to reduce interlimb attraction. The schedule for the dynamical tuning is adopted from the adaptive training method previously applied to tracking tasks. Preliminary evidence is provided in support of this strategy for learning a bimanual task requiring both structural and metrical interlimb decoupling.

Dissociating the structural and metrical specifications of bimanual movement.

Synchronization strength was investigated during the bimanual performance of movements with fundamentally different spatiotemporal features. A flexion (unidirectional) movement was made by the nondominant limb together with a flexion-extension-flexion (reversal) movement by the dominant limb. In contrast with previous studies on bimanual coordination, the movements differed from each other with respect to qualitative (structural) as well as quantitative (metrical) characteristics. Accordingly, the main task goal was to dissociate the limbs' actions at both these levels. Findings of Experiment 1 (within-subject) and Experiment 2 (between-subject) revealed a mutual synchronization effect that was evident at various levels of movement description and that was essentially asymmetric in nature: The unidirectional movement was more attracted to the reversal movement than vice versa. The intrusive nature of synchronization prevented full metrical and structural dissociation of the upper-limbs' actions, although individual differences were apparent and reflected fundamentally different coordination modes.

Toward a movement dynamics perspective on dual-task performance.

The effect of practice on the parallel organization and control of discrete, asymmetrical bimanual movements was investigated. Subjects performed a flexion movement in the left limb together with a flexion-extension-flexion movement in the right limb. Two groups, one of which received kinematic information feedback, were instructed to produce the different patterns simultaneously. A third group performed each movement in isolation at all times, serving as the baseline condition. The degree of success in parallel action organization was assessed at the qualitative (or structural) and quantitative (or metrical) level of movement specification. Findings revealed that the bimanual groups displayed a tendency to synchronize the patterns of motor output, resulting in (mutual) interference. However,the provision of augmented kinematic information feedback resulted in more successful metrical and structural dissociation of the limb actions. The results are discussed in support of a movement dynamics perspective on motoric dual-task performance. The relevance of the approach for human factors is also emphasized.

Control of asymmetrical bimanual movements.

When movements are performed together in the upper-limbs, a strong tendency emerges to synchronize the patterns of motor output. This is most apparent when trying to do different things at the same time. The present experiment explored the simultaneous organization and control of spatiotemporally different movements. There were two practice conditions: symmetrical and asymmetrical. In the symmetrical condition, subjects performed a series of unidirectional elbow flexion movements, followed by a series of elbow flexion-extension-flexion (reversal) movements in both limbs simultaneously. In the asymmetrical practice condition, subjects performed the unidirectional movement in the left limb together with the reversal movement in the right limb. Findings revealed a tendency for each limb movement to assimilate the features of its counterpart under the latter condition. This effect was "asymmetrical" in that the unidirectional movement was more attracted to the reversal movement than vice versa. Nevertheless, subjects were able to partly suppress this synchronization tendency as was evident from the moderate cross correlations between the angular acceleration patterns of both limb movements and from an increasingly successful differentiation of the activity levels in the right and left limb muscles. All together, these findings provide evidence for some degree of parallel control of spatiotemporally different actions. The data are discussed in view of the possible suppression of a bilaterally distributed motor control system, that is mainly held responsible for activiting proximal limb musculature.

Uniqueness of interval and continuous training at the same maintained exercise intensity.

The present study sought to evaluate the inconsistencies previously observed regarding the predominance of continuous or interval training for improving fitness. The experimental design initially equated and subsequently maintained the same relative exercise intensity by both groups throughout the program. Twelve subjects were equally divided into continuous (CT, exercise at 50% maximal work) or interval (IT, 30 s work, 30 s rest at 100% maximal work) training groups that cycled 30 min day-1, 3 days.week-1, for 8 weeks. Following training, aerobic power (VO2max), exercising work rates, and peak power output were all higher (9-16%) after IT than after CT (5-7%). Vastus lateralis muscle citrate synthase activity increased 25% after CT but not after IT. A consistent increase in adenylate kinase activity (25%) was observed only after IT. During continuous cycling testing the CT group had reduced blood lactate (lab) levels and respiratory quotient at both the same absolute and relative (70% VO2max) work rates after training, while the IT group displayed similar changes only at the same absolute work rates. By contrast, both groups responded similarly during intermittent cycling testing with lower lab concentrations seen only at absolute work rates. These results show that, of the two types of training programs currently employed, IT produces higher increases in VO2max and in maximal exercise capacity. Nevertheless, CT is more effective at increasing muscle oxidative capacity and delaying the accumulation of lab during continuous exercise.

Kinetic attraction during bimanual coordination.

Two experiments examined the effects of independent variations in kinetic and kinematic requirements on interlimb coupling during a bimanual task. The goal of the investigation was to provide preliminary evidence regarding one general class of physical variables that constrains discrete bimanual movements. Subjects attempted to execute a smooth unidirectional movement with the left arm, along with a three-segment reversal movement with the right arm. The first experiment manipulated the torque required to produce the reversal action, while movement duration and average angular velocity were held constant for both limbs. Several indications of increased interlimb coupling, due to the kinetic variation, were evident. The converse manipulation was used in the second experiment, with movement time and kinematics (velocity, acceleration) changed independently of joint torque requirements for the reversal limb. No clear effect of kinematics on coupling strength was noted. The results suggest that one variable influencing interlimb attraction toward common spatiotemporal trajectories may be kinetic in nature.