Exploiting online discussions to discover unrecognized drug side effects.

BACKGROUND: Drugs can treat human diseases through chemical interactions between the ingredients and intended targets in the human body. However, the ingredients could unexpectedly interact with off-targets, which may cause adverse drug side effects. Notifying patients and physicians of potential drug effects is an important step in improving healthcare quality and delivery. OBJECTIVE: With the increasing popularity of Web 2.0 applications, more and more patients start discussing drug side effects in many online sources. These online discussions form a valuable source for mining interesting knowledge about side effects. The main goal of this paper is to investigate the feasibility of exploiting these discussions to discover unrecognized drug side effects. METHODS: We propose methods that can 1) build a knowledge base for drug side effects by automatically integrating the information related to drug side effects from different sources; and 2) monitor online discussions about drugs and discover potential unrecognized drug side effects. RESULTS: Experiment results show that the online discussions indeed provide useful information discovering unrecognized drug side effects. We find that the integrated knowledge base contains more information than individual online sources. Moreover, both proposed detection methods can identify the side effects related to the four recently recalled drugs, and the information from online discussions makes it possible to make the detection much earlier than official announcements. Finally, the proposed generative modeling method is shown to be more effective than the discriminative method. CONCLUSIONS: We find that it is possible to monitor online discussions to detect unrecognized drug side effects. The developed system is expected to serve as a complementary tool for drug companies and FDA to receive feedbacks from the patients, and it has the potentials to expedite the discovery process of unrecognized drug side effects and to improve the quality of healthcare.

The influence of ankle joint movement on knee joint kinesthesia at various movement velocities.

The purpose of this study was to determine if gastrocnemius elongation or shortening and direction and velocity of knee movement influenced knee kinesthesia. Healthy volunteers sat with their knee flexed (20 degrees) and was then passively rotated (flexion or extension) at three velocities (0.5, 2, or 10 degrees/s) while the ankle was either fixed or rotated (dorsiflexed or plantar flexed at 0.17, 0.65, or 3.3 degrees/s) creating gastrocnemius elongation or shortening. Subjects activated a thumb switch, stopping motion once they detected onset and direction of the motion. Detection of passive movement sense (DPMS) was the angular movement before activation of a thumb-switch. Significant differences (P=0.003) in the rate of change in DPMS across a variety of movement velocities was observed but shortening or elongation of the gastrocnemius did not affect DPMS. Gastrocnemius elongation/shortening did not affect knee DPMS, simple reaction time plays an important role in testing kinesthesia especially at faster movements. While feedback from the gastrocnemius muscle plays a limited role in healthy subjects, differences in testing velocities may incorporate higher levels of central nervous system processing. Clinical measures of kinesthesia can be affected by both movement direction and movement velocity that are speed dependent.

Gait analysis in rehabilitation medicine: a brief report.

Gait analysis can be a powerful tool for rehabilitation research and clinical practice. However, there has been little coordinated effort to set goals for the application of gait analysis in rehabilitation. Therefore, a priority setting process was engaged to obtain the opinions of a diverse pool of experts related to human motion analysis. The primary goal of this process was to develop priorities for future research, development, and standardization in gait analysis. A multistep approach was used that included expert testimony, group discussions, individually developed priorities, and a ranking process. Several important priorities emerged from this activity. The highest priority was assigned to research on the efficacy, outcomes, and cost-effectiveness of gait analysis.

Kinematic characteristics of standing disequilibrium: reliability and validity of a posturographic protocol.

OBJECTIVE: To investigate retest reliability and concurrent validity of the fundamental measurements made of a posturographic protocol that employs quiet standing to quantify the severity and the nature of patients' postural disturbances. STUDY DESIGN: Retrospective complete block design. SETTING: Geriatric rehabilitation department. PARTICIPANTS: Thirty-six participants (age range, 67 to 86 yrs) having normal, moderate, or severe levels of disequilibrium. METHODS: Quiet standing was evaluated on three occasions using a three-dimensional motion analysis system and a force platform. Eight testing conditions, designed to vary task difficulty by controlling the contributions of vision, foot proprioception, and base-of-support width, were administered. MAIN OUTCOME MEASURES: Retest reliability of body sway, joint alignment, body position, and motor coordination indicators were evaluated by intraclass correlation coefficients (ICCs). Concurrent validity of protocol measures was evaluated by the prediction of disequilibrium from a stepwise linear discriminant analysis. RESULTS: ICCs indicated high level of retest reliability for all variables but those of motor coordination, which was not influenced by testing conditions. Discriminant analysis resulted in a four-factor discriminator that included measures of body sway, position, alignment, and motor coordination. The derived linear discriminate function correctly classified 96% of the patients' level of disequilibrium. CONCLUSIONS: The posturographic protocol has the potential to be a useful tool for evaluating severity and nature of postural instability and the effects of pharmacologic and rehabilitative treatment. Results also indicate that combining direct body measurements with force-plate data has the potential to expose the underlying impairments that cause disequilibrium, determine their pathogenesis, and evaluate compensatory strategies.

Forefoot deformity, pain, and mobility in rheumatoid and nonarthritic subjects.

OBJECTIVE: To evaluate how painful metatarsal arthritis affects foot and ankle mechanics and mobility. METHODS: We studied 16 symptomatic forefeet in 10 patients with rheumatoid arthritis (RA) and compared them with 14 asymptomatic forefeet in 7 nonarthritic subjects. RA limbs with significant disease at other locations were excluded. We measured pain and deformity of the foot using a visual analog scale and a modified articular index. A video based 3 dimensional gait analysis system and force platform were used to collect data on subjects walking barefoot at a self-selected pace according to an established protocol. Mobility level was quantified using the Sickness Impact Profile (SIP) ambulation subscale. RESULTS: We observed considerable pain and deformity of the forefeet of RA subjects. During gait, motion and force measures revealed that RA subjects significantly (p < 0.005) delayed and reduced forefoot loading, which minimized use of the foot as a rigid level for push off. As a result, stride lengths were shorter and gait was slower compared to nonarthritic subjects. SIP scores revealed that these changes in gait resulted in moderate disability in RA subjects (p=0.05). CONCLUSION: Impairments of the forefoot due to RA include pain and deformity, which produce characteristic stance phase abnormalities in foot function, a slow walking speed, and moderate disability.

A three-dimensional musculoskeletal database for the lower extremities.

A three-dimensional musculoskeletal database of the lower extremities has been developed for use in human musculoskeletal models. The locations of idealized muscle attachments on the pelvis, both femurs, both tibias and fibulas, and both feet were accurately digitized for 52 dried skeletal specimens. The mean specimen heights were 177.5 cm (male) and 166.2 cm (female) and the mean specimen age at the time of death was 48.8 yr. Statistical accumulation and scaling techniques were used to generate highly representative normative models, which were divided into groups and tested for differences based on gender and race. From the test results, the pelvis was divided into a male model (RMS = 8.6 mm), a black female model (RMS = 7.0 mm) and a white female model (RMS = 7.3 mm). The foot was separated into black (RMS = 3.7 mm) and white models (RMS = 3.6 mm). Single models were used for the femur (RMS = 6.5 mm) and the tibia/fibula (RMS = 3.7). Containing over 12000 anatomical landmarks digitized from 52 dried skeletons, this study represents an improvement over previous databases by an order of magnitude.

Flexibility of anticipatory postural adjustments revealed by self-paced and reaction-time arm movements.

In standing humans, it is not certain whether anticipatory postural adjustments associated with rapid, voluntary elbow flexion movements (focal movements) originate as a selection from preset synergies or as the result of specific planning of motor commands. We studied these muscle recruitment patterns when the same focal movement was made under behavioral conditions of a self-paced task (SPT) and a reaction-time task (RTT). While standing still, eight normal subjects performed focal movements under the SPT and RTT behavioral conditions and under three different biomechanical conditions: (1) unloaded-upright, (2) loaded-upright (holding a 3800-g metal bar), and (3) unloaded-forward leaning. Anticipatory postural adjustments were quantified using the latency and duration of electromyographic (EMG) data and the center of pressure (COP) displacement data. Postural-kinematic [joint and body center of gravity (COG) motion] data were used to quantify the anticipatory postural program's effectiveness at preventing postural movement. Focal movement kinematics and associated EMG activity differed due to biomechanical but not behavioral (SPT vs. RTT) conditions. The maximum and net displacement of the body COG measurements did not differ between the behavioral conditions. The amplitude, timing, and net movements of lower extremity joints were influenced by the behavioral conditions. However, the behavioral conditions significantly affected the phasing (including order of activation) and duration of anticipatory postural EMG activity and the phasing of COP displacements under certain biomechanical conditions. These findings support the theory that anticipatory postural adjustments are planned in detail.

A technique to evaluate foot function during the stance phase of gait.

A technique to measure foot function during the stance phase of gait is described. Advantages of the method include its three-dimensional approach with anatomically based segment coordinate systems. This allows variables such as ground reaction forces and center of pressure location to be expressed in a local foot coordinate system, which gives more anatomical meaning to the interpretation of results. Application of the measurement technique to case examples of patients with rheumatoid arthritis demonstrated its ability to discriminate normal from various levels of pathological function. Future studies will utilize this technique to study the impact of pathology and treatment on foot function.

Recent advancements in functional movement analysis.

The purpose of this paper is to describe the concept of Functional Movement Analysis (FMA) and review the recent advancements pertaining to the clinical application of FMA. After a brief introduction to the concept of FMA, the role computers have played in FMA development is presented. A generalized movement measurement technique is introduced along with the resulting benefits associated with the implementation of body segment based coordinate systems. Finally, the role of mechanical power estimates and movement synthesis techniques in the future maturation of FMA is considered.

Translational and rotational joint power terms in a six degree-of-freedom model of the normal ankle complex.

We hypothesized that defining joint power (JP) merely on the basis of joint rotations ignores important translational power terms, and may not adequately represent the energy flow profile for a given muscle group. A novel six degree-of-freedom (6 DOF) model of the ankle complex was implemented, accounting for previously ignored joint translations as well as traditional rotations. Foot and shank kinematic and kinetic data were collected over a stride cycle on five male and five female adults, walking five trials each at 0.69 statures s-1. During intra-subject analyses, ensemble averages were calculated (n = 5) for JP associated with each DOF, and for related velocity and force/moment data. Translational joint velocities typically peaked below 10% of the mean walking velocity. The largest peak in JP occurred for the rotational DOF associated with dorsi/plantar flexion (360 W). The next largest peak in JP was for the vertical translational DOF, and was nearly 10% of the predominant peak. Positive work during push-off was significantly less p < or = 0.05) for the 6 DOF model (27.9 J) than for either 1 or 3 DOF rotational models (30.3 and 29.9 J, respectively). Negative work during early stance was significantly less for the 6 DOF model (-10.3 J) than for either the 1 or 3 DOF models (-13.1 and -12.6 J, respectively). Inter-subject analyses (n = 50) were conducted for JP data only, with similar results. We conclude that translational JP terms are of practical importance in mechanical energy studies, and may be of particular concern when evaluating energy storing prostheses, when summing total power at several joints, and when studying pathologies that disturb joint geometry.

Assessment of a method to estimate muscle attachments from surface landmarks: a 3D computer graphics approach.

A method for estimating the locations of muscle origins and insertions from the measurement of surface landmarks was evaluated using two indirect accuracy tests and a three-dimensional computer graphics program. For each of four lower extremity anatomical segments, a least-squares technique was used to map the measured locations of three landmark targets to their anatomically based locations. The residual errors, obtained from the applications of the least squares, supplied the first indirect accuracy test. These residual errors were between 6 and 12 mm for the four anatomical segments when averaged over ten subjects. The second indirect accuracy test was conducted by comparing the predicted locations of end points on two adjacent segments forming a joint. Errors in aligning adjacent end points were between 12 and 29 mm for three anatomical joints when averaged over ten subjects. A three-dimensional computer graphics program was developed by the authors and demonstrated that the static testing techniques alone were insufficient to evaluate the quality of the muscle origin and insertion estimates. Any evaluation of muscle lengths, velocities and lines-of-action from surface landmarks should examine the estimates made from motion data, and should address both the ability of the model to fit the subjects as well as model's ability to represent the geometry of the musculoskeletal system.

Locomotion of autistic adults.

OBJECTIVE: To assess gait in patients with autism. DESIGN: Clinical and physiologic assessment. SETTING: Research hospital. PATIENTS AND SUBJECTS: Five adults with autism and five healthy, age-matched control subjects. MAIN OUTCOME MEASURE(S): Clinical and biomechanical assessment. RESULTS: Clinical assessment showed mild clumsiness in four patients and upper limb posturing during gait in three patients. The velocity of gait, step length, cadence, step width, stance time, and vertical ground reaction forces were normal in all patients. The only significant abnormality was decreased range of motion of the ankle. Some patients exhibited slightly decreased knee flexion in early stance. Clinically, the gait appeared to be irregular in three patients, but the variability was not significantly increased. CONCLUSIONS: The findings in patients with autism indicate a nonspecific, neurological disturbance involving the motor system. The normal velocity of gait and the normal step length argue against a parkinsonian-type disturbance, whereas the clinical picture suggests a disturbance of the cerebellum.

Kinematic and kinetic adaptations in the lower limb during stance in gait of unilateral femoral neuropathy patients.

This study aimed to quantify the impact of a unilateral femoral neuropathy on joint kinematic and kinetic strategies employed in the lower limbs during gait. The stance phase of gait of four subjects with proximal femoral nerve injury occurring 5-15 months previously was investigated with a video-based data collection system. Kinematic and kinetic data of the pelvis and lower limb segments were sampled unilaterally from both the involved and uninvolved lower extremities. Results revealed that the uninvolved limb demonstrated no clear compensatory strategies except for prolonged stance phase in three of the four subjects. In the involved limb the knee was maintained near full extension throughout much of the stance phase. This was accomplished by minimizing the posterior ground reaction force in early stance, increasing eccentric plantarflexor control of the tibia, and increasing concentric hip extensor control of the femur. These adaptations appeared to be more successful in the subject who was stronger in the uninvolved musculature. The strategies in the other three subjects appeared to be less effective, based on the subjects' slow velocity of gait, knee hyperextension, and use of assistive devices. Patients with femoral neuropathy must develop adaptations in the lower limbs to control knee joint position during gait. The kinematic and kinetic compensations described helped to provide insight into the nature of these adaptations. The relative success of these compensations in different subjects may guide the development of rehabilitation treatment programs for these patients.

Biomechanical comparison of the energy-storing capabilities of SACH and Carbon Copy II prosthetic feet during the stance phase of gait in a person with below-knee amputation.

In this study, the energy-storing capabilities of solid-ankle cushion heel (SACH) and Carbon Copy II prosthetic feet during the stance phase of gait were compared. A person with a unilateral below-knee amputation served as a component of the instrumentation to test the feet under dynamic loads. Ten trials per foot of bilateral stride at "free" velocity were collected with a video-based, three-dimensional data-acquisition system and two force plates. There were no differences between the prosthetic conditions in step length, single-limb support time, and swing period (analysis of variance) or in double-limb support time, cadence, and velocity (Student's t test). Angular kinematics and moments of the hip and knee were unaffected bilaterally by the type of foot. The progression of the center of pressure under the Carbon Copy II was delayed from 15% to 80% of stance as compared with the SACH foot. The Carbon Copy II showed slower unloading in late stance and a later peak propulsive force than did the SACH foot. The Carbon Copy II performed greater work in both the energy-storage (Carbon Copy II = 2.33 J, SACH = 1.16 J) and energy-return (Carbon Copy II = 1.33 J, SACH = 0.34 J) phases of stance and returned energy with 57% efficiency. Although the energy returned by the Carbon Copy II was clinically insignificant during level walking, these results confirm that it performs as an energy-storing device.

Kinematic-based technique for event time determination during gait.

A kinematic-based technique for the estimation of the times at which gait events occur is presented. A kinematic-based model (KM) is defined by the trajectory of a point, which has an anatomically fixed location on the subject's body, about a time at which a measurement system defined gait event takes place. The times at which subsequent occurrences of the gait event takes place are determined by identifying the kinematic pattern that best fits the previously defined KM. The results of an experiment that used the gait patterns of a normal and a pathological walker indicate that the accuracy of the algorithm is limited by the kinematic data sampling interval and that optimal kinematic predictors of gait event times occur within the primary (sagittal) plane of motion. The technique is intended to obviate the need for multiple force plates, instrumented floors and instruments which are worn by the subject for the purpose of determining the times at which gait events occur.

A video-based technique for measuring ankle-subtalar motion during stance.

This study was designed to demonstrate that an accurate and reliable technique for measuring the rotational motion between rigid bodies can be developed from a video-based data collection system. Tests on the accuracy of the rotational measurements demonstrated that for each of five trials, under three test condition, mean errors of less than 0.4 degrees and standard deviations of less than 0.2 degrees were found for all three joint axes. The reliability of the technique for evaluating ankle-subtalar motion during stance was also demonstrated, and the technique was then applied to evaluate ankle-subtalar motion during the stance phase of gait. The rotational motion of the combined ankle-subtalar joint was characterized by complexity and inter-subject variability. Two simplified models previously used to describe ankle-subtalar motion were tested using the current data and were proven to be inadequate for describing ankle-subtalar motion during stance.

Bilateral analysis of the knee and ankle during gait: an examination of the relationship between lateral dominance and symmetry.

This study examined the relationship between lower extremity dominance and kinematic symmetry during gait. Fourteen healthy volunteers without any observable gait deviations participated in the study. The subjects (8 male, 6 female) ranged in age from 19 to 56 years. Lower extremity lateral dominance was determined using an assessment method developed by Carol Coogler. Retroreflective spherical markers were placed bilaterally at points over the greater trochanter, the lateral joint line of the knee, the lateral malleolus, and the metatarsal break. A video-based data-acquisition instrument interfaced with a PDP 11/73 computer measured 12 kinematic variables while the subjects walked at self-selected speeds along a 10-m walkway. A multivariate analysis of variance with one repeated measure revealed significant differences between limbs, across subjects, for stance time and maximum knee extension. A within-subject analysis demonstrated significant differences for 10 variables; however, lateral dominance could not be related predictably to these variations. Our results indicate that symmetry cannot be generalized in view of intrasubject variability for these variables. [Valle DR, Gundersen LA, Barr AE, et al: Bilateral analysis of the knee and ankle during gait: An examination of the relationship between lateral dominance and symmetry.

New technique for acquiring three-dimensional orofacial nonspeech movements.

A new video-based motion analysis system is described that permits acquisition of kinematic patterns from multiple structures (upper lip, lower lip, and jaw), movement patterns to be captured in three dimensions, and acquisition of non-speech orofacial movement patterns without restricting natural head motion. The importance of acquiring three-dimensional lip and jaw movements during nonspeech (e.g., oral opening-closing and chewing motions) movements is emphasized.