Unilateral Spastic Cerebral Palsy Research Articles

Changes in diffusion MRI and clinical motor function after physical/occupational therapies in toddler-aged children with spastic unilateral cerebral palsy.

Diffusion-weighted magnetic resonance imaging (DMRI) is a potential tool to assess changes in brain connectivity and microstructure resulting from physical and occupational therapy in young children with cerebral palsy. This works was carried out to assess whether DMRI can detect changes after 36 weeks of physical and occupational therapy in the microstructure and connectivity of the brains of children with cerebral palsy and determine whether imaging findings correlate with changes in clinical measures of motor function. Five children underwent anatomical MRI and DMRI and evaluations of motor function skills at baseline and after 36 weeks of intensive or once-weekly physical and occupational Perception-Action Approach therapies. Diffusion tensor imaging and constrained spherical deconvolution methods were used to calculate fractional anisotropy (FA) and fiber orientation distribution functions (fODFs), respectively. The fODFs were used to generate tractograms of the cerebrospinal tract (CST). After 36 weeks of physical and occupational therapy, all children showed increases in motor function. No changes were observed in anatomical MRI before and after therapy but CST tractography did show small differences indicating possible altered microstructure and connectivity in the brain. FA values along the CSTs, however, showed no significant changes. Reliable longitudinal DMRI can be employed in toddler-aged children with CP and DMRI has the potential to monitor neuroplastic changes in white matter microstructure. However, there is a high variability between subjects and clinical improvements were not always correlated with measures of FA along the CST.

Long-term effects of different number of botulinum toxin injections into the gastrocnemius muscle on function and muscle morphology in children with cerebral palsy

BackgroundBotulinum toxin (BoNT) injections are used to reduce spasticity, and sometimes repeated injections of the toxin are required. The aim of this study is to investigate the effects of the number of injections of BoNT into the gastrocnemius muscle on function, muscle morphology, muscle stiffness and muscle vascularization in children with cerebral palsy (CP). MethodsThe study included 22 children with unilateral or bilateral spastic type CP aged 5-13 years who had previously received one, two, or three BoNT injections into the gastrocnemius muscle. A total of 29 gastrocnemius muscles were evaluated. Gastrocnemius muscle morphology (muscle cross-sectional area, thickness, fascicle length and pennation angle) was examined by ultrasonography, muscle stiffness by shear wave ultrasound elastography and muscle vascularization by Superb Microvascular Imaging. The functional status of the children was evaluated by the Gross Motor Function Measurement, the Timed-Up-and-Go Test, the Squat Test, the Vertical Jumping Test and the Sit-and-Reach Test. ResultsIn the motor functions and muscle morphology values were similar in all three groups (p>0.05). Muscle stiffness values were higher (p=0.035) and vascularization values were lower (p=0.03) in the group that received three injections compared to the groups that received one injection. There was a moderate positive correlation of the number of BoNTs with muscle stiffness (p<0.05, r=0.454) and a moderate negative correlation with muscle vascularization (p<0.05, r=-0.497). ConclusionsRepeated BoNT applications have no effect on motor functions and muscle morphology in children with CP, whereas BoNT injections administered three times increase muscle stiffness and decrease vascularization.

WITHDRAWN: Innovative Combination of focal vibration therapy and botulinum toxin to treat equinus in a child with unilateral spastic cerebral palsy

WITHDRAWN: Innovative Combination of focal vibration therapy and botulinum toxin to treat equinus in a child with unilateral spastic cerebral palsy

Serious Game in Children with Unilateral Spastic Cerebral Palsy and Equinus Gait: Muscle shortening prevalence on the spasticity

Serious Game in Children with Unilateral Spastic Cerebral Palsy and Equinus Gait: Muscle shortening prevalence on the spasticity

Magic-themed motor training on daily bimanual task performance in children with unilateral spastic cerebral palsy: A systematic review and meta-analysis.

Magic-themed motor training on daily bimanual task performance in children with unilateral spastic cerebral palsy: A systematic review and meta-analysis.

The real magic of magic therapy: Improving daily bimanual task performance in children with unilateral spastic cerebral palsy.

The real magic of magic therapy: Improving daily bimanual task performance in children with unilateral spastic cerebral palsy.

HABIT training in unilateral spastic cerebral palsy children having mirror movement disorder.

The single-arm feasibility study was planned to evaluate the therapeutic effect of hand arm bimanual intensive training in improving the fine and gross motor functions of hand, and in the reduction of intensity with respect to mirror movement disorder. The sample comprised unilateral spastic cerebral palsy children aged 6-16 years who were having mirror movement disorder and were able to make a gross grip. The hand arm bimanual intensive training was provided to the participants for 6 hours per day for 15 days for a total of 90 hours. Comparison of baseline and post-intervention showed that the functional independence level of children had improved, with improvement in unimanual and bimanual hand performance (p˂0.05). However, there was no improvement seen in the severity of mirror movements (p>0.05). Hence, hand arm bimanual intensive training was found to be effective in increasing the functional independence of cerebral palsy children by improving the hand function, but there was no effect on mirror movement disorder.

Hemiplegic (unilateral) cerebral palsy in northern Stockholm: Intellectual disability and epilepsy

PurposeThe purpose of this study was to describe intellectual disability and its association with epilepsy and brain imaging, in a population-based group of children with hemiplegic (unilateral) cerebral palsy, previously investigated and published in 2020. Materials and methodsForty-seven children of school age in northern Stockholm, fulfilling the Surveillance of Cerebral Palsy in Europe-criteria of hemiplegic (unilateral spastic) cerebral palsy, were invited to participate in the study. Twenty-one children consented to participate. A WISC (Wechsler Intelligence Scale for Children)-test was performed by an experienced psychologist. ResultsIn the study population of twenty-one children, 57 % (n 12) displayed uneven cognitive profiles, 38 % (n 8) intellectual disability and 62 % (n 13) had a normal IQ. 43 % (n 9) developed epilepsy. Children with extensive brain lesions had more severe intellectual disability. ConclusionsIn this study intellectual disability and/or epilepsy were associated with the type and extent of the underlying brain lesion. Intellectual disability and uneven cognitive profiles were common. We therefore recommend individual cognitive assessment to ensure an optimal school start.

Correlation Between Trunk Control and Gross Motor Function in Sitting among Children with Unilateral Spastic Cerebral Palsy: An Observational Study

Correlation Between Trunk Control and Gross Motor Function in Sitting among Children with Unilateral Spastic Cerebral Palsy: An Observational Study

Single procedure tibialis anterior tendon shortening in combination with Achilles tendon lengthening in unilateral cerebral palsy improves swing phase dorsiflexion in gait.

Tibialis anterior tendon shortening combined with tendon Achilles lengthening showed satisfactory short- and long-term outcomes for pes equinus treatment. This retrospective study aimed to evaluate the effectiveness of a single tibialis anterior tendon shortening-tendon Achilles lengthening procedure for treating pes equinus, in a homogeneous unilateral cerebral palsy patient group. Gait analysis was conducted on 22 unilateral cerebral palsy patients (mean age at surgery = 13.3 years, standard deviation = 3 years) before and within 2.5 years (standard deviation = 0.61 years) after the tibialis anterior tendon shortening-tendon Achilles lengthening procedure. Primary outcome measures included foot drop occurrence in swing, foot dorsiflexion and the first ankle rocker presence compared to healthy reference data. Movement analysis profile and gait profile score were also calculated for the entire gait cycle. The clinical exam and the A2 peak ankle power were analyzed. Statistical analysis used the paired Wilcoxon's sign rank test (p < 0.05). Post-operatively, significant improvements were observed in ankle dorsiflexion during swing (p = 0.0006) and reduced foot drop in swing (p = 0.0107). The occurrence of a first ankle rocker did not significantly change (p = 0.1489). Significant improvements in gait profile score and movement analysis profile for all joints and planes indicate overall gait quality improvement. The foot progression changed significantly (p = 0.0285), with a greater external orientation. Nineteen out of 22 patients were able to quit wearing their ankle foot orthoses. Tibialis anterior tendon shortening and tendon Achilles lengthening combination yielded positive outcomes, showing increased foot dorsiflexion, first ankle rocker presence, and overall improved gait quality. These findings support the effectiveness of this surgical approach for treating pes equinus in children with unilateral spastic cerebral palsy.

Neuroanatomical correlates of gross manual dexterity in children with unilateral spastic cerebral palsy.

Unilateral spastic Cerebral Palsy (UCP) results from congenital brain injury, and Magnetic Resonance Imaging (MRI) has a role in understanding the etiology and severity of brain insult. In UCP, functional impairment predominantly occurs in the upper limb (UL) of the more affected side, where manual ability and dexterity are typically reduced. Also, mirror movements (MMs), are often present in UCP, with a further possible negative functional impact. This study aims to investigate the relationships among neuroanatomical characteristics of brain injury at MRI, manual functional impairment and MMs, in children with UCP. Thirty-five children with UCP participated in the study (20, M = 15, F, mean age 9.2 ± 3.5 years). Brain lesions at MRI were categorized according to the Magnetic Resonance Classification System (MRICS) and by using a semi-quantitative MRI (sqMRI) scale. Gross manual performance was assessed through Manual Ability Classification System (MACS) and the Box and Block Test (BBT), and MMs by Woods and Teuber scale, for both hands. Non-parametric correlation analyses were run to determine the relationship between neuroanatomical and functional features. Regression models were run to explore the contribution of neuroanatomical features and MMs to UL function. Correlation analyses revealed moderate to strong associations between sqMRI scores contralateral to the more affected side and UL functional impairment on MACS and BBT, with more severe brain injuries significantly correlating with poorer function in the more affected hand. No association emerged between brain lesion severity scores and MMs. MRICS showed no association with MACS or BBT, while a significant correlation emerged between MRICS category and MMs in the more affected hand, with brain lesion category that are suggestive of presumed earlier injury being associated with more severe MMs. Finally, exploratory regression analyses showed that neuroanatomical characteristics of brain injury and MMs contributed to the variability of UL functional impairment. This study contributes to the understanding of the neuroanatomical and neurological correlates of some aspects of manual functional impairment in UCP by using a simple clinical brain MRI assessment.

Efficacy of hinged and carbon fiber ankle-foot orthoses in children with unilateral spastic cerebral palsy and drop-foot gait pattern.

In children with unilateral spastic cerebral palsy (USCP), ankle-foot orthoses (AFOs) are widely used to correct common gait deviations such as a drop-foot pattern. Most studies on this topic have investigated specific time points while omitting other parts of the gait cycle. This study investigated the separate effects of prefabricated carbon fiber AFOs and custom-made hinged AFOs compared with barefoot walking in children with USCP with a drop-foot gait pattern using statistical parametric mapping. Retrospective, cross-sectional, repeated measures study. Twenty ambulatory children (9.9 ± 2.5 years) with USCP and a drop-foot gait pattern were included. Kinematics, kinetics, and spatiotemporal parameters assessed during 3-dimensional gait analysis were compared between barefoot and AFO walking. Statistical parametric mapping was used to compare joint angles and moment waveforms. Kinematics, kinetics and spatiotemporal parameters assessed during 3-dimensional gait analysis were compared between barefoot and AFO walking for each AFO type but not between the 2 AFO types. Compared with barefoot walking, there was a steeper sole angle at initial contact, corresponding to a heel strike pattern, and an increased ankle dorsiflexion in swing with the use of both AFOs. The ankle plantar flexion moment during loading response increased. Ankle power generation during pre-swing decreased in the carbon fiber AFO group when walking with AFOs. Both AFOs were beneficial for improving a drop-foot gait pattern in these small patient groups and can, therefore, be recommended to treat this gait deviation in patients with unilateral cerebral palsy. However, the reduction in ankle power generation during push-off and additional goals targeted by AFOs, such as correction of structural or flexible foot deformities, should be considered for prescription.

Gastrocnemius medialis and Achilles tendon properties do not differ between children with unilateral or bilateral spastic cerebral palsy

Spastic cerebral palsy (SCP) is a common neurodevelopmental disorder in children, which can be categorized into unilateral and bilateral subtypes. Most studies examining the muscle-tendon properties of the lower extremities in individuals with SCP do not distinguish between subtypes. However, spastic muscle morphology is an important determinant for its function. Therefore, differences in muscle-tendon pathology might lead to different treatment strategies. The aim of this retrospective study was to investigate the muscle–tendon properties between children with unilateral SCP and those with bilateral SCP.Overall, 33 ambulatory children (15 with unilateral SCP and 18 with bilateral SCP, Gross Motor Function Classification System Level I–III) were included. Ankle joint range of motion, isometric muscle strength, and muscle–tendon properties of the gastrocnemius medialis (GM) muscle–tendon unit (MTU) (e.g., muscle volume, tissue lengthening behavior) were assessed with isokinetic dynamometry, 3D motion capture, and ultrasound, respectively. Independent t-tests or Mann-Whitney tests were used to test for group differences (α = 0.05). Effect sizes (Cohen’s d) were also calculated.No significant differences in any assessed parameter were found between children with unilateral SCP and children with bilateral SCP (p > 0.05, d < 0.57).Our findings suggest that the functional and morphological properties of the GM MTU are similarly developed in children with unilateral SCP and children with bilateral SCP. We assume that activity levels might be the decisive factor. Nonetheless, our investigations need be extended by including gait parameters and associated tissue dynamics.

Serious Game with Electromyography Feedback and Physical Therapy in Young Children with Unilateral Spastic Cerebral Palsy and Equinus Gait: A Prospective Open-Label Study.

The clinical effects of a serious game with electromyography feedback (EMGs_SG) and physical therapy (PT) was investigated prospectively in children with unilateral spastic cerebral palsy (USCP). An additional aim was to better understand the influence of muscle shortening on function. Thirty children with USCP (age 7.6 ± 2.1 years) received four weeks of EMGs_SG sessions 2×/week including repetitive, active alternating training of dorsi- and plantar flexors in a seated position. In addition, each child received usual PT treatment ≤ 2×/week, involving plantar flexor stretching and command strengthening on dorsi- and plantar flexors. Five-Step Assessment parameters, including preferred gait velocity (normalized by height); plantar flexor extensibility (XV1); angle of catch (XV3); maximal active ankle dorsiflexion (XA); and derived coefficients of shortening, spasticity, and weakness for both soleus and gastrosoleus complex (GSC) were compared pre and post treatment (t-tests). Correlations were explored between the various coefficients and gait velocities at baseline. After four weeks of EMGs_SG + PT, there was an increase in normalized gait velocity from 0.72 ± 0.13 to 0.77 ± 0.13 m/s (p = 0.025, d = 0.43), a decrease in coefficients of shortening (soleus, 0.10 ± 0.07 pre vs. 0.07 ± 0.08 post, p = 0.004, d = 0.57; GSC 0.16 ± 0.08 vs. 0.13 ± 0.08, p = 0.003, d = 0.58), spasticity (soleus 0.14 ± 0.06 vs. 0.12 ± 0.07, p = 0.02, d = 0.46), and weakness (soleus 0.14 ± 0.07 vs. 0.11 ± 0.07, p = 0.005, d = 0.55). At baseline, normalized gait velocity correlated with the coefficient of GSC shortening (R = -0.43, p = 0.02). Four weeks of EMGs_SG and PT were associated with improved gait velocity and decreased plantar flexor shortening. A randomized controlled trial comparing EMGs_SG and conventional PT is needed.

Effects of structured training on spinal posture and selective motor control in children with unilateral spastic cerebral palsy

BackgroundChildren with Unilateral Spastic Cerebral Palsy (USCP) have an asymmetrical postural pattern. Although functional limitations are less, deteriorations in spinal posture are observed. Research questionWhat is the effect of structured training on spinal posture and selective motor control of upper extremity? MethodsForty five children with USCP were included in the study. Participants were children ages 3–18 with GMFCS levels 1 and 2. Spinal posture and mobility was assessed by Spinal Mouse (SM) and the Spinal Alignment and Range of Motion Measure (SAROMM), and selective motor control of upper extremity was evaluated by the Selective Control of the Upper Extremity Scale (SCUES). Children were divided into two groups: structured training group (STG) (n = 22) and conventional physiotherapy group (CPG) (n = 23). Groups received treatment sessions lasting 45 min, 2 days a week for 8 weeks. Evaluations were made baseline and after treatment. ResultsIn sagittal plane, there was a significant decrease in the degree of thoracic kyphosis after treatment in the STG (p = 0.004). A significant difference was found in total spine angulation (p = 0.015) and mobility from flexion to extension in the STG group. There was a difference in total spine angulation (p = 0.014) in the CPG group, but no difference in spinal mobility. Post-training differences were found in thoracic angulation (p = 0.006) and lateral flexion mobility to the affected side in the STG in thoracic (p = 0.020), lumbar (p = 0.035) and total spine (p = 0.008) in the frontal plane. When SCUES-shoulder, elbow, wrist, total scores changes was significant in CPG (p < 0.001), SCUES-forearm (p = 0.002) and fingers (p = 0.007) changes was significant in STG. SignificanceThis study showed that although children with USCP are more mildly affected, there are adverse effects on their selective motor control and spinal posture. This study reveals the contribution of structured training in terms of selective movement, spinal smoothness and mobility in children.

Effectiveness of routine physical therapy with or without home-based intensive bimanual training on clinical outcomes in cerebral palsy children: a randomised controlled trial

IntroductionThis study aimed to test how normal physical treatment, with or without home-based intense bimanual training, affected hand coordination and daily living activities in children with cerebral palsy.MethodsA randomised controlled experiment was carried out at DHQ Hospital in Kasur, Pakistan. Thirty children with unilateral spastic cerebral palsy took part in the study. The first group received standard physical treatment, whereas the second group received bimanual training along with routine physical therapy. Follow-ups were performed in the fourth and sixth weeks. The paediatric motor log activity scale and the ABILHAND questionnaire were used to assess daily activities and coordination, respectively.ResultsAt baseline, no significant association was seen between treatment groups and hand coordination outcome among the patients (p = 0.0450) and no significant difference was seen in patients in both treatment groups regarding their activities of daily living. In group A, no significant improvement was seen in hand coordination from baseline until the 6th week (p = 0.257) while in group B, a significant difference was seen in hand coordination from baseline until the 6th week follow-up (p = 0.000).ConclusionsThis study concluded that the combined effect of home-based bimanual exercises and routine physical therapy shows significant achievements in hand coordination and activities of daily living.

Effect of constraint-induced movement therapy in reducing severity of mirror movements in children with unilateral spastic cerebral palsy.

To determine the effec t of constraint-induced movement therapy (CIMT ) in improving hand function and reduction in severity of mirror movements in children with unilateral spastic cerebral palsy who have mirror movement disorder. Spastic hemiplegic CP children of either gender, aged 6 to 16 years, with mirror movements of grade 1 and 2 who were able to make a gross grip, were included in this single arm feasibility study. CIMT was provided as an intervention to these children for six hours per day for 15 consecutive week days. Woods and Teuber criteria was applied for the assessment of mirror m oveme nt s. Pre - and po stinte rventi on assess ment results showed that there was improvemen t in the unimanual and bimanual hand func tion in CP-affected children (p<0.05) and reduction in the severity of mirror movements ( p<0 .05). Constra intinduced movement therapy improved hand function and reduced the severity of mirror movements in children with unilateral spastic cerebral palsy.

Gait and sEMG characteristics of lower limbs in children with unilateral spastic cerebral palsy during walking

BackgroundChildren with unilateral spastic cerebral palsy (USCP) have muscle hypertonia, balance, and coordination defects that affect gross motor skills, especially walking. Understanding the gait characteristics and lower limb muscle activation patterns of USCP children can provide an objective and quantitative basis for patient assessment and treatment plan formulation. ObjectiveThis study compared the gait and lower limb muscle activation characteristics of children with USCP and with typical development (TD) during walking. MethodsWe recorded gait and sEMG data of 20 children with USCP, and 20 with typical development. sEMG signals were acquired from the bilateral tibialis anterior (TA) and lateral gastrocnemius muscles (LG) during walking. The root mean square (RMS) value, integrated electromyographic (iEMG) value and co-contraction ratio (CR) were used to evaluate muscle activity. Student's t Test and non-parametric rank sum Test were used to compare the differences between the data groups (significance level of 0.05). ResultsThe stance time, step length, speed, single leg support time ratio, ground impact, pre-swing angle, and muscle strength of the affected side were significantly decreased compared to those of the unaffected side in children with USCP (P < 0.05), while the swing phase, muscle tonus of LG were significantly prolonged (P < 0.05). Compared with TD children, children with USCP exhibited reduced bilateral walking ability, particularly noticeable in their smaller pre-swing angle(P < 0.05), diminished muscle strength of the TA and LG, as well as LG spasms(P < 0.05). SignificanceChildren with USCP have decreased ambulatory gait stability. Step length, pull acceleration, pre-swing angle, and CR can be used as sensitive indicators for gait assessment. Strengthening the TA muscle and reducing ankle spasm may help improve gait and postural stability in children with USCP.

Immediate effects of kinesio taping and vibration therapy on manual dexterity in children with unilateral spastic cerebral palsy: a randomised controlled trial

Background/Aims In children with unilateral spastic cerebral palsy, the upper extremity is usually more affected than the lower extremity. Somatosensory, functional and developmental disorders cause difficulties in hand function. The aim of this study was to assess the immediate effects of kinesio tape and vibration therapy in addition to conventional physiotherapy on gross and fine manual dexterity in children with unilateral spastic cerebral palsy. Methods A total of 45 children aged 4–18 years with mild to moderate spasticity (at levels 0, 1, 1+, 2 according to the Modified Ashworth Scale) who could grip and release an object, and those who had hand function at levels 1, 2 and 3 according to the Manual Ability Classification System and were diagnosed with unilateral spastic cerebral palsy, were included in the study. The children were randomised into three groups: vibration therapy, kinesio taping and control, with 15 children in each group. While conventional physiotherapy was regularly continued in all three groups, the kinesio taping group had kinesio tape applied to the wrist extensors, with 50% tension on the wrist and thumb and 25% tension on the fingers at the beginning of the session. The vibration therapy group received vibration to the forearm extensor muscle group at the end of the session. Vibration was applied to the widest part of the forearm extensor muscles with a 7 cm tip at a frequency of 80 Hz, amplitude of 1 mm, vibration for 10 seconds and rest for 5 seconds, for a total of 10 minutes. Gross and fine dexterity were assessed by Box and Block Test and Nine-Hole Peg Test before and after treatment. Results When the groups were compared before and after the intervention, a significant improvement was found in the Nine-Hole Peg Test scores of the kinesio taping (105.11± 66.99 vs 86.22 ± 51.88, P&lt;0.05) and vibration therapy (61.70 ± 35.54 vs 57.29 ± 38.05, P&lt;0.05) groups and in the Box and Block Test scores of all three groups: kinesio taping group (25.13 ± 14.33 vs 28.40 ± 14.23, P&lt;0.05), vibration therapy group (35.00 ± 11.69 vs 39.07 ± 12.43, P&lt;0.05), control group (34.60 ± 11.74 vs 37.80 ± 11.22, P&lt;0.05). There was no significant difference in the Nine-Hole Peg Test scores between the groups, while a significant improvement was found in the Box-Block Test scores of the kinesio taping group compared to the vibration therapy and control groups (P&lt;0.05). Conclusions Kinesio taping and vibration have positive immediate effects on gross and fine manual dexterity in children with unilateral spastic cerebral palsy and can be used by physiotherapists to support conventional physiotherapy and rehabilitation programmes.

Bimanual hand use in children and adolescents with unilateral spastic cerebral palsy: an exploratory study

BackgroundIndividuals with unilateral spastic cerebral palsy (USCP) often show difficulties using their hands during activities of daily living. ObjectiveTo investigate the factors that interfere with hand use during bimanual activities in children and adolescents with USCP. MethodsWe conducted a cross-sectional study with 102 children and adolescents with USCP, aged 6 to 18 years. We collected information with the caregivers about the classification of the child's manual ability, according to the Manual Ability Classification System (MACS); child's age; side of the involvement; Children's Hand-Use Experience Questionnaire- CHEQ2.0. Cluster analysis identified groups of children and adolescents who performed CHEQ activities with or without assistance. Multiple linear regression analyses identified the contribution of the factors: age, sex, MACS level, side of hemiparesis, and clusters of assistance, on the outcomes of efficacy, time, and feeling bothered. ResultsMACS and clusters of assistance explained the variance in efficacy (p<0.05; R2=0.31) and time (p<0.05; R2=0.37). MACS explained 22% of the variance in feeling bothered. Children and adolescents with increased difficulty to perform activities that involve hand use (i.e., MACS III) and who receive assistance during most bimanual activities showed less efficacy of use, were slower in their performance, and presented greater feeling of being bothered. ConclusionAssistance in bimanual activities and MACS level contributed to explain the efficacy of use, time, and feeling bothered in performing bimanual activities. Intervention strategies aimed at promoting the performance of bimanual activities in the daily routine of children with USCP should consider these outcomes.