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To evaluate the costs and benefits associated with the use of abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) for lower limb spasticity in children, upper and lower limb spasticity in adults, and cervical dystonia in adults.This pharmacoeconomic analysis compared aboBoNT-A with onaBoNT-A. A decision tree model with a 1-year time horizon was conducted from a UK National Health Service (NHS) perspective using data from a variety of sources: randomized controlled trials (RCTs), network meta-analyses (NMAs), observational studies, and a physician survey investigating treatment patterns and resource utilization. Four patient populations were included: pediatric patients with lower limb spasticity (PLL), and adults with upper limb spasticity (AUL), lower limb spasticity (ALL), and cervical dystonia (CD). Outcomes included costs, quality-adjusted life years (QALYs) gained, cost per responder, and incremental cost per QALY gained. The effectiveness of each treatment was evaluated as a response to treatment. The base case assumption was that all patients in the model continued to receive botulinum toxin type A (BoNT-A) treatments at regular intervals regardless of treatment response status. Scenario analysis evaluated the impact of discontinuing BoNT-A for patients without a response to the first injection.The model found that aboBoNT-A resulted in greater quality-of-life and lower costs compared with onaBoNT-A for the management of spasticity and CD in all included indications. Across populations, cost savings ranged from £304 to £3,963 and QALYs gained ranged from 0.010 to 0.02 over a 1-year time horizon. Results were robust to scenario analyses and were driven by the impact of treatment response on health-related quality-of-life.AboBoNT-A was associated with higher treatment response, improved quality-of-life, and reduced costs in spasticity and CD versus onaBoNT-A. These findings could help deliver more effective and efficient healthcare in the NHS.The objective of this study was to compare the costs and health outcomes associated with abobotulinumtoxinA (aboBoNT-A; Dysport) and onabotulinumtoxinA (onaBoNT-A; Botox) for treating children and adults with a variety of conditions related to limb spasticity and cervical dystonia. Therapies such as aboBoNT-A and onaBoNT-A have been shown to reduce spasticity, deformity, pain, and cervical dystonia symptoms. They can also improve function, movement, and self-care abilities. We estimated the treatment costs for patients with spasticity and patients with cervical dystonia receiving aboBoNT-A and onaBoNT-A in the UK. We also estimated other health-related costs that patients were expected to incur while receiving these treatments, as well as their quality of life.For each indication (spasticity in the upper and lower limbs in adults and children, cervical dystonia in adults), research studies were identified to estimate the likelihood of patient response for aboBoNT-A and onaBoNT-A. Survey studies were assessed to understand use of health services and costs for patients who respond to therapy vs. those who do not. We estimated total costs over one year and expected quality of life for patients. Costs included the costs of aboBoNT-A and onaBoNT-A treatments, as well as other health services.In all identified studies, the likelihood of response was higher for aboBoNT-A than for onaBoNT-A. This was associated with reduced need for other health services (and therefore lower costs), and better quality of life for patients receiving aboBoNT-A. In addition, the cost per year of aboBoNT-A treatment was lower than onaBoNT-A treatment for all indications. Therefore, treatment with aboBoNT-A was consistently associated with lower costs and better quality of life. This outcome is referred to as “economically dominant,” meaning that from a health economic perspective, aboBoNT-A would be preferred to onaBoNT-A for treating patients with spasticity or cervical dystonia.

Objective: Stroke is associated with a high risk of death and cardiovascular events. Rehabilitation therapy is critical for functional recovery, to reduce hospital readmissions, all-cause and cardiovascular mortality, and stroke recurrence (long-term outcomes). Post-stroke spasticity may prevent effective recovery by restricting mobility. AbobotulinumtoxinA is an adjunctive therapy to physical therapy for post-stroke spasticity, but its long-term effects are unknown. The objective was to model the long-term clinical and economic outcomes of abobotulinumtoxinA for post-stroke spasticity.Methods: Effects of abobotulinumtoxinA on treating post-stroke spasticity and evidence linking functional outcomes with long-term outcomes were collected in a focused literature review. A model was developed to estimate health benefits on long-term outcomes, direct medical costs, life- and qualityadjusted life-years for abobotulinumtoxinA injections plus rehabilitation therapy compared with rehabilitation therapy alone, from a UK perspective over a 10-year time-period.Results: AbobotulinumtoxinA + rehabilitation therapy led to a risk reduction of 8.8% for all-cause mortality, and an increase of 13% in life-years and 59% in quality-adjusted life-years compared with rehabilitation therapy alone. AbobotulinumtoxinA + rehabilitation therapy was considered cost-effective compared with rehabilitation therapy alone (incremental cost-effectiveness ratio: £24,602).Conclusion: AbobotulinumtoxinA + rehabilitation therapy may improve long-term outcomes, including post-stroke survival, while being cost-effective for the treatment of post-stroke spasticity. LAY ABSTRACTHere we developed a model to explore and compare the long-term benefits and overall costs of two interventions for the treatment of post-stroke spasticity (PSS): abobotulinumtoxinA injections plus rehabilitation therapy (aboBoNT-A+RT) vs. RT alone. Stroke survivors are known to be at a higher risk of recurrent stroke and death, and more than 25% are affected by spasticity. PSS significantly reduces patients’ mobility, physical functioning, and subsequently their ability to recover after a stroke. AboBoNT-A+RT is an effective treatment for spasticity. This model is the first to highlight that combining aboBoNT-A injections with RT could improve the overall survival of stroke survivors with spasticity by 8.8% and their overall quality of life, while being considered good value for money by UK payers.

Objective: To describe the development of the Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D) and its sensitivity to clinical change (responsiveness). Design: Multicentre, prospective, longitudinal cohort study at 8 UK sites (NCT03442660). Patients: Adults (n = 104) undergoing focal treatment of upper limb spasticity. Methods: No condition-specific health-related quality of life tool is available for upper-limb spasticity of any aetiology. The SQoL-6D was developed to fulfil this need, designed to complement the Upper Limb Spasticity Index (which incorporates the Goal Attainment Scaling evaluation of upper limb spasticity [GASeous] tool) with targeted standardised measures. The 6 dimensions of the SQoL-6D (score range 0–4) map onto common treatment goal areas identified in upper-limb spasticity studies. A Total score (0–100) provides overall spasticity-related health status. To assess responsiveness, the SQoL-6D, Global Assessment of Benefit scale and ”GASeous” were administered at enrolment and 8 weeks. Results: Significant differences in mean SQoL-6D Total score change and effect sizes across patients rating ”some benefit” (0.51) and ”great benefit” (0.88) supported responsiveness. Conclusion: The SQoL-6D is a promising new measure of health status in upper limb spasticity, that enables systematic assessment of the impact of this condition in relation to patients’ priority treatment goals. A psychometric evaluation of SQoL-6D is presented separately. LAY ABSTRACT Upper-limb spasticity is a condition in which muscles become ”tight”, restricting use of the arm and hand. Questionnaires have been developed to assess a person’s quality of life, but are not specifically designed to assess the impact of spasticity on a person. The Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D) was created to address this deficiency. The development of the SQoL-6D is described here, along with analysis of its responsiveness to ensure that the SQoL-6D detects changes in spasticity symptoms following treatment (as reported by patients using other questionnaires). These analyses showed that the SQoL-6D captured changes in the burden of spasticity for people with this problem. Other technical psychometric properties of the SQoL-6D are reported in the companion paper available in this issue

Objective: Psychometric evaluation of the Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D). Design: A clinimetric evaluation conducted in a multicentre, prospective, longitudinal cohort study at 8 UK sites. Patients: Adult patients (n=104) undergoing focal treatment of upper-limb spasticity. Methods: The SQoL-6D was administered in the clinic at enrolment and at 8 weeks, then 1–4 days later at home to assess test-retest reliability. Results: The SQoL-6D demonstrated adequate construct validity and unidimensionality of the scale, allowing the calculation of a Total score. Cronbach’s alpha (0.74) supported the internal consistency reliability, while the intraclass correlation coefficient supported test-retest reliability (0.82). Correlation coefficients with established instruments supported convergent validity, while significant differences between known-groups (of differing clinical severity) in SQoL-6D Total score confirmed its sensitivity to both cross-sectional and longitudinal differences. Conclusion: The SQoL-6D is a promising new measure to assess health status for patients with upper-limb spasticity of any aetiology. Further investigation and exploration of the allocation of weights to convert the SQoL-6D to a health-related quality of life utility index, are required. Lay Abstract In upper-limb spasticity, the use of the arm and hand become restricted due to “tight” muscles. Although questionnaires to assess a person’s quality of life have been developed, they do not specifically assess the impact of upper-limb spasticity. To address this deficiency, the Spasticity-related Quality of Life 6-Dimensions (SQoL-6D) questionnaire was developed (see also the companion “development” paper available in this issue). To test that the SQoL-6D works as expected, it was completed by 104 people living with spasticity and compared with other questionnaires they completed. The results show that the SQoL-6D questions are relevant to people with spasticity. The answers were reliable when the SQoL-6D was repeated, and differences in the burden of spasticity between people grouped by the severity of their condition were captured accurately. The SQoL-6D is a promising new measure to assess aspects of quality of life in people living with spasticity.

This review highlights the importance of osteopathic manipulative treatment (OMT) in headache sufferers. OMT is a viable option for patients who either do not wish to use pharmaceuticals or who have contraindications to pharmaceuticals. Patients with headaches that are refractory to other treatment options may also be candidates for OMT. Multiple headache etiologies are amenable to this non-invasive treatment option and they will be reviewed here. Although there are advantages to using this treatment method, there are also shortcomings in the literature, which will be discussed. Roughly 45 million Americans suffer from headaches every year. Many headache sufferers are unable to find relief through conventional treatment options. OMT is a useful non-invasive treatment option with little to no side effects. There are multiple headache types. Migraine, tension-type headache, combat-related events, post-traumatic headache, sinusitis, tooth extraction, concussions, and others have all shown benefit from OMT. OMT is a non-invasive treatment option for individuals suffering from various types of headaches. This treatment option is tailored to the individual needs of the patient and is delivered by licensed and experienced osteopathic physicians. This review of literature also highlights where there is need for further research in the field.

Neighborhood walkability can influence physical activity. We evaluated the validity of Walk Score(®) for assessing neighborhood walkability based on GIS (objective) indicators of neighborhood walkability with addresses from four US metropolitan areas with several street network buffer distances (i.e., 400-, 800-, and 1,600-meters). Address data come from the YMCA-Harvard After School Food and Fitness Project, an obesity prevention intervention involving children aged 5-11 years and their families participating in YMCA-administered, after-school programs located in four geographically diverse metropolitan areas in the US (n = 733). GIS data were used to measure multiple objective indicators of neighborhood walkability. Walk Scores were also obtained for the participant's residential addresses. Spearman correlations between Walk Scores and the GIS neighborhood walkability indicators were calculated as well as Spearman correlations accounting for spatial autocorrelation. There were many significant moderate correlations between Walk Scores and the GIS neighborhood walkability indicators such as density of retail destinations and intersection density (p0.05). The magnitude varied by the GIS indicator of neighborhood walkability. Correlations generally became stronger with a larger spatial scale, and there were some geographic differences. Walk Score(®) is free and publicly available for public health researchers and practitioners. Results from our study suggest that Walk Score(®) is a valid measure of estimating certain aspects of neighborhood walkability, particularly at the 1600-meter buffer. As such, our study confirms and extends the generalizability of previous findings demonstrating that Walk Score is a valid measure of estimating neighborhood walkability in multiple geographic locations and at multiple spatial scales.

Addressing global sustainability challenges--including climate change, resource depletion, and ecosystem loss--is beyond the individual capabilities of even the largest companies. To tackle these threats, and unleash new value, companies and other stakeholders must collaborate in new ways that treat fragile and complex ecosystems as a whole. In this article, the authors draw on cases including the Latin American Water Funds Partnership, the Sustainable Apparel Coalition (led by Nike, Patagonia, and Walmart), and Action to Accelerate Recycling (a partnership between Alcoa, consumer packaged goods companies, and local governments, among others) to describe four new collaboration models that create shared value and address environmental protection across the value stream. Optimal collaborations focus on improving either business processes or outcomes. They start with a small group of key organizations, bring in project management expertise, link self-interest to shared interest, encourage productive competition, create quick wins, and, above all, build and maintain trust.

Humans appear to share with animals a nonverbal counting process. In a nonverbal counting condition, subjects pressed a key a numeral-specified number of times, while saying “the” at every press. The mean number of presses increased as a power function of the target number, with a constant coefficient of variation (c.v.), both within and beyond the proposed subitizing range (1–4 or 5), suggesting small numbers are represented on the same continuum as larger numbers and subject to the same noise process (scalar variability). By contrast, when subjects counted their presses out loud as fast as they could, the c.v. decreased as the inverse square root of the target value (binomial variability instead of scalar variability). The unexpected power-law relation between target value and mean number of presses in nonverbal counting suggests a new hypothesis about the development of the function relating number symbols to mental magnitudes.

• We recorded magnetoencephalographic auditory evoked fields from the left and right hemispheres of six medicated, paranoid schizophrenic subjects and six normal controls. The magnetic field data were used in estimating the location, orientation, and depth of the source generating the 100-millisecond latency evoked field component (M100). The M100 latencies were slightly shorter than simultaneously recorded vertex electroencephalographic evoked potential N100 latencies, suggesting that magnetoencephalographic and electroencephalographic recordings were examining slightly different aspects of the source(s). The M100 sources demonstrated substantial interhemispheric asymmetry in normal controls, and were located more posteriorly, with more nearly vertical orientations, over the left hemisphere. The M100 sources in schizophrenics did not exhibit the same interhemispheric asymmetry. Left hemisphere source orientation differed significantly between normal controls and schizophrenics. Discriminant function analysis correctly classified normal controls and schizophrenics at 100% using the conservative jackknife procedure on the basis of left hemisphere orientation alone. Our findings, while preliminary, support altered left hemisphere function, or possibly structure, in this group of schizophrenic subjects, and suggest that magnetoencephalographic recordings may be a useful research method in this major mental illness.

We recorded auditory evoked magnetic fields in response to 128 15-msec duration 1-KHz tone pips from both hemispheres of 6 young schizophrenic men. Auditory evoked potentials were recorded conventionally from a vertex lead. The approximately 50-msec latency component was identified in both the magnetic (M50) and electroencephalographic (EEG) (P50) recordings. Isofield topographical contour maps were used to estimate A50 source location and depth. Magnetic resonance imaging was used to identify the neuroanatomical structure(s) present at the estimated source location. M50 sources appeared to reside in the planum temporale in both left and right hemispheres in all subjects. Normal interhemispheric asymmetry (with respect to external bony landmarks) of the M50 source was not found in this patient group. Additionally, left (but not right) hemisphere source anatomy differed in several respects from data previously reported in normals.

We recorded auditory evoked magnetic fields in response to 128 15 msec duration 1 kHz tone pips from both hemispheres of 6 normal adult males. Auditory evoked potentials were recorded conventionally from a vertex lead. An approximately 50 msec latency component was identified in both the magnetic (called the M50) and EEG (called the P50) recordings. Isofield topographical contour maps were used to estimate M50 source location and depth. With respect to extracranial bony landmarks, M50 source locations were significantly higher and tended to be more posterior, over the left hemisphere. M50 and P50 latencies were not significantly different in 5 of 6 subjects; in one, M50 latencies were significantly longer than P50 latencies over the left hemisphere. Magnetic resonance images in 5 subjects were used to identify the neuroanatomical structure(s) present at the estimated source location. M50 sources appeared to reside in the cortex of the planum temporale in both left and right hemispheres in all 5 subjects.