Treatments for spasticity and pain in multiple sclerosis: a systematic review

Objectives: To identify the drug treatments currently available for the management of spasticity and pain in multiple sclerosis (MS), and to evaluate their clinical and cost-effectiveness. Data sources: Electronic bibliographic databases, National Research Register, MRC Clinical Trials Register and the US National Institutes of Health Clinical Trials Register. Review methods: Systematic searches identified 15 interventions for the treatment of spasticity and 15 interventions for treatment of pain. The quality and outcomes of the studies were evaluated. Reviews of the treatment of spasticity and pain when due to other aetiologies were also sought. Results: There is limited evidence of the effectiveness of four oral drugs for spasticity: baclofen, dantrolene, diazepam and tizanidine. Tizanidine appears to be no more effective than comparator drugs such as baclofen and has a slightly different side-effects profile. Despite claims that it causes less muscle weakness, there was very little evidence that tizanidine performed any better in this respect than other drugs, although it is more expensive. The findings of this review are consistent with reviews of the same treatments for spasticity derived from other aetiologies. There is good evidence that both botulinum toxin (BT) and intrathecal baclofen are effective in reducing spasticity, and both are associated with functional benefit. However, they are invasive, and substantially more expensive. None of the studies included in the review of pain were designed specifically to evaluate the alleviation of pain in patients with MS and there was no consistency regarding the use of validated outcome measures. It was suggested that, although expensive, the use of intrathecal baclofen may be associated with significant savings in hospitalisation costs in relation to bed-bound patients who are at risk of developing pressure sores, thus enhancing its cost-effectiveness. No studies of cost-effectiveness were identified in the review of pain. There is evidence, albeit limited, of the clinical effectiveness of baclofen, dantrolene, diazepam, tizanidine, intrathecal baclofen and BT and of the potential cost-effectiveness of intrathecal baclofen in the treatment of spasticity in MS. Conclusions: Many of the interventions identified are not licensed for the alleviation of pain or spasticity in MS and the lack of evidence relating to their effectiveness may also limit their widespread use. Indeed, forthcoming information relating to the use of cannabinoids in MS may result in there being better evidence of the effectiveness of new treatments than of any of the currently used drugs. It may therefore be of value to carry out double-blind randomised controlled trials of interventions used in current practice, where outcomes could include functional benefit and impact on quality of life. Further research into the development and validation of outcomes measures for pain and spasticity may also be useful, as perhaps would cost–utility studies

Do television and electronic games predict children's psychosocial adjustment? Longitudinal research using the UK Millennium Cohort Study

Background: Screen entertainment for young children has been associated with several aspects of psychosocial adjustment. Most research is from North America and focuses on television. Few longitudinal studies have compared the effects of TV and electronic games, or have investigated gender differences. Purpose: To explore how time watching TV and playing electronic games at age 5 years each predicts change in psychosocial adjustment in a representative sample of 7 year-olds from the UK. Methods: Typical daily hours viewing television and playing electronic games at age 5 years were reported by mothers of 11 014 children from the UK Millennium Cohort Study. Conduct problems, emotional symptoms, peer relationship problems, hyperactivity/inattention and prosocial behaviour were reported by mothers using the Strengths and Difficulties Questionnaire. Change in adjustment from age 5 years to 7 years was regressed on screen exposures; adjusting for family characteristics and functioning, and child characteristics. Results: Watching TV for 3 h or more at 5 years predicted a 0.13 point increase (95% CI 0.03 to 0.24) in conduct problems by 7 years, compared with watching for under an hour, but playing electronic games was not associated with conduct problems. No associations were found between either type of screen time and emotional symptoms, hyperactivity/inattention, peer relationship problems or prosocial behaviour. There was no evidence of gender differences in the effect of screen time. Conclusions: TV but not electronic games predicted a small increase in conduct problems. Screen time did not predict other aspects of psychosocial adjustment. Further work is required to establish causal mechanisms

No out for the Federal Government: Enforcing Contractual Arbitration Clauses in Federal Government False Claims Actions - U. S. v. Bankers Ins. Co.

As a party to one-fourth of all civil litigation2 the federal government exerts a looming presence in American judicial proceedings. Thus, attempts by the government to elude obligations under arbitration agreements, if successful, would significantly impact the elite status that pre-dispute contractual arbitration clauses currently hold.\u27 This casenote examines how the United States Court of Appeals for the Fourth Circuit recently addressed this issue in the context of a false claims action

A Myelin Proteolipid Protein-LacZ Fusion Protein Is Developmentally Regulated and Targeted to the Myelin Membrane in Transgenic Mice

Transgenic mice were generated with a fusion gene carrying a portion of the murine myelin proteolipid protein (PLP) gene, including the first intron, fused to the E. coli LacZ gene. Three transgenic lines were derived and all lines expressed the transgene in central nervous system white matter as measured by a histochemical assay for the detection of β-galactosidase activity. PLP-LacZ transgene expression was regulated in both a spatial and temporal manner, consistent with endogenous PLP expression. Moreover, the transgene was expressed specifically in oligodendrocytes from primary mixed glial cultures prepared from transgenic mouse brains and appeared to be developmentally regulated in vitro as well. Transgene expression occurred in embryos, presumably in pre- or nonmyelinating cells, rather extensively throughout the peripheral nervous system and within very discrete regions of the central nervous system. Surprisingly, beta-galactosidase activity was localized predominantly in the myelin in these transgenic animals, suggesting that the NH_2-terminal 13 amino acids of PLP, which were present in the PLP-LacZ gene product, were sufficient to target the protein to the myelin membrane. Thus, the first half of the PLP gene contains sequences sufficient to direct both spatial and temporal gene regulation and to encode amino acids important in targeting the protein to the myelin membrane

A histological study of the spinal cord and peripheral nervous system in scrapie disease of sheep

This work records the results of a study of the spinal cords, spinal sensory ganglia, sympathetic ganglia, Gasserian ganglia and neurones in the adrenal glands of sheep affected with scrapie disease.It was suggested that many minor changes in sympathetic ganglia may be of a non -specific nature and it was concluded that there was no significant morphological difference, including vacuolation of neurones, between the gelglia of clinically healthy sheep and those with scrapie disease

The property finance business in South Africa

Problem Statement: The business of property finance has not been properly documented in South Africa. Available resource material focuses on the perspective of the property developer and investor largely neglecting the business of property finance. Thus comprehensive information on this business was not available to students and researchers This study set out to correct this deficiency. Research Procedure: Key property finance personnel in the major banks in the Republic of South Africa were interviewed to establish how the business of property finance is conducted. Jointly the interviewees represent 77% by volume of business over a period of two years A parallel process of literature research was undertaken to compliment the interview research and provide technical depth to the findings. Findings: The empirical and literature research results were combined to comprehensively document the processes, structures, systems, productsBusiness ManagementM. Com. (Business Management

Impact of a theoretically based sex education programme (SHARE) delivered by teachers on NHS registered conceptions and terminations: final results of cluster randomised trial

<b>Objective</b>: To assess the impact of a theoretically based sex education programme (SHARE) delivered by teachers compared with conventional education in terms of conceptions and terminations registered by the NHS. Design Follow-up of cluster randomised trial 4.5 years after intervention. <b>Setting</b>: NHS records of women who had attended 25 secondary schools in east Scotland. <b>Participants</b>: 4196 women (99.5% of those eligible). <b>Intervention</b>: SHARE programme (intervention group) v existing sex education (control group). <b>Main outcome measure</b>: NHS recorded conceptions and terminations for the achieved sample linked at age 20. <b>Results</b>: In an "intention to treat" analysis there were no significant differences between the groups in registered conceptions per 1000 pupils (300 SHARE v 274 control; difference 26, 95% confidence interval –33 to 86) and terminations per 1000 pupils (127 v 112; difference 15, –13 to 42) between ages 16 and 20. <b>Conclusions</b>: This specially designed sex education programme did not reduce conceptions or terminations by age 20 compared with conventional provision. The lack of effect was not due to quality of delivery. Enhancing teacher led school sex education beyond conventional provision in eastern Scotland is unlikely to reduce terminations in teenagers

Theatrical Deception: Shakespearean Allusion in John Fowles’ \u3cem\u3eThe Magus: A Revised Version \u3c/em\u3e

Readers of either or both versions of John Fowles\u27 The Magus frequently express discomfort in assessing the work. One finds the 1966 original edition too difficult, labeling it pretentious and self-indulgent (Allen 65). Moderating this position, another critic praises its intellectual power and thematic resolution, but then calls the latter a partial failure (Rubenstein 339). Others acknowledge the author\u27s ambitiousness (Scholes 12), one describing the novel as a brilliant puzzle (Rackham 95). The 1978 revision, The Magus: A Revised Version, meets the same uneasy and uncertain reaction as did the earlier edition. According to one reader, The essential opacity of the original novel has not been removed in the revised version, yet the latter is unquestionably superior to the original (Wade 716). Another reader cannot see these improvements (Glasersfeld 444). And a third actually finds the new edition not more polished or elegant than the earlier work … simply duller (Lever 86)

Engaging and Expanding Communities: Widening the circle of stakeholders

The 32 fellows in the 2013 Emerging Leaders Program (ELP) worked with community partners to investigate the theme, “Engaging and Expanding Communities . They worked with six community partners, and identified ways to help them expand beyond their core stakeholders to a wider circle of stakeholders and broader potential impact. The fellows gave their time and professional skills to understand how to reach new business partners, new participants, new advisors, and new donors. They conducted surveys, interviews, and focus groups; explored social media options; examined best practices; and considered ways to tell powerful stories about the vitally important work of the “project sponsor” organizations with whom we partnered. Our six project sponsors – and their widening circle of stakeholders – include: Massachusetts Business Roundtable: Large corporations – & small businesses Girl Scouts of Eastern Mass: Scouts, parents, leaders – & new scouts, volunteers Science from Scientists: Scientists in schools – & engaged donors in this niche Children’s Trust Fund: Struggling families – & supportive young professionals Center for Social Policy: Poor people’s views – and business people’s views Center for Collaborative Leadership: ELP staff - & ELP alumni as ambassador