Pilates based core stability training in ambulant individuals with multiple sclerosis: protocol for a multi-centre randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>People with Multiple Sclerosis (MS) frequently experience balance and mobility impairments, including reduced trunk stability. Pilates-based core stability training, which is aimed at improving control of the body's stabilising muscles, is popular as a form of exercise with people with MS and therapists. A replicated single case series study facilitated by the Therapists in MS Group in the United Kingdom (UK) provides preliminary evidence that this approach can improve balance and mobility in ambulant people with MS; further evidence is needed to substantiate these findings to ensure that limited time, energy, finances and resources are used to best effect.</p> <p>This study builds upon the pilot work undertaken in the case series study by implementing a powered randomised controlled study, with the aims of:</p> <p>1 Establishing the effectiveness of core stability training</p> <p>2 Comparing core stability training with standardised physiotherapy exercise</p> <p>3 Exploring underlying mechanisms of change associated with this intervention</p> <p>Methods</p> <p>This is a multi-centre, double blind, block randomised, controlled trial. Eligible participants will be recruited from 4 UK centres. Participants will be randomly allocated to one of three groups: Pilates based core stability training, standardised physiotherapy exercise or contract-relax relaxation sessions (placebo control). All will receive face to face training sessions over a 12 week period; together with a 15 minute daily home programme. All will be assessed by a blinded assessor before training, at the end of the 12 week programme and at 4 week follow-up. The primary outcome measure is the 10 metre timed walk. Secondary outcome measures are the MS walking Scale (MSWS-12), the Functional Reach (forwards and lateral), a 10 point Numerical Rating Scale to determine "Difficulty in carrying a drink when walking", and the Activities-specific Balance Confidence (ABC) Scale. In addition, ultrasound imaging of the abdominal muscles will be performed before and after intervention to assess changes in abdominal musculature at one of the four centres (Plymouth).</p> <p>Discussion</p> <p>This pragmatic trial will assess the effect of these exercise programmes on ambulatory people with MS. It may not be possible to extrapolate the conclusions to those who are non-ambulatory.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01414725">NCT01414725</a></p

Increasing the options for reducing adverse events: Results from a modified Delphi technique

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: The aim of this paper is to illustrate a simple method for increasing the range of possible options for reducing adverse events in Australian hospitals, which could have been, but was not, adopted in the wake of the landmark 1995 &apos;Quality in Australian Health Care &apos; study, and to report the suggestions and the estimated lapse time before they would impact upon mortality and morbidity. Method: The study used a modified Delphi technique that first elicited options for reducing adverse events from an invited panel selected on the basis of their knowledge of the area of adverse events and quality assurance. Initial suggestions were collated and returned to them for reconsideration and comment. Results: Completed responses from both stages were obtained from 20 of those initially approached. Forty-one options for reducing AEs were identified with an average lapse time of 3.5 years. Hospital regulation had the least delay (2.4 years) and out of hospital information the greatest (6.4 years). Conclusion: Following identification of the magnitude of the problem of adverse events in the &apos;Quality in Australian Health Care &apos; study a more rapid and broad ranging response was possible than occurred. Apparently viable options for reducing adverse events and associated mortality and morbidity remain unexploited

A participatory physical and psychosocial intervention for balancing the demands and resources among industrial workers (PIPPI): study protocol of a cluster-randomized controlled trial

Background: Need for recovery and work ability are strongly associated with high employee turnover, well-being and sickness absence. However, scientific knowledge on effective interventions to improve work ability and decrease need for recovery is scarce. Thus, the present study aims to describe the background, design and protocol of a cluster randomized controlled trial evaluating the effectiveness of an intervention to reduce need for recovery and improve work ability among industrial workers. Methods/Design: A two-year cluster randomized controlled design will be utilized, in which controls will also receive the intervention in year two. More than 400 workers from three companies in Denmark will be aimed to be cluster randomized into intervention and control groups with at least 200 workers (at least 9 work teams) in each group. An organizational resources audit and subsequent action planning workshop will be carried out to map the existing resources and act upon initiatives not functioning as intended. Workshops will be conducted to train leaders and health and safety representatives in supporting and facilitating the intervention activities. Group and individual level participatory visual mapping sessions will be carried out allowing team members to discuss current physical and psychosocial work demands and resources, and develop action plans to minimize strain and if possible, optimize the resources. At all levels, the intervention will be integrated into the existing organization of work schedules. An extensive process and effect evaluation on need for recovery and work ability will be carried out via questionnaires, observations, interviews and organizational data assessed at several time points throughout the intervention period. Discussion: This study primarily aims to develop, implement and evaluate an intervention based on the abovementioned features which may improve the work environment, available resources and health of industrial workers, and hence their need for recovery and work ability

Use of outpatient care in VA and Medicare among disability-eligible and age-eligible veteran patients

<p>Abstract</p> <p>Background</p> <p>More than half of veterans who use Veterans Health Administration (VA) care are also eligible for Medicare via disability or age, but no prior studies have examined variation in use of outpatient services by Medicare-eligible veterans across health system, type of care or time.</p> <p>Objectives</p> <p>To examine differences in use of VA and Medicare outpatient services by disability-eligible or age-eligible veterans among veterans who used VA primary care services and were also eligible for Medicare.</p> <p>Methods</p> <p>A retrospective cohort study of 4,704 disability- and 10,816 age-eligible veterans who used VA primary care services in fiscal year (FY) 2000. We tracked their outpatient utilization from FY2001 to FY2004 using VA administrative and Medicare claims data. We examined utilization differences for primary care, specialty care, and mental health outpatient visits using generalized estimating equations.</p> <p>Results</p> <p>Among Medicare-eligible veterans who used VA primary care, disability-eligible veterans had more VA primary care visits (<it>p </it>< 0.001) and more VA specialty care visits (<it>p </it>< 0.001) than age-eligible veterans. They were more likely to have mental health visits in VA (<it>p </it>< 0.01) and Medicare-reimbursed visits (<it>p </it>< 0.01). Disability-eligible veterans also had more total (VA+Medicare) visits for primary care (<it>p </it>< 0.01) and specialty care (<it>p </it>< 0.01), controlling for patient characteristics.</p> <p>Conclusions</p> <p>Greater use of primary care and specialty care visits by disability-eligible veterans is most likely related to greater health needs not captured by the patient characteristics we employed and eligibility for VA care at no cost. Outpatient care patterns of disability-eligible veterans may foreshadow care patterns of veterans returning from Afghanistan and Iraq wars, who are entering the system in growing numbers. This study provides an important baseline for future research assessing utilizations among returning veterans who use both VA and Medicare systems. Establishing effective care coordination protocols between VA and Medicare providers can help ensure efficient use of taxpayer resources and high quality care for disabled veterans.</p

Synthetic Lethal Screen Identifies NF-κB as a Target for Combination Therapy with Topotecan for patients with Neuroblastoma

<p>Abstract</p> <p>Background</p> <p>Despite aggressive multimodal treatments the overall survival of patients with high-risk neuroblastoma remains poor. The aim of this study was to identify novel combination chemotherapy to improve survival rate in patients with high-risk neuroblastoma.</p> <p>Methods</p> <p>We took a synthetic lethal approach using a siRNA library targeting 418 apoptosis-related genes and identified genes and pathways whose inhibition synergized with topotecan. Microarray analyses of cells treated with topotecan were performed to identify if the same genes or pathways were altered by the drug. An inhibitor of this pathway was used in combination with topotecan to confirm synergism by <it>in vitro </it>and <it>in vivo </it>studies.</p> <p>Results</p> <p>We found that there were nine genes whose suppression synergized with topotecan to enhance cell death, and the NF-κB signaling pathway was significantly enriched. Microarray analysis of cells treated with topotecan revealed a significant enrichment of NF-κB target genes among the differentially altered genes, suggesting that NF-κB pathway was activated in the treated cells. Combination of topotecan and known NF-κB inhibitors (NSC 676914 or bortezomib) significantly reduced cell growth and induced caspase 3 activity <it>in vitro</it>. Furthermore, in a neuroblastoma xenograft mouse model, combined treatment of topotecan and bortezomib significantly delayed tumor formation compared to single-drug treatments.</p> <p>Conclusions</p> <p>Synthetic lethal screening provides a rational approach for selecting drugs for use in combination therapy and warrants clinical evaluation of the efficacy of the combination of topotecan and bortezomib or other NF-κB inhibitors in patients with high risk neuroblastoma.</p

Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

The objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind randomized trial that compared posaconazole with fluconazole antifungal prophylaxis in recipients of allogeneic HSCT with GVHD who were receiving immunosuppressive therapy (Ullmann et al., N Engl J Med 356:335–347, 2007). Clinical events were modeled with chance nodes reflecting probabilities of IFIs, IFI-related death, and death from other causes. Data on life expectancy, quality-of-life, medical resource consumption, and costs were obtained from the literature. The total cost with posaconazole amounted to €9,428 (95% uncertainty interval €7,743–11,388), which is €4,566 (€2,460–6,854) more than those with fluconazole. Posaconazole prophylaxis resulted in 0.17 (0.02–0.36) quality adjusted life year (QALY) gained compared to fluconazole prophylaxis, corresponding to an incremental cost effectiveness ratio (ICER) of €26,225 per QALY gained. A scenario analysis demonstrated that at an increased background IFI risk (from 9% to 15%) the ICER was €13,462 per QALY. Given the underlying data and assumptions, posaconazole prophylaxis is expected to be cost-effective relative to fluconazole in recipients of allogeneic HSCT developing GVHD in the Netherlands. The cost-effectiveness of posaconazole depends on the IFI risk, which can vary by hospital

Influence of phenological barriers and habitat differentiation on the population genetic structure of the balearic endemic Rhamnus ludovici-salvatoris Chodat and R. alaternus L

[EN] Rhamnus ludovici-salvatoris, endemic to the Gymnesian Islands, coexists with the related and widespread R. alaternus in Mallorca and Menorca. In both species, the population genetic structure using RAPD, and flowering during a 3-year period to check for possible phenological barriers, were analyzed. Rhamnus ludovici-salvatoris showed lower genetic diversity and stronger population structure than R. alaternus, the Cabrera population being less diverse and the most differentiated. Rhamnus ludovici-salvatoris flowered one month later, although flowering of both species coincided sporadically. These congeners seem to have diverged through isolation by time and differentiation in habitat. The population genetic structure of R. ludovici-salvatoris could mainly be due to the existence of small populations on the one hand, and a gene flow caused by rare hybridization events on the other, which may also explain the presence of morphologically intermediate individuals in Menorca. The conservation of R. ludovici-salvatoris populations may include population reinforcements and other in situ interventions.Ferriol Molina, M.; Llorens García, L.; Gil, L.; Boira Tortajada, H. (2009). Influence of phenological barriers and habitat differentiation on the population genetic structure of the balearic endemic Rhamnus ludovici-salvatoris Chodat and R. alaternus L. Plant Systematics and Evolution. 277(1-2):105-116. doi:10.1007/s00606-008-0110-3S1051162771-2Affre L, Thompson JD, Debussche M (1997) Genetic structure of continental and island populations of the Mediterranean endemic Cyclamen balearicum (Primulaceae). Amer J Bot 84(4): 437–451BOIB (2005) Decreto 75/2005. BOIB 106: 29–32Bolmgren K, Oxelman B (2004) Generic limits in Rhamnus L. s.l. (Rhamnaceae) inferred from nuclear and chloroplast DNA sequence phylogenies. Taxon 53(2):383–390Bolòs O, Molinier R (1958) Recherches phytosociologiques dans l’île de Majorque. Collectanea Botanica 34:699–865Cardona MA (1979) Consideracions sobre l’endemisme i l’origen de la flora de las Illes Balears. Butlletí del Institut Catalá de Historia Natural 44 (Sec. Bot. 3):7–15Cardona MA, Contandriopoulos J (1979) Endemism and evolution in the islands of the Western Mediterranean. In: Bramwell D (ed) Plants and islands. Academic Press, London, pp 133–169Chodat L (1924) Contributions à la Géo-Botanique de Majorque. PhD Thesis, Université de Genève—Institut de Botanique, SwitzerlandCollins D, Mill RR, Moller M (2003) Species separation of Taxus baccata, T. canadensis, and T. cuspidata (Taxaceae) and origins of their reputed hybrids inferred from RAPD and cpDNA data. Amer J Bot 90(2):175–182Cronk QCB (1997) Islands: stability, diversity, conservation. Biodivers Conserv 6(3):477–493Doyle JJ, Doyle JL (1990) Isolation of plant DNA from fresh tissue. Focus 12:13–15Ducarme V, Wesselingh RA (2005) Detecting hybridization in mixed populations of Rhinanthus minor and Rhinanthus angustifolius. Folia Geobot 40(2/3):151–161Englishloeb GM, Karban R (1992) Consequences of variation in flowering phenology for seed head herbivory and reproductive success in Erigeron glaucus (Compositae). Oecologia 89:588–595Gautier F, Caluzon G, Suk JP, Violanti D (1994) Age et durée de la crise de salinité Messinienne. Comptes Rendus de l’Académie des Sciences de Paris 318:1103–1109Gerard PR, Fernandez-Manjarres JF, Frascaria-Lacoste N (2006) Temporal cline in a hybrid zone population between Fraxinus excelsior L. and Fraxinus angustifolia Vahl. Molec Ecol 15:3655–3667Gil L, Llorens L, Tébar FJ, Costa M (1995) La vegetación de la isla de Cabrera. In: Guía de la excursión geobotánica de las XV Jornadas de Fitosociología. Datos sobre la vegetación de Cabrera. Palma de Mallorca: Universitat de les Illes Balears, pp 51–77Gulías J, Flexas J, Abadía A, Medrano H (2002) Photosynthetic responses to water deficit in six Mediterranean sclerophyll species: possible factors explaining the declining distribution of Rhamnus ludovici-salvatoris, and endemic Balearic species. Tree Physiol 22:687–697Gulías J, Traveset A, Riera N, Mus M (2004) Critical stages in the recruitment process of Rhamnus alaternus L. Ann Bot 93:723–731Gustafsson S, Sjögren-Gulve P (2002) Genetic diversity in the rare orchid, Gymnadenia odoratissima and a comparison with the more common congener, G. conopsea. Conserv Genet 3:225–234Gustafsson S (2003) Population genetic analyses in the orchid genus Gymnadenia—a conservation genetic perspective. PhD Thesis, Uppsala University, SwedenGustafsson S, Lönn M (2003) Genetic differentiation and habitat preference of flowering-time variants within Gymnadenia conopsea. Heredity 91:284–292Harris W (1996) Genecological aspects of flowering patterns of populations of Kunzea ericoides and K. sinclairii (Myrtaceae). New Zealand J Bot 34:333–354Hendry AP, Dray T (2005) Population structure attributable to reproductive time: isolation by time and adaptation by time. Molec Ecol 14:901–916Hosokawa K, Minami M, Kawahara K, Nakamura I, Shibata T (2000) Discrimination among three species of medicinal Scutellaria plants using RAPD markers. Pl Med 66:270–272Huang Z, Liu L, Zhou T, Ju B (2005) Effects of environmental factors on the population genetic structure in chukar partridge (Alectoris chukar). J Arid Environ 62:427–434Juan A, Crespo MB, Cowan RS, Lexer C, Fay F (2004) Patterns of variability and gene flow in Medicago citrina, an endangered endemic of islands in the western Mediterranean, as revealed by amplified fragment length polymorphism (AFLP). Molec Ecol 13:2679–2690Krijgsman W, Hilgen FJ, Raffi I, Sierro FJ, Wilson DS (1999) Chronology, causes and progression of the Messinian salinity crisis. Nature 400:652–655Lamont BB, He T, Enright NJ, Krauss SL, Miller BP (2003) Anthropogenic disturbance promotes hybridization between Banksia species by altering their biology. J Evol Biol 16:551–557Lennartsson T (1997) Seasonal differentiation—a conservative reproductive barrier in two grassland Gentianella (Gentianaceae) species. Pl Syst Evol 208:45–69Martinez-Solis I, Iranzo J, Estrelles E, Ibars AM (1993) Leaf domatia in the section Alaternus (Miller) DC. of the genus Rhamnus (Rhamnaceae). Bot J Linn Soc 112:311–318McIntosh ME (2002) Flowering phenology and reproductive output in two sister species of Ferocactus (Cactaceae). Pl Ecol 159:1–13Nei M (1973) Analysis of gene diversity in subdivided populations. Proc Natl Acad Sci USA 70:3321–3323Nei M (1978) Estimation of average heterozigosity and genetic distance from a small number of individuals. Genetics 89:583–590Nei M, Li W (1979) Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci USA 79:5269–5273Nybom H, Bartish IV (2000) Effects of life history traits and sampling strategies on genetic diversity estimates obtained with RAPD markers in plants. Perspect Pl Ecol Evol Syst 3(2):93–114Oostermeijer JGB, Luijten SH, Ellis-Adam AC, den Nijs JCM (2002) Future prospects for the rare, late-flowering Gentianella germanica and Gentianopsis ciliata in Dutch nutrient-poor calcareous grasslands. Biol Conserv 104:339–350Pease CM, Lande R, Bull JJ (1989) A model of population growth, dispersal and evolution in a changing environment. Ecology 70(6):1657–1664Perron M, Gordon AG, Bousquet J (1995) Species-specific RAPD fingerprints for the closely related Picea mariana and P. rubens. Theor Appl Genet 91:142–149Pierce S, Ceriani RM, Villa M, Cerabolini B (2006) Quantifying relative extinction risks and targeting intervention for the orchid flora of a natural park in the European prealps. Conserv Biol 20(6):1804–1810Richardson JE, Fay MF, Cronk QCB, Bowman D, Chase MW (2000) A phylogenetic analysis of Rhamnaceae using rbcL and trnL-F plastid DNA sequences. Amer J Bot 87(9):1309–1324Roselló JA, Sáez L (2000) Index Balearicum: an annotated check-list of the vascular plants described from the Balearic Islands. Collect Bot 25(1):3–203Roselló JA, Cebrián MC, Mayol M (2002) Testing taxonomic and biogeographical relationships in a narrow mediterranean endemic complex (Hippocrepis balearica) using RAPD markers. Ann Bot 89:321–327Sales E, Nebauer SG, Mus M, Segura J (2001) Population genetic study in the Balearic plant species Digitalis minor (Scrophulariaceae) using RAPD markers. Amer J Bot 88(10):1750–1759Sherwin WB, Moritz C (2000) Managing and monitoring genetic erosion. In: Young AG, Clarke GM (eds) Genetics, demography and viability of fragmented populations. Cambridge University Press, Cambridge, pp 9–34Sneath PHA, Sokal RR (1973) Numerical taxonomy. Freeman and Co., San FranciscoTraveset A, Gulías J, Riera N, Mus M (2003) Transition probabilities from pollination to establishment in a rare dioecious shrub species (Rhamnus ludovici-salvatoris) in two habitats. J Ecol 91:427–437Tutin TG, Heywood VH, Burges NA, Valentine DH, Walters SM, Webb DA (eds) (2001) Flora Europaea, vol 2. Rosaceae to Umbelliferae. Cambridge University Press, CambridgeWright S (1931) Evolution in Mendelian populations. Genetics 16:97–159Zimmerman M (1980a) Reproduction in Polemonium: pre-dispersal seed predation. Ecology 61:502–506Zimmerman M (1980b) Reproduction in Polemonium: competition for pollinators. Ecology 61:497–50

A Polymorphism in a Gene Encoding Perilipin 4 Is Associated with Height but not with Bone Measures in Individuals from the Framingham Osteoporosis Study

There is increasing interest in identifying new pathways and candidate genes that confer susceptibility to osteoporosis. There is evidence that adipogenesis and osteogenesis may be related, including a common bone marrow progenitor cell for both adipocytes and osteoblasts. Perilipin 1 (PLIN1) and Perilipin 4 (PLIN4) are members of the PATS family of genes and are involved in lipolysis of intracellular lipid deposits. A previous study reported gender-specific associations between one polymorphism of PLIN1 and bone mineral density (BMD) in a Japanese population. We hypothesized that polymorphisms in PLIN1 and PLIN4 would be associated with bone measures in adult Caucasian participants of the Framingham Osteoporosis Study (FOS). We genotyped 1,206 male and 1,445 female participants of the FOS for four single-nucleotide polymorphism (SNPs) in PLIN1 and seven SNPs in PLIN4 and tested for associations with measures of BMD, bone ultrasound, hip geometry, and height. We found several gender-specific significant associations with the measured traits. The association of PLIN4 SNP rs8887, G>A with height in females trended toward significance after simulation testing (adjusted P = 0.07) and remained significant after simulation testing in the combined-sex model (adjusted P = 0.033). In a large study sample of men and women, we found a significant association between one SNP in PLIN4 and height but not with bone traits, suggesting that PATS family genes are not important in the regulation of bone. Identification of genes that influence human height may lead to a better understanding of the processes involved in growth and development