Quality of Life with Late-Onset Pompe Disease: Qualitative Interviews and General Public Utility Estimation in the United Kingdom

Background: Late-onset Pompe disease (LOPD) is a rare, progressive neuromuscular condition typically characterized by weakness of skeletal muscles, including those involved in respiration and diaphragmatic dysfunction. Individuals with LOPD typically eventually require mobility and/or ventilatory support. / Objectives: This study aimed to develop health state vignettes and estimate health state utility values for LOPD in the United Kingdom. / Methods: Vignettes were developed for 7 health states of LOPD with states defined in terms of mobility and/or ventilatory support. Vignettes were drafted based on patient-reported outcome data from the Phase 3 PROPEL trial (NCT03729362) and supplemented by a literature review. Qualitative interviews with individuals living with LOPD and clinical experts were conducted to explore the health-related quality-of-life (HRQoL) impact of LOPD and to review the draft vignettes. Vignettes were finalized following a second round of interviews with individuals living with LOPD and used in health state valuation exercises with people of the UK population. Participants rated the health states using the EQ-5D-5L, visual analog scale, and time trade-off interviews. / Results: Twelve individuals living with LOPD and 2 clinical experts were interviewed. Following the interviews, 4 new statements were added regarding dependence on others, bladder control problems, balance issues/fear of falling, and frustration. One hundred interviews with a representative UK population sample were completed. Mean time trade-off utilities ranged from 0.754 (SD = 0.31) (no support) to 0.132 (SD = 0.50) (invasive ventilatory and mobility support-dependent). Similarly, EQ- 5D-5L utilities ranged from 0.608 (SD = 0.12) to -0.078 (SD = 0.22). / Discussion: The utilities obtained in the study are consistent with utilities reported in the literature (0.670-0.853 for nonsupport state). The vignette content was based on robust quantitative and qualitative evidence and captured the main HRQoL impacts of LOPD. The general public rated the health states consistently lower with increasing disease progression. There was greater uncertainty around utility estimates for the severe states, suggesting that participants found it harder to rate them. / Conclusion: This study provides utility estimates for LOPD that can be used in economic modeling of treatments for LOPD. Our findings highlight the high disease burden of LOPD and reinforce the societal value of slowing disease progression

The effectiveness of a motivational interviewing Primary-care based intervention on physical activity and predictors of change in a disadvantaged community

Little research exists on the impact of behavior change interventions in disadvantaged communities. We conducted a prospective study to explore the effectiveness of motivational interviewing on physical activity change within a deprived community and the social- psychological and motivational predictors of change in physical activity including stage of change, self-efficacy, social support, and variables from self-determination theory and the theory of planned behavior. Five motivational interviewing counsellors recruited 207 patients and offered motivational interviewing sessions to support physical activity behavior change. At 6-months there were significant improvements in physical activity, stage of change, and social support. A dose–response relationship was evident; those who attended 2 or more consultations increased their total physical activity, stage of change and family social support more than those who attended just one. Hierarchical regression analyses indicated that number of sessions and change in stage of change predicted 28.4 % of the variance in change in total physical activity and, with social support from friends, 21.0 % of the variance in change walking time. Change in perceived behavioral control and attitudes, friend social support, and number of sessions predicted 16.8 % of the variance in change in vigorous physical activity. Motivational interviewing is an effective approach for promoting physical activity amongst lower socio-economic status groups in the short term. The study demonstrates good translational efficacy, and contributes to a limited number of physical activity interventions targeting low income groups in the UK

Soybean genetic transformation: a valuable tool for the functional study of genes and the production of agronomically improved plants

Transgenic plants represent an invaluable tool for molecular, genetic, biochemical and physiological studies by gene overexpression or silencing, transposon-based mutagenesis, protein sub-cellular localization and/or promoter characterization as well as a breakthrough for breeding programs, allowing the production of novel and genetically diverse genotypes. However, the stable transformation of soybean cannot yet be considered to be routine because it depends on the ability to combine efficient transformation and regeneration techniques. Two methods have been used with relative success to produce completely and stably transformed plants: particle bombardment and the Agrobacterium tumefaciens system. In addition, transformation by Agrobacterium rhizogenes has been used as a powerful tool for functional studies. Most available information on gene function is based on heterologous expression systems. However, as the activity of many promoters or proteins frequently depends on specific interactions that only occur in homologous backgrounds, a final confirmation based on a homologous expression system is desirable. With respect to soybean biotech improvement, transgenic lines with agronomical, nutritional and pharmaceutical traits have been obtained, including herbicide-tolerant soybeans, which represented the principal biotech crop in 2011, occupying 47% of the global biotech area

Rationale, design, implementation, and baseline characteristics of patients in the DIG trial: A large, simple, long-term trial to evaluate the effect of digitalis on mortality in heart failure

This article provides a detailed overview of the rationale for key aspects of the protocol of the Digitalis Investigation Group (DIG) trial. It also highlights unusual aspects of the study implementation and the baseline characteristics. The DIG trial is a large, simple, international placebo-controlled trial whose primary objective is to determine the effect of digoxin on all cause mortality in patients with clinical heart failure who are in sinus rhythm and whose ejection fraction is less than or equal to 0.45. An ancillary study examines the effect in those with an ejection fraction > 0.45. Key aspects of the trial include the simplicity of the design, broad eligibility criteria, essential data collection, and inclusion of various types of centers. A total of 302 centers in the United States and Canada enrolled 7788 patients between February 1991 and September 1993. Follow-up continued until December 1995 with the results available in Spring 1996