ObjectiveFriedreich ataxia (FRDA) is a progressive neurodegenerative disorder of adults and children. This study analyzed neurological outcomes and changes to identify predictors of progression and generate power calculations for clinical trials.MethodsEight hundred and twelve subjects in a natural history study were evaluated annually across 12 sites using the Friedreich Ataxia Rating Scale (FARS), 9‐Hole Peg Test, Timed 25‐Foot Walk, visual acuity tests, self‐reported surveys and disability scales. Cross‐sectional outcomes were assessed from recent visits, and longitudinal changes were gaged over 5 years from baseline.ResultsCross‐sectional outcomes correlated with measures of disease severity. Age, genetic severity (guanine‐adenine‐adenine [GAA] repeat length), and testing site predicted performance. Serial progression was relatively linear using FARS and composite measures of performance, while individual performance outcomes were nonlinear over time. Age strongly predicted change from baseline until removing the effects of baseline FARS scores, when GAA becomes a more important factor. Progression is fastest in younger subjects and subjects with longer GAA repeats. Improved coefficients of variation show that progression results are more reproducible over longer assessment durations.InterpretationWhile age predicted progression speed in simple analyses and may provide an effective way to stratify cohorts, separating the effects of age and genetic severity is difficult. Controlling for baseline severity, GAA is the major determinant of progression rate in FRDA. Clinical trials will benefit from enrollment of younger subjects, and sample size requirements will shrink with longer assessment periods. These findings should prove useful in devising gene therapy trials in the near future.

orldwide, 100 million patients aged 45 years and older undergo inpatient noncardiac surgery each year. 1,2 Although surgery has the potential to improve and prolong quality and duration of life, it is also associated with complications and mortality. During the last several decades, advances in perioperative care have included less invasive surgery, improved anesthetic techniques, enhanced intraoperative monitoring and more rapid mobilization after surgery. 2 At the same time, the age and the number of comorbidities of patients undergoing surgery have increased substantially. 3,4 Hence, in the current context, the frequency and timing of mortality is uncertain, as is the relation between perioperative complications to mortality. In a large prospective study (The Vascular Events in Noncardiac Surgery Patients Cohort Evaluation [VISION] Study), we systematically followed patients who underwent noncardiac surgery and documented perioperative complications and death. Our a priori objectives included establishing the frequency and timing of death after noncardiac surgery, and the association between perioperative complications and postsurgical death. Methods Study design, population and data We previously reported details of the study design and methods. 5,6 VISION was an international, prospective cohort study. Patients were included if they were aged 45 years or older, had undergone noncardiac surgery, had received general or regional anesthesia and remained in hospital for at least 1 night after surgery. Patients were recruited at 28 centres in 14 countries in

We found that spatial segregation of T. diplomenziesii and T. menziesii was accompanied by adaptation to changes in climatic regime. Tolmiea menziesii is not a nascent autotetraploid, having persisted long enough to be established throughout the Pacific Northwest, and therefore both polyploidization and subsequent evolution have contributed to the observed differences between T. menziesii and T. diplomenziesii.

BackgroundCancer is the leading cause of death in the developed world, and yet healthcare practitioners infrequently discuss goals of care (GoC) with hospitalized cancer patients. We sought to identify barriers to GoC discussions from the perspectives of staff oncologists, oncology residents, and oncology nurses.MethodsThis was a single center survey of staff oncologists, oncology residents, and inpatient oncology nurses. Barriers to GoC discussions were assessed on a 7-point Likert scale (1 = extremely unimportant; 7 = extremely important).ResultsBetween July 2013 and May 2014, of 185 eligible oncology clinicians, 30 staff oncologists, 10 oncology residents, and 28 oncology nurses returned surveys (response rate of 37%). The most important barriers to GoC discussions were patient and family factors. They included family members’ difficulty accepting poor prognoses (mean score 5.9, 95% CI [5.7, 6.2]), lack of family agreement in the goals of care (mean score 5.8, 95% CI [5.5, 6.1]), difficulty understanding the limitations of life-sustaining treatments (mean score 5.8, 95% CI [5.6, 6.1]), lack of patients’ capacity to make goals of care decisions (mean score 5.7, 95% CI [5.5, 6.0]), and language barriers (mean score 5.7, 95% CI [5.4, 5.9]). Participants viewed system factors and healthcare provider factors as less important barriers.ConclusionsOncology practitioners perceive patient and family factors as the most limiting barriers to GoC discussions. Our findings underscore the need for oncology clinicians to be equipped with strong communication skills to help patients and families navigate GoC discussions.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5333-x) contains supplementary material, which is available to authorized users.