A Canadian Adult Spinal Muscular Atrophy Outcome Measures Toolkit: Results of a National Consensus using a Modified Delphi Method.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a rare disease that affects 1 in 11 000 live births. Recent developments in SMA treatments have included new disease-modifying therapies that require high quality data to inform decisions around initiation and continuation of therapy. In Canada, there are no nationally agreed upon outcome measures (OM) used in adult SMA. Standardization of OM is essential to obtain high quality data that is comparable among neuromuscular clinics. OBJECTIVE: To develop a recommended toolkit and timing of OM for assessment of adults with SMA. METHODS: A modified delphi method consisting of 2 virtual voting rounds followed by a virtual conference was utilized with a panel of expert clinicians treating adult SMA across Canada. RESULTS: A consensus-derived toolkit of 8 OM was developed across three domains of function, with an additional 3 optional measures. Optimal assessment frequency is 12 months for most patients regardless of therapeutic access, while patients in their first year of receiving disease-modifying therapy should be assessed more frequently. CONCLUSIONS: The implementation of the consensus-derived OM toolkit will improve monitoring and assessment of adult SMA patients, and enrich the quality of real-world evidence. Regular updates to the toolkit must be considered as new evidence becomes available.

Canadian perspectives on the clinical actionability of neuroimaging in disorders of consciousness.

BACKGROUND: Acquired brain injury is a critical public health and socioeconomic problem in Canada, leaving many patients in vegetative, minimally conscious, or locked-in states, unresponsive and unable to communicate. Recent advances in neuroimaging research have demonstrated residual consciousness in a few exemplary patients with acquired brain injury, suggesting potential misdiagnosis and changes in prognosis. Such progress, in parallel with research using multimodal brain imaging technologies in recent years, has promising implications for clinical translation, notwithstanding the many challenges that impact health care and policy development. This study explored the perspectives of Canadian professionals with expertise either in neuroimaging research, disorders of consciousness, or both, on the potential clinical applications and implications of imaging technology. METHODS: Twenty-two professionals from designated communities of neuroimaging researchers, ethicists, lawyers, and practitioners participated in semistructured interviews. Data were analyzed for emergent themes. RESULTS: The five most dominant themes were: (1) validation and calibration of the methods; (2) informed consent; (3) burdens on the health care system; (4) implications for the Canadian health care system; and (5) possibilities for improved prognosis. CONCLUSIONS: Movement of neuroimaging from research into clinical care for acquired brain injury will require careful consideration of legal and ethical issues alongside research reliability, responsible distribution of health care resources, and the interaction of technological capabilities with patient outcome.

Hematological changes associated with egg production: direct evidence for changes in erythropoiesis but a lack of resource dependence?

Reductions in hematological parameters among laying birds are well reported, but the cause of this anemia is not known. We tested specific predictions generated from several, non-mutually exclusive hypotheses for mechanisms underlying reproductive anemia associated with egg production (hemodilution, transient suppression of erythropoiesis, resource dependence) in relation to (1) the time-course of development and recovery from anemia, (2) changes in specific hematological traits, and (3) the effect of diet quality, in female zebra finches (Taeniopygia guttata). Female zebra finches showed marked decreases in hematocrit (approximately 6%), red blood cell counts ( approximately 8%), and plasma hemoglobin concentration (approximately 9%) during egg production, even on a high-quality ad libitum diet, consistent with an effect of hemodilution associated with yolk precursor production. However, our results provide strong support for the hypothesis that erythropoiesis is transiently suppressed during egg-laying and that the recovery from anemia is relatively long-lasting, extending through incubation and hatching periods. Decreased hematocrit, red blood cell counts, and hemoglobin concentration did not recover at clutch completion, but showed evidence of recovery to baseline pre-breeding levels at hatching. More importantly, there was significant time-dependent variation in the proportion of reticulocytes, which increased at clutch completion but peaked at hatching 10-12 days after clutch completion, and in mean red blood cell volume, which showed a significant increase at clutch completion; consistent with enhanced production and release of larger immature cells into the circulation following suppression of erythropoiesis. Finally, we found no evidence for resource dependence of anemia associated with egg production in relation to diet quality, i.e. exogenous lipid and protein resources available to the laying female. This study demonstrates that transient suppression of erythropoiesis and, subsequently, increased reticulocytosis, are key components of reproductive anemia in egg-laying females.

Adrenocortical responses in zebra finches (Taeniopygia guttata): individual variation, repeatability, and relationship to phenotypic quality.

Although individual variation is a key requirement for natural selection, little is known about the magnitude and patterns of individual variation in endocrine systems or the functional significance of that variation. Here we describe (1) the extent and repeatability of inter-individual variation in adrenocortical responses and (2) its relationship to sex-specific phenotypic quality, such as song duration and frequency and timing of egg laying. We measured adrenocortical responses to a standardized stressor in zebra finches (Taeniopygia guttata) at two life history stages: approximately day 16 (nestlings) and 3 months of age (sexually mature adults). Subsequently, we assessed phenotypic (reproductive) quality of all individuals as adults. Marked inter-individual variation in the adrenocortical response was seen in both sexes and ages, e.g., stress-induced corticosterone ranged from 2.2 to 62.5 ng/mL in nestlings and 5.0-64.0 ng/mL in adults. We found sex differences in (a) inter-individual variation in the adrenocortical response, (b) repeatability, and (c) relationships between corticosterone levels and phenotypic quality. In males, variation in nestling corticosterone was weakly but positively correlated with brood size and negatively correlated with nestling mass (though this relationship was dependent on one individual). There was no significant correlation of adrenocortical responses between two stages in males and adult phenotypic quality was significantly correlated only with adult corticosterone levels. In contrast, in females there was no relationship between nestling corticosterone and brood size or mass but adrenocortical response was repeatable between two stages (r2=0.413). Phenotypic quality of adult females was correlated with nestling baseline and adrenocortical response.