Willingness to participate in a randomized trial comparing catheters to fistulas for vascular access in incident hemodialysis patients: an international survey of nephrologists

BACKGROUND: Current guidelines favor fistulas over catheters as vascular access. Yet, the observational literature comparing fistulas to catheters has important limitations and biases that may be difficult to overcome in the absence of randomization. However, it is not clear if physicians would be willing to participate in a clinical trial comparing fistulas to catheters. OBJECTIVES: We also sought to elicit participants' opinions on willingness to participate in a future trial regarding catheters and fistulas. DESIGN: We created a three-part survey consisting of 19 questions. We collected demographic information, respondents' knowledge of the vascular access literature, appropriateness of current guideline recommendations, and their willingness to participate in a future trial. SETTING: Participants were recruited from Canada, Europe, Australia, and New Zealand. PARTICIPANTS: Participants include physicians and trainees who are involved in the care of end-stage renal disease patients requiring vascular access. MEASUREMENTS: Descriptive statistics were used to describe baseline characteristics of respondents according to geographic location. We used logistic regression to model willingness to participate in a future trial. METHODS: We surveyed nephrologists from Canada, Europe, Australia, and New Zealand to assess their willingness to participate in a randomized trial comparing fistulas to catheters in incident hemodialysis patients. RESULTS: Our results show that in Canada, 86 % of respondents were willing to participate in a trial (32 % in all patients; 54 % only in patients at high risk of primary failure). In Europe and Australia/New Zealand, the willingness to participate in a trial that included all patients was lower (28 % in Europe; 25 % in Australia/New Zealand), as was a trial that included patients at high risk of primary failure (38 % in Europe; 39 % in Australia/New Zealand). Nephrologists who have been in practice for a few years, saw a larger volume of patients, or self-identified as experts in vascular access literature were more likely to participate in a trial. LIMITATIONS: Survey distribution was limited to vascular access experts in participating European countries and ultimately led to a discrepancy in numbers of European to non-European respondents overall. Canadian views are likely over-represented in the overall outcomes. CONCLUSIONS: Our survey results suggest that nephrologists believe there is equipoise surrounding the optimal vascular access strategy and that a randomized controlled study should be undertaken, but restricted to those individuals with a high risk of primary fistula failure

Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations.

CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype. We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations. Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism. We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome

Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations

International audiencePurpose:CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.Methods:We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.Results:Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.Conclusion:We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome