Effects of a Feedback-Demanding Stroke Clock on Acute Stroke Management: A Randomized Study.

BACKGROUND AND PURPOSE: This randomized study aimed to evaluate whether the use of a stroke clock demanding active feedback from the stroke physician accelerates acute stroke management. METHODS: For this randomized controlled study, a large-display alarm clock was installed in the computed tomography room, where admission, diagnostic work-up, and intravenous thrombolysis occurred. Alarms were set at the following target times after admission: (1) 15 minutes (neurological examination completed); (2) 25 minutes (computed tomography scanning and international normalized ratio determination by point-of-care laboratory completed); and (3) 30 minutes (intravenous thrombolysis started). The responsible stroke physician had to actively provide feedback by pressing a buzzer button. The alarm could be avoided by pressing the button before time out. Times to therapy decision (primary end point, defined as the end of all diagnostic work-up required for decision for or against recanalizing treatment), neurological examination, imaging, point-of-care laboratory, needle, and groin puncture were assessed by a neutral observer. Functional outcome (modified Rankin Scale) was assessed at day 90. RESULTS: Of 107 participants, 51 stroke clock patients exhibited better stroke-management metrics than 56 control patients. Times from door to (1) end of all indicated diagnostic work-up (treatment decision time; 16.73 versus 26.00 minutes, P<0.001), (2) end of neurological examination (7.28 versus 10.00 minutes, P<0.001), (3) end of computed tomography (11.17 versus 14.00 minutes, P=0.002), (4) end of computed tomography angiography (14.00 versus 17.17 minutes, P=0.001), (5) end of point-of-care laboratory testing (12.14 versus 20.00 minutes, P<0.001), and (6) needle times (18.83 versus 47.00 minutes, P=0.016) were improved. In contrast, door-to-groin puncture times and functional outcomes at day 90 were not significantly different. CONCLUSIONS: This study showed that the use of a stroke clock demanding active feedback significantly improves acute stroke-management metrics and, thus, represents a potential low-cost strategy for streamlining time-sensitive stroke treatment.

Genome-wide linkage analysis of families with primary hyperhidrosis.

Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0-6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH.