Validity and Usability of a Professional Association’s Web-Based Knowledge Translation Portal: American Physical Therapy Association’s PTNow.org

Background: PTNow.org is an evidence-based, on-line portal created by a professional membership association to promote use of evidence in practice and to help decrease unwarranted variation in practice. The site contains synthesis documents designed to promote efficient clinical reasoning. These documents were written and peer-reviewed by teams of content experts and master clinicians. The purpose of this paper is to report on the content and construct validity as well as usability of the site. Methods: Physical therapist participants used clinical summaries (available in 3 formats--as a full summary with hyperlinks, quick takes with hyperlinks, and a portable two-page version) on the PTNow.org site to answer knowledge acquisition and clinical reasoning questions related to four patient scenarios. They also responded to questions about ease of use related to website navigation and about format and completeness of information using a 1-5 Likert scale. Responses were coded to reflect how participants used the site and then were summarized descriptively. Preferences for clinical summary format were analyzed using an analysis of variance (ANOVA) and a Dunnett T3 post hoc analysis. Results: Seventeen participants completed the study. Clinical relevance and completeness ratings by experienced clinicians, which were used as the measure of content validity, ranged from 3.1 to 4.6 on a 5 point scale. Construct validity based on the information on the PTNow.org site was supported for knowledge acquisition questions 66 % of the time and for clinical reasoning questions 40 % of the time. Usability ratings for the full clinical summary were 4.6 (1.2); for the quick takes, 3.5 (.98); and for the portable clinical summary, 4.0 (.45). Participants preferred the full clinical summary over the other two formats (F = 5.908, P = 0.007). One hundred percent of the participants stated that they would recommend the PTNow site to their colleagues. Conclusion: Prelimary evidence supported both content validity and construct validity of knowledge acquisition, and partially supported construct validity of clinical reasoning for the clinical summaries on the PTNow.org site. Usability was supported, with users preferring the full clinical summary over the other two formats. Iterative design is ongoing

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Exploring Neuromuscular Electrical Stimulation Intensity Effects on Multifidus Muscle Activity in Adults With Chronic Low Back Pain: An Ultrasound Imaging–Informed Investigation

Study design: Cross-sectional study. Background: Neuromuscular electrical stimulation (NMES) is an effective tool for stimulating multifidus muscle contractions. Ultrasound imaging (USI) is valid and reliable for quantifying multifidus activity represented by percent thickness change from a resting to contracted state. Thus, USI may be used to help determine optimal NMES intensity. Objectives: To explore NMES intensity effects on multifidus thickening in adults with chronic low back pain (CLBP). Methods: Sixty patients with CLBP participated. L4/5 multifidus ultrasound images were obtained and percent thickness change from a resting to a contracted state was determined at baseline with a limb lift and during NMES application. During NMES, the examiner recorded the intensity, in milliampere, when the multifidus first started to thicken as observed with USI. The examiner also recorded the NMES intensity that resulted in no further multifidus thickening (ie, high-tolerance group) or, in cases where maximal thickening was not observed, the NMES intensity of the submaximal contraction (ie, low-tolerance group). Differences between participants with high versus low NMES tolerance were evaluated. Results: During NMES, the multifidus began thickening at a higher intensity for the high-tolerance group (n = 39), that is, 34 mA, compared with the low-tolerance group (n = 21), that is, 32 mA ( P  = .001). A greater mean intensity in the high-tolerance group, that is, 62 mA, as compared to 45 mA in the low-tolerance group, resulted in a larger percent thickness change, that is, 30.89% compared to 20.60%, respectively ( P  < .001). Conclusions: Results provide clinicians with NMES intensity targets to facilitate multifidus muscle thickening, which provides insight into muscle activity