Creating an ignorance-base: Exploring known unknowns in the scientific literature.

BACKGROUND: Scientific discovery progresses by exploring new and uncharted territory. More specifically, it advances by a process of transforming unknown unknowns first into known unknowns, and then into knowns. Over the last few decades, researchers have developed many knowledge bases to capture and connect the knowns, which has enabled topic exploration and contextualization of experimental results. But recognizing the unknowns is also critical for finding the most pertinent questions and their answers. Prior work on known unknowns has sought to understand them, annotate them, and automate their identification. However, no knowledge-bases yet exist to capture these unknowns, and little work has focused on how scientists might use them to trace a given topic or experimental result in search of open questions and new avenues for exploration. We show here that a knowledge base of unknowns can be connected to ontologically grounded biomedical knowledge to accelerate research in the field of prenatal nutrition. RESULTS: We present the first ignorance-base, a knowledge-base created by combining classifiers to recognize ignorance statements (statements of missing or incomplete knowledge that imply a goal for knowledge) and biomedical concepts over the prenatal nutrition literature. This knowledge-base places biomedical concepts mentioned in the literature in context with the ignorance statements authors have made about them. Using our system, researchers interested in the topic of vitamin D and prenatal health were able to uncover three new avenues for exploration (immune system, respiratory system, and brain development) by searching for concepts enriched in ignorance statements. These were buried among the many standard enriched concepts. Additionally, we used the ignorance-base to enrich concepts connected to a gene list associated with vitamin D and spontaneous preterm birth and found an emerging topic of study (brain development) in an implied field (neuroscience). The researchers could look to the field of neuroscience for potential answers to the ignorance statements. CONCLUSION: Our goal is to help students, researchers, funders, and publishers better understand the state of our collective scientific ignorance (known unknowns) in order to help accelerate research through the continued illumination of and focus on the known unknowns and their respective goals for scientific knowledge.

Body-weight-supported treadmill rehabilitation after stroke.

BACKGROUND: Locomotor training, including the use of body-weight support in treadmill stepping, is a physical therapy intervention used to improve recovery of the ability to walk after stroke. The effectiveness and appropriate timing of this intervention have not been established. METHODS: We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment--moderate (able to walk 0.4 to <0.8 m per second) or severe (able to walk <0.4 m per second)--and randomly assigned them to one of three training groups. One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred (early locomotor training), the second group received this training 6 months after the stroke had occurred (late locomotor training), and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke (home-exercise program). Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks. The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke. RESULTS: At 1 year, 52.0% of all participants had increased functional walking ability. No significant differences in improvement were found between early locomotor training and home exercise (adjusted odds ratio for the primary outcome, 0.83; 95% confidence interval [CI], 0.50 to 1.39) or between late locomotor training and home exercise (adjusted odds ratio, 1.19; 95% CI, 0.72 to 1.99). All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life. Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year. Ten related serious adverse events were reported (occurring in 2.2% of participants undergoing early locomotor training, 3.5% of those undergoing late locomotor training, and 1.6% of those engaging in home exercise). As compared with the home-exercise group, each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment (P=0.008). Among patients with severe walking impairment, multiple falls were more common in the group receiving early locomotor training than in the other two groups (P=0.02). CONCLUSIONS: Locomotor training, including the use of body-weight support in stepping on a treadmill, was not shown to be superior to progressive exercise at home managed by a physical therapist. (Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research; LEAPS ClinicalTrials.gov number, NCT00243919.).

Motor learning in children with hemiplegic cerebral palsy: feedback effects on skill acquisition.

AIM: Motor learning is enhanced with practice and feedback. This cohort control study investigated the effect of different relative feedback frequencies during skill acquisition in children with cerebral palsy (CP) and children with typical development. METHOD: Nineteen children with spastic hemiplegic CP (nine males, 10 females; mean age 11 y 7 mo; range 8-16 y) and 20 children with typical development (12 males, eight females; mean age 10 y 8 mo; range 8-14 y) were assigned to 100% or reduced (62%) feedback subgroups as they practised 200 trials of a discrete arm movement with specific spatiotemporal parameters. Children with CP used their less involved hand. Learning was inferred by delayed (24 h) retention and reacquisition tests. RESULTS: All children improved in accuracy and consistency. Children with typical development demonstrated significantly greater accuracy than children with CP during acquisition (p=0.001), retention (p=0.031), and reacquisition (p=0.001), and greater consistency during retention (p=0.038). The typically developing group who received 100% feedback performed with significantly less error than the 62% feedback group during acquisition (p=0.001), and with greater retention (p=0.017). No statistically significant difference was found between feedback subgroups of children with CP, although the 100% feedback group consistently demonstrated less error. INTERPRETATION: Children with CP use feedback in a manner similar to children with typical development when learning new skills with their less involved hand, but demonstrate less accuracy and consistency.

Impact of Statewide Statute Limiting Days' Supply to Opioid-Naive Patients.

INTRODUCTION: To address the ongoing opioid crisis, states use policy enactment to restrict prescribing by licensed healthcare providers and mandate the use of Prescription Drug Monitoring Programs. There have been mixed results regarding the effectiveness of such state policies. The purpose of this study is to evaluate the impact of Colorado Senate Bill 18-022, which limits opioid prescriptions to ≤7-day supply among patients without an opioid prescription in the previous year (i.e., are opioid naive). METHODS: This is a retrospective interrupted time-series analysis of opioid prescribing to evaluate the weekly percentage of opioid prescriptions consistent with statutory limits for ≤7-day supply among opioid-naive patients before and after enactment using Prescription Drug Monitoring Programs data from May 21, 2017 to May 25, 2019. Statistical analysis was performed in 2021-2022. RESULTS: The weekly percentage of opioid prescriptions ≤7-day supply increased by an average of 0.12% per week (p<0.0001) from 79.7% to 87.4% in the week before enactment. The week after enactment, the average increased by 0.2% (p=0.67). The year after enactment, the average weekly percentage change was 0.07% per week, a 0.05% decrease (p=0.01). CONCLUSIONS: Statutory limits on days' supply among opioid-naive patients had little impact on opioid prescribing in Colorado. Legislating limits on opioid prescribing should be evaluated using Prescription Drug Monitoring Program data and considered for deimplementation when not impactful.

Dual-task practice enhances motor learning: a preliminary investigation.

Practicing a motor task under dual-task conditions can be beneficial to motor learning when the secondary task is difficult (Roche et al. in Percept Psychophys 69(4):513-522, 2007) or when it engages similar processes as the primary motor task (Hemond et al. in J Neurosci 30(2):650-654, 2010). The purpose of this pilot study was to determine which factor, difficulty level or engaged processes, of a secondary task is more critical in determining dual-task benefit. Participants practiced a discrete arm task in conjunction with an audio-vocal reaction time (RT) task. We presented two different RT tasks that differed in difficulty, simple versus choice (i.e., more difficult), at two different arm task phases that differed in engaged processes, preparation versus execution, resulting in four dual-task conditions. A simple RT task is thought to predominantly engage motor execution processes, therefore would engage similar processes as the arm movement task when it is presented during the execution phase, while a choice RT task is thought to engage planning processes and therefore would engage similar processes too when it is presented during the preparation phase. Enhanced motor learning was found in those who engaged similar process as the primary task during dual-tasking (i.e., choice RT presented during preparation and simple RT presented during execution). Moreover, those who showed enhanced learning also demonstrated high dual-task cost (poor RT task performance) during practice, indicating that both tasks were taxing the same resource pool possibly due to engaging similar cognitive processes. To further test the relation between dual-task cost and enhanced learning, we delayed the presentation timing of the choice RT task during the preparation phase and the simple RT task during the execution phase in two control experiments. Dual-task cost was reduced in these delayed timing conditions, and the enhanced learning effect was attenuated. Together, our preliminary findings suggest that it is the similarity hypothesis and not the difficulty hypothesis that mediates the enhanced motor learning under dual-task conditions.

Fugl-Meyer assessment of sensorimotor function after stroke: standardized training procedure for clinical practice and clinical trials.

BACKGROUND AND PURPOSE: Outcome measurement fidelity within and between sites of multi-site, randomized, clinical trials is an essential element to meaningful trial outcomes. As important are the methods developed for randomized, clinical trials that can have practical utility for clinical practice. A standardized measurement method and rater training program were developed for the total Fugl-Meyer motor and sensory assessments; inter-rater reliability was used to test program effectiveness. METHODS: Fifteen individuals with hemiparetic stroke, 17 trained physical therapists across 5 regional clinical sites, and an expert rater participated in an inter-rater reliability study of the Fugl-Meyer motor (total, upper extremity, and lower extremity subscores) and sensory (total, light touch, and proprioception subscores) assessments. RESULTS: Intra-rater reliability for the expert rater was high for the motor and sensory scores (range, 0.95-1.0). Inter-rater agreement (intraclass correlation coefficient, 2, 1) between expert and therapist raters was high for the motor scores (total, 0.98; upper extremity, 0.99; lower extremity, 0.91) and sensory scores (total, 0.93; light touch, 0.87; proprioception, 0.96). CONCLUSIONS: Standardized measurement methods and training of therapist assessors for a multi-site, rehabilitation, randomized, clinical trial resulted in high inter-rater reliability for the Fugl-Meyer motor and sensory assessments. Poststroke sensorimotor impairment severity can be reliably assessed for clinical practice or rehabilitation research with these methods.

Characterization of Anonymous Physician Perspectives on COVID-19 Using Social Media Data.

Physicians' beliefs and attitudes about COVID-19 are important to ascertain because of their central role in providing care to patients during the pandemic. Identifying topics and sentiments discussed by physicians and other healthcare workers can lead to identification of gaps relating to theCOVID-19 pandemic response within the healthcare system. To better understand physicians' perspectives on the COVID-19 response, we extracted Twitter data from a specific user group that allows physicians to stay anonymous while expressing their perspectives about the COVID-19 pandemic. All tweets were in English. We measured most frequent bigrams and trigrams, compared sentiment analysis methods, and compared our findings to a larger Twitter dataset containing general COVID-19 related discourse. We found significant differences between the two datasets for specific topical phrases. No statistically significant difference was found in sentiments between the two datasets, and both trended slightly more positive than negative. Upon comparison to manual sentiment analysis, it was determined that these sentiment analysis methods should be improved to accurately capture sentiments of anonymous physician data. Anonymous physician social media data is a unique source of information that provides important insights into COVID-19 perspectives.

A pilot study of quality of life in children with cerebral palsy after intensive body weight-supported treadmill training.

PURPOSE: This pilot study was designed to examine the effects of a 2-week program of intensive body weight-supported treadmill training (BWSTT) on clinical measures of perceived health-related quality of life and fatigue in children with cerebral palsy. METHODS: Six children with spastic cerebral palsy (aged 6-14 years; all classified as Gross Motor Function Classification System Level I) received two 30-minute sessions of BWSTT daily for 2 weeks, and completed questionnaires preintervention and postintervention. RESULTS: Ratings by children and their parents who completed the Pediatric Quality of Life Inventory and Multidisciplinary Fatigue module resulted in nonsignificant higher mean postscores. However, of the children with complete data, 4 showed minimal clinically important differences by child and parent-proxy report. CONCLUSIONS: Results suggest that positive health-related quality of life changes can be identified after an intensive intervention of BWSTT, and should include ratings from both children and parents.

Application of evidence-based practice strategies: current trends in walking recovery interventions poststroke.

Persons with impaired walking ability poststroke rely on rehabilitation specialists to provide the best available interventions that will maximize walking recovery and, ultimately, improve their community mobility and quality of life. Evidence-based practice (EBP) is a process in which the rehabilitation clinician integrates the "best" research evidence, clinical expertise, and patient circumstances, values, and preferences to provide the most appropriate interventions to address patient expectations and goals. Studies show that clinicians value EBP but are challenged by limited time, skills, and resources to successfully implement it in real-world practice. This article describes a five-step EBP framework and directs clinicians to free online resources designed to improve their ability to become evidence-based practitioners. The framework and tools are illustrated by answering three searchable clinical questions about interventions for walking recovery poststroke. Recommendations for walking recovery interventions poststroke are provided for aerobic conditioning, treadmill training with body weight support, and use of ankle-foot orthoses with and without functional electrical stimulation. To provide added insight related to individual patient application and intervention effectiveness, studies included are appraised to investigate the influence of patient chronicity (i.e., time poststroke), walking impairment severity, and intervention dose on walking outcomes and community mobility.

Survey of Nonprescription Medication and Antibiotic Use in Patients with Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Overlap Syndrome.

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and overlap syndrome (SJS-TEN) are rare, serious skin and mucosa break-down conditions frequently associated with antibiotic use. The role of nonprescription medications alone, or in combination with antibiotics in triggering SJS/TEN, is largely unknown. This study summarized data collected from patient surveys about nonprescription and antibiotic use prior to a SJS/TEN diagnosis. The survey was administered online to members of the U.S. SJS Foundation who had been diagnosed with SJS/TEN or were the parent of a child who had been diagnosed with SJS/TEN. Respondents were asked about nonprescription medications taken within the year before diagnosis, and the approximate point in time before diagnosis that they had taken them. They were also asked about specific prescription medications, including antibiotics, that they took before diagnosis. An estimated 4500 patients received an invitation to complete the survey. 251 patients completed it, resulting in a response rate of 5.6%. The mean age of respondents was 43 years (SD (standard deviation) = 17.3) and 70% were female. 32.3% of respondents indicated that a prescription antibiotic triggered their reaction. 14.1% indicated a nonprescription medication had triggered their SJS/TEN, and 18.1% said a nonprescription medication may have triggered their SJS/TEN. 85.5% of respondents said they took a nonprescription medication within three months of their SJS/TEN diagnosis. Of those respondents who reported that an antibiotic triggered their SJS/TEN, 35.2% reported taking a nonprescription medication within the three months prior to their diagnosis. This survey captured valuable information about nonprescription and antibiotic use in SJS/TEN patients. It is important for future studies to estimate the impact of antibiotics on SJS/TEN, and account for nonprescription medication use in that relationship.

Protocol for the Locomotor Experience Applied Post-stroke (LEAPS) trial: a randomized controlled trial.

BACKGROUND: Locomotor training using body weight support and a treadmill as a therapeutic modality for rehabilitation of walking post-stroke is being rapidly adopted into clinical practice. There is an urgent need for a well-designed trial to determine the effectiveness of this intervention. The objective of the Locomotor Experience Applied Post-Stroke (LEAPS) trial is to determine if there is a difference in the proportion of participants who recover walking ability at one year post-stroke when randomized to a specialized locomotor training program (LTP), conducted at 2- or 6-months post-stroke, or those randomized to a home based non-specific, low intensity exercise intervention (HEP) provided 2 months post-stroke. We will determine if the timing of LTP delivery affects gait speed at 1 year and whether initial impairment severity interacts with the timing of LTP. The effect of number of treatment sessions will be determined by changes in gait speed taken pre-treatment and post-12, -24, and -36 sessions. METHODS/DESIGN: We will recruit 400 adults with moderate or severe walking limitations within 30 days of stroke onset. At two months post stroke, participants are stratified by locomotor impairment severity as determined by overground walking speed and randomly assigned to one of three groups: (a) LTP-Early; (b) LTP-Late or (c) Home Exercise Program -Early. The LTP program includes body weight support on a treadmill and overground training. The LTP and HEP interventions are delivered for 36 sessions over 12 weeks. Primary outcome measure include successful walking recovery defined as the achievement of a 0.4 m/s gait speed or greater by persons with initial severe gait impairment or the achievement of a 0.8 m/s gait speed or greater by persons with initial moderate gait impairment.LEAPS is powered to detect a 20% difference in the proportion of participants achieving successful locomotor recovery between the LTP groups and the HEP group, and a 0.1 m/s mean difference in gait speed change between the two LTP groups. DISCUSSION: The goal of this single-blinded, phase III randomized clinical trial is to provide evidence to guide post-stroke walking recovery programs. TRIAL REGISTRATION: NCT00243919.

Effect of task practice order on motor skill learning in adults with Parkinson disease: a pilot study.

BACKGROUND AND PURPOSE: Random practice of motor tasks has been shown to enhance motor learning. The purpose of this study was to investigate the effects of task practice order (random, blocked) on motor learning in adults with Parkinson disease (PD). SUBJECTS: Twenty adults with mild PD and 20 age-matched adults (controls) participated in the study. METHODS: Participants in both groups (PD and control) practiced 3 movement tasks with either a blocked or a random practice order. This 2 participant group x 2 practice order design resulted in 4 experimental groups. The Trail Making Test was administered to all participants to determine task-switching capability. Motor performance on the arm movement tasks was quantified on the basis of the root-mean-square error difference between the goal movement task and each participant's response. RESULTS: The task-switching capability of the control group was superior to that of the PD group. For acquisition, in general, participants in the control group performed with significantly less error than participants in the PD group. For retention, participants in the control group who practiced with a random order performed more accurately than participants in the control group who practiced with a blocked order. However, for the PD group, the findings were reversed; participants who practiced with a blocked order performed more accurately than participants who practiced with a random order. These findings resulted in a group x practice order interaction. DISCUSSION AND CONCLUSION: These pilot study data suggest that, contrary to the findings for age-matched control learners, for learners with mild PD, a blocked practice order may be better than a random practice order for motor learning.

Effects of task-specific locomotor and strength training in adults who were ambulatory after stroke: results of the STEPS randomized clinical trial.

BACKGROUND AND PURPOSE: A phase II, single-blinded, randomized clinical trial was conducted to determine the effects of combined task-specific and lower-extremity (LE) strength training to improve walking ability after stroke. SUBJECTS: The participants were 80 adults who were ambulatory 4 months to 5 years after a unilateral stroke. METHOD: The exercise interventions consisted of body-weight-supported treadmill training (BWSTT), limb-loaded resistive leg cycling (CYCLE), LE muscle-specific progressive-resistive exercise (LE-EX), and upper-extremity ergometry (UE-EX). After baseline assessments, participants were randomly assigned to a combined exercise program that included an exercise pair. The exercise pairs were: BWSTT/UE-EX, CYCLE/UE-EX, BWSTT/CYCLE, and BWSTT/LE-EX. Exercise sessions were 4 times per week for 6 weeks (total of 24 sessions), with exercise type completed on alternate days. OUTCOMES: were self-selected walking speed, fast walking speed, and 6-minute walk distance measured before and after intervention and at a 6-month follow-up. RESULTS: The BWSTT/UE-EX group had significantly greater walking speed increases compared with the CYCLE/UE-EX group; both groups improved in distance walked. All BWSTT groups increased walking speed and distance whether BWSTT was combined with LE strength training or not. DISCUSSION AND CONCLUSION: After chronic stroke, task-specific training during treadmill walking with body-weight support is more effective in improving walking speed and maintaining these gains at 6 months than resisted leg cycling alone. Consistent with the overtraining literature, LE strength training alternated daily with BWSTT walking did not provide an added benefit to walking outcomes.

Effects of acupuncture treatment on poststroke motor recovery and physical function: a pilot study.

This pilot study obtained preliminary data on the effects of acupuncture treatment combined with a standard inpatient stroke rehabilitation program on poststroke motor recovery and physical function. Thirty-two patients with acute stroke were recruited and randomized to 1 of 2 treatment arms: standard rehabilitation (control group) or a combination of acupuncture and standard rehabilitation (acupuncture group). Baseline and discharge assessments were obtained on motor recovery as measured by the Fugl-Meyer (FM) Assessment and on physical function as measured by the Functional Independence Measure (FIM). Comparisons were made between the acupuncture and control group in total FM and FIM as well as for each subscale of the FM and FIM. No differences between treatment groups were found in the total FM or the total FIM. However, statistically significant benefit due to acupuncture was observed for the FM lower extremity motor function subscale (P = 0.01) and the tub/shower transfer mobility subscale of the FIM (P = 0.03). Marginally significant benefit due to acupuncture was noted for the toilet transfer mobility subscale of the FIM (P = 0.09). The effectiveness of acupuncture as an adjunct to standard poststroke rehabilitation programs may be demonstrated when more specific measures of stroke motor recovery and physical function are used.

Evaluation of attentional demands during motor learning: validity of a dual-task probe paradigm.

The aim of this study was to examine the validity of a 2-choice audio-vocal reaction time (RT) probe task for measuring the changes in attentional demand during practice and learning of a discrete motor task. Twenty participants practiced the motor task across 3 days and were probed with the RT task during either the preparation or execution phase of the primary task. As practice progressed, participants improved in the primary task performance and shortened the RTs to the probe task. This indicated that less attention was required to plan and execute the movement and suggested that the RT probe task was a sensitive and valid tool to measure changes in attentional demands across practice. The authors implemented several additional experimental controls to address possible confounders including unintentional learning of the probe task, primary-secondary task trade-off effects, and compliance with task priority instructions. These experimental controls further ensured the validity of the probe paradigm and interpretability of the dual-task cost findings. Our experimental methods provided confirmatory evidence for the validity of the 2-choice RT task as a means to assess attentional demands during motor learning.