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.

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.

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.

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.

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.

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.

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.

Movement pattern and parameter learning in children: effects of feedback frequency.

Reduced feedback during practice has been shown to be detrimental to movement accuracy in children but not in young adults. We hypothesized that the reduced accuracy is attributable to reduced movement parameter learning but not pattern learning in children. A rapid arm movement task that required the acquisition of a motorpattern scaled to specific spatial and temporal parameters was used to investigate the effects of feedback (FB) frequency (100% vs. 62% faded) on motor learning differences between 19 school-age children and 19 young adults. Adults and children practiced the task for 200 trials under the 100% or faded FB condition on day 1 and returned on day 2 for a no-FB retention test. On the retention test, children who practiced with reduced feedback performed with greater temporal parameter errors, but not pattern error than children who received frequent feedback. Motor skill learning in children is influenced byfeedback frequency during practice that affects parameter learning but not pattern learning.

Transfer of motor learning engages specific neural substrates during motor memory consolidation dependent on the practice structure.

The authors investigated how brain activity during motor-memory consolidation contributes to transfer of learning to novel versions of a motor skill following distinct practice structures. They used 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) immediately after constant or variable practice of an arm movement skill to interfere with primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC). The effect of interference was assessed through skill performance on two transfer targets: one within and one outside the range of practiced movement parameters for the variable practice group. For the control (no rTMS) group, variable practice benefited delayed transfer performance more than constant practice. The rTMS effect on delayed transfer performance differed for the two transfer targets. For the within-range target, rTMS interference had no significant affect on the delayed transfer after either practice structure. However, for the outside-range target, rTMS interference to DLPFC but not M1 attenuated delayed transfer benefit following variable practice. Additionally, for the outside-range target, rTMS interference to M1 but not DLPFC attenuated delayed transfer following constant practice. This suggests that variable practice may promote reliance on DLPFC for memory consolidation associated with outside-range transfer of learning, whereas constant practice may promote reliance on M1 for consolidation and long-term transfer.

Model of disablement and recovery: knowledge translation in rehabilitation research and practice.

Disablement is a multifactorial and complex process that creates a challenge for both the rehabilitation researcher and the clinical practitioner; however, each seeks to improve quality health outcomes for the adult or child with disability. Knowledge translation (KT) is an approach to evidence-based medicine where various evidence sources are aggregated so that clinical decisions regarding intervention selection and dosing result in beneficial care for an individual. Structural equation modeling was used to test a theoretical model of disablement based on the impairment, activity, and participation categories of the International Classification of Functioning, Disability and Health (ICF) level of functioning. Using available cohort data from a randomized controlled trial of people with poststroke walking disability, exploratory and confirmatory factor analysis revealed that the latent variables-impairment and activity-are separate disablement constructs that limit participation for a person with disability. Path analysis revealed that the direct effect of impairment on participation was not statistically significant; however, the indirect path from impairment to participation through activity was significant (indirect effect). The direct effect of activity on participation was significant. Model assumptions were tested with postintervention data from the same cohort. For people with disability after stroke, the probability that functional tasks could be performed with less effort was greater for those individuals who met or exceeded a physiologic walking threshold after a structured, progressive intervention provided by a physical therapist 6 months earlier. This article discusses how structural equation modeling can be used as a statistical method to explore the causal paths from disability to ability. The knowledge inquiry and synthesis phases of the knowledge-to-action KT framework parallel the essential elements of structural equation modeling; knowledge is created that is theoretically driven, supported by prior research, and analyzed, refined, validated, and tailored to address real-world problems. Using a theoretical framework of disablement with clinical judgment and quantitative research methods, a clinically intuitive model of disablement was validated. The positive dimension is a model of recovery where causal paths lead from disablement to ablement. Innovative approaches in rehabilitation research design along with pragmatic application of research to practice are needed to improve today's health outcomes for people with disability.

Secondary mediation and regression analyses of the PTClinResNet database: determining causal relationships among the International Classification of Functioning, Disability and Health levels for four physical therapy intervention trials.

BACKGROUND: Each of the 4 randomized clinical trials (RCTs) hosted by the Physical Therapy Clinical Research Network (PTClinResNet) targeted a different disability group (low back disorder in the Muscle-Specific Strength Training Effectiveness After Lumbar Microdiskectomy [MUSSEL] trial, chronic spinal cord injury in the Strengthening and Optimal Movements for Painful Shoulders in Chronic Spinal Cord Injury [STOMPS] trial, adult stroke in the Strength Training Effectiveness Post-Stroke [STEPS] trial, and pediatric cerebral palsy in the Pediatric Endurance and Limb Strengthening [PEDALS] trial for children with spastic diplegic cerebral palsy) and tested the effectiveness of a muscle-specific or functional activity-based intervention on primary outcomes that captured pain (STOMPS, MUSSEL) or locomotor function (STEPS, PEDALS). OBJECTIVE: The focus of these secondary analyses was to determine causal relationships among outcomes across levels of the International Classification of Functioning, Disability and Health (ICF) framework for the 4 RCTs. METHOD AND DESIGN: With the database from PTClinResNet, we used 2 separate secondary statistical approaches-mediation analysis for the MUSSEL and STOMPS trials and regression analysis for the STEPS and PEDALS trials-to test relationships among muscle performance, primary outcomes (pain related and locomotor related), activity and participation measures, and overall quality of life. RESULTS: Predictive models were stronger for the 2 studies with pain-related primary outcomes. Change in muscle performance mediated or predicted reductions in pain for the MUSSEL and STOMPS trials and, to some extent, walking speed for the STEPS trial. Changes in primary outcome variables were significantly related to changes in activity and participation variables for all 4 trials. Improvement in activity and participation outcomes mediated or predicted increases in overall quality of life for the 3 trials with adult populations. LIMITATIONS: Variables included in the statistical models were limited to those measured in the 4 RCTs. It is possible that other variables also mediated or predicted the changes in outcomes. The relatively small sample size in the PEDALS trial limited statistical power for those analyses. CONCLUSIONS: Evaluating the mediators or predictors of change between each ICF level and for 2 fundamentally different outcome variables (pain versus walking) provided insights into the complexities inherent across 4 prevalent disability groups.

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.).

Survival after resection for metastatic testicular nonseminomatous germ cell cancer to the lung or mediastinum.

BACKGROUND: Since the advent of cisplatin-based chemotherapy, nonseminomatous germ cell tumors (NSGCT) have been considered one of the most curable solid neoplasms and a model for multimodality cancer therapy. We undertook an institutional review of testicular NSGCT patients who underwent operations to remove lung or mediastinal metastases after chemotherapy in the cisplatin era to determine outcomes. METHODS: From 1980 to 2006, 431 patients underwent 640 postchemotherapy surgical procedures to remove lung (n = 159, 36.8%), mediastinal (n = 136, 31.6%), or both lung and mediastinal (n = 136, 31.6%) metastases within 2 years of chemotherapy. Multiple variables potentially predictive of survival were analyzed. RESULTS: The overall median survival was 23.4 years, with 295 (68%) patients alive and well after an average follow-up of 5.6 years. There was no survival difference in patients who underwent removal of lung or mediastinal metastases. Pathologic categories of resected residual disease were necrosis (21.5%), teratoma (52.7%), persistent NSGCT (15.0%), and degenerative non-germ cell cancer (10.1%). Multivariable analysis identified older age at time of diagnosis (p = 0.001), non-germ cell cancer in testes specimen (p = 0.004), and pathology of residual disease (p < 0.001) as significantly predictive of survival. CONCLUSIONS: Patients who undergo resection of residual lung or mediastinal disease for metastatic testicular NSGCT as a planned approach after cisplatin-based chemotherapy have overall excellent long-term survival. Survival is equivalent comparing hematogenous and lymphatic routes of metastases but depends on the pathology of the resected disease. These results justify an aggressive surgical approach, particularly to remove residual teratoma in the lung or mediastinum after chemotherapy, including multiple surgical procedures if necessary.

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.

Neural substrates of motor memory consolidation depend on practice structure.

Motor-skill practice drives subsequent offline activity in functionally related resting human brain networks. We investigated the manner in which offline neural networks are modulated by practice structures that affect motor-skill retention. Interference to dorsolateral-prefrontal cortex (DLPFC), but not to primary motor cortex (M1), after variable practice attenuated motor-skill retention, whereas interference to M1, but not to DLPFC, after constant practice attenuated motor-skill retention. We conclude that neural substrates of motor-memory consolidation are modulated by practice structure.