An Analysis of Changes in Emergency Department Visits After a State Declaration During the Time of COVID-19.

STUDY OBJECTIVE: In the initial period of the coronavirus disease 2019 (COVID-19) pandemic, there has been a substantial decrease in the number of patients seeking care in the emergency department. A first step in estimating the impact of these changes is to characterize the patients, visits, and diagnoses for whom care is being delayed or deferred. METHODS: We conducted an observational study, examining demographics, visit characteristics, and diagnoses for all ED patient visits to an urban level 1 trauma center before and after a state emergency declaration and comparing them with a similar period in 2019. We estimated percent change on the basis of the ratios of before and after periods with respect to 2019 and the decline per week using Poisson regression. Finally, we evaluated whether each factor modified the change in overall ED visits. RESULTS: After the state declaration, there was a 49.3% decline in ED visits overall, 35.2% (95% confidence interval -38.4 to -31.9) as compared with 2019. Disproportionate declines were seen in visits by pediatric and older patients, women, and Medicare recipients, as well as for presentations of syncope, cerebrovascular accidents, urolithiasis, and abdominal and back pain. Significant proportional increases were seen in ED visits for upper respiratory infections, shortness of breath, and chest pain. CONCLUSION: There have been significant changes in patterns of care seeking during the COVID-19 pandemic. Declines in ED visits, especially for certain demographic groups and disease processes, should prompt efforts to understand these phenomena, encourage appropriate care seeking, and monitor for the morbidity and mortality that may result from delayed or deferred care.

Feasibility Trial of a 10-Week Adaptive.

BACKGROUND: This study assessed the feasibility of implementing a yoga intervention adapted for participants diagnosed with chronic pain in a large Midwest neuroscience pain clinic. Although conducted using a small convenience sample, this was a novel program in that it was led by an advanced practice nurse certified in pain management and to teach yoga. She was therefore uniquely qualified to tailor the yoga practice to suit individual needs of study participants. DESIGN: The intervention consisted of a weekly 1-hour class for 10 weeks. Feasibility measures included patient recruitment, program adherence, patient satisfaction, global impression of change, and likelihood of continuing yoga practice. In addition, it was hypothesized that the program would positively affect participants' pain interference, physical function, pain intensity, pain behavior, mood, sleep, and pain medication usage. METHODS: Survey measurements were conducted 10 weeks before class start, immediately before the first class, and immediately after the last class. CONCLUSIONS: Although there is a strong body of research supporting the benefits of yoga for chronic pain conditions, our experience highlights some of the challenges of implementing an adaptive yoga program. Our study found that recruitment of patient through physician referral was highly feasible; however, retention rates for participants were very low. Program adherence is a barrier for research on yoga in chronic pain, as well as for clinical practice. A slight reduction in pain interference and physical function over time and trend toward improvement in all exploratory outcomes was identified. None of these trends were statistically significant, likely because of small sample size.

Screening Positive for Cognitive Impairment: Impact on Healthcare Utilization and Provider Action in Primary and Specialty Care Practices.

BACKGROUND: Alzheimer's disease, the most common cause of dementia, goes unrecognized in half of patients presenting to healthcare providers and is associated with increased acute care utilization. Routine cognitive screening of older adults in healthcare settings could improve rates of dementia diagnosis and patterns of healthcare utilization. OBJECTIVE: To evaluate the impact of screening positive for cognitive impairment on provider action in primary and specialty care practices and patient healthcare utilization. DESIGN: Individuals asymptomatic for cognitive impairment completed cognitive screening with the Mini-Cog (MC). Outcomes included MC screen-positive rates, provider follow-up actions, and healthcare utilization for all participants over a period of 36 months (18 months prior to and following MC screening). Data were extracted from the electronic medical record (EMR). Healthcare provider interventions and healthcare utilization for screen-positive and -negative groups, before and after screening, were compared. PARTICIPANTS: Primary and specialty care patients (n = 787) aged ≥ 65 without history of cognitive impairment seen in HealthPartners, an integrated healthcare system in Minnesota and Western Wisconsin. KEY RESULTS: In primary care and neurology practices combined, over the entire 36-month study window, individuals screening positive showed 32% higher rates of ED visits (p < 0.05) pre and post-screening compared to those screening negative. Screen positive also showed 39% higher rates of hospitalizations pre-screening (p < 0.05) and 58% higher rates post-screening (p < 0.01). While screen-detected cognitive impairment was associated with some relevant provider follow-up action in 32% of individuals, subsequent healthcare utilization did not change between the 18-month pre- and post-screening periods. CONCLUSION: Despite being associated with higher rates of healthcare utilization, screening positive on the MC led to a change in provider action in a minority of cases and did not reduce post-screening healthcare utilization. Screening for cognitive impairment alone is not sufficient to alter patterns of provider practice or patient healthcare utilization.

Selection of Normative Group Affects Rates of Mild Cognitive Impairment in Parkinson's Disease.

OBJECTIVE: The objective of this study was to examine the impact of different methods of standardizing cognitive data in the Parkinson's Progression Marker Initiative. METHODS: Cognitive data from 423 participants with Parkinson's disease were included (age = 61.7 [9.7], education = 15.6 [3.0]). Internal norms were calculated using the group mean and standard deviation of the healthy control group. Published norms were compared to the overall group mean of and to age-stratified norms from healthy controls for each neuropsychological test over 4 visits. Rates of mild cognitive impairment were calculated using established criteria. RESULTS: The use of internal norms resulted in lower standardized scores than published norms on all tests with the exception of memory and processing speed (P ≤ .001). Individuals were 1.5 to 2.1 times more likely to be diagnosed with mild cognitive impairment using internal norms than published norms. CONCLUSIONS: Standardization approaches with cognitive data are not interchangeable. Selection of a normative comparison group impacts research and clinical interpretations of cognitive data. © 2018 International Parkinson and Movement Disorder Society.

Neuropsychological Test Performance in Parkinsonism Without Dopaminergic Deficiency on [123I]-FP-CIT SPECT Imaging.

OBJECTIVES: To examine neuropsychological test performance among individuals clinically diagnosed with Parkinson's disease (PD) without evidence of dopaminergic deficiency on [123]I-CIT single photon emission computed tomography imaging. METHODS: Data were obtained from the Parkinson's Progression Marker Initiative. The sample included 59 participants with scans without evidence of dopaminergic deficiency (SWEDD), 412 with PD, and 114 healthy controls (HC). Tests included Judgment of Line Orientation, Letter-Number Sequencing, Symbol Digit Modalities, Hopkins Verbal Learning Test-Revised, and Letter and Category Fluency. Multivariate analysis of variance was used to compare standardized scores between the groups. RESULTS: There was a statistically significant difference in performances between the groups, F(14,1155)=5.04; p<.001; partial η2=.058. Pairwise comparisons revealed significant differences in Category Fluency between SWEDD (M=0.22; SD=1.08) and HC (M=0.86; SD=1.15) and in Symbol Digit Modalities Test performance between SWEDD (M=45.09; SD=11.54) and HC (M=51.75; SD=9.79). No significant differences between SWEDD and PD were found. Using established criteria, approximately one in four participants in the SWEDD and PD groups met criteria for mild cognitive impairment (MCI). CONCLUSIONS: Individuals with SWEDD demonstrate significantly worse mental processing speed and semantic fluency than HC. The neuropsychological test performances and rates of MCI were similar between the SWEDD group and PD groups, which may reflect a common pathology outside of the nigrostriatal pathway. (JINS, 2018, 24, 646-651).

Acceptability, Adaptation, and Clinical Outcomes of Acupuncture Provided in the Emergency Department: A Retrospective Pilot Study.

Objective: To evaluate acceptability and clinical outcomes of acupuncture on patient-reported pain and anxiety in an emergency department (ED). Design: Observational, retrospective pilot study. Setting: Abbott Northwestern Hospital ED, Minneapolis, MN. Methods: Retrospective data was used to identify patients receiving acupuncture in addition to standard medical care in the ED between 11/1/13 and 12/31/14. Feasibility was measured by quantifying the utilization of acupuncture in a novel setting and performing limited tests of its efficacy. Patient-reported pain and anxiety scores were collected by the acupuncturist using an 11-point (0-10) numeric rating scale before (pre) and immediately after (post) acupuncture. Efficacy outcomes were change in pain and anxiety scores. Results: During the study period, 436 patients were referred for acupuncture, 279 of whom were approached by the acupuncturist during their ED visit. Consent for acupuncture was obtained from 89% (248/279). A total of 182 patients, who had a pre-pain score >0 and non-missing anxiety scores, were included in analyses. Of the 52% (94/182) who did not have analgesics before or during the acupuncture session, the average decrease of 2.37 points (95% CI: 1.92, 2.83) was not different (p > 0.05) than the mean decrease of 2.68 points for those receiving analgesics (95% CI 2.21, 3.15). The average pre-anxiety score was 4.73 points (SD = 3.43) and the mean decrease was 2.27 points (95% CI: 1.89, 2.66). Conclusions: Results from this observational trial indicate that acupuncture was acceptable and effective for pain and anxiety reduction, in conjunction with standard medical care. These results will inform future randomized trials.

Influence of Neck Laceration Protectors on Cervical Range of Motion.

OBJECTIVE: To examine the effect of a hockey neck laceration protector (NLP) on cervical range of motion (ROM) along with the athlete's perception on comfort and restrictiveness. Our hypothesis was that all styles of NLPs would limit cervical ROM compared to no NLP, and that certain designs of NLPs would be perceived as more restrictive and less comfortable. DESIGN: Cross-sectional observational analytic. SETTING: Outpatient sports medicine clinic. PARTICIPANTS: Forty-six male and female high school hockey players (age 14-18). INDEPENDENT VARIABLES: Four commercially available NLPs and no NLP. MAIN OUTCOME MEASURES: Cervical ROM and participant feedback regarding restrictiveness and comfort. RESULTS: ROM values while wearing any of the NLPs were significantly less than no NLP for all cervical motion measurements (P < 0.05) with the exception of the Bauer Premium NLP for left rotation (P = 0.792). Significant differences were found between the 4 NLPs in terms of perceived restrictiveness and comfort (P < 0.05). CONCLUSIONS: NLPs may reduce the risk of a neck laceration, but appear to have a negative impact on cervical ROM. This study challenges manufactures to design NLPs that cover vulnerable neck anatomy but do not limit a player's ROM. NLP designs that are most comfortable and least restrictive are recommended.

Incidence of Treatment for Infection of Buried Versus Exposed Kirschner Wires in Phalangeal, Metacarpal, and Distal Radial Fractures.

PURPOSE: To determine whether there is a difference in the incidence of infection between exposed and buried K-wires when used to treat phalangeal, metacarpal, and distal radius fractures. METHODS: We conducted a retrospective review identifying all patients aged greater than 16 years who underwent fixation of phalangeal, metacarpal, or distal radius fractures with K-wires between 2007 and 2015. We recorded patient demographic data, fracture location, number of K-wires used, whether K-wires were buried or left exposed, and duration of K-wire placement. RESULTS: A total of 695 patients met inclusion criteria. Surgeons buried K-wires in 207 patients and left K-wires exposed in 488. Infections occurred more frequently in exposed K-wire cases than in buried K-wire ones. Subgroup analysis based on fracture location revealed a significantly increased risk of being treated for infection when exposed K-wires were used for metacarpal fractures. CONCLUSIONS: Patients with exposed K-wires for fixation of phalangeal, metacarpal, or distal radius fractures were more likely to be treated for a pin-site infection than those with K-wires buried beneath the skin. Metacarpal fractures treated with exposed K-wires were 2 times more likely to be treated for a pin-site infection (17.6% of exposed K wire cases vs 8.7% of buried K wire cases). TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The Effectiveness of Message Framing and Temporal Context on College Student Alcohol Use and Problems: A Selective E-Mail Intervention.

AIMS: Only one study has examined message framing on college drinking, but did so in a laboratory setting among a general sample of college students. The current study was designed to: (a) compare the efficacy of emailed interventions differing by message framing and temporal context on alcohol involvement among heavy drinking college students and (b) examine need for cognition (NFC), consideration of future consequences (CFC) and self-efficacy as putative moderators. METHODS: Hazardous drinking college students (N = 220) were randomly assigned to conditions in a 2 (Frame: gain vs. loss) × 2 (Temporal Context: long-term vs. short-term consequences) factorial design. Participants received four emails on heavy drinking consequences phrased in a manner consistent with their condition. After each message, participants were given a manipulation check. Participants were sent a 1-month follow-up assessment. Primary outcome measures were heavy episodic drinking (HED) and alcohol-related problems. We hypothesized two main effects (less alcohol consumption in the gain-frame and short-term condition), qualified by a Frame × Temporal Context interaction with substantially less alcohol involvement in the gain-frame/short-term condition. RESULTS: There was very little study attrition (96.4% completed follow-up survey, 93.2-99.5% completed manipulation checks), and strong effects were observed for the manipulations. A 2 × 2 ANCOVA, controlling for baseline alcohol involvement, revealed no consistent main effects or interactions on either outcome. No moderation was observed for any putative moderator. CONCLUSIONS: These results do not replicate prior laboratory-based research. The null findings may be attributed to the heavy drinking sample or electronic means of message delivery.

Relationship between sperm apoptosis and bull fertility: in vivo and in vitro studies.

The objectives of this study were to confirm the relationship of apoptosis-associated membrane and nuclear changes in bull spermatozoa with field fertility, to predict the fertility of beef bulls used for natural breeding and to study the role of DNA-nicked spermatozoa in early embryonic development. In Experiment 1, the relationship between fertility and different sperm populations identified by the Annexin V/propidium iodide (PI) and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assays was determined. Bull fertility was related to live (PPPin vitro cleavage and blastocyst rates was evaluated, using 30000 or 300000 spermatozoa per droplet. Cleavage rate was adversely affected (PP<0.05) in high DNA-nicked spermatozoa at the lower sperm concentration. In conclusion, the incidence of DNA-nicked spermatozoa is a useful marker to predict a bull's fertility potential. DNA-nicked spermatozoa showed adverse effects on early embryonic development.

The Efficacy of Blood Flow Restriction Training to Improve Quadriceps Muscle Function after ACL Reconstruction.

BACKGROUND: Blood flow restriction training (BFRT) is a popular rehabilitation intervention after anterior cruciate ligament reconstruction (ACLR). However, there are a lack of clinical trials establishing the efficacy of using BFRT during rehabilitation to improve quadriceps muscle function. PURPOSE: To evaluate the efficacy of blood flow restriction training to improve quadriceps muscle strength, morphology, and physiology, and knee biomechanics in individuals after ACLR in a double-blind, randomized, placebo-controlled clinical trial (NCT03364647). METHODS: 48 athletes (20 females/28 males) were randomly assigned to low-load strength training with active BFRT or standard of care strength training with a sham unit. Treatment occurred for 1-month pre-surgery and 4-5 months post-surgery with both groups following the same standard rehabilitation protocol. Outcome variables were measured at baseline and 4-5 months post-surgery. Quadriceps muscle strength (isometric and isokinetic peak torque and rate of torque development) was measured on an isokinetic dynamometer. Quadriceps muscle morphology (physiological cross-sectional area, fibrosis) was determined using magnetic resonance imaging. Quadriceps muscle physiology (fiber type, fiber cross-sectional area, satellite cell abundance, collagen content, fibro-/adipo-genic progenitor cells) was evaluated with muscle biopsies of the vastus lateralis. Knee extensor moment and knee flexion angle were measured via three-dimensional gait analysis. Change scores were calculated as: post-intervention-baseline. Two sample t-tests were then used to assess between-group differences for each outcome variable. RESULTS: No significant between-group differences were found for any outcome variable. CONCLUSIONS: The addition of BFRT to a rehabilitation program for athletes pre- and post- ACLR was no more effective than standard rehabilitation for improving quadriceps muscle function. Clinicians should consider the value of BFRT relative to the cost, time, and discomfort for patients in light of these results.

Incidence of Loss of Reduction After Open Reduction Internal Fixation of Metacarpal Shaft Fractures.

BACKGROUND: This study compared the incidence of loss of reduction (LOR) between metacarpal fractures fixed with screws alone and those fixed with plates and screws. Secondary aims included identifying patient or fracture characteristics associated with increased risk of LOR. METHODS: We retrospectively reviewed 138 metacarpal fractures in 106 patients treated with open reduction internal fixation with screws (60 fractures) or plates and screws (78 fractures) with a mean radiographic follow-up of 50 days for evidence of LOR. We compared the incidence of LOR between the screw and plate groups using a χ2 test. We performed logistic regression analysis to determine whether patient age, sex, metacarpal location (index, long, ring, small), the presence of multiple metacarpal fractures, or fracture pattern were associated with increased incidence of LOR. RESULTS: Loss of reduction occurred in 19 (13.8%) of 138 fractures, with no statistically significant difference between lag screw (7 of 60, 11.6%) and plate fixation (12 of 78, 15.4%). Neither fracture pattern nor the presence of multiple metacarpal fractures was associated with an increased incidence of LOR, but patients experienced a 7% increase in the risk of LOR for each additional year of age. Loss of reduction occurred most frequently in index metacarpal fractures (4 of 12, 33%), although this did not reach statistical significance. CONCLUSIONS: We found no difference in LOR incidence between lag screw fixation and plate fixation. The overall incidence of LOR was higher in this study than previously reported and increased with increasing patient age.

Psychosocial factors 3-months after anterior cruciate ligament reconstruction predict 6-month subjective and objective knee outcomes.

The objective of the study was to determine if psychological readiness for sport and knee self-efficacy assessed early (3 months) after anterior cruciate ligament reconstruction (ACLR) are predictive of self-reported functional outcomes, quadriceps strength, and knee mechanics while running at the time of return to sport training (6 months). Thirty athletes with unilateral ACLR completed the ACL Return to Sport after Injury (ACL-RSI) and Knee Self-Efficacy Scale (K-SES) 3 months after ACLR and completed self-reported functional outcomes, isometric quadriceps strength testing, and three-dimensional running gait analysis 6 months after ACLR. The 3-month ACL-RSI significantly correlated with the 6-month International Knee Documentation Committee (IKDC; r = 0.565, p = 0.001), Knee Injury and Osteoarthritis Outcome Score (KOOS) sport/recreational activities (KOOSSport ; r = 0.548, p = 0.002) and quality of life (KOOSQoL ; r = 0.431, p = 0.017), and quadriceps strength (r = 0.528, p = 0.003). The 3-month K-SES significantly correlated with the 6-month IKDC (r = 0.528, p = 0.003), KOOSSport (r = 0.430, p = 0.018), KOOSQoL (r = 0.411, p = 0.024), quadriceps strength (r = 0.465, p = 0.010), and knee flexion excursion (r = 0.472, p = 0.008). With multivariate modeling, both the ACL-RSI and K-SES were predictive of the IKDC (R2 = 0.411; p = 0.001). Only the ACL-RSI was predictive of the KOOSSport (R2 = 0.300; p = 0.002), KOOSQoL (R2 = 0.186; p = 0.017), and quadriceps strength (R2 = 0.279; p = 0.003), whereas only the K-SES was predictive of knee flexion excursion (R2 = 0.173; p = 0.022). Athletes with greater psychological readiness for sport and knee self-efficacy at 3 months demonstrated higher scores on self-reported functional outcomes, greater quadriceps strength, and greater knee flexion excursion at 6 months after ACLR. This study indicates that psychosocial measures may be important to include into early post-surgical evaluations to help guide and facilitate interventions to restore subjective and objective knee function.

Assessing effect heterogeneity of a randomized treatment using conditional inference trees.

Treatment effect heterogeneity occurs when individual characteristics influence the effect of a treatment. We propose a novel approach that combines prognostic score matching and conditional inference trees to characterize effect heterogeneity of a randomized binary treatment. One key feature that distinguishes our method from alternative approaches is that it controls the Type I error rate, that is, the probability of identifying effect heterogeneity if none exists and retains the underlying subgroups. This feature makes our technique particularly appealing in the context of clinical trials, where there may be significant costs associated with erroneously declaring that effects differ across population subgroups. Treatment effect heterogeneity trees are able to identify heterogeneous subgroups, characterize the relevant subgroups and estimate the associated treatment effects. We demonstrate the efficacy of the proposed method using a comprehensive simulation study and illustrate our method using a nutrition trial dataset to evaluate effect heterogeneity within a patient population.

Neuropsychological Test Performances and Depression in Early-Stage De Novo Parkinson's Disease.

OBJECTIVE: Evaluate neuropsychological test performance in depressed patients with early-stage Parkinson's disease. METHOD: Data from 422 participants from the Parkinson's Progression Marker Initiative were examined. The Geriatric Depression Scale-15 was used to categorize depressed and non-depressed participants. Neuropsychological tests measured verbal learning/memory, processing speed, visuospatial ability, verbal fluency, and working memory. Demographic and clinical variables were compared using independent samples t tests and chi-square analyses.Linear regression models were fit to adjust for age, years of education, and symptom duration. RESULTS: The non-depressed group (n = 280) was significantly older; t(246.08) = 2.25, p = .026 and had higher education; t(420) = 2.35, p = .019; and longer duration of PD symptoms; t(170.58) = -2.13, p = .035 than the depressed group (n = 142). The non-depressed group performed better on a working memory task than the depressed group, t(420) = 2.05, p = .041, but the results did not appear to be of clinical significance. There was no significant difference between other cognitive domains. The results were not influenced by age, education, or disease duration. CONCLUSIONS: Among patients with early-stage, untreated Parkinson's disease, depression does not appear to affect neuropsychological test performance. Clinicians should demonstrate caution in over-interpreting the influence of depression on cognition in this population.

Development of standardized regression-based formulas to assess meaningful cognitive change in early Parkinson's disease.

OBJECTIVE: Longitudinal assessment of cognitive and emotional functioning in patients with Parkinson's disease (PD) is helpful in tracking progression of the disease, developing treatment plans, evaluating outcomes, and educating patients and families. Determining whether change over time is meaningful in neurodegenerative conditions, such as PD, can be difficult as repeat assessment of neuropsychological functioning is impacted by factors outside of cognitive change. Regression-based prediction formulas are one method by which clinicians and researchers can determine whether an observed change is meaningful. The purpose of the current study was to develop and validate regression-based prediction models of cognitive and emotional test scores for participants with early-stage idiopathic PD and healthy controls (HC) enrolled in the Parkinson's Progression Markers Initiative (PPMI). METHODS: Participants with de novo PD and HC were identified retrospectively from the PPMI archival database. Data from baseline testing and 12-month follow-up were utilized in this study. In total, 688 total participants were included in the present study (NPD = 508; NHC = 185). Subjects from both groups were randomly divided into development (70%) and validation (30%) subsets. RESULTS: Early-stage idiopathic PD patients and healthy controls were similar at baseline. Regression-based models were developed for all cognitive and self-report mood measures within both populations. Within the validation subset, the predicted and observed cognitive test scores did not significantly differ, except for semantic fluency. CONCLUSIONS: The prediction models can serve as useful tools for researchers and clinicians to study clinically meaningful cognitive and mood change over time in PD.

Comparison of Volar and Dorsal Approach for PIP Arthroplasty.

Background: No consensus exists about whether a volar approach (VA) or dorsal approach (DA) for proximal interphalangeal (PIP) arthroplasty yields better results. Previously reported range of motion (ROM) and complications vary from study to study. This retrospective review compared the ROM and complication rates of VA and DA approaches to PIP arthroplasty. Methods: The study included 66 adults (88 digits) who underwent PIP arthroplasty from 2000 to 2015, with minimum 30-day follow-up. Demographic data, surgical approach, pre- and post-operative ROM, duration of immobilization, timing and duration of hand therapy (occupational therapy [OT]), and major and minor complications were recorded. We compared mean change in ROM, postoperative ROM, and complication rates, and examined the association of duration of immobilization and time to OT initiation with postoperative ROM. Results: While there was no difference in postoperative ROM between volar and dorsal groups (56° and 54°, respectively, P > .05), there was a greater gain in ROM in the DA group (25° vs 2.7°, P = .017). There was no statistically significant difference in overall incidence of complications (VA: 37.8%, DA: 30.3%; P > .05) or revision surgery (VA: 15.6%, DA: 17.1%; P > .05). There were no differences in duration of immobilization, time to OT initiation, or number of OT sessions between the two groups, and none of these correlated with postoperative ROM. Conclusions: We identified no statistical difference in mean postoperative ROM, incidence of complications or revision surgery between volar and dorsal approaches for PIP arthroplasty.

Double-Blind Placebo-Controlled Pilot Investigation of the Safety of a Single Dose of Rapid-Acting Intranasal Insulin in Down Syndrome.

BACKGROUND: Individuals with Down syndrome are likely to develop clinical and neuropathological brain changes resembling Alzheimer's disease dementia by the ages of 35-40 years. Intranasal insulin is a potential treatment for neurodegenerative disease that has been shown to reduce amyloid plaque burden and improve verbal memory performance in normal as well as memory-impaired adults. Investigations have shown that rapid-acting insulins may result in superior cognitive benefits compared with regular insulin. OBJECTIVES: The primary objective of this study was to measure the safety and feasibility of intranasal rapid-acting glulisine in subjects with Down syndrome. Secondarily, we estimated the effects of intranasal glulisine on cognition and memory in Down syndrome. METHODS: A single-center, single-dose, randomized, double-blind, placebo-controlled, cross-over pilot study was performed to test the safety of intranasal glulisine vs placebo in 12 subjects with Down syndrome aged ≥ 35 years. Intranasal administration utilized the Impel NeuroPharma I109 Precision Olfactory Delivery (POD®) device. The primary outcomes were the occurrence of any or related adverse and serious adverse events. Secondary post-treatment cognitive outcome measures included performance on the Fuld Object-Memory Evaluation and Rivermead Behavioral Memory Test. RESULTS: Intranasal glulisine was safe and well tolerated in the Down syndrome population. No adverse or serious adverse events were observed. CONCLUSIONS: Further investigations are necessary to better evaluate the potential cognitive-enhancing role of intranasal insulin in the Down syndrome population. CLINICALTRIALS. GOV ID: NCT02432716.

Quality Improvement in Parkinson's Disease: A Successful Program to Enhance Timely Administration of Levodopa in the Hospital.

BACKGROUND: Patients hospitalized with Parkinson's disease (PD) require timely delivery of carbidopa-levodopa (C/L) medication. Ill-timed administration of C/L doses is associated with greater morbidity and longer lengths of stay. OBJECTIVE: To understand the barriers to timely C/L administration, and implement strategies to improve the administration of the drug to hospitalized PD patients. METHODS: Several key strategies were employed in 2015 to improve the timely delivery of C/L doses: 1. three kinds of nursing alert in the electronic medical record (EMR); 2. staff in-service education; 3. stocking immediate-release C/L into automated medication dispensing machines on key hospital units; 4. reports to nurse unit managers on timeliness of C/L administration; and 5. reconciliation of inpatient and outpatient levodopa orders by the hospital pharmacist upon admission. The primary outcome was the percent of C/L doses administered within 60, 30, and 15 minutes of scheduled time. RESULTS: Our urban hospital, affiliated with a Parkinson's Foundation Center of Excellence, had 5,939 C/L administrations in 2018. There was sustained improvement in timely delivery of doses, from 89.3% in 2012 to 96.5% in 2018 (within 60 minutes of the scheduled time), 65.5% to 86.4% (30 minutes), and 42.3% to 71.1% (15 minutes) (all p < 0.001). CONCLUSIONS: With multifaceted but relatively simple measures, we were able to "change the culture" so that hospitalized patients with Parkinson's disease receive levodopa on time.

Effect of Blood Flow Restriction Training on Quadriceps Muscle Strength, Morphology, Physiology, and Knee Biomechanics Before and After Anterior Cruciate Ligament Reconstruction: Protocol for a Randomized Clinical Trial.

BACKGROUND: Despite best practice, quadriceps strength deficits often persist for years after anterior cruciate ligament reconstruction. Blood flow restriction training (BFRT) is a possible new intervention that applies a pressurized cuff to the proximal thigh that partially occludes blood flow as the patient exercises, which enables patients to train at reduced loads. This training is believed to result in the same benefits as if the patients were training under high loads. OBJECTIVE: The objective is to evaluate the effect of BFRT on quadriceps strength and knee biomechanics and to identify the potential mechanism(s) of action of BFRT at the cellular and morphological levels of the quadriceps. DESIGN: This will be a randomized, double-blind, placebo-controlled clinical trial. SETTING: The study will take place at the University of Kentucky and University of Texas Medical Branch. PARTICIPANTS: Sixty participants between the ages of 15 to 40 years with an ACL tear will be included. INTERVENTION: Participants will be randomly assigned to (1) physical therapy plus active BFRT (BFRT group) or (2) physical therapy plus placebo BFRT (standard of care group). Presurgical BFRT will involve sessions 3 times per week for 4 weeks, and postsurgical BFRT will involve sessions 3 times per week for 4 to 5 months. MEASUREMENTS: The primary outcome measure was quadriceps strength (peak quadriceps torque, rate of torque development). Secondary outcome measures included knee biomechanics (knee extensor moment, knee flexion excursion, knee flexion angle), quadriceps muscle morphology (physiological cross-sectional area, fibrosis), and quadriceps muscle physiology (muscle fiber type, muscle fiber size, muscle pennation angle, satellite cell proliferation, fibrogenic/adipogenic progenitor cells, extracellular matrix composition). LIMITATIONS: Therapists will not be blinded. CONCLUSIONS: The results of this study may contribute to an improved targeted treatment for the protracted quadriceps strength loss associated with anterior cruciate ligament injury and reconstruction.