Tracking Emergence of New Motor and Non-Motor Symptoms Using the MDS-UPDRS: A Novel Outcome Measure for Early Parkinson's Disease?

BACKGROUND: Summary scores of current clinical rating scales do not appear sensitive enough to quantify changes in disease progression in early Parkinson's disease (PD) clinical trials. An alternate approach might be to track the appearance of new or emergent symptoms (ES) over time as a measure of disease progression. OBJECTIVE: Explore the potential utility of patient reported ES as an outcome measure during the early phase of PD. METHODS: We analyzed data from the MDS-UPDRS Parts IB (non-motor) and II (motor) Experiences of Daily Living scales over two years in the STEADY-PD3 study. We assessed the number of ES reported in each part of the scale in both participants who started symptomatic treatment and those who did not (STx-yes/no) in two periods: between 0 and 12-months (Year 1), and 13 and 24-months (Year 2). RESULTS: Of 331 participants, 87% developed ES, and 55% started STx in Year 1. The median number of Part IB ES did not significantly differ between STx groups, but ES in Part II were significantly more frequent in the STx-yes group. Of 148 participants who remained STx-no into Year 2, 77% developed ES, and 42% started STx. Again, Part II, but not Part IB ES were more frequent the STx-yes group. Using these results, a sample size of ∼90 per group would be required to detect a 30% reduction in combined Part IB and II ES over 12 months. CONCLUSION: Assessing ES of patient-reported experiences of daily living may provide a useful marker for tracking PD progression.

Minding the Gap in Vertebroplasty: Vertebral Body Fracture Clefts and Cement Nonunion.

BACKGROUND: Vertebroplasty and kyphoplasty are leading treatments for patients with vertebral body compression fractures. Although cement augmentation has been shown to help relieve pain and instability from fractures containing a cleft, there is some controversy in the literature regarding the procedure's efficacy in these cases. Additionally, some of the literature blurs the distinction between clefts and cement patterns (including cement nonunion and cement fill pattern). Both clefts and cement patterns have been mentioned in the literature as risks for poorer outcomes following cement augmentation, which can result in complications such as cement migration. OBJECTIVES: This study aims to identify the prevalence of fracture clefts and cement nonunion, the relationship between them as well as to cement fill pattern, and their association with demographics and other variables related to technique and outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Interventional radiology department at a single site university hospital. METHODS: This retrospective cohort study assessed 295 vertebroplasties/kyphoplasties performed at the University of Colorado Hospital from 2008 to 2018. Vertebral fracture cleft and cement nonunion were the main variables of interest. Presence and characterization of a fracture cleft was determined on pre-procedural imaging, defined as an air or fluid filled cavity within the fractured vertebral body on magnetic resonance or computed tomography. Cement nonunion was evaluated on post-procedural imaging, defined as air or fluid surrounding the cement bolus on magnetic resonance or computed tomography or imaging evidence of cement migration. Cement fill pattern was assessed on procedural and/or post-procedural imaging. Pain improvement scores were based on a visual analog score immediately prior to the procedure and during clinical visits in the short-term follow-up period. Additional patient demographics, medical history, and procedure details were obtained from electronic medical chart review. RESULTS: Pre-procedural vertebral fracture clefts were demonstrated in 29.8% of our cases. Increasing age, secondary osteoporosis, and thoracolumbar junction location were associated with increased odds of clefts. There was no significant difference in pain improvement outcomes in patients following cement augmentation between clefted and non-clefted compression fractures. Clefts, especially large clefts, and cleft-only fill pattern were associated with increased odds of cement nonunion. Procedure techniques (vertebroplasty, curette, and balloon kyphoplasty) demonstrated similar proportion of cement nonunion and distribution of cement fill pattern. LIMITATIONS: Cement nonunion was observed in only 6.8% of cases. Due to this low proportion, statistical inference tends to have low power. Multiple levels were treated in nearly half of the study's patients undergoing a single vertebroplasty/kyphoplasty session; in these cases, each level was treated as independent rather than spatially correlated within the same study patient. CONCLUSIONS: Vertebral body fracture clefts are not uncommon and are related to (but distinct from) cement nonunion and cement fill patterns. Our study shows that, although patients with clefts will benefit from cement augmentation just as much as patients without a cleft, the performing provider should take note of cement fill and take extra steps to ensure optimal cement fill. These providers should also identify cement nonunion and associated complications (such as cement migration) on follow-up imaging.

The Effect of Operational Stressors on Emergency Department Clinician Scheduling and Patient Throughput.

STUDY OBJECTIVE: We assess the effect of emergency department (ED) operational stressors on clinician scheduling and throughput. METHODS: We evaluated 2014 to 2018 data from a national ED group. Operational stressors included measures of workload, patient acuity, and complexity. We used multilevel linear regression to estimate the effect of operational stressors, temporal factors, and facility characteristics on ED clinician scheduling; patient throughput, measured as shift-level patient departures per corrected clinician hour; and length of stay. RESULTS: In greater than 14 million ED visits across 359 facility-years, the mean of patient departures per corrected clinician hour was 2.23 (95% confidence interval [CI] 2.15 to 2.31). Temporal and facility effects had the greatest influence on patient departures per hour (eg, -0.55 [95% CI -0.75 to -0.36] in 7 am to 3 pm shifts versus midnight to 7 am on Mondays, 0.25 [95% CI 0.03 to 0.47]) in teaching versus nonteaching hospitals, and 0.43 (95% CI 0.24 to 0.61) in larger EDs (30,000 to 59,999 ED visits/year) versus smaller EDs. Operational stressors had significant but small effects on patient departures per hour (eg, length of stay [per-minute increase] 0.002 [95% CI 0.0019 to 0.0023] and percentage admitted [per 1% increase] -0.003 [95% CI -0.004 to -0.001]). Weekday nights, particularly Mondays, had the highest proportion of shifts with increasing length of stay compared with previous years in the same ED. CONCLUSION: ED operational stressors had minimal influence on patient throughput when included in adjusted ED clinician scheduling models, whereas temporal and facility factors were more influential. Therefore, incorporating operational stressors into ED clinician scheduling is less likely to balance workloads than accounting for temporal and facility-level factors alone. Length of stay on some shifts, particularly Monday nights, became increasingly long, suggesting they require additional resources.

Emergency Physician Practice Changes After Being Named in a Malpractice Claim.

STUDY OBJECTIVE: Malpractice fear is a commonly cited cause for defensive medicine, but it is unclear whether being named in a malpractice claim changes physician practice patterns. We study whether there are changes in commonly used measures of emergency physician practice after being named in a malpractice claim. METHODS: We performed a retrospective difference-in-differences study comparing practice patterns of emergency physicians named in a malpractice claim and unnamed matched controls working contemporaneously in the same emergency departments (EDs), using data from a national emergency medicine management group (59 EDs in 11 US states from 2010 to 2015). We studied aggregate measures of care intensity (hospital admission rate and relative value units/visit), studied care speed (relative value units/hour and discharged patients' length of stay), and assessed patient experience (monthly physician Press Ganey percentile rank). RESULTS: A total of 65 emergency physicians named in at least 1 malpractice claim and 140 matched controls met inclusion criteria. After the malpractice claim filing date, there were no significant changes in measures of care intensity or speed. However, named emergency physicians' patient experience scores improved immediately after the malpractice claim filing date and showed sustained improvements by 6.52 Press Ganey percentile ranks (95% confidence interval 0.67 to 12.38), with the increase most prominent among those involved in the 46 failure-to-diagnose claims (10.52; 95% confidence interval 3.72 to 17.32). CONCLUSION: We observed a temporal improvement in patient satisfaction scores for emergency physicians in this sample after their being named in a malpractice claim relative to matched controls. Measures of care intensity and speed did not significantly change.

Geographic variation in morphology in the Mohave Rattlesnake (Crotalus scutulatus Kennicott 1861) (Serpentes: Viperidae): implications for species boundaries.

The Mohave Rattlesnake (Crotalus scutulatus) is a highly venomous pitviper inhabiting the arid interior deserts, grasslands, and savannas of western North America. Currently two subspecies are recognized: the Northern Mohave Rattlesnake (C. s. scutulatus) ranging from southern California to the southern Central Mexican Plateau, and the Huamantla Rattlesnake (C. s. salvini) from the region of Tlaxcala, Veracruz, and Puebla in south-central Mexico. Although recent studies have demonstrated extensive geographic variation in venom composition and cryptic genetic diversity in this species, no modern studies have focused on geographic variation in morphology. Here we analyzed a series of qualitative, meristic, and morphometric traits from 347 specimens of C. scutulatus and show that this species is phenotypically cohesive without discrete subgroups, and that morphology follows a continuous cline in primarily color pattern and meristic traits across the major axis of its expansive distribution. Interpreted in the context of previously published molecular evidence, our morphological analyses suggest that multiple episodes of isolation and secondary contact among metapopulations during the Pleistocene were sufficient to produce distinctive genetic populations, which have since experienced gene flow to produce clinal variation in phenotypes without discrete or diagnosable distinctions among these original populations. For taxonomic purposes, we recommend that C. scutulatus be retained as a single species, although it is possible that C. s. salvini, which is morphologically the most distinctive population, could represent a peripheral isolate in the initial stages of speciation.

Testing the Testers: Are Young Men Who Have Sex With Men Receiving Adequate HIV Testing and Counseling Services?

BACKGROUND: The United States Centers for Disease Control and Prevention promote HIV testing every 6 months among young men who have sex with men (YMSM) to facilitate entry into the HIV prevention and care continuum. Willingness to be tested may be influenced by testing services' quality. Using a novel mystery shopper methodology, we assessed YMSM's testing experiences in 3 cities and recommend service delivery improvements. METHODS: We assessed YMSM's experiences at HIV testing sites in Philadelphia (n = 30), Atlanta (n = 17), and Houston (n = 19). YMSM (18-24) were trained as mystery shoppers and each site was visited twice. After each visit, shoppers completed a quality assurance survey to evaluate their experience. Data were pooled across sites, normed as percentages, and compared across cities. RESULTS: Across cites, visits averaged 30 minutes (SD = 25.5) and were perceived as welcoming and friendly (70.9%). YMSM perceived most sites respected their privacy and confidentiality (84.3%). YMSM noted deficiencies in providers' competencies with sexual minorities (63.4%) and comfort during the visit (65.7%). Sites underperformed on Lesbian, Gay, Bisexual, Transgender visibility (49.6%) and medical forms inclusivity (57.95%). Sites on average did not discuss YMSM's relationship context (49.8%) nor provide risk reduction counseling (56.8%) or safer sex education (24.3%). Sites delivered pre-exposure prophylaxis information and counseling inconsistently (58.8%). CONCLUSIONS: Testing sites' variable performance underscores the importance of improving HIV testing services for YMSM. Strategies are recommended for testing sites to promote cultural sensitivity: funding staff trainings, creating systems to assess adherence to testing guidelines and best practices, and implementing new service delivery models.

A Rare Case of Wilson Disease in a 72-Year-Old Patient.

Wilson disease is an autosomal recessive disorder of abnormal copper metabolism that is prevalent in the younger population, rarely presenting in patients older than 40 years. Clinical presentation may be variable, and diagnosis is often aided by clinical and biochemical tests. We report the case of a 72-year-old woman who presented with acute liver failure initially of unclear etiology. Our patient was initially managed for presumed drug-induced liver injury but ultimately diagnosed with Wilson disease on the basis of clinical presentation, laboratory testing, liver biopsy, quantitative hepatic copper, and abnormal genetic testing.

Procedural Experience With Intubation: Results From a National Emergency Medicine Group.

STUDY OBJECTIVE: Although intubation is a commonly discussed procedure in emergency medicine, the number of opportunities for emergency physicians to perform it is unknown. We determine the frequency of intubation performed by emergency physicians in a national emergency medicine group. METHODS: Using data from a national emergency medicine group (135 emergency departments [EDs] in 19 states, 2010 to 2016), we determined intubation incidence per physician, including intubations per year, intubations per 100 clinical hours, and intubations per 1,000 ED patient visits. We report medians and interquartile ranges (IQRs) for estimated intubation rates among emergency physicians working in general EDs (those treating mixed adult and pediatric populations). RESULTS: We analyzed 53,904 intubations performed by 2,108 emergency physicians in general EDs (53,265 intubations) and pediatric EDs (639 intubations). Intubation incidence varied among general ED emergency physicians (median 10 intubations per year; IQR 5 to 17; minimum 0, maximum 109). Approximately 5% of emergency physicians did not perform any intubations in a given year. During the study, 24.1% of general ED emergency physicians performed fewer than 5 intubations per year (range 21.2% in 2010 to 25.7% in 2016). Emergency physicians working in general EDs performed a median of 0.7 intubations per 100 clinical hours (IQR 0.3 to 1.1) and 2.7 intubations per 1,000 ED patient visits (IQR 1.2 to 4.6). CONCLUSION: These findings provide insights into the frequency with which emergency physicians perform intubations.

Vagrant birds as a dispersal vector in transoceanic range expansion of vascular plants.

Birds are thought to be important vectors underlying the disjunct distribution patterns of some terrestrial biota. Here, we investigate the role of birds in the colonisation by Ochetophila trinervis (Rhamnaceae), a vascular plant from the southern Andes, of sub-Antarctic Marion Island. The location of O. trinervis on the island far from human activities, in combination with a reconstruction of island visitors' travel history, precludes an anthropogenic introduction. Notably, three bird species occurring in the southern Andes inland have been observed as vagrants on Marion Island, with the barn swallow Hirundo rustica as the most common one. This vagrant displays long-distance migratory behaviour, eats seeds when insects are in short supply, and has started breeding in South America since the 1980s. Since naturalised O. trinervis has never been found outside the southern Andes and its diaspores are incapable of surviving in seawater or dispersing by wind, a natural avian dispersal event from the Andes to Marion Island, a distance of >7500 km, remains the only probable explanation. Although one self-incompatible shrub seems doomed to remain solitary, its mere establishment on a Southern Ocean island demonstrates the potential of vagrancy as a driver of extreme long-distance dispersal of terrestrial biota.

Adaptation and evaluation of a monopolar electrosurgical triangle-tip knife for transendoscopic ventriculocordectomy in healthy horses.

OBJECTIVE: To evaluate the efficacy and safety of a transendoscopic monopolar electrosurgical triangle-tip knife as instrumentation to perform unilateral ventriculocordectomy (VC) in healthy adult horses. STUDY DESIGN: In vivo experimental study. STUDY POPULATION: Nine horses donated for medical conditions unrelated to respiratory system. METHODS: The triangle-tip knife was applied in contact fashion. Left VC was performed under standing sedation. Endoscopic images of the upper airway were graded for inflammation by 2 masked surgeons preoperatively and immediately, 24 hours and, in 2 cases, 7 and 14 days postoperatively. Four larynxes were examined for histological evidence of inflammation and collagen deposition at 24 hours (n = 2) and at 14 days (n = 2) after surgery. RESULTS: Ventriculocordectomy was successfully performed in all horses. Endoscopic evidence of inflammation was scored as normal (preoperatively), mild (immediately postoperatively), mild (24 hours postoperatively), mild (7 days postoperatively), and normal (14 days postoperatively). According to histopathology, inflammation of the surgical site and ventricularis muscle was generally increased (variable is common and is present in most high-power fields) 24 hours and 14 days postoperatively. Fibrosis and collagen deposition also seemed increased at the surgical site 14 days postoperatively. CONCLUSION: Ventriculocordectomy was successfully performed with an electrosurgical triangle-tip knife and resulted in acceptable short-term outcomes. CLINICAL SIGNIFICANCE: The use of an electrosurgical triangle-tip knife alternative instrumentation may be offer an alternative option to perform VC in practices when diode laser is not available or is cost prohibitive. Longer term evaluation of the VC site is required to determine the effect on rima glottic cross-sectional area.

Cryptic genetic diversity, population structure, and gene flow in the Mojave rattlesnake (Crotalus scutulatus).

The Mojave rattlesnake (Crotalus scutulatus) inhabits deserts and arid grasslands of the western United States and Mexico. Despite considerable interest in its highly toxic venom and the recognition of two subspecies, no molecular studies have characterized range-wide genetic diversity and population structure or tested species limits within C. scutulatus. We used mitochondrial DNA and thousands of nuclear loci from double-digest restriction site associated DNA sequencing to infer population genetic structure throughout the range of C. scutulatus, and to evaluate divergence times and gene flow between populations. We find strong support for several divergent mitochondrial and nuclear clades of C. scutulatus, including splits coincident with two major phylogeographic barriers: the Continental Divide and the elevational increase associated with the Central Mexican Plateau. We apply Bayesian clustering, phylogenetic inference, and coalescent-based species delimitation to our nuclear genetic data to test hypotheses of population structure. We also performed demographic analyses to test hypotheses relating to population divergence and gene flow. Collectively, our results support the existence of four distinct lineages within C. scutulatus, and genetically defined populations do not correspond with currently recognized subspecies ranges. Finally, we use approximate Bayesian computation to test hypotheses of divergence among multiple rattlesnake species groups distributed across the Continental Divide, and find evidence for co-divergence at this boundary during the mid-Pleistocene.

Minimum area thresholds for rattlesnakes and colubrid snakes on islands in the Gulf of California, Mexico.

We expand a framework for estimating minimum area thresholds to elaborate biogeographic patterns between two groups of snakes (rattlesnakes and colubrid snakes) on islands in the western Gulf of California, Mexico. The minimum area thresholds for supporting single species versus coexistence of two or more species relate to hypotheses of the relative importance of energetic efficiency and competitive interactions within groups, respectively. We used ordinal logistic regression probability functions to estimate minimum area thresholds after evaluating the influence of island area, isolation, and age on rattlesnake and colubrid occupancy patterns across 83 islands. Minimum area thresholds for islands supporting one species were nearly identical for rattlesnakes and colubrids (~1.7 km2), suggesting that selective tradeoffs for distinctive life history traits between rattlesnakes and colubrids did not result in any clear advantage of one life history strategy over the other on islands. However, the minimum area threshold for supporting two or more species of rattlesnakes (37.1 km2) was over five times greater than it was for supporting two or more species of colubrids (6.7 km2). The great differences between rattlesnakes and colubrids in minimum area required to support more than one species imply that for islands in the Gulf of California relative extinction risks are higher for coexistence of multiple species of rattlesnakes and that competition within and between species of rattlesnakes is likely much more intense than it is within and between species of colubrids.

Gulf of Mexico low-frequency ocean soundscape impacted by airguns.

The ocean soundscape of the Gulf of Mexico (GOM) has not been well-studied, although it is an important habitat for marine mammals, including sperm and beaked whales, many dolphin species, and a potentially endangered baleen whale species. The GOM is also home to high levels of hydrocarbon exploration and extraction, heavily used commercial shipping ports, and significant fishery industry activity, all of which are known contributors to oceanic noise. From 2010-2013, the soundscape of three deep and two shallow water sites in the GOM were monitored over 10 - 1000 Hz. Average sound pressure spectrum levels were high, >90 dB re 1 µPa(2)/Hz at <40 Hz for the deep water sites and were associated with noise from seismic exploration airguns. More moderate sound pressure levels, <55 dB re 1 µPa(2)/Hz at >700 Hz, were present at a shallow water site in the northeastern Gulf, removed from the zone of industrial development and bathymetrically shielded from deep water anthropogenic sound sources. During passage of a high wind event (Hurricane Isaac, 2012), sound pressure levels above 200 Hz increased with wind speed, but at low frequencies (<100 Hz) sound pressure levels decreased owing to absence of noise from airguns.

Mercury in western North America: A synthesis of environmental contamination, fluxes, bioaccumulation, and risk to fish and wildlife.

Western North America is a region defined by extreme gradients in geomorphology and climate, which support a diverse array of ecological communities and natural resources. The region also has extreme gradients in mercury (Hg) contamination due to a broad distribution of inorganic Hg sources. These diverse Hg sources and a varied landscape create a unique and complex mosaic of ecological risk from Hg impairment associated with differential methylmercury (MeHg) production and bioaccumulation. Understanding the landscape-scale variation in the magnitude and relative importance of processes associated with Hg transport, methylation, and MeHg bioaccumulation requires a multidisciplinary synthesis that transcends small-scale variability. The Western North America Mercury Synthesis compiled, analyzed, and interpreted spatial and temporal patterns and drivers of Hg and MeHg in air, soil, vegetation, sediments, fish, and wildlife across western North America. This collaboration evaluated the potential risk from Hg to fish, and wildlife health, human exposure, and examined resource management activities that influenced the risk of Hg contamination. This paper integrates the key information presented across the individual papers that comprise the synthesis. The compiled information indicates that Hg contamination is widespread, but heterogeneous, across western North America. The storage and transport of inorganic Hg across landscape gradients are largely regulated by climate and land-cover factors such as plant productivity and precipitation. Importantly, there was a striking lack of concordance between pools and sources of inorganic Hg, and MeHg in aquatic food webs. Additionally, water management had a widespread influence on MeHg bioaccumulation in aquatic ecosystems, whereas mining impacts where relatively localized. These results highlight the decoupling of inorganic Hg sources with MeHg production and bioaccumulation. Together the findings indicate that developing efforts to control MeHg production in the West may be particularly beneficial for reducing food web exposure instead of efforts to simply control inorganic Hg sources.