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Objectives/Goals: Imaging neuromas, benign tumors of nerve tissue, can be difficult in amputees with osseointegrated (OI) prostheses, in which a metal rod is implanted into the residual limb. Magnetic resonance imaging can be inadequate due to the implanted metal. The aim of this study is to assess the use of ultrasound to detect neuromas in patients with OI prostheses. Methods/Study Population: This is a single-institutional observational study of 7 patients undergoing lower limb OI prostheses. Lower extremity nerve ultrasounds with 2-D grayscale and Doppler were completed at postoperative follow-up visits following OI prosthesis implantation. Specifically, the sciatic nerve, tibial nerve, common peroneal nerve, and sural nerve were targeted for imaging. Neuromas found on ultrasound were measured by maximal length in three planes. Results/Anticipated Results: Our study to date includes two patients with OI prostheses. The remaining patients will be accrued by the end of December. The first patient with a left below-the-knee amputation completed imaging 3 years after OI prosthesis implantation. The common peroneal nerve showed preserved fascicular architecture and morphology, with no distinct neuroma formation. However, the sural nerve demonstrated a 6 × 5 × 4 mm neuroma with minimal pain with deep palpation. The tibial nerve demonstrated a 14 × 11 × 8 mm neuroma within the medial calf musculature, with mild pain with deep palpation. The second patient with a right above-the-knee amputation was imaged 10 months after OI prosthesis implantation. The sciatic nerve demonstrated preserved fascicular morphology and terminated in a smooth taper. There was no defined neuroma. Discussion/Significance of Impact: In conclusion, we have preliminarily shown in the first two patients that ultrasound can successfully image neuromas in patients with OI prostheses in the postoperative period. Furthermore, despite a patient that was 3 years postoperative with two neuromas, the neuromas produced minimal to mild pain with targeted palpation.
Objectives/Goals: Mayo Clinic’s Clinical Trials Beyond Walls™ (CTBW) program collaborates with study teams to implement decentralized elements in clinical trials, enabling participation from home or local settings. In cancer treatment trials, traditional paper pill diaries are replaced with real-time digital tracking solutions to monitor chemotherapy adherence. Methods/Study Population: The CTBW team developed a solution to deliver electronic pill diaries to research participants using the electronic health record (EHR) system Epic and patient portal MyChart1. The solution includes a portal message to remind participants to take chemotherapy. Medication dose, date taken, and reasons for missed doses (e.g., “I forgot” or “side effects were bothersome”) are captured. An automated in-basket notification system alerts the study team when predefined conditions are met. Configurable medication schedules ensure diaries are sent according to the prescribed frequency. Reports were generated to allow study teams to monitor all participant diaries. Results/Anticipated Results: The CTBW team implemented this digital pill diary in neuro-oncology trial NCT066250472. We anticipate the pill diary in the patient portal will enhance chemotherapy adherence by capturing real-time data in a platform widely used by Mayo Clinic patients. This patient-reported data is stored in the EHR, where it is accessible to providers and study teams. This allows for continuous monitoring, which facilitates a streamlined review of potential adverse events, improved compliance visibility, and timely treatment adjustments compared to paper-based or external solutions. The system also streamlines data entry, reducing human error and eliminating manual transcription. The created language and workflow templates allow the CTBW to scale this approach to future cancer trials Discussion/Significance of Impact: Decentralized clinical trial participants may never visit Mayo Clinic, making digital recording essential. The EHR-based digital pill diary enables continuous monitoring within a familiar system for providers and patients, increasing study team visibility, and allowing for earlier intervention in cases of non-compliance or adverse events.
Hallucinations are common and distressing symptoms in Parkinson’s disease (PD). Treatment response in clinical trials is measured using validated questionnaires, including the Scale for Assessment of Positive Symptoms-Hallucinations (SAPS-H) and University of Miami PD Hallucinations Questionnaire (UM-PDHQ). The minimum clinically important difference (MCID) has not been determined for either scale. This study aimed to estimate a range of MCIDs for SAPS-H and UM-PDHQ using both consensus-based and statistical approaches.
Methods
A Delphi survey was used to seek opinions of researchers, clinicians, and people with lived experience. We defined consensus as agreement ≥75%. Statistical approaches used blinded data from the first 100 PD participants in the Trial for Ondansetron as Parkinson’s Hallucinations Treatment (TOP HAT, NCT04167813). The distribution-based approach defined the MCID as 0.5 of the standard deviation of change in scores from baseline at 12 weeks. The anchor-based approach defined the MCID as the average change in scores corresponding to a 1-point improvement in clinical global impression-severity scale (CGI-S).
Results
Fifty-one researchers and clinicians contributed to three rounds of the Delphi survey and reached consensus that the MCID was 2 points on both scales. Sixteen experts with lived experience reached the same consensus. Distribution-defined MCIDs were 2.6 points for SAPS-H and 1.3 points for UM-PDHQ, whereas anchor-based MCIDs were 2.1 and 1.3 points, respectively.
Conclusions
We used triangulation from multiple methodologies to derive the range of MCID estimates for the two rating scales, which was between 2 and 2.7 points for SAPS-H and 1.3 and 2 points for UM-PDHQ.
Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence.
Methods:
Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing. Participants were clinically assessed every two months for two years while receiving standard antidepressant treatment. Analyses examined group differences in phenotypic measure using general linear models. Concurrent associations between phenotypic measures and diagnostic groups were examined using LASSO logistic regression.
Results:
Sixty (44%) LLD participants experienced a relapse over the two-year period. Numerous phenotypic measures across all domains differed between remitted LLD and comparison participants. Only residual depressive symptom severity, rumination, medical comorbidity, and executive dysfunction significantly predicted LLD classification. Fewer measures differed between relapsing and sustained remission LLD subgroups, with the relapsing group exhibiting greater antidepressant treatment intensity, greater fatigue, rumination, and disability, higher systolic blood pressure, greater life stress and lower instrumental social support. Relapsing group classification was informed by antidepressant treatment intensity, lower instrumental social support, and greater life stress.
Conclusions:
A wide range of phenotypic factors differed between remitted LLD and comparison groups. Fewer measures differed between relapsing and sustained remission LLD subgroups, with less social support and greater stress informing vulnerability to subsequent relapse. This research suggests potential targets for relapse prevention and emphasizes the need for clinically translatable relapse biomarkers to inform care.
A clinical and translational scientist (CTS) often seeks to increase their knowledge of statistical topics to effectively conduct biomedical research studies. A common method for obtaining this knowledge is through existing online educational materials that are suggested by a biostatistical collaborator or identified by the CTS. However, the volume of available educational materials on diverse statistical topics makes the task of identifying high-quality educational resources at an appropriate level challenging and time consuming for CTSs and collaborative biostatisticians. In response to these challenges, the Biostats4You website was created, where existing online educational materials for a variety of statistical topics are vetted to identify those most appropriate for CTSs. In this manuscript, we describe the resource review process, provide information about statistical topics and resources currently available, and make recommendations for how CTSs and collaborative biostatisticians can utilize the Biostats4You website to improve training, mentoring, and collaborative research practices.
Ordinary product-moment correlation and regression methods are frequently not immediately applicable to qualitative data, whereas multiserial r, point-multiserial r, and multiserial eta can be easily applied. The multiserial r is rejected for prediction since it tells us only what the correlation might be if certain assumptions were true and if we could measure what is not now measured. The point-multiserial r and multiserial eta are identical when the number of categories is two but differ when it is three or greater. The multiserial eta is identical with the product-moment r when categories are assigned scale values equal to their means on the continuous variable. With three or more categories, the point-multiserial r, which assumes linearity with equal step intervals, is always lower than the multiserial eta, which forces linearity by adoption of unequal step intervals based upon difference in criterion attainment. While the multiserial eta expends one degree of freedom with the weighting of each category, this is known and correctable, whereas the vague partial loss of degrees of freedom due to the ordering of categories in the point-multiserial is not correctable.
While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.
The aims of the study were to illustrate the number and type of restrictive practices that were used across two inpatient wards within the Acute Mental Health Inpatient Centre in the Belfast trust over a two year period. This initially would highlight the prevalence and use of such practices and allow for comparison against the data collected after the implementation of the therapy cross. We hoped that with the implementation of the therapy cross we would see a decline in the use of physical interventions, use of IM medications and also the number of aggressive or distressing incidents and behaviours would also decrease.
Methods
We utilized a statistical process control to collate and illustrate data. Daily data collection was carried out and compiled over a 2–3 year period and is ongoing with regards to ward incidents of aggressive behaviour, use of physical intervention, use of IM medications. In early October of 2023 the therapy cross was introduced and the run charts and data collection continued allowing for comparison of such behaviours and interventions pre and post intervention.
Results
A percentage decrease of 50% of the weekly average was noted in incidents of aggressive and violent behaviours on one ward in AMHIC following implementation of therapy. A percentage decrease in average weekly use of IM injections was noted to be 13%. A 12% decrease was found in the use of physical intervention on a weekly average following the therapy cross.
Conclusion
The implementation of a therapy cross in early October 2023 indicated improvement in the incidence of use of restrictive measures on two inpatient wards in the Belfast Trust, including the number of physical interventions such as holds that were required and also decreased the incidence of use of IM medications for rapid tranquillization. The data indicates a significant decrease in the number of cases of violent and aggressive behaviour on wards following implementation of a therapy cross.
Galen Strawson (2004) has championed an influential argument against the view that a life is, or ought to be, understood as a kind of story with temporal extension. The weight of his argument rests on his self-report of his experience of life as lacking the form or temporal extension necessary for narrative. And though this argument has been widely accepted, I argue that it ought to have been rejected. On one hand, the hypothetical non-diachronic life Strawson proposes would likely be psychologically fragmented. On the other, it would certainly be morally diminished, for it would necessarily lack the capacity for integrity.
Cathodes with recessed sample surfaces have several benefits in cesium sputter ion sources, including higher output, more efficient use of sample material, and improved focusing of the extracted ion beam. However, the Ionplus MICADAS uses cathodes with a graphite surface that is essentially flush with the sample holder. To evaluate the performance of recessed graphite with the MICADAS and determine the optimal surface depth, we tested four different depths, including the standard (flush) pressing method, 0.5 mm, 1.0 mm, and 1.5 mm. We found that recessed depths of 1.0 and 1.5 mm resulted in 20% higher ion beam current compared to the standard method under the same source conditions. The results are consistent with the beam produced from the recessed targets being more narrowly focused with a lower emittance, resulting in better transmission through the accelerator. Small graphite samples (200 µg C) with recessed surfaces produced higher currents for longer, leading to a 2–3× increase in sample ionization efficiency. Additionally, there was some evidence that isotopic ratio measurements of recessed samples were more stable over time. Overall, samples recessed to 1 mm depth offered numerous advantages over the standard pressing method and we have subsequently started pressing all MICADAS graphite using this approach.
Chromium(VI) in the environment is of particular concern because it is toxic to both plants and animals, even at low concentrations. As a redox-sensitive element, the fate and toxicity of chromium is controlled by soil reduction-oxidation (redox) reactions. In-situ remediation of chromium combines reduction of Cr(VI) to Cr(III) and immobilization of chromium on mineral surfaces. In this study, Fe-rich smectite, montmorillonite, illite, vermiculite, and kaolinite were examined to determine reactivity in sorption-reduction of Cr(VI). The clays were compared to forms that were reduced by sodium dithionite. Clays containing Fe(II) efficiently removed soluble Cr(VI) from solution. Chromium K-edge X-ray absorption near edge structure (XANES) suggested that clays containing Fe(II) reduced Cr(VI) to Cr(III), immobilizing Cr at the clay/water interface. Adsorption of Cr(VI) by the Fe(II)-containing clay was a prerequisite for the coupled sorption-reduction reaction. Sodium dithionite added directly to aqueous suspensions of non-reduced clays reduced Cr(VI) to Cr(III), but did not immobilize Cr on clay surfaces. The capacity of clays to reduce Cr(VI) is correlated with the ferrous iron content of the clays. For dithionite-reduced smectite, the exchangeable cation influenced the sorption reaction, and thus it also influenced the coupled sorption-reduction reaction of Cr(VI). The pH of the aqueous system affected both the amount of Cr(VI) reduced to Cr(III) and the partition of Cr(III) between aqueous and adsorbed species. A plot of pH vs. amount (adsorption envelope) adsorbed for the coupled sorption-reduction reaction of Cr by reduced smectite exhibited a similar pattern to that of typical anion-sorption.
Ongoing professional development is important for collaborative biostatisticians, as it enables them to remain current with the latest advances in statistical methodology and software, refine their analytical skills, and expand their domain knowledge, thereby facilitating their ability to contribute effectively to biomedical research. Although external opportunities for professional development, such as attending conferences and workshops, are widely recognized and valued in the field of biostatistics, there has been comparatively little attention given to internal opportunities for enhancing the skills and knowledge of biostatisticians which can be implemented with lower financial and time investment than external offerings. The purpose of this paper is to offer guidance for ongoing internal professional development activities that can be employed by collaborative biostatistics units in universities and academic medical centers to complement structured curricula and initial training. Specific examples of activities are provided so that collaborative biostatisticians and/or managers of biostatistical units can flexibly combine components to create an appropriately scaled, customized program that meets the needs of themselves or of the unit.
Adverse effects are a common concern when prescribing and reviewing medication, particularly in vulnerable adults such as older people and those with intellectual disability. This paper describes the development of an app giving information on side-effects, called Medichec, and provides a description of the processes involved in its development and how drugs were rated for each side-effect. Medications with central anticholinergic action, dizziness, drowsiness, hyponatraemia, QTc prolongation, bleeding and constipation were identified using the British National Formulary (BNF) and frequency of occurrence of these effects was determined using the BNF, product information and electronic searches, including PubMed.
Results
Medications were rated using a traffic light system according to how commonly the adverse effect was known to occur or the severity of the effect.
Clinical implications
Medichec can facilitate access to side-effects information for multiple medications, aid clinical decision-making, optimise treatment and improve patient safety in vulnerable adults.
Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another.
Methods
Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort.
Results
Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011).
Conclusion
Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.
The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis.
Aims
To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole.
Method
Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method.
Results
A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml).
Conclusions
The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.
We estimate the impact of sporting events and franchises on local crime rates using the technique developed in Arellano and Bond (2001). For events, we consider the presence of Major League Baseball, National Basketball Association, National Football League and National Hockey League franchises as well as whether a city held one of the respective championships, the Olympics, or World Cup matches. We find little to no evidence that sporting events or franchises are correlated with changes in either property or violent crime with two notable exceptions. The Olympics Games are associated with roughly a 10 per cent increase in property crimes while the Super Bowl is associated with a 2.5 per cent decrease in violent crime. On the whole, however, the presence of spectator sports does not seem to automatically carry with it any improvements in citywide criminal behaviour.
The coronavirus disease 2019 (COVID-19) pandemic challenged not only the health-care industry, but also the public health infrastructure in new and wide-ranging ways. Environmental health (EH) professionals have proven to be an essential component of the interdisciplinary public health solution required to prevent, respond, and recover from the COVID-19 pandemic. The Indian Health Service’s Division of Environmental Health Services is a community-based program offering a broad scope of environmental health services and technical assistance. Significant COVID-19 workload activities were recorded from March 2020 through March 2021. A total of 62.7% of the Division’s federal staff completed a 24-question survey in February/March 2021. Primary roles relating to community-based EH, institutional EH, and incident command system support/teams became apparent. Results indicated Division of Environmental Health Services staff provided critical leadership and used their established, trusted, interdisciplinary partnerships to help ensure critical resources and services were available in Indian Country.
Personality traits (e.g. neuroticism) and the social environment predict risk for internalizing disorders and suicidal behavior. Studying these characteristics together and prospectively within a population confronted with high stressor exposure (e.g. U.S. Army soldiers) has not been done, yet could uncover unique and interactive predictive effects that may inform prevention and early intervention efforts.
Methods
Five broad personality traits and social network size were assessed via self-administered questionnaires among experienced soldiers preparing for deployment (N = 4645) and new soldiers reporting for basic training (N = 6216). Predictive models examined associations of baseline personality and social network variables with recent distress disorders or suicidal behaviors assessed 3- and 9-months post-deployment and approximately 5 years following enlistment.
Results
Among the personality traits, elevated neuroticism was consistently associated with increased mental health risk following deployment. Small social networks were also associated with increased mental health risk following deployment, beyond the variance accounted for by personality. Limited support was found for social network size moderating the association between personality and mental health outcomes. Small social networks also predicted distress disorders and suicidal behavior 5 years following enlistment, whereas unique effects of personality traits on these more distal outcomes were rare.
Conclusions
Heightened neuroticism and small social networks predict a greater risk for negative mental health sequelae, especially following deployment. Social ties may mitigate adverse impacts of personality traits on psychopathology in some contexts. Early identification and targeted intervention for these distinct, modifiable factors may decrease the risk of distress disorders and suicidal behavior.
The Ediacaran rangeomorph Fractofusus misrai is the most common and best-preserved of the E Surface fossil assemblage in the Mistaken Point Ecological Reserve of southeastern Newfoundland, Canada. Fractofusus has been interpreted as a fusiform epifaunal soft-sediment recliner, and like other rangeomorphs it has a self-similar, fractal-like branching morphology. The rangeomorph branching of Fractofusus has been considered to be identical on the upper and lower surfaces; however, study of specimens with complex biostratinomic histories suggests clear differences between the upper and lower surfaces. The first-order branches grew downwards into the sediment from a high point near the midline but grew above the sediment–water interface at their lateral and distal margins. Our new three-dimensional appreciation of rangeomorph branching in Fractofusus explains many of the taphomorphs of Fractofusus including straight, curved, kinked and tousled forms. The three-dimensional morphology, mode of life, taphonomy and palaeoenvironmental interactions of F. misrai are discussed along with a new three-dimensional reconstruction.
Among outpatients with coronavirus disease 2019 (COVID-19) due to the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) δ (delta) variant who did and did not receive 2 vaccine doses at 7 days after symptom onset, there was no difference in viral shedding (cycle threshold difference 0.59, 95% CI, −4.68 to 3.50; P = .77) with SARS-CoV-2 cultured from 2 (7%) of 28 and 1 (4%) of 26 outpatients, respectively.