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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.
This Element provides a fresh approach to the representation and experience of the French Disease, by reassessing a wide range of textual and visual sources through the lens of contemporary medical ideas. It analyses how knowledge about the Great Pox was transmitted to a literate and also a wider public through performance and the circulation of popular prints. Chronicles, satirical and moralistic poems and plays about prostitutes, along with autobiographical accounts, described symptoms and the experience of patients, reflecting how non-medical men and women understood the nature of this terrible new disease and its profound physical and psychological impact. The second major theme is how the French Disease was represented visually. Woodcuts and broadsheets showing the moral and physical decline of courtesans are analysed together with graphic medical illustrations of symptoms and their treatment together with images of the diseased body of St Job, patron saint of the French Disease.
The Whitham equation is a non-local, nonlinear partial differential equation that models the temporal evolution of spatial profiles of surface displacement of water waves. However, many laboratory and field measurements record time series at fixed spatial locations. To directly model data of this type, it is desirable to have equations that model the spatial evolution of time series. The spatial Whitham (sWhitham) equation, proposed as the spatial generalization of the Whitham equation, fills this need. In this paper, we study this equation and apply it to water-wave experiments on shallow and deep water. We compute periodic travelling-wave solutions to the sWhitham equation and examine their properties, including their stability. Results for small-amplitude solutions align with known results for the Whitham equation. This suggests that the systems are consistent in the weakly nonlinear regime. At larger amplitudes, there are some discrepancies. Notably, the sWhitham equation does not appear to admit cusped solutions of maximal wave height. In the second part, we compare predictions from the temporal and spatial Korteweg–de Vries and Whitham equations with measurements from laboratory experiments. We show that the sWhitham equation accurately models measurements of tsunami-like waves of depression, waves of elevation, and solitary waves on shallow water. Its predictions also compare favourably with experimental measurements of waves of depression and elevation on deep water. Accuracy is increased by adding a phenomenological damping term. Finally, we show that neither the sWhitham nor the temporal Whitham equation accurately models the evolution of wave packets on deep water.
To evaluate the impact of administering probiotics to prevent Clostridioides difficile infection (CDI) among patients receiving therapeutic antibiotics.
Design:
Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019.
Setting:
This study was conducted in 4 acute-care hospitals across an integrated health region.
Patients:
Hospitalized patients, aged ≥55 years.
Methods:
Patients were given 2 probiotic capsules daily (Bio-K+, Laval, Quebec, Canada), containing 50 billion colony-forming units of Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2. We measured hospital-acquired CDI (HA-CDI) and the number of positive C. difficile tests per 10,000 patient days as well as adherence to administration of Bio-K+ within 48 and 72 hours of antibiotic administration. Mixed-effects generalized linear models, adjusted for influenza admissions and facility characteristics, were used to evaluate the impact of the intervention on outcomes.
Results:
Overall adherence of Bio-K+ administration ranged from 76.9% to 84.6% when stratified by facility and periods. Rates of adherence to administration within 48 and 72 hours of antibiotic treatment were 60.2% –71.4% and 66.7%–75.8%, respectively. In the adjusted analysis, there was no change in HA-CDI (incidence rate ratio [IRR], 0.92; 95% confidence interval [CI], 0.68–1.23) or C. difficile positivity rate (IRR, 1.05; 95% CI, 0.89–1.24). Discharged patients may not have received a complete course of Bio-K+. Our hospitals had a low baseline incidence of HA-CDI. Patients who did not receive Bio-K+ may have differential risks of acquiring CDI, introducing selection bias.
Conclusions:
Hospitals considering probiotics as a primary prevention strategy should consider the baseline incidence of HA-CDI in their population and timing of probiotics relative to the start of antimicrobial administration.
American Indians and Alaska Natives suffer from disproportionately high rates of chronic mental and physical health conditions. These health inequities are linked to colonization and its downstream consequences. Most of the American Indian and Alaska Native health inequities research uses a deficit framework, failing to acknowledge the resilience of American Indian and Alaska Native people despite challenging historical and current contexts. This scoping review is based on a conceptual model which acknowledges the context of colonization and its consequences (psychological and health risk factors). However, rather than focusing on health risk, we focus on protective factors across three identified domains (social, psychological, and cultural/spiritual), and summarize documented relationships between these resilience factors and health outcomes. Based on the scoping review of the literature, we note gaps in extant knowledge and recommend future directions. The findings summarized here can be used to inform and shape future interventions which aim to optimize health and well-being in American Indian and Alaska Native peoples.
Within the extensive literature on international regionalism, the more limited academic work done on regional financial organizations (RFOs) tends to assume that, by pooling resources to address such common international economic issues as development funding and financial crises, RFOs contribute to economic stability in their parts of the global landscape. Although South America has led the pack in creating such RFOs, their effectiveness is limited by the asymmetry in economic heft of the continent's governments. Rather than weighing the significance of financial regionalism in South America from the point of view of the majority, we assess whether and how this phenomenon has contributed to Brazil's politico-economic rise to near-major-power standing on the world stage in the twenty-first century. Drawing on extensive interviews with Brazilian officials conducted in March 2013, we analyze three instances of South America's international public finance: development lending, crisis lending, and payment systems. Our findings suggest that self-generated unilateral and bilateral financial initiatives have brought Brasília far more significant economic and political results than have RFOs, whose various incarnations have yielded the continental giant few economic and only minor political gains.
To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.
Design:
Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.
Setting:
Community settings and care homes in 26 UK centers.
Participants:
People with probable or possible Alzheimer’s disease and agitation.
Measurements:
Primary outcome included incremental cost of participants’ health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants’ and unpaid carers’ gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives.
Results:
One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment.
Conclusions:
On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.
I have been thinking a lot about environmental pedagogy in American studies, especially since I started teaching a third-year interdisciplinary course, Climate Change & Culture Wars, which focusses on the post-1970s US. I wanted to know more about how others are approaching the topic as we face up to looming climate and ecological collapse. University teachers and learners across disciplines are reckoning with it, but what's going on in American studies in Britain, and what can we learn from each other and from teachers elsewhere? How is the crisis impacting on the framing of our disciplinary fields and how are we incorporating its intellectual and practical demands into pedagogic spaces and syllabi?
This chapter takes the Meditations to act out the jam in autodiegetic biography, 1. through synkrisis with the SHA M. A., 2. through the programmatic/prelusory relations of M1 with 2-12. In representation reticulated through the diplomatics of first-person self-promotion, concentrated absenting delivers strongly motivated presencing. This is a book that wears its status as a book but wears it thin.
Throughout their 250 Myr history, archosaurian reptiles have exhibited a wide array of body sizes, shapes, and locomotor habits, especially in regard to terrestriality. These features make Archosauria a useful clade with which to study the interplay between body size, shape, and locomotor behavior, and how this interplay may have influenced locomotor evolution. Here, digital volumetric models of 80 taxa are used to explore how mass properties and body proportions relate to each other and locomotor posture in archosaurs. One-way, nonparametric, multivariate analysis of variance, based on the results of principal components analysis, shows that bipedal and quadrupedal archosaurs are largely distinguished from each other on the basis of just four anatomical parameters (p < 0.001): mass, center of mass position, and relative forelimb and hindlimb lengths. This facilitates the development of a quantitative predictive framework that can help assess gross locomotor posture in understudied or controversial taxa, such as the crocodile-line Batrachotomus (predicted quadruped) and Postosuchus (predicted biped). Compared with quadrupedal archosaurs, bipedal species tend to have relatively longer hindlimbs and a more caudally positioned whole-body center of mass, and collectively exhibit greater variance in forelimb lengths. These patterns are interpreted to reflect differing biomechanical constraints acting on the archosaurian Bauplan in bipedal versus quadrupedal groups, which may have shaped the evolutionary histories of their respective members.
Background: Transmission of carbapenemase-producing organisms (CPO) threatens patient safety in healthcare facilities. As a result of a 2011 outbreak of blaKPC+ Klebsiella pneumoniae, the NIH Clinical Center (NIHCC) has prioritized early detection and isolation of CPO carriers, using point-prevalence surveys and targeted high-risk ward surveillance since 2011 and admission surveillance since 2013. We describe our experience over 6 years of admission surveillance. Methods: The NIHCC is a 200-bed research hospital that provides care for a highly immunocompromised patient population. From September 2013 to September 2019, perirectal swabs were ordered automatically for all patients on admission to nonbehavioral health wards. Swabs were ordered twice weekly for ICU patients, weekly in other high-risk wards, and monthly for hospital-wide point prevalence (excluding behavioral health). Patients hospitalized in the United States in the previous week or abroad in the previous 6 months were considered high risk for carriage and isolated pending results from 2 swabs. Most swabs (n = 37,526) were cultured onto HardyCHROM CRE. If gram-negative bacilli (GNB) were present, a molecular screen for carbapenemases was performed on a sweep of cultured material (day 1) pending organism isolation. GNB were identified by MALDI-TOF MS. Prior to June 2019, isolates were screened by blaKPC/blaNDM PCR. Starting in June 2019, Enterobacteriaceae and Pseudomonas aeruginosa were screened using the phenotypic modified carbapenem inactivation method (mCIM), reflexing to the GeneXpert CARBA-R molecular assay if positive; other GNB were tested directly with CARBA-R. Selected GNB underwent susceptibility testing (Sensititre). Whole-genome sequencing was used to assess relatedness among CPO isolates. Swabs from high-risk patients were tested directly by blaKPC PCR (n = 699) until August 2019 (most in parallel with culture) and thereafter by CARBA-R (n = 13). Results: Among 54,188 orders for perirectal swabs, 38,238 were collected from 14,497 patients (compliance 71%). Among 33 CPO-colonized patients identified from September 2013 through September 2019, 15 were identified on admission, 6 were identified in point-prevalence surveys, 8 were identified from high-risk ward surveillance, and 4 were identified from clinical cultures. Sequencing demonstrated no relatedness among CPO isolates. Although only 1.4% of patients sampled on admission were colonized with CPO, those meeting high-risk criteria were 21 times as likely to be colonized. Conclusion: Admission surveillance for CPO identified a low rate of colonization, but it detected nearly half of known CPO-colonized NIHCC patients over the past 6 years. Modest compliance with swab collection leaves room for improvement and likely results in missed instances of colonization. Although we cannot determine its effectiveness, we view our strategy as one of several key safety measures for our highly vulnerable patient population.
The landscape of antimicrobial resistance (AMR) surveillance is changing rapidly. The primary objective of this study was to assess the benefit of linking population-based infection prevention and control surveillance data on methicillin-resistant Staphylococcus aureus (MRSA) to hospital discharge abstract data (DAD). We assessed the value of this novel data linkage for the characterization of hospital-acquired (HA) and community-acquired MRSA (CA-MRSA) cases.
Methods:
Incident inpatient MRSA surveillance data for all adults (≥18 years) from 4 acute-care facilities in Calgary, Alberta, between April 1, 2011, and March 31, 2017, were linked to DAD. Personal health number (PHN) and gender were used to identify specific individuals, and specimen collection time-points were used to identify specific hospitalization records. A third common variable on admission date between these databases was used to validate the linkage process. Descriptive statistics were used to characterize HA-MRSA and CA-MRSA cases identified through the linkage process.
Results:
A total of 2,430 surveillance records (94.6%) were successfully linked to the correct hospitalization period. By linking surveillance and administrative data, we were able to identify key differences between patients with HA- and CA-MRSA. These differences are consistent with previously reported findings in the literature. Data linkage to DAD may be a novel tool to enhance and augment the details of base surveillance data.
Conclusion and recommendations:
This is the first Canadian study linking a frontline healthcare-associated infection AMR surveillance database to an administrative population database. This work represents an important methodological step toward complementing traditional AMR surveillance data practices. Data linkage to other data types, such as primary care, emergency, social, and biological data, may be the basis of achieving more precise data focused around AMR.
To determine the attributable cost and length of stay of hospital-acquired Clostridioides difficile infection (HA-CDI) from the healthcare payer perspective using linked clinical, administrative, and microcosting data.
Design:
A retrospective, population-based, propensity-score–matched cohort study.
Setting:
Acute-care facilities in Alberta, Canada.
Patients:
Admitted adult (≥18 years) patients with incident HA-CDI and without CDI between April 1, 2012, and March 31, 2016.
Methods:
Incident cases of HA-CDI were identified using a clinical surveillance definition. Cases were matched to noncases of CDI (those without a positive C. difficile test or without clinical CDI) on propensity score and exposure time. The outcomes were attributable costs and length of stay of the hospitalization where the CDI was identified. Costs were expressed in 2018 Canadian dollars.
Results:
Of the 2,916 HA-CDI cases at facilities with microcosting data available, 98.4% were matched to 13,024 noncases of CDI. The total adjusted cost among HA-CDI cases was 27% greater than noncases of CDI (ratio, 1.27; 95% confidence interval [CI], 1.21–1.33). The mean attributable cost was $18,386 (CAD 2018; USD $14,190; 95% CI, $14,312–$22,460; USD $11,046-$17,334). The adjusted length of stay among HA-CDI cases was 13% greater than for noncases of CDI (ratio, 1.13; 95% CI, 1.07–1.19), which corresponds to an extra 5.6 days (95% CI, 3.10–8.06) in length of hospital stay per HA-CDI case.
Conclusions:
In this population-based, propensity score matched analysis using microcosting data, HA-CDI was associated with substantial attributable cost.
In recent years, researchers in pre-Hispanic Central America have used new approaches that greatly amplify and enhance evidence of plants and their uses. This paper presents a case study from Puerto Escondido, located in the lower Ulúa River valley of Caribbean coastal Honduras. We demonstrate the effectiveness of using multiple methods in concert to interpret ethnobotanical practice in the past. By examining chipped-stone tools, ceramics, sediments from artifact contexts, and macrobotanical remains, we advance complementary inquiries. Here, we address botanical practices “in the home,” such as foodways, medicinal practices, fiber crafting, and ritual activities, and those “close to home,” such as agricultural and horticultural practices, forest management, and other engagements with local and distant ecologies. This presents an opportunity to begin to develop an understanding of ethnoecology at Puerto Escondido, here defined as the dynamic relationship between affordances provided in a botanical landscape and the impacts of human activities on that botanical landscape.
OBJECTIVES/SPECIFIC AIMS: To understand the mechanisms of how a non-antimicrobial can reshape a commensal microbe community to cure a ubiquitous human disease. METHODS/STUDY POPULATION: Whole genome sequencing of bacterial isolates, metabolomic investigations of previously collected skin microbe isolates from patients, and structural investigations of a protein from these skin microbes. RESULTS/ANTICIPATED RESULTS: Metabolic pathways associated with adaptation to a changing skin microenvironment, novel antimicrobial characterization, and a structural understanding of a novel nutrient acquisition protein. DISCUSSION/SIGNIFICANCE OF IMPACT: Multiple angles of this investigation are poised to improve current non-antimicrobial dermatologic treatments and they have the potential to impact microbe-related diseases in other human microenvironments.