Seracam: characterisation of a new small field of view hybrid gamma camera for nuclear medicine.

BACKGROUND: Portable gamma cameras are being developed for nuclear medicine procedures such as thyroid scintigraphy. This article introduces Seracam® - a new technology that combines small field of view gamma imaging with optical imaging - and reports its performance and suitability for small organ imaging. METHODS: The count rate capability, uniformity, spatial resolution, and sensitivity for 99mTc are reported for four integrated pinhole collimators of nominal sizes of 1 mm, 2 mm, 3 mm and 5 mm. Characterisation methodology is based on NEMA guidelines, with some adjustments necessitated by camera design. Two diagnostic scenarios - thyroid scintigraphy and gastric emptying - are simulated using clinically relevant activities and geometries to investigate application-specific performance. A qualitative assessment of the potential benefits and disadvantages of Seracam is also provided. RESULTS: Seracam's performance across the measured characteristics is appropriate for small field of view applications in nuclear medicine. At an imaging distance of 50 mm, corresponding to a field of view of 77.6 mm × 77.6 mm, spatial resolution ranged from 4.6 mm to 26 mm and sensitivity from 3.6 cps/MBq to 52.2 cps/MBq, depending on the collimator chosen. Results from the clinical simulations were particularly promising despite the challenging scenarios investigated. The optimal collimator choice was strongly application dependent, with gastric emptying relying on the higher sensitivity of the 5 mm pinhole whereas thyroid imaging benefitted from the enhanced spatial resolution of the 1 mm pinhole. Signal to noise ratio in images was improved by pixel binning. Seracam has lower measured sensitivity when compared to a traditional large field of view gamma camera, for the simulated applications this is balanced by advantages such as high spatial resolution, portability, ease of use and real time gamma-optical image fusion and display. CONCLUSION: The results show that Seracam has appropriate performance for small organ 99mTc imaging. The results also show that the performance of small field of view systems must be considered holistically and in clinically appropriate scenarios.

Integration of Disability Awareness Improves Medical Students' Attitudes Toward People with Disabilities.

Persons with disabilities (PWD) often require special accommodations and more comprehensive healthcare yet frequently have encounters with physicians who are unprepared to provide tailored and complete care. A multipronged disability awareness curriculum for second-year medical students was implemented, including content on disability etiquette, patient-centered and interprofessional learning sessions for individuals with physical disabilities and intellectual and developmental disabilities, and a debriefing session with physiatrists. The objective of this study was to utilize a mixed methods approach to evaluate the disability awareness curriculum in undergraduate medical education (UME). Assessment was conducted using course evaluations, pre- and post-surveys including the Attitudes and Perspectives Towards Persons with Disabilities (APPD) scale and Multidimensional Attitudes Scale Toward Persons with Disabilities (MAS), and student focus groups. The mean scores from both the APPD (2.11 ± 0.43 pre-score vs. 1.7 ± 0.39 post-score) and MAS (2.45 ± 0.43 pre-score vs. 2.25 ± 0.55 post-score) indicate the curriculum improved medical students' attitudes toward PWD (p < 0.05), with lower numbers representing more favorable attitudes. After completing the curriculum, medical students' attitudes were comparable to those of doctor of physical therapy (DPT) students. Qualitative analysis from focus groups highlighted four major themes: education, comfort level, impact on future practice, and disability differences. This curriculum has potential as a valuable framework for delivering effective disability education to medical students to prepare future physicians to serve PWD and their unique needs. It meets core competencies, provides an opportunity to learn in interprofessional environments, and integrates PWD into the educational process. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-024-02004-0.

Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia.

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10-12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10-12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10-8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.

Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial.

Importance: Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD). Objective: To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment. Design, Setting, and Participants: From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD. Carriers of gene variants were assigned 3:1 to either drug or placebo. The present analysis was conducted from April to June 2023. DIAN-TU-001 spans 25 study sites in 7 countries. Biofluids and neuroimaging from carriers of DIAD gene variants in the gantenerumab, solanezumab, and placebo groups were analyzed. Interventions: In 2016, initial dosing of gantenerumab, 225 mg (subcutaneously every 4 weeks) was increased every 8 weeks up to 1200 mg. In 2017, initial dosing of solanezumab, 400 mg (intravenously every 4 weeks) was increased up to 1600 mg every 4 weeks. Main Outcomes and Measures: Longitudinal changes in CSF levels of neurogranin, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3-like 1 protein (YKL-40), glial fibrillary acidic protein (GFAP), neurofilament light protein (NfL), and plasma levels of GFAP and NfL. Results: Of 236 eligible participants screened, 43 were excluded. A total of 142 participants (mean [SD] age, 44 [10] years; 72 female [51%]) were included in the study (gantenerumab, 52 [37%]; solanezumab, 50 [35%]; placebo, 40 [28%]). Relative to placebo, gantenerumab significantly reduced CSF neurogranin level at year 4 (mean [SD] ß = -242.43 [48.04] pg/mL; P < .001); reduced plasma GFAP level at year 1 (mean [SD] ß = -0.02 [0.01] ng/mL; P = .02), year 2 (mean [SD] ß = -0.03 [0.01] ng/mL; P = .002), and year 4 (mean [SD] ß = -0.06 [0.02] ng/mL; P < .001); and increased CSF sTREM2 level at year 2 (mean [SD] ß = 1.12 [0.43] ng/mL; P = .01) and year 4 (mean [SD] ß = 1.06 [0.52] ng/mL; P = .04). Solanezumab significantly increased CSF NfL (log) at year 4 (mean [SD] ß = 0.14 [0.06]; P = .02). Correlation analysis for rates of change found stronger correlations between CSF markers and fluid markers with Pittsburgh compound B positron emission tomography for solanezumab and placebo. Conclusions and Relevance: This randomized clinical trial supports the importance of fibrillar amyloid reduction in multiple AD-related processes of neuroinflammation and neurodegeneration in CSF and plasma in DIAD. Additional studies of antiaggregated amyloid therapies in sporadic AD and DIAD are needed to determine the utility of nonamyloid biomarkers in determining disease modification. Trial Registration: ClinicalTrials.gov Identifier: NCT04623242.

Widening the Road to Health Professions Education: Expanding Access for Diverse and Underserved Populations.

The Spring 2023 Webinar Audio Seminar (WAS) of the International Association of Medical Science Educators (IAMSE), titled "Widening the Road to Health Professions Education: Expanding Access for Diverse and Underserved Populations," was designed to help health science educators explore innovative practices in recruiting and enrolling students from underserved populations into health sciences programs. From March 2, 2023, to March 30, 2023, this five-part webinar series was broadcast live to institutions and educators worldwide. This series helped participants learn about creating pathways for students to meet the unique needs of their communities.

Faith and facts: Exploring the intersection of religion and science among anatomy educators.

The intersection of religion and science often elicits polarizing views among scientists, though approximately half of American scientists identify as religious. Mounting evidence also supports the role of spirituality in comprehensive patient care. The purpose of this study was to explore the religiosity of faculty who teach in the anatomical sciences at U.S. colleges and universities. Surveys were administered to anatomists through two professional societies. Two-thirds (64.9%, 74/114) of respondents identified as religious, 26.3% (30/114) as atheist, and 8.8% (10/114) as agnostic. Most respondents (64.9%, 74/114) disagreed with the statement, "There is no place for religion and science to intersect." Approximately one in three respondents expressed concern that sharing/disclosing their religious beliefs would negatively affect the perceptions of colleagues (32.5%, 37/114) and students (28.9%, 33/114) toward them. Faculty at faith-based institutions were more open to disclosing their beliefs (p = 0.045), and highly religious individuals were more concerned (p = 0.001). Fewer than one-fifth of respondents 17.5% (20/114) personally experienced mistreatment or discrimination within academic settings due to their religious beliefs. Most respondents held politically liberal-leaning views (71.0%, 76/107). Highly religious individuals were more likely to be politically conservative (p < 0.001). Overall, this study demonstrates that the number of anatomists who identify as religious may be higher than that of other biological disciplines and that mistreatment due to religious views remains a challenge for some in the profession. Continued dialogue regarding the role of religion in professional identity expression may be an important step in mitigating religion-focused mistreatment and discrimination in academic settings.

Changes in Cognitive Function After Kidney Transplantation: A Longitudinal Cohort Study.

RATIONALE & OBJECTIVE: Kidney disease negatively affects cognition. We assessed the effect of kidney transplantation (KT) on different cognitive domains. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We examined pre- versus post-KT cognition in patients waitlisted for KT at an academic center. PREDICTORS: Transplant status. We measured cognitive function before KT (n=101), 3 months after KT (n=78), and 1 year after KT (n = 83). OUTCOMES: Our primary outcome was change in cognitive function before versus after KT. We used standard neuropsychological tests to assess global cognition (Mini-Mental State Exam [MMSE]), episodic/declarative memory (Logical Memory), psychomotor speed/visuospatial function (Digit Symbol Substitution Test [DSST], Trail Making Test [TMT] A), working memory/attention (Digit Span), executive function (TMT B), and semantic memory/verbal fluency/language (Category Fluency). ANALYTICAL APPROACH: Using linear mixed model analysis, we evaluated the changes in neuropsychological test scores adjusted for age, sex, race, education, and number of assessments. RESULTS: Before KT, Logical Memory I and II, DSST, MMSE, Category Fluency (animal naming), and Digit Span backward scores were low compared with normative values from the National Alzheimer's Coordinating Center data. Logical Memory I and II scores improved after KT (pre- vs post-KT, estimated group difference [d]=3.3, P<0.001 for Logical Memory I; d=4.27, P<0.001 for Logical Memory II), such that post-KT scores were similar to normative values (post-KT vs normative values, d = -0.37, P=0.06 for Logical Memory I; d = -0.89, P=0.08 for Logical Memory II). Category Fluency (animal naming; d=2.4, P<0.001) and DSST (d=3.12, P=0.01) scores also improved with KT, but post-KT DSST scores remained lower than normative values (post-KT vs normative values, d = -5.17, P<0.001). MMSE, Digit Span, and TMT A and B scores did not change after KT. LIMITATIONS: Single-center study. CONCLUSIONS: Episodic and verbal declarative memory normalize after KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function show partial improvement. Cognitive impairment in kidney disease is therefore at least partly reversible with KT. PLAIN-LANGUAGE SUMMARY: Cognitive impairment in kidney disease affects self-esteem, vocational abilities, quality of life, health care costs, and mortality. It is not clear whether kidney transplantation (KT) improves cognition and whether the improvement is uniform across cognitive domains. The distinction between reversible and irreversible cognitive impairment has important implications in the clinical care of patients before and after KT. We assessed cognition before KT and 3 months and 12 months after KT and discovered that episodic and verbal declarative memory normalized with KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function also improved with KT but did not reach normal levels. Cognitive impairment in kidney disease is therefore at least partly reversible.

Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.

INTRODUCTION: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages. METHODS: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition. RESULTS: Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures. DISCUSSION: We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials. HIGHLIGHTS: Mutation position influences Aß burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aß burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.

Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease.

INTRODUCTION: Increasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double-blind phase 3 DIAN-TU-001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab. METHODS: We used latent class (LC) analysis on data from the Dominantly Inherited Alzheimer Network Trials Unit 001 trial to test amyloid positron emission tomography (PET) reduction as a potential surrogate biomarker. RESULTS: LC analysis categorized participants into three classes: amyloid no change, amyloid reduction, and amyloid growth, based on longitudinal amyloid Pittsburgh compound B PET standardized uptake value ratio data. The amyloid-no-change class was at an earlier disease stage for amyloid amounts and dementia. Despite similar baseline characteristics, the amyloid-reduction class exhibited reductions in the annual decline rates compared to the amyloid-growth class across multiple biomarker, clinical, and cognitive outcomes. DISCUSSION: LC analysis indicates that amyloid reduction is associated with improved clinical outcomes and supports its use as a surrogate biomarker in clinical trials. HIGHLIGHTS: We used latent class (LC) analysis to test amyloid reduction as a surrogate biomarker. Despite similar baseline characteristics, the amyloid-reduction class exhibited remarkably better outcomes compared to the amyloid-growth class across multiple measures. LC analysis proves valuable in testing amyloid reduction as a surrogate biomarker in clinical trials lacking significant treatment effects.

Traumatic Brain Injury Alters the Trajectory of Age-Related Mitochondrial Change.

Background: Some epidemiologic studies associate traumatic brain injury (TBI) with Alzheimer's disease (AD). Objective: To test whether a TBI-induced acceleration of age-related mitochondrial change could potentially mediate the reported TBI-AD association. Methods: We administered unilateral controlled cortical impact (CCI) or sham injuries to 5-month-old C57BL/6J and tau transgenic rTg4510 mice. In the non-transgenics, we assessed behavior (1-5 days, 1 month, and 15 months), lesion size (1 and 15 months), respiratory chain enzymes (1 and 15 months), and mitochondrial DNA copy number (mtDNAcn) (1 and 15 months) after CCI/sham. In the transgenics we quantified post-injury mtDNAcn and tangle burden. Results: In the non-transgenics CCI caused acute behavioral deficits that improved or resolved by 1-month post-injury. Protein-normalized complex I and cytochrome oxidase activities were not significantly altered at 1 or 15 months, although complex I activity in the CCI ipsilesional cortex declined during that period. Hippocampal mtDNAcn was not altered by injury at 1 month, increased with age, and rose to the greatest extent in the CCI contralesional hippocampus. In the injured then aged transgenics, the ipsilesional hippocampus contained less mtDNA and fewer tangles than the contralesional hippocampus; mtDNAcn and tangle counts did not correlate. Conclusions: As mice age their brains increase mtDNAcn as part of a compensatory response that preserves mitochondrial function, and TBI enhances this response. TBI may, therefore, increase the amount of compensation required to preserve late-life mitochondrial function. If TBI does modify AD risk, altering the trajectory or biology of aging-related mitochondrial changes could mediate the effect.

Survey response rates in health sciences education research: A 10-year meta-analysis.

Growth in the online survey market may be increasing response burden and possibly jeopardizing higher response rates. This meta-analysis evaluated survey trends over one decade (2011-2020) to determine: (1) changes in survey publication rates over time, (2) changes in response rates over time, (3) typical response rates within health sciences education research, (4) the factors influencing survey completion levels, and (5) common gaps in survey methods and outcomes reporting. Study I estimated survey publication trends between 2011 and 2020 using articles published in the top three health sciences education research journals. Study II searched the anatomical sciences education literature across six databases and extracted study/survey features and survey response rates. Time plots and a proportional meta-analysis were performed. Per 2926 research articles, the annual estimated proportion of studies with survey methodologies has remained constant, with no linear trend (p > 0.050) over time (Study I). Study II reported a pooled absolute response rate of 67% (95% CI = 63.9-69.0) across 360 studies (k), totaling 115,526 distributed surveys. Despite response rate oscillations over time, no significant linear trend (p = 0.995) was detected. Neither survey length, incentives, sponsorship, nor population type affected absolute response rates (p ≥ 0.070). Only 35% (120 of 339) of studies utilizing a Likert scale reported evidence of survey validity. Survey response rates and the prevalence of studies with survey methodologies have remained stable with no linear trends over time. We recommend researchers strive for a typical absolute response rate of 67% or higher and clearly document evidence of survey validity for empirical studies.

Adjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial.

BACKGROUND: Clinical trials of anti-inflammatories in schizophrenia do not show clear and replicable benefits, possibly because patients were not recruited based on elevated inflammation status. Interleukin 1-beta (IL-1ß) mRNA and protein levels are increased in serum, plasma, cerebrospinal fluid, and brain of some chronically ill patients with schizophrenia, first episode psychosis, and clinical high-risk individuals. Canakinumab, an approved anti-IL-1ß monoclonal antibody, interferes with the bioactivity of IL-1ß and interrupts downstream signaling. However, the extent to which canakinumab reduces peripheral inflammation markers, such as, high sensitivity C-reactive protein (hsCRP) and symptom severity in schizophrenia patients with inflammation is unknown. TRIAL DESIGN: We conducted a randomized, placebo-controlled, double-blind, parallel groups, 8-week trial of canakinumab in chronically ill patients with schizophrenia who had elevated peripheral inflammation. METHODS: Twenty-seven patients with schizophrenia or schizoaffective disorder and elevated peripheral inflammation markers (IL-1ß, IL-6, hsCRP and/or neutrophil to lymphocyte ratio: NLR) were randomized to a one-time, subcutaneous injection of canakinumab (150 mg) or placebo (normal saline) as an adjunctive antipsychotic treatment. Peripheral blood hsCRP, NLR, IL-1ß, IL-6, IL-8 levels were measured at baseline (pre injection) and at 1-, 4- and 8-weeks post injection. Symptom severity was assessed at baseline and 4- and 8-weeks post injection. RESULTS: Canakinumab significantly reduced peripheral hsCRP over time, F(3, 75) = 5.16, p = 0.003. Significant hsCRP reductions relative to baseline were detected only in the canakinumab group at weeks 1, 4 and 8 (p's = 0.0003, 0.000002, and 0.004, respectively). There were no significant hsCRP changes in the placebo group. Positive symptom severity scores were significantly reduced at week 8 (p = 0.02) in the canakinumab group and week 4 (p = 0.02) in the placebo group. The change in CRP between week 8 and baseline (b = 1.9, p = 0.0002) and between week 4 and baseline (b = 6.0, p = 0.001) were highly significant predictors of week 8 change in PANSS Positive Symptom severity scores. There were no significant changes in negative symptoms, general psychopathology or cognition in either group. Canakinumab was well tolerated and only 7 % discontinued. CONCLUSIONS: Canakinumab quickly reduces peripheral hsCRP serum levels in patients with schizophrenia and inflammation; after 8 weeks of canakinumab treatment, the reductions in hsCRP are related to reduced positive symptom severity. Future studies should consider increased doses or longer-term treatment to confirm the potential benefits of adjunctive canakinumab in schizophrenia. Australian and New Zealand Clinical Trials Registry number: ACTRN12615000635561.

The value of co-creating a clinical outcome assessment strategy for clinical trial research: process and lessons learnt.

BACKGROUND: In support of UCB pharmaceutical research programs, the aim of this research was to implement a novel process for patient involvement in a multidisciplinary research group to co-create a clinical outcome assessment strategy to accurately reflect the experience of people living with early-stage Parkinson's. Patient experts were an integral part of the decision-making process for patient-reported outcome (PRO) research and instrument development. METHODS: In partnership with two patient organizations (Parkinson's UK and the Parkinson's Foundation), 6 patient experts were recruited into a multidisciplinary research group alongside clinical, patient engagement and involvement, regulatory science, and outcome measurement experts. The group was involved across two phases of research; the first phase identified what symptoms are cardinal to the experience of living with early-stage Parkinson's and the second phase involved the development of PRO instruments to better assess the symptoms that are important to people living with early-stage Parkinson's. Patient experts were important in performing a variety of roles, in particular, qualitative study protocol design, conceptual model development, and subsequent co-creation of two PRO instruments. RESULTS: Involving people with Parkinson's in PRO research ensured that the expertise of these representatives from the Parkinson's community shaped and drove the research; as such, PRO instruments were being developed with the patient at the forefront. Working with patient experts required considerable resource and time allocation for planning, communication, document development, and organizing meetings; however, their input enriched the development of PRO instruments and was vital in developing PRO instruments that are more meaningful for people with Parkinson's and clinicians. CONCLUSIONS: Conducting PRO research, in the context of clinical development involving pharmaceutical companies, requires balancing regulatory and scientific rigor with tight time constraints. Incorporating a multi-stakeholder perspective, which included patient experts as joint investigators, had a strong positive impact on our research, despite the logistical complexities of their involvement. Due to the input of patient experts, the innovative clinical outcome assessment strategy and the co-created novel PRO instruments were more relevant and holistic to the patient experience of early-stage Parkinson's.

Patient-reported outcome (PRO) instruments allow people living with a disease and participating in a clinical study to describe the symptoms and experiences that they consider meaningful. PRO instruments use tools such as questionnaires and scales to capture patient perspectives on a treatment that might not be captured by a clinical measurement. It is recommended that the patient community and patient experts are included in the development of PRO instruments to accurately capture information that is important to them. Building on the experience of a recent PRO research project in support of UCB pharmaceutical programs, this article provides recommendations on how pharmaceutical companies can partner with patient organizations and involve patient experts as joint investigators in the co creation of PRO instruments. Despite the additional resource and time required, involving patient experts and patient organizations into the research collaboration had a strong positive impact and ensured that the PROs were meaningful to patients (in this instance, people living with early-stage Parkinson's). Patient organizations facilitated patient engagement and recruitment in research activities, maintained communication with the pharmaceutical company's research team, and built trust between collaborators by implementing patient engagement tools and best practices. Patient experts contributed to several parts of the PRO instrument development process: study design, identifying key symptoms and experiences, and developing individual PRO questions. Co-creation between the pharmaceutical company, patient experts, and patient organizations resulted in considerable improvements to typical PRO instrument development for use in clinical trials and is thus recommended.

A Novel Protocol for Nasal Decolonization Using Prolonged Application of an Alcohol-Based Nasal Antiseptic Reduces Surgical Site Infections in Total Joint Arthroplasty Patients: A Retrospective Cohort Study.

Background: Current nasal decolonization strategies utilize pre-operative agents without consideration for short-term re-colonization or de novo colonization. Many strategies utilize an antibiotic-based agent, raising concerns of limited gram-negative antimicrobial coverage and the emergence of resistant bacterial strains. This study evaluated the clinical utility of a non-antibiotic, alcohol-based nasal decolonization agent in decreasing surgical site infection (SSI) rates after total joint arthroplasty. Patients and Methods: We retrospectively compared an 18-month cohort of elective primary total joint arthroplasty patients treated peri-operatively with an alcohol-based sanitizer to historical controls. The alcohol-based agent was administered pre-operatively the day of surgery and for two weeks after surgery. Patients were followed for 90 days and assessed for signs or symptoms of SSI. Patient and caregiver compliance was recorded. There were 779 patients included in the experimental group and 647 included in the historical control group. Results: Patients receiving alcohol-based nasal decolonization had a lower rate of SSI compared with controls not receiving nasal decolonization (0.64% [5/779] vs. 1.55% [10/647]; p = 0.048; odds ratio, 2.43). Utilization of an alcohol-based nasal sanitizer in the pre-operative and prolonged post-operative setting decreased infection rates by 41.3% in our elective total joint arthroplasty setting. Conclusions: When used pre- and post-operatively, alcohol-based nasal decolonization of bacteria in patients undergoing total joint arthroplasty led to a substantial decrease in SSIs.

Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN).

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual's point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of 'sporadic' AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers.

The Association of Tacrolimus Formulation on Cerebral Blood Flow and Cognitive Function.

Calcineurin inhibitors are inherent vasoconstrictors. Cerebral vasoconstriction can reduce cerebral blood flow (CBF), and negatively impact cerebrovascular response (CVR) to exercise, and cognitive function. The once-daily extended-release (LCP) tacrolimus has fewer side effects than the immediate-release (IR) tacrolimus. The role of calcineurin inhibitors on CBF and the impact of specific formulations of tacrolimus on CBF, CVR, and cognitive function are unknown. In this pilot study, we evaluated whether changing from IR tacrolimus to LCP tacrolimus modulates CBF, CVR, or cognitive function in kidney transplant (KT) recipients. Methods: We randomized (2:1) 30 stable KT recipients on IR tacrolimus to intervention (switch to LCP tacrolimus) and control (continue IR tacrolimus) arms. We measured CBF, CVR, and cognitive function at baseline and at 12 wk. We used ANCOVA to evaluate changes in outcome variables, with baseline values and study arm as covariates. We used descriptive statistics with mean changes in outcome variables to compare the 2 groups. Results: Participants were 51 ± 13 y old. There was no difference in plasma tacrolimus levels at baseline and at 12 wk in the 2 arms. The changes in CBF, resting middle cerebral artery velocity, CVR, and cognitive function were more favorable in the intervention arm than in the control group. Conclusions: Changing IR tacrolimus to LCP tacrolimus may improve CBF, cerebrovascular dynamics, and cognitive function in KT recipients. Larger studies are needed to confirm these results.