An update on simulation training in rhinology: a systematic review of evidence.

BACKGROUND: Rhinological procedures demand a high degree of technical expertise and anatomical knowledge. Because of limited surgical opportunities, ethical considerations and the complexity of these procedures, simulation-based training has become increasingly important. This review aimed to evaluate the effectiveness of simulation models used in rhinology training. METHODS: Searches were conducted on PubMed, Embase, Cochrane and Google Scholar for studies conducted between July 2012 and July 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis ('PRISMA') protocol defined a final list of articles. Each validated study was assigned a level of evidence and a level of recommendation based on the Oxford Centre of Evidence-Based Medicine classification. RESULTS: Following exclusions, 42 articles were identified which encompassed six types of simulation models and 26 studies evaluated validity. The rhinological skills assessed included endoscopic sinus surgery (n = 28), skull base/cerebrospinal fluid leak repair (n = 14), management of epistaxis and/or sphenopalatine artery ligation (n = 8), and septoplasty and septorhinoplasty (n = 6). All studies reported the beneficial impact of their simulation models on trainee development. CONCLUSION: Simulation training in rhinology is a valuable adjunct to traditional surgical education. Although evidence is of moderate quality, the findings highlight the importance of simulation-based training in rhinology training.

The role of ChatGPT in enhancing ENT surgical training - a trainees' perspective.

OBJECTIVE: ChatGPT, developed by Open AI (November 2022) is a powerful artificial intelligence language model, designed to produce human-like text from user-written prompts. Prompts must give context-specific information to produce valuable responses. Otolaryngology is a specialist field that sees limited exposure during undergraduate and postgraduate education. Additionally, otolaryngology trainees have seen a reduction in learning opportunities since the coronavirus disease 2019 pandemic. METHOD: This article aims to give guidance on optimising the ChatGPT system in the context of education for otolaryngology by reviewing barriers to otolaryngology education and suggesting ways that ChatGPT can overcome them by providing examples using the authors' experience. RESULTS: Overall, the authors saw that ChatGPT demonstrated some useful qualities, particularly with regards to assistance with communication skills and individualised patient responses. CONCLUSION: Although ChatGPT cannot replace traditional mentorship and practical surgical experience, it can serve as an invaluable supplementary resource to education in otolaryngology.

Validation of the Rainbow Model of Integrated Care Measurement Tool in Parkinson's Disease.

BACKGROUND: Integrated care is essential for improving the management and health outcomes for people with Parkinson's disease (PD); reliable and objective measures of care integration are few. OBJECTIVE: The aim of this study was to test the psychometric properties of the Rainbow Model of Integrated Care Measurement Tool (RMIC-MT, provider version) for healthcare professionals involved in PD care. METHODS: A cross-sectional survey was administered online to an international network representing 95 neurology centers across 41 countries and 588 healthcare providers. Exploratory factor analysis with principal axis extraction method was used to assess construct validity. Confirmatory factor analysis was used to evaluate model fit of the RMIC-MT provider version. Cronbach's alpha was used to assess the internal consistency reliability. RESULTS: Overall, 371 care providers (62% response rate) participated in this study. No item had psychometric sensitivity problems. Nine factors (professional coordination, cultural competence, triple aims outcome, system coordination, clinical coordination, technical competence, community-centeredness, person-centeredness, and organizational coordination) with 42 items were determined by exploratory factor analysis. Cronbach's alpha ranged from 0.76 (clinical coordination) to 0.94 (system coordination) and showed significant correlation among all items in the scale (>0.4), indicating good internal consistency reliability. The confirmatory factor analysis model passed most goodness-of-fit tests, thereby confirming the factor structure of nine categories with a total of 40 items. CONCLUSIONS: The results provide evidence for the construct validity and other psychometric properties of the provider version of the RMIC-MT to measure integrated care in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Immune contexture of paediatric cancers.

BACKGROUND: The clinical development of immune checkpoint-targeted immunotherapies has been disappointing so far in paediatric solid tumours. However, as opposed to adults, very little is known about the immune contexture of paediatric malignancies. METHODS: We investigated by gene expression and immunohistochemistry (IHC) the immune microenvironment of five major paediatric cancers: Ewing sarcoma (ES), osteosarcoma (OS), rhabdomyosarcoma (RMS), medulloblastoma (MB) and neuroblastoma (NB; 20 cases each; n = 100 samples total), and correlated them with overall survival. RESULTS: NB and RMS tumours had high immune cell gene expression values and high T-cell counts but were low for antigen processing cell (APC) genes. OS and ES tumours showed low levels of T-cells but the highest levels of APC genes. OS had the highest levels of macrophages (CSF1R, CD163 and CD68), whereas ES had the lowest. MB appeared as immune deserts. Tregs (FOXP3 staining) were higher in both RMS and OS. Most tumours scored negative for PD-L1 in tumour and immune cells, with only 11 of 100 samples positive for PD-L1 staining. PD-L1 and OX40 levels were generally low across all five indications. Interestingly, NB had comparable levels of CD8 by IHC and by gene expression to adult tumours. However, by gene expression, these tumours were low for T-cell cytotoxic molecules GZMB, GZMA and PRF1. Surprisingly, the lower the level of tumour infiltrative CD8 T-cells, the better the prognosis was in NB, RMS and ES. Gene expression analyses showed that MYCN-amplified NB have higher amounts of immune suppressive cells such as macrophages, myeloid-derived suppressor cells and Tregs, whereas the non-MYCN-amplified tumours were more infiltrated and had higher expression levels of Teff. CONCLUSIONS: Our results describe the quality and quantity of immune cells across five major paediatric cancers and provide some key features differentiating these tumours from adult tumour types. These findings explain why anti-PD(L)1 might not have had single agent success in paediatric cancers. These results provides the rationale for the development of biologically stratified and personalised immunotherapy strategies in children with relapsing/refractory cancers.

A systematic review and meta-analysis of intellectual, neuropsychological, and psychoeducational functioning in neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) is a common genetic disorder frequently associated with cognitive deficits. Despite cognitive deficits being a key feature of NF1, the profile of such impairments in NF1 has been shown to be heterogeneous. Thus, we sought to quantitatively synthesize the extant literature on cognitive functioning in NF1. A random-effects meta-analysis of cross-sectional studies was carried out comparing cognitive functioning of patients with NF1 to typically developing or unaffected sibling comparison subjects of all ages. Analyses included 50 articles (Total NNF1 = 1,522; MAge = 15.70 years, range = 0.52-69.60), yielding 460 effect sizes. Overall moderate deficits were observed [g = -0.64, 95% CI = (-0.69, -0.60)] wherein impairments differed at the level of cognitive domain. Deficits ranged from large [general intelligence: g = -0.95, 95% CI = (-1.12, -0.79)] to small [emotion: g = -0.37, 95% CI = (-0.63, -0.11)]. Moderation analyses revealed nonsignificant contributions of age, sex, educational attainment, and parental level of education to outcomes. These results illustrate that cognitive impairments are diffuse and salient across the lifespan in NF1. Taken together, these results further demonstrate efforts should be made to evaluate and address cognitive morbidity in patients with NF1 in conjunction with existing best practices.

T-Cell Heterogeneity in Baseline Tumor Samples: Implications for Early Clinical Trial Design and Analysis.

Background: In early stage clinical trials, changes to levels of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment (TME) are critical biomarkers of the mechanism of action of novel immunotherapies. However, baseline heterogeneity of tumor samples, both between and within patients, and the resultant impact on the validity of clinical trial data is not well defined. Here we identify and quantify the impact of baseline variables on the heterogeneity of FoxP3+ and proliferating CD8+ T-cells levels (MKi67+CD8A+) in the TME both between and within patients for the purpose of informing clinical trial design and analysis. Methods: We compared levels of FoxP3+ and MKi67+CD8+ cell densities (counts/mm2) from >1000 baseline tumor samples from clinical trials and commercially available sources. Using multivariate hierarchical regression techniques, we investigated whether inter-person heterogeneity of activated or regulatory T-cells could be attributed to baseline characteristics including demographics, indication, lesion type, tissue of excision, biopsy method, prior cancer treatment, and tissue type i.e., "fresh" or "archival" status. We also sought to characterize within-patient heterogeneity by lesion type and tissue type. Results: Prior cancer treatment with hormone therapy or chemotherapy that induces immunogenic cell death may alter the TME. Archival tissue is an unreliable substitute for fresh tissue for determining baseline TIL levels. Baseline and on treatment biopsies should be matched by lesion type to avoid bias.

Modelling falls in Parkinson's disease and normal ageing in mice using a complex motor task.

Falls resulting from multifactorial deficits are common in both normal ageing and Parkinson's disease. Resultant injuries can lead to increased hospitalisation and excess mortality. As the disease progresses, gait and balance deficits are relatively refractory to dopaminergic treatments suggesting another system is involved. Attentional impairment is a significant risk factor for falls, and disruption to both the cortical cholinergic system and striatal dopaminergic system increases falls in rats undergoing a complex motor task with high attentional load. However, it is unclear whether this translates to mice and whether normal ageing induces similar deficits. In this study, we use a complex motor task to test the effects of acute dopaminergic and cholinergic antagonism using alpha-flupentixol and scopolamine, respectively, in mice. We also test the effects of normal ageing on complex motor performance and whether these changes are sensitive to a clinical dose of the non-steroidal anti-inflammatory Rimadyl. Consistent with previous work, we show that cholinergic but not dopaminergic antagonism impaired task performance. However, a combined approach did not potentiate the deficit beyond observed with cholinergic antagonism alone. We also show that task performance is impaired in aged mice relative to younger controls, and that Rimadyl reduces number of foot slips in an age-specific manner. Overall, these data support prior work showing the importance of the cholinergic system in falls. The studies in aged mice found age-related impairments and a role for inflammation but did not find evidence of an interaction with attentional load, although only one manipulation was tested.

Mental health clinician perspectives regarding factors impacting implementation of evidence-based psychotherapies in Veterans Health Administration community-based outpatient clinics.

OBJECTIVE: Uptake of Evidence-Based Psychotherapies (EBPs) by mental health (MH) clinicians, especially in community settings, remains highly variable. This formative pilot study aimed to understand the attitudes and practices of Veterans Health Administration community-based MH clinicians regarding EBPs and to identify multi-level factors that enable and hinder EBP implementation in this unique context. METHODS: Semi-structured interviews were conducted with MH clinicians (N = 40) working in community-based outpatient clinics (CBOCs) in metro/urban (n = 20) and non-metro/rural (n = 20) locations. Interviews were guided by the Consolidated Framework for Implementation Research and were analyzed using rapid content analysis. Results were organized by system-, clinician-, patient-, and innovation-levels. RESULTS: EBPs were consistently perceived as important to delivering quality MH care, with most clinicians having received training in at least one VHA EBP. However, limited EBP training and consultation opportunities, inadequate autonomy to schedule EBP sessions, high and complex caseloads, and feelings of isolation at CBOCs decreased EPB use. Social workers perceived disparities in EBP training access relative to psychologists. Some barriers were more salient in non-metro/rural settings (e.g., patient-level privacy concerns). CONCLUSIONS: Increased EBP training opportunities- particularly for social workers-, greater flexibility over schedules and caseloads, and more mechanisms for consultation and professional development may increase EBP uptake in community-based clinics.

Assessment of Automated Nucleic Acid Extraction Systems in Combination with MinION Sequencing As Potential Tools for the Detection of Microbial Biosignatures.

The utilization of nanopore technologies for the detection of organic biogenic compounds has garnered significant focus in recent years. Oxford Nanopore Technologies' (ONT) MinION instrument, which can detect and sequence nucleic acids (NAs), is one such example. These technologies have much promise for unambiguous life detection but require significant development in terms of methods for extraction and preparation of NAs for biosignature detection and their feasibility for use in astrobiology-focused field missions. In this study, we tested pre-existing, automated, or semiautomated NA extraction technologies, coupled with automated ONT VolTRAX NA sample preparation, and verification with Nanopore MinION sequencing. All of the extraction systems tested (SuperFastPrep2, ClaremontX1, and SOLID-Sample Preparation Unit) showed potential for extracting DNA from Canadian High Arctic environments analogous to Mars, Europa, and Enceladus, which could subsequently be detected and sequenced with the MinION. However, they differed with regard to efficacy, yield, purity, and sequencing and annotation quality. Overall, bead beating-based systems performed the best for these parameters. In addition, we showed that the MinION could sequence unpurified DNA contained in crude cell lysates. This is valuable from an astrobiology perspective because purification steps are time-consuming and complicate the requirements for an automated extraction and life detection system. Our results indicate that semiautomated NA extraction and preparation technologies hold much promise, and with increased optimization and automation could be coupled to a larger platform incorporating nanopore detection and sequencing of NAs for life detection applications.

Diagnosing Mild Cognitive Impairment Among Racially Diverse Older Adults: Comparison of Consensus, Actuarial, and Statistical Methods.

BACKGROUND: Actuarial and statistical methods have been proposed as alternatives to conventional methods of diagnosing mild cognitive impairment (MCI), with the aim of enhancing diagnostic and prognostic validity, but have not been compared in racially diverse samples. OBJECTIVE: We compared the agreement of consensus, actuarial, and statistical MCI diagnostic methods, and their relationship to race and prognostic indicators, among diverse older adults. METHODS: Participants (N = 354; M age = 71; 68% White, 29% Black) were diagnosed with MCI or normal cognition (NC) according to clinical consensus, actuarial neuropsychological criteria (Jak/Bondi), and latent class analysis (LCA). We examined associations with race/ethnicity, longitudinal cognitive and functional change, and incident dementia. RESULTS: MCI rates by consensus, actuarial criteria, and LCA were 44%, 53%, and 41%, respectively. LCA identified three MCI subtypes (memory; memory/language; memory/executive) and two NC classes (low normal; high normal). Diagnostic agreement was substantial, but agreement of the actuarial method with consensus and LCA was weaker than the agreement between consensus and LCA. Among cases classified as MCI by actuarial criteria only, Black participants were over-represented, and outcomes were generally similar to those of NC participants. Consensus diagnoses best predicted longitudinal outcomes overall, whereas actuarial diagnoses best predicted longitudinal functional change among Black participants. CONCLUSION: Consensus diagnoses optimize specificity in predicting dementia, but among Black older adults, actuarial diagnoses may be more sensitive to early signs of decline. Results highlight the need for cross-cultural validity in MCI diagnosis and should be explored in community- and population-based samples.

Impact of carbamazepine on vitamin D levels: A meta-analysis.

PURPOSE: There are longstanding concerns about the impact of enzyme-inducing anti-seizure medications (ASMs) on vitamin D, an important molecule in both bone metabolism and inflammation pathways. The relationship between chronic use of carbamazepine and vitamin D levels has been studied, but no comprehensive review to inform practitioners and policymakers is currently available. We performed a meta-analysis on studies that measured 25-hydroxyvitamin D (25OHD) levels in persons taking carbamazepine to determine whether this drug significantly reduces circulating 25OHD. PRINCIPAL RESULTS: From a literature search of the terms "carbamazepine" and "vitamin D", we identified 12 studies that measured 25OHD levels in persons on carbamazepine monotherapy groups and controls. Persons taking carbamazepine had significantly lower 25OHD levels than persons not taking carbamazepine. The average 25OHD levels of carbamazepine-treated patients across all studies was 21.8 ng/mL (IQR 15.4,26.0) whereas 25OHD levels of control subjects was 28.0 ng/mL (IQR 20.8,30.4). The weighted difference of means was 4.00 ng/mL of 25OHD. Neither age nor sex nor duration of carbamazepine therapy had a significant impact on this finding. The effect was similar irrespective of whether the comparator group consisted of healthy controls or epilepsy patients taking non-inducing medications. MAJOR CONCLUSIONS: Carbamazepine use is associated with a reduction of 25OHD levels. In combination with other literature establishing the problematic metabolic effects of carbamazepine, this meta-analysis provides additional evidence in favor of the use of alternative ASMs as first-line agents. At minimum, vitamin D supplementation should be strongly considered for patients prescribed carbamazepine.

MinION sequencing from sea ice cryoconites leads to de novo genome reconstruction from metagenomes.

Genome reconstruction from metagenomes enables detailed study of individual community members, their metabolisms, and their survival strategies. Obtaining high quality metagenome-assembled genomes (MAGs) is particularly valuable in extreme environments like sea ice cryoconites, where the native consortia are recalcitrant to culture and strong astrobiology analogues. We evaluated three separate approaches for MAG generation from Allen Bay, Nunavut sea ice cryoconites-HiSeq-only, MinION-only, and hybrid (HiSeq + MinION)-where field MinION sequencing yielded a reliable metagenome. The hybrid assembly produced longer contigs, more coding sequences, and more total MAGs, revealing a microbial community dominated by Bacteroidetes. The hybrid MAGs also had the highest completeness, lowest contamination, and highest N50. A putatively novel species of Octadecabacter is among the hybrid MAGs produced, containing the genus's only known instances of genomic potential for nitrate reduction, denitrification, sulfate reduction, and fermentation. This study shows that the inclusion of MinION reads in traditional short read datasets leads to higher quality metagenomes and MAGs for more accurate descriptions of novel microorganisms in this extreme, transient habitat and has produced the first hybrid MAGs from an extreme environment.

Measurement invariance of the Childhood Autism Rating Scale (CARS) across six countries.

The Childhood Autism Rating Scale (CARS) is a simple and inexpensive tool for Autism spectrum disorder (ASD) assessments, with evidenced psychometric data from different countries. However, it is still unclear whether ASD symptoms are measured the same way across different societies and world regions with this tool, since data on its cross-cultural validity are lacking. This study evaluated the cross-cultural measurement invariance of the CARS among children with ASD from six countries, for whom data were aggregated from previous studies in India (n = 101), Jamaica (n = 139), Mexico (n = 72), Spain (n = 99), Turkey (n = 150), and the United States of America (n = 186). We analyzed the approximate measurement invariance based on Bayesian structural equation modeling. The model did not fit the data and its measurement invariance did not hold, with all items found non-invariant across the countries. Items related to social communication and interaction (i.e., relating to people, imitation, emotional response, and verbal and nonverbal communication) displayed lower levels of cross-country non-invariance compared to items about stereotyped behaviors/sensory sensitivity (i.e., body and object use, adaptation to change, or taste, smell, and touch response). This study found that the CARS may not provide cross-culturally valid ASD assessments. Thus, cross-cultural comparisons with the CARS should consider first which items operate differently across samples of interest, since its cross-cultural measurement non-invariance could be a source of cross-cultural variability in ASD presentations. Additional studies are needed before drawing valid recommendations in relation to the cultural sensitivity of particular items.

Cellular Therapy for the Treatment of Paediatric Respiratory Disease.

Respiratory disease is the leading cause of death in children under the age of 5 years old. Currently available treatments for paediatric respiratory diseases including bronchopulmonary dysplasia, asthma, cystic fibrosis and interstitial lung disease may ameliorate symptoms but do not offer a cure. Cellular therapy may offer a potential cure for these diseases, preventing disease progression into adulthood. Induced pluripotent stem cells, mesenchymal stromal cells and their secretome have shown great potential in preclinical models of lung disease, targeting the major pathological features of the disease. Current research and clinical trials are focused on the adult population. For cellular therapies to progress from preclinical studies to use in the clinic, optimal cell type dosage and delivery methods need to be established and confirmed. Direct delivery of these therapies to the lung as aerosols would allow for lower doses with a higher target efficiency whilst avoiding potential effect of systemic delivery. There is a clear need for research to progress into the clinic for the treatment of paediatric respiratory disease. Whilst research in the adult population forms a basis for the paediatric population, varying disease pathology and anatomical differences in paediatric patients means a paediatric-centric approach must be taken.

A dose escalation study of RO6870810/TEN-10 in patients with acute myeloid leukemia and myelodysplastic syndrome.

Bromodomain and extra-terminal (BET) proteins can drive carcinogenesis and therapy resistance. RO6870810 (RO) is a novel, small-molecule BET inhibitor. We conducted a study in 32 patients with relapsed/refractory acute myeloid leukemia and hypomethylating agent-refractory myelodysplastic syndrome (NCT02308761). Pharmacodynamic assessments showed decreases in CD11b in peripheral blood mononuclear cells at RO concentrations above 120 ng/mL. Treatment emergent adverse events were generally mild and the most frequent were fatigue, injection site reactions, diarrhea, decreased appetite and nausea. There were no treatment-related deaths. Potential drug-related dose limiting toxicities included decreased appetite, congestive cardiac failure, hypertension, fatigue, increased conjugated bilirubin and increased gamma glutamyltransferase. One AML patient achieved complete remission after withdrawal from study. Eleven AML patients experienced SD. For AML, the median OS was 72.0 days. For MDS, two patients experienced SD. Further development of RO as monotherapy was discontinued due to lack of efficacy, but combinations with other agents are under consideration.

Establishing a taxonomy of potential hazards associated with communicating medical science in the age of disinformation.

OBJECTIVES: Disinformation on medical matters has become an increasing public health concern. Public engagement by scientists, clinicians and patient advocates can contribute towards public understanding of medicine. However, depth of feeling on many issues (notably vaccination and cancer) can lead to adverse reactions for those communicating medical science, including vexatious interactions and targeted campaigns. Our objective in this work is to establish a taxonomy of common negative experiences encountered by those communicating medical science, and suggest guidelines so that they may be circumvented. DESIGN: We establish a taxonomy of the common negative experiences reported by those communicating medical science, informed by surveying medical science communicators with public platforms. PARTICIPANTS: 142 prominent medical science communicators (defined as having >1000 Twitter followers and experience communicating medical science on social and traditional media platforms) were invited to take part in a survey, with 101 responses. RESULTS: 101 responses were analysed. Most participants experienced abusive behaviour (91.9%), including persistent harassment (69.3%) and physical violence and intimidation (5.9%). A substantial number (38.6%) received vexatious complaints to their employers, professional bodies or legal intimidation. The majority (62.4%) reported negative mental health sequelae due to public outreach, including depression, anxiety and stress. A significant minority (19.8%) were obligated to seek police advice or legal counsel due to actions associated with their outreach work. While the majority targeted with vexatious complaints felt supported by their employer/professional body, 32.4% reported neutral, poor or non-existent support. CONCLUSIONS: Those engaging in public outreach of medical science are vulnerable to negative repercussions, and we suggest guidelines for professional bodies and organisations to remedy some of these impacts on front-line members.

Influence of pubertal development on urinary oxidative stress biomarkers in adolescent girls in the New York LEGACY cohort.

Puberty is a time of intense growth and differentiation of breast tissue and a window of susceptibility (WOS) for breast cancer. Although oxidative stress markers have been associated with breast cancer risk, it is unclear whether oxidative stress levels are different during the pubertal WOS, and if so, whether these differences are related to breast cancer susceptibility. We measured urinary biomarkers of whole body oxidative stress (urinary F2-Isoprostanes and 8-oxodeoxyguanosine (8-oxodG)) in 158 girls (ages 6-13 years), 71 with and 87 without a breast cancer family history (BCFH) from a cohort of adolescent girls from the New York site of the LEGACY cohort (Lessons in Epidemiology and Genetics in Adults Cancer from Youth). We compared levels of urinary oxidative stress biomarkers (F2-Isoprostanes and 8-oxodG) across the pubertal window, defined by Tanner Stage (TS) of breast development, both cross-sectionally and longitudinally within girls over an 18-month follow up period. Urinary oxidative stress biomarkers were unrelated to pubertal stages in cross-sectional analyses after considering adjustments for body mass index (BMI) and BCFH. In our longitudinal analysis, we found that urinary 8-oxodG levels, but not F2-Isoprostane levels, increased with age in BCFH + girls (ß = 6.12, 95% CI = 0.08-12.16) compared to BCFH-girls. Higher BMI was associated with higher level of F2-Isoprostane in both cross-sectional (ß = 0.02, 95% CI = 0.0004-0.05) and longitudinal analysis (ß = 0.02, 95% CI = 0.0002-0.05). These findings support that higher BMI increases oxidative stress biomarkers over the pubertal window and that there are changes in 8-oxodG oxidative stress biomarkers in girls with a BCFH compared to girls without a BCFH.

Subjective Cognitive Complaint in Parkinson's Disease Patients With Normal Cognition: Canary in the Coal Mine?

OBJECTIVE: The objective of this study was to determine the frequency and impact of subjective cognitive complaint (SCC) in Parkinson's disease (PD) patients with normal cognition. METHODS: Patients with PD with expert consensus-determined normal cognition at baseline were asked a single question regarding the presence of SCC. Baseline (N = 153) and longitudinal (up to 4 follow-up visits during a 5-year period; N = 121) between-group differences in patients with PD with (+SCC) and without (-SCC) cognitive complaint were examined, including cognitive test performance and self-rated and informant-rated functional abilities. RESULTS: A total of 81 (53%) participants reported a cognitive complaint. There were no between-group differences in global cognition at baseline. Longitudinally, the +SCC group declined more than the -SCC group on global cognition (Mattis Dementia Rating Scale-2 total score, F1,431 = 5.71, P = 0.02), processing speed (Symbol Digit Modalities Test, F1,425 = 7.52, P = 0.006), and executive function (Trail Making Test Part B, F1,419 = 4.48, P = 0.04), although the results were not significant after correction for multiple testing. In addition, the +SCC group was more likely to progress to a diagnosis of cognitive impairment over time (hazard ratio = 2.61, P = 0.02). The +SCC group also demonstrated significantly lower self-reported and knowledgeable informant-reported cognition-related functional abilities at baseline, and declined more on an assessment of global functional abilities longitudinally. CONCLUSIONS: Patients with PD with normal cognition, but with SCC, report poorer cognition-specific functional abilities, and are more likely to be diagnosed with cognitive impairment and experience global functional ability decline long term. These findings suggest that SCC and worse cognition-related functional abilities may be sensitive indicators of initial cognitive decline in PD. © 2020 International Parkinson and Movement Disorder Society.

Integrated Care in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Quality of life in Parkinson's disease (PD) is affected by motor and nonmotor symptoms, necessitating an integrated care approach. Existing care models vary considerably in numerous domains. The objectives of this study were to perform a systematic review and meta-analysis of PD integrated care models and develop recommendations for a representative model. METHODS: We conducted a systematic review of published integrated care models and a meta-analysis of randomized, controlled trials examining integrated care versus standard care. The primary outcome was health-related quality of life using a validated PD scale. We evaluated levels of care integration using the Rainbow Model of Integrated Care. RESULTS: Forty-eight publications were identified, including 8 randomized, controlled trials with health-related quality of life data (n = 1,149 total PD patients). Qualitative evaluation of individual care model integration guided by the Rainbow Model of Integrated Care revealed frequent clinical and professional integration, but infrequent organizational and population-based integration elements. Meta-analysis of randomized, controlled trials revealed significant heterogeneity (I2 = 90%, P < 0.0001). Subgroup analysis including only outpatient care models (n = 5) indicated homogeneity of effects (I2 = 0%, P = 0.52) and improved health-related quality of life favoring integrated care, with a small effect size (standardized mean difference [SMD], -0.17; 95% CI, -0.31 to -0.03; P = 0.02). CONCLUSIONS: Outpatient integrated PD care models may improve patient-reported health-related quality of life compared with standard care; however, because of variable methodological approaches and a high risk of bias related to inherent difficulties in study design (eg, blinding of participants and interventionists), generalizability of these results are difficult to establish. The Rainbow Model of Integrated Care is a promising method of evaluating elements and levels of integration from individual patient care to population health in a PD context. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, LLC. on behalf of International Parkinson and Movement Disorder Society.