Impact of an intergenerational program to improve loneliness and social isolation in older adults initiated at the time of emergency department discharge: study protocol for a three-arm randomized clinical trial.

BACKGROUND: Social isolation and loneliness (SIL) worsens mortality and other outcomes among older adults as much as smoking. We previously tested the impact of the HOW R U? intervention using peer support from similar-aged volunteers and demonstrated reduced SIL among older adults discharged from the emergency department (ED). Generativity, defined as "the interest in establishing and guiding the next generation," can provide an alternative theoretical basis for reducing SIL via intergenerational programs between members of younger and older generations. The current protocol will examine the impact of younger intergenerational volunteers providing the HOW RU? METHODS: In this randomized clinical trial, we will compare the following three arms: (1) the standard same-generation peer support HOW R U? intervention, (2) HOW R U? intervention delivered by intergenerational volunteers, and (3) a common wait-list control group. Outcome assessors will be blinded to the intervention. Trained volunteers will deliver 12 weekly telephone support calls. We will recruit participants ≥ 70 years of age with baseline loneliness (six-item De Jong loneliness score of 2 or greater) from two EDs. Research staff will assess SIL, depression, quality of life, functional status, generativity, and perceived benefit at baseline, at 12 weeks, and 24 weeks post-intervention. DISCUSSION: We hypothesize participants receiving the intergenerational intervention will show improved outcomes compared to the control group and peer support HOW R U? INTERVENTION: We also hypothesize that participants with higher perceptions of generativity will have greater reductions in SIL than their lower generativity counterparts. Aging is experienced diversely, and social interventions combatting associated SIL should reflect that diversity. As part of a program of research following the Obesity-Related Behavioral Intervention Trials (ORBIT) model, the findings of this RCT will be used to define which intervention characteristics are most effective in reducing SIL. TRIAL REGISTRATION: ClinicalTrials.gov NCT05998343 Protocol ID:21-0074E. Registered on 24 July 2023.

Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy.

Introduction: Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD. Methods: The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene-disease relationships (GDR) using the ClinGen gene-disease clinical validity framework to evaluate 31 genes implicated in LGMD. Results: The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as Definitive, 4 (11%) as Moderate and 1 (3%) as Limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD. Conclusions: The expert-reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case-level data that help clarify disputed or novel LGMD associations.

Pathogenic Variants in USH1G/SANS Alter Protein Interaction with Pre-RNA Processing Factors PRPF6 and PRPF31 of the Spliceosome.

Pre-mRNA splicing is an essential process orchestrated by the spliceosome, a dynamic complex assembled stepwise on pre-mRNA. We have previously identified that USH1G protein SANS regulates pre-mRNA splicing by mediating the intranuclear transfer of the spliceosomal U4/U6.U5 tri-snRNP complex. During this process, SANS interacts with the U4/U6 and U5 snRNP-specific proteins PRPF31 and PRPF6 and regulates splicing, which is disturbed by variants of USH1G/SANS causative for human Usher syndrome (USH), the most common form of hereditary deaf-blindness. Here, we aim to gain further insights into the molecular interaction of the splicing molecules PRPF31 and PRPF6 to the CENTn domain of SANS using fluorescence resonance energy transfer assays in cells and in silico deep learning-based protein structure predictions. This demonstrates that SANS directly binds via two distinct conserved regions of its CENTn to the two PRPFs. In addition, we provide evidence that these interactions occur sequentially and a conformational change of an intrinsically disordered region to a short α-helix of SANS CENTn2 is triggered by the binding of PRPF6. Furthermore, we find that pathogenic variants of USH1G/SANS perturb the binding of SANS to both PRPFs, implying a significance for the USH1G pathophysiology.

Electroencephalogram measured functional connectivity for delirium detection: a systematic review.

Objective: Delirium is an acute alteration of consciousness marked by confusion, inattention, and changes in cognition. Some speculate that delirium may be a disorder of functional connectivity, but the requirement to lay still may limit measurement with existing functional imaging modalities in this population. Electroencephalography (EEG) may allow for a more feasible approach to the study of potential connectivity disturbances in delirium. We conducted a systematic review to investigate whether there are EEG-measurable differences in brain functional connectivity in the resting state associated with delirium. Methods: Medline, PubMed, PsychInfo, Embase and CINAHL were searched for relevant articles containing original data studying EEG functional connectivity measures in delirium. Results: The search yielded 1,516 records. Following strict inclusion criteria, four studies were included in the review. The studies used a variety of EEG measures including phase lag index, coherence, entropy, shortest path length, minimum spanning tree, and network clustering coefficients to study functional connectivity between scalp electrodes. Across connectivity measures, delirium was associated with decreased brain functional connectivity. All four studies found decreased alpha band connectivity for patients with delirium. None of the studies directly compared the different motor subtypes of delirium. Significance: This systematic review provides converging evidence for disturbances in oscillatory-based functional connectivity in delirium.

Diagnostic Performance of Ultrasonography-Based Risk Models in Differentiating Between Benign and Malignant Ovarian Tumors in a US Cohort.

Importance: Ultrasonography-based risk models can help nonexpert clinicians evaluate adnexal lesions and reduce surgical interventions for benign tumors. Yet, these models have limited uptake in the US, and studies comparing their diagnostic accuracy are lacking. Objective: To evaluate, in a US cohort, the diagnostic performance of 3 ultrasonography-based risk models for differentiating between benign and malignant adnexal lesions: International Ovarian Tumor Analysis (IOTA) Simple Rules with inconclusive cases reclassified as malignant or reevaluated by an expert, IOTA Assessment of Different Neoplasias in the Adnexa (ADNEX), and Ovarian-Adnexal Reporting and Data System (O-RADS). Design, Setting, and Participants: This retrospective diagnostic study was conducted at a single US academic medical center and included consecutive patients aged 18 to 89 years with adnexal masses that were managed surgically or conservatively between January 2017 and October 2022. Exposure: Evaluation of adnexal lesions using the Simple Rules, ADNEX, and O-RADS. Main Outcomes and Measures: The main outcome was diagnostic performance, including area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. Surgery or follow-up were reference standards. Secondary analyses evaluated the models' performances stratified by menopause status and race. Results: The cohort included 511 female patients with a 15.9% malignant tumor prevalence (81 patients). Mean (SD) ages of patients with benign and malignant adnexal lesions were 44.1 (14.4) and 52.5 (15.2) years, respectively, and 200 (39.1%) were postmenopausal. In the ROC analysis, the AUCs for discriminative performance of the ADNEX and O-RADS models were 0.96 (95% CI, 0.93-0.98) and 0.92 (95% CI, 0.90-0.95), respectively. After converting the ADNEX continuous individualized risk into the discrete ordinal categories of O-RADS, the ADNEX performance was reduced to an AUC of 0.93 (95% CI, 0.90-0.96), which was similar to that for O-RADS. The Simple Rules combined with expert reevaluation had 93.8% sensitivity (95% CI, 86.2%-98.0%) and 91.9% specificity (95% CI, 88.9%-94.3%), and the Simple Rules combined with malignant classification had 93.8% sensitivity (95% CI, 86.2%-98.0%) and 88.1% specificity (95% CI, 84.7%-91.0%). At a 10% risk threshold, ADNEX had 91.4% sensitivity (95% CI, 83.0%-96.5%) and 86.3% specificity (95% CI, 82.7%-89.4%) and O-RADS had 98.8% sensitivity (95% CI, 93.3%-100%) and 74.4% specificity (95% CI, 70.0%-78.5%). The specificities of all models were significantly lower in the postmenopausal group. Subgroup analysis revealed high performances independent of race. Conclusions and Relevance: In this diagnostic study of a US cohort, the Simple Rules, ADNEX, and O-RADS models performed well in differentiating between benign and malignant adnexal lesions; this outcome has been previously reported primarily in European populations. Risk stratification models can lead to more accurate and consistent evaluations of adnexal masses, especially when used by nonexpert clinicians, and may reduce unnecessary surgeries.

Estimating body mass of wild pigs (Sus scrofa) using body morphometrics.

Wild pigs (Sus scrofa) are invading many areas globally and impacting biodiversity and economies in their non-native range. Thus, wild pigs are often targeted for eradication efforts. Age- and sex-specific body measurements are important for informing these eradication efforts because they reflect body condition, resource availability, and fecundity, which are common indicators of population trajectory. However, body mass is often difficult to collect, especially on large individuals that require specialized equipment or multiple people to weigh. Measurements that can be rapidly taken by a single land or wildlife manager on any size wild pig without aid from specialized equipment would be beneficial if they accurately infer wild pig body mass. Our goals were to assess whether morphometric measurements could accurately predict wild pig body mass, and to provide tools to directly input these measures and estimate wild pig body mass. Using linear models, we quantified the relationship between body mass and morphometric measurements (i.e., body length, chest girth, ear length, eye to snout length, hindfoot length, shoulder length, and tail length) from a subset (n = 102) of wild pigs culled at the Mississippi Alluvial Valley, Mississippi, USA. We evaluated separate models for each individual morphometric measurement. We then used the model coefficients to develop equations to predict wild pig body mass. We validated these equations predicting body mass of 1592 individuals collected across eight areas in Australia, Guam, and the USA for cross-validation. Each developed equation remained accurate when cross-validated across regions. Body length, chest girth, and shoulder length were the morphometrics that best predicted wild pig body mass. Our analyses indicated it is possible to use the presented equations to infer wild pig body mass from simple metrics.

Glucose-Regulated Protein 78 Is a Potential Serum and Imaging Marker for Early Detection of Ovarian Cancer.

BACKGROUND: Understanding malignant transformation associated with ovarian cancer (OVCA) is important to establish early detection tests. This study examined whether expression of glucose-regulated protein 78 (GRP78, marker of cellular stress) increases during OVCA development, and whether GRP78 can be detected by targeted-transvaginal ultrasound (TVUS) imaging. METHODS: Normal ovaries (n = 10), benign (n = 10) and malignant ovarian tumors at early (n = 8) and late stages (n = 16), hens with and without ovarian tumors at early and late stages (n = 10, each) were examined for GRP78 expression during OVCA development by immunohistochemistry, immunoblotting, gene expression and immunoassay. Feasibility of GRP78-targeted TVUS imaging in detecting early OVCA was examined. RESULTS: Compared with normal ovaries and benign tumors, intensity of GRP78 expression was higher (p < 0.0001) in OVCA patients. Compared with normal (9007.76 ± 816.54 pg/mL), serum GRP78 levels were significantly higher (p < 0.05) in patients with early (12,730.59 ± 817.35 pg/mL) and late-stage OVCA (13,930.12 ± 202.35) (p < 0.01). Compared with normal (222.62 ± 181.69 pg/mL), serum GRP78 levels increased (p < 0.05) in hens with early (590.19 ± 198.18 pg/mL) and late-stage OVCA (1261.38 ± 372.85) (p < 0.01). Compared with non-targeted, GRP78-targeted imaging enhanced signal intensity of TVUS (p < 0.0001). CONCLUSIONS: Tissue and serum levels of GRP78 increase in association with OVCA. GRP78 offers a potential serum and imaging marker for early OVCA detection.

Prospective Validation of Computed Tomography to Identify Patients at High Risk for Stroke After Transient Ischemic Attack or Minor Stroke.

BACKGROUND: Computed tomography (CT) findings of acute and chronic ischemia are associated with subsequent stroke risk in patients with transient ischemic attack. We sought to validate these associations in a large prospective cohort of patients with transient ischemic attack or minor stroke. METHODS: This prospective cohort study enrolled emergency department patients from 13 hospitals with transient ischemic attack who had CT imaging. Primary outcome was stroke within 90 days. Secondary outcomes were stroke within 2 or 7 days. CT findings were abstracted from radiology reports and classified for the presence of acute ischemia, chronic ischemia, or microangiopathy. Multivariable logistic regression was used to test associations with primary and secondary end points. RESULTS: From 8670 prospectively enrolled patients between May 2010 and May 2017, 8382 had a CT within 24 hours. From this total population, 4547 (54%) patients had evidence of acute ischemia, chronic ischemia, or microangiopathy on CT, of whom 175 had a subsequent stroke within 90 days (3.8% subsequent stroke rate; adjusted odds ratio [aOR], 2.33 [95% CI, 1.62-3.36]). This was in comparison to those with CT imaging without ischemia. Findings associated with an increased risk of stroke at 90 days were isolated acute ischemia (6.0%; aOR, 2.42 [95% CI, 1.03-5.66]), acute ischemia with microangiopathy (10.7%; aOR, 3.34 [95% CI, 1.57-7.14]), chronic ischemia with microangiopathy (5.2%; aOR, 1.83 [95% CI, 1.34-2.50]), and acute ischemia with chronic ischemia and microangiopathy (10.9%; aOR, 3.49 [95% CI, 1.54-7.91]). Acute ischemia with chronic ischemia and microangiopathy were most strongly associated with subsequent stroke within 2 days (aOR, 4.36 [95% CI, 1.31-14.54]) and 7 days (aOR, 4.50 [95% CI, 1.73-11.69]). CONCLUSIONS: In patients with transient ischemic attack or minor stroke, CT evidence of acute ischemia with chronic ischemia or microangiopathy significantly increases the risk of subsequent stroke within 90 days of index visit. The combination of all 3 findings results in the greatest early risk.

Ovarian Masses: The Value of Acoustic Shadowing on Ultrasound Examination.

Adnexal lesions are a common finding in women and pose a clinical challenge since ovarian cancer is a highly lethal disease. However, most adnexal masses are benign, benefiting from a more conservative approach. In preoperative assessment, transvaginal ultrasound plays a key role in evaluating morphologic features that correlate with the risk of malignancy. The acoustic shadow is the loss of echo behind sound-absorbing components, such as calcifications or fibrous tissues, which are predominantly found in benign lesions. However, recognizing the acoustic shadow is a difficult skill to master, and its usefulness may be underappreciated.

Understanding why delirium is often missed in older emergency department patients: a qualitative descriptive study.

OBJECTIVES: Unrecognized delirium is associated with significant adverse outcomes. Despite decades of effort and educational initiatives, validated screening tools have not improved delirium recognition in the emergency department (ED). There remains a fundamental knowledge gap of why it is consistently missed. The objective of this study was to explore the perceptions of ED physicians and nurses regarding factors contributing to missed delirium in older ED patients. METHODS: We conducted a qualitative descriptive study at two academic tertiary care EDs in Toronto, Canada. Emergency physicians and nurses were interviewed by a trained qualitative researcher using a semi-structured interview guide. We coded transcripts with an iteratively developed codebook. Interviews were conducted until thematic saturation occurred. Thematic data analysis occurred in conjunction with data collection to continuously monitor emerging themes and areas for further exploration. RESULTS: We interviewed 26 ED physicians and nurses. We identified key themes at four levels: clinical practice, provider attitudes, systematic processes, and education. The four themes include: (1) there are varied approaches to delirium recognition and infrequent use of screening tools; (2) delirium assessment is perceived as overly time consuming and of lower priority than other symptoms and syndromes; (3) it is unclear whose responsibility it is to recognize delirium; and (4) there is a need for a deeper or "functional" understanding of delirium that includes its consequences. CONCLUSIONS: Our findings demonstrate a need for ED leadership to identify clear team roles for delirium recognition, standardize use of delirium screening tools, and prioritize delirium as a symptom of an acute medical emergency.

RéSUMé: OBJECTIFS: Le délire non reconnu est associé à des résultats négatifs importants. Malgré des décennies d'efforts et d'initiatives éducatives, les outils de dépistage validés n'ont pas amélioré la reconnaissance du délire au service des urgences (SU). Il reste une lacune fondamentale dans la connaissance des raisons pour lesquelles elle est systématiquement manquée. L'objectif de cette étude était d'explorer les perceptions des médecins et des infirmières de l'urgence au sujet des facteurs contribuant au délire manqué chez les patients âgés des urgences. MéTHODES: Nous avons mené une étude qualitative descriptive dans deux urgences universitaires de soins tertiaires à Toronto, au Canada. Les médecins et les infirmières des urgences ont été interrogés par un chercheur qualitatif formé à l'aide d'un guide d'entretien semi-structuré. Nous avons codé les transcriptions à l'aide d'un livre de codes développé de manière itérative. Les entretiens ont été menés jusqu'à saturation thématique. L'analyse thématique des données s'est déroulée conjointement avec la collecte des données afin de surveiller continuellement les thèmes émergents et les domaines à explorer davantage. RéSULTATS: Nous avons interrogé 26 médecins et infirmières des urgences. Nous avons identifié des thèmes clés à quatre niveaux : la pratique clinique, les attitudes des prestataires, les processus systématiques et l'éducation. Les quatre thèmes abordés sont les suivants : 1) les approches de la reconnaissance du délire sont variées et les outils de dépistage peu utilisés ; 2) l'évaluation du délire est perçue comme prenant trop de temps et moins prioritaire que d'autres symptômes et syndromes ; 3) il n'est pas clair à qui revient la responsabilité de reconnaître le délire ; et 4) il est nécessaire d'avoir une compréhension plus profonde ou "fonctionnelle" du délire, qui inclut ses conséquences. CONCLUSIONS: Nos résultats démontrent la nécessité pour les responsables des urgences de définir clairement les rôles de l'équipe pour la reconnaissance du delirium, de normaliser l'utilisation des outils de dépistage du delirium et d'accorder la priorité au delirium en tant que symptôme d'une urgence médicale aiguë.

Can we improve delirium prevention and treatment in the emergency department? A systematic review.

BACKGROUND: This systematic review was conducted to evaluate any interventions to prevent incident delirium, or shorten the duration of prevalent delirium, in older adults presenting to the emergency department (ED). METHODS: Health sciences librarian designed electronic searches were conducted from database inception through September 2021. Two authors reviewed studies, and included studies that evaluated interventions for the prevention and/or treatment of delirium and excluded non-ED studies. The risk of bias (ROB) was evaluated by the Cochrane ROB tool or the Newcastle-Ottawa (NOS) scale. Meta-analysis was conducted to estimate a pooled effect of multifactorial programs on delirium prevention. RESULTS: Our search strategy yielded 11,900 studies of which 10 met study inclusion criteria. Two RCTs evaluated pharmacologic interventions for delirium prevention; three non-RCTs employed a multi-factorial delirium prevention program; three non-RCTs evaluated regional anesthesia for hip fractures; and one study evaluated the use of Foley catheter, medication exposure, and risk of delirium. Only four studies demonstrated a significant impact on delirium incidence or duration of delirium-one RCT of melatonin reduced the incidence of delirium (OR 0.19, 95% CI 0.06 to 0.62), one non-RCT study on a multi-factorial program decreased inpatient delirium prevalence (41% to 19%) and the other reduced incident delirium (RR 0.37, 95% CI 0.22 to 0.61). One case-control study on the use of ED Foley catheters in the ED increased the duration of delirium (proportional OR 3.1, 95% CI 1.3 to 7.4). A pooled odds ratio for three multifactorial programs on delirium prevention was 0.46 (95% CI 0.31-0.68, I2  = 0). CONCLUSION: Few interventions initiated in the ED were found to consistently reduce the incidence or duration of delirium. Delirium prevention and treatment trials in the ED are still rare and should be prioritized for future research.

Prevalence, management and outcomes of unrecognized delirium in a National Sample of 1,493 older emergency department patients: how many were sent home and what happened to them?

BACKGROUND: Retrospective studies estimate Emergency Department (ED) delirium recognition at <20%; few prospective studies have assessed delirium recognition and outcomes for patients with unrecognized delirium. OBJECTIVES: To prospectively measure delirium recognition by ED nurses and physicians, document their confidence in diagnosis and disposition, actual dispositions, and patient outcomes. METHODS: Prospective observational study of people ≥65 years. We assessed delirium using the Confusion Assessment Method, then asked ED staff if the patient had delirium, confidence in their assessment, if the patient could be discharged, and contacted patients 1 week postdischarge. We report proportions and 95% confidence intervals (Cls). RESULTS: We enrolled 1,493 participants; mean age was 77.9 years; 49.2% were female, 79 (5.3%, 95% CI 4.2-6.5%) had delirium. ED nurses missed delirium in 43/78 cases (55.1%, 95% CI 43.4-66.4%). Nurses considered 12/43 (27.9%) patients with unrecognized delirium safe to discharge. Median confidence in their delirium diagnosis for patients with unrecognized delirium was 7.0/10. Physicians missed delirium in 10/20 (50.0%, 95% CI 27.2-72.8) cases and considered 2/10 (20.0%) safe to discharge. Median confidence in their delirium diagnosis for patients with unrecognized delirium was 8.0/10. Fifteen patients with unrecognized delirium were sent home: 6.7% died at 1 week follow-up vs. none in those with recognized delirium and 1.1% in the rest of the cohort. CONCLUSION: Delirium recognition by nurses and physicians was sub-optimal at ~50% and may be associated with increased mortality. Research should explore root causes of unrecognized delirium, and novel strategies to systematically improve delirium recognition and patient outcomes.

Ultrasound for Aesthetic Applications: A Review of Biophysical Mechanisms and Safety.

Aesthetic ultrasound is used for fat reduction and to improve skin appearance. In this review, the fundamental mechanisms by which ultrasound can alter tissue are outlined. The technologies that are commercially available or under development are discussed. Finally, recommendations are made for safe and effective use of aesthetic ultrasound.

World Federation for Ultrasound in Medicine Review Paper: Incidental Findings during Obstetrical Ultrasound.

Although the prevalence of incidental findings revealed during an obstetric ultrasound examination is low, the findings may include adnexal and cervical masses, uterine or urinary congenital malformations, free fluid in the pouch of Douglas or tortuous vessels (varices). Adnexal masses are the most common finding and vary in imaging characteristics. They are mainly unilateral, cystic masses with a low risk of malignancy that are treated conservatively. The International Ovarian Tumor Analysis scoring models may be helpful in differentiating benign from malignant masses. For those masses >5 cm, follow-up is recommended, and resection could be considered to avoid risk of torsion, rupture and hemorrhage, which may compromise pregnancy outcome. Uterine masses such as fibroids are commonly diagnosed early in the first trimester and should be followed up during pregnancy to evaluate any changes. Transabdominal and transvaginal ultrasound is the first-line test for the diagnosis of such incidentalomas; however, magnetic resonance ultrasound may have a useful role in excluding malignancy potential. As a result of their low frequency and the lack of good evidence, there are no specific guidelines on the management of incidentalomas detected at obstetric scans. Their management should follow the related general guidelines for ovarian, cervical and uterine masses, with individualized management depending on the pregnancy status.