Quantifying differences in pill swallow patterns in adults

Difficulty swallowing pills has become an increasing complaint among patients visiting swallow evaluation centers across the globe. Deficits are reported in healthy individuals as well as in clinical populations. In the USA, 40% of 679 persons responding to a survey reported difficulty swallowing pills (Business Wire, 2009). In an effort to facilitate pill intake, several modifications have been reported: use of liquid formulations, crushing tablet, opening capsule, whole pill mixed with food or via feeding tube (Cornish, 2005). A survey of 40 nurses revealed the most common modification was to use apple sauce (Riquelme et al., 2009). Current literature on swallowing pills focuses mostly on esophageal transit of pills in adults and on how to feed pills to children. However, little attention has been given to the physiology responsible for pill swallowing. The purpose of this prospective study was to identify patterns employed by adults during self-administration of pills and determine differences by medium used (thin liquid water, semi-solid applesauce). Participants included 42 adults, 28 female, referred for videofluoroscopy (VFSS). Age range was 86-27; mean of 66 years. Fluoroscopy data were captured on the Kay Pentax DSW. The contrast material employed was a barium-filled capsule. Participants completed two trials with water and two with applesauce. A total of 129 swallows were analyzed: 71 pill + water and 58 pill + apple sauce. Results revealed 13 patterns for swallowing pills, with cohesive swallow (38.85%), lingual pumping (16.56%), and lingual hesitation (15.92%) among the most prevalent. Additionally, it was found that 63% of the sample utilized different patterns based on medium employed to transport the pill (water vs apple sauce), and 18.2% utilized different patterns across all trials. This study supports the need to further understand changes to the swallow mechanism inherent in transporting a pill, so as to improve management and compliance and reduce unnecessary changes in formulations

Feeding/Swallowing Disorders: Maintaining Quality of Life in Persons with Intellectual Disability

Persons with intellectual disability (ID) have received little attention in systematic studies of healthcare and quality of life. Less attention has been provided to specific disorders, such as those impacting the swallowing mechanism. In comparison to the general population, persons with ID experience noticeably greater healthcare inequalities and despite greater life expectancy, it is still lower than the general population. This paper serves as an introduction to healthcare colleagues regarding the risks involved in choking and swallowing disorders in persons with ID, how to evaluate these potential risks and possible treatments. Associated etiologies are presented. A discussion on feeding disorders versus swallowing disorders is also introduced. The inadequacy of swallowing assessment services to persons with ID may be related to the lack of professionals with specialized training in working with this population, reduced funding for research to explore options for improved nutrition and reduced risk of choking and minimal research on changes in feeding skills and/or swallow physiology in this select group of individual

Creation and Initial Validation of the International Dysphagia Diet Standardisation Initiative Functional Diet Scale

OBJECTIVE: To assess consensual validity, interrater reliability, and criterion validity of the International Dysphagia Diet Standardisation Initiative Functional Diet Scale, a new functional outcome scale intended to capture the severity of oropharyngeal dysphagia, as represented by the degree of diet texture restriction recommended for the patient. DESIGN: Participants assigned International Dysphagia Diet Standardisation Initiative Functional Diet Scale scores to 16 clinical cases. Consensual validity was measured against reference scores determined by an author reference panel. Interrater reliability was measured overall and across quartile subsets of the dataset. Criterion validity was evaluated versus Functional Oral Intake Scale (FOIS) scores assigned by survey respondents to the same case scenarios. Feedback was requested regarding ease and likelihood of use. SETTING: Web-based survey. PARTICIPANTS: Respondents (N=170) from 29 countries. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Consensual validity (percent agreement and Kendall tau), criterion validity (Spearman rank correlation), and interrater reliability (Kendall concordance and intraclass coefficients). RESULTS: The International Dysphagia Diet Standardisation Initiative Functional Diet Scale showed strong consensual validity, criterion validity, and interrater reliability. Scenarios involving liquid-only diets, transition from nonoral feeding, or trial diet advances in therapy showed the poorest consensus, indicating a need for clear instructions on how to score these situations. The International Dysphagia Diet Standardisation Initiative Functional Diet Scale showed greater sensitivity than the FOIS to specific changes in diet. Most (\u3e70%) respondents indicated enthusiasm for implementing the International Dysphagia Diet Standardisation Initiative Functional Diet Scale. CONCLUSIONS: This initial validation study suggests that the International Dysphagia Diet Standardisation Initiative Functional Diet Scale has strong consensual and criterion validity and can be used reliably by clinicians to capture diet texture restriction and progression in people with dysphagia

Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The DAPA-MODA study.

AIMS Dapagliflozin improves the prognosis of patients with heart failure (HF), regardless of left ventricular ejection fraction (LVEF). However, its effect on cardiac remodelling parameters, specifically left atrial (LA) remodelling, is not well established. METHODS AND RESULTS The DAPA-MODA trial (NCT04707352) is a multicentre, single-arm, open-label, prospective and interventional study that aimed to evaluate the effect of dapagliflozin on cardiac remodelling parameters over 6 months. Patients with stable chronic HF receiving optimized guideline-directed therapy, except for any sodium-glucose cotransporter 2 inhibitor, were included. Echocardiography was performed at baseline, 30 and 180 days, and analysed by a central core-lab in a blinded manner to both patient and time. The primary endpoint was the change in maximal LA volume index (LAVI). A total of 162 patients (64.2% men, 70.5 ± 10.6 years, 52% LVEF >40%) were included in the study. At baseline, LA dilatation was observed (LAVI 48.1 ± 22.6 ml/m2 ) and LA parameters were similar between LVEF-based phenotypes (≤40% vs. >40%). LAVI showed a significant reduction at 180 days (-6.6% [95% confidence interval -11.1, -1.8], p = 0.008), primarily due to a decrease in reservoir volume (-13.8% [95% confidence interval -22.5, -4], p = 0.007). Left ventricular geometry improved with significant reductions in left ventricular mass index (-13.9% [95% confidence interval -18.7, -8.7], p < 0.001), end-diastolic volume (-8.0% [95% confidence interval -11.6, -4.2], p < 0.001) and end-systolic volume (-11.9% [95% confidence interval -16.7, -6.8], p < 0.001) at 180 days. N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed a significant reduction at 180 days (-18.2% [95% confidence interval -27.1, -8.2], p < 0.001), without changes in filling Doppler measures. CONCLUSION Dapagliflozin administration in stable out-setting patients with chronic HF and optimized therapy results in global reverse remodelling of cardiac structure, including reductions in LA volumes and improvement in left ventricular geometry and NT-proBNP concentrations.This study has been sponsored by Sociedad Española de Cardiología and has received funding by a non-conditional investigational grant from AstraZeneca Farmacéutica Spain.S

Automatic Mapping of Discontinuity Persistence on Rock Masses Using 3D Point Clouds

Finding new ways to quantify discontinuity persistence values in rock masses in an automatic or semi-automatic manner is a considerable challenge, as an alternative to the use of traditional methods based on measuring patches or traces with tapes. Remote sensing techniques potentially provide new ways of analysing visible data from the rock mass. This work presents a methodology for the automatic mapping of discontinuity persistence on rock masses, using 3D point clouds. The method proposed herein starts by clustering points that belong to patches of a given discontinuity. Coplanar clusters are then merged into a single group of points. Persistence is measured in the directions of the dip and strike for each coplanar set of points, resulting in the extraction of the length of the maximum chord and the area of the convex hull. The proposed approach is implemented in a graphic interface with open source software. Three case studies are utilized to illustrate the methodology: (1) small-scale laboratory setup consisting of a regular distribution of cubes with similar dimensions, (2) more complex geometry consisting of a real rock mass surface in an excavated cavern and (3) slope with persistent sub-vertical discontinuities. Results presented good agreement with field measurements, validating the methodology. Complexities and difficulties related to the method (e.g. natural discontinuity waviness) are reported and discussed. An assessment on the applicability of the method to the 3D point cloud is also presented. Utilization of remote sensing data for a more objective characterization of the persistence of planar discontinuities affecting rock masses is highlighted herein

Development of a Non-invasive Device for Swallow Screening in Patients at Risk of Oropharyngeal Dysphagia : Results from a Prospective Exploratory Study

Oropharyngeal dysphagia is prevalent in several at-risk populations, including post-stroke patients, patients in intensive care and the elderly. Dysphagia contributes to longer hospital stays and poor outcomes, including pneumonia. Early identification of dysphagia is recommended as part of the evaluation of at-risk patients, but available bedside screening tools perform inconsistently. In this study, we developed algorithms to detect swallowing impairment using a novel accelerometer-based dysphagia detection system (DDS). A sample of 344 individuals was enrolled across seven sites in the United States. Dual-axis accelerometry signals were collected prospectively with simultaneous videofluoroscopy (VFSS) during swallows of liquid barium stimuli in thin, mildly, moderately and extremely thick consistencies. Signal processing classifiers were trained using linear discriminant analysis and 10,000 random training-test data splits. The primary objective was to develop an algorithm to detect impaired swallowing safety with thin liquids with an area under receiver operating characteristic curve (AUC) > 80% compared to the VFSS reference standard. Impaired swallowing safety was identified in 7.2% of the thin liquid boluses collected. At least one unsafe thin liquid bolus was found in 19.7% of participants, but participants did not exhibit impaired safety consistently. The DDS classifier algorithms identified participants with impaired thin liquid swallowing safety with a mean AUC of 81.5%, (sensitivity 90.4%, specificity 60.0%). Thicker consistencies were effective for reducing the frequency of penetration-aspiration. This DDS reached targeted performance goals in detecting impaired swallowing safety with thin liquids. Simultaneous measures by DDS and VFSS, as performed here, will be used for future validation studies.Peer reviewe

Lupus risk variants in the PXK locus alter B-cell receptor internalization

Genome wide association studies have identified variants in PXK that confer risk for humoral autoimmune diseases, including systemic lupus erythematosus (SLE or lupus), rheumatoid arthritis and more recently systemic sclerosis. While PXK is involved in trafficking of epidermal growth factor Receptor (EGFR) in COS-7 cells, mechanisms linking PXK to lupus pathophysiology have remained undefined. In an effort to uncover the mechanism at this locus that increases lupus-risk, we undertook a fine-mapping analysis in a large multi-ancestral study of lupus patients and controls. We define a large (257kb) common haplotype marking a single causal variant that confers lupus risk detected only in European ancestral populations and spans the promoter through the 3' UTR of PXK. The strongest association was found at rs6445972 with P &lt; 4.62 × 10-10, OR 0.81 (0.75 - 0.86). Using stepwise logistic regression analysis, we demonstrate that one signal drives the genetic association in the region. Bayesian analysis confirms our results, identifying a 95% credible set consisting of 172 variants spanning 202 kb. Functionally, we found that PXK operates on the B-cell antigen receptor (BCR); we confirmed that PXK influenced the rate of BCR internalization. Furthermore, we demonstrate that individuals carrying the risk haplotype exhibited a decreased rate of BCR internalization, a process known to impact B cell survival and cell fate. Taken together, these data define a new candidate mechanism for the genetic association of variants around PXK with lupus risk and highlight the regulation of intracellular trafficking as a genetically regulated pathway mediating human autoimmunity

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMEDPlus study

Background: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Methods: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≥3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Results: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). Conclusions: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals