A Core Outcome Set for Research Evaluating Interventions to Enable Communication in Patients With an Artificial Airway: An International Delphi Consensus Study (Comm-COS).

OBJECTIVES: Critically ill adults requiring artificial airways experience profound communication deficits. Studies of interventions supporting communication report disparate outcomes, creating subsequent challenges in the interpretation of their effectiveness. Therefore, we aimed to develop international consensus for a communication core outcome set (Comm-COS) for future trials of communication interventions in this population. DESIGN: 1) Systematic review, 2) patient/family interviews, 3) two-round modified Delphi, and 4) virtual consensus meetings with a final voting round. A multidisciplinary expert steering committee oversaw all stages. SETTING: Interviews and consensus meetings were conducted via videoconferencing. Digital methods were used for Delphi and final Comm-COS voting. SUBJECTS: Three stakeholder groups: 1) patient and family members with lived experience within 3 years, 2) clinicians with experience working in critical care, and 3) researchers publishing in the field. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We identified 59 outcomes via our systematic review, 3 unique outcomes from qualitative interviews, and 2 outcomes from our steering committee. Following item reduction, 32 outcomes were presented in Delphi round 1; 134 participants voted; 15 patient/family (11%), 91 clinicians (68%), and 28 researchers (21%). Nine additional outcomes were generated and added to round 2; 106 (81%) participants voted. Following completion of the consensus processes, the Comm-COS includes seven outcomes: 1) changes in emotions and wellbeing associated with ability to communicate, 2) physical impact of communication aid use, 3) time to functional communication, 4) ability to communicate healthcare needs (comfort/care/safety/decisions), 5) conversation agency, 6) ability to establish a communication connection to develop and maintain relationships, and 7) acceptability of the communication intervention. CONCLUSIONS: This is the first COS to specifically focus on communication for critically ill adults. Limitations for operationalization include selection of measures to use with these outcomes. Identification of suitable measures and adoption of the Comm-COS in future trials will help establish effective interventions to ameliorate the highly prevalent and negative experience of communicative incapacity.

'Patient unable to express why he was on the floor, he has aphasia.' A content thematic analysis of medical records and incident reports on the falls of hospital patients with communication disability following stroke.

BACKGROUND: People with communication disability following stroke are at risk of falls during inpatient rehabilitation. However, they are often excluded from hospital falls research, and little is known about the circumstances or outcomes of their falls to inform risk management strategies. AIMS: To examine hospital medical records and incident reports relating to falls of patients with communication disability following stroke for content codes, categories and themes relating to communication. METHODS & PROCEDURES: This medical record chart review examined data on 72 patients and 265 falls. A content thematic analysis was used to identify how patient communication is characterized in relation to falls, and their prevention and management strategies. OUTCOMES & RESULTS: The data reflected that staff viewed patients having difficulty following simple instructions as contributing to falls. Gaining the attention of staff and communicating basic needs were also considered to be contributing factors for falls. Patients were often described as experiencing a fall when taking a risk or attempting to address an unmet basic need. Furthermore, written notes for patients with more severe communication disability reflected that the patient's communication impairments prevented staff from establishing the circumstances of some falls and complicated the assessment for injury following a fall. CONCLUSIONS & IMPLICATIONS: The medical records and incident reports of patients with communication disability following stroke reveal that hospital staff recognize the impact of communication disability as potential risk factors for falls for this group. It was difficult for staff to report the circumstances of the fall for patients with severe communication disability. Despite the recognition of communication as a potential contributing factor, few medical record entries documented strategies related to communication interventions to improve patients' ability to understand instructions, gain attention or communicate basic needs. WHAT THIS PAPER ADDS: What is already known on the subject People with stroke are at a high risk of falls during their hospital admission. However, little is known about the circumstances of their falls and the influence of communication disability on these falls. What this paper adds to existing knowledge Patients with communication disability have unique factors that contribute to their falls in the hospital. Patients were described as experiencing a fall when taking a risk or attempting to address an unmet need, and these falls were often related to a patient's difficulties communicating their basic needs, gaining attention from staff, and following simple instructions. What are the potential or actual clinical implications of this work? Communication disability as a risk factor for a fall, and fall prevention strategies tailored to the communication disability, were typically identified and documented by physiotherapists, occupational therapists and nursing staff. The inclusion of speech pathologists in fall risk assessment, management, and prevention strategies may provide crucial information regarding the patient's communication disability that may enhance their fall prevention plan.

Falls in hospital patients with acquired communication disability secondary to stroke: A systematic review and meta-analysis.

BACKGROUND: Falls are a common safety incident in people with stroke. Studies report that between 14% and 65% of people with stroke fall at least once during their hospital admission. Risk factors for falls in people with stroke have been reported to include neglect, balance and dependence for activities of daily living. Communication disability has been identified as a risk factor for patient safety incidents in hospital that has not been closely examined as a potential risk factor for falls in people with stroke. AIM: To determine the association between communication disability secondary to stroke and falls in people with stroke in hospital. METHODS & PROCEDURES: Systematic searches of five electronic databases were conducted in June 2019 using the key concepts of 'falls' and 'stroke' (PROSPERO CRD 42019137199). Included studies provided comparative data of falls in patients with stroke with and without communication disability. The methodological quality of the studies was examined using the Quality Assessment Tool for Studies with Diverse Designs (QATSDD). Both a narrative synthesis and a meta-analysis were completed. MAIN CONTRIBUTION: A total of 15 studies met the criteria for inclusion and 11 were included in a meta-analysis. Three studies found people with communication disability had an increased rate of falls in hospital. However, a meta-analysis showed no significant association between a non-specific classification of communication disability and an increased risk of falls. There was some indication from individual studies that higher risk of falls may be associated with severe communication disability, but there were insufficient data reported on the severity of the communication disability to draw robust conclusions. CONCLUSION & IMPLICATIONS: The results of this systematic review suggest that a generic classification of communication disability following stroke is not a risk factor for falls. However, further research that is inclusive of this population and considers severity of communication disability more specifically is required. What this paper adds What is already known on the subject The association between communication disability following stroke and falls in hospital is unclear. The literature reports mixed results regarding the impact of a communication disability following stroke on falls risk or rates of falls during hospital admission. What this paper adds to existing knowledge This review is the first to bring together this diverse literature to examine the association between communication disability following stroke and falls in hospital. The results suggest that a generic classification of communication disability following stroke is not a risk factor for falls. What are the potential or actual clinical implications of this work? There is a possibility that moderate to severe communication disability may be related to falls in patients in hospital. Further research is indicated to be more inclusive of people with communication disability, including those with severe communication disability.

[18F]FDG cardiac PET imaging in a canine model of radiation-induced cardiovascular disease associated with breast cancer radiotherapy.

Radiotherapy for the treatment of left-sided breast cancer increases the long-term risk of cardiovascular disease. The purpose of the present study was to noninvasively image the progression of radiation-induced cardiac inflammation in a large animal model using a hybrid PET and MRI system. Five canines were imaged using [18F]fluorodeoxyglucose PET to assess changes in myocardial inflammation. All animals were imaged at baseline, 1 wk, and 1, 3, 6, and 12 mo after focused cardiac external beam irradiation with image guidance. Radiation was delivered in a single fraction. The linear quadratic model was used to convert a typical multifractionated heart dose to a corrected single-fraction biologically equivalent dose. Immunohistochemistry was performed on excised left ventricular tissue samples from all five irradiated canines and one nonirradiated control canine to confirm the presence of inflammation. The mean doses delivered to the entire heart, left ventricle, left anterior descending artery, and left circumflex artery were 1.7 ± 0.2, 2.7 ± 0.2, 5.5 ± 0.9, and 1.1 ± 0.4 Gy, respectively. FDG standard uptake values remained persistently elevated compared with baseline (1.1 ± 0.03 vs. 2.6 ± 0.19, P < 0.05). The presence of myocardial inflammation was confirmed histologically and correlated with myocardial dose. This study suggests a global inflammatory response that is persistent up to 12 mo postirradiation. Inflammation PET imaging should be considered in future clinical studies to monitor the early changes in cardiac function that may play a role in the ultimate development of radiation-induced cardiac toxicity. NEW & NOTEWORTHY Using advanced cardiac PET imaging, we have shown the spatial and quantitative relationship between radiation dose deposition and temporal changes in inflammation. We have shown that the progression of radiation-induced cardiac inflammation is immediate and does not subside for up to 1 yr after radiation. Results are presented in a large animal model that closely resembles the size and vessel architecture of humans. The proposed imaging protocol can be easily replicated for clinical use.

Three-Month Randomized Clinical Trial of Nasal Calcitonin in Adults with X-linked Hypophosphatemia.

Previous work has demonstrated that a single subcutaneous dose of salmon calcitonin leads to a transient decline in circulating levels of FGF23 in patients with X-linked hypophosphatemia (XLH). Since the calcitonin receptor is expressed on osteocytes, this raises the possibility that interdicting signals through that receptor could modulate circulating levels of FGF23 in XLH. In the present study, 21 subjects with XLH were randomly assigned to receive either placebo nasal spray or 400 IU of nasal salmon calcitonin daily for three months. On the first and last day of the study, serial measurements of FGF23, 1,25-dihydroxyvitamin D, and TmP/GFR were made over 27 h. At the beginning of Visit 2 (the first day of month 2) and the beginning of Visit 3 (the first day of month 3), single, first-morning, fasting measurements of these same parameters were made before the next administered dose of study drug. Following the initial or final dose of study drug, there were no differences in area under the curve, based on treatment assignment, for the three principal outcome variables. Similarly, there were no differences in the fasting measures taken at the beginning of Visit 2 or Visit 3 compared to the fasting values on either day 2 of Visit 1 or the fasting values on day 2 of Visit 4. There were also no significant changes over time in serum phosphorus, serum calcium, circulating levels of PTH, CTx, or P1NP. The reasons why nasal salmon calcitonin did not recapitulate the findings with subcutaneously administered drug may relate to the kinetics of drug delivery, the bioavailability of drug or peak drug dose achieved. It remains possible, however, that other means of altering calcitonin receptor signaling may still provide an opportunity for regulating FGF23 production.

Mechanisms for the effective implementation of an allied health assistant trainee: a qualitative study of a speech language pathology assistant.

OBJECTIVE: This paper explores the impact and mechanisms for successful implementation of a speech language pathology assistant (SLPA) role into a rehabilitation setting using a traineeship approach. METHODS: Multiple data sources were used, including interviews with key stakeholders, documentary evidence and a workload audit. RESULTS: The SLPA role increased clinical service capacity by 28 h per week across the service and required a total of 3 h per week of supervision input (the equivalent of 38 min per speech and language pathologist (SLP)). The SLPA used non-clinical time for training and administration. Mechanisms that facilitated the implementation of the SLPA role were: support for existing staff; formal knowledge and skills in training; consultation and engagement; access to a competency framework; close working with the registered training organisation; clearly defined role and delegation boundaries; clear supervision structures; confidence in own role; supportive organisational culture; vision for expansion of the role; engaging the SLPs in training and development; and a targeted recruitment approach. CONCLUSION: The development and implementation of a new trainee SLPA role using a traineeship approach required a large amount of supervision and training input from the SLPs. However, it was perceived that these efforts were offset by the increased service capacity provided by the introduction of a trainee role and the high levels of satisfaction with the new role.

Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women.

Increasing dietary protein within a physiologic range stimulates intestinal calcium absorption, but it is not known if specific amino acids or dietary protein as a whole are responsible for this effect. Therefore, we selectively supplemented a low-protein (0.7 g/kg) diet with either the calcium-sensing receptor-activating amino acids (CaSR-AAAs) L-tryptophan, L-phenylalanine, and L-histidine, or the dibasic amino acids (DAAs) L-arginine and L-lysine, to achieve intakes comparable to the content of a high-protein diet (2.1 g/kg) and measured intestinal calcium absorption. Fourteen young women took part in a placebo-controlled, double-blind, crossover feeding trial in which each participant ingested a 6-d low-protein diet supplemented with CaSR-AAAs, DAAs, or methylcellulose capsules (control) after an 11-d adjustment period. All participants ingested all 3 diets in random order. Intestinal calcium absorption was measured between days 5 and 6 using dual-stable calcium isotopes ((42)Ca, (43)Ca, and (44)Ca). There was no difference in calcium absorption between the diet supplemented with CaSR-AAAs (22.9 ± 2.0%) and the control diet (22.3 ± 1.4%) (P = 0.64). However, calcium absorption tended to be greater during the DAA supplementation period (25.2 ± 1.4%) compared with the control diet period (22.3 ± 1.4%) (P < 0.10). Larger and longer clinical trials are needed to clarify the possible benefit of arginine and lysine on calcium absorption.

Effect of Burosumab on Muscle Function and Strength, and Rates of ATP Synthesis in Skeletal Muscle in Adults With XLH.

CONTEXT: In clinical trials, burosumab ameliorates symptoms of pain, fatigue, and stiffness and improves performance on certain muscle function studies in patients with X-linked hypophosphatemia (XLH). OBJECTIVE: This work aimed to determine if burosumab increases adenosine triphosphate (ATP) synthesis in skeletal muscle of treatment-naive adults with XLH, and if so, whether that correlates with improved muscle function. METHODS: Ten untreated, symptomatic adults with XLH had ATP synthesis rates measured in the right calf using the 31P magnetic resonance spectroscopy saturation transfer technique. Baseline muscle function tests and symptoms of pain, fatigue, stiffness, and lower-extremity joint pain were quantified. All participants were treated with burosumab, 1 mg/kg every 4 weeks for 12 weeks. ATP synthesis rates and muscle function tests were repeated 2 weeks ("peak") and 4 weeks ("trough") after the third dose of burosumab. RESULTS: All symptoms improved with treatment. Performance on the 6-Minute Walk Test (6MWT) and Sit to Stand (STS) tests also improved. Muscle strength and ATP synthesis rates did not change over the 3 months of the study. When individuals whose performances on the 6MWT and STS test were at or better than the median outcome for those tests were compared to those whose outcomes were below the median, no difference was observed in the rate of change in ATP synthesis. Intracellular muscle concentrations of phosphate were normal. CONCLUSION: The improvement in the 6MWT and STS test without changes in muscle strength or ATP synthesis rates suggests that reductions in pain, fatigue, and stiffness may partly explain the improved performance. Intracellular phosphate in skeletal muscle is insulated from hypophosphatemia in XLH.

Design, Synthesis, and Preclinical Evaluation of a High-Affinity 18F-Labeled Radioligand for Myocardial Growth Hormone Secretagogue Receptor Before and After Myocardial Infarction.

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post-myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with 18F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with 18F a quinazolinone derivative ([18F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [18F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [18F]LCE470 was determined by time-activity curve and SUV analysis in 3 regions of the left ventricle-area of infarct, territory served by the left circumflex coronary artery, and remote myocardium-over a period of 1.5 y. Changes in cardiac perfusion were tracked by [13N]NH3 PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [18F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [18F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [18F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [18F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

Social determinants of health influencing the adherence to post-endoscopic mucosal resection surveillance.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a global health challenge, particularly in Alabama, where the incidence rates exceed national averages. This study investigated the factors influencing adherence to post-endoscopic mucosal resection (EMR) colonoscopies, focusing on travel distance and socioeconomic status. This study aimed to provide evidence-based insights to improve patient care in CRC management. METHODS: This retrospective study in a tertiary care referral center analyzed 465 patients who underwent EMR. The data included demographics, clinical details, and travel-related variables. Descriptive statistics, logistic regression, and spatial analysis were used to assess the factors affecting adherence. RESULTS: Of 465 patients, 36.6 % had adequate follow-up, 21.8 % had inadequate follow-up, and 41.6 % were lost to follow-up. Noteworthy demographic variations were observed, with median ages differing across adherence groups. Traveled distances showcased compelling insights, indicating a median distance of 22.2 miles for adequate follow-up, 15.7 miles for inadequate follow-up, and 31.6 miles for the lost-to-follow-up group (p<0.001). Longer travel distances were associated with better adherence. Longer travel distances from the hospital were associated with significantly lower odds of inadequate follow-up: 10-25 miles OR:0.29, 25-85 miles OR:0.35, and >80 miles OR:0.24 compared to the first quartile (<10 miles). Socioeconomic factors, particularly educational attainment, significantly influenced the follow-up rates. CONCLUSIONS: This study revealed suboptimal post-EMR follow-up rates and underscored the impact of travel distance and socioeconomic factors. Targeted interventions addressing distance-related barriers can enhance treatment adherence and ensure timely CRC surveillance after EMR. Further research is needed in diverse healthcare settings.

Hospital policies on falls in relation to patients with communication disability: a scoping review and content analysis.

Objective Falls in hospital are a significant public health issue and patients with communication disability have unique risk factors that have the potential to contribute to falls. The aim of this study is to determine how the content of hospital falls policies relate to patients with communication disability and to identify gaps in policy that need to be addressed. Methods A scoping review and content analysis of (a) policies and related documents, from a target health service in Victoria, Australia, and all relevant Australian state and territory health departments, and (b) national guidelines was performed. Data were analysed for content relating to inclusion of patients with communication disability. Results Communication disability is not captured as a risk factor for a fall in assessment tools. When included, aspects of communication disability were often conflated with cognitive impairments. There was little guidance for staff on adapting falls prevention education to suit the needs of patients with communication disability and limited identified role for speech pathologists. Conclusion This study suggests that a patient's communication disability is not visible in hospital falls policies and guidelines.

Falls in Patients With Communication Disability Secondary to Stroke.

Patients with stroke are at high risk of falls during inpatient rehabilitation admission. Communication disability is common following stroke; however, this population is often excluded from falls research. This study aimed to examine the falls of patients with communication disability following stroke, including the circumstances, contributing factors, and outcomes of the fall. This medical record review used the Generic Reference Model of patient safety as the analytical lens and data were analyzed descriptively. The study included 109 patients who experienced 308 falls. The most common type of fall was an "unwitnessed roll from bed." Patient factors contributed to half of all falls, injuries occurred in 15% of falls, and impacts to the hospital system included additional costs and staffing. Understanding the reasons why patients are attempting to get out of bed may identify ways to reduce the risk and incidence of falls in this population.

Myocardial glucose suppression may interfere with the detection of inflammatory cells with FDG-PET as suggested in a canine model of myocardial infarction.

BACKGROUND: After myocardial infarction, fibrosis and an ongoing dysregulated inflammatory response have been shown to lead to adverse cardiac remodeling. FDG PET is an imaging modality sensitive to inflammation as long as suppression protocols are observed while gadolinium enhanced MRI can be used to determine extracellular volume (ECV), a measure of fibrosis. In patients, glucose suppression is achieved variously through a high fat diet, fasting and injection of heparin. To emulate this process in canines, a heparin injection and lipid infusion are used, leading to similar fatty acids in the blood. The aim of this study was to examine the effect of glucose suppression on the uptake of FDG in the infarcted myocardial tissue and also on the determination of ECV in both the infarcted tissue and in the myocardium remote to the zone of infarction during a long constant infusion of FDG and Gd-DTPA. RESULTS: Extracellular volume was affected neither by suppression nor the length of the constant infusion in remote and infarcted tissue. Metabolic rate of glucose in infarcted tissue decreased during and after suppression of glucose uptake by lipid infusion and heparin injection. An increase in fibrosis and inflammatory cells was found in the center of the infarct as compared to remote tissue. CONCLUSION: The decrease in the metabolic rate of glucose in the infarcted tissue suggests that inflammatory cells may be affected by glucose suppression through heparin injection and lipid infusion.

Glucose Infusion Induced Change in Intracellular pH and Its Relationship with Tumor Glycolysis in a C6 Rat Model of Glioblastoma.

INTRODUCTION: The reliance on glycolytic metabolism is a hallmark of tumor metabolism. Excess acid and protons are produced, leading to an acidic tumor environment. Therefore, we explored the relationship between the tumor glycolytic metabolism and tissue pH by comparing 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and hyperpolarized [1-13C]pyruvate MR spectroscopy imaging (MRSI) to chemical exchange saturation transfer (CEST) MRI measurements of tumor pH. METHODS: 106 C6 glioma cells were implanted in the brains of male Wistar rats (N = 11) using stereotactic surgery. A 60-min PET acquisition after a bolus of FDG was performed at 11-13 days post implantation, and standardized uptake value (SUV) was calculated. CEST measurements were acquired the following day before and during constant infusion of glucose solution. Tumor intracellular pH (pHi) was evaluated using amine and amide concentration-independent detection (AACID) CEST MRI. The change of pHi (∆pHi) was calculated as the difference between pHi pre- and during glucose infusion. Rats were imaged immediately with hyperpolarized [1-13C]pyruvate MRSI. Regional maps of the ratio of Lac:Pyr were acquired. The correlations between SUV, Lac:Pyr ratio, and ∆pHi were evaluated using Pearson's correlation. RESULTS: A decrease of 0.14 in pHi was found after glucose infusion in tumor region. Significant correlations between tumor glycolysis measurements of Lac:Pyr and ∆pHi within the tumor (ρ = 0.83, P = 0.01) and peritumoral region (ρ = 0.76, P = 0.028) were observed. No significant correlations were found between tumor SUV and ∆pHi within the tumor (ρ = - 0.45, P = 0.17) and peritumor regions (ρ = - 0.6, P = 0.051). CONCLUSION: AACID detected the changes in pHi induced by glucose infusion. Significant correlations between tumor glycolytic measurement of Lac:Pyr and tumoral and peritumoral pHi and ∆pHi suggest the intrinsic relationship between tumor glycolytic metabolism and the tumor pH environment as well as the peritumor pH environment.

Differing effects of oral conjugated equine estrogen and transdermal estradiol on vitamin D metabolism in postmenopausal women: a 4-year longitudinal study.

OBJECTIVE: The aim of this study was to examine the effect of either conjugated equine estrogen or transdermal estradiol on vitamin D metabolism in postmenopausal women. METHODS: Twenty-five women from the Kronos Early Estrogen Prevention Study who were randomized to conjugated equine estrogen 0.45 mg/d and 20 women who were treated with transdermal estradiol 50 mg/d (patch replaced weekly) were analyzed in the present study. All participants received micronized progesterone for 12 days per month. RESULTS: There was no significant treatment effect on serum total 25-hydroxyvitamin D over 48 months in either study group, and there were no significant differences between treatment arms. In contrast, at 12 months, directly measured free 25-hydroxyvitamin D was significantly higher in the transdermal estradiol group than in the conjugated equine estrogen group. Directly measured free 25-hydroxyvitamin D subsequently increased significantly from 12 to 48 months in both treatment arms. Calculated free 25-hydroxyvitamin D was also significantly higher in the transdermal estradiol group at 36 months. Vitamin D-binding protein decreased significantly in both treatment groups from 12 to 48 months, but at 48 months, least square mean values were no different based on treatment assignment. CONCLUSIONS: Directly measured free 25-hydroxyvitamin D levels, but not serum total 25-hydroxyvitamin D levels, are different within the first 12 months of estrogen replacement depending on the preparation. However, this difference is transient, in that there were no differences at 36 or 48 months. These findings suggest that there may be a short-term benefit to prescribing transdermal estradiol for women who are either vitamin D deficient or vitamin D insufficient.

Assessment of left atrial fibrosis progression in canines following rapid ventricular pacing using 3D late gadolinium enhanced CMR images.

BACKGROUND: Atrial fibrillation (AF) is associated with extracellular matrix (ECM) remodelling and often coexists with myocardial fibrosis (MF); however, the causality of these conditions is not well established. OBJECTIVE: We aim to corroborate AF to MF causality by quantifying left atrial (LA) fibrosis in cardiac magnetic resonance (CMR) images after persistent rapid ventricular pacing and subsequent AF using a canine model and histopathological validation. METHODS: Twelve canines (9 experimental, 3 control) underwent baseline 3D LGE-CMR imaging at 3T followed by insertion of a pacing device and 5 weeks of rapid ventricular pacing to induce AF (experimental) or no pacing (control). Following the 5 weeks, pacing devices were removed to permit CMR imaging followed by excision of the hearts and histopathological imaging. LA myocardial segmentation was performed manually at baseline and post-pacing to permit volumetric %MF quantification using the image intensity ratio (IIR) technique, wherein fibrosis was defined as pixels > mean LA myocardium intensity + 2SD. RESULTS: Volumetric %MF increased by an average of 2.11 ± 0.88% post-pacing in 7 of 9 experimental dogs. While there was a significant difference between paired %MF measurements from baseline to post-pacing in experimental dogs (P = 0.019), there was no significant change in control dogs (P = 0.019 and P = 0.5, Wilcoxon signed rank tests). The median %MF for paced animals was significantly greater than that of non-paced dogs at the 5-week post-insertion time point (P = 0.009, Mann Whitney U test). Histopathological imaging yielded an average %MF of 19.42 ± 4.80% (mean ± SD) for paced dogs compared to 1.85% in one control dog. CONCLUSION: Persistent rapid ventricular pacing and subsequent AF leads to an increase in LA fibrosis volumes measured by the IIR technique; however, quantification is limited by inherent image acquisition parameters and observer variability.

Ventilator autotriggering: a caution in brain death diagnosis.

The Uniform Determination of Death Act and the American Academy of Neurology's Guidelines for Determination of Death define procedures for diagnosis of brain death before organ procurement for transplantation, including clinical assessment and apnea test. Autotriggering of mechanical ventilators can occur in both brain dead and living patients. A case is reported in which procurement was delayed because ventilator self-cycling was confused for brainstem-mediated respiratory effort. Background knowledge to effectively troubleshoot ventilator self-cycling is offered so that unnecessary delays in brain death testing can be avoided.

The role of ablation in the treatment of dysplastic Barrett's esophagus.

Endoscopic eradication therapy for Barrett's esophagus has been established as an effective management strategy for patients with Barrett's esophagus with dysplasia and early esophageal cancer. Among the endoscopic therapies, ablation techniques such as radiofrequency ablation and cryoablation are effective primary treatment interventions with acceptable low complication rates forming the spectrum of a multimodal approach. Appropriate selection of patients, high-definition endoscopic evaluation, and dedicated histological assessment are important cornerstones to help navigate to the best effective treatment method. Carefully structured surveillance programs and preventive measures will be needed to provide long-term durability for maintaining complete remission.

Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease.

BACKGROUND: The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR are altered significantly in late stages of heart failure (HF) and cardiomyopathy, when left ventricular (LV) function is failing. We examined the relationship of GHSR with ghrelin in cardiac tissue from patients with valvular disease with no detectable changes in LV function. METHODS: Biopsy samples from the left ventricle and left atrium were obtained from 25 patients with valvular disease (of whom 13 also had coronary artery disease) and preserved LV ejection fraction, and compared to control samples obtained via autopsy. Using quantitative confocal fluorescence microscopy, levels of GHSR were determined using [Dpr3(n-octanoyl),Lys19(sulfo-Cy5)]ghrelin(1-19), and immunofluorescence determined ghrelin, the heart failure marker natriuretic peptide type-B (BNP), and contractility marker sarcoplasmic reticulum ATPase pump (SERCA2a). RESULTS: A positive correlation between GHSR and ghrelin was apparent in only diseased tissue. Ghrelin and BNP significantly correlated in the left ventricle and strongly colocalized to the same intracellular compartment in diseased and control tissue. GHSR, ghrelin, and BNP all strongly and significantly correlated with SERCA2a in the left ventricle of diseased tissue only. CONCLUSIONS: Our results suggest that the dynamics of the myocardial ghrelin-GHSR axis is altered in cardiovascular disease in the absence of measurable changes in heart function, and might accompany a regional shift in endocrine programming.

CONTEXTE: L'hormone ghréline et son récepteur, le récepteur sécrétagogue de l'hormone de croissance (GHSR, de l'anglais growth hormone secretagogue receptor), sont exprimés dans le myocarde. La liaison au récepteur GHSR active les voies de signalisation associées à la survie et à la contractilité des cardiomyocytes. Ces propriétés font de l'axe ghréline-récepteur GHSR un bon candidat biomarqueur de la fonction cardiaque. En effet, la dynamique de cet axe est considérablement altérée aux stades avancés de l'insuffisance cardiaque et de la cardiomyopathie, lorsque la fonction ventriculaire gauche décline. Nous avons donc étudié la relation entre le récepteur GHSR et la ghréline dans le tissu cardiaque de patients présentant une valvulopathie sans changements détectables dans la fonction ventriculaire gauche. MÉTHODOLOGIE: Des échantillons de tissus du ventricule et de l'oreillette gauches ont été prélevés par biopsie chez 25 patients présentant une valvulopathie (dont 13 avaient aussi une coronaropathie) et une fraction d'éjection ventriculaire gauche préservée, puis comparés avec des échantillons témoins prélevés à l'autopsie. Les taux du récepteur GHSR ont été mesurés par microscopie en fluorescence confocale quantitative à l'aide de [Dpr3(n-octanoyl),Lys19(sulfo-Cy5)] ghréline(1-19); les taux de ghréline, de peptide natriurétique de type B (BNP, un marqueur de l'insuffisance cardiaque), et de pompe ATPase du réticulum sarcoplasmique (SERCA2a; un marqueur de la contractilité) ont quant à eux été mesurés par immunofluorescence. RÉSULTATS: Nous avons noté une corrélation positive entre le récepteur GHSR et la ghréline uniquement dans les tissus lésés. Il existe une corrélation significative entre les taux de ghréline et de BNP dans le ventricule gauche, les deux substances étant fortement localisées dans le même compartiment intracellulaire, tant dans les tissus malades que dans les tissus témoins. Le récepteur GHSR, la ghréline et le BNP sont tous fortement et significativement corrélés avec la SERCA2a SERCA2a dans le tissu ventriculaire gauche malade seulement. CONCLUSIONS: Nos résultats semblent indiquer que la dynamique de l'axe ghréline-récepteur GHSR dans le myocarde est altérée en cas de maladie cardiovasculaire même en l'absence de changements mesurables de la fonction cardiaque, et que cette altération pourrait être attribuable à une modification régionale de la programmation endocrinienne.

Evidence-based prescription of antibiotics in urology: a 5-year review of microbiology.

OBJECTIVE: To analyse the results of positive urine cultures over a 5-year period in a large hospital and urology department (amongst both inpatients and outpatients), assess the prevalence of different organisms and the resistance profiles of a range of antibiotics, and thus provide information on which organisms are likely to cause urosepsis. METHODS: The use of antibiotics should be based on knowledge of which pathogens are present and what resistance patterns are emerging, particularly relevant in surgical disciplines like urology, as antibiotics are now routinely administered peri-operatively, whereby evidence-based prescription is preferable to generic guidelines. We therefore examined almost 25,000 positive urine cultures in our hospital over a 5-year period, and focused on the infections encountered amongst urology patients during this time. RESULTS: A significant proportion of inpatient urinary infection (40%) is caused by Gram-positive bacteria such as Streptococcus faecalis, underlining the need for including Gram-positive cover during urological prophylaxis. The commonest pathogen remains Escherichia coli among both inpatients and outpatients. The ineffectiveness of common antibiotics such as ciprofloxacin and trimethoprim was identified, as was the increase in gentamicin resistance. CONCLUSION: We propose using an aminoglycoside with a penicillin for high-risk cases (e.g. endoscopic stone surgery) while low-risk cases (e.g. flexible cystoscopy with no risk factors) might be managed without such prophylaxis. Pathogenic patterns and resistance rates should be monitored regularly.