Metabolomic associations of impaired awareness of hypoglycaemia in type 1 diabetes.

This study investigates impaired awareness of hypoglycaemia (IAH), a complication of insulin therapy affecting 20-40% of individuals with type 1 diabetes. The exact pathophysiology is unclear, therefore we sought to identify metabolic signatures in IAH to elucidate potential pathophysiological pathways. Plasma samples from 578 individuals of the Dutch type 1 diabetes biomarker cohort, 67 with IAH and 108 without IAH (NAH) were analysed using the targeted metabolomics Biocrates AbsoluteIDQ p180 assay. Eleven metabolites were significantly associated with IAH. Genome-wide association studies of these 11 metabolites identified significant single nucleotide polymorphisms (SNPs) in C22:1-OH and phosphatidylcholine diacyl C36:6. After adjusting for the SNPs, 11 sphingomyelins and phosphatidylcholines were significantly higher in the IAH group in comparison to NAH. These metabolites are important components of the cell membrane and have been implicated to play a role in cell signalling in diabetes. These findings demonstrate the potential role of phosphatidylcholine and sphingomyelins in IAH.

Relationship between arm span to height ratio, aortic root diameter, and systolic blood pressure in collegiate athletes.

Study objective: Sudden cardiac death is the most common cause of non-traumatic death in collegiate athletes. Marfan syndrome poses a risk for sudden cardiac death secondary to aortic root dilation leading to aortic dissection or rupture. Arm span to height ratio (ASHR) > 1.05 has been proposed as a screening tool for Marfan syndrome in pre-participation examinations (PPE) for collegiate athletes but limited data exists on the association between ASHR and aortic root diameter (ARD). This study examines the relationship between ASHR and ARD and assesses for predictors of ARD. Design: Retrospective chart review. Setting: National Collegiate Athletic Association Division I University. Participants: 793 athletes across thirteen sports between 2012 and 2022 evaluated with PPE and screening echocardiogram. Interventions: Not applicable. Main outcome measures: (1) Relationships between ASHR, SBP, BSA, and ARD amongst all athletes as well as stratified by ASHR >1.05 or ≤1.05 using univariate analysis. (2) Predictors of ARD using multivariate analysis using linear regression. Results: 143 athletes (18 %) had ASHRs > 1.05. Athletes with ASHR > 1.05 had higher ARD (2.99 cm) than athletes with ASHR ≤ 1.05 (2.85 cm). Weak correlations were noted between ASHR, ARD, and SBP. Multivariate analysis showed that BSA, male sex, and participation in swimming were predictors of ARD. ASHR was not predictive of ARD in regression analysis. Conclusions: These findings showed a tendency towards higher ARD in athletes with ASHR >1.05 but this observation was not statistically significant in multivariate analysis.

Implementation effort: Reducing the ordering of inappropriate echocardiograms through a point-of-care decision support tool.

Study objective: Reduce inappropriate transthoracic echocardiograms (TTEs) using a series of Plan-Do-Study-Act (PDSA) quality improvement cycles. Design: Three PDSA cycles were designed with the first integrating a previously published decision support tool (DST) into the electronic TTE order, the second tailoring the DST to reflect the most common inappropriately ordered TTEs at our institution, and the third integrating direct clinician education. Setting: Malcom Randall Veterans Administration Medical Center, Gainesville, Florida, USA. Participants: Consecutive patients were studied using the database of all TTEs performed at our institution without regard for specific patient characteristics. Interventions: Three PDSA Cycles as described above. Main outcome measure: Reduction in inappropriate TTEs at our institution. Results: After implementing our DST during the first cycle, no difference in inappropriate TTEs was observed (relative risk [RR] 0.71, p = 0.12, 95 % confidence interval [CI] 0.46-1.09). After the second cycle, we observed a reduction in the proportion of inappropriate TTEs (RR = 0.69, p = 0.014, 95 % CI 0.5-0.94), however two of the four inappropriate TTEs targeted by the DST increased. Feedback gathered from clinicians in the third cycle showed significant knowledge gaps regarding appropriate use criteria for TTE. Conclusions: At our facility, implementation of a DST failed to substantially reduce inappropriate TTEs, even when adapted to facility-specific ordering patterns. Gaps in clinician knowledge about TTEs may have contributed to the inefficacy of our DST.

Blood pressure characteristics of collegiate female athletes: A call for more focused attention on young women's health.

Background: There is a paucity of data describing the association between blood pressure (BP) and cardiac remodeling in female collegiate athletes. Methods: This retrospective cohort review describes the BP characteristics and echocardiographic features of female collegiate athletes during preparticipation evaluation. We evaluated data from 329 female athletes at two National Collegiate Athletic Association (NCAA) Division I universities who underwent preparticipation evaluation that included medical history, physical examination, 12-lead electrocardiography, and 2-dimensional transthoracic echocardiography. BP values were divided into categories of normal, elevated, stage 1 and stage 2 hypertension based on 2017 ACC/AHA Guidelines. Left ventricular mass index was calculated and indexed to body surface area and further classified into concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Results: Normal BP values were noted in 184 (56%) female athletes, 88 (26.7%) had elevated BP and 57 (17.3%) had BP values indicating stage 1 or 2 hypertension. The majority of participants were white (n = 136, 73.9%). There was significantly higher body surface area in female athletes with higher BP values: 1.85 ± 0.18 in the stage 1 and 2 hypertension range, 1.82 ± 0.18 in the elevated BP range versus 1.73 ± 0.16 in the normal BP range (p < 0.001). Conclusions: There was a trend toward higher incidence of concentric and eccentric hypertrophy in athletes with higher than normal BP, however no statistical significance was noted. Elevated BP values were frequent among female collegiate athletes, and there is evidence of cardiac remodeling associated with higher BP values.

Preparticipation Cardiac Evaluation Findings in a Cohort of Collegiate Female Athletes.

Knowledge of cardiovascular adaptations in athletes has predominantly focused on males, with limited data available on females who compromise a substantial percentage of all collegiate athletes. A multicenter retrospective cohort review of preparticipation cardiovascular screening data of 329 National Collegiate Athletic Association Division I female athletes was performed. This included physical exams, electrocardiograms, and echocardiograms. Female athletes in class IB sports had elevated systolic blood pressure (p = 0.01). For electrocardiograms, 7 (2%) had abnormal findings: 100% were white; 6 of 7 (86%) participated in IIC sports. Black athletes had longer PR intervals (p ≤ 0.001), whereas white athletes had longer QTc and QRS durations (p = 0.02 and 0.01, respectively). Athletes in IC and IIC sports had longer QTc intervals (p = 0.01). For echocardiographic parameters, no differences were noted based on race. However, significant differences were noted based on classification of sport: athletes in class IC sports had higher left-atrial volume indexes and E/A ratios. Athletes in class IB and IIC had increased left-ventricular wall thicknesses and aortic root dimensions. In conclusion, among one of the largest cohorts of collegiate female athlete preparticipation cardiac screening data to date, significant differences in various parameters based on classification of sport and race were observed. These categorizations should be considered when interpreting cardiovascular screening in female collegiate athletes to improve screening and guide future research.

Advances in small-molecule therapy for managing angina pectoris in the elderly.

Introduction: As our population ages, the prevalence of angina is growing, leading to increased morbidity and decreased quality of life. The management of angina in the elderly is challenging due to drug intolerance and/or drug resistance as well as frailty. Over the past decades, many new therapeutic small molecules have been investigated for the management of angina. Although none of these studies have specifically focused on the therapies for the elderly, they offer promising new avenues for the treatment of angina in the elderly. Areas covered: Herein, the authors provide a review of the recently published literature on the use of small-molecule therapies for angina management in the elderly and provide a brief overview of these therapies. Expert opinion: A variety of therapeutic classes of existing and newer small molecules are emerging for the management of angina in the elderly. An individualized approach to the management of angina in this growing population is critical for good outcomes. Many small molecules are in their initial stages of clinical use, and further research should be conducted on their utility, especially in the elderly.

Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction ancillary study.

BACKGROUND: In a prior trial of late sodium channel inhibition (ranolazine) among symptomatic subjects without obstructive coronary artery disease (CAD) and limited myocardial perfusion reserve index (MPRI), we observed no improvement in angina or MPRI, overall. Here we describe the clinical characteristics and myocardial perfusion responses of a pre-defined subgroup who had coronary flow reserve (CFR) assessed invasively. METHODS: Symptomatic patients without obstructive CAD and limited MPRI in a randomized, double-blind, crossover trial of ranolazine vs. placebo were subjects of this prespecified substudy. Because we had previously observed that adverse outcomes and beneficial treatment responses occurred in those with lower CFR, patients were subgrouped by CFR <2.5 vs ≥2.5. Symptoms were assessed using the Seattle Angina Questionnaire and the SAQ-7, and left-ventricular volume and MPRI were assessed by magnetic resonance imaging (MRI). Coronary angiograms, CFR, and MRI data were analyzed by core labs masked to treatment and patient characteristics. RESULTS: During qualifying coronary angiography, 81 patients (mean age 55 years, 98% women) had invasively determined CFR 2.69 ±â€¯0.65 (mean ±â€¯SD; range 1.4-5.5); 43% (n = 35) had CFR <2.5. Demographic and symptomatic findings did not differ comparing CFR subgroups. Those with low CFR had improved angina (p = 0.04) and midventricular MPRI (p = 0.03) with ranolazine vs placebo. Among patients with low CFR, reduced left-ventricular end-diastolic volume predicted a beneficial angina response. CONCLUSIONS: Symptomatic patients with CFR <2.5 and no obstructive CAD had improved angina and myocardial perfusion with ranolazine, supporting the hypothesis that the late sodium channel is important in management of coronary microvascular dysfunction. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT01342029.

Using Simulation to Teach Echocardiography: A Systematic Review.

STATEMENT: We identified 24 studies of high-fidelity simulation being used to teach echocardiography. A variety of study designs were used with outcomes ranging from reports of learner self-confidence up to improvement in organizational practice. Most studies were carried out in graduate medical populations, specifically in anesthesia trainees. The substantial majority of studies (91.6%) concluded that simulation has positive outcomes for teaching echocardiography. Future investigations would benefit from application of educational theory and should focus on demonstrating whether simulation can improve care delivery and patient outcomes.

Optimum Antithrombotic Therapy in Patients Requiring Long-Term Anticoagulation and Undergoing Percutaneous Coronary Intervention.

Management of patients on long-term anticoagulation requiring percutaneous coronary intervention is challenging. Triple therapy with oral anticoagulant and dual antiplatelet therapy is the standard of care. However, there is no strong evidence to support this strategy. There is emerging data regarding the safety and efficacy of dual therapy with oral anticoagulant and single antiplatelet therapy in these patients. In this comprehensive review we highlight available evidence regarding various antithrombotic regimens' efficacy and safety in patient with coronary artery disease undergoing percutaneous coronary intervention with long-term anticoagulation therapy requirements.

Learning from errors: unnecessary intensive care unit admissions.

An elderly man was transferred to our emergency department with reported ventricular tachycardia requiring intravenous amiodarone and intensive care unit admission. Device interrogation, the following day, revealed only frequent premature ventricular contractions and non-sustained ventricular tachycardia in a patient with a known history of these conditions. The patient underwent unnecessary invasive monitoring after being emergently transferred to our facility and admitted to the intensive care unit. Fortunately, our patient did not suffer any unwarranted side effects from intravenous amiodarone. This case reports on some negative consequences of inappropriate intensive care unit admissions and how they could have been avoided.

Migraine Headache and Long-Term Cardiovascular Outcomes: An Extended Follow-Up of the Women's Ischemia Syndrome Evaluation.

BACKGROUND: The association between migraine headache and cardiovascular events has been inconsistent. This study determines the long-term risk of cardiovascular events among women with and without a history of migraine headache who were under evaluation for suspected myocardial ischemia in the Women's Ischemia Syndrome Evaluation (WISE). METHODS: The WISE is a National Heart, Lung and Blood Institute-sponsored prospective, multicenter study that aims to improve myocardial ischemia evaluation in women. A total of 936 women presenting with symptoms of myocardial ischemia underwent structured data collection and coronary angiography. Information pertaining to migraine headache was available in 917 women. All-cause mortality data were available on all women for a median of 9.5 years, and nonfatal cardiovascular event data were available on 888 women for a median of 6.5 years. RESULTS: A total of 224 (24.4%) women reported a history of migraine headache. Compared with women who did not report a history of migraine headache, women with a history of migraine headache had an increased adjusted risk of cardiovascular event (cardiovascular death, nonfatal myocardial infarction, heart failure, or stroke) (hazard ratio 1.83; 95% confidence interval, 1.22-2.75) at a median follow-up of 6.5 years. This result was driven mainly by a twofold increase in the risk of stroke (hazard ratio 2.33; 95% confidence interval, 1.16-4.68). CONCLUSION: Among women being evaluated for ischemic heart disease, those reporting a history of migraine headache had increased risk of future cardiovascular events on long-term follow-up. This risk was primarily driven by a more-than twofold increase in the risk of stroke.

A group therapist reflects on violence in America.

In this paper, the author draws on his experience as a group therapist, noting parallels between the often intense but well contained dynamics of therapy groups and what they can tell us about violence in America. He examines the tension between bearing and understanding feelings and the desire to act on them, sometimes destructively in therapy groups and in society. He notes the omnipresent desire to find scapegoats rather than bear our own discomforts and notes the same in the abuse through which those in power scapegoat those under their control. Using the ideas of Roche, Volkan, and others, he also notes that current violence emerges from threats to individual or group identities often embedded in unfinished crises in the past, whether in a therapy group or in American society. Unresolved racial tensions reaching into the past is one outstanding example. He concludes noting the important role of reparation and forgiveness in therapy groups and society to slow the forward movement of violence.

Storming the gates of interprofessional collaboration.

This type of collaboration is the way of the future; are you aware of its benefits for leaders?

Changes in paediatric hospital ENT service utilisation following the implementation of a mobile, indigenous health screening service.

In 2009, we established a mobile ear-screening service for children in a remote community approximately 350 km north-west of Brisbane. We compared pre-implementation health service utilisation data (2006-2008) with data for the following three years. The study included only children in schools that had participated in screening since the start of the screening programme and for which data for the 6-year study period were available. In the baseline period there were 329 ear, nose and throat (ENT) outpatient appointments at the Royal Children's Hospital (RCH) in Brisbane for children from the selected catchment area. Of these, 166 (51%) were failure-to-attends (FTAs). In the following three years, there were 105 appointments, of which 40 (38%) were FTAs. In the baseline period, 100 children received surgical procedures at the RCH; in the following three years there were 43. In the three years following implementation, 136 children were booked to receive surgical procedures locally at the Cherbourg hospital, and 117 (86%) were completed. Since no other major health service changes occurred in the region during the study period, we conclude that the telemedicine-enabled screening service improved access to specialist care in the community and resulted in fewer outpatient and surgical appointments at the tertiary centre in Brisbane.

Evaluating a novel panel of sperm function tests for utility in predicting intracytoplasmic sperm injection (ICSI) outcome.

PURPOSE: The objective of this study was to evaluate a panel of three sperm function tests; tests known to assess different aspects of sperm functionality and genomic integrity, the: 1) Sperm DNA Accelerated Decondensation (SDAD(TM)) Test, 2) Sperm DNA Decondensation (SDD(TM)) Test, and 3) Sperm Penetration Assay (SPA), determining if positive and negative test scores correlated with failed and successful ICSI outcomes, respectfully. METHODS: A prospective, double blinded, cohort study was performed. One study sample (ejaculated semen) was collected by each of the 60 male partners of the 60 couples enrolled in the study; males whose female partners were found to have no major female factor issues. The sperm from each male was analyzed in the SPA, and SDAD and SDD Tests, and used for ICSI (1 ICSI cycle per couple). RESULTS: The ICSI cycle pregnancy rate for this study was 50 %, with a delivery rate=40 % (n=60 ICSI cycles). The SPA and SDD Test scores did not significantly predict ICSI outcome when used as stand-alone tests (p>>0.05). However, when the SPA and SDD Test scores were used together, ICSI outcomes for a subgroup of 10 (16.7 %) males, were significantly predicted (p=0.03), with 1 live birth, and 9 negatives where the transferred embryos did not implant. In total, 38.4 % of the couples in this study were found to have a very poor chance for a successful ICSI cycle. CONCLUSION: SDAD Test scores alone, and SPA and SDD Test scores used together, significantly predicted failed ICSI outcomes. This indicates that the scores obtained when analyzing patients' sperm using a panel of sperm function tests; specifically, the SPA, and SDAD and SDD Tests, can be used to identify infertile couples who should not be directed to ICSI.

Analyzing Thiol-Dependent Redox Networks in the Presence of Methylene Blue and Other Antimalarial Agents with RT-PCR-Supported in silico Modeling.

BACKGROUND: In the face of growing resistance in malaria parasites to drugs, pharmacological combination therapies are important. There is accumulating evidence that methylene blue (MB) is an effective drug against malaria. Here we explore the biological effects of both MB alone and in combination therapy using modeling and experimental data. RESULTS: We built a model of the central metabolic pathways in P. falciparum. Metabolic flux modes and their changes under MB were calculated by integrating experimental data (RT-PCR data on mRNAs for redox enzymes) as constraints and results from the YANA software package for metabolic pathway calculations. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, chloroquine resistance based on pfmdr/and pfcrt transporters, as well as pyrimethamine/sulfadoxine resistance (by mutations in DHF/DHPS), were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs. CONCLUSIONS: Theoretical and experimental results support that methylene blue should, because of its resistance-breaking potential, be further tested as a key component in drug combination therapy efforts in holoendemic areas.