Frequency of Comfort Care and Palliative Care Consultation after ST-elevation Myocardial Infarction.

INTRODUCTION: ST-elevation myocardial infarction (STEMI) remains a leading cause of death despite advances in revascularization and post-STEMI care. Especially for patients with a poor prognosis, there is increasing emphasis on comfort-focused care. METHODS: We conducted a single-center retrospective cohort study of patients with STEMI at a large tertiary care academic medical center, abstracting patient-level data, causes of death, and use of palliative care consultation from the medical records. We sought to investigate the frequency of comfort-focused approaches and palliative care consultation after STEMI. RESULTS: A total of 536 patients presented with or were transferred with STEMI from January 2010 to July 2018, of whom 61/536 (11.4%) died during index hospitalization. Among those who underwent percutaneous intervention (PCI), the in-hospital mortality rate was 6.8%. Median (IQR) and time to death was 2 (0-6) days. Among those who died, 25/61 (41%) were treated with mechanical circulatory support (MCS). A total of 25/61 (41%) patients died following transition to a comfort-focused approach. Rate of MCS utilization during hospitalization was higher in the group that was ultimately transitioned to comfort-focused measures than the group who received full treatment measures. Palliative care was consulted in the case of 6/61 (9.8%) patients. Median time to consultation was 5 (1-7) days and time to death was 6.5 (2-28) days. DISCUSSION: Transition to comfort-focused care before death after STEMI is common, particularly in those with cardiogenic shock and/or treated with MCS, highlighting the critical status of such patients. Although increasingly employed in recent years, palliative care consults remain rare and are often employed late in the hospitalization.

Emotional preparedness for human body donor dissection in premedical education: A pilot program evaluation.

Dissection of bodies provided by donors continues to be utilized as a critical part of medical education. It also represents a rite of passage that socializes students to prepare them for the stress that comes with working in a clinical environment as a medical professional. Just as proper guidance in acquiring technical skills is critical in anatomy education, there is an important need for proper emotional guidance throughout the human dissection process. A pilot curriculum was developed by an interdisciplinary faculty team to emotionally prepare students for their first visit to the anatomy laboratory. Students were first-year foundation premedical students who had expressed an interest in visiting the laboratory. Pre- and post-visit surveys were conducted to explore students' emotional responses to a first visit to the anatomy laboratory and their utilization of coping strategies. The survey findings show an overwhelming favorable feeling in anticipation of the human gross anatomy laboratory visit. About 20% of the students experienced anxiety at the anticipation of the laboratory visit, but only 5.3% experienced anxiety during the visit. The decrease in the number of students experiencing anxiety may be attributed to the interventions introduced before and during the visit. Talking with a close friend was the main coping strategy utilized by 63% of students experiencing fear or anxiety during and after the laboratory visit. The findings from this program evaluation provide a better understanding of student emotional preparedness and utilization of coping strategies, which may help prepare and guide future students for the dissection experience.

Parental emotional, social and transitional health in the first 6 months after childhood critical illness: A longitudinal qualitative study.

AIM: To explore the experiences and support needs of parents in the first 6 months after paediatric critical care. DESIGN: Longitudinal qualitative design. METHODS: Sequential semi-structured qualitative interviews were conducted with a sample of 28 parents in succession at 1 month and at 6 months (n = 22) after their child's discharge from paediatric critical care using purposive sampling. Data were analysed using the adapted five-stage framework analysis. RESULTS: Data were developed into eight synthesized themes, three domains and an overarching theme: Regaining Normalcy. Families of children requiring medical treatment at 6 months showed signs of adaption to daily care routines. The two domains were Parental Emotional Health and Parental Social Health. Parental Transitional Health, a third domain, was added to the Post Intensive Care Syndrome-paediatric framework. Parents were forward-looking and discussed emotional health, relating to current caregiving issues. Emotional attention was related to present challenges and concerns about current health and possible readmission to the hospital. In terms of Parental Social Health, families isolated themselves for infection control while remaining connected with families using chat applications. Parents were selective to whom they allowed access to their lives. The impact of parental transitional health was evident and emphasized the daily challenges associated with integration back to home life. Flexible work arrangements allowed working parents to support caregiving needs in the first 6 months after discharge. CONCLUSION: In the first 6 months after paediatric critical illness, most families reported having moved past the experiences while having provoking memories of the admission period. Parents viewed the point of normalcy as child returned to school or when all medications were discontinued. Extension of transitional support can facilitate discharge experiences between paediatric critical care and normalcy. The findings highlight the importance of understanding the medium- and longer-term impact of paediatric critical care. IMPACT: What problem did the study address? ○ Limited understanding of long-term parental experiences and support needs after PICU discharge. What were the main findings? ○ Most families regained normalcy when child returns to school or when medications were discontinued. Some families continued to show signs of adaptations at 6 months after PICU discharge. Where and on whom did the research have an impact? ○ The research has an impact on improving the understanding of long-term parental experiences and support needs after PICU discharge, informing clinical practice, guiding policy development and shaping parental support programs. REPORTING METHOD: We reported this study using the COREQ guidelines. PATIENT OR PUBLIC CONTRIBUTION: Prior to confirming the interview guide, three parents of critically ill children actively participated by reviewing and providing feedback on its content. They provided suggestions to refine the wording and ensure clarity to enhance the participants' understanding. By including the perspectives of these parents, we aimed to improve the overall quality and relevance of the interview guide.

Alterations in the sarcopenia index are associated with inflammation, gut, and oral microbiota among heart failure, left ventricular assist device, and heart transplant patients.

BACKGROUND: Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and predicts poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate for skeletal muscle mass, in HF, left ventricular assist device (LVAD), and heart transplant (HT), and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. METHODS: We enrolled 460 HF, LVAD, and HT patients. Repeated measures pre/post-procedures were obtained prospectively in a subset of LVAD and HT patients. SI (serum creatinine/cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S ribosomal ribonucleic acid sequencing among 335 stool and 341 saliva samples. Multivariable regression assessed the relationship between SI and (1) New York Heart Association class; (2) pre- versus post-LVAD or HT; and (3) biomarkers of inflammation and microbial diversity. RESULTS: Median (interquartile range) natural logarithm (ln)-SI was -0.13 (-0.32, 0.05). Ln-SI decreased across worsening HF class, further declined at 1 month after LVAD and HT, and rebounded over time. Ln-SI was correlated with inflammation (r = -0.28, p < 0.01), gut (r = 0.28, p < 0.01), and oral microbial diversity (r = 0.24, p < 0.01). These associations remained significant after multivariable adjustment in the combined cohort but not for all individual cohorts. The presence of the gut taxa Roseburia inulinivorans was associated with increased SI. CONCLUSIONS: SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. In the combined cohort, SI levels covaried with inflammation in a similar fashion and were significantly related to overall microbial (gut and oral) diversity, including specific taxa compositional changes.

Aortic Root Thrombosis in patients with HeartMate 3 left ventricular assist device support.

BACKGROUND: Aortic root thrombosis(ART) is a complication of continuous-flow left ventricular assist device therapy. However, the incidence and related complications of ART in HeartMate 3 (HM3) patients remain unknown. METHODS: Patients who underwent HM3 implantation from November 2014 to August 2020 at a quaternary academic medical center were included. Demographics and outcomes were abstracted from the medical record. Echocardiograms and contrast-enhanced computed tomography studies were reviewed to identify patients who developed ART and/or moderate or greater aortic insufficiency (AI) on HM3 support. RESULTS: The study cohort included 197 HM3 patients with a median postimplant follow-up of 17.5 months. Nineteen patients (9.6%) developed ART during HM3 support, and 15 patients (7.6%) developed moderate or greater AI. Baseline age, gender, race, implantation strategy, and INTERMACS classification were similar between the ART and no-ART groups. ART was associated with an increased risk of death, stroke, or aortic valve (AV) intervention (subhazard ratio [SHR] 3.60 [95% confidence interval (CI) 1.71-7.56]; p = 0.001) and moderate or greater AI (SHR 11.1 [CI 3.60-34.1]; p < 0.001) but was not associated with a statistically significantly increased risk of death or stroke on HM3 support (2.12 [0.86-5.22]; p = 0.10). Of the 19 patients with ART, 6 (31.6%) developed moderate or greater AI, necessitating more frequent AV interventions (ART: 5 AV interventions [3 surgical repairs, 1 surgical replacement, 1 transcatheter replacement; 26.3%]; no-ART: 0). CONCLUSIONS: Nearly 10% of HM3 patients developed ART during device support. ART was associated with increased risk of a composite end-point of death, stroke, or AV intervention as well as moderate or greater AI.

Cardioprotective and Antianginal Efficacy of Nicorandil: A Comprehensive Review.

ABSTRACT: Angina pectoris remains a significant burden despite advances in medical therapy and coronary revascularization. Many patients (up to 30%) with angina have normal coronary arteries, with coronary microvascular disease and/or coronary artery vasospasm being major drivers of the myocardial demand-supply mismatch. Even among patients revascularized for symptomatic epicardial coronary stenosis, recurrent angina remains highly prevalent. Medical therapy for angina currently centers around 2 disparate goals, viz secondary prevention of hard clinical outcomes and symptom control. Vasodilators, such as nitrates, have been first-line antianginal agents for decades, along with beta-blockers and calcium channel blockers. However, efficacy in symptoms control is heterogenous, depending on underlying mechanism(s) of angina in an individual patient, often necessitating multiple agents. Nicorandil (NCO) is an antianginal agent first discovered in the late 1970s with a uniquely dual mechanism of action. Like a typical nitrate, it mediates medium-large vessel vasodilation through nitric oxide. In addition, NCO has adenosine triphosphate (ATP)-dependent potassium channel agonist activity (K ATP ), mediating microvascular dilatation. Hence, it has proven effective in both coronary artery vasospasm and coronary microvascular disease, typically challenging patient populations. Moreover, emerging evidence suggests that cardiomyocyte protection against ischemia through ischemic preconditioning may be mediated through K ATP agonism. Finally, there is now fairly firm evidence in favor of NCO in terms of hard event reduction among patients with stable coronary artery disease, following myocardial infarction, and perhaps even among patients with congestive heart failure. This review aims to summarize the mechanism of action of NCO, its efficacy as an antianginal, and current evidence behind its impact on hard outcomes. Finally, we review other cardiac and emerging noncardiac indications for NCO use.

The Difference Between Cystatin C- and Creatinine-Based Estimated GFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF.

RATIONALE & OBJECTIVE: The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. STUDY DESIGN: Post-hoc analysis of randomized trial data. SETTING & PARTICIPANTS: 1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. EXPOSURE: Intraindividual differences between eGFR based on cysC (eGFRcysC) and Scr (eGFRScr; eGFRdiffcysC-Scr). OUTCOMES: Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. ANALYTICAL APPROACH: Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiffcysC-Scr. Logistic regression was used to investigate the association of baseline eGFRdiffcysC-Scr with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFRcysC, eGFRScr, and eGFRdiffcysC-Scr at 8-month follow-up. RESULTS: Baseline eGFRdiffcysC-Scr was higher than +10 and lower than-10mL/min/1.73m2 in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiffcysC-Scr were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1-standard-deviation decrease in eGFRdiffcysC-Scr, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFRcysC than in eGFRScr, resulting in a change in 8-month eGFRdiffcysC-Scr of-4.67mL/min/1.73m2 (P<0.001). LIMITATIONS: Lack of gold-standard assessment of kidney function. CONCLUSIONS: In patients with HFrEF, discrepancies between eGFRcysC and eGFRScr are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFRcysC than with eGFRScr. PLAIN-LANGUAGE SUMMARY: Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFRcysC) and Scr (eGFRScr). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFRcysC and eGFRScr. More negative values (ie, eGFRScr>eGFRcysC) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.

The impact of pre-existing hematologic disorders on morbidity and mortality following heart transplantation: Focus on early graft dysfunction.

BACKGROUND: Heart transplantation (HT) is the gold standard therapy for advanced heart failure, providing excellent long-term outcomes. However, postoperative outcomes are limited by bleeding, infections, and primary graft dysfunction (PGD) that contribute to early mortality after HT. HT candidates with pre-existing hematologic disorders, bleeding, and clotting, may represent a higher risk population. We assessed the short- and long-term outcomes of patients with pre-existing hematologic disorders undergoing HT. METHODS AND RESULTS: Medical records of all adult patients who received HT from January 2010 to December 2019 at our institution were retrospectively reviewed. Hematologic disorders were identified via chart review and adjudicated by a board-certified hematologist. Inverse probability weighting and multivariable models were used to adjust for potential pretransplant confounders. Four hundred and ninety HT recipients were included, of whom 29 (5.9%) had a hematologic disorder. Hematologic disorders were associated with severe PGD requiring mechanical circulatory support (aOR 3.15 [1.01-9.86]; p = .049), postoperative infections (aOR 2.93 [1.38-6.23]; p = .01), and 3-year acute cellular rejection (ACR) (≥1R/1B) (aSHR 2.06 [1.09-3.87]; p = .03). There was no difference in in-hospital mortality (aOR 1.23 [.20-7.58], p = .82) or 3-year mortality (aHR 1.58 [.49-5.12], p = .44). CONCLUSIONS: Patients with hematologic disorders undergoing HT are at increased risk of severe PGD, postoperative infections, and ACR, while in-hospital and 3-year mortality remain unaffected.

Ethnic differences in parental experiences during the first six months after PICU discharge in Singapore: a qualitative study.

Introduction: Literature on parental experiences after childhood critical illness has limited representation from diverse ethnic backgrounds. Parents from global ethnic majority groups have reported worst psychological outcomes and required more social support after childhood critical illness. Aim: To explore the experiences of Chinese, Malay, and Indian parents in the first six months after Pediatric Intensive Care Unit (PICU) discharge of their child in Singapore. Methods: Sequential semi-structured qualitative interviews were conducted to collect data from a convenience sample of 28 parents at one month (n = 28) and at six months (n = 22) after their child's discharge from a multidisciplinary PICU. Framework Analysis was adopted as the qualitative analysis strategy. The PICS-p framework was applied a priori in the Framework Analysis. Findings: Three interdependent domains and seven themes framed the 28 accounts in which ethnically diverse parents reported psychological stressors (PICS-p: emotional health), support received (PICS-p: social health) and practical challenges (transitional health) in the first six months after childhood critical illness. In the emotional health domain, parents were affected by different stressors and had different priorities over their child's survivorship. Only Indian parents reported experiences of stress symptoms, at six months post discharge. Malay parents sought solace from their religion more than Chinese and Indian parents. In the social health domain, parents reported various sources and degree of support received. Familial supports were strong across all groups, while community support was more prominent in Malay as compared to Chinese and Indian parents. A third domain, transitional health, was introduced to capture the difficulties parents faced during the transition from PICU survival to home. Parents from non-Chinese families were more likely to report financial challenges and more involvement of spouses after discharge. Complementary medicine or commercial health products were utilized by Chinese and Malay families. Conclusion: These findings reveal preferred strategies that parents from a global ethnic employ to address the emotional, social and transitional health impacts of their child's critical illness. Future care delivery may consider tailored care plans, communication strategies, and emotional support in PICUs that address the unique ethnic needs of parents during the critical six-months post their child's illness.

Molecular Origins of Transcriptional Heterogeneity in Diazotrophic Klebsiella oxytoca.

Phenotypic heterogeneity in clonal bacterial batch cultures has been shown for a range of bacterial systems; however, the molecular origins of such heterogeneity and its magnitude are not well understood. Under conditions of extreme low-nitrogen stress in the model diazotroph Klebsiella oxytoca, we found remarkably high heterogeneity of nifHDK gene expression, which codes for the structural genes of nitrogenase, one key enzyme of the global nitrogen cycle. This heterogeneity limited the bulk observed nitrogen-fixing capacity of the population. Using dual-probe, single-cell RNA fluorescent in situ hybridization, we correlated nifHDK expression with that of nifLA and glnK-amtB, which code for the main upstream regulatory components. Through stochastic transcription models and mutual information analysis, we revealed likely molecular origins for heterogeneity in nitrogenase expression. In the wild type and regulatory variants, we found that nifHDK transcription was inherently bursty, but we established that noise propagation through signaling was also significant. The regulatory gene glnK had the highest discernible effect on nifHDK variance, while noise from factors outside the regulatory pathway were negligible. Understanding the basis of inherent heterogeneity of nitrogenase expression and its origins can inform biotechnology strategies seeking to enhance biological nitrogen fixation. Finally, we speculate on potential benefits of diazotrophic heterogeneity in natural soil environments. IMPORTANCE Nitrogen is an essential micronutrient for both plant and animal life and naturally exists in both reactive and inert chemical forms. Modern agriculture is heavily reliant on nitrogen that has been "fixed" into a reactive form via the energetically expensive Haber-Bosch process, with significant environmental consequences. Nitrogen-fixing bacteria provide an alternative source of fixed nitrogen for use in both biotechnological and agricultural settings, but this relies on a firm understanding of how the fixation process is regulated within individual bacterial cells. We examined the cell-to-cell variability in the nitrogen-fixing behavior of Klebsiella oxytoca, a free-living bacterium. The significance of our research is in identifying not only the presence of marked variability but also the specific mechanisms that give rise to it. This understanding gives insight into both the evolutionary advantages of variable behavior as well as strategies for biotechnological applications.

Impact of ethnicity on parental health outcomes and experiences after paediatric intensive care unit discharge: a mixed-methods systematic review.

The impact of ethnicity on parental health outcome after paediatric intensive care unit (PICU) discharge remains unclear. Thirteen medical and healthcare databases, unpublished studies and grey literature were searched up to November 5, 2021. We performed a mixed-method systematic review to understand the impact of ethnicity on parental outcomes after PICU discharge, including eight quantitative and eight qualitative studies. Among 1529 parents included, 1064 (72%) were White. Higher prevalence of post-traumatic stress disorder was seen in Black parents (17% White vs 36% Black, p = .03). Latino ethnicity was found to have protective effect against anxiety as compared to White parents (coefficient - 4.27, p < .001). A total of 91 findings were aggregated into 14 categories, and the five synthesized themes from the eight qualitative studies were long-term psychological impact after PICU, use of coping strategies, challenges of re-integration, changes in relationships and the utilization of formal support services and resources. Mixed-method synthesis found that parents of ethnic minority group were underrepresented (18%) and had higher attrition rates in a longitudinal study as compared to White parents following childhood critical illness.   Conclusion: There are significant gaps in evidence related to the impact of ethnicity on long-term parental health outcomes after PICU discharge. Ethnic diversity and inclusiveness in long-term PICU research may aid understanding of the parental experiences and outcomes to close the gap in health disparity.

Ion-Pairing Chromatography and Amine Derivatization Provide Complementary Approaches for the Targeted LC-MS Analysis of the Polar Metabolome.

Liquid chromatography coupled to mass spectrometry is a key metabolomics/metabonomics technology. Reversed-phase liquid chromatography (RPLC) is very widely used as a separation step, but typically has poor retention of highly polar metabolites. Here, we evaluated the combination of two alternative methods for improving retention of polar metabolites based on 6-aminoquinoloyl-N-hydroxysuccinidimyl carbamate derivatization for amine groups, and ion-pairing chromatography (IPC) using tributylamine as an ion-pairing agent to retain acids. We compared both of these methods to RPLC and also to each other, for targeted analysis using a triple-quadrupole mass spectrometer, applied to a library of ca. 500 polar metabolites. IPC and derivatization were complementary in terms of their coverage: combined, they improved the proportion of metabolites with good retention to 91%, compared to just 39% for RPLC alone. The combined method was assessed by analyzing a set of liver extracts from aged male and female mice that had been treated with the polyphenol compound ampelopsin. Not only were a number of significantly changed metabolites detected, but also it could be shown that there was a clear interaction between ampelopsin treatment and sex, in that the direction of metabolite change was opposite for males and females.

Mapping sex differences in the effects of protein and carbohydrates on lifespan and reproduction in Drosophila melanogaster: is measuring nutrient intake essential?

Understanding how diet affects reproduction and survival is a central aim in evolutionary biology. Although this relationship is likely to differ between the sexes, we lack data relating diet to male reproductive traits. One exception to this general pattern is Drosophila melanogaster, where male dietary intake was quantified using the CApillary FEeder (CAFE) method. However, CAFE feeding reduces D. melanogaster survival and reproduction, so may distort diet-fitness outcomes. Here, we use the Geometric Framework of Nutrition to create nutrient landscapes that map sex-specific relationships between protein, carbohydrate, lifespan and reproduction in D. melanogaster. Rather than creating landscapes with consumption data, we map traits onto the nutrient composition of forty agar-based diets, generating broad coverage of nutrient space. We find that male and female lifespan was maximised on low protein, high carbohydrate blends (~ 1P:15.9C). This nutrient ratio also maximised male reproductive rates, but females required more protein to maximise daily fecundity (1P:1.22C). These results are consistent with CAFE assay outcomes. However, the approach employed here improved female fitness relative to CAFE assays, while effects of agar versus CAFE feeding on male fitness traits depended on the nutrient composition of experimental diets. We suggest that informative nutrient landscapes can be made without measuring individual nutrient intake and that in many cases, this may be preferable to using the CAFE approach. The most appropriate method will depend on the question and species being studied, but the approach adopted here has the advantage of creating nutritional landscapes when dietary intake is hard to quantify.

Orodispersible and transmucosal alternative medications for symptom control in adults.

BACKGROUND: Paediatric palliative care makes frequent use of orodispersible and transmucosal drug delivery routes. The limited published experience of this practice suggests that it enables the delivery of needle-free symptom relief, with the potential to train family carers to administer anticipatory medications without reliance on trained health professionals. AIMS: To identify orodispersible and potential transmucosal alternatives that may be used in adults in the event of a patient having no oral or intravenous route and no access to subcutaneous injections. METHODS: The author panel identified medications through review of multiple drug formularies, review of the published evidence and their experience. Where possible, licensed alternatives were identified and any 'off label' or unlicensed medications clearly highlighted. RESULTS: A list of 27 medications is provided, which could be used either via the orodispersible or transmucosal alternative route for healthcare professionals delivering end of life care to consider when the licensed alternative routes are unavailable. All users of this guide are encouraged to use their professional judgement whenever selecting a medication for a patient, recognising that this review is neither a guideline nor a systematic review, and taking account of licensing considerations, adverse effects, potential unpredictability of time to effect and contraindications. CONCLUSION: Should it be necessary to use these orodispersible or transmucosal alternatives then any experience gained should be reported in the literature. Combined with further research, this experience offers the possibility of reducing injection frequency and inherent delays in medication administration, particularly in the community setting during the COVID-19 pandemic.

Fan therapy for cough: case report and literature review.

This case report describes the care of a 59-year-old woman with metastatic small cell lung cancer and chronic obstructive pulmonary disease who was highly symptomatic with an intractable cough. The patient reported a subjective benefit from a table fan. The authors observed an objective improvement with a marked reduction in cough frequency when the fan was in use. A literature review was undertaken and identified one randomised controlled trial assessing the use of fan for cough. The proposed underlying mechanism of cough relief is stimulation of the trigeminal nerve, possibly by cooling. This mechanism is well described in breathlessness. It presents the possibility of a novel therapeutic approach to managing cough. Further studies of both the role of nasal receptors in cough pathophysiology and the role of fan therapy in cough, where there is no concern of an airborne infectious pathogen such as COVID-19, are warranted.

Withdrawal of Temporary Mechanical Circulatory Support in Patients With Capacity.

CONTEXT: Little is known about the real-time decision-making process of patients with capacity to choose withdrawal of temporary mechanical circulatory support (MCS). OBJECTIVES: To assess how withdrawal of temporary MCS occurs when patients possess the capacity to make this decision themselves. METHODS: This retrospective case series included adults supported by CentriMag Acute Circulatory Support or Veno-Arterial Extracorporeal Membrane Oxygenation from February 2, 2007 to May 27, 2020 at a tertiary academic medical center who possessed capacity to participate in end-of-life discussions. Authors performed chart review to determine times between "initiation of temporary MCS," "determination of 'bridge to nowhere,'" "patient expressing desire to withdraw," "agreement to withdraw," "withdrawal," and "death," as well as reasons for withdrawal and the role of ethics, psychiatry, and palliative care. RESULTS: A total of 796 individuals were included. MCS was withdrawn in 178 (22.4%) of cases. Six of these 178 patients (3.4%) possessed the capacity to decide to withdraw MCS. Time between "patient expressing desire to withdraw" and "agreement to withdraw" ranged from 0 to 3 days; time between "agreement to withdraw" and "withdrawal" ranged from 0 to 6 days. Common reasons for withdrawal include perceived decline in quality of life or low probability of recovery. Ethics and psychiatry were consulted in 3 of 6 cases and palliative care in 5 of 6 cases. CONCLUSION: While it is rare for patients on MCS to request withdrawal, such cases provide insight into reasons for withdrawal and the important roles of multidisciplinary teams in helping patients and families through end-of-life decision-making.

Prevalence and Significance of Patient Prosthesis Mismatch Following Edwards SAPIEN XT and SAPIEN 3 Transcatheter Aortic Valve Replacement.

Background Severe patient prosthesis mismatch (sPPM) after surgical aortic valve replacement is associated with worse outcomes. Limited data exists on the impact of sPPM on outcomes after transcatheter aortic valve replacement (TAVR), especially regarding the newer generation valves. The aim of this study was to evaluate the incidence, determinants, and outcomes of sPPM in patients undergoing TAVR with Edwards SAPIEN XT (ES XT) and Edwards SAPIEN 3 (ES3) valves (Edwards Lifesciences, Irvine, CA, USA). Methods We retrospectively reviewed 366 patients who underwent TAVR with ES XT (n = 114) or ES3 (n = 252) valves between July 2012 and June 2018. sPPM was defined as indexed effective orifice area (iEOA) <0.65 cm2/m2. Kaplan-Meier survival estimates were used to determine outcomes. Results Multivariate linear regression analysis was utilized to determine potential independent effects of PPM on outcomes. sPPM was present in 40 (11%) of the patients [8 (7%) ES XT and 32 (13%) ES3] and was associated with female sex, smaller left ventricular outflow tract (LVOT) diameter and aortic valve annular area, absence of prior coronary artery bypass graft (CABG) surgery, shorter height, higher body mass index, and smaller pre-TAVR valve area (all p < 0.05). Among those with ES3 valves, the incidence of sPPM was inversely proportional to the valve size (50%, 25%, 5% and 3% for 20-, 23-, 26- and 29-mm valve sizes, respectively; p < 0.001). At a mean follow-up period of 3.5 ± 1.5 years, there was no difference in all-cause mortality (22.5% vs. 25.6%, p = 0.89) or a composite endpoint of heart failure, arrhythmias, stroke, and myocardial infarction (30% vs. 34%, p = 0.24) in those with or without sPPM. Conclusion ES3 was associated with a higher incidence of sPPM, particularly with smaller valve sizes. However, the presence of sPPM as defined by iEOA was not an independent predictor of adverse outcomes in patients undergoing TAVR within an intermediate follow-up period.