Myocardial Infarction with Nonobstructive Coronary Arteries.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is an important subtype of myocardial infarction (MI) that occurs in approximately 6-8% of patients with spontaneous MI who are referred for coronary angiography. MINOCA disproportionately affects women, but men are also affected. Pathogenesis is more variable than in MI with obstructive coronary artery disease (MI-CAD). Dominant mechanisms include atherosclerosis, thrombosis, and coronary artery spasm. Management of MINOCA varies based on the underlying mechanism of infarction. Therefore, systematic approaches to diagnosis are recommended. The combination of invasive coronary angiography, multivessel intracoronary imaging, provocative testing for coronary spasm, and cardiac magnetic resonance imaging provides the greatest diagnostic yield. Current clinical practice guidelines for the secondary prevention of MI are based largely on data from patients with MI-CAD. Thus, optimal medications after MINOCA are uncertain. Clinical trials focused on the treatment of patients with MINOCA are urgently needed to define optimal care.

Telehealth Support of Managed Care for a Correctional System: The Open Architecture Telehealth Model.

INTRODUCTION: The intent was to evaluate time to match initial investment of a new, statewide correctional system telehealth program based upon cumulative savings by avoidance of transportation and custody-related costs. MATERIALS AND METHODS: The setting was a statewide correctional system where prisoners received medical care through enhanced telemedicine technology supported by newly recruited specialty providers delivered through an open architecture system. The patients were incarcerated persons requiring nonemergent consultations in 10 specialties. A financial model was created to estimate transportation expenses, including vehicular use and custody staff, during the out of prison travel for traditional face-to-face care. Cost savings were then estimated by multiplying transportation expenses by the number of telehealth encounters (avoided cost) and summed cumulatively. Savings were mapped monthly. Private sector specialists were recruited, provided security clearance, trained in the use of the technology, and provided a secure site to provide services. MEASUREMENTS AND MAIN RESULTS: Based on the financial model, 1.2 million dollars in savings, equaling the initial capital investment, were achieved at 32 months. The total number of patient telemedicine encounters increased from 2,365 (±98/month) to 3,748 during the first 32 months of operation (July 2013 through January 2016: ±117/month) with 89% of the established specialties performed by telemedicine technologies. DISCUSSION: It was initially estimated to require 48 months to achieve the investment savings, but savings were achieved in 32 months, demonstrating greater adoption than expected. While finances were quantifiable, enhanced public safety by avoidance of out of prison time is unquantifiable, but judged to be significant.

Measurement of charged-particle stopping in warm dense plasma.

We measured the stopping of energetic protons in an isochorically heated solid-density Be plasma with an electron temperature of ∼32 eV, corresponding to moderately coupled [(e^{2}/a)/(k_{B}T_{e}+E_{F})∼0.3] and moderately degenerate [k_{B}T_{e}/E_{F}∼2] "warm-dense matter" (WDM) conditions. We present the first high-accuracy measurements of charged-particle energy loss through dense plasma, which shows an increased loss relative to cold matter, consistent with a reduced mean ionization potential. The data agree with stopping models based on an ad hoc treatment of free and bound electrons, as well as the average-atom local-density approximation; this work is the first test of these theories in WDM plasma.

Critical care telemedicine: evolution and state of the art.

OBJECTIVES: To review the growth and current penetration of ICU telemedicine programs, association with outcomes, studies of their impact on medical education, associations with medicolegal risks, identify program revenue sources and costs, regulatory aspects, and the ICU telemedicine research agenda. DATA SOURCES: Review of the published medical literature, governmental documents, and opinions of experts from the Society of Critical Care Medicine ICU Telemedicine Committee. DATA SYNTHESIS: Formal ICU telemedicine programs now support 11% of nonfederal hospital critically ill adult patients. There is increasingly robust evidence of association with lower ICU (0.79; 95% CI, 0.65-0.96) and hospital mortality (0.83; 95% CI, 0.73-0.94) and shorter ICU (-0.62 d; 95% CI, -1.21 to -0.04 d) and hospital (-1.26 d; 95% CI, -2.49 to -0.03 d) length of stay. Physicians in training report experiences with telemedicine intensivists that are positive and increased patient safety. Early studies suggest that implementation of ICU telemedicine programs has been associated with lower numbers of malpractice claims and costs. The requirements for Medicare reimbursement and states with legislation addressing providing professional services by telemedicine are detailed. CONCLUSIONS: The inclusion of an ICU telemedicine program as a major part of their critical care delivery paradigm has been implemented for 11% of critically ill U.S. adults as a solution for the problem of access to adult critical care services. Implementation of an ICU telemedicine program is one practical way to increase access and reduce mortality as well as length of stay. ICU telemedicine research including comparative effectiveness studies is urgently needed.

Wild bees visiting cucumber on midwestern U.S. organic farms benefit from near-farm semi-natural areas.

Wild bees that provide pollination services to vegetable crops depend on forage resources, nesting sites, and overwintering sites in the agricultural landscape. The scale at which crop-visiting bees use resources in the landscape can vary regionally, and has not been characterized in the Midwestern United States. We investigated the effects of seminatural land cover on wild bee visitation frequency to cucumber (Cucumis sativus L.) and on wild bee species richness on 10 organic farms in Indiana. We estimated the spatial scale at which the effects of land cover were strongest, and also examined the effects of nonlandscape factors on wild bees. The visitation frequency of wild bees to cucumber was positively related to the proportion of seminatural land in the surrounding landscape, and this relationship was strongest within 250 m of the cucumber patch. The species richness of wild cucumber visitors was not affected by land cover at any spatial scale, nor by any of the nonlandscape factors we considered. Our results indicate that wild, crop visiting bees benefit from seminatural areas in the agricultural landscape, and benefit most strongly from seminatural areas within 250 m of the crop field. This suggests that setting aside natural areas in the near vicinity of vegetable fields may be an effective way to support wild, crop-visiting bees and secure their pollination services.

Solid-organ transplantation in older adults: current status and future research.

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.

System-based factors influencing intraoperative decision-making in rectal cancer by surgeons: an international assessment.

AIM: Sound surgical judgement is the goal of training and experience; however, system-based factors may also colour selection of options by a surgeon. We analysed potential organizational characteristics that might influence rectal cancer decision-making by an experienced surgeon. METHOD: One hundred and seventy-three international centres treating rectal cancer were invited to participate in a survey assessment of key treatment options for patients undergoing curative rectal-cancer surgery. The key organizational characteristics were analysed using multivariate methods for association with intra-operative surgical decision-making. RESULTS: The response rate was 71% (123 centres). Sphincter-saving surgery was more likely to be performed at university hospitals (OR=3.63, P=0.01) and by high-caseload surgeons (OR=2.77 P=0.05). A diverting stoma was performed more frequently in departments with clinical audits (OR=3.06, P=0.02), and a diverting stoma with coloanal anastomosis was more likely in European centres (OR=4.14, P=0.004). One-stage surgery was less likely where there was assessment by a multidisciplinary team (OR=0.24, P=0.02). Multivariate analysis showed that university hospital, clinical audit, European centre, multidisciplinary team and high caseload significantly impacted on surgical decision-making. CONCLUSION: Treatment variance of rectal cancer surgeons appears to be significantly influenced by organizational characteristics and complex team-based decision-making. System-based factors may need to be considered as a source of outcome variation that may impact on quality metrics.

Different systems and formats for tele-ICU coverage: designing a tele-ICU system to optimize functionality and investment.

Technology always changes, yet change or evolution within the tele-ICU has been slow. In developing a modern telemedicine system to manage acute illness, there are several concepts the developer/administrator should consider to include "scalability," centralized/decentralized systems, open/closed architecture, inclusivity of the medical community, mobile technology, price set, and governmental regulation. The intent of this manuscript is to apply these concepts to current tele-ICU technology, explain the concepts in some depth, and finally, to speculate as to how the future tele-ICU might look.

Utilization of robotic "remote presence" technology within North American intensive care units.

OBJECTIVE: To describe remote presence robotic utilization and examine perceived physician impact upon care in the intensive care unit (ICU). STUDY DESIGN: Data were obtained from academic, university, community, and rural medical facilities in North America with remote presence robots used in ICUs. Objective utilization data were extracted from a continuous monitoring system. Physician data were obtained via an Internet-based survey. RESULTS: As of 2010, 56 remote presence robots were deployed in 25 North American ICUs. Of 10,872 robot activations recorded, 10,065 were evaluated. Three distinct utilization patterns were discovered. Combining all programs revealed a pattern that closely reflects diurnal ICU activity. The physician survey revealed staff are senior (75% >40 years old, 60% with >16 years of clinical practice), trained in and dedicated to critical care. Programs are mature (70% >3 years old) and operate in a decentralized system, originating from cities with >50,000 population and provided to cities >50,000 (80%). Of the robots, 46.6% are in academic facilities. Most physicians (80%) provide on-site and remote ICU care, with 60% and 73% providing routine or scheduled rounds, respectively. All respondents (100%) believed patient care and patient/family satisfaction were improved. Sixty-six percent perceived the technology was a "blessing," while 100% intend to continue using the technology. CONCLUSIONS: Remote presence robotic technology is deployed in ICUs with various patterns of utilization that, in toto, simulate normal ICU work flow. There is a high rate of deployment in academic ICUs, suggesting the intensivists shortage also affects large facilities. Physicians using the technology are generally senior, experienced, and dedicated to critical care and highly support the technology.

Myocardial first-pass perfusion: influence of spatial resolution and heart rate on the dark rim artifact.

Myocardial perfusion images can be affected by the dark rim artifact. This study aimed to evaluate the effects of the spatial resolution and heart rate on the transmural extent of the artifact. Six pigs under anesthesia were scanned at 1.5T using an echo-planar imaging/fast gradient echo sequence with a nonselective saturation preparation pulse. Three short-axis slices were acquired every heart beat during the first pass of a contrast agent bolus. Two different in-plane spatial resolutions (2.65 and 3.75 mm) and two different heart rates (normal and tachycardia) were used, generating a set of four perfusion scans. The percentage drop of signal in the subendocardium compared to the epicardium and the transmural extent of the artifact were extracted. Additionally, the signal-to-noise and the contrast-to-noise ratios were evaluated. The signal drop as well as the width of the dark rim artifact increased with decreased spatial resolution and with increased heart rates. No significant slice-to-slice variability was detected for signal drop and width of the rim within the four considered groups. signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) ratios decreased with increasing spatial resolution. In conclusion, low spatial and temporal resolution could be correlated with increased extent of the dark-rim artifact and with lower SNR and CNR.

Melatonin exerts direct inhibitory actions on ACTH responses in the human adrenal gland.

In nonhuman primates and rodents, melatonin acting directly on the adrenal gland, inhibits glucocorticoid response to ACTH. In these species, an intrinsic adrenal circadian clock is involved in ACTH-stimulated glucocorticoid production. We investigated whether these findings apply to the human adrenal gland by determining i) expression of clock genes in vivo and ii) direct effects of melatonin in ACTH-stimulated adrenal explants over a) expression of the clock genes PER1 (Period 1) mRNA and BMAL1 [Brain-Muscle (ARNT)-like] protein, ACTH-induced steroidogenic acute regulatory protein (StAR), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and b) over cortisol and progesterone production. Adrenal tissue was obtained from 6 renal cancer patients undergoing unilateral nephrectomy-adrenalectomy. Expression of the clock genes PER1, PER2, CRY2 (Cryptochrome 2), CLOCK (Circadian Locomotor Output Cycles Kaput) and BMAL1, was investigated by RT-PCR in a normal adrenal and in an adenoma. In independent experiments, explants from 4 normal adrenals were preincubated in culture medium (6 h) followed by 12 h in: medium alone; ACTH (100 nM); ACTH plus melatonin (100 nM); and melatonin alone. The explants' content of PER1 mRNA (real-time PCR) and StAR, 3ß-HSD, BMAL1 (immuno slot-blot), and their cortisol and progesterone production (RIA) were measured. The human adrenal gland expresses the clock genes PER1, PER2, CRY2, CLOCK, and BMAL1. ACTH increased PER1 mRNA, BMAL1, StAR, and 3ß-HSD protein levels, and cortisol and progesterone production. Melatonin inhibited these ACTH effects. Our study demonstrates, for the first time, direct inhibitory effects of melatonin upon several ACTH responses in the human adrenal gland.

Perioperative management of clopidogrel therapy: the effects on in-hospital cardiac morbidity in older patients with hip fractures.

BACKGROUND: Increasing numbers of older patients prescribed clopidogrel are presenting for urgent hip fracture surgery. Best practice for the management of clopidogrel therapy is unknown, although delays to surgery are associated with increased mortality. We investigated the influence of perioperative management of clopidogrel therapy on in-hospital cardiac morbidity and transfusion in this population. METHODS: Retrospective review of all patients aged >60 yr, admitted to a single centre with hip fractures between June 2005 and November 2008. Acute coronary syndrome (ACS) was defined as a raised plasma troponin concentration >0.04 µg litre(-1) associated with chest pain, new ECG changes, or both. RESULTS: Of 1381 patients admitted with hip fractures, 114 were receiving regular clopidogrel therapy with a median age of 83.7 (60-98) yr. Clopidogrel was withheld perioperatively in 111 (98%) of these patients. Twenty-three patients (20.2%) suffered an ACS. Risk peaked for ACS [odds ratio (OR) 6.7 (95% confidence interval, CI, 1.7-25.8)] (P=0.006) between days 4 and 8 after clopidogrel withdrawal. The OR for requiring a blood transfusion during or after surgery peaked at day 1 after clopidogrel withdrawal [OR 2.31 (95% CI, 1.02-5.21)] (P=0.044). CONCLUSIONS: The length of withdrawal of clopidogrel therapy perioperatively was associated with a significantly increased incidence of ACS. An association between shorter withdrawal and increased blood transfusion requirements was also seen. The study emphasizes the cardiovascular risks of routinely interrupting clopidogrel therapy in this at-risk population and that a more considered, individualized, evidenced-based approach is needed.

The tele-intensive care unit during a disaster: seamless transition from routine operations to disaster mode.

Disaster plans, during the actual disaster, often do not function as conceived and designed. Disaster or emergency situations may not present as anticipated in planning sessions confounding the intent of disaster planners. Systems that are created and shelved awaiting the disaster may be dysfunctional when needed due to problems such as failed batteries, forgotten training, misplaced equipment, the retraining curve, or software that has not been updated. We report here the smooth and seamless transition to disaster mode from a system in daily use and therefore operational when needed.

A working lexicon for the tele-intensive care unit: we need to define tele-intensive care unit to grow and understand it.

Telemedicine in the intensive care unit (Tele-ICU) has grown exponentially since the first formalized program in 2000. Initially, there was limited product choice, and certain capabilities have been engineered into the process with the implication of necessity. New technology is evolving, and new vendors are entering the market place, which should yield a multitude of technologies from which to select. To date, there has been no organized lexicon designed to facilitate communication, comparison, or evaluation. This article is designed as a starting point to develop a lexicon applicable to all technologies for the Tele-ICU with the goal of facilitating clinical comparisons and administrative choices.

Standard versus hypofractionated intensity-modulated radiotherapy for prostate cancer: assessing the impact on dose modulation and normal tissue effects when using patient-specific cancer biology.

Hypofractionation of prostate cancer radiotherapy achieves tumour control at lower total radiation doses, however, increased rectal and bladder toxicities have been observed. To realise the radiobiological advantage of hypofractionation whilst minimising harm, the potential reduction in dose to organs at risk was investigated for biofocused radiotherapy. Patient-specific tumour location and cell density information were derived from multiparametric imaging. Uniform-dose plans and biologically-optimised plans were generated for a standard schedule (78 Gy/39 fractions) and hypofractionated schedules (60 Gy/20 fractions and 36.25 Gy/5 fractions). Results showed that biologically-optimised plans yielded statistically lower doses to the rectum and bladder compared to isoeffective uniform-dose plans for all fractionation schedules. A reduction in the number of fractions increased the target dose modulation required to achieve equal tumour control. On average, biologically-optimised, moderately-hypofractionated plans demonstrated 15.3% (p-value: <0.01) and 23.8% (p-value: 0.02) reduction in rectal and bladder dose compared with standard fractionation. The tissue-sparing effect was more pronounced in extreme hypofractionation with mean reduction in rectal and bladder dose of 43.3% (p-value: < 0.01) and 41.8% (p-value: 0.02), respectively. This study suggests that the ability to utilise patient-specific tumour biology information will provide greater incentive to employ hypofractionation in the treatment of localised prostate cancer with radiotherapy. However, to exploit the radiobiological advantages given by hypofractionation, greater attention to geometric accuracy is required due to increased sensitivity to treatment uncertainties.

Using millimeter-sized carbon-deuterium foils for high-precision deuterium-tritium neutron spectrum measurements in direct-drive inertial confinement fusion at the OMEGA laser facility.

Millimeter-sized CD foils fielded close (order mm) to inertial confinement fusion (ICF) implosions have been proposed as a game-changer for improving energy resolution and allowing time-resolution in neutron spectrum measurements using the magnetic recoil technique. This paper presents results from initial experiments testing this concept for direct drive ICF at the OMEGA Laser Facility. While the foils are shown to produce reasonable signals, inferred spectral broadening is seen to be high (∼5 keV) and signal levels are low (by ∼20%) compared to expectation. Before this type of foil is used for precision experiments, the foil mount must be improved, oxygen uptake in the foils must be better characterized, and impact of uncontrolled foil motion prior to detection must be investigated.

Cluster randomised trial of the uptake of a take-home infant dose of nevirapine in Kenya.

OBJECTIVE: To test whether a single take home dose of infant nevirapine increased infant uptake without decreasing institutional deliveries. DESIGN: Cluster randomised post-test only study with control group. SETTING: Ten hospitals in urban areas of Coast, Rift Valley, and Western provinces, Kenya. PARTICIPANTS: Pregnant women with HIV, 18 years and older, and at least 32 weeks gestation recruited during antenatal care and followed up at home approximately one week after delivery. INTERVENTION: In the intervention group, women were given a single infant's dose of nevirapine to take home prior to delivery. In the control group, no changes were made to the standard of care. MAIN OUTCOME MEASURES: Mothers' reports of infant uptake of nevirapine and place of delivery. RESULTS: Uptake of the infant's nevirapine dose was high, 94% in the intervention group and 88% in the control group (p=0.096). Among women who delivered at home, uptake was higher significantly among infants whose mothers got the take home dose compared to women who did not get the dose (93% vs. 53%, p<0.01). The intervention did not influence place of delivery. Providers were positive about the take home dose concept; difficulties were attributed to HIV-related stigma. CONCLUSIONS: Making take home infant nevirapine available, either as a single dose administered within 72 hours of birth or as part of a more complex six week postnatal regimen, will increase infant uptake especially among women who deliver at home without affecting place of delivery.

Voxel-level biological optimisation of prostate IMRT using patient-specific tumour location and clonogen density derived from mpMRI.

AIMS: This study aimed to develop a framework for optimising prostate intensity-modulated radiotherapy (IMRT) based on patient-specific tumour biology, derived from multiparametric MRI (mpMRI). The framework included a probabilistic treatment planning technique in the effort to yield dose distributions with an improved expected treatment outcome compared with uniform-dose planning approaches. METHODS: IMRT plans were generated for five prostate cancer patients using two inverse planning methods: uniform-dose to the planning target volume and probabilistic biological optimisation for clinical target volume tumour control probability (TCP) maximisation. Patient-specific tumour location and clonogen density information were derived from mpMRI and geometric uncertainties were incorporated in the TCP calculation. Potential reduction in dose to sensitive structures was assessed by comparing dose metrics of uniform-dose plans with biologically-optimised plans of an equivalent level of expected tumour control. RESULTS: The planning study demonstrated biological optimisation has the potential to reduce expected normal tissue toxicity without sacrificing local control by shaping the dose distribution to the spatial distribution of tumour characteristics. On average, biologically-optimised plans achieved 38.6% (p-value: < 0.01) and 51.2% (p-value: < 0.01) reduction in expected rectum and bladder equivalent uniform dose, respectively, when compared with uniform-dose planning. CONCLUSIONS: It was concluded that varying the dose distribution within the prostate to take account for each patient's clonogen distribution was feasible. Lower doses to normal structures compared to uniform-dose plans was possible whilst providing robust plans against geometric uncertainties. Further validation in a larger cohort is warranted along with considerations for adaptive therapy and limiting urethral dose.

Digitizing clinical trials.

Clinical trials are a fundamental tool used to evaluate the efficacy and safety of new drugs and medical devices and other health system interventions. The traditional clinical trials system acts as a quality funnel for the development and implementation of new drugs, devices and health system interventions. The concept of a "digital clinical trial" involves leveraging digital technology to improve participant access, engagement, trial-related measurements, and/or interventions, enable concealed randomized intervention allocation, and has the potential to transform clinical trials and to lower their cost. In April 2019, the US National Institutes of Health (NIH) and the National Science Foundation (NSF) held a workshop bringing together experts in clinical trials, digital technology, and digital analytics to discuss strategies to implement the use of digital technologies in clinical trials while considering potential challenges. This position paper builds on this workshop to describe the current state of the art for digital clinical trials including (1) defining and outlining the composition and elements of digital trials; (2) describing recruitment and retention using digital technology; (3) outlining data collection elements including mobile health, wearable technologies, application programming interfaces (APIs), digital transmission of data, and consideration of regulatory oversight and guidance for data security, privacy, and remotely provided informed consent; (4) elucidating digital analytics and data science approaches leveraging artificial intelligence and machine learning algorithms; and (5) setting future priorities and strategies that should be addressed to successfully harness digital methods and the myriad benefits of such technologies for clinical research.