Patient-reported outcome measures and patient engagement in heart failure clinical trials: multi-stakeholder perspectives

There are many consequences of heart failure (HF), including symptoms, impaired health-related quality of life (HRQoL), and physical and social limitations (functional status). These have a substantial impact on patients' lives, yet are not routinely captured in clinical trials. Patient-reported outcomes (PROs) can quantify patients' experiences of their disease and its treatment. Steps can be taken to improve the use of PROs in HF trials, in regulatory and payer decisions, and in patient care. Importantly, PRO measures (PROMs) must be developed with involvement of patients, family members, and caregivers from diverse demographic groups and communities. PRO data collection should become more routine not only in clinical trials but also in clinical practice. This may be facilitated by the use of digital tools and interdisciplinary patient advocacy efforts. There is a need for standardization, not only of the PROM instruments, but also in procedures for analysis, interpretation and reporting PRO data. More work needs to be done to determine the degree of change that is important to patients and that is associated with increased risks of clinical events. This ‘minimal clinically important difference’ requires further research to determine thresholds for different PROMs, to assess consistency across trial populations, and to define standards for improvement that warrant regulatory and reimbursement approvals. PROs are a vital part of patient care and drug development, and more work should be done to ensure that these measures are both reflective of the patient experience and that they are more widely employed.     

Genotyping of clinical and environmental Aspergillus flavus isolates from Iran using microsatellites

Aspergillus flavus is the second most important Aspergillus species causing human infections in tropical countries. Despite an increasing number of infections of A. flavus in Iran, the molecular epidemiology of clinical and environmental strains has not been well studied. We used a panel of nine microsatellite markers to analyse the genetic relatedness of A. flavus. Microsatellite typing of 143 (n = 119 clinical and n = 24 environmental) isolates demonstrated 118 different genotypes. A possible outbreak at a pulmonary ward was discovered. The discriminatory power for the individual markers ranged from 0.4812 to 0.9457 and the panel of all nine markers combined yielded a diversity index of 0.9948. This high‐resolution typing method assists in better understanding of the molecular epidemiology of A. flavus.     

Metabolic response of Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) to essential oil of Ajwain and thymol

The effects of Carum copticum essential oil (CC EO) and thymol were assayed against fourth instar of Ephestia kuehniella Zeller by determining insecticidal activities and enzymatic responses. Concentrations of 5.42 and 6.81?μl/ml were obtained as LC₅₀ values for CC EO and thymol, respectively. The activities of esterases, aminotransferases, aldolase, and lactate dehydrogenase significantly decreased in the treated larvae by CC EO and thymol. Significant increases in glutathione S-transferases, γ-glutamyl transferase, and phosphatases were observed after treatment. Results revealed that CC EO and thymol significantly influenced the enzymatic activities of E. kuehniella leading to disruption of survival and metabolic responses.     

Crimean-Congo hemorrhagic fever among health care workers in Iran: a seroprevalence study in two endemic regions

Crimean-Congo hemorrhagic fever (CCHF) has repeatedly caused nosocomial outbreaks among hospital staff. In the summer of 2003, we studied the seroprevalence of anti-CCHF IgG among health care workers who had come in contact with Crimean-Congo hemorrhagic fever patients from three referral hospitals in endemic regions of Iran. A total of 223 eligible staff were examined. Whereas 5 of 129 (3.87%) exposed health care workers tested positive, none of the 94 in the unexposed group did (P=0.075). Seropositivity was more frequent among those whose intact skin had come in contact with nonsanguineous body fluids (9.52%) and those who had had percutaneous contacts (7.14%). Health care workers exposed to Crimean-Congo hemorrhagic fever patients, those who live in Systan-Baluchestan province, and older health care workers were more prone to seropositivity. Where introduction of high-risk modes of contact cannot be confined, we propose that health care workers take all the protective measures when handling Crimean-Congo hemorrhagic fever patients, particularly their blood and other body fluids.     

An FBG magnetic sensor for oil flow monitoring in sandstone core

Monitoring the oil movement using a non-contact optical fiber probe during enhanced oil recovery is a novel technique to increase the efficiency of the process by distinguishing the oil position in the reservoir. A partially unclad fiber Bragg grating (FBG) coated with Fe₃O₄ nanoparticles as a magnetic field sensor is experimentally demonstrated. A series of six FBGs reflecting different wavelengths are fixed on the surface of sandstone. Nanofluids containing magnetite nanoparticles and alkaline-surfactant-polymer are injected continuously in two separate steps into the sandstone, which is saturated with 20% oil and 80% brine. The chamber is equipped with a solenoid that acts as a magnetic field generator. The changes in the magnetic field strength depended on the FBG-solenoid distance and the density of localized injected nanoparticles near the FBGs leads to a shift of the reflected wavelength of each single FBG accordingly. The shift is caused by the interference of different propagating modes reflected from the core-cladding and cladding-magnetite layer interfaces. The intensity of the FBG spectra decreases by injecting the nanofluid and vice versa for surfactant injection. The sensor response time of ∼21 s confirms the high reliability and repeatability of the sensing scheme. Movement of oil along the sandstone alters the wavelength shift in the FBG spectra.

Monitoring the oil movement using a non-contact optical fiber probe during enhanced oil recovery is a novel technique to increase the efficiency of the process by distinguishing the oil position in the reservoir.     

Impact of antioxidant supplementations on cardio‐renal protection in cardiac surgery: an updated and comprehensive meta‐analysis and systematic review

This systematic review with meta‐analysis sought to determine the strength of evidence in terms of the impact of common antioxidant supplementations, such as N‐acetylcysteine (NAC), vitamin C, and polyunsaturated fatty acids (PUFA) on perioperative outcomes after cardiac surgery with particular focus on the incidence of atrial fibrillation (AF) and acute kidney injury (AKI) with associated mortality. A total of 29 trials were identified that reported incidence of AF and 17 trials that reported incidence of AKI. Pooled analysis reported that NAC (OR=0.5; P=.001), vitamin C (OR=0.4; P=.001), and PUFA (OR=0.8; P=.01) administration were associated with significantly reduced incidence of AF. In terms of postoperative AKI, only NAC was shown to be a beneficial supplement that was able to significantly reduce the incidence of AKI (OR=0.7; P=.01), and NAC could also significantly decrease overall mortality (OR=0.3; P=.03) following cardiac surgery. The use of NAC in patients undergoing cardiac surgery should be strongly recommended due to its combined cardio‐renal protective effects and reduced mortality. Also, PUFA and vitamin C might be able to significantly decrease the incidence of arrhythmia; however, reno‐protective effects and impact on overall mortality of these supplements seem to be less impressive.     

Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures

Metabolic Brain Disease - 2-Arachidonoylglycerol (2-AG) and anandamide are two major endocannabinoids produced, released and eliminated by metabolic pathways. Anticonvulsive effect of 2-AG and CB1...     

From the Cover: Warming enabled upslope advance in western US forest fires

Increases in burned area and large fire occurrence are widely documented over the western United States over the past half century. Here, we focus on the elevational distribution of forest fires in mountainous ecoregions of the western United States and show the largest increase rates in burned area above 2,500 m during 1984 to 2017. Furthermore, we show that high-elevation fires advanced upslope with a median cumulative change of 252 m (−107 to 656 m; 95% CI) in 34 y across studied ecoregions. We also document a strong interannual relationship between high-elevation fires and warm season vapor pressure deficit (VPD). The upslope advance of fires is consistent with observed warming reflected by a median upslope drift of VPD isolines of 295 m (59 to 704 m; 95% CI) during 1984 to 2017. These findings allow us to estimate that recent climate trends reduced the high-elevation flammability barrier and enabled fires in an additional 11% of western forests. Limited influences of fire management practices and longer fire-return intervals in these montane mesic systems suggest these changes are largely a byproduct of climate warming. Further weakening in the high-elevation flammability barrier with continued warming has the potential to transform montane fire regimes with numerous implications for ecosystems and watersheds.

Fire is an integral component of most forested lands and provides significant ecological services (1). However, burned area, fire size, the number of large fires, and the length of fire season have increased in the western United States in recent decades (2, 3). Increasing fire activity and the expansion of wildland urban interface (4) collectively amplified direct and indirect fire-related loss of life and property (5, 6) and contributed to escalating fire suppression costs (7). While increased biomass due to a century of fire exclusion efforts is hypothesized to have partially contributed to this trend (8), climate change is also implicated in the rise of fire activity in the western United States (9–11).Although increases in forest fire activity are evident in all major forested lands in the western United States (2, 12, 13), an abundance of moisture—due to snowpack persistence, cooler temperatures, and delayed summer soil and fuel drying—provides a strong buffer of fire activity (13) and longer fire-return intervals (14) at high elevations. Recent studies, however, point to changing fire characteristics across many ecoregions of the western United States (15), including high-elevation areas of the Sierra Nevada (16), Pacific Northwest, and Northern Rockies (12, 17). These studies complement documented changes in montane environments including amplified warming with elevation (18), widespread upward elevational shift in species (19), and increased productivity in energy-limited high-elevation regions that enhance fuel growth and connectivity (20). These changes have been accompanied by longer snow-free periods (21), increased evaporative demand (9), and regional declines in fire season precipitation frequency (11) across the western United States promoting increased fuel ignitability and flammability that have well-founded links to forest burned area. A warmer climate is also conducive to a higher number of convective storms and more frequent lightning strikes (22).In this study, we explore changes in the elevational distribution of burned forest across the western United States and how changes in climate have affected the mesic barrier for high-elevation fire activity. We focus on changes in high-elevation forests that have endured fewer direct anthropogenic modifications compared to drier low-elevation forests that had frequent low-severity fires prior to European colonization and have been more subject to changes in settlement patterns as well as fire suppression and harvest (23, 24); we also pose the following questions: 1) Has the elevational distribution of fire in the western US forests systematically changed? and 2) What changes in biophysical factors have enabled such changes in high-elevation fire activity? We explore these questions across 15 mountainous ecoregions of the western United States using records from large fires (>405 ha) between 1984 and 2017 [Monitoring Trends in Burn Severity (MTBS) (25)], a 10-m–resolution digital elevation model, and daily high-spatial–resolution surface meteorological data [gridMET (26)].We focus on the trends in Z₉₀—defined as the 90th percentile of normalized annual elevational distribution of burned forest in each ecoregion. Here, the term “normalized” essentially refers to the fraction of forest area burned by elevation. We complement this analysis by examining trends in burned area by elevational bands and using quantile regression of normalized annual forest fire elevation. We then assess the interannual relationships between Z₉₀ and vapor pressure deficit (VPD) and compare the upslope advance in montane fire to elevational climate velocity of VPD during 1984 to 2017. Specifically, we use VPD trends and VPD–high-elevation fire regression to estimate VPD-driven changes in Z₉₀ and BA₉₀— defined as annual burned area above the 90th percentile of forest elevational distribution in each ecoregion—during 1984 to 2017.