Physical impairment during and between migraine attacks: A daily diary study of patients with chronic migraine.

OBJECTIVE: While a substantial body of research describes the disabling impacts of migraine attacks, less research has described the impacts of migraine on physical functioning between migraine attacks. The objective of this study is to describe physical impairment during and between migraine attacks as a dimension of burden experienced by people living with chronic migraine. METHODS: The physical impairment domain of the Migraine Physical Function Impact Diary was recorded in headache diaries from the Medication Overuse Treatment Strategy trial. Days with moderate to severe headache were used to approximate migraine attacks. Factor analysis and regression analysis were used to describe associations between migraine and physical impairment. RESULTS: 77,662 headache diary entries from 720 participants were analyzed, including 25,414 days with moderate to severe headache, 19,149 days with mild headache, and 33,099 days with no headache. Mean physical impairment score was 41.5 (SD = 26.1) on days with moderate to severe headache, 12.8 (SD = 15.0) on days with mild headache, and 5.2 (SD = 13.1) on days with no headache. Physical impairment on days with mild headache and days with no headache was significantly associated with days since last moderate to severe headache, physical impairment with last moderate to severe headache, mild headache (compared to no headache), depression, hypersensitivities and cranial autonomic symptoms. CONCLUSIONS: Physical impairment occurs on migraine and non-migraine days. Study participants with frequent headaches, symptoms of depression, hypersensitivities and cranial autonomic symptoms experience physical impairment at a higher rate on days with no headache and days with mild headache.Clinical Trial Registration: ClinicalTrials.gov (NCT02764320).

Capnography-An Essential Monitor, Everywhere: A Narrative Review.

Capnography is now recognized as an indispensable patient safety monitor. Evidence suggests that its use improves outcomes in operating rooms, intensive care units, and emergency departments, as well as in sedation suites, in postanesthesia recovery units, and on general postsurgical wards. Capnography can accurately and rapidly detect respiratory, circulatory, and metabolic derangements. In addition to being useful for diagnosing and managing esophageal intubation, capnography provides crucial information when used for monitoring airway patency and hypoventilation in patients without instrumented airways. Despite its ubiquitous use in high-income-country operating rooms, deaths from esophageal intubations continue to occur in these contexts due to incorrect use or interpretation of capnography. National and international society guidelines on airway management mandate capnography's use during intubations across all hospital areas, and recommend it when ventilation may be impaired, such as during procedural sedation. Nevertheless, capnography's use across high-income-country intensive care units, emergency departments, and postanesthesia recovery units remains inconsistent. While capnography is universally used in high-income-country operating rooms, it remains largely unavailable to anesthesia providers in low- and middle-income countries. This lack of access to capnography likely contributes to more frequent and serious airway events and higher rates of perioperative mortality in low- and middle-income countries. New capnography equipment, which overcomes cost and context barriers, has recently been developed. Increasing access to capnography in low- and middle-income countries must occur to improve patient outcomes and expand universal health care. It is time to extend capnography's safety benefits to all patients, everywhere.

The northern corn leaf blight resistance gene Ht1 encodes an nucleotide-binding, leucine-rich repeat immune receptor.

Northern corn leaf blight, caused by the fungal pathogen Exserohilum turcicum, is a major disease of maize. The first major locus conferring resistance to E. turcicum race 0, Ht1, was identified over 50 years ago, but the underlying gene has remained unknown. We employed a map-based cloning strategy to identify the Ht1 causal gene, which was found to be a coiled-coil nucleotide-binding, leucine-rich repeat (NLR) gene, which we named PH4GP-Ht1. Transgenic testing confirmed that introducing the native PH4GP-Ht1 sequence to a susceptible maize variety resulted in resistance to E. turcicum race 0. A survey of the maize nested association mapping genomes revealed that susceptible Ht1 alleles had very low to no expression of the gene. Overexpression of the susceptible B73 allele, however, did not result in resistant plants, indicating that sequence variations may underlie the difference between resistant and susceptible phenotypes. Modelling of the PH4GP-Ht1 protein indicated that it has structural homology to the Arabidopsis NLR resistance gene ZAR1, and probably forms a similar homopentamer structure following activation. RNA sequencing data from an infection time course revealed that 1 week after inoculation there was a threefold reduction in fungal biomass in the PH4GP-Ht1 transgenic plants compared to wild-type plants. Furthermore, PH4GP-Ht1 transgenics had significantly more inoculation-responsive differentially expressed genes than wild-type plants, with enrichment seen in genes associated with both defence and photosynthesis. These results demonstrate that the NLR PH4GP-Ht1 is the causal gene underlying Ht1, which represents a different mode of action compared to the previously reported wall-associated kinase northern corn leaf blight resistance gene Htn1/Ht2/Ht3.

A Composite System Based upon Hydroxypropyl Cyclodextrins and Soft Hydrogel Contact Lenses for the Delivery of Therapeutic Doses of Econazole to the Cornea, In Vitro.

Fungal keratitis, a disease in which the cornea becomes inflamed due to an invasive fungal infection, remains difficult to treat due in part to limited choices of available treatments. Topical eye drops are first-line treatment, but can be ineffective as low levels of drug reach the target site due to precorneal losses and the impenetrability of the cornea. The aim of this study was to determine the corneal delivery of econazole using a novel topical enhancement approach using a composite delivery system based upon cyclodextrins and soft hydrogel contact lenses. Excess econazole nitrate was added to hydroxypropyl-α-cyclodextrin (HP-α-CD) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) solutions, and the solubility determined using HPLC. Proprietary soft hydrogel contact lenses were then impregnated with saturated solutions and applied to freshly enucleated porcine eyeballs. Econazole nitrate 'eye drops' at the same concentrations served as the control. After 6 h, the corneas were excised and drug-extracted, prior to quantification using HPLC. Molecular dynamic simulations were performed to examine econazole−HP-ß-CD inclusion complexation and dissociation. The minimum inhibitory concentration (MIC) of econazole was determined against four fungal species associated with keratitis, and these data were then related to the amount of drug delivered to the cornea, using an average corneal volume of 0.19 mL. The solubility of econazole increased greatly in the presence of HP-ß-CD and more so with HP-α-CD (p < 0.001), with ratios >> 2. Hydrogel contact lenses delivered ×2.8 more drug across the corneas in comparison to eye drops alone, and ×5 more drug delivered to the cornea when cyclodextrin was present. Molecular graphics demonstrated dynamic econazole release, which would create transient enhanced drug concentration at the cornea surface. The solution-only drops achieved the least satisfactory result, producing sub-MIC levels with factors of ×0.81 for both Fusarium semitectum and Fusarium solani and ×0.40 for both Scolecobasidium tshawytschae and Bipolaris hawaiiensis. All other treatments delivered econazole at > MIC for all four fungal species. The efficacies of the delivery platforms evaluated were ranked: HP-α-CD contact lens > HP-ß-CD contact lens > contact lens = HP-α-CD drops > HP-ß-CD drops > solution-only drops. In summary, the results in this study have demonstrated that a composite drug delivery system based upon econazole−HP-ß-CD inclusion complexes loaded into contact lenses can achieve significantly greater corneal drug delivery with the potential for improved clinical responses.

European standard internal telephone number 2222 for in-hospital emergency calls: A national survey in all French military training hospitals.

Background: In 2016, three European scientific societies called for standardization to the "2222" as a European unique phone number in case of in-hospital emergencies. This study describes the management of in-hospital emergency calls in all French military training hospitals and aims to detail their original transition, for the first time in France, to the "2222". Methods: An electronic standardized questionnaire was emailed to heads of rapid response teams in the eight French military training hospitals. Results: All participants answered the questionnaire (100%). The eight French military training hospitals had a specific procedure for management of in-hospital emergencies. Six hospitals already used a unique phone number for in-hospital emergencies, but none of them were using the 2222 in March 2019. Two hospitals still used several phone numbers for in-hospital emergencies, mainly due to historical and local arrangements. Rapid response teams included at least a physician and a nurse. There was a discussion to switch to "2222" as the unique phone number for in-hospital emergencies in two hospitals. In both, the discussions involved hospital executive officers, medical teams, rapid response teams and technical teams leading to a step-by-step transition. Finally, in October 2019, these two hospitals launched the "2222" procedure for in-hospital emergencies. Conclusion: This study found a large disparity in the eight French military training hospitals, concerning in-hospital emergency protocols. Two French military training hospitals launched the "2222" procedure for the first time in France. Further efforts are still needed to continue to promote the use of the 2222 as a European unique phone number for in-hospital emergencies.

Diagnosing Cardiac Amyloidosis: From Heart Failure to Electrical Storm.

Cardiac amyloidosis is a condition when amyloid fibers are deposited in the extracellular space of the heart causing tachyarrhythmias, heart failure, or sudden cardiac death. We present a 71-year-old woman presenting with dyspnea on admission. Echocardiogram revealed diastolic heart failure and left ventricular hypertrophy with strain pattern concerning for an infiltrative process. She was discharged with diuretic therapy and scheduled for a cardiac magnetic resonance imaging. One week after discharge, she was readmitted with progressive shortness of breath and syncope. She was found to be in shock and had multiple episodes of cardiac arrest with both ventricular tachycardia and pulseless electrical activity. She developed electrical storm and eventually passed within 24 hours. Autopsy revealed gross cardiomegaly and left ventricular hypertrophy with Congo red staining revealing amyloid fibrils with apple-green birefringence. This case demonstrates the rapid progression of cardiac amyloidosis from acute-onset diastolic heart failure to uncontrollable ventricular tachycardia, and eventually death. We review the literature regarding multiple diagnostic modalities that facilitate the confirmation of cardiac amyloidosis.

Current status of variations in in-hospital cardiac arrest call numbers in Japan: a nationwide survey.

The use of standardized internal hospital phone numbers for cardiac arrest is advocated in Europe. We evaluated the current status of variations in medical emergency call numbers for in-hospital patients in Japan and whether anesthesiologists would approve a standardized number. From June 2018 to August 2018, a questionnaire survey was mailed to anesthesiologists in 1373 Japanese Society of Anesthesiologists (JSA)-accredited hospitals. The basis for opinions on using a standardized cardiac arrest call number in all Japanese hospitals was evaluated. Of 1373 facilities (response rate, 58%, n = 800), 741/776 (96%) reported a response system for in-hospital cardiac arrest; 638/710 (90%) responded to cardiac arrest through loudspeaker broadcast, audible to both patients and staff; 346/777 (48%) used a number between one and five digits long, four-digit numbers being the most common. Across Japan, 370 different numbers were reported. Only 385/688 (56%) of respondents had the emergency number memorized. Finally, 423/776 (55%) respondents approved standardizing a hospital telephone number for summoning help. Multivariate analysis showed that facilities where the anesthesiologists already memorized the call number were the only reason identified for opposition to the standardization. Although 96% of JSA-accredited hospitals had a response system for in-hospital cardiac arrests, discussions for standardization of a unified number need to be encouraged for improved emergency response.

European minimum standards for obstetric analgesia and anaesthesia departments: An experts' consensus.

: An important variability of anaesthetic standards of care was discovered in the obstetric departments of many European Union countries. After discussing this issue in various meetings of the European Society of Anaesthesiology (ESA) board and its obstetric subcommittee, European Board of Anaesthesiology of the European Union of Medical Specialists (EBA-UEMS) executive members, ESA obstetric subcommittee members and European experts in obstetric anaesthesiology have participated in the elaboration of this document. This experts' opinion is focused mainly on obstetric patients and safety concerns in terms of minimum standards of practice. An initial bibliographical search was performed in medical databases and general literature, searching for obstetric anaesthesiology standards to select the most important safety issues. After the initial presentation of the project during EBA-UEMS and ESA obstetric subcommittee meetings, participants were asked to review the document; several rounds of revisions were performed by the experts, to reach a common opinion concerning the topics considered central to patient safety in the obstetric setting. After three rounds of revision, a consensus was reached and is presented in this document, which includes the list of topics considered relevant by the involved areas, and the respective recommendations. These recommendations covered some EBA-UEMS strategic key areas, in addition to several clinical aspects of common obstetric practice.

Publisher Correction: Temporal rate is not a distinct perceptual metric.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ten years of the Helsinki Declaration on patient safety in anaesthesiology: An expert opinion on peri-operative safety aspects.

: Patient safety is an activity to mitigate preventable patient harm that may occur during the delivery of medical care. The European Board of Anaesthesiology (EBA)/European Union of Medical Specialists had previously published safety recommendations on minimal monitoring and postanaesthesia care, but with the growing public and professional interest it was decided to produce a much more encompassing document. The EBA and the European Society of Anaesthesiology (ESA) published a consensus on what needs to be done/achieved for improvement of peri-operative patient safety. During the Euroanaesthesia meeting in Helsinki/Finland in 2010, this vision was presented to anaesthesiologists, patients, industry and others involved in health care as the 'Helsinki Declaration on Patient Safety in Anaesthesiology'. In May/June 2020, ESA and EBA are celebrating the 10th anniversary of the Helsinki Declaration on Patient Safety in Anaesthesiology; a good opportunity to look back and forward evaluating what was achieved in the recent 10 years, and what needs to be done in the upcoming years. The Patient Safety and Quality Committee (PSQC) of ESA invited experts in their fields to contribute, and these experts addressed their topic in different ways; there are classical, narrative reviews, more systematic reviews, political statements, personal opinions and also original data presentation. With this publication we hope to further stimulate implementation of the Helsinki Declaration on Patient Safety in Anaesthesiology, as well as initiating relevant research in the future.

Temporal rate is not a distinct perceptual metric.

Sensory adaptation experiments have revealed the existence of 'rate after-effects' - adapting to a relatively fast rate makes an intermediate test rate feel slow, and adapting to a slow rate makes the same moderate test rate feel fast. The present work aims to deconstruct the concept of rate and clarify how exactly the brain processes a regular sequence of sensory signals. We ask whether rate forms a distinct perceptual metric, or whether it is simply the perceptual aggregate of the intervals between its component signals. Subjects were exposed to auditory or visual temporal rates (a 'slow' rate of 1.5 Hz and a 'fast' rate of 6 Hz), before being tested with single unfilled intervals of varying durations. Results show adapting to a given rate strongly influences the perceived duration of a single empty interval. This effect is robust across both interval reproduction and duration discrimination judgments. These findings challenge our understanding of rate perception. Specifically, they suggest that contrary to some previous assertions, the perception of sequence rate is strongly influenced by the perception of the sequence's component duration intervals.

In Vitro Topical Delivery of Chlorhexidine to the Cornea: Enhancement Using Drug-Loaded Contact Lenses and ß-Cyclodextrin Complexation, and the Importance of Simulating Tear Irrigation.

Microbial keratitis is a severe, sight-threatening condition caused by various pathogens. Eyedrops are the standard delivery modality for treating these disorders; however, blinking reflex, elevated tear production, and nasolacrimal drainage eliminate much of the instilled dose within a few seconds. Therefore, eyedrops must be applied repeatedly for prolonged periods. The present study aimed to probe more effective ocular delivery of chlorhexidine based upon drug-loaded hydrogel contact lenses and ß-cyclodextrin (ß-CD), while also determining the effect of constant irrigation with simulated tear fluid (STF) in in vitro experiments. Chlorhexidine digluconate (as 0.2 and 2% solutions, ß-CD inclusion complexes, and loaded hydrogel contact lenses) were applied to enucleated porcine eyes as single or multiple 10 µL doses, or as drug-loaded contact lenses, with and without ß-CD. The corneas were then excised and drug-extracted quantified by high-performance liquid chromatography (HPLC). The effect of constant irrigation by STF was evaluated to test the effect of increased tear production on corneal delivery. Potential antimicrobial activity of the delivered drug was also assessed. Results showed that drug-loaded contact lenses delivered the greatest amount of chlorhexidine into the cornea over a 24 h period, while the eyedrop solution comparator delivered the least. The ß-CD significantly enhanced chlorhexidine delivery to the cornea from eyedrop solution, although contact lenses loaded with chlorhexidine-ß-CD failed to enhance delivery. ß-CD within the hydrogel matrix impeded drug release. Constant irrigation with STF significantly reduced the amount of drug delivered to the cornea in all cases. Chlorhexidine retained antimicrobial activity in all delivery methods. Hydrogel contact lenses loaded with chlorhexidine delivered significantly higher levels to the cornea compared to eyedrops, either multiple hourly doses or a single dose. They also offer reduced application, in particular, to a nonulcerated corneal infection. Finally, the importance of fully accounting for tear production in in vitro ocular delivery experiments was highlighted.

Evidence-Based Design in Hospital Renovation Projects: A Study of Design Implementation for User Controls.

PURPOSE: The purpose of this article was to investigate and report the implementation of evidence-based design (EBD) principles relating to user controls into hospital renovation projects. BACKGROUND: Progress requires the application of the most recent knowledge and technology. When it comes to the design and construction of healthcare facilities, the latest knowledge comes in the form of EBD research. EBD is the process of basing decisions about the built environment on credible research to achieve the best possible outcomes. The desired outcomes of EBD recommendations include improvements to enhance user control. User control factors include the individual control over bed position, air temperature, lights, sound, and natural light. METHOD: A list of recommendations from existing EBD literature related to user controls was compiled. Construction documents from 30 recent healthcare facility renovation projects across the United States were obtained and analyzed. Implementation levels for the EBD categories of user controls were reported. RESULTS: The findings indicate relatively extensive industry use of EBD principles relating to user control of temperature, lights, and natural lighting. CONCLUSIONS: The findings indicate that EBD recommendations related to user controls are being adopted in practice at consistently high levels. These findings also reveal that there are still areas of potential improvement which could inform those who influence or determine building design, codes, standards, and guidelines. The results are helpful to owners, designers, and contractors by providing a glimpse into how well the industry is recognizing and implementing known best practices. The findings likewise introduce new opportunities for further research which could lead to additional improvement in the healthcare facilities of the future.

Controlled in vitro delivery of voriconazole and diclofenac to the cornea using contact lenses for the treatment of Acanthamoeba keratitis.

Acanthamoeba keratitis is caused by a protozoal infection of the cornea, with 80% of cases involving the improper use of contact lenses. The infection causes intense pain and is potentially blinding. However, early diagnosis improves treatment efficacy and the chances of healing. Despite the apparent accessibility of the cornea, patients do not always respond well to current eye drop treatments largely due to rapid dose loss due to blinking and nasolacrimal drainage. Here, the topical drug delivery of voriconazole alone and in combination with diclofenac via drug-loaded contact lenses, were investigated in vitro. The contact lenses were applied onto excised porcine eyeballs and maintained at 32 °C under constant irrigation, with simulated tear fluid applied to mimic in vivo conditions. The drug delivered to the corneas was quantified by HPLC analysis. The system was further tested in terms of cytotoxicity and a scratch wound repopulation model, using resident cell types. Sustained drug delivery to the cornea was achieved and for voriconazole, the MIC against Acanthamoeba castellanii was attained alone and in combination with diclofenac. MTT and scratch wound data showed reasonable cell proliferation and wound repopulation at the drug doses used, supporting further development of the system to treat Acanthamoeba keratitis.

Adaptation reveals multi-stage coding of visual duration.

In conflict with historically dominant models of time perception, recent evidence suggests that the encoding of our environment's temporal properties may not require a separate class of neurons whose raison d'être is the dedicated processing of temporal information. If true, it follows that temporal processing should be imbued with the known selectivity found within non-temporal neurons. In the current study, we tested this hypothesis for the processing of a poorly understood stimulus parameter: visual event duration. We used sensory adaptation techniques to generate duration aftereffects: bidirectional distortions of perceived duration. Presenting adapting and test durations to the same vs different eyes utilises the visual system's anatomical progression from monocular, pre-cortical neurons to their binocular, cortical counterparts. Duration aftereffects exhibited robust inter-ocular transfer alongside a small but significant contribution from monocular mechanisms. We then used novel stimuli which provided duration information that was invisible to monocular neurons. These stimuli generated robust duration aftereffects which showed partial selectivity for adapt-test changes in retinal disparity. Our findings reveal distinct duration encoding mechanisms at monocular, depth-selective and depth-invariant stages of the visual hierarchy.

The role of Peripheral Vision in the Flashed Face Distortion Effect.

The flashed face distortion effect is a phenomenon whereby images of faces, presented at 4-5 Hz in the visual periphery, appear distorted. It has been hypothesized that the effect is driven by cortical, rather than retinal, components. Here, we investigated the role of peripheral viewing on the effect. Normally sighted participants viewed the stimulus peripherally, centrally, and centrally with a blurring lens (to match visual acuity in the peripheral location). Participants rated the level of distortion using a Visual Analogue Scale. Although optical defocus did have a significant effect on distortion ratings, peripheral viewing had a much greater effect, despite matched visual acuity. We suggest three potential mechanisms for this finding: increased positional uncertainty in the periphery, reduced deployment of attention to the visual periphery, or the visual crowding effect.