Search

This article provides a comprehensive overview of the assessment and treatment of reflux-like symptoms in the community. It emphasizes the limitations of using proton pump inhibitors (PPIs) as a first-line treatment and advocates for a holistic approach that considers various factors contributing to symptoms. The article offers practical strategies for patients to identify triggers and provides tailored lifestyle advice. The goal is to empower patients to manage their symptoms through a combination of treatments and self-care practices. The article also highlights the potential for collaboration between primary care and community pharmacies to support patients. Further research in this area is needed. [Extracted from the article]

Invasions by non-native plant species after fire can negatively affect important ecosystem services and lead to invasion-fire cycles that further degrade ecosystems. The relationship between fire and plant invasion is complex, and the risk of invasion varies greatly between functional types and across geographic scales. Here, we examined patterns and predictors of non-native plant invasion following fire across the western United States. We specifically analyzed how the abundance of non-native plants after fire was related to fire characteristics and environmental conditions, such as climate, soil, and topography, in 26,729 vegetation plots from government networks and individual studies. Non-native plant cover was higher in plots measured after wildfires compared to prescribed burns or unburned plots. The post-fire cover of non-native species varied by plant functional type, and only the cover of short-lived (i.e., annual and biennial) forbs and short-lived C3 grasses was significantly higher in burned plots compared to unburned plots. Cool-season short-lived grasses composed most of the non-native post-fire vegetation, with cheatgrass (Bromus tectorum) being the most recorded species in the dataset. Climate variables were the most influential predictors of the cover of non-native short-lived grasses and forbs after fires, with invasion being more common in areas with drier summers and a higher proportion of yearly precipitation falling in October through March. Models using future projected climate for mid (2041–2070) and end (2071–2100) of century showed a potential for increasing post-fire invasion risk at higher elevations and latitudes. These findings highlight priorities for mitigation, monitoring, and restoration efforts to reduce post-fire plant invasion risk across the western United States. [ABSTRACT FROM AUTHOR]

Managed low‐severity surface fires are frequently implemented in efforts to restore disturbance processes to forests of North America; although the effects of managed fire on forest structure are well‐studied, few studies investigate whether these disturbances cascade to impact pollinator communities.We analysed bee‐habitat relationships in fire‐treated (1‐ and 3‐years post‐treatment) and non‐treated ponderosa pine stands in Colorado to test wild bee population responses.Observed bee richness and α‐diversity were highest in stands 1‐year post‐fire and had more Anthophora, Bombus, Osmia and Lasioglossum spp. in comparison to 3‐year post‐fire and non‐treated stands. Bee functional groups were responsive to treatments, with more below‐ground nesting taxa present in stands 3 years post‐fire.Floral richness was the highest mid‐growing season (June, July) and within 1‐year post‐fire stands.A model analysing the effects of foraging and nesting habitat variation on bee assemblages indicated positive association between floral richness and bee α‐diversity, but negative relationships with stand basal area. Nesting habitat was not associated with variation in bee assemblages.We conclude that managed fire has positive short‐term effects on bee biodiversity that are likely mediated by floral richness. However, these effects were not detectable by 3 years post‐treatment in the southern Rocky Mountain region. [ABSTRACT FROM AUTHOR]

Summary: Background: Healthcare service provision in inflammatory bowel disease (IBD) is often designed to meet targets set by healthcare providers rather than those of patients. It is unclear whether this meets the needs of patients, as assessed by patients themselves. Aims: To assess patients' experience of IBD and the healthcare they received, aiming to identify factors in IBD healthcare provision associated with perceived high‐quality care. Methods: Using the 2019 IBD standards as a framework, a national benchmarking tool for quality assessment in IBD was developed by IBD UK, comprising a patient survey and service self‐assessment. Results: 134 IBD services and 9757 patients responded. Perceived quality of care was lowest in young adults and increased with age, was higher in males and those >2 years since diagnosis. No hospital services met all the national IBD standards for recommended workforce numbers. Key metrics associated with patient‐reported high‐ quality care were: identification as a tertiary centre, patient information availability, shared decision‐ making, rapid response to contact for advice, access to urgent review, joint medical/surgical clinics, and access to research (all p < 0.001). Higher numbers of IBD nurse specialists in a service was strongly associated with patients receiving regular reviews and having confidence in self‐management and reporting high‐ quality care. Conclusions: This extensive patient and healthcare provider survey emphasises the importance of aspects of care less often measured by clinicians, such as communication, shared decision‐ making and provision of information. It demonstrates that IBD nurse specialists are crucial to meeting the needs of people living with IBD. [ABSTRACT FROM AUTHOR]

After a two-decade moratorium on psychedelic research in the United States, new studies on psychedelic assisted psychotherapy have shown promising results in the treatment of psychiatric disorders and the betterment of well people. Little has been written in contemporary psychoanalytic journals about the possible use of psychoanalytic theory as an underpinning for this research. This paper examines three concepts from psychoanalytic thinkers that may contribute to an understanding of what is curative in psychedelic assisted psychotherapy. First, I examine the possibility of psychedelics as a catalyst in changing a patient's implicit relational patterns. Second, I use the work of Winnicott and Christopher Bollas to explore the psychedelic experience. Finally, I look at the role of mystical experience in psychedelic assisted psychotherapy. [ABSTRACT FROM AUTHOR]

The recognition and management of stroke in the prehospital setting has become increasingly important to improve patient outcomes. Several strategies to advance prehospital stroke care have been developed, including the mobile stroke unit and the telemedicine-enabled ambulance-or "mini-MSU." These strategies both incorporate ambulance-based audio-visual telemedicine evaluation with a vascular neurologist to facilitate faster treatment but differ in several areas including upfront and recurring costs, scalability or growth potential, ability to integrate into existing emergency medical services systems, and interoperability across multiple specialties or conditions. While both the mobile stroke unit and mini-mobile stroke unit model are valid approaches to improve stroke care, the authors aim to compare these models based on costs, scalability, integration, and interoperability in order to guide our prehospital leaders to find the best solutions for their communities. [ABSTRACT FROM AUTHOR]

Introduction: We assessed patients' perceptions of physician empathy during telemedicine consultations as compared to in-person consultations during clinical encounters for acute stroke.Methods: This prospective cohort study was undertaken at a comprehensive stroke centre hub in collaboration with a distant community hospital spoke site. Eligible participants presented to hub or spoke emergency departments with suspected acute stroke within three hours of symptom onset. Participants were evaluated at the hub site in person or at the remote site via telemedicine by the same group of neurologists. Following acute care decisions, single-visit data including participant-reported assessments of physician empathy were collected within 24 h. The primary outcome was the Consultation and Relational Empathy score. The secondary outcome for the telemedicine cohort was the Telemedicine Patient Satisfaction Measure score.Results: Between 31 May 2013-13 March 2019, 70 patients completed the study. Fifty patients were seen by telemedicine and 20 patients were seen in person. Median Consultation and Relational Empathy scores (with a possible score of 10-50) were 49 (range 27-50) for telemedicine and 45 (range 26-50) for in-person consultations (Wilcoxon rank sum p = 0.18). Each item of the Consultation and Relational Empathy questionnaire was rated very good or excellent by at least 87% of participants in the telemedicine group. The median Telemedicine Patient Satisfaction Measure score was 54 (range 12-60), with each item rated agree or strongly agree by at least 84% of participants.Discussion: We found no difference between telemedicine and in-person visits in patient perception of physician empathy in acute stroke care. Therefore, we conclude that empathy can be conveyed by facial expression, voice and attentiveness in a telemedicine encounter and, in the setting of acute stroke care, does not require physical touch or proximity. [ABSTRACT FROM AUTHOR]

Peatland complexes in the humid highlands of Hawai'i are vital refuges of biodiversity and freshwater resources. Hawaiian peat deposits are also rare repositories of terrestrial ecosystem archives located in an otherwise vast expanse of ocean. We investigated the potential for researching the paleohydrological history of Hawaiian montane peatlands on Kohala, Hawai'i Island through analyses of testate amoebae and Cladocera. Surface peat was collected from a variety of ecohydrological habitats (from water pools to hummocks) and analyzed for modern testate amoeba and cladoceran species relative abundance. We identified 54 morphotype taxa from 21 genera of testate amoebae, 4 taxa and genera of littoral Cladocera, and the common peat rotifer Habrotrocha angusticollis. Testate amoeba diversity and morphotype occurrence mirrored observations from many high-latitude peatland studies. Constrained and unconstrained ordinations support the hypothesis that surface moisture, measured as water-table depth, is an important control on the distribution of testate amoebae and Cladocera in Hawaiian peatlands. Transfer functions relying on weighted-averaging and modern analogs were developed to predict water-table depths from species relative abundance data, and these perform well under leave-one-site-out cross-validation: RMSEP = 9.75–10.3 cm, R2 = 0.56–0.62. Including cladoceran abundance data in the calibration dataset produced modest model improvement: RMSEP = 1–8% and R2 = 2–13%. A weighted-average partial-least-squares transfer function was applied to microfossil assemblages from a 0.5 m-long peat core with a 210Pb decay chronology anchored by ten existing measurements of 210Pb activity and a Bayesian statistical framework. Microfossils were well-preserved in the peat core. The water-table depth optima of an abundant down-core taxa, Hyalosphenia subflava, is not precisely constrained in the calibration data set, but estimates match those of other tropical studies. A reconstruction of water-table depth indicates dry early nineteenth-century conditions, wet conditions in the late 19th to early twentieth centuries, followed by progressive drying for much of the twentieth-century. Testate amoeba composition appears to have been sensitive to severe drought in recent decades. The results signal that assemblages of testate amoebae and Cladocera are useful proxies of Hawaiian peatland paleohydrology and should be considered alongside other archives of Hawaiian environmental history. [ABSTRACT FROM AUTHOR]

Background Infammatory bowel disease (IBD) has a signifcant impact on quality of life for many people. Objective To assess the prevalence of common mental health conditions in IBD and the combined impact of IBD and mental health conditions on healthcare use and time off work. Methods A UK population- based primary care database (Royal College of General Practitioners Research and Surveillance Centre) was used to identify adults with IBD (n=19 011) (Crohn's disease (CD) or ulcerative colitis (UC)), and matched controls (n=76 044). Prevalences of anxiety, depressive episodes and depressive disorder recorded in primary care were assessed between 2016 and 2018. Outcomes comprised of rates of primary care visits, emergency secondary care visits, certifcates for time off work, antidepressant and anxiolytic prescriptions. Findings Mental health conditions were more common in people with CD than controls: anxiety episodes (3.5% vs 3.0%; p=0.02), depressive episodes (5.7% vs 4.1%; p<0.001) and depressive disorder (17.5% vs 12.9%; p<0.001), and people with UC versus controls: depressive episodes (4.4% vs 3.6%; p<0.001) and depressive disorder (14.2% vs 12.4%; p<0.001). Healthcare utilisation rates were higher in people with IBD than controls (primary care visits incidence rate ratio 1.47 (95% CI 1.43 to 1.51); emergency secondary care visits 1.87 (1.79 to 1.95); ftness for work certifcates 1.53 (1.44 to 1.62); antidepressant use 1.22 (1.13 to 1.32); anxiolytic use 1.20 (1.01 to 1.41)). In people with IBD, mental health conditions were associated with additional increases in healthcare use and time off work. Conclusion Depression and anxiety are more common in people with IBD than matched controls. Healthcare utilisation and prescribing of psychotropic medications are also higher in people with IBD. Mental health conditions in people with IBD are associated with additional healthcare use and time off work. Clinical implications Evidence- based mental health support programmes, including psychological treatments, are needed for people with IBD. [ABSTRACT FROM AUTHOR]

Background: With Panamanian golden frogs (Atelopus zeteki; PGFs) likely extirpated from the wild, ensuring long-term sustainability of captive populations is crucial in order to conserve this critically endangered species. Unfortunately, PGFs display a unique reproductive behavior involving a prolonged period of amplexus leading to challenges in their successful captive propagation. The Maryland Zoo in Baltimore has observed high levels of mortality during the breeding season and suboptimal reproductive success leading to the use of hormone stimulation to aid in reproduction and health management. Methods: This project aimed to develop induced ovulation and health management protocols by (1) evaluating different doses of gonadotropin releasing hormone analogue (GnRHa), (2) comparing the efficacy of GnRHa and GnRHa + metoclopramide, (3) determining latency periods and the effects of pulsed hormone sequences; and (4) establish if mortality is impacted by hormone therapy. Female PGFs (n = 174) were given GnRHa either in various concentrations (Experiment 1) or combined with metoclopramide (Experiment 2), and oviposition success, latency, and mortality were measured as binary response variables. Results: Overall, the use of exogenous hormones significantly decreased mortality when compared to the control data of natural egg-laying females. GnRHa doses of 0.05 μg/g body weight produced similar ovulation rates compared to higher doses, and the addition of metoclopramide did not increase oviposition success compared to GnRHa alone. Lastly, results indicate the majority of female PGFs will release eggs within 48 h following the initial pulse of hormones with a small percentage ovipositing after a second pulse. Conclusion: Findings from this study will benefit captive management of PGFs by documenting the increased survival of females when given hormone stimulation and defining appropriate GnRHa doses and expected latency to spawning. [ABSTRACT FROM AUTHOR]

Introduction: People with inflammatory bowel disease (IBD) are at increased risk of pneumonia and herpes zoster, yet other common infection types have not been explored. Anxiety and depression are more prevalent in IBD; however, the impact of these conditions on primary care healthcare use in IBD is not known. Methods and analysis: We will perform two retrospective studies using a large English population-based primary care cohort to compare the following outcomes in people with IBD and matched controls: incident infections (Study 1) and prevalent mental health problems and healthcare use, overall and in those with and without mental health problems (Study 2). All adults registered with general practices contributing to Royal College of General Practitioners Research and Surveillance Centre database between 1 January 2014 and 1 January 2019 are eligible. Infection outcomes comprise the incidence of common infections (upper respiratory tract infections, pneumonia, acute bronchitis, influenza and influenza-like illnesses, skin infections, herpes simplex and herpes zoster infections, genital infections, urinary tract infections and gastrointestinal infections) and any viral infection. Mental health and healthcare use outcomes are: prevalence of depressive episodes; anxiety episodes; recurrent depression; rates of primary care and emergency secondary care visits; primary-care issued sick notes (reflecting time off work). Analyses will be adjusted for sociodemographic factors recorded in the primary care record. Discussion: These studies will quantify the infection risk in IBD, the excess burden of anxiety and depression in a population-based IBD cohort, and the impact of mental health conditions on healthcare use and time off work. Greater understanding and awareness of infection risk and common mental health issues will benefit people with IBD and healthcare practitioners and will guide policy makers as allocation of resource may be guided by the real-world information produced by these studies. Trial registration number: NCT03836612. [ABSTRACT FROM AUTHOR]

Background:With increasing demand for neurologists, nontraditional health care delivery mechanisms have been developed to leverage this limited resource. Introduction:Telemedicine has emerged as an effective digital solution. Over the past three decades, telemedicine use has steadily grown; however, neurologists often learn on the job, rather than as part of their medical training. The current literature regarding telestroke training during neurology training is sparse, focusing on cerebrovascular fellowship curricula. We sought to enhance telestroke training in our neurology residency by incorporating real-life application. Materials and Methods:We implemented a formal educational model for neurology residents to use telemedicine for remote acquisition of the National Institutes of Health Stroke Scale (NIHSS) for patients with suspected acute ischemic stroke (AIS) before arrival at our comprehensive stroke center. This three-phase educational model involved multidisciplinary classroom didactics, simulation exercises, and real-world experience. Training and feedback were provided by neurologists experienced in telemedicine. Results:All residents completed formal training in telemedicine prehospital NIHSS acquisition and had the opportunity to participate in additional simulation exercises. Currently, residents are gaining additional experience by performing prehospital NIHSS acquisition for patients in whom AIS is suspected. Our preliminary data indicate that resident video encounters average 10.6 min in duration, thus saving time once patients arrive at our hospital. Discussion:To our knowledge, this is the first report of a telestroke-integrated neurology residency program in a comprehensive stroke center resulting in shortened time to treatment in patients with suspected AIS. Conclusions:We present a model that can be adopted by other neurology residency programs as it provides real-world telemedicine training critical to future neurologists. [ABSTRACT FROM AUTHOR]

Importance: Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown.Objectives: To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke.Design, Setting, and Participants: The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria.Interventions: Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours.Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity.Results: Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 529 [46%] women, 920 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08], P = .55; unadjusted risk difference, -0.83% [95% CI, -5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]).Conclusions and Relevance: Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting.Trial Registration: ClinicalTrials.gov Identifier: NCT01369069. [ABSTRACT FROM AUTHOR]

The 2013-2016 epidemic of Ebola virus disease (EVD) that originated in West Africa underscored many of the challenges to conducting clinical research during an ongoing infectious disease epidemic, both in the most affected countries of Guinea, Liberia, and Sierra Leone, as well as in the United States and Europe, where a total of 27 patients with EVD received care in biocontainment units. The Special Pathogens Research Network (SPRN) was established in the United States in November 2016 to provide an organizational structure to leverage the expertise of the 10 Regional Ebola and Other Special Pathogen Treatment Centers (RESPTCs); it was intended to develop and support infrastructure to improve readiness to conduct clinical research in the United States. The network enables the rapid activation and coordination of clinical research in the event of an epidemic and facilitates opportunities for multicenter research when the RESPTCs are actively caring for patients requiring a biocontainment unit. Here we provide an overview of opportunities identified in the clinical research infrastructure during the West Africa EVD epidemic and the SPRN activities to meet the ongoing challenges in the context of Ebola virus and other special pathogens. The 2013-2016 epidemic of Ebola virus disease (EVD) that originated in West Africa underscored many of the challenges to conducting clinical research during an ongoing infectious disease epidemic. The authors provide an overview of opportunities identified in the clinical research infrastructure during the West Africa EVD epidemic and the Special Pathogens Research Network activities to meet the ongoing challenges in the context of Ebola virus and other special pathogens. [ABSTRACT FROM AUTHOR]

Rationale: Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim: Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design: CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg. Study outcomes: The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes. Sample size: Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion: Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone. Whether carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested. Trial registration: United States National Institutes of Health Clinicaltrials.gov NCT02089217 [ABSTRACT FROM AUTHOR]

Background Ischemic stroke is a time-sensitive disease, with improved outcomes associated with decreased time from onset to treatment. It was hypothesised that ambulance-based assessment of the National Institutes of Health Stroke Scale (NIHSS) using a Health Insurance Portability and Accountability Act (HIPAA)-compliant mobile platform immediately prior to arrival is feasible. Methods This is a proof-of-concept feasibility pilot study in two phases. The first phase consisted of an ambulance-equipped HIPAA-compliant video platform for remote NIHSS assessment of a simulated stroke patient. The second phase consisted of remote NIHSS assessment by a hospital-based neurologist of acute stroke patients en route to our facility. Five ambulances were equipped with a 4G/LTE-enabled tablet preloaded with a secure HIPAA-compliant telemedicine application. Secondary outcomes assessed satisfaction of staff with the remote platform. Results Phase one was successful in the assessment of three out of three simulated patients. Phase two was successful in the assessment of 10 out of 11 (91%) cases. One video attempt was unsuccessful because local LTE was turned off on the device. The video signal was dropped transiently due to weather, which delayed NIHSS assessment in one case. Average NIHSS assessment time was 7.6 minutes (range 3-9.8 minutes). Neurologists rated 83% of encounters as 'satisfied' to 'very satisfied', and the emergency medical service (EMS) rated 90% of encounters as 'satisfied' to 'very satisfied'. The one failed video attempt was associated with 'poor' EMS satisfaction. Conclusion This proof-of-concept pilot demonstrates that remote ambulance-based NIHSS assessment is feasible. This model could reduce door-to-needle times by conducting prehospital data collection. [ABSTRACT FROM AUTHOR]

Background: Unique challenges posed by emerging infectious diseases often expose inadequacies in the conventional phased investigational therapeutic development paradigm. The recent Ebola outbreak in West Africa presents a critical case-study highlighting barriers to faster development. During the outbreak, clinical trials were implemented with unprecedented speed. Yet, in most cases, this fast-tracked approach proved too slow for the rapidly evolving epidemic. Controversy abounded as to the most appropriate study designs to yield safety and efficacy data, potentially causing delays in pivotal studies. Preparation for research during future outbreaks may require acceptance of a paradigm that circumvents, accelerates, or reorders traditional phases, without losing sight of the traditional benchmarks by which drug candidates must be assessed for activity, safety and efficacy.Methods: We present the design of an adaptive, parent protocol, ongoing in West Africa until January 2016. The exigent circumstances of the outbreak and limited prior clinical experience with experimental treatments, led to more direct bridging from preclinical studies to human trials than the conventional paradigm would typically have sanctioned, and required considerable design flexibility.Results: Preliminary evaluation of the "barely Bayesian" design was provided through computer simulation studies. The understanding and public discussion of the study design will help its future implementation. [ABSTRACT FROM AUTHOR]

Background and objective Anti-pyretic treatment is recommended in the management of influenza infection. In animal models anti-pyretic treatment increases mortality from influenza. We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection. Methods This is a randomized, double-blind, placebo-controlled trial of adults aged 18-65 years with influenza-like illness and positive influenza rapid antigen test. Treatments were 1 g paracetamol four times a day, or matching placebo, for 5 days. Pernasal swabs were taken for influenza quantitative RT-PCR at Baseline and Days 1, 2 and 5. Temperature and symptom scores were recorded for 5-14 days or time of resolution respectively. The primary outcome variable was area under the curve ( AUC) for quantitative PCR log10 viral load from Baseline to Day 5. Results A total of 80 participants were randomized: no one was lost to follow up, and one withdrew after 4 days. There were 22 and 24 participants who were influenza PCR-positive in placebo and in paracetamol groups respectively. Mean ( SD) AUC PCR log10 viral load was 4.40 (0.91) in placebo and 4.64 (0.88) in paracetamol; difference was −0.24, 95% CI: −0.78 to 0.29, P = 0.36. In all participants there were no differences in symptom scores, temperature, time to resolution of illness and health status, with no interaction between randomized treatment and whether influenza was detected by PCR. Conclusion Regular paracetamol had no effect on viral shedding, temperature or clinical symptoms in patients with PCR-confirmed influenza. There remains an insufficient evidence base for paracetamol use in influenza infection. Clinical trial registration: ACTRN12611000497909 at the Australian New Zealand Clinical Trials Registry. [ABSTRACT FROM AUTHOR]

Background: Influenza virus (IFV) infection is associated with increased morbidity and mortality in people with underlying lung disease. Treatment options for IFV are currently limited and antiviral resistance is a growing concern. DAS181, an inhaled antiviral with a unique mechanism of action, has shown promise in early clinical trials involving generally healthy human subjects. This study was undertaken to assess the safety and tolerability of DAS181 in individuals with underlying reactive airway disease.Methods: This was a randomized, double-blind, placebo-controlled, crossover phase 1 study of DAS181-F02. Dry particle inhaler administration of 10 mg was done on 3 consecutive days in ten adult volunteers with well-controlled asthma. The primary outcome was the frequency of adverse events (AEs), grade 1 or higher that occurred during each study period.Results: There were 280 AEs among ten evaluable subjects (56.8 % active; 43.2 % placebo); 90.7 % were grade 1. No grade 3 or higher AEs occurred. A statistically significant association between exposure to DAS181 and experiencing any AE, a grade 1 AE, or a grade 2 AE was not detected. Overall, the majority of AEs were classified as possibly related (35.7 %), unlikely related (38.9 %), or unrelated (15.4 %) to study drug administration. However, there was a statistically significant association between exposure to DAS181 and experiencing a definitely or probably related AE. Respiratory effects, including dyspnea, dry cough, and chest discomfort related to respirations, accounted for all of the definitely related AEs and one of the most common probably related AEs.Conclusions: DAS181 was safe in this small study of otherwise healthy subjects with well-controlled asthma. However, the generalizability of these results is limited by the small sample size and generally mild nature of the subjects' asthma at baseline. The increased association of respiratory events classified as probably or definitely related to DAS181 administration suggests caution may need to be employed when administering DAS181 to individuals with less stable reactive airway disease. Further investigation in a controlled setting of the safety and efficacy of DAS181 in a larger population of asthmatic subjects with varying disease activity is warranted.Trial Registration: ClinicalTrials.gov NCT01113034 Trial Registration Date: April 27, 2010. [ABSTRACT FROM AUTHOR]

Evidence-based therapeutic options for stroke continue to emerge based on results from well-designed clinical studies. Ischemic stroke far exceeds hemorrhagic stroke in terms of prevalence and incidence, both in the USA and worldwide. The public health effect of reducing death and disability related to ischemic stroke justifies the resources that have been invested in identifying safe and effective treatments. The emergence of novel oral anticoagulants for ischemic stroke prevention in atrial fibrillation has introduced complexity to clinical decision making for patients with this common cardiac arrhythmia. Some accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment, given advances in risk factor management, antithrombotic therapy, and surgical techniques. Intra-arterial therapy, particularly with stent retrievers after intravenous tissue plasminogen activator, has recently been demonstrated to improve functional outcomes and will require investment in system-based care models to ensure that effective treatments are received by patients in a timely fashion. The purpose of this review is to describe recent advances in medical and surgical approaches to ischemic stroke prevention and acute treatment. Results from recently published clinical trials will be highlighted along with ongoing clinical trials addressing key questions in ischemic stroke management and prevention where equipoise remains. [ABSTRACT FROM AUTHOR]

Background: More than 26 000 cases of Ebola virus disease (EVD) have been reported in western Africa, with high mortality. Several patients have been medically evacuated to hospitals in the United States and Europe. Detailed clinical data are limited on the clinical course and management of patients with EVD outside western Africa. Objective: To describe the clinical characteristics and management of a cluster of patients with EVD, including the first cases of Ebola virus (EBOV) infection acquired in the United States. Design: Retrospective clinical case series. Setting: Three U.S. hospitals in September and October 2014. Patients: First imported EVD case identified in the United States and 2 secondary EVD cases acquired in the United States in critical care nurses who cared for the index case patient. Measurements: Clinical recovery, EBOV RNA level, resolution of Ebola viremia, survival with discharge from hospital, or death. Results: The index patient had high EBOV RNA levels, developed respiratory and renal failure requiring critical care support, and died. Both patients with secondary EBOV infection had nonspecific signs and symptoms and developed moderate illness; EBOV RNA levels were moderate, and both patients recovered. Limitation: Both surviving patients received uncontrolled treatment with multiple investigational agents, including convalescent plasma, which limits generalizability of the results. Conclusion: Early diagnosis, prompt initiation of supportive medical care, and moderate clinical illness likely contributed to successful outcomes in both survivors. The inability to determine the potential benefit of investigational therapies and the effect of patient-specific factors that may have contributed to less severe illness highlight the need for controlled clinical studies of these interventions, especially in the setting of a high level of supportive medical care. [ABSTRACT FROM AUTHOR]

Migraine is a common disabling neurological disorder resulting from excessive cortical excitation and trigeminovascular afferent sensitization. In addition to aberrant neuronal processing, migraineurs are also at significant risk of vascular disease. Consequently, the impact of migraine extends well beyond the ictal headache and includes a well-documented association with acute ischemic stroke, particularly in young women with a history of migraine with aura. The association between migraine and stroke has been acknowledged for 40 years or more. However, examining the pathobiology of this association has become a more recent and critically important undertaking. The diversity of mechanisms underlying the association between migraine and stroke likely reflects the heterogenous nature of this disorder. Vasospasm, endothelial injury, platelet aggregation and prothrombotic states, cortical spreading depression, carotid dissection, genetic variants, and traditional vascular risk factors have been offered as putative mechanisms involved in migraine-related stroke risk. Assimilating these seemingly divergent pathomechanisms into a cogent understanding of migraine-related stroke will inform future studies and the development of new strategies for the prevention and treatment of migraine and stroke. [ABSTRACT FROM AUTHOR]