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Background: Atrial fibrillation (AF) is a risk for stroke. The Canadian Cardiovascular Society advises patients who are CHADS65 positive should be started on oral anticoagulation (OAC). Our local emergency department (ED) review showed that only 16% of CHADS65 positive patients were started on OAC and that 2% of our patients were diagnosed with stroke within 90 days. We implemented a new pathway for initiation of OAC in the ED (the SAFE pathway). Aim Statement: We report the effectiveness and safety of the SAFE pathway for initiation of OAC in patients treated for AF in the ED. Measures & Design: A multidisciplinary group of physicians and pharmacist developed the SAFE pathway for patients who are discharged home from the ED with a diagnosis of AF. Step 1: contraindications to OAC, Step 2: CHADS65 score, Step 3: OAC dosing if indicated. The pathway triggers referral to AF clinic, family physician letter and follow up call from the ED pharmacist. Patients are followed for 90 days by a structured medical record review and a structured telephone interview. We record persistence with OAC, stroke, TIA, systemic arterial embolism and major bleeding (ISTH criteria). Patient outcomes are fed back to the treating ED physician. Evaluation/ Results: The SAFE pathway was introduced in two EDs in June 2018. In total, 177 patients have had the pathway applied. The median age was 70 (interquartile range (IQR) 61-78), 48% male, median CHADS2 score 2 (IQR 0-2). 19/177 patients (11%) had a contraindication to initiating OAC. 122 patients (69%) had no contraindication to OAC and were CHADS65 positive. Of these 122 patients, 109 were given a prescription for OAC (96 the correct dose, 9 too high a dose and 4 too low a dose). 6 patients declined OAC and the physician did not want to start OAC for 7 patients. 73/122 were contacted by phone at 90 days, 15 could not be reached and 34 have not completed 90 days of follow up since their ED visit. Of the 73 who were reached by phone after 90 days, 65 were still taking an anticoagulant. To date, 1 patient who declined OAC (CHADS2 score of 2) had a stroke within 90 days and one patient prescribed OAC had a gastrointestinal bleed. Discussion/Impact: The SAFE pathway appears safe and effective although we continue to evaluate and improve the process.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Both blood- and milk-based biomarkers have been analysed for decades in research settings, although often only in one herd, and without focus on the variation in the biomarkers that are specifically related to herd or diet. Biomarkers can be used to detect physiological imbalance and disease risk and may have a role in precision livestock farming (PLF). For use in PLF, it is important to quantify normal variation in specific biomarkers and the source of this variation. The objective of this study was to estimate the between- and within-herd variation in a number of blood metabolites (β-hydroxybutyrate (BHB), non-esterified fatty acids, glucose and serum IGF-1), milk metabolites (free glucose, glucose-6-phosphate, urea, isocitrate, BHB and uric acid), milk enzymes (lactate dehydrogenase and N-acetyl-β-D-glucosaminidase (NAGase)) and composite indicators for metabolic imbalances (Physiological Imbalance-index and energy balance), to help facilitate their adoption within PLF. Blood and milk were sampled from 234 Holstein dairy cows from 6 experimental herds, each in a different European country, and offered a total of 10 different diets. Blood was sampled on 2 occasions at approximately 14 days-in-milk (DIM) and 35 DIM. Milk samples were collected twice weekly (in total 2750 samples) from DIM 1 to 50. Multilevel random regression models were used to estimate the variance components and to calculate the intraclass correlations (ICCs). The ICCs for the milk metabolites, when adjusted for parity and DIM at sampling, demonstrated that between 12% (glucose-6-phosphate) and 46% (urea) of the variation in the metabolites’ levels could be associated with the herd-diet combination. Intraclass Correlations related to the herd-diet combination were generally higher for blood metabolites, from 17% (cholesterol) to approximately 46% (BHB and urea). The high ICCs for urea suggest that this biomarker can be used for monitoring on herd level. The low variance within cow for NAGase indicates that few samples would be needed to describe the status and potentially a general reference value could be used. The low ICC for most of the biomarkers and larger within cow variation emphasises that multiple samples would be needed - most likely on the individual cows - for making the biomarkers useful for monitoring. The majority of biomarkers were influenced by parity and DIM which indicate that these should be accounted for if the biomarker should be used for monitoring.
Epilepsy is a common neurological condition that shows a marked genetic predisposition. The advent of next-generation sequencing (NGS) has transformed clinical genetic testing by allowing the rapid screen for causative variants in multiple genes. There are currently no NGS-based multigene panel diagnostic tests available for epilepsy as a licensed clinical diagnostic test in Ontario, Canada. Eligible patient samples are sent out of country for testing by commercial laboratories, which incurs significant cost to the public healthcare system.
An expert Working Group of medical geneticists, pediatric neurologists/epileptologists, biochemical geneticists, and clinical molecular geneticists from Ontario was formed by the Laboratories and Genetics Branch of the Ontario Ministry of Health and Long-Term Care to develop a programmatic approach to implementing epilepsy panel testing as a provincial service.
The Working Group made several recommendations for testing to support the clinical delivery of care in Ontario. First, an extension of community healthcare outcomes-based program should be incorporated to inform and educate ordering providers when requesting and interpreting a genetic panel test. Second, any gene panel testing must be “evidence-based” and takes into account varied clinical indications to reduce the chance of uncertain and secondary results. Finally, an ongoing evaluative process was recommended to ensure continued test improvement for the future.
This epilepsy panel testing implementation plan will be a model for genetic care directed toward a specific set of conditions in the province and serve as a prototype for genetic testing for other genetically heterogeneous diseases.
Little is known about prescribers’ attitudes regarding clinical nurses and antimicrobial stewardship. We conducted focus groups of prescribers and inquired about attitudes regarding nurses and stewardship. During 6 focus groups, prescribers were receptive to nursing involvement in stewardship activities, but noted structural barriers and knowledge gaps that should be addressed.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Multiple genes/variants have been implicated in various epileptic conditions. However, there is little general guidance available on the circumstances in which genetic testing is indicated and test selection in order to guide optimal test appropriateness and benefit. This is an account of the development of guidelines for genetic testing in epilepsy, which have been developed in Ontario, Canada. The Genetic Testing Advisory Committee was established in Ontario to review the clinical utility and validity of genetic tests and the provision of genetic testing in Ontario. As part of their mandate, the committee also developed recommendations and guidelines for genetic testing in epilepsy. The recommendations include mandatory prerequisites for an epileptology/geneticist/clinical biochemical geneticist consultation, prerequisite diagnostic procedures, circumstances in which genetic testing is indicated and not indicated and guidance for selection of genetic tests, including their general limitations and considerations. These guidelines represent a step toward the development of evidence-based gene panels for epilepsy in Ontario, the repatriation of genetic testing for epilepsy into Ontario molecular genetic laboratories and public funding of genetic tests for epilepsy in Ontario.
Increasing the representation of women in science, technology, engineering, and mathematics (STEM) is one of our nation's most pressing imperatives. As such, there has been increased lay and scholarly attention given to understanding the causes of women's underrepresentation in such fields. These explanations tend to fall into two main groupings: individual-level (i.e., her) explanations and social-structural (i.e., our) explanations. These two perspectives offer different lenses for illuminating the causes of gender inequity in STEM and point to different mechanisms by which to gain gender parity in STEM fields. In this article, we describe these two lenses and provide three examples of how each lens may differentially explain gender inequity in STEM. We argue that the social-structural lens provides a clearer picture of the causes of gender inequity in STEM, including how gaining gender equity in STEM may best be achieved. We then make a call to industrial/organizational psychologists to take a lead in addressing the societal-level causes of gender inequality in STEM.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
Transient storage and erosion of valley fills, or sediment buffering, is a fundamental but poorly quantified process that may significantly bias fluvial sediment budgets and marine archives used for paleoclimatic and tectonic reconstructions. Prolific sediment buffering is now recognized to occur within the mountainous upper Indus River headwaters and is quantified here for the first time using optically stimulated luminescence dating, petrography, detrital zircon U-Pb geochronology, and morphometric analysis to define the timing, provenance, and volumes of prominent valley fills. This study finds that climatically modulated sediment buffering occurs over 103–104 yr time scales and results in biases in sediment compositions and volumes. Increased sediment storage coincides with strong phases of summer monsoon and winter westerlies precipitation over the late Pleistocene (32–25 ka) and mid-Holocene (~8–6 ka), followed by incision and erosion with monsoon weakening. Glacial erosion and periglacial frost-cracking drive sediment production, and monsoonal precipitation mediates sediment evacuation, in contrast to the arid Transhimalaya and monsoonal frontal Himalaya. Plateau interior basins, although volumetrically large, lack transport capacity and are consequently isolated from the modern Indus River drainage. Marginal plateau catchments that both efficiently produce and evacuate sediment may regulate the overall compositions and volumes of exported sediment from the Himalayan rain shadow.
The provision of healthcare education in developing countries is a complex problem that simulation has the potential to help. This study aimed to evaluate the effectiveness of a low-cost ear surgery simulator, the Ear Trainer.
The Ear Trainer was assessed in two low-resource environments in Cambodia and Uganda. Participants were video-recorded performing four specific middle-ear procedures, and blindly scored using a validated measurement tool. Face validity, construct validity and objective learning were assessed.
The Ear Trainer provides a realistic representation of the ear. Construct validity assessment confirmed that experts performed better than novices. Participants displayed improvement in all tasks except foreign body removal, likely because of a ceiling effect.
This study validates the Ear Trainer as a useful training tool for otological microsurgical skills in developing world settings.
To achieve their conservation goals individuals, communities and organizations need to acquire a diversity of skills, knowledge and information (i.e. capacity). Despite current efforts to build and maintain appropriate levels of conservation capacity, it has been recognized that there will need to be a significant scaling-up of these activities in sub-Saharan Africa. This is because of the rapid increase in the number and extent of environmental problems in the region. We present a range of socio-economic contexts relevant to four key areas of African conservation capacity building: protected area management, community engagement, effective leadership, and professional e-learning. Under these core themes, 39 specific recommendations are presented. These were derived from multi-stakeholder workshop discussions at an international conference held in Nairobi, Kenya, in 2015. At the meeting 185 delegates (practitioners, scientists, community groups and government agencies) represented 105 organizations from 24 African nations and eight non-African nations. The 39 recommendations constituted six broad types of suggested action: (1) the development of new methods, (2) the provision of capacity building resources (e.g. information or data), (3) the communication of ideas or examples of successful initiatives, (4) the implementation of new research or gap analyses, (5) the establishment of new structures within and between organizations, and (6) the development of new partnerships. A number of cross-cutting issues also emerged from the discussions: the need for a greater sense of urgency in developing capacity building activities; the need to develop novel capacity building methodologies; and the need to move away from one-size-fits-all approaches.
There is increasing interest in the use of additive manufacturing (AM) for Ni-based superalloys due to their various applications in the aerospace and power-generation sectors. Ni-based superalloys are known to have a complex chemistry, with over a dozen alloying elements in most alloys, enabling them to achieve outstanding high-temperature mechanical performance as well as oxidation resistance when processed using conventional routes (e.g., casting and forging). Nonetheless, this complex chemistry results in the formation of various phases that could affect their processability using AM, resulting in cracking. Furthermore, due to the directional solidification and rapid cooling associated with AM processes, the alloys experience significant anisotropy due to the epitaxially grown microstructure, as well as the residual stresses that can sometimes be difficult to mitigate using thermal postprocessing techniques. This article highlights the outstanding issues in Ni-based superalloys AM processing, with special emphasis on defect formation mechanisms, process optimization, and residual stress development.
Impulse control disorders (ICDs) have become a widely recognized non-motor complication of Parkinson's disease (PD) in patients taking dopamine replacement therapy (DRT). There are no current evidence-based recommendations for their treatment, other than reducing their dopaminergic medication.
This study reviews the current literature of the treatment of ICDs including pharmacological treatments, deep brain stimulation, and psychotherapeutic interventions.
Dopamine agonist withdrawal is the most common and effective treatment, but may lead to an aversive withdrawal syndrome or motor symptom degeneration in some individuals. There is insufficient evidence for all other pharmacological treatments in treating ICDs in PD, including amantadine, serotonin selective reuptake inhibitors, antipsychotics, anticonvulsants, and opioid antagonists (e.g. naltrexone). Large randomized control trials need to be performed before these drugs can be routinely used for the treatment of ICDs in PD. Deep brain stimulation remains equivocal because ICD symptoms resolve in some patients after surgery but may appear de novo in others. Cognitive behavioral therapy has been shown to improve ICD symptoms in the only published study, although further research is urgently needed.
Further research will allow for the development of evidence-based guidelines for the management of ICDs in PD.
Dogs participating in endurance exercise, including herding, hunting and racing have a greater energy requirement and may be more susceptible to nutrient depletion, electrolyte imbalance and metabolic stress. The objective of the present study was to investigate the acute response to unstructured mixed exercise in American Foxhounds fed a nutrient-fortified endurance diet. Thirty-nine adult Foxhound dogs (median age: 5·0, range: 2–10 years and median body weight (BW): 36·4, range: 24·9–49·5 kg) were allotted to a standard performance diet (Control) or nutrient-fortified endurance diet for adult dogs (Test). Dogs were balanced by sex, age, BW and athletic performance between diets. All male dogs were intact, whereas all the female dogs were spayed. After 80 d on diet, blood samples were collected via jugular puncture at baseline (0 h), and at 3 and 25 h post-exercise (mean: 17·7 (sem 0·92) km run over 2–3 h). Plasma taurine concentration and complete amino acid (AA) profile, serum chemistry and creatine kinase were measured. Serum chemistry profile remained within normal ranges throughout the study. A significant (P < 0·05) diet by time interaction was observed for calcium, alkaline phosphatase and most AA. Plasma taurine and most essential AA were increased (P < 0·05) after exercise and remained greater (P < 0·05) in dogs fed the Test diet, including the branched-chain AA (isoleucine, leucine and valine). Creatine kinase increased (P = 0·01) after 3 h and returned to baseline after 25 h post-exercise, but was not altered by diet. These data indicate that dogs undergoing a moderate bout of exercise did not suffer from electrolyte imbalance, and that a nutrient-fortified diet resulted in greater plasma taurine and essential AA concentrations.