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1.
mBio ; : e0162324, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39140743

ABSTRACT

As the closest living relatives of animals, choanoflagellates offer insights into the ancestry of animal cell physiology. Here, we report the isolation and characterization of a colonial choanoflagellate from Mono Lake, California. The choanoflagellate forms large spherical colonies that are an order of magnitude larger than those formed by the closely related choanoflagellate Salpingoeca rosetta. In cultures maintained in the laboratory, the lumen of the spherical colony is filled with a branched network of extracellular matrix and colonized by bacteria, including diverse Gammaproteobacteria and Alphaproteobacteria. We propose to erect Barroeca monosierra gen. nov., sp. nov. Hake, Burkhardt, Richter, and King to accommodate this extremophile choanoflagellate. The physical association between bacteria and B. monosierra in culture presents a new experimental model for investigating interactions among bacteria and eukaryotes. Future work will investigate the nature of these interactions in wild populations and the mechanisms underpinning the colonization of B. monosierra spheres by bacteria. IMPORTANCE: The diversity of organisms that live in the extreme environment of Mono Lake (California, USA) is limited. We sought to investigate whether the closest living relatives of animals, the choanoflagellates, exist in Mono Lake, a hypersaline, alkaline, arsenic-rich environment. We repeatedly isolated members of a new species of choanoflagellate, which we have named Barroeca monosierra. Characterization of B. monosierra revealed that it forms large spherical colonies containing diverse co-isolated bacteria, providing an opportunity to investigate mechanisms underlying physical associations between eukaryotes and bacteria.

2.
J Patient Saf ; 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39194332

ABSTRACT

BACKGROUND: Emergency and urgent care settings face challenges with routinely obtaining performance feedback related to diagnostic care. Patients and their care partners provide an important perspective on the diagnostic process and outcome of care in these settings. We sought to develop and test psychometric properties of Patient-Report to IMprove Diagnostic Excellence in Emergency Department settings (PRIME-ED), a measure of patient-reported diagnostic excellence in these care settings. METHODS: We developed PRIME-ED based on literature review, expert feedback, and cognitive testing. To assess psychometric properties, we surveyed AmeriSpeak, a probability-based panel that provides sample coverage of approximately 97% of the U.S. household population, in February 2022 to adult patients, or their care partners, who had presented to an emergency department or urgent care facility within the last 30 days. Respondents rated their agreement on a 5-point Likert scale with each of 17 statements across multiple domains of patient-reported diagnostic excellence. Demographics, visit characteristics, and a subset of the Emergency Department Consumer Assessment of Healthcare Providers & Systems were also collected. We conducted psychometric testing for reliability and validity. RESULTS: Over a thousand (n = 1116) national panelists completed the PRIME-ED survey, of which 58.7% were patients and 40.9% were care partners; 49.6% received care at an emergency department and 49.9% at an urgent care facility. Responses had high internal consistency within 3 patient-reported diagnostic excellence domain groupings: diagnostic process (Cronbach's alpha 0.94), accuracy of diagnosis (0.93), and communication of diagnosis (0.94). Domain groupings were significantly correlated with concurrent Emergency Department Consumer Assessment of Healthcare Providers & Systems items. Factor analyses substantiated 3 domain groupings. CONCLUSIONS: PRIME-ED has potential as a tool for capturing patient-reported diagnostic excellence in emergency and urgent care.

5.
Vet J ; 300-302: 106040, 2023.
Article in English | MEDLINE | ID: mdl-37898456

ABSTRACT

Arrhythmias are commonly reported in exercising horses, however due to regulatory constraints electrocardiograms (ECGs) are acquired during training but not competition, raising questions about the repeatability of findings. The aims were (1) compare training and competition arrhythmias and (2) describe the repeatability of arrhythmias during maximal-intensity exercise. A convenience sample of 52 healthy Thoroughbreds (aged 8.7 ± 2.5 years) competing in the World Professional Chuckwagon Association were obtained, totaling 152 training or competition ECGs (2-7 ECGs/horse). Speed, heart rate (HR) and arrhythmias (supraventricular premature complex, SVPC; ventricular premature complex, VPC) were examined. Pre- and post-recovery (approximately 6 min) blood samples measured lactate and high-sensitivity troponin-T. Training and competition arrythmias were compared (Friedman's test) and reliability of repeated ECGs assessed (intraclass correlation; P < 0.05). Training vs. competition: Forty horses had clean tracing from training and competition (n = 80 ECGs); the number and type of arrhythmias were not different. In training, VPCs were present in 7/40 horses (median [interquartile range, IQR]/ECG; range; 0 [0,0]; 0-4) and 9/40 horses (0 [0,0]; 0-5) in active-recovery. In competition, VPCs were present in 7/40 horses (0 [0,0]; 0-8) and 8/40 horses (0 [0,0]; 0-5) in active-recovery. Arrhythmias were primarily single premature complexes. Training and competition speed, HR, lactate and troponin-T did not differ however, sampling was too early for peak serum Troponin-T levels. Repeatability: total arrhythmias between serial ECGs did not differ. The reliability to detect SVPCs and VPCs was poor to moderate, and poor, respectively. Overall, the total number of arrhythmias was repeatable, but the reliability of arrhythmia type was poor to moderate.


Subject(s)
Horse Diseases , Physical Conditioning, Animal , Ventricular Premature Complexes , Horses , Animals , Troponin T , Reproducibility of Results , Horse Diseases/diagnosis , Ventricular Premature Complexes/diagnosis , Ventricular Premature Complexes/veterinary , Physical Conditioning, Animal/physiology , Lactates
6.
Brain Behav Immun ; 108: 279-291, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36549577

ABSTRACT

Age-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections are emerging as potential drivers of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task, and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression, as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with subtle but significantly impaired cognition among normally aging mice. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia.


Subject(s)
Lipopolysaccharides , Long-Term Potentiation , Mice , Animals , Male , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Quality of Life , Mice, Inbred C57BL , Cognition/physiology , Aging/metabolism , Inflammation/complications , Hippocampus/metabolism , Maze Learning
8.
Clin Toxicol (Phila) ; 60(8): 979-984, 2022 08.
Article in English | MEDLINE | ID: mdl-35546568

ABSTRACT

BACKGROUND: Toronto's Drug Checking Service (DCS) provides people who use drugs with information on the chemical composition of their substances and conducts real-time monitoring of the unregulated drug supply. Presented are first known data of three newly detected synthetic cannabinoids (SCs) in Toronto, Ontario. METHODS: The present data are from samples analyzed between April and November 2020. Samples were collected at partnering harm reduction agencies in Toronto and analyzed using gas or liquid chromatography-mass spectrometry. An intake survey queried about the sample characteristics on submission, including expected drug(s). RESULTS: Samples were analyzed between 1 April and 20 November 2020 (N = 19), which marks the period immediately following imposed COVID-19 border and movement restrictions in Canada. The newly detected, unexpected SCs were ACHMINACA (n = 15), AB-FUBINACA (n = 3), and 4-fluoro-MDMB-BUTINACA (n = 1). Fentanyl was expected in 74% (n = 14). Most SCs were detected in samples containing fentanyl or related analogues (n = 18; 95%), or benzodiazepine-related drugs (i.e., etizolam and flualprazolam) (n = 15; 79%). CONCLUSIONS: This information can inform overdose prevention efforts and drug market monitoring of SCs in Toronto and regions served by the same drug trafficking routes. The detection of SCs during a period marked by COVID-19-related restrictions can contribute to efforts to identify global drug market trends during this time.


Subject(s)
COVID-19 , Cannabinoids , Drug Overdose , Illicit Drugs , Benzodiazepines , COVID-19/epidemiology , Cannabinoids/chemistry , Drug Overdose/prevention & control , Fentanyl , Humans , Illicit Drugs/analysis , Ontario/epidemiology
9.
Anim Reprod Sci ; 246: 106838, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34507847

ABSTRACT

Artificial insemination using semen from genetically superior sires remains one of the most effective biotechnologies ever commercialized for animal breeding purposes. Genetic progress, however, cannot begin until conception occurs. Processing laboratories that provide cryopreserved bull semen for commercial use depend on in vitro assays of semen quality to identify samples that are expected to result in less than desirable conception rates. These identified samples are discarded, rather than released to salable inventories, with the desired effect of minimizing variance in field fertility among both sires and individual collections. Although the industry was successfully founded on subjective assessment of motility and acrosome integrity, flow cytometric and computer-assisted sperm analysis offer more objective and repeatable measures of sperm quality attributes. Albeit more expensive to implement, the increased precision and repeatability when using these objective assays lends to greater confidence in the accuracy of decisions for individual collections and (or) bulls. The efficacy of a quality control program is evidenced by the range in sire fertility estimates calculated from field fertility data, which have historically indicated >90% of all sires achieve fertility deviation within ±3% points of the breed average. This impressive precedent implies somewhat limited opportunity for transition to objective assessments to have a meaningful impact on an already narrow range of fertility distributions. Nonetheless, flow cytometric assessments of novel attributes of sperm quality hold promise for detection of truly sub-fertile sires (deviations < -3) that presently elude detection with use of existing semen bioassays.


Subject(s)
Semen Analysis , Sperm Motility , Cattle , Male , Animals , Semen Analysis/veterinary , Semen , Flow Cytometry/veterinary , Spermatozoa , Insemination, Artificial/veterinary
10.
J Intellect Disabil Res ; 65(10): 941-948, 2021 10.
Article in English | MEDLINE | ID: mdl-34369629

ABSTRACT

BACKGROUND: Historically, people with intellectual disability have been exploited in and excluded from scientific research. To facilitate greater representation of adults with intellectual disability as research respondents, we sought to understand their interest in research participation and factors affecting their willingness to volunteer to participate, such as the core value of trust. METHODS: Our survey measured attitudes of adults with intellectual disability towards research in general and research specifically involving adults with intellectual disability as respondents, as well as their prior research experiences, trust of researchers and interest in future research participation. RESULTS: Participants reported positive attitudes towards research and strong interest in future participation opportunities, and trust of researchers was positively correlated to both. The belief that 'research about adults with intellectual disability is very important' also predicted participants' interest in future research participation. CONCLUSIONS: Our findings indicate that adults with intellectual disability support the direct involvement of adults with intellectual disability in research as respondents. Trustworthy rapport with researchers and positive views about research foster greater inclusion of this population.


Subject(s)
Intellectual Disability , Adult , Attitude , Humans , Surveys and Questionnaires
11.
Cell Mol Life Sci ; 78(10): 4735-4763, 2021 May.
Article in English | MEDLINE | ID: mdl-33792748

ABSTRACT

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease. The thirteen forms of NCL are caused by mutations in thirteen CLN genes. Mutations in one CLN gene, CLN5, cause variant late-infantile NCL, with an age of onset between 4 and 7 years. The CLN5 protein is ubiquitously expressed in the majority of tissues studied and in the brain, CLN5 shows both neuronal and glial cell expression. Mutations in CLN5 are associated with the accumulation of autofluorescent storage material in lysosomes, the recycling units of the cell, in the brain and peripheral tissues. CLN5 resides in the lysosome and its function is still elusive. Initial studies suggested CLN5 was a transmembrane protein, which was later revealed to be processed into a soluble form. Multiple glycosylation sites have been reported, which may dictate its localisation and function. CLN5 interacts with several CLN proteins, and other lysosomal proteins, making it an important candidate to understand lysosomal biology. The existing knowledge on CLN5 biology stems from studies using several model organisms, including mice, sheep, cattle, dogs, social amoeba and cell cultures. Each model organism has its advantages and limitations, making it crucial to adopt a combinatorial approach, using both human cells and model organisms, to understand CLN5 pathologies and design drug therapies. In this comprehensive review, we have summarised and critiqued existing literature on CLN5 and have discussed the missing pieces of the puzzle that need to be addressed to develop an efficient therapy for CLN5 Batten disease.


Subject(s)
Lysosomal Membrane Proteins/genetics , Lysosomes/metabolism , Mutation , Neuronal Ceroid-Lipofuscinoses/pathology , Animals , Humans , Lysosomal Membrane Proteins/metabolism , Neuronal Ceroid-Lipofuscinoses/etiology , Neuronal Ceroid-Lipofuscinoses/metabolism
12.
Vet J ; 267: 105583, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33375959

ABSTRACT

The prevalence and severity of cardiac arrhythmias in healthy racehorses undergoing competition is not well defined. The aim was to characterize arrhythmias in Thoroughbreds participating in official Chuckwagon races and to determine normal beat-to-beat (R-R) variability during supramaximal exercise. Electrocardiograph (ECG) recordings were obtained during pre-race, race, and active-recovery from 82 clinically healthy Thoroughbreds. ECG recordings were analyzed for arrhythmias and mean percent R-R deviation. Plasma lactate and high-sensitivity troponin (hs-cTnT) were also measured. Fifty-two ECGs were included in the analysis. Arrhythmias were seen in 48/52 horses (92%) and were predominantly isolated events. No complex rhythms were observed. During the race, 92% of horses had arrhythmias (81% supraventricular premature complex [SVPC]; 33% ventricular premature complex [VPC]). Eleven percent of racing arrhythmias were VPCs (all singlets except for two couplets). During active-recovery, 58% of horses had arrhythmias (56% SVPC; 15% VPCs): Three horses had VPC couplets and one horse had a VPC triplet. All plasma hs-cTnT were within normal limits. The measured lactate was 28.5 ± 4.5 mmol/L, confirming supramaximal exercise. R-R variation ranged between -9.5 to +18.8% during pre-race (mean heart rate [HR], 155 ± 22 beats per min [bpm]), -27.8 to +45.3% during racing (mean HR, 200 ± 9 bpm) and -16.4 to +40.1% during active-recovery (mean HR, 165 ± 14 bpm). Maximal and 1st percentile R-R shortening and lengthening were significantly greater at race than pre-race and active-recovery (P < 0.0001). Racing and active-recovery maximal R-R lengthening were significantly greater than pre-race (P = 0.0003). Supraventricular premature complexes and VPCs are prevalent in healthy horses undergoing Chuckwagon racing. R-R variation is greater during racing than has previously been described.


Subject(s)
Arrhythmias, Cardiac/veterinary , Electrocardiography/veterinary , Horse Diseases/epidemiology , Horse Diseases/physiopathology , Animals , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/physiopathology , Atrial Premature Complexes/epidemiology , Atrial Premature Complexes/veterinary , Electrocardiography/methods , Heart Rate/physiology , Horses , Lactic Acid/blood , Male , Physical Exertion/physiology , Running/physiology , Troponin T/blood , Ventricular Premature Complexes/epidemiology , Ventricular Premature Complexes/veterinary
13.
Harm Reduct J ; 17(1): 9, 2020 01 28.
Article in English | MEDLINE | ID: mdl-32204713

ABSTRACT

BACKGROUND: The increasing incidence of fatal opioid overdose is a public health crisis in Canada. Given growing consensus that this crisis is related to the presence of highly potent opioid adulterants (e.g., fentanyl) in the unregulated drug supply, drug checking services (DCS) have emerged as part of a comprehensive approach to overdose prevention. In Canada's largest city, Toronto, a network of DCS launched in 2019 to prevent overdose and overdose-related risk behaviors. This network employs mass spectrometry technologies, with intake sites co-located with supervised consumption services (SCS) at three frontline harm reduction agencies. The protocol and rationale for assessing the impact of this multi-site DCS network in Toronto is described herein. The aims of this study are to (1) evaluate the impact of DCS access on changes in and factors influencing overdose and related risk behaviors, (2) investigate the perceived capacity of DCS to prevent overdose, and (3) identify composition (qualitative and quantitative) trends in Toronto's unregulated drug supply. METHODS: We will use a parallel-mixed-methods design with complementary data sources (including data from chemical analysis of drug samples, quantitative intake and post-test surveys, SCS, coroners, paramedic services, and qualitative interviews), followed by a meta-inference process wherein results from analyses are synthesized. RESULTS: Whereas most DCS globally target "recreational drug users," in Toronto, this networked DCS will primarily target marginalized people who use drugs accessing frontline services, many of whom use drugs regularly and by injection. This evolution in the application of DCS poses important questions that have not yet been explored, including optimal service delivery models and technologies, as well as unique barriers for this population. Increasing information on the unregulated drug supply may modify the risk environment for this population of people who use drugs. CONCLUSIONS: This study addresses evidence gaps on the emerging continuum of overdose prevention responses and will generate critical evidence on a novel approach to reducing the ongoing high incidence of drug-related morbidity and mortality in Canada and elsewhere.


Subject(s)
Drug Contamination/prevention & control , Drug Overdose/prevention & control , Fentanyl/poisoning , Harm Reduction , Program Evaluation/methods , Research Design , Humans , Ontario
14.
Parkinsons Dis ; 2019: 5258493, 2019.
Article in English | MEDLINE | ID: mdl-31428303

ABSTRACT

OBJECTIVES: We piloted a computerised cognitive training battery in a group of participants with Parkinson's disease without dementia to investigate the relevance of the training to daily life and the feasibility and the acceptability of the tasks. Previous studies of CT have had limited success in the benefits of training, extending to improvements in everyday function. By taking a pragmatic approach and targeting training to the cognitive skills affected by Parkinson's disease (planning, attention, and recollection), whilst using tasks that emulated real-life scenarios, we sought to understand whether participants perceived the training to be effective and to identify the elements of the training that elicited beneficial effects. METHODS: Four participants completed a cognitive training session comprising three distinct tasks 5 days a week over two weeks. Participants completed baseline questionnaires examining health-related quality of life, everyday cognition, and apathy before the training period, after the last session, and two weeks after the last session. An interview was held after participants had completed the training. RESULTS: The findings indicated that participants felt the training was acceptable, enhanced their awareness, and encouraged them to monitor their thinking abilities. The group interview indicated that the training was feasible; participants felt the tasks had potential to improve everyday performance, but more supporting information should be provided to facilitate this transfer. Responses to the questionnaires reflected these findings, indicating improvement for some participants' cognition and quality of life. Objective measures supported the subjective reports; there were improvements in some but not all domains. Performance on the planning and recollection tasks improved over the training period, and the evidence for improvement on the attention task was mixed. CONCLUSION: This study has found that pragmatic computer-based training with real-life outcomes is both feasible and acceptable and should be evaluated more extensively using controlled methods.

15.
BMC Infect Dis ; 19(1): 445, 2019 May 21.
Article in English | MEDLINE | ID: mdl-31113382

ABSTRACT

BACKGROUND: Candidaemia is associated with high mortality. Variables associated with mortality have been published previously, but not developed into a risk predictive model for mortality. We sought to describe the current epidemiology of candidaemia in Australia, analyse predictors of 30-day all-cause mortality, and develop and validate a mortality risk predictive model. METHODS: Adults with candidaemia were studied prospectively over 12 months at eight institutions. Clinical and laboratory variables at time of blood culture-positivity were subject to multivariate analysis for association with 30-day all-cause mortality. A predictive score for mortality was examined by area under receiver operator characteristic curves and a historical data set was used for validation. RESULTS: The median age of 133 patients with candidaemia was 62 years; 76 (57%) were male and 57 (43%) were female. Co-morbidities included underlying haematologic malignancy (n = 20; 15%), and solid organ malignancy in (n = 25; 19%); 55 (41%) were in an intensive care unit (ICU). Non-albicans Candida spp. accounted for 61% of cases (81/133). All-cause 30-day mortality was 31%. A gastrointestinal or unknown source was associated with higher overall mortality than an intravascular or urologic source (p < 0.01). A risk predictive score based on age > 65 years, ICU admission, chronic organ dysfunction, preceding surgery within 30 days, haematological malignancy, source of candidaemia and antibiotic therapy for ≥10 days stratified patients into < 20% or ≥ 20% predicted mortality. The model retained accuracy when validated against a historical dataset (n = 741). CONCLUSIONS: Mortality in patients with candidaemia remains high. A simple mortality risk predictive score stratifying patients with candidaemia into < 20% and ≥ 20% 30-day mortality is presented. This model uses information available at time of candidaemia diagnosis is easy to incorporate into decision support systems. Further validation of this model is warranted.


Subject(s)
Candidemia/mortality , Aged , Antifungal Agents/therapeutic use , Australia/epidemiology , Candida/classification , Candida/genetics , Candida/isolation & purification , Candidemia/drug therapy , Candidemia/epidemiology , Candidemia/microbiology , Female , Hematologic Neoplasms/complications , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prospective Studies , ROC Curve , Risk Factors
16.
Ir Med J ; 111(4): 741, 2018 04 19.
Article in English | MEDLINE | ID: mdl-30488685

ABSTRACT

Several selection methods have been used to aid selection into orthopaedic training programs but no process exists to aid in sub-speciality selection. A process which is continuous, unbiased and encompasses technical skill and decision making would be the gold standard. This paper analyses the use of a daily clinical task that assesses many of the desirable traits of a prospective trainee. A retrospective review of 13,474 orthopaedic procedures was under taken. The results showed a clear distinction between orthopaedic sub-specialities in time taken to perform this task. The authors suggest that this could provide a low cost insight into the appropriate subspecialty for orthopaedic trainees.


Subject(s)
Education, Medical , Hand Disinfection , Medicine , Orthopedic Procedures/education , Orthopedics/education , Personnel Selection/methods , Task Performance and Analysis , Clinical Competence , Decision Making , Humans , Retrospective Studies , Time Factors
18.
Sci Rep ; 8(1): 9130, 2018 06 14.
Article in English | MEDLINE | ID: mdl-29904060

ABSTRACT

Archaeological evidence suggests that dogs were introduced to the islands of Oceania via Island Southeast Asia around 3,300 years ago, and reached the eastern islands of Polynesia by the fourteenth century AD. This dispersal is intimately tied to human expansion, but the involvement of dogs in Pacific migrations is not well understood. Our analyses of seven new complete ancient mitogenomes and five partial mtDNA sequences from archaeological dog specimens from Mainland and Island Southeast Asia and the Pacific suggests at least three dog dispersal events into the region, in addition to the introduction of dingoes to Australia. We see an early introduction of dogs to Island Southeast Asia, which does not appear to extend into the islands of Oceania. A shared haplogroup identified between Iron Age Taiwanese dogs, terminal-Lapita and post-Lapita dogs suggests that at least one dog lineage was introduced to Near Oceania by or as the result of interactions with Austronesian language speakers associated with the Lapita Cultural Complex. We did not find any evidence that these dogs were successfully transported beyond New Guinea. Finally, we identify a widespread dog clade found across the Pacific, including the islands of Polynesia, which likely suggests a post-Lapita dog introduction from southern Island Southeast Asia.


Subject(s)
Dogs/genetics , Genome, Mitochondrial , Animals , Oceania , Polynesia
19.
J Viral Hepat ; 25(9): 1089-1098, 2018 09.
Article in English | MEDLINE | ID: mdl-29660212

ABSTRACT

To increase access to treatment, the Australian government enabled general practitioners (GPs) to prescribe direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV)-in consultation with a specialist if inexperienced in HCV management. This study describes the establishment and outcomes of a remote consultation pathway supporting GPs to treat HCV. Key stakeholders from primary and tertiary healthcare services in the Barwon South Western region developed and implemented an HCV remote consultation pathway. Pharmaceutical Benefits Schedule prescription data were used to evaluate GP DAA prescription 12 months pre-and post- pathway implementation. A retrospective review of patients referred for remote consultation for 12 months post- pathway inception was undertaken to determine the care cascade. HCV treatment initiation by GPs increased after implementation of the remote consultation pathway. In the 12-month study period, 74 GPs referred 169 people for remote consultation; 114 (67%) were approved for GP DAA treatment; 48 (28%) were referred for specialist assessment. In total, 119 (71%) patients commenced DAA; 69 were eligible for SVR12 assessment. Post-treatment HCV RNA data were available for 52 (75%) people; 37 achieved SVR12; 15 achieved SVR ranging from week 5 to 11 post-treatment. No treatment failure was detected. Collaborative development and implementation of a remote consultation pathway has engaged regional GPs in managing HCV. Follow-up post-treatment could be improved; however, no treatment failure has been documented. To eliminate HCV as a public health threat, it is vital that specialists support GPs to prescribe DAA.


Subject(s)
Antiviral Agents/therapeutic use , General Practitioners , Health Services Accessibility , Hepatitis C, Chronic/drug therapy , Patient Acceptance of Health Care , Remote Consultation/organization & administration , Remote Consultation/statistics & numerical data , Adult , Australia , Female , Humans , Male , Middle Aged , RNA, Viral/blood , Retrospective Studies , Sustained Virologic Response , Treatment Outcome
20.
J Vet Intern Med ; 31(4): 1193-1201, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28568169

ABSTRACT

BACKGROUND: Airway hyperresponsiveness (AWHR), expressed as hypersensitivity (PC75 RL ) or hyperreactivity (slope of the histamine dose-response curve), is a feature of inflammatory airway disease (IAD) or mild equine asthma in horses. Glucocorticoids are used empirically to treat IAD. OBJECTIVES: To determine whether dexamethasone (DEX) (0.05 mg/kg IM q24h) and inhaled fluticasone (FLUT) (3,000 µg q12h) administered by inhalation are effective in decreasing AWHR, lung inflammation, and clinical signs in horses with IAD. METHODS: A randomized crossover study design was used. Eight horses with IAD were assigned to a treatment group with either DEX or FLUT. Measured outcomes included lung mechanics during bronchoprovocative challenges, bronchoalveolar lavage fluid (BALF) cytology, and scoring of clinical signs during exercise. RESULTS: Dexamethasone and FLUT abolished the increase in RL by 75% at any histamine bronchoprovocative dose in all horses after the first week of treatment. However, after 2 weeks of FLUT treatment, 1 horse redeveloped hypersensitivity. There was a significant decrease in the number of lymphocytes after treatment with both DEX and FLUT (P = .039 for both) but no significant differences in other BALF cell types or total cell counts (P > .05). There was no difference in the scoring of the clinical signs during each treatment and washout period (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Both DEX and FLUT treatments significantly inhibit airway hypersensitivity and hyperreactivity in horses with IAD. There are no significant effects on the clinical signs or the number of inflammatory cells (except lymphocytes) in BALF. The treatments have no residual effect 3 weeks after discontinuation.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Dexamethasone/therapeutic use , Fluticasone/therapeutic use , Horse Diseases/drug therapy , Respiratory Hypersensitivity/veterinary , Animals , Asthma/drug therapy , Asthma/veterinary , Bronchial Provocation Tests/veterinary , Bronchoalveolar Lavage Fluid/cytology , Cross-Over Studies , Female , Horses , Male , Respiratory Function Tests/veterinary , Respiratory Hypersensitivity/drug therapy
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