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1.
Aust Crit Care ; 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38065796

ABSTRACT

BACKGROUND: A mobile chest X-ray is traditionally performed to confirm the position of an internal jugular central venous catheter (CVC) after placement in the intensive care unit (ICU). Using chest radiography to confirm CVC position often results in delays in authorising the use of the CVC, requires the deployment of additional human resources, and is costly. OBJECTIVE: This study aimed to determine the feasibility and accuracy of using the central venous pressure (CVP) waveform to confirm the placement of internal jugular CVCs. METHODS: This retrospective study was conducted in a single quaternary ICU over a 6-month period. We included adult patients who had internal jugular CVC inserted and CVP transduced as part of their routine care in the ICU. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CVP waveform analysis in confirming the position of internal jugular CVC relative to chest radiography were calculated. RESULTS: A total of 241 internal jugular CVCs were inserted (in 219 patients, 35.6% female), and the CVP waveform was assessed. In 231 cases, this suggested adequate placement in a central vein, which corresponded with a correct position on subsequent chest X-ray. On six occasions, the CVP waveforms were interpreted as suboptimal; however, on chest X-rays, the CVCs were noted to be in a suitable position (sensitivity: 97.5%). Four suboptimal CVP waveforms were obtained, and they correctly identified CVC malposition on subsequent chest X-ray (specificity: 100%). The average time from CVC insertion to radiological completion was 118 minutes. CONCLUSION: CVP waveform analysis provides a feasible and reliable method for confirming adequate internal jugular CVC position. The use of chest radiography can be limited to cases where suboptimal CVP waveforms are obtained.

2.
J Palliat Care ; : 8258597231214485, 2023 Nov 19.
Article in English | MEDLINE | ID: mdl-37981855

ABSTRACT

OBJECTIVE: Palliative care is unavailable and/or inaccessible for the majority of people in low- and middle-income countries (LMIC). This study aims to determine the availability and accessibility of palliative care services in Malaysia, a middle-income country that has made good progress toward universal health coverage (UHC). METHOD: Publicly available data, and databases of registered palliative care services were obtained from governmental and nongovernmental sources. Google Maps and Rome2Rio web-based applications were used to assess geographical disparities by estimating the median distance, travel time, and travel costs from every Malaysian district to the closest palliative care service. RESULTS: Substantial variations in availability, components, and accessibility (distance, time, and cost to access care) of palliative care services were observed. In the highly developed Central Region of Peninsular Malaysia, specialty care was available within 4 km whereas in the less-developed East Coast of Peninsular Malaysia, patients had to travel approximately 46 km. In the predominantly rural East Malaysia, basic palliative care services were 82 km away and, in some instances, where land connectivity was scarce, it took 2.5 h to access care via boat. The corresponding median travel costs were USD2 (RM9) and USD23 (RM114) in Peninsular Malaysia and East Malaysia. CONCLUSION: The stark urban-rural divide in the availability and accessibility of palliative care services even in a setting that has made good progress toward UHC highlights the urgent need for decentralization of palliative care in the LMICs. This may be achieved by capacity building and task shifting in primary care and community settings.

3.
J Pain Symptom Manage ; 66(3): 221-229, 2023 09.
Article in English | MEDLINE | ID: mdl-37295564

ABSTRACT

INTRODUCTION AND OBJECTIVES: This national audit involving Ministry of Health (MOH) Hospitals aimed to map out the levels of development of palliative care services and essential palliative medication availability in Malaysia. MATERIALS AND METHODS: An online survey coupled with manual follow up was conducted throughout all MOH hospitals in Malaysia. Data collected described elements of the palliative care service(PCS) based on the WHO public health model. Data was computed using a novel matrix to determine three key indices which were the 1) palliative care development score (PCDS), 2)essential medications availability score (EMAS) and 3) opioid availability score (OAS). These scores then allowed mapping of PCS according to scores of 1-4 (1=least developed, 4=most developed). FINDINGS: Out of all 140 MOH hospitals 88.6% (124) completed the PCDS survey, 120(85.7%) for the EMAS survey and 140 (100%) for the OAS survey. A total of 32(25.8%) hospitals had formal PCS with 8(25%) having resident palliative physicians (RPP), 8(25%) visiting palliative physicians(VPP) and 16(50%) no palliative physician (NPP). Out of these services, 17 (53%) had dedicated palliative care beds. In the PCDS survey, hospitals with PCS had significantly higher mean PCDS of 2.59 compared to 1.02 for non-PCS hospitals (P<0.001). The EMAS survey showed 109(90.8%) hospitals had EMAS of four and the OAS survey showed that 135(96.4%) hospitals had oral morphine available. CONCLUSION: This study shows that palliative care service development in MOH hospitals is still very limited however, majority of MOH hospitals in Malaysia have all the essential medications and oral morphine available.


Subject(s)
Palliative Care , Public Health , Humans , Hospitals, Public , Analgesics, Opioid/therapeutic use , World Health Organization , Morphine Derivatives
4.
Ecancermedicalscience ; 17: 1514, 2023.
Article in English | MEDLINE | ID: mdl-37113719

ABSTRACT

Background: Primary care doctors play an important role in providing palliative care as they are often the first point of contact for most healthcare needs in the community. This mixed-method study aims to 1) determine the accessibility of palliative care services in Malaysia, an upper middle-income country with universal health coverage, 2) explore the knowledge, challenges and opportunities faced by primary care doctors in providing palliative care and 3) identify if minimum standards for palliative care service are clearly defined, available and achieved in primary care facilities. Methods: Data on availability of palliative care services will be sourced from governmental and non-governmental databases and reports. Accessibility will be examined by estimating the distance, travel time and cost to the nearest facility offering palliative care services from various locations throughout Malaysia. In-depth interviews will be conducted with primary care doctors to explore their knowledge, challenges and opportunities in providing palliative care. Alongside, a survey will be conducted to evaluate whether components of palliative care services are available in primary care facilities using the Minimum Standard Tool for Palliative Care from India, which covers all the domains recommended by the World Health Organization. All findings will be inductively analysed and integrated, followed by a strengths, weaknesses, opportunities and threats analysis and a threats, opportunities, weaknesses and strength analysis with relevant stakeholders. Expected results: The mapping study will provide empirical data on availability and accessibility of palliative care services in Malaysia. The qualitative inquiry will provide insights on the experiences and concerns of primary care physicians in providing palliative care in the community settings. The survey meanwhile will provide real-world data on availability of basic palliative care service components in the primary care facilities. Expected conclusion: Findings will facilitate development of framework and policies aiming to optimise provision of sustainable palliative care services at the primary care level in local settings.

5.
Ecol Evol ; 12(10): e9433, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36311402

ABSTRACT

The breakdown of allochthonous organic matter, is a central step in nutrient cycling in stream ecosystems. There is concern that increased temperatures from climate change will alter the breakdown rate of organic matter, with important consequences for the ecosystem functioning of alpine streams. This study investigated the rate of leaf litter breakdown and how temperature and other factors such as microbial and invertebrate activities influenced this over elevational and temporal gradients. Dried leaves of Snow Gum (Eucalyptus pauciflora) and cotton strips were deployed in coarse (6 mm), and fine (50 µm) mesh size bags along an 820 m elevation gradient. Loss of mass in leaf litter and cotton tensile strength per day (k per day), fungal biomass measured as ergosterol concentration, invertebrate colonization of leaf litter, and benthic organic matter (mass and composition) were determined. Both microbial and macroinvertebrate activities were equally important in leaf litter breakdown with the abundance of shredder invertebrate taxa. The overall leaf litter breakdown rate and loss of tensile strength in cotton strips (both k per day) were greater during warmer deployment periods and at lower elevations, with significant positive relationships between mean water temperature and leaf breakdown and loss of tensile strength rate, but no differences between sites, after accounting for the effects of temperature. Despite considerably lower amounts of benthic organic matter in streams above the tree line relative to those below, shredders were present in coarse mesh bags at all sites. Ergosterol concentration was greater on leaves in coarse mesh bags than in fine mesh bags, implying differences in the microbial communities. The importance of water temperatures on the rate of leaf litter breakdown suggests the potential effects of climate change-induced temperature increases on ecological processes in such streams.

6.
BMJ Support Palliat Care ; 12(e1): e129-e136, 2022 May.
Article in English | MEDLINE | ID: mdl-32826260

ABSTRACT

OBJECTIVES: To estimate past trends and future projection of adult palliative care needs in Malaysia. METHODS: This is a population-based secondary data analysis using the national mortality registry from 2004 to 2014. Past trend estimation was conducted using Murtagh's minimum and maximum methods and Gómez-Batiste's method. The estimated palliative care needs were stratified by age groups, gender and administrative states in Malaysia. With this, the projection of palliative care needs up to 2030 was conducted under the assumption that annual change remains constant. RESULTS: The palliative care needs in Malaysia followed an apparent upward trend over the years regardless of the estimation methods. Murtagh's minimum estimation method showed that palliative care needs grew 40% from 71 675 cases in 2004 to 100 034 cases in 2014. The proportion of palliative care needs in relation to deaths hovered at 71% in the observed years. In 2030, Malaysia should anticipate the population needs to be at least 239 713 cases (240% growth from 2014), with the highest needs among age group ≥80-year-old in both genders. Sarawak, Perak, Johor, Selangor and Kedah will become the top five Malaysian states with the highest number of needs in 2030. CONCLUSION: The need for palliative care in Malaysia will continue to rise and surpass its service provision. This trend demands a stepped-up provision from the national health system with advanced integration of palliative care services to narrow the gap between needs and supply.


Subject(s)
Hospice and Palliative Care Nursing , Palliative Care , Adult , Aged, 80 and over , Female , Forecasting , Humans , Malaysia/epidemiology , Male , Palliative Care/methods , Registries
7.
J Physiol ; 599(17): 4183-4195, 2021 09.
Article in English | MEDLINE | ID: mdl-34174090

ABSTRACT

KEY POINTS: Recent animal and human physiology studies indicate that noradrenergic and muscarinic processes are key mechanisms that mediate pharyngeal muscle control during sleep. The noradrenergic agent reboxetine combined with the anti-muscarinic hyoscine butylbromide has recently been shown to improve upper airway function during sleep in healthy individuals. However, whether these findings translate to the clinically relevant patient population of people with obstructive sleep apnoea (OSA), and the effects of the agents on OSA severity, are unknown. We found that reboxetine plus hyoscine butylbromide reduced OSA severity, including overnight hypoxaemia, via increases in pharyngeal muscle responsiveness, improvements in respiratory control and airway collapsibility without changing the respiratory arousal threshold. These findings provide mechanistic insight into the role of noradrenergic and anti-muscarinic agents on upper airway stability and breathing during sleep and are important for pharmacotherapy development for OSA. ABSTRACT: The noradrenergic agent reboxetine combined with the anti-muscarinic hyoscine butylbromide has recently been shown to improve upper airway function during sleep in healthy individuals. However, the effects of this drug combination on obstructive sleep apnoea (OSA) severity are unknown. Accordingly, this study aimed to determine if reboxetine plus hyoscine butylbromide reduces OSA severity. Secondary aims were to investigate the effects on key upper airway physiology and endotypic traits. Twelve people with OSA aged 52 ± 13 years, BMI = 30 ± 5 kg/m2 , completed a double-blind, randomised, placebo-controlled, crossover trial (ACTRN12617001326381). Two in-laboratory sleep studies with nasal mask, pneumotachograph, epiglottic pressure sensor and bipolar fine-wire electrodes into genioglossus and tensor palatini muscles were performed separated by approximately 1 week. Each participant received either reboxetine (4 mg) plus hyoscine butylbromide (20 mg), or placebo immediately prior to sleep. Polysomnography, upper airway physiology and endotypic estimates of OSA were compared between conditions. Reboxetine plus hyoscine butylbromide reduced the apnoea/hypopnoea index by (mean ± SD) 17 ± 17 events/h from 51 ± 30 to 33 ± 22 events/h (P = 0.005) and nadir oxygen saturation increased by 6 ± 5% from 82 ± 5 to 88 ± 2% (P = 0.002). The drug combination increased tonic genioglossus muscle responsiveness during non-REM sleep (median [25th, 75th centiles]: -0.007 [-0.0004, -0.07] vs. -0.12 [-0.02, -0.40] %maxEMG/cmH2 O, P = 0.02), lowered loop gain (0.43 ± 0.06 vs. 0.39 ± 0.07, P = 0.01), and improved airway collapsibility (90 [69, 95] vs. 93 [88, 96] %eupnoea, P = 0.02), without changing the arousal threshold (P = 0.39). These findings highlight the important role that noradrenergic and muscarinic processes have on upper airway function during sleep and the potential for pharmacotherapy to target these mechanisms to treat OSA.


Subject(s)
Muscarinic Antagonists , Sleep Apnea, Obstructive , Continuous Positive Airway Pressure , Cross-Over Studies , Humans , Hydrocarbons, Brominated , Reboxetine , Scopolamine , Sleep , Sleep Apnea, Obstructive/drug therapy
8.
Hosp Pract (1995) ; 49(4): 292-297, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34030568

ABSTRACT

Introduction: Although in-person hospitalist presence, increasingly staffed by dedicated nocturnists, has become the norm overnight in the hospital, the scope of nocturnist practice and typical workload has not been defined. This study examines the clinical responsibilities and patient safety perceptions of hospitalists who work night shifts in the United States.Methods: In the fall of 2019, a cross-sectional, web-based survey was administered to physician and nurse practitioner/physician assistant (NP/PA) hospitalists who work night shifts. The questionnaire assessed night staffing structure, typical responsibilities, patient volume, perceptions of safety overnight, as well as demographic information. The survey was posted on the Society of Hospital Medicine (SHM) Hospital Medicine Exchange (HMX) Online Discussion Forum. Additionally, the survey was distributed by 'snowball method' by respondents to other night hospitalists. Responses were collected anonymously.Results: Of the 167 respondents, 157 reported working night shifts. There was at least one respondent from 32 different states. In addition to performing admissions to medicine services and covering inpatients, night hospitalists cover ICU patients, participate in RRT/Code teams and procedure teams, perform consults, participate in medical education, and take outpatient calls. Across institutions, there was a large distribution in numbers of patients covered in a night shift; however, patient volume fell into typical ranges: 5-10 admissions for physicians, 0-6 admissions for NP/PAs, and 25-75 patient cross-coverage census. When physicians perform more than five admissions per night, hospitalists were less likely to agree that they could provide safe care (88% vs. 63%, p = 0.0006).Conclusions: This is the first national study to examine the clinical responsibilities of hospitalists working overnight. Overnight responsibilities are heterogeneous across institutions. As hospitals are increasingly employing nocturnists, more research is needed to guide night staffing and optimize patient safety.


Subject(s)
Hospitalists/organization & administration , Patient Safety/standards , Shift Work Schedule , Hospitalists/standards , Humans , Patient Admission/statistics & numerical data , Socioeconomic Factors , United States
9.
J Appl Physiol (1985) ; 130(5): 1373-1382, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33734828

ABSTRACT

The combination of the noradrenergic agent atomoxetine plus the antimuscarinic oxybutynin has recently been shown to improve upper airway physiology and reduce obstructive sleep apnea (OSA) severity. However, the effects of different antimuscarinics when combined with atomoxetine is limited. This study aimed to determine the effects of atomoxetine combined with two different antimuscarinics with varying M-subtype receptor selectivity on OSA severity and upper airway physiology. Ten people with predominantly severe OSA completed a double-blind, randomized, placebo-controlled, cross-over trial. Participants completed three overnight in-laboratory sleep studies after either 80 mg atomoxetine + 5 mg solifenacin succinate (ato-sol) or 80 mg atomoxetine + 2 mg biperiden hydrochloride (ato-bip) or placebo. OSA severity, ventilatory stability (loop gain), respiratory-arousal threshold (via epiglottic manometry), next-day subjective sleepiness [Karolinska Sleepiness Scale (KSS)], and alertness were compared between conditions. Neither drug combination altered the apnea/hypopnea index versus placebo (P = 0.63). Ato-sol caused a shift toward milder respiratory events with reduced frequency of obstructive apneas (13 ± 14 vs. 22 ± 17 events/h; means ± SD, P = 0.04) and increased hypopneas during nonrapid eye movement (NREM) (38 ± 21 vs. 24 ± 18 events/h, P = 0.006) with improved nadir oxygenation versus placebo (83 ± 4 vs. 80 ± 8%, P = 0.03). Both combinations reduced loop gain by ∼10% versus placebo; sleep efficiency and arousal threshold were unaltered. Ato-bip reduced next-day sleepiness versus placebo (KSS = 4.3 ± 2.2 vs. 5.6 ± 1.6, P = 0.03). Atomoxetine + biperiden hydrochloride reduces perceived sleepiness, and atomoxetine + solifenacin modestly improves upper airway function in people with OSA but to a lesser extent versus recently published atomoxetine + oxybutynin (broad M-subtype receptor selectivity) findings. These results provide novel mechanistic insight into the role of noradrenergic and antimuscarinic agents on sleep and breathing and are important for pharmacotherapy development for OSA.NEW & NOTEWORTHY In contrast to recent findings of major reductions in OSA severity when atomoxetine is combined with a nonspecific antimuscarinic, oxybutynin (broad M-subtype receptor selectivity), addition of solifenacin succinate (M2 and M3 muscarinic receptor selectivity) or biperiden (M1 muscarinic receptor selectivity) with atomoxetine had modest effects on upper airway function during sleep, which provide mechanistic insight into the role of noradrenergic and antimuscarinic agents on sleep and breathing and are important for pharmacotherapy development for OSA.


Subject(s)
Muscarinic Antagonists , Sleep Apnea, Obstructive , Atomoxetine Hydrochloride , Humans , Polysomnography , Sleep , Wakefulness
10.
Int J Cardiol Heart Vasc ; 30: 100643, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33015315

ABSTRACT

BACKGROUND: The present study is a prospective observational single arm clinical investigation, with parallel bench test interrogation, aimed at investigating the technical feasibility, safety and clinical outcomes with the cone flare crush modified-T (CFCT) bifurcation stenting technique. Bifurcation percutaneous coronary intervention (PCI) remains an area of ongoing procedural evolution. More widely applicable and reproducible techniques are required. METHODS: From April 2018 until March 2019, 20 consecutive patients underwent bifurcation PCI using the CFCT technique with a Pt-Cr everolimus drug-eluting stent with a bioresorbable polymer. Exercise stress echocardiography was performed at 12-month follow-up. The primary outcome was a composite of cardiac related mortality, myocardial infarction, target lesion/vessel revascularization and stroke. Safety secondary endpoints included bleeding, all-cause mortality and stent thrombosis. RESULTS: All patients underwent a successful CFCT bifurcation procedure with no complications to 30-day follow-up. One patient met the primary endpoint requiring target lesion revascularization at 9 months for stable angina. There were no other primary or secondary outcome events in the cohort. There were no strokes, deaths, stent thrombosis or myocardial infarction during the follow-up period. The mean CCS score improved from 2.25 to 0.25 (p < 0.0001). Optical coherence tomography (OCT) and bench test findings indicated optimal side branch ostial coverage and minimal redundant strut material crowding the neo-carina. CONCLUSIONS: The CFCT technique appears to be a safe, efficacious and feasible strategy for managing coronary artery bifurcation disease. Expanded and randomized datasets with longer term follow-up are required to further explore confirm this feasibility data. (ANZCTR ID: ACTRN12618001145291).

11.
J Physiol ; 598(20): 4681-4692, 2020 10.
Article in English | MEDLINE | ID: mdl-32864734

ABSTRACT

KEY POINTS: A decreased respiratory arousal threshold is one of the main contributors to obstructive sleep apnoea (OSA) pathogenesis. Several recent studies have sought to find a drug capable of increasing the respiratory arousal threshold without impairing pharyngeal muscle activity to reduce OSA severity, with variable success. Here we show that zolpidem increases the respiratory arousal threshold by ∼15%, an effect size which was insufficient to systematically decrease OSA severity as measured by the apnoea-hypopnoea index. Unlike recent physiological findings that showed paradoxical increases in pharyngeal muscle responsiveness during transient manipulations of airway pressure, zolpidem did not alter pharyngeal muscle responsiveness during natural sleep. It did, however, increase sleep efficiency without changing apnoea length, oxygen desaturation, next-day perceived sleepiness and alertness. These novel findings indicate that zolpidem was well tolerated and effective in promoting sleep in people with OSA, which may be therapeutically useful for people with OSA and comorbid insomnia. ABSTRACT: A recent physiology study performed using continuous positive airway pressure (CPAP) manipulations indicated that the hypnotic zolpidem increases the arousal threshold and genioglossus responsiveness in people with and without obstructive sleep apnoea (OSA). Thus, zolpidem may stabilise breathing and reduce OSA severity without CPAP. Accordingly, we sought to determine the effects of zolpidem on OSA severity, upper airway physiology and next-day sleepiness and alertness. Nineteen people with OSA with low-to-moderate arousal threshold received 10 mg zolpidem or placebo according to a double-blind, randomised, cross-over design. Participants completed two overnight in-laboratory polysomnographies (1-week washout), with an epiglottic catheter, intramuscular genioglossus electromyography, nasal mask and pneumotachograph to measure OSA severity, arousal threshold and upper airway muscle responsiveness. Next-morning sleepiness and alertness were also assessed. Zolpidem did not change the apnoea-hypopnoea index versus placebo (40.6 ± 12.3 vs. 40.3 ± 16.4 events/h (means ± SD), p = 0.938) or nadir oxyhaemoglobin saturation (79.6 ± 6.6 vs. 79.7 ± 7.4%, p = 0.932), but was well tolerated. Zolpidem increased sleep efficiency by 9 ± 14% (83 ± 11 vs. 73 ± 17%, p = 0.010). Arousal threshold increased by 15 ± 5% with zolpidem throughout all sleep stages (p = 0.010), whereas genioglossus muscle responsiveness did not change. Next-morning sleepiness and alertness were not different between nights. In summary, a single night of 10 mg zolpidem is well tolerated and does not cause next-day impairment in alertness or sleepiness, or overnight hypoxaemia in OSA. However, despite increases in arousal threshold without any change in pharyngeal muscle responsiveness, zolpidem does not alter OSA severity. It does, however, increase sleep efficiency by ∼10%, which may be beneficial in people with OSA and insomnia.


Subject(s)
Arousal , Continuous Positive Airway Pressure , Humans , Pharyngeal Muscles , Sleep , Zolpidem
12.
Integr Environ Assess Manag ; 15(6): 917-935, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31273905

ABSTRACT

Environmental challenges persist across the world, including the Australasian region of Oceania, where biodiversity hotspots and unique ecosystems such as the Great Barrier Reef are common. These systems are routinely affected by multiple stressors from anthropogenic activities, and increasingly influenced by global megatrends (e.g., the food-energy-water nexus, demographic transitions to cities) and climate change. Here we report priority research questions from the Global Horizon Scanning Project, which aimed to identify, prioritize, and advance environmental quality research needs from an Australasian perspective, within a global context. We employed a transparent and inclusive process of soliciting key questions from Australasian members of the Society of Environmental Toxicology and Chemistry. Following submission of 78 questions, 20 priority research questions were identified during an expert workshop in Nelson, New Zealand. These research questions covered a range of issues of global relevance, including research needed to more closely integrate ecotoxicology and ecology for the protection of ecosystems, increase flexibility for prioritizing chemical substances currently in commerce, understand the impacts of complex mixtures and multiple stressors, and define environmental quality and ecosystem integrity of temporary waters. Some questions have specific relevance to Australasia, particularly the uncertainties associated with using toxicity data from exotic species to protect unique indigenous species. Several related priority questions deal with the theme of how widely international ecotoxicological data and databases can be applied to regional ecosystems. Other timely questions, which focus on improving predictive chemistry and toxicology tools and techniques, will be important to answer several of the priority questions identified here. Another important question raised was how to protect local cultural and social values and maintain indigenous engagement during problem formulation and identification of ecosystem protection goals. Addressing these questions will be challenging, but doing so promises to advance environmental sustainability in Oceania and globally.


Subject(s)
Biodiversity , Climate Change , Ecotoxicology , Environmental Monitoring , Environmental Pollutants/adverse effects , Australasia , Environmental Exposure/adverse effects
14.
Sleep ; 42(4)2019 04 01.
Article in English | MEDLINE | ID: mdl-30590857

ABSTRACT

STUDY OBJECTIVES: Recent findings indicate that noradrenergic and antimuscarinic processes are crucial for sleep-related reductions in pharyngeal muscle activity. However, there are few human studies. Accordingly, this study aimed to determine if a combined noradrenergic and antimuscarinic intervention increases pharyngeal dilator muscle activity and improves airway function in sleeping humans. METHODS: Genioglossus (GG) and tensor palatini electromyography (EMG), pharyngeal pressure, upper airway resistance, and breathing parameters were acquired in 10 healthy adults (5 female) during two overnight sleep studies after 4 mg of reboxetine (REB) plus 20 mg of hyoscine butylbromide (HBB) or placebo using a double-blind, placebo-controlled, randomized, cross-over design. RESULTS: Compared with placebo, peak and tonic GG EMG were lower (Mean ± SD: 83 ± 73 vs. 130 ± 75, p = 0.021 and 102 ± 102 vs. 147 ± 123 % wakefulness, p = 0.021, respectively) but the sleep-related reduction in tensor palatini was less (Median [25th, 75th centiles]: 53[45, 62] vs. 34[28, 38] % wakefulness, p = 0.008) with the drug combination during nonrapid eye movement (non-REM) sleep. These changes were accompanied by improved upper airway function including reduced pharyngeal pressure swings, airway resistance, respiratory load compensation, and increased breathing frequency during N2. REB and HBB significantly reduced rapid eye movement sleep compared with placebo (0.6 ± 1.1 vs. 14.5 ± 6.8 % total sleep time, p < 0.001). CONCLUSIONS: Contrary to our hypothesis, GG muscle activity (% wakefulness) during non-REM sleep was lower with REB and HBB. However, sleep-related reductions in tensor palatini activity were less and upper airway function improved. These findings provide mechanistic insight into the role of noradrenergic and antimuscarinic processes on upper airway function in humans and have therapeutic potential for obstructive sleep apnea. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, https://www.anzctr.org.au, trial ID: ACTRN12616000469415.


Subject(s)
Butylscopolammonium Bromide/pharmacology , Parasympatholytics/pharmacology , Pharyngeal Muscles/physiology , Reboxetine/pharmacology , Sleep Apnea, Obstructive/drug therapy , Sleep, REM/physiology , Adult , Airway Resistance/physiology , Australia , Cross-Over Studies , Double-Blind Method , Electromyography , Female , Humans , Male , Nose , Pharynx/physiopathology , Polysomnography , Pressure , Respiration , Scopolamine/pharmacology , Sleep/physiology , Sleep Apnea, Obstructive/physiopathology , Tongue/physiopathology , Wakefulness/physiology
15.
Water Res ; 141: 96-108, 2018 Sep 15.
Article in English | MEDLINE | ID: mdl-29778871

ABSTRACT

The survival of aquatic biota in stream ecosystems depends on both water quantity and quality, and is particularly susceptible to degraded water quality in regulated rivers. Maintenance of environmental flows (e-flows) for aquatic biota with optimum water quantity and quality is essential for sustainable ecosystem services, especially in developing regions with insufficient stream monitoring of hydrology, water quality and aquatic biota. Few e-flow methods are available that closely link aquatic biota tolerances to pollutant concentrations in a simple and practical manner. In this paper a new method was proposed to assess e-flows that aimed to satisfy the requirements of aquatic biota for both the quantity and quality of the streamflow by linking fish tolerances to water quality criteria, or the allowable concentration of pollutants. For better operation of water projects and control of pollutants discharged into streams, this paper presented two coefficients for streamflow adjustment and pollutant control. Assessment of e-flows in the Wei River, the largest tributary of the Yellow River, shows that streamflow in dry seasons failed to meet e-flow requirements. Pollutant influx exerted a large pressure on the aquatic ecosystem, with pollutant concentrations much higher than that of the fish tolerance thresholds. We found that both flow velocity and water temperature exerted great influences on the pollutant degradation rate. Flow velocity had a much greater influence on pollutant degradation than did the standard deviation of flow velocity. This study provides new methods to closely link the tolerance of aquatic biota to water quality criteria for e-flow assessment. The recommended coefficients for streamflow adjustment and pollutant control, to dynamically regulate streamflow and control pollutant discharge, are helpful for river management and ecosystems rehabilitation. The relatively low data requirement also makes the method easy to use efficiently in developing regions, and thus this study has significant implications for managing flows in polluted and regulated rivers worldwide.


Subject(s)
Environmental Monitoring/methods , Fishes , Rivers , Water Quality , Animals , Hydrology , Seasons , Water Pollution/prevention & control
16.
Heart Lung Circ ; 27(12): 1437-1445, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29102437

ABSTRACT

BACKGROUND: Revascularisation of left main coronary artery (LMCA) disease can be potentially managed with percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). Recent randomised controlled trial (RCT) data have added to the literature on this subject and this meta-analysis aims to assess the state of the data to assist in guiding patient treatment decisions. METHODS: A systematic literature search of Cochrane Library, EMBASE, OVID, and PubMed Medline was performed. Randomised controlled trials of patients with LMCA disease undergoing PCI with drug eluting stents or CABG were included. Clinical outcomes and adverse events were assessed and analysed. RESULTS: Four suitable RCTs of adequate quality and follow-up were identified. The incidence of major adverse cardiac and cerebrovascular events (MACCE) at 3 to 5 years of follow-up was significantly increased with PCI compared to CABG (23.3% vs 18.2%, OR 1.37; 95% CI: 1.18-1.58; p=<0.0001; I2=0%) and was largely driven by more repeat revascularisation procedures among patients treated with PCI. There was no statistically significant difference in rates of mortality, myocardial infarction or stroke (either individually or when these outcomes were combined as a composite endpoint). CONCLUSIONS: Coronary artery bypass grafting and PCI both represent reasonable treatment modalities for LMCA disease in appropriately selected patients. However, where CABG is feasible it offers superior long-term freedom from repeat revascularisation. Longer-term follow-up is required to further clarify the durability of mortality outcomes, especially in patients treated with PCI.


Subject(s)
Coronary Artery Bypass/methods , Coronary Artery Disease/surgery , Coronary Vessels/surgery , Decision Making , Drug-Eluting Stents , Percutaneous Coronary Intervention/methods , Randomized Controlled Trials as Topic , Humans
17.
Sci Total Environ ; 616-617: 1638-1648, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29079092

ABSTRACT

There are over 40,000 chemical compounds registered for use in Australia, and only a handful are monitored in the aquatic receiving environments. Their effects on fish species in Australia are largely unknown. Mosquitofish (Gambusia holbrooki) were sampled from six river sites in Southeast Queensland identified as at risk from a range of pollutants. The sites selected were downstream of a wastewater treatment plant discharge, a landfill, two agricultural areas, and two sites in undeveloped reaches within or downstream of protected lands (national parks). Vitellogenin analysis, histopathology of liver, kidney and gonads, morphology of the gonopodium, and chemical body burden were measured to characterize fish health. Concentrations of trace organic contaminants (TrOCs) in water were analyzed by in vitro bioassays and chemical analysis. Estrogenic, anti-estrogenic, anti-androgenic, progestagenic and anti-progestagenic activities and TrOCs were detected in multiple water samples. Several active pharmaceutical ingredients (APIs), industrial compounds, pesticides and other endocrine active compounds were detected in fish carcasses at all sites, ranging from <4-4700ng/g wet weight, including the two undeveloped sites. While vitellogenin protein was slightly increased in fish from two of the six sites, the presence of micropollutants did not cause overt sexual endocrine disruption in mosquitofish (i.e., no abnormal gonads or gonopodia). A correlation between lipid accumulation in the liver with total body burden warrants further investigation to determine if exposure to low concentrations of TrOCs can affect fish health and increase stress on organs such as the liver and kidneys via other mechanisms, including disruption of non-sexual endocrine axes involved in lipid regulation and metabolism.


Subject(s)
Cyprinodontiformes/physiology , Environmental Monitoring , Vitellogenins/metabolism , Water Pollutants, Chemical/metabolism , Animals , Body Burden , Endocrine Disruptors/analysis , Endocrine Disruptors/metabolism , Queensland , Water Pollutants, Chemical/analysis
18.
Aquat Toxicol ; 189: 200-208, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28651182

ABSTRACT

Diffuse agricultural runoff into rivers can result in contamination with herbicides for prolonged periods of time. Chronic exposure to herbicides has the potential to alter toxic impacts in primary producers such as benthic diatoms. Determining how individual diatom taxa respond to herbicide exposure over varied exposure durations is essential for assessing herbicide impacts. This study investigated the responses of various benthic diatom taxa and effects at the community level over 12days of atrazine exposure. Diatom communities were collected from two sites with differing exposure histories; a relatively unpolluted site (Alligator Creek) and an agricultural stream (Barratta Creek) known to be polluted by atrazine and other herbicides. Diatom community composition and the proportion of healthy cells per taxon were assessed at 0, 2, 3, 6, 9 and 12days of atrazine exposure. Pollution history altered the response of the diatom community to atrazine exposure. In the Alligator Creek diatom community there was a shift in composition towards more tolerant taxa and the loss of sensitive taxa in atrazine exposed treatments. The sensitive taxon (Gomphonema truncatum) was consistently affected by atrazine toxicity. Conversely, the polluted Barratta Creek diatom community was not strongly affected by atrazine exposure. Our study shows that during chronic atrazine exposure some taxa demonstrated the ability to recover despite initial toxicity response. Recovery could be an important trait for understanding the ecological effect of herbicide exposure on diatom species in nature and in applied circumstances such as biomonitoring indices.


Subject(s)
Atrazine/toxicity , Diatoms/drug effects , Environmental Monitoring/methods , Herbicides/toxicity , Rivers/chemistry , Water Pollutants, Chemical/toxicity , Dose-Response Relationship, Drug , Queensland , Time Factors , Toxicity Tests
20.
Aquat Toxicol ; 185: 105-120, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28208107

ABSTRACT

In Australia, trace organic contaminants (TrOCs) and endocrine active compounds (EACs) have been detected in rivers impacted by sewage effluent, urban stormwater, agricultural and industrial inputs. It is unclear whether these chemicals are at concentrations that can elicit endocrine disruption in Australian fish species. In this study, native rainbowfish (Melanotaenia fluviatilis) and introduced invasive (but prevalent) mosquitofish (Gambusia holbrooki) were exposed to the individual compounds atrazine, estrone, bisphenol A, propylparaben and pyrimethanil, and mixtures of compounds including hormones and personal care products, industrial compounds, and pesticides at environmentally relevant concentrations. Vitellogenin (Vtg) protein and liver Vtg mRNA induction were used to assess the estrogenic potential of these compounds. Vtg expression was significantly affected in both species exposed to estrone at concentrations that leave little margin for safety (p<0.001). Propylparaben caused a small but statistically significant 3× increase in Vtg protein levels (p=0.035) in rainbowfish but at a concentration 40× higher than that measured in the environment, therefore propylparaben poses a low risk of inducing endocrine disruption in fish. Mixtures of pesticides and a mixture of hormones, pharmaceuticals, industrial compounds and pesticides induced a small but statistically significant increase in plasma Vtg in rainbowfish, but did not affect mosquitofish Vtg protein or mRNA expression. These results suggest that estrogenic activity represents a low risk to fish in most Australian rivers monitored to-date except for some species of fish at the most polluted sites.


Subject(s)
Cyprinodontiformes/metabolism , Introduced Species , Organic Chemicals/analysis , Rivers/chemistry , Smegmamorpha/metabolism , Vitellogenins/metabolism , Water Pollutants, Chemical/analysis , Animals , Australia , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Vitellogenins/genetics
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