Using central venous pressure waveform to confirm the placement of an internal jugular central venous catheter in the intensive care unit.

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.

The noradrenergic agent reboxetine plus the antimuscarinic hyoscine butylbromide reduces sleep apnoea severity: a double-blind, placebo-controlled, randomised crossover trial.

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.

Zolpidem increases sleep efficiency and the respiratory arousal threshold without changing sleep apnoea severity and pharyngeal muscle activity.

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.

Drug-Eluting Stents Versus Coronary Artery Bypass Grafts for Left Main Coronary Disease: A Meta-Analysis and Review of Randomised Controlled Trials.

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.

Lab-on-a-Drone: Toward Pinpoint Deployment of Smartphone-Enabled Nucleic Acid-Based Diagnostics for Mobile Health Care.

We introduce a portable biochemical analysis platform for rapid field deployment of nucleic acid-based diagnostics using consumer-class quadcopter drones. This approach exploits the ability to isothermally perform the polymerase chain reaction (PCR) with a single heater, enabling the system to be operated using standard 5 V USB sources that power mobile devices (via battery, solar, or hand crank action). Time-resolved fluorescence detection and quantification is achieved using a smartphone camera and integrated image analysis app. Standard sample preparation is enabled by leveraging the drone's motors as centrifuges via 3D printed snap-on attachments. These advancements make it possible to build a complete DNA/RNA analysis system at a cost of ∼$50 ($US). Our instrument is rugged and versatile, enabling pinpoint deployment of sophisticated diagnostics to distributed field sites. This capability is demonstrated by successful in-flight replication of Staphylococcus aureus and λ-phage DNA targets in under 20 min. The ability to perform rapid in-flight assays with smartphone connectivity eliminates delays between sample collection and analysis so that test results can be delivered in minutes, suggesting new possibilities for drone-based systems to function in broader and more sophisticated roles beyond cargo transport and imaging.

Heavy metals in Australian grown and imported rice and vegetables on sale in Australia: health hazard.

Dietary exposure to heavy metals is a matter of concern for human health risk through the consumption of rice, vegetables and other major foodstuffs. In the present study, we investigated concentrations of cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) in Australian grown and imported rice and vegetables on sale in Australia. The mean concentrations of Cd, Co, Cr, Cu, Mn, Ni, Pb, and Zn in Australian grown rice were 7.5 µg kg(-1), 21 µg kg(-1), 144 µg kg(-1), 2.9 mg kg(-1), 24.4 mg kg(-1), 166 µg kg(-1), 375 µg kg(-1), and 17.1 mg kg(-1) dry weight (d. wt.), respectively. Except Cd, heavy metal concentrations in Australian grown rice were higher than Bangladeshi rice on sale in Australia. However, the concentrations of Cd, Cr, Cu, and Ni in Indian rice on sale in Australia were higher than Australian grown rice. The concentrations of Cu and Ni in Vietnamese rice, and that of Cd, Cr, Cu, Ni, and Pb in Thai rice on sale in Australia were also higher than Australian grown rice. Heavy metal concentrations in Pakistani rice on sale in Australia were substantially lower than that in Australian grown rice. In Australian grown rice varieties, the concentrations of heavy metals were considerably higher in brown rice varieties than white rice varieties, indicating Australian brown rice as a potential source of dietary heavy metals for Australian consumers. The mean concentrations of heavy metals in Australian grown and Bangladeshi vegetables on sale in Australia were also determined. Some of the Australian grown and Bangladeshi vegetables contained heavy metals higher than Australian standard maximum limits indicating them as potential sources of dietary heavy metals for Australian consumers. Further investigation is required to estimate health risks of heavy metals from rice and vegetables consumption for Australian consumers.

Toxicity of arsenic species to three freshwater organisms and biotransformation of inorganic arsenic by freshwater phytoplankton (Chlorella sp. CE-35).

In the environment, arsenic (As) exists in a number of chemical species, and arsenite (As(III)) and arsenate (As(V)) dominate in freshwater systems. Toxicity of As species to aquatic organisms is complicated by their interaction with chemicals in water such as phosphate that can influence the bioavailability and uptake of As(V). In the present study, the toxicities of As(III), As(V) and dimethylarsinic acid (DMA) to three freshwater organisms representing three phylogenetic groups: a phytoplankton (Chlorella sp. strain CE-35), a floating macrophyte (Lemna disperma) and a cladoceran grazer (Ceriodaphnia cf. dubia), were determined using acute and growth inhibition bioassays (EC50) at a range of total phosphate (TP) concentrations in OECD medium. The EC50 values of As(III), As(V) and DMA were 27 ± 10, 1.15 ± 0.04 and 19 ± 3 mg L(-1) for Chlorella sp. CE-35; 0.57 ± 0.16, 2.3 ± 0.2 and 56 ± 15 mg L(-1) for L. disperma, and 1.58 ± 0.05, 1.72 ± 0.01 and 5.9 ± 0.1 mg L(-1) for C. cf. dubia, respectively. The results showed that As(III) was more toxic than As(V) to L. disperma; however, As(V) was more toxic than As(III) to Chlorella sp. CE-35. The toxicities of As(III) and As(V) to C. cf. dubia were statistically similar (p>0.05). DMA was less toxic than iAs species to L. disperma and C. cf. dubia, but more toxic than As(III) to Chlorella sp. CE-35. The toxicity of As(V) to Chlorella sp. CE-35 and L. disperma decreased with increasing TP concentrations in the growth medium. Phosphate concentrations did not influence the toxicity of As(III) to either organism. Chlorella sp. CE-35 showed the ability to reduce As(V) to As(III), indicating a substantial influence of phytoplankton on As biogeochemistry in freshwater aquatic systems.

A national survey of trace organic contaminants in Australian rivers.

Trace organic contaminant (TrOC) studies in Australia have, to date, focused on wastewater effluents, leaving a knowledge gap of their occurrence and risk in freshwater environments. This study measured 42 TrOCs including industrial compounds, pesticides, and pharmaceuticals and personal care products by liquid chromatography tandem mass spectrometry at 73 river sites across Australia quarterly for 1 yr. Trace organic contaminants were found in 92% of samples, with a median of three compounds detected per sample (maximum 18). The five most commonly detected TrOCs were the pharmaceuticals salicylic acid (82%, maximum = 1530 ng/L), paracetamol (also known as acetaminophen; 45%, maximum = 7150 ng/L), and carbamazepine (27%, maximum = 682 ng/L), caffeine (65%, maximum = 3770 ng/L), and the flame retardant (2-chloroethyl) phosphate (44%, maximum = 184 ng/L). Pesticides were detected in 28% of the samples. To determine the risk posed by the detected TrOCs to the aquatic environment, hazard quotients were calculated by dividing the maximum concentration detected for each compound by the predicted no-effect concentrations. Three of the 42 compounds monitored (the pharmaceuticals carbamazepine and sulfamethoxazole and the herbicide simazine) had a hazard quotient >1, suggesting that they may be causing adverse effects at the most polluted sites. A further 10 compounds had hazard quotients >0.1, indicating a potential risk; these included four pharmaceuticals, three personal care products, and three pesticides. Most compounds had hazard quotients significantly <0.1. The number of TrOCs measured in this study was limited and further investigations are required to fully assess the risk posed by complex mixtures of TrOCs on exposed biota.

Proposal for improving access to palliative care by enhancing primary care services in an upper middle-income country.

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.

Mapping Levels of Palliative Care Service Development in Malaysian Public Hospitals Using the WHO Public Health Model of Palliative Care.

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.

Mapping Palliative Care Availability and Accessibility: A First Step to Eradicating Access Deserts in the Low- and Middle-Income Settings.

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.

Bioaccumulation, biotransformation and trophic transfer of arsenic in the aquatic food chain.

The occurrence, distribution, speciation, and biotransformation of arsenic in aquatic environment (marine and freshwater) have been studied extensively by several research groups during last couple of decades. However, most of those studies have been conducted in marine waters, and the results are available in a number of reviews. Speciation, bioaccumulation, and biotransformation of arsenic in freshwaters have been studied in recent years. Although inorganic arsenic (iAs) species dominates in both marine and freshwaters, it is biotransformed to methyl and organoarsenic species by aquatic organisms. Phytoplankton is considered as a major food source for the organisms of higher trophic levels in the aquatic food chain, and this autotrophic organism plays important role in biotransformation and distribution of arsenic species in the aquatic environment. Bioaccumulation and biotransformation of arsenic by phytoplankton, and trophic transfer of arsenic in marine and freshwater food chains have been important concerns because of possible human health effects of the toxic metalloid from dietary intake. To-date, most of the studies on arsenic biotransformation, speciation, and trophic transfer have focused on marine environments; little is known about these processes in freshwater systems. This article has been reviewed the bioaccumulation, biotransformation, and trophic transfer of arsenic in marine and freshwater food chain.

Use of duckweed (Lemna disperma) to assess the phytotoxicity of the products of Fenton oxidation of metsulfuron methyl.

Because of pressure on water supplies world-wide, there is increasing interest in methods of remediating contaminated ground waters. However, with some remediation processes, the breakdown products are more toxic than the original contaminant. Organic matter and salinity may also influence degradation efficiency. This study tested the efficiency of Fenton oxidation in degrading the sulfonylurea herbicide metsulfuron methyl (MeS), and tested the reaction products for phytotoxicity with the Lemna (duckweed) bioassay. The efficiency of degradation by Fenton's reagent (Fe(2+)=0.09 mM; H(2)O(2)=1.76 mM, 4h) decreased with increasing initial MeS concentration, from 98% with 5 mg/L MeS, to 63% with 70 mg/L MeS. Addition of NaCl (10mM) and organic matter (humic acid at 0.2 and 2.0mg C/L as Total Organic Carbon) reduced the efficiency of degradation at low initial MeS concentrations (5 and 10 mg/L), but had no effect at high concentrations. The residual Fenton's reagent after Fenton's oxidation was toxic to Lemna. After removal of residual iron and H(2)O(2), the measured toxicity to Lemna in the treated samples could be explained by the concentrations of MeS as measured by HPLC/UV detection, so there was no evidence of additional toxicity or amelioration due to the by-products or formulation materials.

Leaf litter breakdown along an elevational gradient in Australian alpine streams.

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.

Adult palliative care 2004-2030 population study: estimates and projections in Malaysia.

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.

Different antimuscarinics when combined with atomoxetine have differential effects on obstructive sleep apnea severity.

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.

The scope of hospital medicine practice at night: a national survey of night shift hospitalists.

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.

Benthic macroinvertebrate assemblages in remediated wetlands around Sydney, Australia.

To investigate potential high organisational level impacts of persistent organic pollution in the wetlands in the Sydney Olympic Park (SOP) remediated site, the benthic macroinvertebrate assemblages of seven wetlands within SOP and two off-site reference wetlands were examined. Sediment cores were collected, stained and preserved from each study site and the macroinvertebrates identified to the appropriate taxonomic level (Class, Order, Family, Subfamily). Data were analysed for taxon richness and macroinvertebrate abundance and multivariate techniques were used to identify chemical/physical characteristics of the sediment, which were important influences on the differences in the assemblage between study sites. Macroinvertebrate abundance was highly variable between study sites and taxon richness was low across all sites. Oligochaetes, nematodes, ostracods and chironomids were the most common taxa found and were the most important in influencing differences between the macroinvertebrate assemblages among the study sites. Sediment grain size and chemical characteristics of the sediments (ΣPAH, ΣPCB, TCDDeq and heavy metal concentrations) were important in separating the study sites based on taxon richness and abundance. Canonical correspondence analysis separated the macroinvertebrate assemblages at newly two created wetlands from those at other study sites including the urban reference sites. Increased sediment POP contamination (particularly as measured TCDDeq and ΣDDT concentrations) is a likely contributor in excluding pollution sensitive taxa and, therefore, alterations to benthic macroinvertebrate assemblages. Further, the influence of TOC suggests the significance of catchment inputs in contributing to changes in macroinvertebrate assemblage. The SOP remediation led to the establishment of wetlands with benthic communities representative of those expected in urban wetlands.

The Cone Flare Crush Modified-T (CFCT) stenting technique for coronary artery bifurcation lesions.

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).