Non-fatal opioid overdose, naloxone access, and naloxone training among people who recently used opioids or received opioid agonist treatment in Australia: The ETHOS Engage study.

BACKGROUND: Overdose is a major cause of morbidity and mortality among people who use opioids. Naloxone can reverse opioid overdoses and can be distributed and administered with minimal training. People with experience of overdose are a key population to target for overdose prevention strategies. This study aims to understand if factors associated with recent non-fatal opioid overdose are the same as factors associated with naloxone access and naloxone training in people who recently used opioids or received opioid agonist treatment (OAT). METHODS: ETHOS Engage is an observational study of people who inject drugs in Australia. Logistic regression models were used to estimate odds ratios for non-fatal opioid overdose, naloxone access and naloxone training. RESULTS: Between May 2018-September 2019, 1280 participants who recently used opioids or received OAT were enrolled (62% aged >40 years; 35% female, 80% receiving OAT, 62% injected drugs in the preceding month). Recent opioid overdose (preceding 12 months) was reported by 7% of participants, lifetime naloxone access by 17%, and lifetime naloxone training by 14%. Compared to people receiving OAT with no additional opioid use, recent opioid, benzodiazepine (preceding six months), and hazardous alcohol use was associated with recent opioid overdose (aOR 3.91; 95%CI: 1.68-9.10) and lifetime naloxone access (aOR 2.12; 95%CI 1.29-3.48). Among 91 people who reported recent overdose, 65% had never received take-home naloxone or naloxone training. CONCLUSIONS: Among people recently using opioids or receiving OAT, benzodiazepine and hazardous alcohol use is associated with non-fatal opioid overdose. Not all factors associated with non-fatal overdose correspond to factors associated with naloxone access. Naloxone access and training is low across all groups. Additional interventions are needed to scale up naloxone provision.

Brief intense exercise followed by passive recovery modifies the pattern of fuel use in humans during subsequent sustained intermittent exercise.

The role of work period duration as the principal factor influencing carbohydrate metabolism during intermittent exercise has been investigated. Fuel oxidation rates and muscle glycogen and free carnitine content were compared between two protocols of sustained intermittent intense exercise with identical treadmill speed and total work duration. In the first experiment subjects (n=6) completed 40 min of intermittent treadmill running involving a work : recovery cycle of 6 : 9 s or 24 : 36 s on separate days. With 24 : 36 s exercise a higher rate of carbohydrate oxidation approached significance (P=0.057), whilst fat oxidation rate was lower (P < or = 0.01) and plasma lactate concentration higher (P < or = 0.01). Muscle glycogen was lower post-exercise with 24 : 36 s (P < or = 0.05). Muscle free carnitine decreased (P < or = 0.05), but there was no difference between protocols. In the second experiment a separate group of subjects (n=5) repeated the intermittent exercise protocols with the addition of a 10-min bout of intense exercise, followed by 43 +/- 5 min passive recovery, prior to sustained (40 min) intermittent exercise. For this experiment the difference in fuel use observed previously between 6 : 9 s and 24 : 36 s was abolished. Carbohydrate and fat oxidation, plasma lactate and muscle glycogen levels were similar in 6 : 9 s and 24 : 36 s. When compared with the first experiment, this result was because of reduced carbohydrate oxidation in 24 : 36 s (P < or = 0.05). There was no difference, and no change, in muscle free carnitine between protocols. A 10-min bout of intense exercise, followed by 43 +/- 5 min of passive recovery, substantially modifies fuel use during subsequent intermittent intense exercise.

A comparison of skeletal muscle oxygenation and fuel use in sustained continuous and intermittent exercise.

In this study we compared substrate oxidation and muscle oxygen availability during sustained intermittent intense and continuous submaximal exercise with similar overall (i.e. work and recovery) oxygen consumption (VO2). Physically active subjects (n = 7) completed 90 min of an intermittent intense (12 s work:18 s recovery) and a continuous submaximal treadmill running protocol on separate days. In another experiment (n = 5) we compared oxygen availability in the vastus lateralis muscle between these two exercise protocols using near-infrared spectroscopy. Initially, overall VO(2) (i.e. work and recovery) was matched, and from 37.5 min to 67.5 min of exercise was similar, although slightly higher during continuous exercise (8%; P < 0.05). Energy expenditure was constant (22.5-90 min of exercise) and was not different in intermittent intense [0.81 (0.01) kJ x min(-1). kg(-1)] and continuous submaximal [0.85 (0.01) kJ x min(-1) x kg(-1)] exercise. Overall exercise intensity, represented as a proportion of peak aerobic power (VO2(peak)), was 68.1 (2.5)% VO2(peak) and 71.8 (1.8)% VO2(peak) for intermittent and continuous exercise protocols, respectively. Fat oxidation was almost 3 times lower (P < 0.05) and carbohydrate oxidation was approximately 1.2 times higher (P < 0.05) during intermittent compared to continuous exercise, despite the same overall energy expenditure. Capillary plasma lactate was constant from 15 to 90 min of exercise, and pyruvate was constant from 15 to 75 min, although both were higher (P < 0.0001, lactate; P < 0.001, pyruvate) during intermittent [5.05 (0.28) mM, 200 (7) microM, respectively] compared to continuous exercise [2.41 (0.10) mM, 114 (4) microM, respectively]. There was no difference between protocols for either plasma glycerol or non-esterified fatty acids. The decrease in muscle oxygenation during work periods of intermittent exercise resulted in a lower nadir oxygenation [54.62 (0.41)%] compared to continuous exercise [58.82 (0.21)%, P < 0.001]. The decline in oxygenation was correlated with treadmill speed (r = 0.72; P < 0.05). These results show a difference in substrate utilisation and muscle oxygen availability during sustained intermittent intense and continuous submaximal exercise, despite a similar overall VO(2) and identical energy expenditure.

Effect of work and recovery duration on skeletal muscle oxygenation and fuel use during sustained intermittent exercise.

The purpose of this study was to compare rates of substrate oxidation in two protocols of intermittent exercise, with identical treadmill speed and total work duration, to reduce the effect of differences in factors such as muscle fibre type activation, hormonal responses, muscle glucose uptake and non-esterified fatty acid (NEFA) availability on the comparison of substrate utilisation. Subjects (n = 7) completed 40 min of intermittent intense running requiring a work:recovery ratio of either 6 s:9 s (short-interval exercise, SE) or 24 s:36 s (long-interval exercise, LE), on separate days. Another experiment compared O(2) availability in the vastus lateralis muscle across SE (10 min) and LE (10 min) exercise using near-infrared spectroscopy (RunMan, NIM. Philadelphia, USA). Overall (i.e. work and recovery) O(2) consumption (VO(2)) and energy expenditure were lower during LE (P < 0.01, P < 0.05, respectively). Overall exercise intensity, represented as a proportion of peak aerobic power (VO2(peak)), was [mean (SEM)] 64.9 (2.7)% VO2(peak) (LE) and 71.4 (2.4)% VO2(peak) (SE). Fat oxidation was three times lower (P < 0.01) and carbohydrate oxidation 1.3 times higher (P < 0. 01) during LE, despite the lower overall exercise intensity. Plasma lactate was constant and was higher throughout exercise in LE [mean (SEM) 5.33 (0.53) mM, LE; 3.28 (0.31) mM, SE; P < 0.001)]. Plasma pyruvate was higher and glycerol was lower in LE [215 (17) microM, 151 (13) microM, P < 0.05, pyruvate; 197 (19) microM, 246 (19) microM, P < 0.05, glycerol]. There was no difference between protocols for plasma NEFA concentration (n = 4) or plasma noradrenaline and adrenaline. Muscle oxygenation declined in both protocols (P < 0.001), but the nadir during LE was lower [52.04 (0. 60)%] compared to SE [61.85 (0.51)%; P < 0.001]. The decline in muscle oxygenation during work was correlated with mean lactate concentration (r = 0.68; P < 0.05; n = 12). Lower levels of fat oxidation occurred concurrent with accelerated carbohydrate metabolism, increases in lactate and pyruvate and reduced muscle O(2) availability. These changes were associated with proportionately longer work and recovery periods, despite identical treadmill speed and total work duration. The proposal that a metabolic regulatory factor within the muscle fibre retards fat oxidation under these conditions is supported by the current findings.

A semiautomated enzymatic method for determination of nonesterified fatty acid concentration in milk and plasma.

An enzymatic assay for the determination of nonesterified fatty acid concentrations in milk and plasma is described. The procedure is semiautomated for use with a plate luminometer or plate spectrophotometer and enables routine batch processing of large numbers of small samples (< or =5 microL). Following the activation of nonesterified fatty acids (NEFA) by acylCoA synthetase, the current assay utilizes UDP-glucose pyrophosphorylase to link inorganic pyrophosphate to the production of NADH through the reactions catalyzed by phosphoglucomutase and glucose-6-phosphate 1-dehydrogenase. With this assay sequence the formation of NADH from NEFA is complete within 50 min at 37 degrees C. Enzymatic spectrophotometric techniques were unsuitable for NEFA determination in human milk due to the opacity of the sample. The use of the NADH-luciferase system has overcome this problem, allowing the enzymatic determination of NEFA in human milk. Sample collection and treatment procedures for milk and plasma have been developed to prevent enzymatic lipolysis and to limit interference from enzymes present in milk. The recovery of palmitic acid added to milk and plasma samples was 94.9+/-2.9 and 100+/-4.5%, respectively. There was no difference (P = 0.13) in plasma NEFA concentrations determined by the current method and a commercially available enzymatic spectrophotometric technique (Wako NEFA-C kit). Plasma NEFA concentrations determined by gas chromatography were 28% higher compared to both the Wako NEFA-C kit and the current method.

Exercise intensity and metabolic response in singles tennis.

The aim of this study was to determine exercise intensity and metabolic response during singles tennis play. Techniques for assessment of exercise intensity were studied on-court and in the laboratory. The on-court study required eight State-level tennis players to complete a competitive singles tennis match. During the laboratory study, a separate group of seven male subjects performed an intermittent and a continuous treadmill run. During tennis play, heart rate (HR) and relative exercise intensity (72 +/- 1.9% VO2max; estimated from measurement of heart rate) remained constant (83.4 +/- 0.9% HRmax; mean +/- s(x)) after the second change of end. The peak value for estimated play intensity (1.25 +/- 0.11 steps x s(-1); from video analysis) occurred after the fourth change of end (P< 0.005). Plasma lactate concentration, measured at rest and at the change of ends, increased 175% from 2.13 +/- 0.32 mmol x l(-1) at rest to a peak 5.86 +/- 1.33 mmol x l(-1) after the sixth change of end (P < 0.001). A linear regression model, which included significant terms for %HRmax (P< 0.001), estimated play intensity (P < 0.001) and subject (P < 0.00), as well as a %HRmax subject interaction (P < 0.05), accounted for 82% of the variation in plasma lactate concentration. During intermittent laboratory treadmill running, % VO2peak estimated from heart rate was 17% higher than the value derived from the measured VO2 (79.7 +/- 2.2% and 69.0 +/- 2.5% VO2peak respectively; P< 0.001). The %VO2peak was estimated with reasonable accuracy during continuous treadmill running (5% error). We conclude that changes in exercise intensity based on measurements of heart rate and a time-motion analysis of court movement patterns explain the variation in lactate concentration observed during singles tennis, and that measuring heart rate during play, in association with preliminary fitness tests to estimate VO2, will overestimate the aerobic response.

A comparison of the high and low backspin backhand drives in tennis using different grips.

Three-dimensional, high-speed cinematography was used to compare backspin backhand techniques of high performance players hitting low (5.4 cm below hip height) and high (41.6 cm above hip height) bouncing balls using their preferred method of holding the racket (eastern backhand or continental grip: hand generally on top of the handle) and non-preferred ('behind the handle') grip. The Direct Linear Transformation method was used for three-dimensional space reconstruction from two-dimensional images recorded from laterally placed phase-locked cameras operating at 200 Hz. The only significant differences (P < 0.05) caused by the change in grip were that the ball was impacted further in front of the body when using the non-preferred grip, and a lower peak racket-shoulder speed was recorded for a high bouncing ball when using the non-preferred grip. Irrespective of the type of grip, the players significantly modified (P < 0.01) their technique to hit a high bouncing ball by adopting a more upright trunk, more rotated shoulder alignment (racket shoulder pointing more towards opponent), a larger front knee angle and a more abducted upper arm. Hitting a high ball was also characterized by a less inclined approach trajectory of the racket, a more vertical racket-face and a different speed profile for the segments of the upper limb and racket.