Epidemiology and Management of invasive infections among people who Use drugs (EMU): protocol for a prospective, multicentre cohort study.

INTRODUCTION: People who inject drugs (PWID) are at risk of invasive infections such as bloodstream infections, endocarditis, osteomyelitis and septic arthritis. Such infections require prolonged antibiotic therapy, but there is limited evidence about the optimal care model to deliver to this population. The Epidemiology and Management of invasive infections among people who Use drugs (EMU) study aims to (1) describe the current burden, clinical spectrum, management and outcomes of invasive infections in PWID; (2) determine the impact of currently available models of care on completion of planned antimicrobials for PWID admitted to hospital with invasive infections and (3) determine postdischarge outcomes of PWID admitted with invasive infections at 30 and 90 days. METHODS AND ANALYSIS: EMU is a prospective multicentre cohort study of Australian public hospitals who provide care to PWIDs with invasive infections. All patients who have injected drugs in the previous six months and are admitted to a participating site for management of an invasive infection are eligible. EMU has two components: (1) EMU-Audit will collect information from medical records, including demographics, clinical presentation, management and outcomes; (2) EMU-Cohort will augment this with interviews at baseline, 30 and 90 days post-discharge, and data linkage examining readmission rates and mortality. The primary exposure is antimicrobial treatment modality, categorised as inpatient intravenous antimicrobials, outpatient antimicrobial therapy, early oral antibiotics or lipoglycopeptide. The primary outcome is confirmed completion of planned antimicrobials. We aim to recruit 146 participants over a 2-year period. ETHICS AND DISSEMINATION: EMU has been approved by the Alfred Hospital Human Research Ethics Committee (Project number 78815.) EMU-Audit will collect non-identifiable data with a waiver of consent. EMU-Cohort will collect identifiable data with informed consent. Findings will be presented at scientific conferences and disseminated by peer-review publications. TRIAL REGISTRATION NUMBER: ACTRN12622001173785; Pre-results.

Gait-specific energetics contributes to economical walking and running in emus and ostriches.

A widely held assumption is that metabolic rate (E(met)) during legged locomotion is linked to the mechanics of different gaits and this linkage helps explain the preferred speeds of animals in nature. However, despite several prominent exceptions, E(met) of walking and running vertebrates has been nearly uniformly characterized as increasing linearly with speed across all gaits. This description of locomotor energetics does not predict energetically optimal speeds for minimal cost of transport (E(cot)). We tested whether large bipedal ratite birds (emus and ostriches) have gait-specific energetics during walking and running similar to those found in humans. We found that during locomotion, emus showed a curvilinear relationship between E(met) and speed during walking, and both emus and ostriches demonstrated an abrupt change in the slope of E(met) versus speed at the gait transition with a linear increase during running. Similar to human locomotion, the minimum net E(cot) calculated after subtracting resting metabolism was lower in walking than in running in both species. However, the difference in net E(cot) between walking and running was less than is found in humans because of a greater change in the slope of E(met) versus speed at the gait transition, which lowers the cost of running for the avian bipeds. For emus, we also show that animals moving freely overground avoid a range of speeds surrounding the gait-transition speed within which the E(cot) is large. These data suggest that deviations from a linear relation of metabolic rate and speed and variations in transport costs with speed are more widespread than is often assumed, and provide new evidence that locomotor energetics influences the choice of speed in bipedal animals. The low cost of transport for walking is probably ecologically important for emus and ostriches because they spend the majority of their active day walking, and thus the energy used for locomotion is a large part of their daily energy budget.

Energetics of bipedal running. I. Metabolic cost of generating force.

Similarly sized bipeds and quadrupeds use nearly the same amount of metabolic energy to run, despite dramatic differences in morphology and running mechanics. It has been shown that the rate of metabolic energy use in quadrupedal runners and bipedal hoppers can be predicted from just body weight and the time available to generate force as indicated by the duration of foot-ground contact. We tested whether this link between running mechanics and energetics also applies to running bipeds. We measured rates of energy consumption and times of foot contact for humans (mean body mass 78.88 kg) and five species of birds (mean body mass range 0.13-40.1 kg). We find that most (70-90%) of the increase in metabolic rate with speed in running bipeds can be explained by changes in the time available to generate force. The rate of force generation also explains differences in metabolic rate over the size range of birds measured. However, for a given rate of force generation, birds use on average 1.7 times more metabolic energy than quadrupeds. The rate of energy consumption for a given rate of force generation for humans is intermediate between that of birds and quadrupeds. These results support the idea that the cost of muscular force production determines the energy cost of running and suggest that bipedal runners use more energy for a given rate of force production because they require a greater volume of muscle to support their body weight.