Neuroprotection by anaesthetics in rodent models of traumatic brain injury: a systematic review and network meta-analysis.

BACKGROUND: Anaesthetic neuroprotection in the setting of traumatic brain injury (TBI) remains unproved and is based upon the results in preclinical experiments. Here, we sought to synthesise the results in rodent models of TBI, and to evaluate the effects of publication bias, experimental manipulation, and poor study quality on the effect estimates. METHODS: After a systematic review, we used pairwise meta-analysis to estimate the effect of anaesthetics, opioids, and sedative-hypnotics on neurological outcome, and network meta-analysis to compare their relative efficacy. We sought evidence of bias related to selective publication, experimental manipulation, and study quality. RESULTS: Sixteen studies, involving 32 comparisons, were included (546 animals). The treatment improved the neurological outcomes by 35%; 95% confidence interval: 26-44%; P<0.001. The statistical heterogeneity was small (12%), but the 95% prediction interval for the estimate was wide (15-56%). The statistical power was low: 61% (90% confidence interval: 22-86%). The small sample size in the studies was a serious shortcoming reducing the statistical heterogeneity and obscuring differences in outcome between drugs and between experimental conditions. CONCLUSIONS: Anaesthetics do provide neuroprotection in rodent models of TBI. The effect-size estimates do not appear to be exaggerated by selective publication, experimental manipulation, or study design. The main shortcoming of the included studies were small sample sizes leading to low power and imprecision, which precluded the network meta-analysis from providing a meaningful ranking for efficacy amongst the drugs. Reliable preclinical investigations of neuroprotection by anaesthetics will require larger sample sizes.

Point-of-care paediatric gastric sonography: can antral cut-off values be used to diagnose an empty stomach?

BACKGROUND: Gastric sonography is emerging as a valuable clinical point-of-care tool to assess aspiration risk. A recent study proposed that a single cut-off cross-sectional area (CSA) in the supine position could diagnose an empty stomach in the parturient. This study establishes the sensitivity and specificity of a single CSA cut-off measurement in both supine and right lateral decubitus (RLD) positions in the diagnosis of an empty antrum in paediatric patients. METHODS: Following induction of anaesthesia, antral sonography was performed in supine and RLD positions in 100 fasted paediatric patients prior to upper endoscopic evaluation. Following upper endoscopy, any residual stomach content was suctioned under direct visualization and antral sonography was immediately performed. Antral CSA values were compared using Wilcoxon signed rank test. Receiver operator characteristic (ROC) curves were plotted to estimate the discriminating power of antral sonography position in the diagnosis of an empty antrum. RESULTS: Significant differences were found between pre-suctioned and post-suctioned CSA values in the RLD position. The cut-off CSAs of the empty antrum in the supine and RLD positions were 2.19 cm2 (sensitivity 75%, specificity 36%) and 3.07 cm2 (sensitivity 76%, specificity 67%), respectively. CONCLUSIONS: The RLD position produces the most sensitive and specific CSA cut-off value where an antral CSA of ≤ 3.07 cm2 in the RLD position presents with acceptable performance in the ability to discriminate an empty antrum in paediatric patients over 1 yr of age. As age increases, the sensitivity and specificity of this test increases in the RLD position.

Optimizing Outcomes in Pediatric Renal Transplantation Through the Australian Paired Kidney Exchange Program.

Kidney paired donation (KPD) programs offer the opportunity to enable living kidney donation when immunological and other barriers prevent safe directed donation. Children are likely to require multiple transplants during their lifetime; therefore, high-level histocompatibility and organ quality matching are key priorities. Details are given for a cohort of seven pediatric renal transplantations performed through the Australian Kidney Exchange (AKX), including barriers to alternative transplantation and outcomes after KPD. Reasons for entering the KPD program were preformed donor-specific antibodies to their registered donor in five cases, ABO mismatch, and avoidance of the risk of exposure to hepatitis B virus. Four recipients were highly sensitized. All patients received transplants with organs of lower immunological risk compared with their registered donors. HLA eplet mismatch scores were calculated for donor-recipient pairs; three patients had improved eplet mismatch load with AKX donor compared with their registered donor. All grafts are functioning, with a mean estimated glomerular filtration rate of 77 mL/min/1.73 m2 (range 46-94 mL) and a follow-up range of 8-54 months, and no patient experienced clinical or histological rejection. KPD is a viable strategy to overcome many barriers to living donation for pediatric patients who have an otherwise suitable donor and provides an opportunity to minimize immunological risks.

The kinematics and kinetics of riding a racehorse: A quantitative comparison of a training simulator and real horses.

Movement of a racehorse simulator differs to that of a real horse, but the effects of these differences on jockey technique have not been evaluated. We quantified and compared the kinematics and kinetics of jockeys during gallop riding on a simulator and real horses. Inertial measurement units were attached mid-shaft to the long bones of six jockeys and the sacrum of the horse or simulator. Instrumented stirrups were used to measure force. Data were collected during galloping on a synthetic gallop or while riding a racehorse simulator. Jockey kinematics varied more on a real horse compared to the simulator. Greater than double the peak stirrup force was recorded during gallop on real horses compared to the simulator. On the simulator stirrup forces were symmetrical, whereas on a real horse peak forces were higher on the opposite side to the lead limb. Asymmetric forces and lateral movement of the horse and jockey occurs away from the side of the lead leg, likely a result of horse trunk roll. Jockeys maintained a more upright trunk position on a real horse compared to simulator, with no change in pitch. The feet move in phase with the horse and simulator exhibiting similar magnitude displacements in all directions. In contrast the pelvis was in phase with the horse and simulator in the dorso-ventral and medio-lateral axes while a phase shift of 180° was seen in the cranio-caudal direction indicating an inverted pendulum action of the jockey.

How realistic is a racehorse simulator?

Race jockey training is demanding and technical. Increased horse care costs and demands on time have led to greater availability and use of racehorse simulators during training. Little is known about the accuracy of the simulated movement and therefore how effective they are for developing the desired technique. We quantified and compared sacral rotation and displacement vectors for a racehorse simulator and a real galloping horse. A single inertial measurement unit was placed on the sacrum of six horses (horse) during a training gallop along an all-weather seven furlong gallop and on the highest speed setting 'four' on the simulator. Displacements were calculated in all three axes before being cut into cycles and analysed along with roll and pitch. Displacement and rotation amplitudes were extracted and compared for the horse and simulator. Horse sacral movement parameters were more varied than those recorded on the simulator. The real horse exhibited greater dorso-ventral, medio-lateral and roll amplitude but smaller cranio-caudal displacement amplitude and no difference in pitch amplitude. Displacement trajectory of the simulator when viewed laterally from the left side, was anticlockwise, the opposite direction to that of the real horse leaving the regular use of a simulator during jockey training under question. Use of the racehorse simulator is beneficial to develop specific fitness and to enable physical manipulation into the optimal position. Care must be taken to avoid any detrimental effects of training with the opposite movement trajectory to that experienced during a race. The programming of the simulators may benefit from adaptations to maximise their benefits.

Dopamine treatment during acute hypoxia is neuroprotective in the developing sheep brain.

Dopamine is often used to treat hypotension in preterm infants; these infants are at risk of developing brain injury due to impaired autoregulation and cerebral hypoperfusion. However the effects of dopamine on the immature brain under conditions of cerebral hypoxia are not known. We hypothesized that pretreatment with dopamine would protect the immature brain from injury caused by cerebral hypoxia. Preterm fetal sheep were used to determine the effects of intravenous dopamine on hypoxia-induced brain injury. In 16 pregnant sheep at 90days of gestation (0.6 of term, term=147days) catheters were implanted aseptically into the fetal carotid artery and jugular vein; an inflatable occluder was placed loosely around the umbilical cord for later induction of fetal hypoxemia. At 5days after surgery, dopamine (10µg/kg/min, n=7 fetuses) or saline (n=9 fetuses) was infused for 74h. Two hours after commencing the dopamine/saline infusion, we induced umbilical cord occlusion (UCO) for up to 25min to produce fetal asphyxia. Fetuses were allowed to recover, and brains were collected 72h later for assessment of neuropathology. Un-operated twin fetuses were used as age-matched non-UCO controls (n=8). In UCO+saline fetuses, microglial and apoptotic cell density in the subcortical and periventricular white matter, caudate nucleus and hippocampus was greater than that in age-matched controls; oxidative stress was elevated in the subcortical and periventricular white matter and caudate nucleus compared to that in age-matched controls. In UCO+dopamine fetuses microglial density and oxidative stress in the cerebral white matter and caudate nucleus were not different to that of age-matched controls. Apoptotic cell death was decreased in the cerebral white matter of UCO+dopamine brains, relative to UCO+saline brains. We conclude that pretreatment with dopamine does not exacerbate hypoxia-induced injury in the immature brain and may be neuroprotective because it led to decreased apoptosis, oxidative stress and neuroinflammation in the cerebral white matter and decreased neuroinflammation in the caudate nucleus.

Long-term follow-up of working dogs in New Zealand following pancarpal arthrodesis using dorsal hybrid plating.

AIM: To determine the long-term prognosis for working dogs in New Zealand following pancarpal arthrodesis (PCA) utilising a dorsal hybrid plate. METHODS: Owners of 14 dogs who had a PCA performed as part of a previous study conducted at two small animal veterinary surgical hospitals were contacted via phone and asked to participate in a short survey. RESULTS: A phone survey was completed for seven dogs. Five of the seven dogs had returned to full work, one dog had a moderate persistent lameness that prevented returning to normal work and the remaining dog did not return to normal work for reasons unrelated to the study. Removal of the implants was required in four of seven cases at a median interval of 2 (min 0.5, max 2) years following surgery. One dog had no gait abnormality, but developed an occasional mild lameness after jumping, one dog had a constant gait abnormality with a moderate, persistent lameness, and the remaining five dogs had a constant gait abnormality with a mild, intermittent lameness. All owners contacted were very satisfied with the procedure. CONCLUSIONS: Working dogs undergoing a standardised surgical procedure for unilateral PCA using a hybrid carpal arthrodesis bone plate applied dorsally have a good prognosis for return to work. CLINICAL RELEVANCE: Although this study has a small number of cases, this study provides subjective longer-term follow-up data than previously reported for working dogs that have undergone PCA. Owners should be warned that plate removal may be required in approximately 60% of dogs and additional expenditure should be planned for.

Reflections on HIS 2014: In praise of enthusiasts.

Medical conferences have had a bad press recently. They have been accused of leaving nothing but indifferent research and an enormous carbon footprint. They are also likely to contribute to 'intervention bias' in healthcare, in that the speakers tend to be selected from among the more enthusiastic interventionists and charismatic optimists. But this weakness is arguably also an important strength, for they can be the vehicle by which participants are inspired to innovate and evaluate. It is difficult to predict the outcome of interventions aimed at prevention and control of infection because they involve interactions between people and complex systems, not to mention the invisible agents of infection. Progress therefore depends largely on the empirical approach - trial and error. In this context we need both enthusiasts to inspire trial and sceptics to expose error. Conferences deserve support for encouraging debate between enthusiasts and sceptics, for providing a forum for cross-fertilization between sub-specialties, and for inspiring trainees as well as practitioners. The papers presented in this issue of JHI illustrate the wide range of contemporary challenges in healthcare-associated infection, and summarize the 'state of the art' of infection prevention and control.

Both prolactin (PRL) and a molecular mimic of phosphorylated PRL, S179D-PRL, protect the hippocampus of female rats against excitotoxicity.

Prolactin (PRL) has many functions in the CNS, including neuroprotection. During lactation, the dorsal hippocampus is protected from excitotoxic kainic acid (KA)-induced cellular damage. We have previously reported that systemic pre-treatment with ovine PRL had similar protective effects in female rats. Here, we asked (1) whether intracerebral human PRL (hPRL) would have the same action, (2) because phosphorylated PRL is high in lactation, whether a mimic of phosphorylated hPRL, human prolactin in which the normally phosphorylated serine at position 179 is replaced with an aspartate (S179D-PRL), had similar activity, and (3) what signaling pathways mediated the protective effect. Female ovariectomized (OVX, 1 month) rats were implanted with micro-osmotic pumps connected to unilateral icv cannulae directed at the right lateral ventricle. The pumps delivered 0.10 ng/h of hPRL, S179D-PRL, a combination of hPRL+S179D-PRL, or saline vehicle for 7 days prior to a systemic dose of 7.5mg/kg of KA. Rats were sacrificed 48 h after KA injection. Immunostaining for neuronal nuclei (Neu-N) revealed a significant KA-induced decrease in cell number in the CA1, CA3, and CA4 hippocampal areas of rats (∼55% of control). Treatment with either hPRL or S179D-PRL or the combination prevented the damaging effect of KA in these hippocampal regions (∼95% of corresponding control), but was not completely effective at preventing early seizure-related behaviors such as staring and wet dog shakes. Analysis of signals generated by hPRL and S179D-PRL showed no activation of signal transducer and activation of transcription 5 (Stat5) or other signaling molecules in the hippocampus, but activation of extracellular-regulated kinase (ERK)1/2 in the amygdala. These results support a central protective effect of both PRL forms and suggest that PRL could be exerting its protective action by indirectly modulating input signals to the hippocampus and thus regulating excitability.

Anguillids: conserving a global fishery.

Concern has increased in recent years over the sustainability of anguillid populations worldwide in the face of sustained consumer demand. This is as true of the more numerous tropical species as it is for the better known temperate species. There are, however, critical gaps in knowledge of anguillid biology and ecology, and these hold back measures designed to conserve and enhance anguillid populations, including aquaculture. Developing a more integrated understanding of anguillid biology, and resolving challenges faced by stakeholders and policy makers, is now more urgent than ever. World experts from Japan, the U.S.A., Canada, the European Union and New Zealand led a 3 day event where >200 scientists drawn from >30 countries across the globe converged to share their experience and expert knowledge of anguillids. The session covered the full range of issues affecting anguillid stocks across the globe, and also highlighted advances in the understanding of fundamental aspects of anguillid biology. Overall, 49 oral presentations and 68 posters were presented and, while these were dominated by Anguilla anguilla, Anguilla rostrata and Anguilla japonica, a further eight anguillid species were represented. What was experienced by all was the facilitation of a more integrated understanding of anguillid biology, and how this understanding can interface with the challenges faced by fishermen, consumers, engineers, producers and managers. The highlights are reviewed, important trends in anguillid stocks and research identified and the consensus for future science and management direction reported.

Increase in nephrology advanced trainee numbers in Australia and associated reduction in clinical exposure over the past decade.

BACKGROUND: Advanced training in nephrology should provide broad experience in all aspects of nephrology. In Australia, the Specialist Advisory Committee in Nephrology oversees nephrology training, and recent increases in advanced trainee numbers have led to concern about dilution of training experience. No study has examined variations in clinical exposure for nephrology trainees in Australia. AIM: To assess the changes in nephrology advanced training in Australia with respect to trainee numbers and exposure to patients and procedures over the past 10 years. METHODS: A retrospective study was performed by obtaining all available Royal Australasian College of Physician supervisor reports from 2000 to 2010 to determine differences in clinical exposure and procedures performed by nephrology trainees. RESULTS: Five hundred and forty-two reports were reviewed involving 208 nephrology trainees in Australia across 53 different training sites. In 2000, 22 trainees were undertaking a core clinical year of training. Trainee numbers have steadily risen from 33 in 2004 to 84 in 2010. The greatest increases have occurred in New South Wales, Victoria and Queensland (sixfold, threefold and fivefold increases respectively). Trainee exposure to dialysis patients has gradually decreased in the past decade. The average number per trainee per year in 2000 compared with 2010 were 66 versus 43 (P = 0.02) and 28 versus 16 (P = 0.01) for haemodialysis and peritoneal dialysis respectively. Acute kidney injury cases per trainee showed a gradual nonsignificant reduction over time and average procedural numbers per trainee decreased significantly from 2000 to 2010 with fewer temporary dialysis catheters inserted per year (39 vs 10, P < 0.01) and fewer renal biopsies performed per year (65 vs 41, P < 0.01). The proportion of trainees working in a hospital that does not provide exposure to acute transplantation has steadily increased from 15% in 2003 to 44% in 2010. CONCLUSIONS: There has been a dramatic and significant increase in nephrology advanced trainee numbers over the past decade at a more rapid rate than the growth in dialysis and transplant patient numbers. This study suggests that training experience has diminished over the past decade and supports a 3-year core clinical nephrology training programme in Australia.

Active safety monitoring of newly marketed medications in a distributed data network: application of a semi-automated monitoring system.

We developed a semi-automated active monitoring system that uses sequential matched-cohort analyses to assess drug safety across a distributed network of longitudinal electronic health-care data. In a retrospective analysis, we show that the system would have identified cerivastatin-induced rhabdomyolysis. In this study, we evaluated whether the system would generate alerts for three drug-outcome pairs: rosuvastatin and rhabdomyolysis (known null association), rosuvastatin and diabetes mellitus, and telithromycin and hepatotoxicity (two examples for which alerting would be questionable). Over >5 years of monitoring, rate differences (RDs) in comparisons of rosuvastatin with atorvastatin were -0.1 cases of rhabdomyolysis per 1,000 person-years (95% confidence interval (CI): -0.4, 0.1) and -2.2 diabetes cases per 1,000 person-years (95% CI: -6.0, 1.6). The RD for hepatotoxicity comparing telithromycin with azithromycin was 0.3 cases per 1,000 person-years (95% CI: -0.5, 1.0). In a setting in which false positivity is a major concern, the system did not generate alerts for the three drug-outcome pairs.

Comparison of kinematic symmetry index calculations and the effects of straight and circular trotting.

REASONS FOR PERFORMING STUDY: When assessing lameness in horses, left to right ratios of kinematic parameters are often used to quantify movement symmetry. Different methods of symmetry related measures have been proposed and inertial sensor data was used to evaluate the application of 3 methods of symmetry calculation during straight and circular trotting. OBJECTIVES: To compare 3 sensor based methods of symmetry index calculation to assess; tuber coxae vs. sacrum motion, the effects of circular trotting and effect of using whole trials in place of individual stride calculations. METHODS: Inertial sensors were attached to the sacrum, left and right tuber coxae (LTC/RTC) of 21 non-lame horses. Straight and circular trotting data were collected. Symmetry indices based on vertical movement were calculated for each stride using 3 previously published methods. RESULTS: Method 2 (Fourier analysis) had significantly higher ratio values than method 1 (displacement amplitude ratio; tuber coxae) and methods 1 (displacement amplitude ratio; sacrum) and 3 (difference between LTC/RTC displacement). The effect of circular trotting within methods was highly variable, but was not significantly different between methods. No significant differences were found between whole trial and individual stride calculations. Method 2 when compared to method 1 underestimates the asymmetry present in a non-uniform way due to the use of squared amplitudes. Methods 2 and 3 become less accurate during circular trotting due to changes in amplitude timing. CONCLUSIONS: On the same data substantial differences in symmetry indices are found when using different methods and locations. Further differences exist in accuracy when used on circular data. Interpretation and direct comparison of different symmetry indices should be approached with caution.

Surgical management of suspected congenital luxation of the radial head in three dogs.

CASE HISTORIES: Three dogs, aged between 11 and 20 weeks, were presented with unilateral forelimb lameness, with an associated bony prominence on the lateral elbow. CLINICAL FINDINGS AND DIAGNOSIS: Radiographs revealed a caudolateral luxation of the radial head in all cases, consistent with a diagnosis of suspected congenital luxation of the radial head. Surgical reduction and stabilisation involved open reduction of the radial head, and in two cases the use of a trans articular pin. CLINICAL RELEVANCE: Congenital luxation of the radial head is an uncommon condition that has conflicting reports in the literature regarding its cause, heritability, breed predisposition, treatment and prognosis. The three cases here occurred in young dogs of English Bull Terrier, Jack Russell Terrier, and Staffordshire Bull Terrier breeds. Surgical reduction and stabilisation provided successful outcomes, in all cases. Only six cases of congenital luxation of the radial head managed surgically have previously been reported in the literature.

Assessment of dairy cow locomotion in a commercial farm setting: the effects of walking speed on ground reaction forces and temporal and linear stride characteristics.

Objectives of this study were to determine the effects of walking speed on ground reaction force (GRF) parameters and to explore inter- and intra-individual variability with unsupervised data collection in a commercial farm setting. We used eight high producing loose-housed Holstein Friesian cows consistently scored sound, with no veterinary treatment during the collection period. Cows walked freely (0.52-1.37 m/s) over a five force platform array, twice daily, following milking. GRF data were split into speed categories and temporal and kinetic gait parameters extracted. A general linear model was carried out to determine effects of speed. Variation in parameters between cows is inconsistent, while between speed categories (containing data from multiple cows) the parameters which vary are consistent. Stance and stride time were reduced with increasing speed but no change in peak vertical GRF or duty factor was found. This ability to track parameters within an individual over time aids detection of subtle changes associated with lameness.

Prospective evaluation of pancarpal arthrodesis for carpal injuries in working dogs in New Zealand, using dorsal hybrid plating.

AIM: To determine whether working dogs in New Zealand with carpal injuries and treated with unilateral pancarpal arthrodesis (PCA), using a dorsal hybrid-plating method, are able to return to satisfactory working ability. METHODS: Fourteen working dogs presented to the Veterinary Specialist Group (VSG) and the Massey University Veterinary Teaching Hospital (MUVTH) with carpal injuries were prospectively treated using dorsal hybrid plating. Dogs were eligible if actively involved in farm, hunting or police work. Dogs had a standardised PCA surgical procedure performed, and similar instructions for post-operative care were provided. Dogs were re-evaluated clinically and radiographically at 6 weeks, 6 months, and 12 months after surgery. A questionnaire was completed by 12 owners, to assess each dog's working ability. RESULTS: Twelve months following arthrodesis, 10/12 (83%) dogs could perform most or all duties normally. Eleven owners (92%) reported that the result of the surgery met their expectations, and nine owners (75%) were very satisfied with the outcome of the surgery. No owners were disappointed or very disappointed with the surgical outcome. Post-operative complications requiring surgical removal of the implant occurred in three (25%) dogs. CONCLUSIONS: Unilateral PCA using a standardised surgical procedure and dorsal hybrid plating of carpal injuries has a good prognosis for working dogs in New Zealand to return to work. CLINICAL RELEVANCE: These results may allow veterinarians to provide a more accurate prognosis to owners of working dogs that have debilitating carpal injury.

Evaluation of discriminant analysis based on dorsoventral symmetry indices to quantify hindlimb lameness during over ground locomotion in the horse.

REASONS FOR PERFORMING STUDY: Advances in gait analysis techniques have led to assessment tools that can aid in detecting and quantifying lameness; here, bilateral tubera coxae and pelvic movement during over ground locomotion are compared in order to investigate a practical method to assess hindlimb lameness in the horse. OBJECTIVES: To evaluate which parameters from anatomical landmarks on trunk and proximal hindlimbs are the best indicators of degree and side of hindlimb lameness. METHODS: Fifteen horses (age 11-23 years, 6 nonlame and 9 unilaterally hindlimb lame horses 1/10 to 2/10 lame) were fitted with 4 inertial sensors: tuber sacrale, left and right tubera coxae and withers; 889 strides were collected from 6 trot trials per horse. Horses were assessed for lameness by a qualified equine orthopaedic surgeon from videos. Vertical displacement data for each sensor were used to calculate symmetry indices as well as published Fourier analysis based parameters. Linear discriminant analysis was used to determine the most discriminative parameters for 2 scenarios: grading of severity of lameness and identification of the affected limb. RESULTS: Pelvic energy ratio gave the best indication for the degree of lameness. Directional symmetry index of the tubera coxae sensors yielded the highest discriminative power for identification of the lame limb. CONCLUSIONS AND POTENTIAL RELEVANCE: A good indication of the degree of hindlimb lameness can be obtained from vertical displacement data of the pelvic midline, collected from inertial sensors during over ground locomotion. The trunk mounted inertial sensor system allows for a time efficient collection of a representative database from horses with differing grade and site of lameness in a clinical setting. This is crucial for future work on a robust definition of the best parameters for lameness classification under practical conditions.

Variability of Manson and Leaver locomotion scores assigned to dairy cows by different observers.

The gait scoring system developed by Manson and Leaver was used by five experienced observers to assess the gait of 83 milking Holstein-Friesian cows in a live recording session, and video recordings were made. The agreement between the scores of the observers at the live session, and between each observer's scores at the live session and a video session, were compared at three levels of stringency. The scores of the observers were highly variable at all but the least stringent threshold - whether a cow had a score of less than 3 or 3 or more, that is, whether it was not lame or lame.

Incidence of hepatitis C in drug injectors: the role of homelessness, opiate substitution treatment, equipment sharing, and community size.

A prospective cohort study estimated the incidence of hepatitis C virus (HCV) in drug injectors in South Wales (UK). In total, 286/481 eligible seronegative individuals were followed up after approximately 12 months. Dried blood spot samples were collected and tested for anti-HCV antibody and behavioural data were collected at baseline and follow-up. HCV incidence was 5.9/100 person-years [95% confidence interval (CI) 3.4-9.5]. HCV incidence was predicted by community size [incident rate ratio (IRR) 6.6, 95% CI 2.11-20.51, P = 0.001], homelessness (IRR 2.9, 95% CI 1.02-8.28, P = 0.047) and sharing injecting equipment (IRR 12.7, 95% CI 1.62-99.6, P = 0.015). HCV incidence was reduced in individuals in opiate substitution treatment (IRR 0.34, 95% CI 0.12-0.99, P = 0.047). In order to reduce follow-up bias we used multiple imputation of missing data using switching regression; after imputation estimated HCV incidence was 8.5/100 person-years (95% CI 5.4-12.7). HCV incidence varies with community size, equipment sharing and homelessness are associated with increased HCV incidence and opiate substitution treatment may be protective against HCV.