Metastatic renal cell carcinoma to the brain: optimizing patient selection for gamma knife radiosurgery.

INTRODUCTION: The effects of single-fraction gamma knife radiosurgery (sf-GKRS) on patients with renal cell carcinoma (RCC) brain metastases (BM) in the era of targeted agents (TA) and immune checkpoint inhibitors (ICI) are insufficiently studied. METHODS AND MATERIALS: Clear cell metastatic RCC patients treated with sf-GKRS due to BM in 2005-2014 at three European centres were retrospectively analysed (n = 43). Median follow-up was 56 months. Ninety-five percent had prior nephrectomy, 53% synchronous metastasis and 86% extracranial disease at first sf-GKRS. Karnofsky performance status (KPS) ranged from 60 to 100%. Outcome measures were overall survival (OS), local control (LC) and adverse radiation effects (ARE). RESULTS: One hundred and ninety-four targets were irradiated. The median number of targets at first sf-GKRS was two. The median prescription dose was 22.0 Gy. Thirty-seven percent had repeated sf-GKRS. Eighty-eight percent received TA. LC rates at 12 and 18 months were 97% and 90%. Median OS from the first sf-GKRS was 15.7 months. Low serum albumin (HR for death 5.3), corticosteroid use pre-sf-GKRS (HR for death 5.8) and KPS < 80 (HR for death 9.1) were independently associated with worse OS. No further prognostic information was gleaned from MSKCC risk group, synchronous metastasis, age, number of BM or extracranial metastases. Other prognostic scores for BM radiosurgery, including DS-GPA, renal-GPA, LLV-SIR and CITV-SIR, again, did not add further prognostic value. ARE were seldom symptomatic and were associated with tumour volume, 10-Gy volume and pre-treatment perifocal oedema. ARE were less common among patients treated with TA within 1 month of sf-GKRS. CONCLUSIONS: We identified albumin, corticosteroid use and KPS as independent prognostic factors for sf-GKRS of clear cell RCC BM. Studies focusing on the prognostic significance of albumin in sf-GKRS are rare. Further studies with a larger number of patients are warranted to confirm the above analytical outcome. Also, in keeping with previous studies, our data showed optimal rates of local tumour control and limited toxicity post radiosurgery, rendering GKRS the tool of choice in the management of RCC BM.

Gambling harm is everybody's business: A public health approach and call to action.

There is a growing consensus that gambling is a public health issue and that preventing gambling related harms requires a broad response. Although many policy decisions regarding gambling are made at a national level in the UK, there are clear opportunities to take action at local and regional levels to prevent the negative impacts on individuals, families and local communities. This response goes beyond the statutory roles of licencing authorities to include amongst others the National Health Service (NHS), the third sector, mental health services, homelessness and housing services, financial inclusion support. As evidence continues to emerge to strengthen the link between gambling and a wide range of risk factors and negative consequences, there is also a strong correlation with health inequalities. Because the North of England experiences increasing health inequalities, it offers an opportunity as a specific case study to share learning on reducing gambling-related harms within a geographic area. This article describes an approach to gambling as a public health issue identifying it as needing a cross-cutting, systemwide multisectoral approach to be taken at local and regional levels. Challenges at national and local levels require policy makers to adopt a 'health in all policy' approach and use the best evidence in their future decisions to prevent harm. A whole systems approach which aims to reduce poverty and health inequalities needs to incorporate gambling harm within place-based planning and draws on the innovative opportunities that exist to engage local stakeholders, builds local leadership and takes a collaborative approach to tackling gambling-related harms. This whole systems approach includes the following: (1) understanding the prevalence of gambling related harms with insights into the consequences and how individuals, their family and friends and wider community are affected; (2) ensuring tackling gambling harms is a key public health commitment at all levels by including it in strategic plans, with meaningful outcome measures, and communicating this to partners; (3) understanding the assets and resources available in the public, private and voluntary sectors and identifying what actions are underway; (4) raising awareness and sharing data, developing a compelling narrative and involving people who have been harmed and are willing to share their experience; (5) ensuring all regulatory authorities help tackle gambling-related harms under a 'whole council' approach.

Adaptive radiosurgery based on two simultaneous dose prescriptions in the management of large renal cell carcinoma brain metastases in critical areas: Towards customization.

BACKGROUND: The long-term benefits of local therapy in metastatic renal cell carcinoma (mRCC) have been widely documented. In this context, single fraction gamma knife radiosurgery (SF-GKRS) is routinely used in the management of brain metastases. However, SF-GKRS is not always feasible due to volumetric and regional constraints. We intend to illustrate how a dose-volume adaptive hypofractionated GKRS technique based on two concurrent dose prescriptions termed rapid rescue radiosurgery (RRR) can be utilized in this particular scenario. CASE DESCRIPTION: A 56-year-old man presented with left-sided hemiparesis; the imaging showed a 13.1 cc brain metastasis in the right central sulcus (Met 1). Further investigation confirmed the histology to be a metastatic clear cell RCC. Met 1 was treated with upfront RRR. Follow-up magnetic resonance imaging (MRI) at 10 months showed further volume regression of Met 1; however, concurrently, a new 17.3 cc lesion was reported in the boundaries of the left frontotemporal region (Met 2) as well as a small metastasis (<1 cc) in the left temporal lobe (Met 3). Met 2 and Met 3 underwent RRR and SF-GKRS, respectively. RESULTS: Gradual and sustained tumor ablation of Met 1 and Met 2 was demonstrated on a 20 months long follow- up. The patient succumbed to extracranial disease 21 months after the treatment of Met 1 without evidence of neurological impairment post-RRR. CONCLUSION: Despite poor prognosis and precluding clinical factors (failing systemic treatment, eloquent location, and radioresistant histology), RRR provided optimal tumor ablation and salvage of neurofunction with limited toxicity throughout follow-up.

Effect of weaning age on growth, mammary gland development, and immune function in Holstein Friesian calves fed conserved alfalfa (FiberStart).

This study aimed to evaluate intake, body growth, and the development of the rumen, mammary gland, and immune system in Holstein Friesian calves reared for 100 d on the commercially available feed FiberStart (conserved alfalfa, Medicago sativa; Fiber Fresh Feeds Ltd., Reporoa, New Zealand) and fed calf milk replacer (CMR) for either 56 or 91 d. Eighty calves (40 bulls and 40 heifer calves) were reared indoors in groups (n = 5 of the same sex/pen). All calves were fed 4 L of CMR/d (175 g/L of CMR) in 2 feeds/d for the first 10 d and then 1 feed/d until d 49 or 84. The calves were gradually weaned by d 56 (earlier weaned; n = 8 pens) and d 91 (later weaned; n = 8 pens). All calves were fed FiberStart ad libitum as the only solid feed source from d 1 to 100 of the study. Irrespective of treatment, all calves had similar body weights at d 0 (40.9 ± 3.0 kg) and d 49 (74.2 ± 5.1 kg) of the study. Calf sex had no effect on intake, growth, blood, and immune system parameters. Earlier-weaned calves consumed 18% more solid feed dry matter but had 16% lower body weight gain (28.9 vs. 38.5 kg, respectively) from d 56 to 100 relative to later-weaned calves, resulting in different body weight at 100 d (104 vs. 121 ± 1.3 kg). Although earlier-weaned calves could compensate for the loss of CMR dry matter and crude protein intake from d 56 to 100 by increasing forage intake, they were unable to compensate for the loss of energy from the CMR by increasing solid feed consumption. Plasma ß-hydroxybutyrate concentrations were 52% greater in earlier-weaned calves than in later-weaned calves at d 84, indicating greater metabolic activity of the rumen wall. The duration of CMR feeding had no influence on humoral or cell-mediated immune functions of the calves, as evidenced by a lack of effect on antivaccine antibody responses as well as on immune gene expression. Earlier- versus later-weaned heifer calves had 5% lower mammary gland mass, indicating that greater energy supply increased mammary mass. The results of this experiment demonstrate the ability to artificially rear dairy calves on a conserved alfalfa as the only solid feed. Furthermore, earlier weaning off CMR promotes solid feed intake and an associated increase in blood ß-hydroxybutyrate, an indicator of rumen development, but increasing the duration of CMR feeding improves growth and mammary gland mass by d 100. The implications of these findings on lifetime growth, health, and milk production in dairy heifers warrant further investigation.

Putting the public (back) into public health: leadership, evidence and action.

There is a strong evidence-based rationale for community capacity building and community empowerment as part of a strategic response to reduce health inequalities. Within the current UK policy context, there are calls for increased public engagement in prevention and local decision-making in order to give people greater control over the conditions that determine health. With reference to the challenges and opportunities within the English public health system, this essay seeks to open debate about what is required to mainstream community-centred approaches and ensure that the public is central to public health. The essay sets out the case for a reorientation of public health practice in order to build impactful action with communities at scale leading to a reduction in the health gap. National frameworks that support local practice are described. Four areas of challenge that could potentially drive an implementation gap are discussed: (i) achieving integration and scale, (ii) effective community mobilization, (iii) evidencing impact and (iv) achieving a shift in power. The essay concludes with a call to action for developing a contemporary public health practice that is rooted in communities and offers local leadership to strengthen local assets, increase community control and reduce health inequalities.

Equal North: how can we reduce health inequalities in the North of England? A prioritization exercise with researchers, policymakers and practitioners.

BACKGROUND: The Equal North network was developed to take forward the implications of the Due North report of the Independent Inquiry into Health Equity. The aim of this exercise was to identify how to reduce health inequalities in the north of England. METHODS: Workshops (15 groups) and a Delphi survey (3 rounds, 368 members) were used to consult expert opinion and achieve consensus. Round 1 answered open questions around priorities for action; Round 2 used a 5-point Likert scale to rate items; Round 3 responses were re-rated alongside a median response to each item. In total, 10 workshops were conducted after the Delphi survey to triangulate the data. RESULTS: In Round 1, responses from 253 participants generated 39 items used in Round 2 (rated by 144 participants). Results from Round 3 (76 participants) indicate that poverty/implications of austerity (4.87 m, IQR 0) remained the priority issue, with long-term unemployment (4.8 m, IQR 0) and mental health (4.7 m, IQR 1) second and third priorities. Workshop 3 did not diverge from findings in Round 1. CONCLUSIONS: Practice professionals and academics agreed that reducing health inequalities in the North of England requires prioritizing research that tackles structural determinants concerning poverty, the implications of austerity measures and unemployment.

Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy.

BACKGROUND: The effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single-session stereotactic radiosurgery (SRS) and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy. PATIENTS AND METHODS: Patients were included if MBMs were treated with single-session SRS within 3 months of receiving systemic therapy. The primary end point of this study was distant MBM control. Secondary end points were local MBM control defined as a >20% volume increase on follow-up MRI, systemic progression-free survival, overall survival (OS) from both SRS and cranial metastases diagnosis, and neurotoxicity. Images were reviewed alongside two neuro-radiologists at our institution. RESULTS: Ninety-six patients were treated to 314 MBMs over 119 SRS treatment sessions between January 2007 and August 2015. No significant differences were noted in age (P = 0.27), gender (P = 0.85), treated gross tumor volume (P = 0.26), or the diagnosis-specific graded prognostic assessment (P = 0.51) between the treatment cohorts. Twelve-month Kaplan-Meier (KM) distant MBM control rates were 38%, 21%, 20%, 8%, and 5% (P = 0.008) for SRS with anti-PD-1 therapies, anti-CTLA-4 therapy, BRAF/MEKi, BRAFi, and conventional chemotherapy, respectively. No significant differences were noted in the KM local MBM control rates among treatment groups (P = 0.25). Treatment with anti-PD-1 therapy, anti-CTLA-4 therapy, or BRAF/MEKi significantly improved OS on both univariate and multivariate analyses when compared with conventional chemotherapy. CONCLUSION: In our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.

Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy.

BACKGROUND: The anti-programmed death-1 (anti-PD-1) therapy nivolumab has significant clinical activity in patients with metastatic melanoma. However, little is known about the safety and outcomes in patients receiving anti-PD-1 therapy and stereotactic radiation for the treatment of brain metastases (BMs). PATIENTS AND METHODS: Data were analyzed retrospectively from two prospective nivolumab protocols enrolling 160 patients with advanced resected and unresectable melanoma at a single institution. Patients were included if BMs were diagnosed and treated with stereotactic radiation within 6 months of receiving nivolumab. The primary end point of this study was neurotoxicity; secondary end points included BM control and survival. RESULTS: Twenty-six patients with a total of 73 BMs treated over 30 sessions were identified. Radiation was administered before, during and after nivolumab in 33 lesions (45%), 5 lesions (7%), and 35 lesions (48%), respectively. All BMs were treated with stereotactic radiosurgery (SRS) in a single session except 12 BMs treated with fractionated stereotactic radiation therapy, nine of which were in the postoperative setting. One patient experienced grade 2 headaches following SRS with symptomatic relief with steroid treatment. No other treatment-related neurologic toxicities or scalp reactions were reported. Eight (11%) local BM failures with a ≥20% increase in volume were noted. Of these lesions, hemorrhage was noted in 4, and edema was noted in 7. Kaplan-Meier estimates for local BM control following radiation at 6 and 12 months were 91% and 85%, respectively. Median overall survival (OS) from the date of stereotactic radiation and nivolumab initiation was 11.8 and 12.0 months, respectively, in patients receiving nivolumab for unresected disease (median OS was not reached in patients treated in the resected setting). CONCLUSIONS: In our series, stereotactic radiation to melanoma BMs is well tolerated in patients who received nivolumab. BM control and OS appear prolonged compared with standard current treatment. Prospective evaluation is warranted.

The effects of depriving feed to facilitate transport and slaughter in sheep--a case study of cull ewes held off pasture for different periods.

AIM: To determine the ability of sheep to mobilise their body reserves after being deprived of feed prior to transport for slaughter. METHODS: A total of 240 3- and 4-year-old cull ewes were held off pasture for 0, 9, 18 or 30 hours (n=60 per group) then transported 1 hour by road, unloaded and washed, held in lairage for 3 hours then slaughtered. Blood samples were collected from a subsample of 60 unfasted ewes 1 week earlier, and from all ewes at exsanguination to determine concentrations of serum metabolites indicative of adaptation to fasting. In addition, several attributes of carcass quality were measured. RESULTS: At slaughter, increased time off pasture prior to transport resulted in no change in glucose concentrations in serum (p=0.140). There were differences (p<0.001) between the group fasted for 30 compared with 0 hours in mean concentrations of free fatty acids (0.98 (SD 0.32) vs. 0.58 (SD 0.23) mmol/L), ß-hydroxybutyrate (0.69 (SD 0.17) vs. 0.42 (SD 0.11) mmol/L), triglycerides (0.29 (min 0.13, max 0.83) vs. 0.22 (min 0.06, max 0.96) mmol/L) and urea (10.17 (SD 1.80) vs. 6.94 (SD 2.03) mmol/L). Different periods of feed deprivation had no effect (p>0.05) on carcass weights (mean 22.7, min 13.2, max 32.9 kg) or dressing out percentages (mean 40.9, min 27, max 49%). Meat ultimate pH was unaffected (p>0.05) by the period of feed deprivation but meat became darker (p<0.05) and had reduced redness (p<0.001) with increasing time off feed. CONCLUSIONS: The results suggest that sheep in variable body condition adapted to the periods of feed deprivation by mobilising their energy reserves without any evidence of metabolic depletion (e.g. depleted blood glucose or high meat pH). However, being deprived of feed they probably experience a degree of hunger.

Observations on the phenotypic relationships between anti-CarLA salivary IgA antibody response, nematode infection levels and growth rates in farmed red (Cervus elaphus) and wapiti hybrid deer (Cervus elaphus canadensis).

Nematode parasites are one of the most significant production limiting factors in farmed deer in New Zealand. One long term strategy to reduce reliance on anthelmintics is to select deer that develop resistance to parasites. It has been shown in sheep that secretory antibody (IgA) in the saliva against a Carbohydrate Larval Antigen (CarLA) on infective larvae (L3) of a wide range of gastro-intestinal nematodes protects against reinfection. This paper describes a longitudinal slaughter study undertaken to measure anti-CarLA IgA antibody (CarLA-IgA) levels in the saliva of 5-12 month old farmed red and wapiti-cross-red deer (wapx) grazed together and to attempt to relate these levels to parasite burdens and productivity. The study showed that salivary CarLA-IgA levels peaked in June (late autumn) and October (mid spring), but the levels in wapx deer were significantly lower than in red deer. Over the May-December period 55% of red deer had CarLA-IgA values ≥2 units compared with 26% of wapx deer and over this period red deer had consistently lower adult abomasal parasite burdens than wapx deer. The average number of adult abomasal nematodes was significantly lower at each slaughter from May to December for all deer with CarLA-IgA ≥2 units vs <2 units. There were no demonstrable correlations with liveweight gain in these small groups of deer.

Reduced efficacy of moxidectin and abamectin in young red deer (Cervus elaphus) after 20 years of moxidectin pour-on use on a New Zealand deer farm.

A study was undertaken on weaned 4-5 month old farmed red deer to test the efficacy of moxidectin and abamectin anthelmintics, given by three different routes of administration, compared with an untreated control. Faecal samples were collected on days 0, 7 and 14 for a faecal egg count reduction test (FECRT), blood samples were collected on days 0, 0.5, 1, 2, 3, 5, 7, 10 and 14 for pharmacokinetics, and the deer were killed on days 14 or 15 for total nematode count. The control group averaged 1264 adult Ostertagia-type nematode parasite species and treatment efficacy was 77.4% for moxidectin injection, 26% for oral moxidectin and 27.6% for pour-on moxidectin, while the treatment efficacy was 72.4% for abamectin injection, 70.1% for oral abamectin (Hi-Mineral) and 34.1% for pour-on abamectin. Both moxidectin and abamectin injections were significantly more efficacious than their equivalent pour-ons. There was a significant difference in efficacy between oral abamectin (Hi-Mineral) and oral moxidectin (P<0.01). The control group averaged 2956 adult lungworm (Dictyocaulus eckerti) and 50 Oesophagostomum venulosum in the large intestine and treatment efficacy against these nematodes was 100% for all treatments. There were negligible numbers of other gastro-intestinal nematodes. At slaughter, there was a significant correlation (P=0.02) between FEC and Ostertagia-type nematodes in the untreated controls. Relatively few eggs were found in faeces from treated animals at 7 and 14 days post-treatment despite significant worm burdens in all six treatment groups, suggesting egg-laying suppression in resistant nematodes, and all three different FECRT calculations tended to overestimate the efficacy of the treatments compared with actual nematode counts. Peak plasma concentrations (Cmax) for both actives were measured 12h after treatment for injection and oral and at 5 days for pour-on. Cmax (ng/ml) for moxidectin injection, oral and pour-on were 71.8, 8.3 and 0.4, respectively, and for abamectin injection, oral and pour-on were 62.1, 30.3 and 10.0, respectively. Area under the curve (AUC) estimates for moxidectin injection, oral and pour-on were 106.6, 12.9 and 6.1, respectively, and for abamectin injection, oral and pour-on were 162.7, 57.5 and 74.3, respectively. The results demonstrate that significant anthelmintic resistance to moxidectin and abamectin is present on this deer farm. However, the injection was the most effective route of administration in young deer for both anthelmintics, although <80% efficacious. We conclude that the FECRT is unreliable in deer when anthelmintic resistance is present.

Effects of immunization against androstenedione or bone morphogenetic protein 15 (BMP15) on reproductive performance in sheep.

Partial neutralization of bone morphogenetic protein 15 (BMP15) bioactivity by immunization is known to increase ovulation rate in sheep. However, it remains uncertain whether BMP15 vaccination would be a suitable procedure for increasing lambing rate. The aim of this study was to compare the efficacy of a BMP15 vaccination treatment on lamb production to that of commercially-available androstenedione-based vaccines that are used for this purpose. Ewes were immunized for 3 yr against androstenedione, BMP15, or no antigen (control). Vaccination with androstenedione or BMP15 altered (P < 0.05) ovulation rate as well as litter size at midpregnancy, birth, and weaning compared with controls. No differences were detected in the proportions of ewes conceiving in the first cycle or partial failure of multiple ovulations. Both gender and litter size affected birth weight of the lamb (P < 0.05), but no effect of treatment was found. Growth rate was significantly affected (P < 0.05) by gender, birth weight, and the number of lambs raised, but not treatment. In conclusion, immunization against either androstenedione or BMP15 increased ovulation rate. Androstenedione vaccination also increased the number of lambs weaned (P < 0.05). Bone morphogenetic protein 15 vaccination altered the pattern of the number of lambs weaned, but no increase in lamb production was observed as more ewes produced zero or three lambs. Overall, androstenedione or BMP15 vaccination did not significantly affect embryo or fetal survival or lamb performance independently of the effects of these treatments on ovulation rate.

An invisible enemy: Panton-Valentine leukocidin Staphylococcus aureus on deployed troops.

Over the last seven years Primary Care establishments in the Royal Navy and Royal Marines have dealt with a number of severe and fatal infections caused by Panton-Valentine leukocidin (PVL) producing Staphylococcus aureus, and appear to be seeing these infections more commonly than their civilian colleagues. This retrospective study looked at the levels of PVL S. aureus isolated in deployed personnel during Op HERRICK 14 to determine if the levels seen in British military troops are higher than the national average. We found that the percentage of PVL positive S. aureus isolates sent to the UK HPA reference laboratory from the Camp Bastion laboratory during OP Herrick 14 was 41%, considerably higher rate than the UK civilian rate. Future research, including a larger study into the carriage levels of PVL S. aureus in the military will hopefully shed more light on the spread and transmission of this potentially deadly bacterium.

Prolonged survival after episiotomy recurrence of cervical cancer complicating pregnancy.

BACKGROUND: We report a case of recurrent cervical cancer in an episiotomy scar and the late treatment-related sequelae. CASE: Cervical cancer was diagnosed following a vaginal delivery, and was treated with surgery and radiotherapy. The patient developed a recurrence in her episiotomy scar, and was treated with chemoradiation. She remains without evidence of disease ten years later. CONCLUSION: Successful treatment of recurrent cervical cancer with chemoradiation is possible, but may be associated with significant normal tissue toxicity.

An automated in-line clinical mastitis detection system using measurement of conductivity from foremilk of individual udder quarters.

AIM: To assess a novel method for automatic in-line detection of clinical mastitis. METHODS: For a brief period at the start of milking for each cow, electrical conductivity of foremilk was measured for each quarter in turn, using a single sensor installed in the long milk tube (LMT) about 1.5 m downstream from the milking-machine claw. Sequential separation of flow between udder quarters was achieved by control of pulsation to individual teat cups within a conventional cluster. The ratio of conductivity values between quarters was used as an indicator of mastitis status. The concept was evaluated initially in a pilot trial in a 200-cow herd milked in a 23-stall swing-over herringbone milking parlour. It was then tested rigorously in a field trial in a 640-cow herd milked in a 50-stall rotary milking parlour. Both trials were conducted in the Waikato region of New Zealand. In the latter trial, sensor results were compared with visual inspection of a commercial in-line mastitis filter fitted to each milking unit. These filters were inspected for clots immediately after every cow's milking, for 3 weeks. The dataset of approximately 27,000 individual milkings was tested against several published or potential alternative 'gold standards' for diagnosing clinical mastitis. RESULTS: In the pilot trial, 12-14 clinical events were detected out of 19 true clinical quarters, with a false-alert rate of between three and five false electrical-conductivity alerts per 1,000 individual milkings. In the more rigorous field trial, sensitivity ranged from 68 to 88%, and the false-alert rate (false-alert episodes per 1,000 individual milkings) ranged from 2.3 to 7.0. CONCLUSION: The novel clinical mastitis detection system, based on separation of the flow and measurement of electrical conductivity from foremilk of individual udder quarters, has the potential to provide a new tool for helping farmers to monitor clinical mastitis in herds milked with conventional clusters.

The presenting complaints of low income adults for emergency dental care: an analysis of 35,000 episodes in Victoria, Australia.

OBJECTIVE: This study examined the mix of presenting problems faced by a large diverse dental service treating low-income Australian adults and provides a basis for communities to understand and manage demand for dental services. DESIGN: A retrospective analysis in a state-wide multi-centre dental health service. Data for all patients (in all public adult dental clinics in the state of Victoria during May-Aug 2005) who used the emergency services in a 12 week period were recorded and analysed. A triage question tree was developed and embedded into a neural network based computer triage tool. RESULTS: Approximately 52% of low income adults presenting for emergency treatment required treatment on the day of triage. The main problem was with natural teeth (89.6%). Of those with natural teeth problems, 41.3% had pain disturbing their sleep patterns and 14.7% had experienced a swelling. Metropolitan patients accessed the services 2.3 times more than rural patients. CONCLUSION: These data clearly highlight that there is significant opportunity to reduce nearly 48% of on-day demand for emergency dental care through the application of appropriately clinical based triage.

Efficacy, immune responses and side-effects of vaccines against Johne's disease in young red deer (Cervus elaphus) experimentally challenged with Mycobacterium avium subsp paratuberculosis.

AIMS: To test the efficacy of a commercially available and an experimental vaccine against Johne's disease in young red deer (Cervus elaphus), using experimental challenge with live virulent Mycobacterium avium subsp paratuberculosis (M. ptb), measure injection-site reactions, and assess the effects of vaccination and challenge on results of subsequent skin tests and ancillary blood tests for bovine tuberculosis (Tb). METHODS: Ninety 6-8-week-old red deer fawns were randomly allocated to three equal groups of 30, and received either a 1-ml S/C injection of either a commercially available whole-cell killed vaccine with a mineral-oil adjuvant (COM), or a live attenuated M. ptb experimental vaccine with a lipid adjuvant (EXP), or were unvaccinated controls. Ten weeks later (Week 10), all 90 fawns received an oral challenge with approximately 10(8) cfu of a bovine strain of M. ptb daily for 4 days. The fawns were regularly weighed and monitored for clinical signs of Johne's disease, and regularly blood-sampled and tested for antibodies to M. ptb, using the Paralisa test, an IgG1 ELISA, and for antibodies to Mycobacterium bovis, using a similar test. A mid-cervical tuberculin skin test (MCT) was administered at Week 23, and comparative cervical skin tests (CCTs) were administered at Weeks 37 and 57. All animals were electively killed at Week 59, injection sites inspected, gastrointestinal tracts examined for gross lesions, and samples taken for culture and histopathology. RESULTS: There were no clinical cases of Johne's disease but, at slaughter, more gross lesions in intestinal lymph nodes were observed in Control (20%) than COM animals (0%; p<0.05). This latter group also had less severe histopathological lesions in samples of intestines and lymph nodes compared with the Control group (p<0.05), but not deer in the EXP group. Over 89% of deer in all three groups were shown by culture to be infected with M. ptb, while only 21-33% of faecal samples were culture-positive. Time to positive culture was longer for COM vs EXP and Control groups (p<0.01), reflecting fewer M. ptb organisms in samples from the ileocaecal valve (ICV) in that group. Almost all (>or=90%) deer reacted to the MCT at Week 23, and there were no significant differences between groups. One or two deer in each group were classified as Tb reactors to the CCT at Week 37, and none were classified as Tb reactors to the CCT at Week 57. At the time of challenge, over 50% of deer in the COM group were classified as positive (9/28) or suspicious (7/28) for M. ptb antibodies in the Paralisa test, one animal in the EXP group was classified as suspicious, and all the Controls were negative. From Week 23 to the end of the trial, 25/28 (89%) deer in the COM group were Paralisa-positive or -suspicious. The proportion of animals in the EXP and Control groups that were Paralisa-positive peaked at Week 39 (60% and 55%, respectively). The majority of deer in the COM group had significant levels of antibody to M. bovis 10 weeks after vaccination, while the proportion of M. bovis-antibody positive Control deer rose gradually throughout the trial, reaching 23/30 (77%) at slaughter. Injection-site lesions in COM deer ranged from 10-38 mm in diameter 4 weeks after vaccination, and then resolved. Minimal injection-site lesions were observed in EXP deer. At slaughter, 14 months after vaccination, 19/28 deer in the COM group had 5-15-mm nodules that were easily trimmed from the carcass. CONCLUSIONS: The experimental challenge with M. ptb produced subclinical Johne's disease in the majority of deer, but did not cause any clinical disease. The number and severity of gross and microscopic lesions was significantly reduced in the COM compared with Control and EXP groups; vaccination of the EXP group did not appear to give significant protection. Deer vaccinated with the commercial vaccine are likely to give a false-positive reaction to the MCT but should have an avian reaction to the CCT, if it is carried out >12 months after vaccination. Most of the deer vaccinated with the commercial vaccine produced significant levels of antibodies against both M. ptb and M. bovis, which interfered with ancillary Tb tests. If this vaccine or similar oil-based vaccines are used on deer farms in the future, it may be advisable to only vaccinate animals destined for slaughter, that would not need to be Tb-tested, but would be 'works-monitored' for evidence of Tb instead.

Length of hospitalisation for people with severe mental illness.

BACKGROUND: In high income countries, over the last three decades, the length of hospital stays for people with serious mental illness has reduced drastically. Some argue that this reduction has led to revolving door admissions and worsening mental health outcomes despite apparent cost savings, whilst others suggest longer stays may be more harmful by institutionalising people to hospital care. OBJECTIVES: To determine the clinical and service outcomes of planned short stay admission policies versus a long or standard stay for people with serious mental illnesses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register of trials (July 2007). SELECTION CRITERIA: We included all randomised trials comparing planned short with long/standard hospital stays for people with serious mental illnesses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated fixed effects weighted mean differences (WMD). MAIN RESULTS: We included six relevant trials. We found no significant difference in hospital readmissions between planned short stays and standard care at one year (n=651, 4 RCTs, RR 1.26 CI 1.0 to 1.6). Short hospital stay did not confer any benefit in terms of 'loss to follow up compared with standard care (n=453, 3 RCTs, RR 0.87 CI 0.7 to 1.1). There were no significant differences for the outcome of 'leaving hospital prematurely' (n=229, 2 RCTs, RR 0.77 CI 0.3 to 1.8). More post-discharge day care was given to participants in the short stay group (n=247, 1 RCT, RR 4.52 CI 2.7 to 7.5, NNH 3 CI 2 to 6) and people from the short stay groups were more likely to be employed at two years (n=330, 2 RCTs, RR 0.61 CI 0.5 to 0.8, NNT 5 CI 4 to 8). Economic data were few but, once discharged, costs may be more for those allocated to an initial short stay. AUTHORS' CONCLUSIONS: The effects of hospital care and the length of stay is important for mental health policy. We found limited data, although outcomes do suggest that a planned short stay policy does not encourage a 'revolving door' pattern of admission and disjointed care for people with serious mental illness. More large, well-designed and reported trials are justified.

Field parasitism of nontarget weevil species (Coleoptera: Curculionidae) by the introduced biological control agent Microctonus aethiopoides Loan (Hymenoptera: Braconidae) over an altitude gradient.

The parasitoid, Microctonus aethiopoides Loan (Hymenoptera: Braconidae) was introduced into New Zealand in 1982 to control the alfalfa pest, Sitona discoideus Gyllenhal (Coleoptera: Curculionidae). Studies have shown that a number of nontarget weevil species are attacked in the field by this parasitoid. A field study was carried out to investigate nontarget parasitism by M. aethiopoides over an altitudinal sequence from the target host habitat (alfalfa) into native grassland. Three locations were selected for the study, and at each, the alfalfa growing in the valley floor was sampled annually for parasitism of the target pest that ranged between 17 and 78%. At progressively higher altitudes, three further grassland sites at each location were sampled monthly during spring to autumn for up to 6 yr. Weevil densities were estimated, species identified, and dissections carried out to determine reproductive status and parasitism. Almost 12,000 weevils were collected during the study, which were identified as 36 species in total from the three locations. Eight weevil species were found to be parasitized, including S. discoideus, the target host that was found at all sites. Parasitism of nontarget species was approximately 2% overall but varied with location, site, and season. Substantial nontarget parasitism was found at only one of the locations, with up to 24% parasitism of a native weevil, Nicaeana fraudator Broun (Coleoptera: Curculionidae), recorded. Another species, Irenimus egens (Broun) (Coleoptera: Curculionidae), was also found at this location at similar population densities but was attacked far less by M. aethiopoides. Results are discussed in relation to weevil phenology.