The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial.

Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure >25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 h, 24 h and 12 weeks and alpha set a priori at less than 0.1. Among the 16 women recruited, 15 completed the study (mean age 28 ± 9, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 h -5.7 ± 2.9 cmCSF (P = 0.048); 24 h -6.4 ± 2.9 cmCSF (P = 0.030); and 12 weeks -5.6 ± 3.0 cmCSF (P = 0.058). No serious safety signals were noted. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.

Evaluation of diurnal and postural intracranial pressure employing telemetric monitoring in idiopathic intracranial hypertension.

OBJECTIVES: Intracranial pressure (ICP) has been thought to vary diurnally. This study evaluates diurnal ICP measurements and quantifies changes in ICP occurring with changes in body posture in active idiopathic intracranial hypertension (IIH). METHODS: This prospective observational study utilized telemetric ICP monitoring in people with active IIH. Participants had the Raumedic p-Tel ICP intraparenchymal device (Raumedic, Hembrechts, Germany) surgically inserted. Changes in ICP in the supine position were evaluated. Then, the ICP was measured in the standing, sitting, supine, left lateral decubitus positions and with coughing and bending. Ultimately, changes in ICP over the course of 24 h were recorded. ISRCTN registration number 12678718. RESULTS: 15 women were included, mean (standard deviation) age 29.5 (9.5) years, body mass index 38.1 (6.2) kg/m2, and baseline mean ICP of 21.2 (4.8) mmHg (equivalent to 28.8 (6.5) cmCSF). Mean ICP rose with the duration in the supine position 1.2 (3.3) mmHg over 5-minutes (p = 0.175), 3.5 (2.8) mmHg over 30-minutes (p = 0.0002) and by a further 2.1 (2.2) mmHg over 3 h (p = 0.042). Mean ICP decreased by 51% when moving from the supine position to standing (21.2 (4.8) mmHg to 10.3 (3.7) mmHg respectively, p = 0.0001). Mean ICP increased by 13% moving from supine to the left lateral decubitus position (21.2 (4.8) mmHg to 24.0 (3.8) mmHg, p = 0.028). There was no significant difference in ICP measurements at any point during the daytime, or between 5-minute standing or supine recordings and prolonged ambulatory daytime and end of night supine recordings respectively. ICP, following an initial drop, increased progressively in conjunction with lying supine position from 23:00 h to 07:00 h by 34% (5.2 (1.9) mmHg, p = 0.026). CONCLUSION: This analysis demonstrated that ICP does not appear to have a diurnal variation in IIH, but varies by position and duration in the supine position. ICP rose at night whilst the patient was continuously supine. Furthermore, brief standing and supine ICP measures in the day predicted daytime prolonged ambulatory measures and end of night peak ICP respectively. This knowledge gives reassurance that ICP can be accurately measured and compared at any time of day in an ambulant IIH patient. These are useful findings to inform clinical measurements and in the interpretation of ICP analyses in IIH. TRIAL REGISTRATION: ISTCRN (12678718).

The Implications of Policies on the Welfare of Free-Roaming Cats in New Zealand.

A lack of national legislation for cat management in New Zealand poses challenges for ensuring that practices are consistently humane and effective. In this paper, we review the current cat management policies in New Zealand and the implications they have on the welfare of free-roaming cats (from here on, referred to as 'cats'). Our review demonstrates that there are multiple policy mechanisms used to manage cats in New Zealand for a variety of reasons, including animal welfare, pest management, and nuisance, and that these different policies have both positive and negative implications for cat welfare. We provide context pertaining to New Zealanders' acceptance of current or future laws and regulations and compare the New Zealand policy landscape with other countries, with a particular emphasis on Australia, to identify potential directions and outcomes of increased regulation. We discuss the future of the regulatory environment in New Zealand, including the need to better understand the impact of policies on cats, people, and other animals in urban, rural, and wild spaces. We further discuss the need to better understand the cat-human relationship for future policy decisions and offer a solution based on national cat legislation.

Epidemiology of disease-activity related ophthalmological manifestations in Systemic Lupus Erythematosus: A systematic review.

OBJECTIVE: Ophthalmic complications in Systemic Lupus Erythematosus (SLE) are broad and can occur in up to a third of patients. The British Isles Lupus Assessment Group (BILAG) 2004 Index identifies 13 ocular manifestations of active SLE, as opposed to those related to previous disease activity and/or the consequences of therapy. We conducted a systematic review of published literature to determine the frequency of ophthalmic manifestations of active SLE. METHODS: A systematic literature search of Ovid MEDLINE and EMBASE from their respective inceptions to July 2020 was conducted to identify cohort, case-control and cross-sectional studies. RESULTS: 22 studies meeting eligibility criteria were included. Most studies featured small sample sizes and were judged to have a high risk of methodological bias. The number and quality of studies did not allow us to confidently estimate the incidence of the conditions. No studies reported epidemiological data for orbital inflammation/myositis/proptosis. The prevalence of each of the other ocular manifestations, with the exception of retinal vaso-occlusive disease, was consistently less than 5%. Retinal vasculitis, uveitis and isolated cotton wool spots tended to be associated with more active SLE disease. CONCLUSION: The prevalence of eye disease due to SLE activity is uncommon, but clinicians should be aware that some conditions tend to be associated with more active systemic disease. Further studies to determine the incidence and risk factors for these ophthalmic manifestations are needed.

Using Optical Coherence Tomography as a Surrogate of Measurements of Intracranial Pressure in Idiopathic Intracranial Hypertension.

Importance: There is an unmet need for noninvasive biomarkers of intracranial pressure (ICP), which manifests as papilledema that can be quantified by optical coherence tomography (OCT) imaging. Objective: To determine whether OCT of the optic nerve head in papilledema could act as a surrogate measure of ICP. Design, Setting, and Participants: This longitudinal cohort study used data collected from 3 randomized clinical trials that were conducted between April 1, 2014, and August 1, 2019. Participants who were female and had active idiopathic intracranial hypertension were enrolled from 5 National Health Service hospitals in the UK. Automated perimetry and OCT imaging were followed immediately by ICP measurement on the same day. Cohort 1 used continuous sitting telemetric ICP monitoring (Raumedic Neurovent P-tel device) on 1 visit. Cohort 2 was evaluated at baseline and after 3, 12, and 24 months and underwent lumbar puncture assessment of ICP. Main Outcomes and Measures: Optical coherence tomography measures of the optic nerve head and macula were correlated with ICP levels, Frisén grading, and perimetric mean deviation. The OCT protocol included peripapillary retinal nerve fiber layer, optic nerve head, and macular volume scans (Spectralis [Heidelberg Engineering]). All scans were validated for quality and resegmented manually when required. Results: A total of 104 women were recruited. Among cohort 1 (n = 15; mean [SD] age, 28.2 [9.4] years), the range of OCT protocols was evaluated, and optic nerve head central thickness was found to be most closely associated with ICP (right eye: r = 0.60; P = .02; left eye: r = 0.73; P = .002). Subsequently, findings from cohort 2 (n = 89; mean [SD] age, 31.8 [7.5] years) confirmed the correlation between central thickness and ICP longitudinally (12 and 24 months). Finally, bootstrap surrogacy analysis noted a positive association between central thickness and change in ICP at all points (eg, at 12 months, a decrease in central thickness of 50 µm was associated with a decrease in ICP of 5 cm H2O). Conclusions and Relevance: In this study, optic nerve head volume measures on OCT (particularly central thickness) reproducibly correlated with ICP and surrogacy analysis demonstrated its ability to inform ICP changes. These data suggest that OCT has the utility to not only monitor papilledema but also noninvasively prognosticate ICP levels in idiopathic intracranial hypertension.

The Need for a National Accreditation Programme for Professionals Working in the Field of Animal Training and Behavioural Modification in New Zealand.

Companion animals are at risk of psychological (and physical) harm if outdated, incorrect or aversive methods of training or equipment are used during training and behavioural modification. Companion animal guardians often engage professional animal behaviour and training services, yet this industry is not regulated in New Zealand. A voluntary national accreditation and registration programme could act to protect the welfare of animals by robustly evaluating the experience, qualifications and training methods of industry professionals. To investigate industry readiness for a national accreditation programme, we conducted an online survey and analysed the responses of 262 animal trainers, behavioural consultants, dog safety educators, veterinarians and veterinary nurses. A national accreditation programme, promoting the use of reward-based training and behavioural modification techniques, was generally supported, especially by individuals holding qualifications and membership of professional organisations. The implementation of such a programme would ensure that those seeking these services are able to source professionals that use best practice when it comes to training and behavioural modification, with lasting benefits to animal welfare.

United Kingdom CSF Disorders Day 2018.

The multi-specialty approach to managing patients with cerebrospinal fluid (CSF) disorders requires neurology, neurosurgery, neuroradiology and neuro-ophthalmology. The annual United Kingdom CSF disorders meeting presented the first guidelines for idiopathic intracranial hypertension focusing on protecting the vision, managing the underlying disease and reducing headache morbidity. The most recent scientific concepts in CSF disorders were presented, as was the applied understanding of shunt and valve technology.

Predation and Risk Behaviors of Free-Roaming Owned Cats in Auckland, New Zealand via the Use of Animal-Borne Cameras.

Free-roaming cats are at increased risk of injuring themselves as well as other domestic and fauna species, yet relatively little is known about the frequency at which risk and predation behaviors occur in a typical day. In this study, cat risk, and predation behavioral information was collected using animal-borne video cameras and global positioning system (GPS) units that were attached to break-free cat collars. The observation period was one to three consecutive days for 37 convenience sampled free-roaming owned cats in Auckland, New Zealand. Video footage was manually reviewed and all predation and risk behavior events were recorded. These included stalking, pursuing, and seizing prey as well as altercations with other cats, ingesting harmful substances, and venturing into hazardous locations such as roads and storm drains. During the observation period, 23 of the 37 cats (62.2%) engaged in a total of 121 predation events. Of these, 40 resulted in successful prey capture with 18 of the 40 captures involving New Zealand native fauna species. Invertebrates were the most common taxa preyed upon (n = 55; 46%), followed by skinks (n = 8; 7%). No mammalian, avian or amphibian prey were captured and no cat took prey back to their residence. A total of 326 risk behaviors were observed for 32 out of the 37 cats (86.5%) with the most common being cats venturing onto the road (n = 132; 41%). Younger cats (aged 1-6 six years) engaged in significantly more predation and risk behaviors than older cats (aged 7 years and above). Sex, breed, number of cats in a household, and geographic location were not found to be predictors of cats' participation in predation or risk behaviors. Given the high frequency of predation and risk behaviors in free-roaming owned cats, it may be beneficial to educate owners about strategies to minimize risk such as housing them indoors, containing them to their properties or monitoring their time spent outdoors.

A Survey of Public Opinion on Cat (Felis catus) Predation and the Future Direction of Cat Management in New Zealand.

Cat predation is a prominent issue in New Zealand that provokes strong and opposing views. We explored, via 1011 face-to-face questionnaires, public opinion on (a) support for a National Cat Management Strategy (78% support); (b) concern regarding predation of wildlife by owned and un-owned cats (managed stray, unmanaged stray, and feral cats); (c) the acceptability of management techniques for owned cats; and (d) the acceptability of population management techniques for un-owned cats. The highest concern was expressed regarding the predation of non-native and native wildlife by feral cats (60 and 86% repectively), followed by unmanaged stray cats (59 and 86% respectively), managed stray cats (54 and 82% respectively), and finally owned cats (38 and 69% repectively). Limits to the number of cats owned and cat restriction zones received high levels of support (>65%), and compulsory microchipping, Council registration, and de-sexing were supported by the majority (>58%). Public support of population control methods for unowned cats was explored, and the influence of participant demographic variables on responses is described. These findings provide insight into public opinion regarding the management of cats in New Zealand, which should be considered during the development of legislation in this area.

Owners' Perceptions of Their Animal's Behavioural Response to the Loss of an Animal Companion.

The loss of a companion animal is recognised as being associated with experiences of grief by the owner, but it is unclear how other animals in the household may be affected by such a loss. Our aim was to investigate companion animals' behavioural responses to the loss of a companion through owner-report. A questionnaire was distributed via, and advertised within, publications produced by the Royal Society for the Prevention of Cruelty to Animals (RSPCA) across Australia and New Zealand, and through a selection of veterinary clinics within New Zealand. A total of 279 viable surveys were returned pertaining to 159 dogs and 152 cats. The two most common classes of behavioural changes reported for both dogs and cats were affectionate behaviours (74% of dogs and 78% of cats) and territorial behaviours (60% of dogs and 63% of cats). Both dogs and cats were reported to demand more attention from their owners and/or display affiliative behaviour, as well as spend time seeking out the deceased's favourite spot. Dogs were reported to reduce the volume (35%) and speed (31%) of food consumption and increase the amount of time spent sleeping (34%). Cats were reported to increase the frequency (43%) and volume (32%) of vocalisations following the death of a companion. The median duration of reported behavioural changes in both species was less than 6 months. There was consensus that the behaviour of companion animals changed in response to the loss of an animal companion. These behavioural changes suggest the loss had an impact on the remaining animal.

The effect of conspecific removal on behavioral and physiological responses of dairy cattle.

Adverse social and welfare implications of mixing dairy cows or separating calves from their mothers have been documented previously. Here we investigated the behavioral and physiological responses of individuals remaining after conspecifics were removed. We conducted a series of 4 experiments incorporating a range of types of different dairy cattle groupings [experiment 1 (E1), 126 outdoor lactating dairy cows; experiment 2 (E2), 120 housed lactating dairy cows; experiment 3 (E3), 18 housed dairy calves; and experiment 4 (E4), 22 housed dairy bulls] from which a subset of individuals were permanently removed (E1, n=7; E2, n=5; E3, n=9; E4, n=18). Associations between individuals were established using near-neighbor scores (based upon identities and distances between animals recorded before removal) in E1, E2, and E3. Behavioral recordings were taken for 3 to 5 d, before and after removal on a sample of cattle in all 4 experiments (E1, n=20; E2, n=20; E3, n=9; E4, n=4). In 2 experiments with relatively large groups of dairy cows, E1 and E2, the responses of cows that did and did not associate with the removed cows were compared. An increase in time that both nonassociates and associates spent eating was observed after conspecific removal in E1. In E2, this increase was restricted to cows that had not associated with the removed cows. A reduction in ruminating in remaining cattle was observed in E3 and eating in E4. Immunoglobulin A concentrations increased after separation in both E3 and E4 cattle, but did not differ significantly between associates and nonassociates in E2. Blood and milk cortisol concentrations were not affected by conspecific removal. These findings suggest that some animals had affected feeding behavior and IgA concentrations after removal of conspecifics.