The pain course: a randomised controlled trial comparing a remote-delivered chronic pain management program when provided in online and workbook formats.

This study compared a remote-delivered pain management program, the Pain Course, when delivered in online and workbook formats. Participants (n = 178) were randomised into 2 groups: (1) an Internet Group (n = 84) who were provided with secure accounts to the program in an online format; or (2) a Workbook Group (n = 94) who were mailed workbook versions of the program. The content of both programs was identical and comprised 5 core lessons, which participants were encouraged to work through over an 8-week period, according to a prescribed timetable. All participants were provided with weekly contact with a clinical psychologist through email and telephone throughout the program. The overall findings suggest that the workbook format was no less effective or acceptable than the validated online format. Significant improvements (avg. improvement; Internet Group vs Workbook Group) in levels of disability (PDI: 16% vs 24%; RMDQ: 12% vs 15%), anxiety (GAD-7: 36% vs 26%), and depression (PHQ-9: 36% vs 36%) were observed in both groups immediately posttreatment. Further improvements were observed in disability levels to 3-month follow-up, and improvements across the other primary outcomes were maintained until 12-month follow-up. High treatment completion rates and levels of satisfaction were reported in both groups, and both groups required a similarly small amount of clinician contact per participant (M = 74.85 minutes; SD = 41.03). These results highlight the public health potential of remote-delivered pain management programs, delivered in either workbook or online formats, as methods of increasing access to pain management.

The Pain Course: exploring predictors of clinical response to an Internet-delivered pain management program.

There is significant interest in the potential of Internet-delivered pain management programs for adults with chronic pain. Understanding the characteristics of people who do and do not benefit from Internet-delivered programs will help to guide their safe and effective use. Using a large sample from a previous randomised controlled trial of an established Internet-delivered pain management program, the Pain Course, this study (n = 463) examined whether several demographic, clinical, psychological, and treatment-related variables could be used to predict clinical response in levels of disability, depression, anxiety, or average pain. Multiple univariate and multivariate stepwise logistic regressions were used to identify unique predictors of clinical improvement, which, consistent with recommendations, was defined as a ≥30% reduction in symptoms or difficulties from baseline. Several unique predictors of clinical improvement were found. However, no particularly decisive or dominant predictors emerged that were common across time points or across the outcome domains. Reflecting this, the identified predictors explained only 18.1%, 13.7%, 7.6%, and 9.5% of the variance in the likelihood of making a clinical improvement in disability, depression, anxiety, and average pain levels, respectively. The current findings suggest that a broad range of patients may benefit from emerging Internet-delivered pain management programs and that it may not be possible to predict who will or will not benefit on the basis of patients' demographic, clinical, and psychological characteristics.

Transdiagnostic Internet-delivered cognitive behaviour therapy in Canada: An open trial comparing results of a specialized online clinic and nonspecialized community clinics.

Effects of Internet-delivered cognitive behaviour therapy (ICBT) for anxiety and depression are not well understood when delivered in non-specialized as compared to specialized clinic settings. This open trial (n=458 patients) examined the benefits of transdiagnostic-ICBT when delivered in Canada by therapists (registered providers or graduate students) working in either a specialized online clinic or one of eight nonspecialized community clinics. Symptoms of depression and anxiety were assessed at pre-treatment, post-treatment and at 3-month follow-up. Completion rates and satisfaction were high. Significant and large reductions (effect sizes 1.17-1.31) were found on symptom measures. Completion rates, satisfaction levels and outcomes did not differ whether ICBT was delivered by therapists working in a specialized online clinic or nonspecialized community clinics. Differences were also not found between registered providers and graduate students, or therapists trained in psychology or another discipline. The findings support the public health potential of ICBT.

Transdiagnostic versus disorder-specific and clinician-guided versus self-guided internet-delivered treatment for Social Anxiety Disorder and comorbid disorders: A randomized controlled trial.

Disorder-specific (DS-CBT) and transdiagnostic (TD-CBT) cognitive behaviour therapy have both been used to treat social anxiety disorder (SAD). This study compared internet-delivered DS-CBT and TD-CBT for SAD across clinician-guided (CG-CBT) and self-guided (SG-CBT) formats. Participants with SAD (n=233) were randomly allocated to receive internet-delivered TD-CBT or DS-CBT and CG-CBT or SG-CBT. Large reductions in symptoms of SAD (Cohen's d≥1.01; avg. reduction≥30%) and moderate-to-large reductions in symptoms of comorbid depression (Cohen's d≥1.25; avg. reduction≥39%), generalised anxiety disorder (Cohen's d≥0.86; avg. reduction≥36%) and panic disorder (Cohen's d≥0.53; avg. reduction≥25%) were found immediately post-treatment and were maintained or further improved to 24-month follow-up. No marked differences were observed between TD-CBT and DS-CBT or CG-CBT and SG-CBT highlighting the potential of each for the treatment of SAD and comorbid disorders.

Disorder-specific versus transdiagnostic and clinician-guided versus self-guided internet-delivered treatment for panic disorder and comorbid disorders: A randomized controlled trial.

Transdiagnostic cognitive behaviour therapy (TD-CBT) aims to target the symptoms of multiple disorders whereas disorder-specific CBT (DS-CBT) targets the symptoms of principal disorders. This study compared the relative benefits of internet-delivered TD-CBT and DS-CBT when provided in clinician-guided (CG-CBT) and self-guided (SG-CBT) formats for people with a principal diagnosis of Panic Disorder (PD). Participants (n=145) were randomly allocated to receive TD-CBT or DS-CBT and CG-CBT or SG-CBT. Large reductions in symptoms of PD (Cohen's d ≥ 0.71; avg. reduction ≥ 36%) and moderate-to-large reductions in symptoms of comorbid depression (Cohen's d ≥ 0.71; avg. reduction ≥ 33%), generalised anxiety disorder (Cohen's d ≥ 0.91; avg. reduction ≥ 34%) and social anxiety disorder (Cohen's d ≥ 0.50; avg. reduction ≥ 15%) were found over the 24-month follow-up period. Highlighting their efficacy and acceptability, no marked and consistent differences were observed between TD-CBT and DS-CBT or CG-CBT and DS-CBT.

Disorder-specific versus transdiagnostic and clinician-guided versus self-guided treatment for major depressive disorder and comorbid anxiety disorders: A randomized controlled trial.

Disorder-specific cognitive behavior therapy (DS-CBT) is effective at treating major depressive disorder (MDD) while transdiagnostic CBT (TD-CBT) addresses both principal and comorbid disorders by targeting underlying and common symptoms. The relative benefits of these two models of therapy have not been determined. Participants with MDD (n=290) were randomly allocated to receive an internet delivered TD-CBT or DS-CBT intervention delivered in either clinician-guided (CG-CBT) or self-guided (SG-CBT) formats. Large reductions in symptoms of MDD (Cohen's d≥1.44; avg. reduction≥45%) and moderate-to-large reductions in symptoms of comorbid generalised anxiety disorder (Cohen's d≥1.08; avg. reduction≥43%), social anxiety disorder (Cohen's d≥0.65; avg. reduction≥29%) and panic disorder (Cohen's d≥0.45; avg. reduction≥31%) were found. No marked or consistent differences were observed across the four conditions, highlighting the efficacy of different forms of CBT at treating MDD and comorbid disorders.

Transdiagnostic versus disorder-specific and clinician-guided versus self-guided internet-delivered treatment for generalized anxiety disorder and comorbid disorders: A randomized controlled trial.

Generalized anxiety disorder (GAD) can be treated effectively with either disorder-specific cognitive behavior therapy (DS-CBT) or transdiagnostic CBT (TD-CBT). The relative benefits of DS-CBT and TD-CBT for GAD and the relative benefits of delivering treatment in clinician guided (CG-CBT) and self-guided (SG-CBT) formats have not been examined. Participants with GAD (n=338) were randomly allocated to receive an internet-delivered TD-CBT or DS-CBT intervention delivered in either CG-CBT or SG-CBT formats. Large reductions in symptoms of GAD (Cohen's d ≥ 1.48; avg. reduction ≥ 50%) and comorbid major depressive disorder (Cohen's d ≥ 1.64; avg. reduction ≥ 45%), social anxiety disorder (Cohen's d ≥ 0.80; avg. reduction ≥ 29%) and panic disorder (Cohen's d ≥ 0.55; avg. reduction ≥ 33%) were found across the conditions. No substantive differences were observed between DS-CBT and TD-CBT or CG-CBT and SG-CBT, highlighting the public health potential of carefully developed TD-CBT and SG-CBT.

The orexin-1 receptor antagonist SB-334867 decreases anxiety-like behavior and c-Fos expression in the hypothalamus of rats exposed to cat odor.

Increasing evidence suggests that the orexin system is involved in modulating anxiety, and we have recently shown that cat odor-induced anxiety in rats is attenuated by the orexin receptor antagonist SB-334867. In the current experiment, c-Fos expression was used to map changes in neuronal activation following SB-334867 administration in the cat odor anxiety model. Male Wistar rats were exposed to cat odor with or without SB-334867 pre-treatment (10 mg/kg, i.p.). A naïve control group not exposed to cat odor was also used. Following cat odor exposure, brains were processed for c-Fos expression. Vehicle-treated rats showed an increase in anxiety-like behaviors (increased hiding and decreased approach toward the cat odor), and increased c-Fos expression in the posteroventral medial amygdala (MePV), paraventricular hypothalamus (PVN) and dorsal premammillary nucleus (PMd). In rats pretreated with SB-334867, approach scores increased and c-Fos expression decreased in the PVN and PMd. These results provide both behavioral and neuroanatomical evidence for the attenuation of cat odor-induced anxiety in rats via the orexin system.

Vaccination of feral pigs (Sus scrofa) using iophenoxic acid as a simulated vaccine.

OBJECTIVES: To develop an encapsulation method for delivery of vaccines to feral pigs, and quantify the effect of iophenoxic acid on captive feral pig blood iodine concentrations to assist in investigation of factors affecting vaccine uptake. DESIGN AND METHODS: Feral pigs were administered iophenoxic acid by oral gavage, and consumption was assessed for different encapsulation methods in baits. Blood iodine concentrations were monitored for eight days after consumption. The relationship between dose rate, time since dosing and blood iodine concentration was assessed for gavaged and baited captive feral pigs. Wild feral pigs were baited with PIGOUT baits containing 20 mg of encapsulated iophenoxic acid to simulate a vaccination program. Using knowledge from the pen studies, bait uptake and factors affecting bait uptake were investigated. RESULTS: Bait-delivered iophenoxic acid led to variable and inconsistent changes in blood iodine concentrations, in contrast to pigs receiving iophenoxic acid by gavage. This precluded accurate assessment of the quantity consumed, but still allowed a conservative determination of bait uptake. Iophenoxic acid in smaller capsules was consumed readily. Increasing baiting intensity appeared to increase bait uptake by wild feral pigs, and pigs of varying sexes, ages and weights appeared equally likely to consume baits. CONCLUSIONS: Encapsulated liquids can be delivered to feral pigs within baits, should the need to vaccinate feral pigs for fertility or disease management arise. High baiting intensities may be required.

Cat odor, but not trimethylthiazoline (fox odor), activates accessory olfactory and defense-related brain regions in rats.

Cat odor and trimethylthiazoline (TMT, a component of fox feces) are two stimuli widely used in rodent models of fear and anxiety. Recent studies suggest that these odorants have distinct behavioral effects, raising questions as to whether TMT is a true "predator odor." Here we used c-Fos immunohistochemistry to compare patterns of neural activation produced by cat odor and TMT. Rats were exposed to either (1) three pieces of a collar that had been worn by a domestic cat, (2) three collar pieces impregnated with TMT (30 microl/piece), (3) three collar pieces impregnated with 4% formaldehyde (200 microl/piece, an acrid but non-predatory odor), or (4) three control (no odor) collar pieces. Odors were presented in a small well-ventilated plastic box. All odorants (cat odor, TMT and formaldehyde) produced increased defecation in rats compared with the control group, and formaldehyde exposure also decreased rearing. Cat odor increased contact with the stimulus relative to all other groups, while TMT increased contact compared with the formaldehyde and clean air groups. Only cat odor decreased grooming and elicited escape attempts. In addition, only cat odor caused pronounced activation of Fos in the accessory olfactory bulb and its projection areas, anterior olfactory nucleus, medial prefrontal cortex, striatum, and a medial hypothalamic circuit associated with defensive behavior. In contrast, the only areas activated by TMT were the internal granular layer of the main olfactory bulb and central amygdala, while both cat odor and TMT activated the glomeruli of the main olfactory bulb, piriform cortex, ventral orbital cortex and anterior cortical amygdala. Results indicate that the effects of cat odor and TMT are easily distinguished both behaviorally and at a neural level, and suggest that TMT lacks the "pheromone-like" quality of cat odor that engages key hypothalamic sites involved in defensive behavior.

Field evaluation of melatonin implants to advance the breeding season in 1-year-old farmed red deer hinds.

The efficacy of controlled-release melatonin implants to advance the onset of the breeding season was assessed in 1-year-old red deer hinds on five commercial deer farms in various localities in the North Island of New Zealand. Between 44 and 60 hinds in each of six herds were equally divided among treatment and control groups at each site. Melatonin treatment commenced between 27 November and 16 December and was achieved by the subcutaneous administration of two 18 mg melatonin implants. Three doses were given at about 30 day intervals. Two adult stags for each hind group were treated with three 18 mg melatonin implants concurrently on either two or three occasions. On each property, treated and control hinds were joined as one herd to treated stags commencing 30 January-10 February and concluding 15 May-2 June. The hinds in the four experimental herds underwent rectal ultrasound examination May-June to estimate conception rate and foetal age. Calving dates, hind and calf mortalities, weaning weights, and the antler growth cycle and harvesting data were recorded. Overall, treatment with melatonin resulted in an average advance of the median calving date of 22 days (range 12-36 days) when compared with untreated controls in the same herds. Pregnancy rates were 91.3-100% in treated hinds and 63.6-100% in untreated hinds. There were no differences in calf mortality or calf sex ratio between treated and untreated groups. No hind deaths could be attributed to melatonin treatment. The weaning weights of calves were 5.68 kg and 4.43 kg heavier for the male and female offspring of treated hinds respectively, compared with those of control hinds. Treated stags commenced rutting behaviour earlier than normal and the antler casting and growth cycle was advanced. Treatment resulted in advancement of the seasonal pattern of coat changes in hinds and stags, but no untoward side effects of the melatonin treatments were observed.

Effects of subcutaneous melatonin implants on reproductive seasonality of farmed fallow deer (Dama dama).

A total of 18 fallow does, including pubertal, non-pregnant and pregnant adult does (6 per class), each received a single subcutaneous implant containing 18 mg melatonin on 4 occasions at 29-30-day intervals from 10 November 1986 (approximately 120-day treatment period). A further 18 contemporary does served as herd-mate controls. Two adult fallow bucks were treated the same and were run with the does until 16 March. Thereafter, 1 of 4 control bucks was run with the does until 1 June. Of the 6 pregnant does receiving implants within the last 40 days of their gestation, 4 failed to lactate after parturition in December 1986. The remaining 2 does successfully reared their fawns, as did the 6 contemporary controls. Mean (+/- s.e.m.) dates of first oestrus in 1987 were 27.6 February (+/- 3.0 days) and 22.9 April (+/- 0.8 days) for all treated and all control does respectively (P less than 0.001). Pubertal does were generally later to exhibit first oestrus than were older does within their respective treatment groups. Return oestrus occurred only in 2 pubertal does (1 treated and 1 control) with remaining does conceiving to their first oestrus, as verified by plasma progesterone profiles. However, 5 (28%) of the treated does and 3 (17%) of the control does failed to maintain pregnancy and fawn in 1987. The mean (+/- s.e.m.) 1987 fawning date of the remaining does was 22.4 October (+/- 2.7 days) for the treated group (N = 13) and 13.1 December (+/- 0.8 days) for the control group (N = 15; P less than 0.001). Mean (+/- s.e.m.) gestation length of treated does (238.9 +/- 0.6 days) was significantly longer than that of control does (234.5 +/- 0.4 days; P less than 0.001). Of 13 fawns born to treated does, 4 (31%) died within 24 h of birth (mainly due to hypothermia) whereas all 15 fawns born to control does survived to weaning. Melatonin-treated bucks exhibited a marked advancement of neck muscle hypertrophy during the treatment period and displayed normal rutting activity (e.g. vocalization) in response to early oestrus in the treated does.

S(-)DP-5,6-ADTN as an in vivo dopamine receptor ligand: relation between displacement by dopamine agonists and their pharmacological effects.

The use of (-)DP-5,6-ADTN as a non-radioactively labeled ligand for an in vivo DA receptor assay is described and compared with racemic DP-5,6-ADTN, previously used for that purpose. The effects of four DA agonists (NPA, bromocriptine, DP-7-OH-ATN and 3-PPP) on the specific (-)DP-5,6-ADTN binding are related to their potencies to decrease striatal HVA concentrations and to induce stereotypy in rats. NPA and DP-7-OH-ATN caused a maximal decrease in HVA levels, when only a fraction of the receptors were occupied, while the occurrence of stereotypy was associated with a high receptor occupation, reflecting the higher affinity of these agonists for presynaptic than for postsynaptic receptors. Bromocriptine did not show this effect, as the dose-response relationships for HVA decrease, for induction of stereotypy and for the decrease in specific (-)DP-5,6-ADTN binding were all virtually equal to each other. While NPA and bromocriptine behaved as full postsynaptic agonists, in that maximal stereotyped behavior was observed after high doses, DP-7-OH-ATN was found to be a partial postsynaptic agonist, as it did not induce maximal stereotypy at a maximal receptor occupation. Racemic 3-PPP only caused a state of hypoactivity, but did neither affect specific (-)DP-5,6-ADTN binding nor striatal HVA levels. Our results are discussed in view of theories on the relation between receptor occupation and pharmacological effects and it is concluded that the in vivo receptor binding method using (-)DP-5,6-ADTN is a very useful tool for such investigations.

Inhibin secretion by the sheep ovary.

An in-vitro bioassay for inhibin based on FSH content or release by rat pituitary cells was validated for measuring inhibin activity in ovine plasma and lymph. Dose-dependent increases in inhibin activity were detected in peripheral plasma of 4 ovariectomized ewes 1 min after i.v. injections of ovine follicular fluid, and the half-life of inhibin in plasma for 2 ewes was 45 and 50 min, respectively. Inhibin was detected in ovarian lymph but not in ovarian or jugular venous plasma, even after treatment of ewes with PMSG to induce folliculogenesis. Destruction of visible follicles (greater than 0.5 mm diameter) on the ovaries of 4 PMSG-treated ewes by electrocautery was followed by a rapid and sustained decline in secretion of inhibin in ovarian lymph for up to 4 h. Ovarian lymph flow rates were either unchanged or slightly increased after cautery. Oestrogen concentrations in peripheral venous plasma declined within 15-30 min of cautery, but concentrations remained well above baseline. There was a significant decrease in peripheral progesterone concentrations in these same samples, but not until 2-3 h after cautery. FSH in peripheral plasma was depressed or non-detectable in PMSG-treated ewes and neither FSH nor LH concentrations in peripheral plasma were significantly altered up to 4 h after cautery of ovarian follicles. It is concluded that (a) antral follicles (greater than 0.5 mm) are the source of inhibin present in ovarian lymph, and (b) the ovarian lymphatic system is a route by which inhibin could reach the peripheral circulation, particularly in the luteal phase when ovarian lymph flow rates are high.

SCH23390 causes persistent antidopaminergic effects in vivo: evidence for longterm occupation of receptors.

SCH23390 has neurochemical properties characteristic of a specific D1 dopamine receptor antagonist. However, it is a potent inhibitor of dopamine-mediated behaviors which previously had been thought to be linked to D2 receptors. The metabolism of SCH23390 following parenteral administration to rats was much more rapid in the periphery than in brain, and SCH23390 had behavioral effects long after its circulating concentration had declined below detectable levels. Furthermore, the stimulation of adenylate cyclase by dopamine was attenuated in striatal homogenates taken from rats treated with SCH23390 as much as twelve hours before sacrifice. Pretreatment with cis-flupenthixol, a compound with equivalent D1 potency in vitro, failed to inhibit dopamine-stimulated adenylate cyclase activity one or four hours following injection, despite the fact that this dose produced significant behavioral effects. These data indicate that SCH23390 may act with unusual tenacity at certain sites in the central nervous system.

Structural requirements for steroid inhibition of sheep lymphocyte mitogenesis in vitro.

The inhibitory effects of different steroids and related compounds on sheep peripheral blood lymphocytes (PBL) during exposure to the mitogen, phytohemagglutinin (PHA), have been measured by the reduction of [3H]thymidine incorporation into DNA. Dose-response curves showed that a maximum (or near maximum effect) was achieved at a steroid concentration of 12.5 microM. At this dose 19 of 41 compounds significantly reduced thymidine incorporation by activated PBL (P less than 0.01 to P less than 0.001). The greatest reduction was observed with 17-hydroxyprogesterone (-59%, i.e. reduced by 59% compared with vehicle control, 100%) greater than androstenedione greater than epitestosterone greater than estradiol-3-methyl ether greater than 20 alpha-dihydroprogesterone greater than medroxyprogesterone acetate greater than 5 beta-pregnane-3,20-dione greater than 5 alpha-pregnane-3,20-dione (-24%). Among the steroids which showed the greatest inhibitory effect, 6 had a 4-en-3-one group in ring A, 4 had a saturated ring A (pregnane or androstane) and one had a 3-methyl ether group and a phenolic ring A. The wide range of structures represented by these inhibitory steroids suggests that inhibition of lymphocyte mitogenesis involves more than one mechanism.