The safety of overdose and repeat administrations of BCG Danish strain 1331 vaccine in calves and pregnant heifers.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis infection, is a zoonotic disease in cattle that represents a significant ongoing challenge to cattle farming productivity and the livelihoods of livestock farmers in the UK. Vaccination of cattle with BCG could directly target the ability of M. bovis to proliferate within vaccinates, restricting bTB pathogenesis and onward disease transmission, and represent a step change in the tools available to help control bTB in farmed cattle. A Marketing Authorisation (MA) is required before a cattle BCG vaccine could be sold and supplied as a veterinary medicine within the UK and this requires comprehensive data supporting vaccine quality, efficacy and, most importantly, its safety. We carried out two independent Good Laboratory Practice (GLP) studies in which the safety of BCG vaccination in cattle was stringently tested through overdose and repeat vaccine administrations in young calves and pregnant heifers. Mild and generally short-lived reactions to vaccinations were observed in some animals, most commonly increases in body temperature and swelling at vaccine injection sites, but these did not have a negative impact on the overall health status of vaccinates. BCG was not shed in the saliva, faeces, milk or urine from vaccinated animals and its dissemination was limited to injection site tissues and associated lymph nodes. Overall, young calves and pregnant heifers vaccinated with BCG remained in good general health, and the vaccinated pregnant heifers had normal pregnancies and gave birth to healthy calves. Obtaining a Marketing Authorisation for a cattle BCG vaccine is a critical milestone in the progress towards the eventual use of BCG vaccination in cattle as an additional bTB control tool within the UK; these pivotal GLP vaccine safety studies generated the detailed and essential target animal safety data needed to support this.

Practical management of oral treprostinil in patients with pulmonary arterial hypertension: Lessons from ADAPT, EXPEDITE, and expert consensus.

BACKGROUND: Oral treprostinil is a prostacyclin analogue approved to treat pulmonary arterial hypertension (PAH) by delaying disease progression and improving exercise capacity. Higher doses of oral treprostinil correlate with increased treatment benefit. Titrations may be challenging due to common side effects of prostacyclin-class therapies. STUDY DESIGN AND METHODS: The multicenter, prospective, real-world, observational ADAPT Registry study followed adult patients with PAH for up to 78 weeks after initiating oral treprostinil (NCT03045029). Dosing, titration, and transitions of oral treprostinil were at the discretion of the prescriber. Patient-reported incidence and treatment of common side effects were collected to understand side effect management and tolerability. Insights from literature and expert recommendations were added to provide a consolidated resource for oral treprostinil use. RESULTS: In total, 139 participants in ADAPT completed ≥1 weekly survey; (median age 60.0 years, 76 % female). Median treatment duration of oral treprostinil was 13.1 months. During early therapy (Months 1-5), 62 % (78/126) of patients reported headache and diarrhea, and 40 % (50/126) reported nausea. At Month 6, many patients who reported side effects during early therapy reported an improvement (61 % headache, 44 % diarrhea, 70 % nausea). Common side effect treatments, including acetaminophen, loperamide, and ondansetron, were effective. Approximately one-quarter of patients reporting the most common side effects were untreated at Month 6. CONCLUSION: Patient selection for, and initiation and titration of, oral treprostinil should be individualized and may include parenteral treprostinil induction-transition for faster titration. Assertive side effect management may help patients reach higher and more efficacious doses of oral treprostinil.

Cannabidiol (CBD) for the treatment of subcutaneous treprostinil (Remodulin®) site pain: a case report.

Background: Pulmonary arterial hypertension occurs as a result of vascular remodeling and dysregulation of endothelial cells that narrows small pulmonary arteries and raises precapillary pressures. Pulmonary arterial hypertension is a rare and progressive disease characterized by dyspnea, chest pain, and syncope. Parenteral treprostinil is indicated for the treatment of pulmonary arterial hypertension to diminish symptoms associated with exercise. Up to 92% of patients treated with treprostinil via subcutaneous delivery experienced infusion site pain and approximately 23% discontinued treatment due to site pain. Cannabidiol salve may have analgesic and anti-inflammatory properties and could be an additional option for patients with infusion site pain. Case report: Two patients with pulmonary arterial hypertension were treated with cannabidiol salve. Both patients reported a reduction in infusion site pain without the need for narcotics. Conclusion: These two cases suggest that cannabidiol salve may help to minimize redness and alleviate pain at the infusion site. Additional studies are required to test the effectiveness of cannabidiol in a larger group of patients with infusion site pain.

Clinical application of risk assessment in PAH: Expert center APRN recommendations.

Performing longitudinal and consistent risk assessments for patients with pulmonary arterial hypertension (PAH) is important to help guide treatment decisions to achieve early on and maintain a low-risk status and improve patient morbidity and mortality. Clinical gestalt or expert perception alone may over or underestimate a patient's risk status. Indeed, regular and continued use of validated risk assessment tools more accurately predict patients' survival. Effective PAH risk assessments are often underutilized even though many seasoned clinicians will attest to using these tools routinely. We present recommendations based on real-world experience in varied clinical practice settings around the United States for overcoming barriers to facilitate regular, serial formal risk assessment. Expert advanced practice provider clinicians from mid to large-size medical centers collaborated to formulate recommendations based on multiple discourses and discussions. Enlisting the help of support staff, such as medical assistants and nurses, to fill in available risk parameters in risk assessment tools can save time for providers and increase efficiency, as can technology-based solutions such as integrating risk assessments into electronic medical records. Modified, abbreviated risk assessment tools can be applied to a patient's clinical scenario when all of a patient's data are not available to complete a more comprehensive assessment. Initial discussions regarding the overall meaning and prognostic importance of risk scores may assist patients to take on a more active role in terms of informed decision-making regarding their care. A collaborative approach can help clinics establish consistent use of risk assessment.

An expert panel Delphi consensus statement on the use of palliative care in the management of patients with pulmonary arterial hypertension.

Mortality in pulmonary arterial hypertension (PAH) remains high and referral to palliative or supportive care (P/SC) specialist services is recommended when appropriate. However, access to P/SC is frequently a challenge for patients with a noncancer diagnosis and few patients living with PAH report P/SC involvement in their care. A modified Delphi process of three questionnaires completed by a multidisciplinary panel (N = 15) was used to develop expert consensus statements regarding the use of P/SC to support patients with PAH. Panelists rated their agreement with each statement on a Likert scale. There was a strong consensus that patients should be referred to P/SC when disease symptoms become unmanageable or for end-of-life care. Services that achieved consensus were pain management techniques, end-of-life care, and psychosocial recommendations. Palliative or supportive care should be discussed with patients, preferably in-person, when disease symptoms become unmanageable, when starting treatment, when treatment-related adverse events occur or become refractory to initial intervention. Care partners and patient support groups were considered important in improving a patient's overall health outcomes, treatment adherence, and perception of care. Most patients with PAH experience cognitive and/or psychosocial changes and those who receive psychosocial management have better persistence and/or compliance with their treatment. These consensus statements provide guidance to healthcare providers on the "who and when" of referral to palliative care services, as well as the importance of focusing on the psychosocial aspects of patient care and quality of life.

The Sources of Strength Australia project: A cluster randomised controlled trial of a peer-connectedness school-based program to promote help-seeking in adolescents.

BACKGROUND: Suicide is a significant public health problem and there is a clear need for interventions to improve help seeking for suicide and psychological distress in young people. This trial aimed to assess the effectiveness of the school-based Sources of Strength program in increasing help-seeking intentions and behaviours in adolescents. METHODS: A cluster, randomised controlled trial was conducted in 13 Australian secondary schools (N = 1633), with each school randomly allocated to the intervention (n = 7) or wait-list control condition (n = 6). Participants in the intervention condition received the Sources of Strength program over two years and all participants completed self-report measures of help-seeking intentions and behaviour at four time-points. Staff and students in the intervention condition also provided qualitative feedback on the perceived impact of the program. RESULTS: Mixed model repeated measures analyses demonstrated no significant effect of the Sources of Strength program on help-seeking intentions or behaviour at post-intervention or 6- or 18-month follow-up. Staff and students reported, through qualitative feedback, that the program increased awareness of and openness to help seeking and promoted a common language and school community. LIMITATIONS: The current study only included self-report measures that may have been influenced by situational factors or biases. CONCLUSIONS: Although the Sources of Strength program may have increased awareness of help seeking, there was no evidence that it is effective in increasing help-seeking intentions or behaviours in this cohort. The program may be more suitable for schools in disadvantaged areas where there may be limited existing connections to trusted adults.

Improving communication between healthcare providers and pulmonary arterial hypertension patients: a survey of patient preferences.

Effective communication within the patient-provider relationship is a key aspect of shared decision-making and associated with several positive patient outcomes. Although previous studies suggest that patients' and providers' conceptualization of what constitutes effective communication differ, there is no available literature discussing patient preferences for communication. The objective of this study was to determine the words and phrases pulmonary arterial hypertension patients prefer to hear when discussing their disease with their physician. A total of 227 pulmonary arterial hypertension patients completed a survey that included a 20-item questionnaire specifically designed to assess patient preference for words and phrases when discussing their disease and treatment; statistically significant differences were observed across all items of the questionnaire. Patients preferred their physician ask them how they have "been feeling" (63%) rather than how they have "been doing". In addition, 96% of patients indicated that they wanted to hear that this is "… the best medicine for you" rather than this is "the best medicine". Considerably more patients (60%) indicated they want their physician to say, "We want you to have fewer symptoms" rather than "We want you to feel more normal." They also indicated they wanted the "most effective" medicine (82%) rather than the "most aggressive" medicine (7%). The results of this study suggest that pulmonary arterial hypertension patients have strong preferences for the language their providers use when discussing their disease and treatment options. Given the role that effective communication has on important health outcomes, pulmonary arterial hypertension providers need to consider these findings when communicating with patients.

Online screening and feedback to increase help-seeking for mental health problems: population-based randomised controlled trial.

BACKGROUND: Community-based screening for mental health problems may increase service use through feedback to individuals about their severity of symptoms and provision of contacts for appropriate services. AIMS: The effect of symptom feedback on service use was assessed. Secondary outcomes included symptom change and study attrition. METHOD: Using online recruitment, 2773 participants completed a comprehensive survey including screening for depression (n=1366) or social anxiety (n=1407). Across these two versions, approximately half (n=1342) of the participants were then randomly allocated to receive tailored feedback. Participants were reassessed after 3 months (Australian New Zealand Clinical Trials Registry ANZCTR12614000324617). RESULTS: A negative effect of providing social anxiety feedback to individuals was observed, with significant reductions in professional service use. Greater attrition and lower intentions to seek help were also observed after feedback. CONCLUSIONS: Online mental health screening with feedback is not effective for promoting professional service use. Alternative models of online screening require further investigation. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

The Sources of Strength Australia Project: study protocol for a cluster randomised controlled trial.

BACKGROUND: The school system has been identified as an ideal setting for the implementation of prevention and early intervention programs for suicide. However, in Australia, suicide-prevention programs that are routinely delivered in the schools are lacking. Internationally, evidence exists for the effectiveness of peer-led interventions that take a social connectedness approach to improve help-seeking for suicide. The aim of the current trial is to test the effectiveness of the Sources of Strength program to promote help-seeking for suicide in adolescents in Australian high schools. METHODS/DESIGN: This study is a two-arm, cluster-randomised, controlled trial that will compare the evidence-based Sources of Strength program to a wait-list control condition. Sixteen Australian high schools will be recruited to the trial, with all adolescents in years 7 to 10 (12-16 years of age) invited to participate. Peer leaders from intervention-condition schools will receive training in the Sources of Strength program and will integrate positive messages, across 3 months, with the support of adult advisors. Activities may take the form of class presentations, posters, videos, and messages on social media sites and will aim to change help-seeking norms, strengthen youth-adult connections, and promote positive coping. The primary outcome measure for the study is help-seeking intentions, whereas secondary outcomes include help-seeking behaviour, help-seeking attitudes and norms, referral of distressed peers, availability of adult help, positive coping, and suicidal behaviour. Data will be collected pre-intervention, post-intervention (after the initial 3 months of messaging), and at the end of the first (6-month follow-up) and the second year after implementation (18-month follow-up). Primary analyses will compare changes in help-seeking intentions for the intervention condition relative to the wait-list control condition using mixed-effect repeated-measures analyses to account for clustering within schools. DISCUSSION: If proven effective, this universal social connectedness program for suicide could be more widely delivered in Australian high schools, providing a valuable new resource. The Sources of Strength program has the potential to significantly contribute to the mental health of young people in Australia by improving help-seeking for suicide. The findings from this research will also contribute to the evidence-base for peer-leadership programs internationally. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000048482 . Registered on 19 January 2016.

A pilot randomized controlled trial of the e-couch anxiety and worry program in schools.

The aim of this pilot study was to evaluate the acceptability and feasibility of delivering an online anxiety prevention program in schools, and to assess the effectiveness of the intervention in reducing symptoms of anxiety. Three schools located in South Australia and the Australian Capital Territory were recruited to participate in the trial, with classes randomly allocated to the intervention or wait-list control condition. All participants (N = 225) were invited to complete a pre-intervention, post-intervention and 3-month follow-up questionnaire. Participants in the intervention condition completed the online e-couch Anxiety and Worry program during one class period a week for six weeks. No significant differences were found between the intervention and control conditions at post-intervention or 3-month follow-up for generalised anxiety (Cohen's d = - 0.09-0.08), social anxiety (d = 0.09 & - 0.26), anxiety sensitivity (d = 0.19 & - 0.15), depressive symptoms (d = 0.01 & 0.08) or mental wellbeing (d = 0.17 & 0.30). Online anxiety prevention programs are acceptable and can be feasibly delivered in schools. Although not significant, the sizes of some of the effects obtained in this pilot trial are consistent with earlier studies, and warrant further investigation in a larger trial.

Systematic item selection process applied to developing item pools for assessing multiple mental health problems.

OBJECTIVES: Given high rates of comorbidity among mental disorders, better methods to rapidly screen across multiple mental disorders are needed. Building on existing Patient Reported Outcomes Measurement Information System (PROMIS) item banks, the present study aimed to select items to assess panic disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, adult attention-deficit hyperactivity disorder, substance use disorder, suicidal thoughts and behaviors, and psychosis. STUDY DESIGN AND SETTING: A four-stage process to select items involved systematic literature searches, item refinement and standardization, obtaining feedback from consumers and experts, and reduction of item pools in preparation for calibration in a population-based sample. RESULTS: From 6,900 items collected across the eight mental health conditions, 2,002 were standardized and rated by small groups of consumers and experts. Expert ratings of item relevance tended to correlate moderately with consumer ratings, with variation across conditions. An algorithm was used to generate final item pools ranging from 45 to 75 items. CONCLUSION: The study successfully applied a systematic process to select items for assessing a range of mental disorders. This process for item selection may be applied to additional mental and physical health conditions. The calibration of the present item pools into final item banks will enable the development of flexible measures to assess risk of mental health problems, although more effectively accounting for comorbidity.

A systematic review and evaluation of measures for suicidal ideation and behaviors in population-based research.

The use of measures of suicidal ideation and behavior with sound measurement properties is critical in identifying people most at risk of suicide. In particular, brief self-report measures of suicidal ideation and behaviors are needed for use in large-scale population-based research and in the development and evaluation of suicide prevention programs in the community. This review aimed to identify and recommend psychometrically sound self-report measures of suicidal ideation and behaviors that could be used in population-based research of adults. To identify existing self-report measures for adult use, a systematic search was conducted using MEDLINE (Medical Literature Analysis and Retrieval System Online) and PsycINFO (Psychological Information Database) databases. Abstracts, reference lists, and previous review papers were screened. Once measures were identified, we used a hierarchical criterion-based approach to assess their utility, psychometric properties, and appropriateness for population-based research. Nineteen measures were evaluated against 6 criteria. Three brief measures that met all criteria of the evaluation and demonstrated adequate psychometric properties were the Depressive Symptom Index Suicidality Subscale (DSI-SS), Suicidal Behaviors Questionnaire-Revised (SBQ-R), and Suicidal Ideation Attributes Scale (SIDAS). None of the comprehensive measures met all criteria for use in population-based studies, due to financial costs imposed on use, although the Beck Scale for Suicide Ideation (BSSI) and the Adult Suicidal Ideation Questionnaire (ASIQ) had considerable evidence of psychometric robustness. Suicide researchers are encouraged to further establish the validity of scores on these measures across diverse adult populations.

A systematic review of help-seeking interventions for depression, anxiety and general psychological distress.

BACKGROUND: Depression and anxiety are treatable disorders, yet many people do not seek professional help. Interventions designed to improve help-seeking attitudes and increase help-seeking intentions and behaviour have been evaluated in recent times. However, there have been no systematic reviews of the efficacy or effectiveness of these interventions in promoting help-seeking. Therefore, this paper reports a systematic review of published randomised controlled trials targeting help-seeking attitudes, intentions or behaviours for depression, anxiety, and general psychological distress. METHODS: Studies were identified through searches of PubMed, PsycInfo, and the Cochrane database in November 2011. Studies were included if they included a randomised controlled trial of at least one intervention targeting help-seeking for depression or anxiety or general psychological distress, and contained extractable data on help-seeking attitudes or intentions or behaviour. Studies were excluded if they focused on problems or conditions other than the target (e.g., substance use, eating disorder). RESULTS: Six published studies of randomised controlled trials investigating eight different interventions for help-seeking were identified. The majority of trials targeted young adults. Mental health literacy content was effective (d = .12 to .53) in improving help-seeking attitudes in the majority of studies at post-intervention, but had no effect on help-seeking behaviour (d = -.01, .02). There was less evidence for other intervention types such as efforts to destigmatise or provide help-seeking source information. CONCLUSIONS: Mental health literacy interventions are a promising method for promoting positive help-seeking attitudes, but there is no evidence that it leads to help-seeking behaviour. Further research investigating the effects of interventions on attitudes, intentions, and behaviour is required.

Mycobacterial disease in a population of 339 cats in Great Britain: II. Histopathology of 225 cases, and treatment and outcome of 184 cases.

This study investigated 339 cases of feline mycobacterial infection, with histopathology findings from 225 cases, and treatment and outcome information from 184 cases. Tissue samples from cats with cutaneous lesions or suspicious masses at exploratory laparotomy were submitted to the Veterinary Laboratories Agency for mycobacterial culture over a 4-year period to December 2008. The study reviewed the files for information about histopathology, treatment and outcome, and blindly reviewed histopathological changes (including staining for acid-fast bacteria [AFB]) in a sub-set of 45 cases. When a cat is suspected of having a mycobacterial infection, accurate identification of the species involved helps to determine possible treatment options and prognosis. The study confirmed that histopathology and the presence of AFB are useful tools in the recognition of mycobacterial infection. Unfortunately, they did little to help determine the species of mycobacteria involved. The study identified a group of cats that were negative for AFB at the primary laboratory, but from which mycobacteria could be cultured; commonly Mycobacterium bovis or Mycobacterium microti. The study also identified a group of cats which where culture negative, despite typical signs of mycobacterial infection and positive AFB staining. Many cases responded favourably to treatment (56% of the cases where information was available), and many cats gained complete remission (42%). However, relapses were common (64%) and often followed by pulmonary and/or systemic spread that may have resulted from treatment with short courses of single drugs. This study shows that the diagnosis and treatment of feline mycobacteriosis is complex and challenging.

Mycobacterial disease in cats in Great Britain: I. Culture results, geographical distribution and clinical presentation of 339 cases.

This study investigated 339 cases of feline mycobacterial disease from cats with cutaneous lesions or masses found at exploratory laparotomy. Tissue samples were submitted to the Veterinary Laboratories Agency for mycobacterial culture over a 4-year period to December 2008. The study assessed which species of culturable mycobacteria were involved, where the cats lived, and their clinical presentation (physical findings, serum biochemistry, radiography, feline leukaemia virus and feline immunodeficiency virus status). Mycobacterium microti was cultured from 19%, Mycobacterium bovis 15%, Mycobacterium avium 7%, non-M avium non-tuberculous mycobacteria 6%, with no growth in 53% of samples. M microti, M bovis and M avium were found in almost mutually exclusive clusters within Great Britain (GB) (ie, M bovis in South-West England/Wales/Welsh Border, M avium in eastern England and M microti south of London and in South-West Scotland). While differences were seen in the clinical presentation and distribution of lesions caused by the different infections, these were not sufficiently different to be diagnostic. Cats commonly presented with single or multiple cutaneous lesions (74%), which were sometimes ulcerated or discharging, located most frequently on the head (54%). Lymph nodes were usually involved (47%); typically the submandibular nodes. Systemic or pulmonary signs were rarely seen (10-16%). When a cat is suspected of having mycobacteriosis, accurate identification of the species involved helps to determine appropriate action. Our findings show that knowing the cat's geographic location can be helpful, while the nature of the clinical presentation is less useful. Most cases of feline mycobacterial disease in GB are cutaneous.

Familiar other-race faces show normal holistic processing and are robust to perceptual stress.

Other-race individuals are remembered more poorly and receive less holistic/configural processing than same-race individuals, at least when faces are novel. Here, we examine the amelioration of these effects with familiarity, using distinctiveness-matched Caucasian and Asian stimulus sets. We confirmed a cross-race deficit for upright faces following a single encoding trial, which disappeared rapidly with practice on a small set of other-race 'friends' and did not re-emerge when perceptual processing was put under stress (presentation in the periphery). We also examined holistic/configural processing for familiarised faces using the peripheral inversion effect (McKone, 2004 Journal of Experimental Psychology: Learning, Memory, and Cognition 30 181 - 197). A test for faces and nonface objects (dogs) confirmed the validity of this technique as providing a direct measure of holistic processing; we then showed that, after 1 h of training, holistic processing was as strong for other-race as same-race faces. We conclude that practice with other-race individuals can rapidly engage normal face-processing mechanisms.