Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK

Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history. Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted

CXC chemokines and antimicrobial peptides in rhinovirus-induced experimental asthma exacerbations

RATIONALE: Rhinoviruses (RVs) are the major triggers of asthma exacerbations. We have shown previously that lower respiratory tract symptoms, airflow obstruction, and neutrophilic airway inflammation were increased in experimental RV-induced asthma exacerbations. OBJECTIVES: We hypothesized that neutrophil-related CXC chemokines and antimicrobial peptides are increased and related to clinical, virologic, and pathologic outcomes in RV-induced exacerbations of asthma. METHODS: Protein levels of antimicrobial peptides (SLPI, HNP 1–3, elafin, and LL-37) and neutrophil chemokines (CXCL1/GRO-α, CXCL2/GRO-β, CXCL5/ENA-78, CXCL6/GCP-2, CXCL7/NAP-2, and CXCL8/IL-8) were determined in bronchoalveolar lavage (BAL) fluid of 10 asthmatics and 15 normal controls taken before, at day four during and 6 weeks post-experimental infection. RESULTS: BAL HNP 1–3 and Elafin were higher, CXCL7/NAP-2 was lower in asthmatics compared with controls at day 4 (P = 0.035, P = 0.048, and P = 0.025, respectively). BAL HNP 1–3 and CXCL8/IL-8 were increased during infection (P = 0.003 and P = 0.011, respectively). There was a trend to increased BAL neutrophils at day 4 compared with baseline (P = 0.076). BAL HNP 1–3 was positively correlated with BAL neutrophil numbers at day 4. There were no correlations between clinical parameters and HNP1–3 or IL-8 levels. CONCLUSIONS: We propose that RV infection in asthma leads to increased release of CXCL8/IL-8, attracting neutrophils into the airways where they release HNP 1–3, which further enhances airway neutrophilia. Strategies to inhibit CXCL8/IL-8 may be useful in treatment of virus-induced asthma exacerbations

Implementation of routine outcome measurement in child and adolescent mental health services in the United Kingdom: a critical perspective

The aim of this commentary is to provide an overview of clinical outcome measures that are currently recommended for use in UK Child and Adolescent Mental Health Services (CAMHS), focusing on measures that are applicable across a wide range of conditions with established validity and reliability, or innovative in their design. We also provide an overview of the barriers and drivers to the use of Routine Outcome Measurement (ROM) in clinical practice

Soluble major histocompatibility complex class I-related chain B molecules are increased and correlate with clinical outcomes during rhinovirus infection in healthy subjects

BACKGROUND: Surface major histocompatibility complex class I-related chain (MIC) A and B molecules are increased by IL-15 and have a role in the activation of natural killer group 2 member D-positive natural killer and CD8 T cells. MICA and MICB also exist in soluble forms (sMICA and sMICB). Rhinoviruses (RVs) are the major cause of asthma exacerbations, and IL-15 levels are decreased in the airways of subjects with asthma. The role of MIC molecules in immune responses in the lung has not been studied. Here, we determine the relationship between MICA and MICB and RV infection in vitro in respiratory epithelial cells and in vivo in healthy subjects and subjects with asthma. METHODS: Surface MICA and MICB, as well as sMICA and sMICB, in respiratory epithelial cells were measured in vitro in response to RV infection and exposure to IL-15. Levels of sMICA and sMICB in serum, sputum, and BAL were measured and correlated with blood and bronchoalveolar immune cells in healthy subjects and subjects with asthma before and during RV infection. RESULTS: RV increased MICA and MICB in vitro in epithelial cells. Exogenous IL-15 upregulated sMICB levels in RV-infected epithelial cells. Levels of sMICB molecules in serum were increased in healthy subjects compared with subjects with stable asthma. Following RV infection, airway levels of sMIC are upregulated, and there are positive correlations between sputum MICB levels and the percentage of bronchoalveolar natural killer cells in healthy subjects but not subjects with asthma. CONCLUSIONS: RV infection induces MIC molecules in respiratory epithelial cells in vitro and in vivo. Induction of MICB molecules is impaired in subjects with asthma, suggesting these molecules may have a role in the antiviral immune response to RV infections

An intervention modelling experiment to change GP's intentions to implement evidence-based practice : using theory-based interventions to promote GP management of upper respiratory tract infection without prescribing antibiotics #2

Background: Psychological theories of behaviour may provide a framework to guide the design of interventions to change professional behaviour. Behaviour change interventions, designed using psychological theory and targeting important motivational beliefs, were experimentally evaluated for effects on the behavioural intention and simulated behaviour of GPs in the management of uncomplicated upper respiratory tract infection (URTI). Methods: The design was a 2 × 2 factorial randomised controlled trial. A postal questionnaire was developed based on three theories of human behaviour: Theory of Planned Behaviour; Social Cognitive Theory and Operant Learning Theory. The beliefs and attitudes of GPs regarding the management of URTI without antibiotics and rates of prescribing on eight patient scenarios were measured at baseline and post-intervention. Two theory-based interventions, a "graded task" with "action planning" and a "persuasive communication", were incorporated into the post-intervention questionnaire. Trial groups were compared using co-variate analyses. Results: Post-intervention questionnaires were returned for 340/397 (86%) GPs who responded to the baseline survey. Each intervention had a significant effect on its targeted behavioural belief: compared to those not receiving the intervention GPs completing Intervention 1 reported stronger self-efficacy scores (Beta = 1.41, 95% CI: 0.64 to 2.25) and GPs completing Intervention 2 had more positive anticipated consequences scores (Beta = 0.98, 95% CI = 0.46 to 1.98). Intervention 2 had a significant effect on intention (Beta = 0.90, 95% CI = 0.41 to 1.38) and simulated behaviour (Beta = 0.47, 95% CI = 0.19 to 0.74). Conclusion: GPs' intended management of URTI was significantly influenced by their confidence in their ability to manage URTI without antibiotics and the consequences they anticipated as a result of doing so. Two targeted behaviour change interventions differentially affected these beliefs. One intervention also significantly enhanced GPs' intentions not to prescribe antibiotics for URTI and resulted in lower rates of prescribing on patient scenarios compared to a control group. The theoretical frameworks utilised provide a scientific rationale for understanding how and why the interventions had these effects, improving the reproducibility and generalisability of these findings and offering a sound basis for an intervention in a "real world" trial. Trial registration: Clinicaltrials.gov NCT00376142This study is funded by the European Commission Research Directorate as part of a multi-partner program: Research Based Education and Quality Improvement (ReBEQI): A Framework and tools to develop effective quality improvement programs in European healthcare. (Proposal No: QLRT-2001-00657)

Translating clinicians' beliefs into implementation interventions (TRACII) : a protocol for an intervention modeling experiment to change clinicians' intentions to implement evidence-based practice

Background: Biomedical research constantly produces new findings, but these are not routinely incorporated into health care practice. Currently, a range of interventions to promote the uptake of emerging evidence are available. While their effectiveness has been tested in pragmatic trials, these do not form a basis from which to generalise to routine care settings. Implementation research is the scientific study of methods to promote the uptake of research findings, and hence to reduce inappropriate care. As clinical practice is a form of human behaviour, theories of human behaviour that have proved to be useful in other settings offer a basis for developing a scientific rationale for the choice of interventions. Aims: The aims of this protocol are 1) to develop interventions to change beliefs that have already been identified as antecedents to antibiotic prescribing for sore throats, and 2) to experimentally evaluate these interventions to identify those that have the largest impact on behavioural intention and behavioural simulation. Design: The clinical focus for this work will be the management of uncomplicated sore throat in general practice. Symptoms of upper respiratory tract infections are common presenting features in primary care. They are frequently treated with antibiotics, and research evidence is clear that antibiotic treatment offers little or no benefit to otherwise healthy adult patients. Reducing antibiotic prescribing in the community by the "prudent" use of antibiotics is seen as one way to slow the rise in antibiotic resistance, and appears safe, at least in children. However, our understanding of how to do this is limited. Participants will be general medical practitioners. Two theory-based interventions will be designed to address the discriminant beliefs in the prescribing of antibiotics for sore throat, using empirically derived resources. The interventions will be evaluated in a 2 × 2 factorial randomised controlled trial delivered in a postal questionnaire survey. Two outcome measures will be assessed: behavioural intention and behavioural simulation.This study is funded by the European Commission Research Directorate as part of a multi-partner program: Research Based Education and Quality Improvement (ReBEQI): A Framework and tools to develop effective quality improvement programs in European healthcare. (Proposal No: QLRT-2001-00657)

Bronchial mucosal inflammation and illness severity in response to experimental rhinovirus infection in COPD

Background Respiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity. Objectives We sought to determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16–induced COPD exacerbations and its relationship to disease severity. Methods Bronchial mucosal inflammatory cell phenotypes were determined at preinfection baseline and following experimental RV infection in 17 Global Initiative for Chronic Obstructive Lung Disease stage II subjects with COPD and as controls 20 smokers and 11 nonsmokers with normal lung function. No subject had a history of asthma/allergic rhinitis: all had negative results for aeroallergen skin prick tests. Results RV infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T lymphocytes in patients with COPD and nonsmokers. Monocytes/macrophages, CD4+ T lymphocytes, and CD20+ B lymphocytes were increased in all subjects. At baseline, compared with nonsmokers, subjects with COPD and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T lymphocytes but fewer numbers of CD4+ T lymphocytes and CD20+ B lymphocytes. The virus-induced inflammatory cells in patients with COPD were positively associated with virus load, illness severity, and reductions in lung function. Conclusions Experimental RV infection induces bronchial mucosal eosinophilia and neutrophilia only in patients with COPD and monocytes/macrophages and lymphocytes in both patients with COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load and illness severity. Antiviral/anti-inflammatory therapies could attenuate bronchial inflammation and ameliorate virus-induced COPD exacerbations

Entangled-State Cycles of Atomic Collective-Spin States

We study quantum trajectories of collective atomic spin states of $N$ effective two-level atoms driven with laser and cavity fields. We show that interesting ``entangled-state cycles'' arise probabilistically when the (Raman) transition rates between the two atomic levels are set equal. For odd (even) $N$, there are $(N+1)/2$ ($N/2$) possible cycles. During each cycle the $N$-qubit state switches, with each cavity photon emission, between the states $(|N/2,m>\pm |N/2,-m>)/\sqrt{2}$, where $|N/2,m>$ is a Dicke state in a rotated collective basis. The quantum number $m$ ($>0$), which distinguishes the particular cycle, is determined by the photon counting record and varies randomly from one trajectory to the next. For even $N$ it is also possible, under the same conditions, to prepare probabilistically (but in steady state) the Dicke state $|N/2,0>$, i.e., an $N$-qubit state with $N/2$ excitations, which is of particular interest in the context of multipartite entanglement.Comment: 10 pages, 9 figure

The use of routine outcome measures in two child and adolescent mental health services: a completed audit cycle

Background: Routine outcome measurement (ROM) is important for assessing the clinical effectiveness of health services and for monitoring patient outcomes. Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption of ROM in CAMHS has been supported by both national and local initiatives (such as government strategies, local commissioning policy, and research). Methods: With the aim of assessing how these policies and initiatives may have influenced the uptake of ROM within two different CAMHS we report the findings of two case-note audits: a baseline audit conducted in January 2011 and a re-audit conducted two years later in December 2012-February 2013. Results: The findings show an increase in both the single and repeated use of outcome measures from the time of the original audit, with repeated use (baseline and follow-up) of the Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing from 10% to 50% of cases. Re-audited case-notes contained more combined use of different outcome measures, with greater consensus on which measures to use. Outcome measures that were applicable across a wide range of clinical conditions were more likely to be used than symptom-specific measures, and measures that were completed by the clinician were found more often than measures completed by the service user. Conclusions: The findings show a substantial improvement in the use of outcome measures within CAMHS. These increases in use were found across different service organisations which were subject to different types of local service priorities and drivers

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial

Oral capecitabine (Xeloda<sup>®</sup>) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK