Effect of intramuscular methadone on pharmacokinetic data and thermal and mechanical nociceptive thresholds in the cat

Objectives The aim of the study was to assess simultaneous pharmacokinetics and thermal and mechanical antinociception after intramuscular methadone (0.6 mg/kg) in 10 cats. Methods Thermal and mechanical threshold (TT and MT, respectively) testing and blood collection were conducted at baseline and up to 24 h after administration. Methadone plasma concentrations were determined by liquid chromatography–tandem mass spectrometry and pharmacokinetic parameters were estimated by a non-compartmental method. TT and MT were analysed using ANOVA ( P &lt;0.05). Time of maximum plasma concentration (Tmax), time of onset of antinociception and time of reaching cut-out threshold (TT 55°C; MT 30 Newtons [N]) were determined. Results TT and MT increased above baseline from 20–240 mins and 5–40 mins, respectively, after intramuscular (IM) administration ( P &lt;0.005). Mean maximum delta T (measured as TT minus baseline threshold) was 7.9°C (95% confidence interval [CI] 4.3–11.6) at 60 mins and mean maximum delta F (measured as MT minus baseline threshold) was 4.2 (95% CI 1.6–6.7) N at 45 mins. IM methadone concentration–time data decreased curvilinearly, and gave a clearance estimate of mean 9.1 ml/kg/min (range 5.2–15.7) with median Tmax at 20 mins (range 5–360 mins). Conclusions and relevance IM data followed classical disposition and elimination in all cats. Plasma concentrations after IM administration were associated with an antinociceptive effect, including negative hysteresis. These data can be used for devising dosing schedules for methadone in clinical feline practice. </jats:sec

Data Collection for the Fourth Multicentre Confidential Enquiry into Perioperative Equine Fatalities (CEPEF4) Study:New Technology and Preliminary Results

It is almost 20 years since the largest observational, multicentre study evaluating the risks of mortality associated with general anaesthesia in horses. We proposed an internet-based method to collect data (cleaned and analysed with R) in a multicentre, cohort, observational, analytical, longitudinal and prospective study to evaluate peri-operative equine mortality. The objective was to report the usefulness of the method, illustrated with the preliminary data, including outcomes for horses seven days after undergoing general anaesthesia and certain procedures using standing sedation. Within six months, data from 6701 procedures under general anaesthesia and 1955 standing sedations from 69 centres were collected. The results showed (i) the utility of the method; also, that (ii) the overall mortality rate for general anaesthesia within the seven-day outcome period was 1.0%. In horses undergoing procedures other than exploratory laparotomy for colic (“noncolics”), the rate was lower, 0.6%, and in “colics” it was higher, at 3.4%. For standing sedations, the overall mortality rate was 0.2%. Finally, (iii) we present some descriptive data that demonstrate new developments since the previous CEPEF2. In conclusion, horses clearly still die unexpectedly when undergoing procedures under general anaesthesia or standing sedation. Our method is suitable for case collection for future studies

Disruption of MEF2C signaling and loss of sarcomeric and mitochondrial integrity in cancer-induced skeletal muscle wasting

Cancer cachexia is a highly debilitating paraneoplastic disease observed in more than 50% of patients with advanced cancers and directly contributes to 20% of cancer deaths. Loss of skeletal muscle is a defining characteristic of patients with cancer cachexia and is associated with poor survival. The present study reveals the involvement of a myogenic transcription factor Myocyte Enhancer Factor (MEF) 2C in cancer-induced skeletal muscle wasting. Increased skeletal muscle mRNA expression of Suppressor of Cytokine Signaling (Socs) 3 and the IL-6 receptor indicative of active IL-6 signaling was seen in skeletal muscle of mice bearing the Colon 26 (C26) carcinoma. Loss of skeletal muscle structural integrity and distorted mitochondria were also observed using electron microscopy. Gene and protein expression of MEF2C was significantly downregulated in skeletal muscle from C26-bearing mice. MEF2C gene targets myozenin and myoglobin as well as myokinase were also altered during cachexia, suggesting dysregulated oxygen transport capacity and ATP regeneration in addition to distorted structural integrity. In addition, reduced expression of calcineurin was observed which suggested a potential pathway of MEF2C dysregulation. Together, these effects may limit sarcomeric contractile ability and also predispose skeletal muscle to structural instability; associated with muscle wasting and fatigue in cachexia

Intravenous postoperative fluid prescriptions for children: A survey of practice

<p>Abstract</p> <p>Background</p> <p>Postoperative deaths and neurological injury have resulted from hyponatraemia associated with the use of hypotonic saline solutions following surgery. We aimed to determine the rates and types of intravenous fluids being prescribed postoperatively for children in the UK.</p> <p>Methods</p> <p>A questionnaire was sent to members of the British Association of Paediatric Surgeons (BAPS) and Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI) based at UK paediatric centres. Respondents were asked to prescribe postoperative fluids for scenarios involving children of different ages. The study period was between May 2006 and November 2006.</p> <p>Results</p> <p>The most frequently used solution was sodium chloride 0.45% with glucose 5% although one quarter of respondents still used sodium chloride 0.18% with glucose 4%. Isotonic fluids were used by 41% of anaesthetists and 9.8% of surgeons for the older child, but fewer for infants. Standard maintenance rates or greater were prescribed by over 80% of respondents.</p> <p>Conclusion</p> <p>Most doctors said they would prescribe hypotonic fluids at volumes equal to or greater than traditional maintenance rates at the time of the survey. A survey to describe practice since publication of National Patient Safety Agency (NPSA) recommendations is required.</p

Delivering cognitive therapy for adolescent social anxiety disorder in NHS CAMHS: a clinical and cost analysis

Background: Cognitive therapy, based on the Clark & Wells (1995) model, is a first-line treatment for adults with social anxiety disorder (SAD), and findings from research settings suggest it has promise for use with adolescents (Cognitive Therapy for Social Anxiety disorder in Adolescents; CT-SAD-A). However, for the treatment to be suitable for delivery in routine clinical care, two questions need to be addressed. Aims: Can therapists be trained to achieve good outcomes in routine Child and Adolescent Mental Health Services (CAMHS), and what are the costs associated with training and treatment. Methods: CAMHS therapists working in two NHS trusts received training in CT-SAD-A. They delivered the treatment to adolescents with SAD during a period of supervised practice. We examined the clinical outcomes for the 12 patients treated during this period, and estimated costs associated with treatment and training. Results: Treatment produced significant improvements in social anxiety symptoms, general anxiety and depression symptoms, and reductions in putative process measures. 75% (9 out of 12) patients showed a reliable and clinically significant improvement in social anxiety symptoms and 64% (7/11) lost their primary diagnosis of SAD. The total cost to the NHS of the CT-SAD-A treatment was £4047 (SD=1003) per adolescent treated, of which £1861 (SD=£358) referred to the specific estimated cost of face-to-face delivery; the remaining cost was for training and supervising therapists who were not previously familiar with the treatment. Conclusions: This study provides preliminary evidence that clinicians can deliver good patient outcomes for adolescents with SAD in routine CAMHS during a period of supervised practice after receiving a two-day training workshop. Furthermore, the cost of delivering CT-SAD-A with adolescents appeared to be no more than the cost of delivering CT-SAD with adults

Cognitive therapy compared with CBT for social anxiety disorder in adolescents: a feasibility study

Background: Social anxiety disorder (SAD) is common, typically starts in adolescence and has a low natural recovery rate. Existing psychological treatments for adolescent SAD are only moderately effective. It is possible that recovery rates for adolescents could be substantially improved by adapting a psychological therapy that is highly effective among adults with SAD. Objectives: To train child and adolescent mental health services (CAMHS) therapists to deliver cognitive therapy for SAD in adolescents (CT-SAD-A) and assess therapist competence. To estimate the costs to the NHS of training therapists to deliver CT-SAD-A and the mean cost per adolescent treated. To examine the feasibility of a randomised controlled trial (RCT) to compare CT-SAD-A with the general form of cognitive-behavioural therapy that is more commonly used. Design: During the training phase of the study, it became clear that the RCT would not be feasible because of high staff turnover and unfilled posts within CAMHS and changes in the nature of referrals, which meant that few young people with primary SAD were accessing some of the participating services. The study design was altered to comprise the following: a training case series of CT-SAD-A delivered in routine CAMHS, an estimate of the cost to the NHS of training therapists to deliver CT-SAD-A and of the mean cost per adolescent treated, and qualitative interviews with participating young people, parents, therapists and service managers/leads. Setting: Five CAMHS teams within Berkshire Healthcare and Oxford Health NHS Foundation Trusts. Participants: Eight therapists received training in CT-SAD-A. Twelve young people received CT-SAD-A, delivered by six therapists. Six young people, six parents, seven therapists and three managers participated in qualitative interviews. Interventions: Cognitive therapy for social anxiety disorder in adolescents (CT-SAD-A). Main outcome measures: Measured outcomes included social anxiety symptoms and diagnostic status, comorbid symptoms of anxiety and depression, social and general functioning, concentration in class and treatment acceptability. Patient level utilisation of the intervention was collected using clinicians’ logs. Results: Nine out of 12 participants achieved good outcomes across measures (r ≥ 0.60 across social anxiety measures). The estimated cost of delivering CT-SAD-A was £1861 (standard deviation £358) per person. Qualitative interviews indicated that the treatment was acceptable to young people, parents and therapists, but therapists and managers experienced challenges when implementing the training and treatment within the current CAMHS context. Limitations: Findings were based on a small, homogeneous sample and there was no comparison arm. Conclusions: CT-SAD-A is a promising treatment for young people with SAD, but the current CAMHS context presents challenges for its implementation