Changes in immunoglobulin levels during clozapine treatment in schizophrenia.

BACKGROUND AND HYPOTHESIS: Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored. DESIGN: This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS). RESULTS: IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: ß = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: ß = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: ß = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: ß = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03). CONCLUSIONS: The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

A survey of foot disinfection practices for control of bovine digital dermatitis; evaluating solution depth, footbath hygiene, and the potential of footbaths as infection reservoirs for Treponema species.

Bovine digital dermatitis remains a widespread endemic disease of dairy cattle worldwide. Footbathing is commonly used as a control measure and has significant economic and environmental impact. There are few studies documenting footbathing practices on dairy farms, or evaluating their suitability for achieving foot disinfection. This study describes footbathing practices on 32 farms observed in the United Kingdom, Ireland, and the Netherlands. We measured solution depth throughout footbathing and observed levels below 7cm on 9/32 farms, which leads to inadequate foot coverage. Solution depth was associated with the number of cow passages, decreasing by 1.2cm for every 100 cow passages. We also describe levels of organic matter content (g/L) throughout footbathing as a proxy for footbath hygiene. Our data indicates that almost half of footbaths (15/32) became contaminated above the 20g/L threshold to which veterinary biocides are tested for efficacy, and that organic matter content is associated with the number of cow passages per liter of footbathing solution provided. A multivariable mixed model predicted that one liter of footbathing solution per cow should be sufficient to prevent excess contamination. As a further measure of hygiene, we tested a subset of footbath samples to quantify the amount of DNA present from the Treponema species which are considered instrumental in the etiology of digital dermatitis. We did not detect Treponema DNA in footbath samples, suggesting they are unlikely to act as infection reservoirs for this disease. Multivariable mixed models including farm identity as a random effect demonstrated that for both change in solution depth and organic matter content the effect of farm-level factors was large. Because of the magnitude of this farm effect, applying model predictions will not translate to adequate solution depth and hygiene on all farms. Our data highlights the importance of footbath auditing on individual farms.

Online behavioural activation during the COVID-19 pandemic decreases depression and negative affective bias.

BACKGROUND: The COVID-19 pandemic highlighted the need for mental health interventions that can be easily disseminated during a crisis. Behavioural activation (BA) is a cost-effective treatment that can be administered by non-specialists; however, it is unclear whether it is still effective during a time of lockdown and social distancing, when opportunities for positive activity are significantly constrained. METHODS: Between May and October 2020, we randomised 68 UK participants with mild to moderate low mood to either a 4-week online programme of non-specialist administered BA or to a passive control group. Before and after the intervention, we collected self-report data on mood and COVID-related disruption, as well as measuring emotional cognition as an objective marker of risk for depression. RESULTS: In comparison to the control group, the BA group showed a significant decrease in depression, anxiety and anhedonia after the intervention, as well as an increase in self-reported activation and social support. Benefits persisted at 1-month follow-up. BA also decreased negative affective bias on several measures of the Facial Emotion Recognition Task and early change in bias was associated with later therapeutic gain. Participants rated the intervention as highly acceptable. CONCLUSION: This study highlights the benefits of online BA that can be administered by non-specialists after brief training. These findings can help inform the policy response towards the rising incidence of mental health problems during a crisis situation such as a pandemic. They also highlight the use of objective cognitive markers of risk across different treatment modalities.

Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial.

BACKGROUND: This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. METHODS: This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18-60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. RESULTS: A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. CONCLUSIONS: After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

Translating the promise of 5HT4 receptor agonists for the treatment of depression.

Animal experimental studies suggest that 5-HT4 receptor activation holds promise as a novel target for the treatment of depression and cognitive impairment. 5-HT4 receptors are post-synaptic receptors that are located in striatal and limbic areas known to be involved in cognition and mood. Consistent with this, 5-HT4 receptor agonists produce rapid antidepressant effects in a number of animal models of depression, and pro-cognitive effects in tasks of learning and memory. These effects are accompanied by molecular changes, such as the increased expression of neuroplasticity-related proteins that are typical of clinically useful antidepressant drugs. Intriguingly, these antidepressant-like effects have a fast onset of their action, raising the possibility that 5-HT4 receptor agonists may be a particularly useful augmentation strategy in the early stages of SSRI treatment. Until recently, the translation of these effects to humans has been challenging. Here, we review the evidence from animal studies that the 5-HT4 receptor is a promising target for the treatment of depression and cognitive disorders, and outline a potential pathway for the efficient and cost-effective translation of these effects into humans and, ultimately, to the clinic.

Measuring the impact of bovine digital dermatitis research on knowledge and practice of biosecurity during cattle foot-trimming.

This research communication reports the results from questionnaires used to identify the impact of recent research into the disinfection of cattle foot-trimming equipment to prevent bovine digital dermatitis (BDD) transmission on (a) biosecurity knowledge and (b) hygiene practice of foot health professionals. An initial questionnaire found that more than half of participating farmers, veterinary surgeons and commercial foot-trimmers were not considering hand or hoof-knife hygiene in their working practices. The following year, after the release of a foot-trimming hygiene protocol and a comprehensive knowledge exchange programme by the University of Liverpool, a second survey showed 35/80 (43.8%) farmers, veterinary surgeons and commercial foot-trimmers sampled considered they were now more aware of the risk of spreading BDD during foot- trimming. Furthermore, 36/80 (45.0%) had enhanced their hygiene practice in the last year, impacting an estimated 1383 farms and 5130 cows trimmed each week. Participants who reported having seen both the foot-trimming hygiene protocol we developed with AHDB Dairy and other articles about foot-trimming hygiene in the farming and veterinary press, were significantly more likely to have changed their working practices. Difficulties accessing water and cleaning facilities on farms were identified as the greatest barrier to improving biosecurity practices. Participants' preferred priority for future research was continued collection of evidence for the importance and efficacy of good foot-trimming hygiene practices.

Mental health workers perceptions of disaster response in China.

BACKGROUND: The post-disaster mental health crisis intervention (MHCI) system in China remains immature and unsystematic. We aim to report the perceptions of a large sample of MHCI workers and government administrators and provide recommendations for developing a national mental health disaster response management plan in China. METHODS: An in-depth qualitative study was conducted, collecting data from 20 focus-group discussions and 25 key stakeholder interviews. These recruited participants who had been involved in different types of disaster rescue across 7 provinces/cities where disasters have recently occurred. We used thematic analysis to analyze the data and relevant findings were extracted for policy recommendation. RESULTS: Mental health workers' perspectives were examined in detailed according to four core themes: forms of organization, intervention pathway, intervention strategy and technique, and public health information. Post-disaster MHCI should be approached in teams that are integrated with emergency medicine systems, and be led by unified command management. All levels of local health and family planning commission should prepare post-disaster MHCI work plans and build response teams/emergency centres. Future training for MHCI workers should focus on: building a sense of trust within the team; clarifying each member's role; strengthening the screening, assessment and referrals training for psychological professionals; and providing psychological intervention training for Chinese psychiatrists. It is necessary to set up guiding principles for disaster research ethics, mental health rehabilitation and media interaction. CONCLUSIONS: Through exploring and analyzing the perceptions of current disaster response mental health workers and government administrators, our findings provide essential recommendations for developing a national to county level post-disaster MHCI emergency management plan and can guide the formulation of relevant laws and regulation in China.

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review.

BACKGROUND: Schizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes. METHOD: A systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics). RESULTS: Nineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons. CONCLUSIONS: Tentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs.

Positive and negative personality descriptors: UK dataset of self-referential valence, imageability and subjective frequency ratings of 300 adjectives for use in cognitive-emotional tasks.

Experimental tasks comparing participants' performance for categorising, remembering, and recognising positive and negative words are widely used in the emotional cognitive domain. Such tasks are commonly used in experimental psychology and psychiatry research, and have been shown to be sensitive biomarkers of depression and antidepressant drug action [1,2]. In addition, several of these tasks investigate self-referential processing i.e., the processing of information relevant to oneself; this has been shown to modify the way emotional words are encoded and remembered and may be a target that is amenable to treatment [3,4]. In practice, the development of such tasks for implementation in research studies often depends on the selection and matching of words according to characteristics such as valence or arousal, imageability, word frequency and word length to investigate differences in a chosen domain of interest whilst keeping important confounds constant. This introduces a need for ratings covering a range of word attributes that have been shown to affect processing. In particular, ratings of self-referential valence (how positively or negatively subjects feel about a word when this is used to describe themselves/their circumstances) have been seldom included in databases, despite the frequent investigation of the concept in research [1,5]. Other important attributes often considered in the process of matching and selection are word imageability and subjective frequency [6,7]. To facilitate the word selection and matching process required in cognitive-emotional task development, the present dataset provides subjective ratings for 150 positive and 150 negative adjectives describing personality characteristics. Across four online surveys, the 300 words were rated on self-referential valence, imageability and subjective frequency by representative samples of 200 UK-based, English-speaking adults. Basic demographics and data on depressive symptoms and state anxiety were collected from all participants. Comprehensive descriptive statistics and word length were calculated for each of the 300 words. All data cleaning and statistical analysis was performed in R. Our work is based on years of experience using the Oxford Emotional Task Battery [1,5] and may be particularly relevant for researchers using self-referential cognitive tasks with UK-based samples.

An online experimental medicine trial on the effect of 28-day simvastatin administration on emotional processing, reward learning, working memory and salivary cortisol in healthy volunteers at risk for depression: OxSTEP protocol.

BACKGROUND: Evidence suggests inflammation may be a key mechanism by which psychosocial stress, including loneliness, predisposes to depression. Observational and clinical studies have suggested simvastatin, with its anti-inflammatory properties, may have a potential use in the treatment of depression. Previous experimental medicine trials investigating 7-day use of statins showed conflicting results, with simvastatin displaying a more positive effect on emotional processing compared with atorvastatin. It is possible that statins require longer administration in predisposed individuals before showing the expected positive effects on emotional processing. AIMS: Here, we aim to test the neuropsychological effects of 28-day simvastatin administration versus placebo, in healthy volunteers at risk for depression owing to loneliness. METHOD: This is a remote experimental medicine study. One hundred participants across the UK will be recruited and randomised to either 28-day 20 mg simvastatin or placebo in a double-blind fashion. Before and after administration, participants will complete an online testing session involving tasks of emotional processing and reward learning, processes related to vulnerability to depression. Working memory will also be assessed and waking salivary cortisol samples will be collected. The primary outcome will be accuracy in identifying emotions in a facial expression recognition task, comparing the two groups across time.

Evaluation of Horn Bud Wound Healing Following Cautery Disbudding of Dairy Calves With and Without the Use of Oxytetracycline Aerosol Spray.

Oxytetracycline is commonly applied as a topical agent to burn lesions post cautery disbudding of calves. Judicial use of antibiotics dictates that they should only be used where necessary to reduce the development of resistance in target bacteria. The objective of this study, therefore, was to evaluate the efficacy of topical oxytetracycline spray on wound healing post cautery disbudding of dairy calves over a 6-week period. Dairy calves were disbudded by veterinarians, technicians, or veterinary surgeons, using a standard cautery disbudding protocol. Oxytetracycline spray was randomly applied to the right or left horn bud of each animal (OXY), while the other horn bud received no antibiotic spray (NA). The outcomes measured were wound diameter (WD) and lesion score (LS), either normal healing (NH) or abnormal healing (AH). These assessments were conducted every 14 days following disbudding, until 42 days. A total of 360 animals completed the study. There was a difference in wound diameter and lesion score on day 14 post disbudding between the two groups. Cautery lesions sprayed with oxytetracycline (OXY) were 0.5 ± 0.15 mm smaller than NA lesions (P = 0.001), and there were fewer abnormal healing lesions for OXY compared to the NA (2.5 vs. 11%, respectively; P ≤ 0.001). There were no differences at day 28 and day 42 post disbudding, and on day 42, 34% of wounds had healed in both groups. In summary, the authors were unable to demonstrate a difference in healing between the groups using the described methods.

Associations Between Statin Use and Negative Affective Bias During COVID-19: An Observational, Longitudinal UK Study Investigating Depression Vulnerability.

BACKGROUND: There is growing interest in the antidepressant potential of statins. We tested whether statin use is associated with cognitive markers previously found to indicate psychological vulnerability to depression within the context of the COVID-19 pandemic. METHODS: Between April 2020 and February 2021, we conducted an observational online study of 2043 adults in the United Kingdom. Participants completed cognitive tasks assessing processes related to depression vulnerability, including affective bias and reward processing. We also measured working memory, medication use, and current psychiatric symptoms. Using mixed analysis of covariance and regression models, we compared participants on statins alone (n = 81), antihypertensive medication alone (n = 126), both medications (n = 111), and on neither medication (n = 1725). RESULTS: Statin use was associated with reduced recognition of angry and fearful faces (F1 = 9.19, p = .002; F1 = 6.9, p = .009) and with increased misclassification of these expressions as positive. Increased recognition of angry faces at baseline predicted increased levels of depression and anxiety 10 months later (ß = 3.61, p = .027; ß = 2.37, p = .002). Statin use was also associated with reduced learning about stimuli associated with loss (F1,1418 = 9.90, p = .002). These indicators of reduced negative bias were not seen in participants taking antihypertensive medication alone, suggesting that they were related to statin use in particular rather than nonspecific demographic factors. In addition, we found no evidence of an association between statin use and impairment in working memory. CONCLUSIONS: Statin use was associated with cognitive markers indicative of reduced psychological vulnerability to depression, supporting their potential use as a prophylactic treatment for depression.

Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research.

Impaired cognition is often overlooked in the clinical management of depression, despite its association with poor psychosocial functioning and reduced clinical engagement. There is an outstanding need for new treatments to address this unmet clinical need, highlighted by our consultations with individuals with lived experience of depression. Here we consider the evidence to support different pharmacological approaches for the treatment of impaired cognition in individuals with depression, including treatments that influence primary neurotransmission directly as well as novel targets such as neurosteroid modulation. We also consider potential methodological challenges in establishing a strong evidence base in this area, including the need to disentangle direct effects of treatment on cognition from more generalised symptomatic improvement and the identification of sensitive, reliable and objective measures of cognition.

Subcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia.

The neurobiological effects of clozapine are under characterised. We examined the effects clozapine treatment on subcortical volume and cortical thickness and investigated whether macrostructural changes were linked to alterations in glutamate or N-acetylaspartate (NAA). Data were acquired in 24 patients with treatment-resistant schizophrenia before and 12 weeks after switching to clozapine. During clozapine treatment we observed reductions in caudate and putamen volume, lateral ventricle enlargement (P < 0.001), and reductions in thickness of the left inferior temporal cortex, left caudal middle frontal cortex, and the right temporal pole. Reductions in right caudate volume were associated with local reductions in NAA (P = 0.002). None of the morphometric changes were associated with changes in glutamate levels. These results indicate that clozapine treatment is associated with subcortical volume loss and cortical thinning and that at least some of these effects are linked to changes in neuronal or metabolic integrity.

Changes in Brain Glutamate on Switching to Clozapine in Treatment-Resistant Schizophrenia.

It has been suggested that the antipsychotic clozapine may modulate brain glutamate, and that this effect could contribute to its efficacy in treatment-resistant schizophrenia (TRS). The aim of this study was to examine the effects of clozapine on brain glutamate in TRS longitudinally. This study examined individuals with TRS before and 12 weeks after switching from a non-clozapine antipsychotic to treatment with clozapine as part of their normal clinical care. Proton magnetic resonance spectroscopy (1H-MRS) measured concentrations, corrected for voxel tissue content, of glutamate (Glucorr), and glutamate plus glutamine (Glxcorr) in the anterior cingulate cortex (ACC) and right caudate nucleus. Symptoms were monitored using the Positive and Negative Syndrome Scale (PANSS). Of 37 recruited patients (27 men, 39.30 years old, 84% clozapine naïve), 25 completed 1H-MRS at both timepoints. 12 weeks of clozapine was associated with a longitudinal reduction in Glucorr in the caudate (n = 23, F = 7.61 P = .01) but not in the ACC (n = 24, F = 0.02, P = .59). Percentage reduction in caudate Glucorr was positively correlated with percentage improvement in symptoms (total PANSS score, n = 23, r = .42, P = .04). These findings indicate that reductions in glutamate in the caudate nucleus may contribute to symptomatic improvement during the first months of clozapine treatment.

DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia.

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

Survival of bovine digital dermatitis treponemes on hoof knife blades and the effects of various disinfectants.

BACKGROUND: Bovine digital dermatitis (BDD) is a painful infectious foot disease of cattle, and much evidence implicates a pathogenic role for treponemes. This study measured the survival of BDD treponemes on hoof knife blades and tested the efficacy of relevant disinfectants under laboratory conditions. METHODS: Two strains of BDD treponemes were applied to hoof knife blades under aerobic conditions. Swabs were taken at different time points (10 minutes, one hour, two hours, four hours and 18 hours) and again after 20-second disinfection time with one of five disinfectants. Swabs were used directly for nested PCR to detect treponemes or inoculated for anaerobic growth, and subsequently examined using phase contrast microscopy and PCR. RESULTS: BDD treponeme DNA was detectable by nested PCR at all survival time points, and these organisms were culturable from hoof knives for two hours after exposure under aerobic conditions in the laboratory. Three of the five disinfectants-1 per cent volume per volume (v/v) FAM30®, 2 per cent weight per volume (w/v) Virkon® or 2 per cent (v/v) sodium hypochlorite-were effective at preventing visible growth of treponemes following 20-seconds contact, and 1 per cent (v/v) FAM30® also prevented detection of treponemes by PCR. CONCLUSION: Treponeme viability of two hours under aerobic conditions suggests BDD treponemes could be transmitted between cows on hoof knives. It is therefore important to apply a disinfection protocol during foot-trimming; the authors have identified three common disinfectants that may be suitable.

Repeatability and Feasibility of Pressure Algometry for Quantifying Mechanical Nociceptive Threshold in the Thoracic Region of Calves.

Pressure algometry can be used to quantify mechanical nociceptive threshold (MNT) in humans and animals. If reliable this may be a useful tool to examine calves for increased mechanical sensitivity, which may be induced by disease or pain. This study measures the repeatability and feasibility of pressure algometry using a handheld digital pressure algometer (PRODPlus, Top Cat metrology) using three serial measurements applied to six sites on the thoraces of 35 healthy calves by two different operators. The range of MNTs recorded in healthy calves was 1.2-25 Newtons (median = 10.1 IQR = 7.1-14.0). A multivariable mixed effects model identified that the MNT's recorded were influenced by Operator, Site, and Calf. Intra and inter-operator reliability were measured by intra-class correlation coefficients (ICCs). Based on average ICCs, intra-operator reliability at two sites was good; one site overlying the ventral aspect of the 6th intercostal space [ICC = 0.79 95% CI (0.63-0.89)] and the other overlying the dorsal aspect of the 9th intercostal space [ICC = 0.75 95% CI (0.56-0.87)]. Average ICCs for three other measurement sites were moderate or poor, and one site proved unfeasible. For inter-operator agreement average ICCs showed that agreement was also good at the same 6 and 9th intercostal space, [ICCs = 0.77 95% CI (0.35-0.90) and 0.77 95% CI (0.54-0.88), respectively], agreement was moderate for the remainder of the sites. This study identifies two sites that are potentially useful for monitoring of thoracic sensitivity as an indicator of pain in calves by means of pressure algometry using the average of three measurements. It also identifies sources of variability to be considered when applying the tool for clinical or research purposes.

Targeting relapse prevention and positive symptom in first-episode schizophrenia using brief cognitive behavioral therapy: A pilot randomized controlled study.

The present study aimed to provide preliminary evaluation of the effectiveness of a brief CBT intervention focusing on relapse prevention and positive symptom in a Chinese first episode schizophrenia (FES) population. This randomized controlled trial recruited eighty outpatients with FES (as determined using the DSM-IV), aged 16-45 years, and on a current atypical antipsychotic. Patients were randomized to either 10 sessions of individual CBT (intervention group) adjunctive to treatment as usual (TAU) or TAU alone (control group). Outcome assessment of symptoms, relapse, hospitalization, insight and social functioning were administered at baseline and then post treatment (10 weeks), and at 6-month and 12-month follow ups. At 12 months, patients in the intervention group had significantly greater improvements in positive symptoms, general psychopathology and social functioning, as well as significantly lower rates of relapse, compared to the control group. Although patients in both groups demonstrated significantly improved negative symptom and insight scores from baseline, no group differences were found. This RCT demonstrates that FES patient can greatly benefit from CBT designed to target relapse prevention and positive symptom, with improvements sustained for 1 year following treatment.