Depression predicts emergency care use in people with chronic obstructive pulmonary disease: a large cohort study in primary care.

Background: Depression is common in people with chronic obstructive pulmonary disease (COPD) and has been associated with a variety of poor outcomes. A large proportion of health care costs in the UK are spent on emergency care. This study examined the prospective relationship between depression and use of emergency care in patients with COPD managed in primary care. Methods: This was a twelve-month, prospective longitudinal study of 355 patients with COPD in six primary care practices in the UK. Baseline measures included demographic characteristics, depression and anxiety, severity of COPD, presence or absence of other chronic diseases, and prior use of emergency care. Outcome measures were (a) number of emergency department (ED) visits; or (b) an emergency hospital admission in the follow-up year. Results: Older age, number of comorbid physical health conditions, severity of COPD, prior use of emergency care, and depression were all independently associated with both ED attendance and an emergency hospital admission in the follow-up year. Subthreshold depression (HADS depression score 4-7) was associated with a 2.8 times increased odds of emergency hospital admission, and HADS depression >8 was associated with 4.8 times increased odds. Conclusion: Depression is a predictor of emergency care in COPD, independent of severity of disease or physical comorbidity. Even mild (subthreshold) symptoms of depression more than double the risk of using emergency care, suggesting there is a strong case to develop and deploy integrated preventive strategies in primary care that can promote mental health in people with COPD.

The effect of socioeconomic status on treatment and pregnancy outcomes in women with epilepsy in Scotland.

Compared to the background population, people with epilepsy tend to have lower rates of education and employment, lower rates of marriage and childbearing, and lower overall socioeconomic status (SES). Disparities in epilepsy care based on sociodemographic factors have been observed in the literature, but it is not known whether any such disparities exist in the UK. The UK Epilepsy and Pregnancy Register is a prospective, observational, registration and follow-up study that was set up to determine the relative safety of all AEDs taken in pregnancy. Here, we report outcomes of registered pregnancies to women with epilepsy living in Scotland from December 1996 to June 2012, based on the degree of socioeconomic deprivation of their postcode area. The Scottish Index of Multiple Deprivation (SIMD) quintile scores from 2006 were used to determine degree of socioeconomic deprivation, and group 1 (most deprived) and group 5 (least deprived) were compared. There were 1526 pregnancies with complete outcome data to women living in Scotland. Of these, 1453 (95.1%) resulted in a live birth and 68 (4.7%) had a major congenital malformation (MCM). Postcodes could not be reliably identified or verified for an additional three women, who have been excluded from SIMD group analysis. Of all women included in this study, 32.4% were in group 1 and 13.2% in group 5. No difference in MCM rate was observed between the two groups (4.4% in group 1 compared to 4.7% in group 5, p=0.84). Women in group 5 were more likely to take preconceptual folic acid (56.8% compared to 14.0%, relative risk: 4.1; 95% CI: 3.1-5.2) and less likely to have generalized tonic-clonic seizures in pregnancy (13.0% compared to 29.2%, relative risk: 0.4; 95% CI: 0.3-0.7) than those in group 1. Women in group 5 were more likely to be on monotherapy regimens (80.2% compared to 65.9%, relative risk: 1.2; 95% CI: 1.1-1.3), less likely to be on valproate (19.5% compared to 28.0%, p=0.05), and more likely to be on lower doses of the drug (825.9mg/day compared to 1012.0mg/day, p=0.05) compared to those in group 1. Although no change in MCM rate was seen based on SES, differences in treatment between socioeconomic groups do exist, particularly for preconceptual folic acid consumption, AED regimen, and seizure frequency. Greater emphasis on the importance of preconceptual counseling, both to discuss AED choice and folic acid intake, would be of benefit, particularly to those living in areas of high socioeconomic deprivation, to improve equity of healthcare delivery for women with epilepsy in Scotland.

Specific collaborative group intervention for patients with medically unexplained symptoms in general practice: a cluster randomized controlled trial.

BACKGROUND: Patients with medically unexplained symptoms (MUS) are frequent in primary care and substantially impaired in their quality of life (QoL). Specific training of general practitioners (GPs) alone did not demonstrate sustained improvement at later follow-up in current reviews. We evaluated a collaborative group intervention. METHODS: We conducted a cluster randomized controlled trial. Thirty-five GPs recruited 304 MUS patients (intervention group: 170; control group: 134). All GPs were trained in diagnosis and management of MUS (control condition). Eighteen randomly selected intervention GPs participated in training for a specific collaborative group intervention. They conducted 10 weekly group sessions and 2 booster meetings in their practices, together with a psychosomatic specialist. Six and 12 months after baseline, QoL was assessed with the Short-Form 36. The primary outcome was the physical composite score (PCS), and the secondary outcome was the mental composite score (MCS). RESULTS: At 12 months, intention-to-treat analyses showed a significant between-group effect for the MCS (p = 0.023) but not for the PCS (p = 0.674). This effect was preceded by a significant reduction of somatic symptom severity (15-item somatic symptom severity scale of the Patient Health Questionnaire, PHQ-15) at 6 months (p = 0.008) that lacked significance at 12 months (p = 0.078). As additional between-group effects at 12 months, per-protocol analyses showed less health anxiety (Whiteley-7; p = 0.038) and less psychosocial distress (PHQ; p = 0.024); GP visits were significantly (p = 0.042) reduced in the intervention group. CONCLUSIONS: Compared to pure GP training, collaborative group intervention achieved a progressive, clinically meaningful improvement in mental but not physical QoL. It could bridge gaps between general practice and mental health care.

ASC-dependent RIP2 kinase regulates reduced PGE2 production in chronic periodontitis.

Levels of prostaglandin E(2) (PGE(2)) and its processing enzyme, prostaglandin-endoperoxide-synthase-2/ cyclooxygenase-2 (PTGS2/COX-2), are elevated in actively progressing periodontal lesions, but suppressed in chronic disease. COX-2 expression is regulated through inflammatory signaling that converges on the mitogen-activated protein kinase (MAPK) pathway. Emerging evidence suggests a role for the inflammatory adaptor protein, ASC/Pycard, in MAPK activation. We postulated that ASC may represent a mediator of the MAPK-mediated regulatory network of PGE(2) production. Using RNAi-mediated gene slicing, we demonstrated that ASC regulates COX-2 expression and PGE(2) production in THP1 monocytic cells following infection with Porphyromonas gingivalis (Pg). Production of PGE(2) did not require the inflammasome adaptor function of ASC, but was dependent on MAPK activation. Furthermore, the MAP kinase kinase kinase CARD domain-containing protein RIPK2 was induced by Pg in an ASC-dependent manner. Reduced ASC and RIPK2 levels were revealed by orthogonal comparison of the expression of the RIPK family in ASC-deficient THP1 cells with that in chronic periodontitis patients. We show that pharmacological inhibition of RIPK2 represses PGE(2) secretion, and RNAi-mediated silencing of RIPK2 leads to diminished MAPK activation and PGE(2) secretion. These findings identify a novel ASC-RIPK2 axis in the generation of PGE(2) that is repressed in patients diagnosed with chronic adult periodontitis.

Brief psychodynamic interpersonal psychotherapy for patients with multisomatoform disorder: randomised controlled trial.

BACKGROUND: Multisomatoform disorder is characterised by severe and disabling bodily symptoms, and pain is one of the most common and impairing of these. Furthermore, these bodily symptoms cannot be explained by an underlying organic disorder. Patients with multisomatoform disorder are commonly found at all levels of healthcare and are typically difficult to treat for physicians as well as for mental health specialists. AIMS: To test whether brief psychodynamic interpersonal therapy (PIT) effectively improves the physical quality of life in patients who have had multisomatoform disorder for at least 2 years. METHOD: We recruited 211 patients (from six German academic outpatient centres) who met the criteria for multisomatoform disorder for a randomised, controlled, 12-week, parallelgroup trial from 1 July 2006 to 1 January 2009 (International Standard Randomised Controlled Trial Number ISRCTN23215121). We randomly assigned the patients to receive either 12 weekly sessions of PIT (n = 107) or three sessions of enhanced medical care (EMC, n = 104). The physical component summary of the Short Form Health Survey (SF-36) was the pre-specified primary outcome at a 9-month follow-up. RESULTS: Psychodynamic interpersonal therapy improved patients' physical quality of life at follow-up better than EMC (mean improvement in SF-36 score: PIT 5.3, EMC 2.2), with a small to medium between-group effect size (d = 0.42, 95% CI 0.15-0.69, P = 0.001). We also observed a significant improvement in somatisation but not in depression, health anxiety or healthcare utilisation. CONCLUSIONS: This trial documents the long-term efficacy of brief PIT for improving the physical quality of life in patients with multiple, difficult-to-treat, medically unexplained symptoms.

A preliminary study of a measure of role-play competence in psychodynamic interpersonal therapy.

We report a 15-item role-play competence measure. Ratings by three judges of 34 role plays from psychodynamic interpersonal therapy training showed good inter-rater (.73-.79) and internal reliability (.84-.96). Validity was supported as scores were statistically significantly associated with psychotherapy experience. Most participants achieved satisfactory ratings supporting the training.

Levetiracetam in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register.

It is not known whether the antiepileptic drug (AED) levetiracetam can be used safely in human pregnancy. As part of a study to determine the risks of major congenital malformations (MCMs) for infants exposed to AEDs in utero, we identified all cases exposed to levetiracetam. Three of 117 exposed pregnancies had an MCM (2.7%; 95% CI 0.9% to 7.7%); all 3 were exposed to other AEDs.

Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register.

OBJECTIVE: To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs). METHODS: Prospective data collected by the UK Epilepsy and Pregnancy Register were analysed. The presence of MCMs recorded within the first three months of life was the main outcome measure. RESULTS: Full outcome data were collected on 3607 cases. The overall MCM rate for all AED exposed cases was 4.2% (95% confidence interval (CI), 3.6% to 5.0%). The MCM rate was higher for polytherapy (6.0%) (n = 770) than for monotherapy (3.7%) (n = 2598) (crude odds ratio (OR) = 1.63 (p = 0.010), adjusted OR = 1.83 (p = 0.002)). The MCM rate for women with epilepsy who had not taken AEDs during pregnancy (n = 239) was 3.5% (1.8% to 6.8%). The MCM rate was greater for pregnancies exposed only to valproate (6.2% (95% CI, 4.6% to 8.2%) than only to carbamazepine (2.2% (1.4% to 3.4%) (OR = 2.78 (p<0.001); adjusted OR = 2.97 (p<0.001)). There were fewer MCMs for pregnancies exposed only to lamotrigine than only to valproate. A positive dose response for MCMs was found for lamotrigine (p = 0.006). Polytherapy combinations containing valproate carried a higher risk of MCM than combinations not containing valproate (OR = 2.49 (1.31 to 4.70)). CONCLUSIONS: Only 4.2% of live births to women with epilepsy had an MCM. The MCM rate for polytherapy exposure was greater than for monotherapy exposure. Polytherapy regimens containing valproate had significantly more MCMs than those not containing valproate. For monotherapy exposures, carbamazepine was associated with the lowest risk of MCM.

Cluster analysis of symptoms and health seeking behaviour differentiates subgroups of patients with severe irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous condition which is diagnosed according to specific bowel symptom clusters. The aim of the present study was to identify subgroups of IBS subjects using measures of rectal sensitivity and psychological symptoms, in addition to bowel symptoms. Such groupings, which cross conventional diagnostic approaches, may provide greater understanding of the pathogenesis of the condition and its treatment. METHOD: A K means cluster analysis was used to group 107 clinic patients with IBS according to physiological, physical, and psychological parameters. All patients had severe IBS and had failed to respond to usual medical treatment. Twenty nine patients had diarrhoea predominant IBS, 26 constipation predominant, and 52 had an alternating bowel habit. RESULTS: The clusters were most clearly delineated by two variables: "rectal perceptual threshold (volume)" and "number of doctor visits". Three subgroups were formed. Group I comprised patients with low distension thresholds and high rates of psychiatric morbidity, doctor consultations, interpersonal problems, and sexual abuse. Group II also had low distension thresholds but low rates of childhood abuse and moderate levels of psychiatric disorders. Group III had high distension thresholds, constipation or alternating IBS, and low rates of medical consultations and sexual abuse. CONCLUSION: The marked differences across the three groups suggest that each may have a different pathogenesis and respond to different treatment approaches. Inclusion of psychosocial factors in the analysis enabled more clinically meaningful groups to be identified than those traditionally determined by bowel symptoms alone or rectal threshold.

Randomised controlled trial of brief psychological intervention after deliberate self poisoning.

OBJECTIVES: To determine the effects of a brief psychological intervention (brief psychodynamic interpersonal therapy) for patients after deliberate self poisoning compared with usual treatment. To compare the impact of the active intervention and usual treatment on patients' satisfaction with care. DESIGN: Randomised controlled trial. PARTICIPANTS: 119 adults who had deliberately poisoned themselves and presented to the emergency department of a teaching hospital. SETTING: Community based study. INTERVENTION: Four sessions of therapy delivered in the patient's home. Control patients received "treatment as usual," which in most cases consisted of referral back to their general practitioner. OUTCOME MEASURES: Severity of suicidal ideation six months after treatment as assessed by the Beck scale for suicidal ideation. Secondary outcome measures at six month follow up included depressive symptoms as measured by the Beck depression inventory, patient satisfaction with treatment, and self reported subsequent attempts at self harm. RESULTS: Participants randomised to the intervention had a significantly greater reduction in suicidal ideation at six month follow up compared with those in the control group (reduction in the mean (SD) Beck scale 8.0 v 1.5). They were more satisfied with their treatment and were less likely to report repeated attempts to harm themselves at follow up (proportion repeating 9% v 28% in control group; difference 19%, 95% confidence interval 9% to 30 %, P=0.009). CONCLUSION: Brief psychodynamic interpersonal therapy may be a valuable treatment after people have deliberately tried to poison themselves.

Epstein-Barr virus immediate-early protein BRLF1 interacts with CBP, promoting enhanced BRLF1 transactivation.

The Epstein-Barr virus (EBV) immediate-early protein BRLF1 is a transcriptional activator that mediates the switch from latent to lytic viral replication. Many transcriptional activators function, in part, due to an interaction with histone acetylases, such as CREB-binding protein (CBP). Here we demonstrate that BRLF1 interacts with the amino and carboxy termini of CBP and that multiple domains of the BRLF1 protein are necessary for this interaction. Furthermore, we show that the interaction between BRLF1 and CBP is important for BRLF1-induced activation of the early lytic EBV gene SM in Raji cells.

Health-related quality of life and health care costs in severe, refractory irritable bowel syndrome.

BACKGROUND: The irritable bowel syndrome (IBS) may lead to considerable impairment of health-related quality of life and high health care costs. It is not clear whether these poor outcomes directly result from severe bowel symptoms or reflect a coexisting psychiatric disorder. OBJECTIVE: To determine whether bowel symptom severity and psychological symptoms directly influence health-related quality of life and health care costs. DESIGN: Cross-sectional survey. SETTING: Secondary and tertiary gastroenterology clinics. PATIENTS: 257 patients with severe IBS who did not respond to usual treatments and were recruited for a trial of psychological treatment. MEASUREMENTS: Predictors were abdominal pain, entries in a diary of 10 IBS symptoms, and measures of psychological symptoms. Outcomes were inability to work, health-related quality of life (measured by Medical Outcomes Survey 36-item short-form questionnaire [SF-36] physical component summary scores), and health care and productivity costs. Predictor and outcome measures were compared by using multiple regression and logistic regression analyses. RESULTS: Abdominal pain occurred on average 24 days per month and activities were restricted on 145 days of the previous 12 months. The mean (+/-SD) Hamilton depression score was 11.3 +/- 6.1. The SF-36 physical component summary score was low (37.7 +/- 10.6), and the patients had incurred high health care costs ($1743 +/- $2263) over the previous year. Global severity and somatization scores on the Symptom Checklist 90 Revised, abdominal pain, and Hamilton depression scores independently contributed to the physical component score of the SF-36 (adjusted R(2) = 35.2%), but only psychological scores were associated with disability due to ill health. These variables did not accurately predict health care or other costs (adjusted R(2) = 9.3%). History of sexual abuse was not an independent predictor of outcome. CONCLUSIONS: Both abdominal and psychological symptoms are independently associated with impaired health-related quality of life in patients with severe IBS. Optimal treatment is likely to require a holistic approach. Since health care and loss of productivity costs are not clearly associated with these symptoms, alleviation of them will not necessarily lead to reduced costs.

Psychiatric status, somatisation, and health care utilization of frequent attenders at the emergency department: a comparison with routine attenders.

Seventy-seven frequent attenders at an emergency department (ED) in an inner-city hospital in the UK (defined as seven or more visits in the previous 12 months) were compared with 182 patients who were attending the same department on a routine basis. Patients completed the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and the Short Form (SF)-36. Information was obtained on 64% of the frequent attenders and 45% underwent a detailed psychiatric assessment. Of the frequent attenders, 45% had psychiatric disorder and 49% had some form of an alcohol-related disorder. Compared with routine attenders, frequent attenders reported lower health status, had more psychiatric disorder (odds ratio: OR=8.2, 95% confidence interval: CI=3.8--18.1), had more general hospital admissions (OR=19.9, 95% CI=8.3--47.8), more psychiatric admissions (OR=167.5, 95% CI=9.5--2959.0), and more GP visits (95% CI for difference=-10.2 to -5.7). There was no evidence that frequent attenders had more somatisation than routine attenders. Specific treatment and management strategies need to be developed for this group of patients, although a substantial proportion may be difficult to engage in the treatment process.

Comparing two different methods of identifying alcohol related problems in the emergency department: a real chance to intervene?

OBJECTIVES: To examine the feasibility of screening for alcohol problems in a representative flow sample of patients attending a busy UK emergency department. To compare two methods of identifying alcohol related problems in the emergency department. METHODS: Brief interview administered by the same interviewer to a representative flow sample of 429 patients attending a single accident and emergency department over a six week period. Measures included a CAGE questionnaire and assessments by the patient and staff as to whether the attendance was alcohol related. RESULTS: 413 patients (96%) were successfully screened. Of these, 115 (28%) patients were considered to have an alcohol related attendance on the basis of the CAGE questionnaire or the staff assessment. Head injuries and psychiatric presentations were particularly likely to be associated with alcohol misuse. Compared with those identified by staff, patients scoring above threshold on the CAGE were more likely to attend during routine working hours and recognise they had an alcohol problem. CONCLUSIONS: Emergency departments may provide an opportunity for the early prevention of alcohol related difficulties. However, patients with alcohol problems who present to the emergency department are not a homogenous group. Different screening methods identify different groups of patients, who in turn may respond to different forms of intervention. Further research examining the efficacy and feasibility of different alcohol treatment approaches is needed to enable us to target specific interventions to those patients who might most benefit.

Functional evolution of the Myb oncogene family.

Three Myb-related genes (A-Myb, B-Myb, and c- Myb) have been found in all vertebrates examined thus far including mammals, birds, and amphibians. Two invertebrates, the sea urchin and the fruit fly, have only one Myb-related gene. Our laboratory has used Drosophila as a model system to explore the function of its sole Myb gene. We have also reintroduced the three different vertebrate Myb genes into Drosophila in order to begin to understand how their different functions may have arisen following gene duplication during evolution.

Psychotherapy for patients with complex disorders and chronic symptoms. The need for a new research paradigm.

BACKGROUND: A clear distinction has been made between efficacy and effectiveness in relation to the methods of evaluation of new psychological treatments in psychiatry. Efficacy trials target patients with relatively pure conditions, who may not be representative of the patients who are usually referred for psychological treatment in a clinical setting. Few studies have explored the benefits of psychotherapy in patients with complex disorders and enduring symptoms. AIMS: To explore the rationale for the distinction between efficacy and effectiveness, particularly in relation to outcome studies of patients with complex and enduring disorders. METHOD: A narrative review with examples drawn from the literature, and an illustration of a recent naturalistic outcome study which combines features of both efficacy and effectiveness. RESULTS: Studies of patients with complex and mixed disorders can be designed so that they retain internal validity, but also have external validity and are relevant to clinical practice. CONCLUSION: Studies which evaluate psychological interventions should be carried out in populations of patients clinically representative of those who are likely to receive the intervention, should it be shown to be of benefit.