Royal South Hants Hospital

Goal-directed behavior requires the continuous monitoring and dynamic adjustment of ongoing actions. Here, we report a direct coupling between the event-related electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), and behavioral measures of performance monitoring in humans. By applying independent component analysis to EEG signals recorded simultaneously with fMRI, we found the single-trial error-related negativity of the EEG to be systematically related to behavior in the subsequent trial, thereby reflecting immediate behavioral adjustments of a cognitive performance monitoring system. Moreover, this trial-by-trial EEG measure of performance monitoring predicted the fMRI activity in the rostral cingulate zone, a brain region thought to play a key role in processing of response errors. We conclude that investigations of the dynamic coupling between EEG and fMRI provide a powerful approach for the study of higher order brain functions.

BACKGROUND: This paper presents a structured review of the published information on the mortality of schizophrenia. METHOD: A meta-analysis of the literature. RESULTS: Schizophrenia has a significantly increased mortality from natural and unnatural causes. Twenty-eight percent of the excess mortality is attributable to suicide and 12% to accidents. The rest of the excess mortality is from the same broad range of conditions which cause deaths in the general population. Further interpretation is hampered by confounding variables, wide confidence intervals and reservations about generalising from individual cohorts. CONCLUSIONS: The available evidence suggests that schizophrenia is associated with a large increased mortality from suicide and a moderate increased mortality from natural causes. A number of possible interventions have been identified, but we do not yet have reliable means of detecting any changes in mortality which might result.

BACKGROUND: Nucleoside analogues against herpes simplex virus (HSV) have been shown to suppress shedding of HSV type 2 (HSV-2) on genital mucosal surfaces and may prevent sexual transmission of HSV. METHODS: We followed 1484 immunocompetent, heterosexual, monogamous couples: one with clinically symptomatic genital HSV-2 and one susceptible to HSV-2. The partners with HSV-2 infection were randomly assigned to receive either 500 mg of valacyclovir once daily or placebo for eight months. The susceptible partner was evaluated monthly for clinical signs and symptoms of genital herpes. Source partners were followed for recurrences of genital herpes; 89 were enrolled in a substudy of HSV-2 mucosal shedding. Both partners were counseled on safer sex and were offered condoms at each visit. The predefined primary end point was the reduction in transmission of symptomatic genital herpes. RESULTS: Clinically symptomatic HSV-2 infection developed in 4 of 743 susceptible partners who were given valacyclovir, as compared with 16 of 741 who were given placebo (hazard ratio, 0.25; 95 percent confidence interval, 0.08 to 0.75; P=0.008). Overall, acquisition of HSV-2 was observed in 14 of the susceptible partners who received valacyclovir (1.9 percent), as compared with 27 (3.6 percent) who received placebo (hazard ratio, 0.52; 95 percent confidence interval, 0.27 to 0.99; P=0.04). HSV DNA was detected in samples of genital secretions on 2.9 percent of the days among the HSV-2-infected (source) partners who received valacyclovir, as compared with 10.8 percent of the days among those who received placebo (P<0.001). The mean rates of recurrence were 0.11 per month and 0.40 per month, respectively (P<0.001). CONCLUSIONS: Once-daily suppressive therapy with valacyclovir significantly reduces the risk of transmission of genital herpes among heterosexual, HSV-2-discordant couples.

Summary: Different strains of staphylococci vary in ability to produce free coagulase. Methods are given for the selection of suitable strains and for the production and concentration of coagulase from one of them. Of animal plasmas examined, cow, sheep, dog, guinea-pig and mouse showed a relative deficiency in coagulase activator, while plasma of man, monkey, horse, cat, pig, fowl and rabbit contained the most. Coagulase activator resembles prothrombin closely in physical properties such as thermolability, behaviour during salting out and removal by adsorbents. They are both partly lost in blood clotting and in dicumarol poisoning, but while prothrombin is apparently removed from plasma by repeated Seitz filtration there is no loss of activator. The question of probable identity is discussed. Antibody to coagulase is present in the sera many normal individuals and in those suffering from chronic staphylococcal infections. The intramuscular injection of coagulase adsorbed on aluminium phosphate produces similar antibodies in the sera of rabbits.

Nonadherence to immunosuppressants is recognized to occur after renal transplantation, but the size of its impact on transplant survival is not known. A systematic literature search identified 325 studies (in 324 articles) published from 1980 to 2001 reporting the frequency and impact of nonadherence in adult renal transplant recipients. Thirty-six studies meeting the inclusion criteria for further review were grouped into cross-sectional and cohort studies and case series. Meta-analysis was used to estimate the size of the impact of nonadherence on graft failure. Only two studies measured adherence using electronic monitoring, which is currently thought to be the most accurate measure. Cross-sectional studies (n=15) tended to rely on self-report questionnaires, but these were poorly described; a median (interquartile range) of 22% (18%-26%) of recipients were nonadherent. Cohort studies (n=10) indicated that nonadherence contributes substantially to graft loss; a median (interquartile range) of 36% (14%-65%) of graft losses were associated with prior nonadherence. Meta-analysis of these studies showed that the odds of graft failure increased sevenfold (95% confidence interval, 4%-12%) in nonadherent subjects compared with adherent subjects. Standardized methods of assessing adherence in clinical populations need to be developed, and future studies should attempt to identify the level of adherence that increases the risk of graft failure. However, this review shows nonadherence to be common and to have a large impact on transplant survival. Therefore, significant improvements in graft survival could be expected from effective interventions to improve adherence.

A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.

OBJECTIVE: To assess the reliability and validity of the Southampton mindfulness questionnaire (SMQ), a 16-item measure of mindful awareness of distressing thoughts and images. METHODS: A total of 256 people participated, comprising a non-clinical community sample of 134 (83 meditators and 51 non-meditators) and a clinical sample of 122 people with a current distressing psychosis. To assess concurrent validity, non-clinical participants and half clinical participants (total 197 participants) completed the mindful attention awareness scale (MAAS). Predicted links were assessed with affect, and 59 patients completed a validated measure to assess link between mindfulness and intensity of 'delusional' experience. RESULTS: The scale has a single factor structure, was internally reliable, significantly correlated with the MAAS, showed expected associations with affect, and distinguished among meditators, non-meditators and people with psychosis. CONCLUSIONS: The data support use of the SMQ in clinical practice and research to assess mindful responding to distressing thoughts and images.

BACKGROUND: The role of prophylactic antibacterial agents after chemotherapy remains controversial. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary, severe neutropenia (fewer than 500 neutrophils per cubic millimeter). Patients were randomly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period. The primary outcome was the incidence of clinically documented febrile episodes (temperature of more than 38 degrees C) attributed to infection. Secondary outcomes included the incidence of all probable infections, severe infections, and hospitalization but did not include a systematic evaluation of antibacterial resistance. RESULTS: A total of 1565 patients underwent randomization (784 to placebo and 781 to levofloxacin). The tumors included breast cancer (35.4 percent), lung cancer (22.5 percent), testicular cancer (14.4 percent), and lymphoma (12.8 percent). During the first cycle of chemotherapy, 3.5 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 7.9 percent in the placebo group (P<0.001). During the entire chemotherapy course, 10.8 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 15.2 percent of patients in the placebo group (P=0.01); the respective rates of probable infection were 34.2 percent and 41.5 percent (P=0.004). Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group (P=0.004). The respective rate of severe infection was 1.0 percent and 2.0 percent (P=0.15), with four infection-related deaths in each group. An organism was isolated in 9.2 percent of probable infections. CONCLUSIONS: Among patients receiving chemotherapy for solid tumors or lymphoma, the prophylactic use of levofloxacin reduces the incidence of fever, probable infection, and hospitalization.

A Cognitive View of Delusions and Voices. The Practice of Therapy and the Problem of Engagement. Delusions: Assessment and Formulation. Challenging Delusions. Voices: Engagement and Assessment. Disputing and Testing Beliefs about Voices. Cognitive Therapy for Paranoia. Challenging Cases and Issues. From a Symptom Model to a Person Model. References. Appendices. Index.

The 2020 edition of the European guideline on the management of syphilis is an update of the 2014 edition. Main modifications and updates include: -The ongoing epidemics of early syphilis in Europe, particularly in men who have sex with men (MSM) -The development of dual treponemal and non-treponemal point-of-care (POC) tests -The progress in non-treponemal test (NTT) automatization -The regular episodic shortage of benzathine penicillin G (BPG) in some European countries -The exclusion of azithromycin as an alternative treatment at any stage of syphilis -The pre-exposure or immediate post-exposure prophylaxis with doxycycline in populations at high risk of acquiring syphilis.

BACKGROUND: Syphilis remains a major public health problem in Europe (both in Eastern Europe since the 1990's and in Western Europe since the re-emergence of the disease in the late 1990's-early 2000's). METHODS: This guideline is an update of the IUSTI: 2008 European guideline on the management of syphilis and is produced by the European Guideline Editorial Board (http://www.iusti.org/regions/Europe/pdf/2013/Editorial_Board.pdf) and EDF Guideline Committee. RESULTS: It provides recommendations concerning the diagnosis and management of syphilis in Europe. Major advances include (1) broader use of PCR, immunohistochemistry, subtyping of the etiological agent Treponema pallidum subspecies pallidum, new treponemal tests, and rapid-point-of-care (POC) tests detecting both treponemal and non-treponemal antibodies, (2) more flexible options for screening (TT-treponemal test- first or NTT -non treponemal test- first or both TT and NTT), and (3) procaine penicillin is no longer the first line therapy option in any phase of the disease, i.e. long acting penicillin G (i.e. benzathine penicillin G-BPG) is the only first line therapy regimen in early syphilis and in late latent syphilis. CONCLUSIONS: Syphilis is a disease that is relatively easy to detect by appropriate serological tests, however, all laboratory results should be considered together with clinical data and sexual risk anamnesis. Syphilis is also easy to treat with BPG. A major concern about the supply of BPG in many European countries could threaten the efficacy of the policies of eradication of the disease in Europe.

PURPOSE: To test the equivalence of three versus four cycles of bleomycin, etoposide, and cisplatin (BEP) and of the 5-day schedule versus 3 days per cycle in good-prognosis germ cell cancer. PATIENTS AND METHODS: The study was designed as a 2 x 2 factorial trial. The aim was to rule out a 5% decrease in the 2-year progression-free survival (PFS) rate. The study included the assessment of patient quality of life. A cycle of BEP consisted of etoposide 500 mg/m(2), administered at either 100 mg/m(2) days 1 through 5 or 165 mg/m(2) days 1 through 3, cisplatin 100 mg/m(2), administered at either 20 mg/m(2) days 1 through 5 or 50 mg/m(2) days 1 and 2. Bleomycin 30 mg was administered on days 1, 8, and 15 during cycles 1 through 3. The randomization procedure allowed some investigators to participate only in the comparison of three versus four cycles. RESULTS: From March 1995 until April 1998, 812 patients were randomly assigned to receive three or four cycles: of these, 681 were also randomly assigned to the 5-day or the 3-day schedule. Histology, marker values, and disease extent are well balanced in the treatment arms of the two comparisons. The projected 2-year PFS is 90.4% on three cycles and 89.4% on four cycles. The difference in PFS between three and four cycles is -1.0% (80% confidence limit [CL], -3.8%, +1.8%). Equivalence for three versus four cycles is claimed because both the upper and lower bounds of the 80% CL are less than 5%. In the 5- versus 3-day comparison, the projected 2-year PFS is 88.8% and 89.7%, respectively (difference, -0.9%, (80% CL, -4.1%, +2.2%). Hence, equivalence is claimed in this comparison also. Frequencies of hematologic and nonhematologic toxicities were essentially similar. Quality of life was maintained better in patients receiving three cycles; no differences were detected between 3 and 5 days of treatment. CONCLUSION: We conclude that three cycles of BEP, with etoposide at 500 mg/m(2), is sufficient therapy in good-prognosis germ cell cancer and that the administration of the chemotherapy in 3 days has no detrimental effect on the effectiveness of the BEP regimen.

PURPOSE: We report the clinical features and treatment of 31 patients with a diagnosis of enteropathy-type intestinal T-cell lymphoma treated at the Wessex Regional Medical Oncology Unit in Southampton between 1979 and 1996 (23 men, eight women). PATIENTS AND METHODS: Patients were identified from our lymphoma database. Details of history, physical examination, staging investigations, treatment, and outcome were taken from patient records. RESULTS: Twelve patients (35%) had a documented clinical history of adult-onset celiac disease, and a further three had histologic features consistent with celiac disease in resected areas of the small bowel not infiltrated with lymphoma. After diagnosis, 24 (77%) of the 31 patients were treated with chemotherapy; the remaining seven had surgical treatment alone. More than half were unable to complete their planned chemotherapy courses, often because of poor nutritional status; 12 patients required enteral or parenteral feeding. A response to initial chemotherapy was observed in 14 patients (complete response, n = 10; partial response, n = 4). Observed complications of treatment were gastrointestinal bleeding, small-bowel perforation, and the development of enterocolic fistulae. Relapses occurred 1 to 60 months from diagnosis in 79% of those who responded to initial therapy. Of the total 31 patients, 26 (84%) have died, all from progressive disease or from complications of the disease and/or its treatment. The actuarial 1- and 5-year survival rates are 38.7% and 19.7%, respectively, with 1- and 5-year failure-free survival rates of 19.4% and 3.2%, respectively. CONCLUSION: The prognosis for these patients is poor. This, in part, reflects late diagnosis and poor performance status at the time of presentation. The role of salvage treatments and high-dose chemotherapy at relapse is not clear. However, it is encouraging that there are five long-term survivors in our patient population.

The Eating Attitudes Test (Garner & Garfinkel, 1979) was administered to 578 students (446 females and 132 males) at a College of Technology and to 14 "control" subjects fulfilling strict diagnostic criteria for anorexia nervosa. Although no male students scored highly, a total of 28 female students (6.3% of the female student sample) scored in the "anorexic" range. These "high scorers", together with a random control group of 28 "non-high scorers", were subsequently interviewed. Interview revealed that the symptoms of anorexia nervosa were common in the high scoring group but virtually absent in the student control group. It is concluded that a substantial proportion of post-pubertal females (approximately 5%) develop a subclinical form of anorexia nervosa. The implications of these findings are discussed in relation to the aetiology, prevention and treatment of disturbances in eating behaviour.

BACKGROUND: We present a revised Beliefs About Voices Questionnaire (BAVQ-R), a self-report measure of patients' beliefs, emotions and behaviour about auditory hallucinations. AIMS: To improve measurement of omnipotence, a pivotal concept in understanding auditory hallucinations, and elucidate links between beliefs about voices, anxiety and depression. METHODS: Seventy-one participants with chronic auditory hallucinations completed the BAVQ-R, and 58 also completed the Hospital Anxiety and Depression Scale. RESULTS: The mean Cronbach's alpha for the five sub-scales was 0.86 (range 0.74-0.88). The study supports hypotheses about links between beliefs, emotions and behaviour, and presents original data on how these relate to the new omnipotence sub-scale. Original data are also presented on connections with anxiety and depression. CONCLUSIONS: The BAVQ-R is more reliable and sensitive to individual differences than the original version, and reliably measures omnipotence.

An interview schedule was used to record the personality traits of 130 psychiatric patients, 65 with a primary clinical diagnosis of personality disorder and 65 with other diagnoses. The results were analysed by factor analysis and three types of cluster analysis. Factor analysis showed a similar structure of personality variables in both groups of patients, supporting the notion that personality disorders differ only in degree from the personalities of other psychiatric patients. Cluster analysis revealed five discrete categories; sociopathic, passive-dependent, anankastic, schizoid and a non-personality-disordered group. Of all the personality-disordered patients 63 per cent fell into the passive-dependent or sociopathic category. The results suggest that the current classification of personality disorder could be simplified.

BACKGROUND: A preliminary report by the authors suggested that the range of affect generated by voices (anger, fear, elation) was linked not to the form, content or topography of voice activity, but to the beliefs patients held about them, in particular their supposed power and authority. We argued that this conformed to a cognitive model; that is, voice beliefs represent an attempt to understand the experience of voices, and cannot be understood by reference to the form/content of voices alone. This study puts this cognitive model to empirical test. METHODS: Sixty-two voice hearers conforming to ICD-10 schizophrenia or schizoaffective diagnoses were interviewed and completed standardized measures of voice activity; beliefs about voices and supporting evidence, coping behaviour; affect and depression. RESULTS: Beliefs about the power and meaning of voices showed a close relationship with coping behaviour and affect (malevolent voices were associated with fear and anger and were resisted; benevolent voices were associated with positive effect and were engaged) and accounted for the high rate of depression in the sample (53%). Measures of voice form and topography did not show any link with behaviour or affect and in only one-quarter of cases did neutral observers rate voice beliefs as 'following directly' from voice content. CONCLUSION: The study found support for our cognitive model and therapeutic approach. Factors governing the genesis of these key beliefs remain unknown. A number of hypotheses are discussed, which centre around the possibility that voice beliefs develop as part of an adaptive process to the experience of voices, and are underpinned by core beliefs about the individuals self-worth and interpersonal schemata.

The study's objective was to assess the impact on clinical functioning of group based mindfulness training alongside standard psychiatric care for people with current, subjectively distressing psychosis. Data are presented from the first 10 people to complete one of four Mindfulness Groups, each lasting six sessions. People were taught mindfulness of the breath, and encouraged to let unpleasant experiences come into awareness, to observe and note them, and let them go without judgment, clinging or struggle. There was a significant pre-post drop in scores on the CORE (z=−2.655, p =.008). Secondary data indicated improvement in mindfulness skills, and the subjective importance of mindfulness to the group process ( N =11). The results are encouraging and warrant further controlled outcome and process research.

The P300 component of the human event-related brain potential has often been linked to the processing of rare, surprising events. However, the formal computational processes underlying the generation of the P300 are not well known. Here, we formulate a simple model of trial-by-trial learning of stimulus probabilities based on Information Theory. Specifically, we modeled the surprise associated with the occurrence of a visual stimulus to provide a formal quantification of the "subjective probability" associated with an event. Subjects performed a choice reaction time task, while we recorded their brain responses using electroencephalography (EEG). In each of 12 blocks, the probabilities of stimulus occurrence were changed, thereby creating sequences of trials with low, medium, and high predictability. Trial-by-trial variations in the P300 component were best explained by a model of stimulus-bound surprise. This model accounted for the data better than a categorical model that parametrically encoded the stimulus identity, or an alternative model of surprise based on the Kullback-Leibler divergence. The present data demonstrate that trial-by-trial changes in P300 can be explained by predictions made by an ideal observer keeping track of the probabilities of possible events. This provides evidence for theories proposing a direct link between the P300 component and the processing of surprising events. Furthermore, this study demonstrates how model-based analyses can be used to explain significant proportions of the trial-by-trial changes in human event-related EEG responses.

The association between suicide and medical disorder has not received as much attention as the association between suicide and psychiatric disorder. We identified by statistical overview medical disorders with an altered suicide risk. We found reports on the mortality of 63 medical disorders (ICD9 001-289, 320-999) said to have an altered suicide risk. English-language reports were located on MEDLINE with the search terms "disease name with mortality and follow-up"; and from the reference lists of these reports. We abstracted 235 reports of mortality studies of medical disorders with 2 years or more of follow-up, less than 10% loss of subjects, observed numbers of suicides given, and either the expected number or the facts from which to derive this. The ratio of the sum of the observed to the sum of the expected suicides, for each disorder, tested by the Poisson distribution gave an assessment of altered risk of death from suicide. Increased risk (p < 0.05) was seen for HIV/AIDS, malignant neoplasms as a group, head and neck cancers, Huntington disease, multiple sclerosis, peptic ulcer, renal disease, spinal cord injury, and systemic lupus erythematosus. Inconclusive evidence for increased risk was observed for amputation, heart valve replacement and surgery, disorders of the intestine (Crohn disease, ileostomy, ulcerative colitis), hormone replacement therapy, alcoholic liver disease, neurofibromatosis, systemic sclerosis, and Parkinson disease. Pregnancy and the puerperium had decreased risks (p < 0.05). There was no evidence of either increased or decreased risk for any of the other disorders studied.