The effect of environmental change, planned and unplanned life events on the long-term outcome of common mental disorders

PURPOSE: To examine the nature of positive and negative environmental change on clinical outcome in 210 patients presenting with anxiety and depression and followed up over 30 years. METHODS: In addition to clinical assessments, major environmental changes, particularly after 12 and 30 years, were recorded in all patients by a combination of self-report and taped interviews. Environmental changes were separated into two major groups, positive or negative, determined by patient opinion. RESULTS: In all analyses positive changes were found to be associated with better outcome at 12 years with respect to accommodation (P = 0.009), relationships (P = 007), and substance misuse (P = 0.003), with fewer psychiatric admissions (P = 0.011) and fewer social work contacts at 30 years (P = 0.043). Using a consolidated outcome measure positive changes were more likely than negative ones to be associated with a good outcome at 12 and 30 years (39% v 3.6% and 30.2% v 9.1%, respectively). Those with personality disorder at baseline had fewer positive changes (P = 0.018) than others at 12 years and fewer positive occupational changes at 30 years (P = 0.041). Service use was greatly reduced in those with positive events with 50-80% more time free of all psychotropic drug treatment (P < 0.001). Instrumental positive change had greater effects than imposed changes. CONCLUSIONS: Positive environmental change has a favourable impact on clinical outcome in common mental disorders. Although studied naturalistically in this study the findings suggest that if harnessed as a therapeutic intervention, as in nidotherapy and social prescribing, it would yield therapeutic dividends

Impact of personality status on the outcomes and cost of cognitive–behavioural therapy for health anxiety

BACKGROUND: Health anxiety, hypochondriasis and personality disturbance commonly coexist. The impact of personality status was assessed in a secondary analysis of a randomised controlled trial (RCT). AIMS: To test the impact of personality status using ICD-11 criteria on the clinical and cost outcomes of treatment with cognitive-behavioural therapy for health anxiety (CBT-HA) and standard care over 2 years. METHOD: Personality dysfunction was assessed at baseline in 444 patients before randomisation and independent assessment of costs and outcomes made on four occasions over 2 years. RESULTS: In total, 381 patients (86%) had some personality dysfunction with 184 (41%) satisfying the ICD criteria for personality disorder. Those with no personality dysfunction showed no treatment differences (P = 0.90) and worse social function with CBT-HA compared with standard care (P<0.03) whereas all other personality groups showed greater improvement with CBT-HA maintained over 2 years (P<0.001). Less benefit was shown in those with more severe personality disorder (P<0.05). Costs were less with CBT-HA except for non-significant greater differences in those with moderate or severe personality disorder. CONCLUSIONS: The results contradict the hypothesis that personality disorder impairs response to CBT in health anxiety in both the short and medium term

CHAMP: Cognitive behaviour therapy for health anxiety in medical patients, a randomised controlled trial

BACKGROUND: Abnormal health anxiety, also called hypochondriasis, has been successfully treated by cognitive behaviour therapy (CBT) in patients recruited from primary care, but only one pilot trial has been carried out among those attending secondary medical clinics where health anxiety is likely to be more common and have a greater impact on services. The CHAMP study extends this work to examine both the clinical and cost effectiveness of CBT in this population. METHOD/DESIGN: The study is a randomized controlled trial with two parallel arms and equal randomization of 466 eligible patients (assuming a 20% drop-out) to an active treatment group of 5-10 sessions of cognitive behaviour therapy and to a control group. The aim at baseline, after completion of all assessments but before randomization, was to give a standard simple explanation of the nature of health anxiety for all participants. Subsequently the control group was to receive whatever care might usually be available in the clinics, which is normally a combination of clinical assessment, appropriate tests and reassurance. Those allocated to the active treatment group were planned to receive between 5 and 10 sessions of an adapted form of cognitive behaviour therapy based on the Salkovskis/Warwick model, in which a set of treatment strategies are chosen aimed at helping patients understand the factors that drive and maintain health anxiety. The therapy was planned to be given by graduate research workers, nurses or other health professionals trained for this intervention whom would also have their competence assessed independently during the course of treatment. The primary outcome is reduction in health anxiety symptoms after one year and the main secondary outcome is the cost of care after two years. DISCUSSION: This represents the first trial of adapted cognitive behaviour therapy in health anxiety that is large enough to test not only the clinical benefits of treatment but also whether the cost of treatment is offset by savings from reduced use of other health services in comparison to the control group.Cognitive behaviour therapy for Health Anxiety in Medical Patients (CHAMP) TRIAL REGISTRATION: Current Controlled Trials ISRCTN14565822

Technology for automated analysis of maize pollen used as a marker for mutation: 1. Flow-through systems.

Maize pollen is used as a monitor for environmental pollutants. Mutant pollen grains (induced by environmental pollutants) are detectable above a background frequency of 5 or less in 10(5). To enumerate a satisfactory number of mutant grains, it is necessary to count 10(6) grains in a sample, a laborious, time-consuming process which should be amenable to automated analysis techniques. High resolution image analysis technology has been used in the morphologic assessment of rare cells in a sample, provided a suitable training set could be devised to instruct the computer on the characteristics of the rare cells. On the other hand, flow cytometry uses primarily cytochemical means for detection and has been shown to detect rare events. Hence, the two technologies, which may be viewed as complementary, are suitable for the task. Alternatively, a hybrid technology employing both cell sorter and image analysis techniques may be extremely desirable for this problem. The potential for archival storage of analyzed samples is very attractive when considering the possibility of an adversary relationship between a putative regulator and polluter

Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes

Alzheimer\u27s disease (AD) is characterized by the deposition of Beta-Amyloid (Aβ) peptides in the brain. Aβ peptides are generated by cleavage of the Amyloid Precursor Protein (APP) by the β - and γ - secretase enzymes. Although this process is tightly linked to the internalization of cell surface APP, the compartments responsible are not well defined. We have found that APP can be rapidly internalized from the cell surface to lysosomes, bypassing early and late endosomes. Here we show by confocal microscopy and electron microscopy that this pathway is mediated by macropinocytosis. APP internalization is enhanced by antibody binding/crosslinking of APP suggesting that APP may function as a receptor. Furthermore, a dominant negative mutant of Arf6 blocks direct transport of APP to lysosomes, but does not affect classical endocytosis to endosomes. Arf6 expression increases through the hippocampus with the development of Alzheimer\u27s disease, being expressed mostly in the CA1 and CA2 regions in normal individuals but spreading through the CA3 and CA4 regions in individuals with pathologically diagnosed AD. Disruption of lysosomal transport of APP reduces both Aβ40 and Aβ42 production by more than 30 %. Our findings suggest that the lysosome is an important site for Aβ production and that altering APP trafficking represents a viable strategy to reduce Aβ production

Desulfurization Effects on a Light-Duty Diesel Vehicle NOx Adsorber Exhaust Emission Control System

Analyzes the effects on gaseous emissions, before and after desulfurization, on a light-duty diesel vehicle with a NOx adsorber catalyst

Symptom burden in patients with chronic kidney disease not requiring renal replacement therapy

Background: Although evidence shows that patients with end stage renal disease (ESRD) experience a high symptom burden which impacts on quality of life (QoL), less is known about patients with earlier stages of chronic kidney disease (CKD). This study aimed to explore symptom burden and potential contributing factors in patients with CKD Stage 1-5 not requiring renal replacement therapy (RRT). Methods: Patients with CKD Stage 1-5 and not on RRT were asked to report their symptoms using the Leicester Uraemic Symptom Score (LUSS), a questionnaire which assesses the frequency and intrusiveness of 11 symptoms commonly reported by kidney patients. Results: Symptoms were assessed in 283 CKD Stage 1-5 patients: 54% male, mean age 60.5 standard error± 1.0, mean eGFR 38ml/min/1.73m2. Some 96% (95% confidence interval 93.2-98.0) of participants reported experiencing at least one symptom, the median reported being six. Excessive tiredness (81%;76.0-85.6), sleep disturbance (70%;64.3-75.3) and pain in bones/joints (69%;63.4-74.6) were reported most commonly. Overall, few significant associations were found between biochemical markers of disease severity and symptom burden. Men tended to report fewer symptoms than women and South Asian patients often described experiencing symptoms with a greater severity. Older patients found musculoskeletal symptoms more intrusive whereas younger patients found reduced concentration more intrusive. Conclusions: Our findings suggest that patients with CKD stages 1-5 experience a multitude of symptoms that could potentially impact QoL. Using multidimensional tools like the LUSS, more exploration and focus could provide a greater opportunity for patient focussed symptom control from the earliest stages of CKD.Peer-reviewedPublisher Versio

Service evaluation of a nurse-led dental anxiety management service for adult patients

Objective: Evaluate patients’ and professionals’ experiences of a Nurse-led Dental Anxiety Management Service (NDAMS). Design: Service evaluation. Setting: The NDAMS operates as part of Sheffield Salaried Primary Dental Care Service. Subjects and methods: Questionnaire survey of anxious patients and qualitative interviews with patients and professionals Interventions: Dental nurses delivered low-level psychological interventions as part of an Integrated Care Pathway (ICP) for dental anxiety. Main outcome Measures: Dental anxiety and oral health-related quality of life (OHRQoL) questionnaires were completed by patients prior to and following NDAM. Results: A total of 187 patients were assessed as suitable for NDAM (mean age= 33.7, 77% female) and 33 had completed it at the time of the service evaluation. Of those patients who had completed the intervention significant improvements in dental anxiety and OHRQoL were reported. Professionals highlighted the importance of integrated working, adequate support and training and assessing the suitability of patients for NDAM. Conclusion: ICPs that combine pharmacological and psychological management approaches can help meet the needs of dentally anxious patients, however, early identification of patients most likely to benefit from psychological intervention should be a priority

Parenting interventions for male young offenders: a review of the evidence on what works

Approximately one in four incarcerated male young offenders in the UK is an actual or expectant father. This paper reviews evidence on the effectiveness of parenting interventions for male young offenders. We conducted systematic searches across 20 databases and consulted experts. Twelve relevant evaluations were identified: 10 from the UK, of programmes for incarcerated young offenders, and two from the US, of programmes for young parolees. None used experimental methods or included a comparison group. They suggest that participants like the courses, find them useful, and the interventions may improve knowledge about, and attitudes to, parenting. Future interventions should incorporate elements of promising parenting interventions with young fathers in the community, for example, and/or with older incarcerated parents. Young offender fathers have specific developmental, rehabilitative, and contextual needs. Future evaluations should collect longer-term behavioural parent and child outcome data and should use comparison groups and, ideally, randomization

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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