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

Severe COVID anxiety among adults in the United Kingdom: cohort study and nested feasibility trial

BACKGROUND: People with severe COVID anxiety have poor mental health and impaired functioning, but the course of severe COVID anxiety is unknown and the quality of evidence on the acceptability and impact of psychological interventions is low. METHODS: People with severe COVID anxiety have poor mental health and impaired functioning, but the course of severe COVID anxiety is unknown and the quality of evidence on the acceptability and impact of psychological interventions is low. RESULTS: 204 (70.2%) of 285 people who took part in the cohort study completed the six month follow-up, for whom levels of COVID anxiety fell from 12.4 at baseline to 6.8 at six months (difference = -5.5, 95% CI = -6.0 to -4.9). Reductions in COVID anxiety were lower among older people, those living with a vulnerable person, those with lower baseline COVID anxiety, and those with higher levels of generalised anxiety and health anxiety at baseline. 36 (90%) of 40 participants enrolled in the nested feasibility trial were followed up at six months. 17 (80.9%) of 21 people in the active arm of the trial received four or more sessions of CBT-HA. We found improved mental health and social functioning among those in the active, but not the control arm of the trial (Mean difference in total score on the Work and Social Adjustment Scale between baseline and follow up, was 9.7 (95% CI = 5.8–13.6) among those in the active, and 1.0 (95% C.I. = -4.6 to 6.6) among those in the control arm of the trial. CONCLUSIONS: While the mental health of people with severe COVID anxiety appears to improve over time, many continue to experience high levels of anxiety and poor social functioning. Health anxiety is highly prevalent among people with severe COVID anxiety and may provide a target for psychological treatment. TRIAL REGISTRATION: Retrospectively registered at ISRCTN14973494 on 09/09/2021

The admixture maximum likelihood test to test for association between rare variants and disease phenotypes.

BACKGROUND: The development of genotyping arrays containing hundreds of thousands of rare variants across the genome and advances in high-throughput sequencing technologies have made feasible empirical genetic association studies to search for rare disease susceptibility alleles. As single variant testing is underpowered to detect associations, the development of statistical methods to combine analysis across variants - so-called "burden tests" - is an area of active research interest. We previously developed a method, the admixture maximum likelihood test, to test multiple, common variants for association with a trait of interest. We have extended this method, called the rare admixture maximum likelihood test (RAML), for the analysis of rare variants. In this paper we compare the performance of RAML with six other burden tests designed to test for association of rare variants. RESULTS: We used simulation testing over a range of scenarios to test the power of RAML compared to the other rare variant association testing methods. These scenarios modelled differences in effect variability, the average direction of effect and the proportion of associated variants. We evaluated the power for all the different scenarios. RAML tended to have the greatest power for most scenarios where the proportion of associated variants was small, whereas SKAT-O performed a little better for the scenarios with a higher proportion of associated variants. CONCLUSIONS: The RAML method makes no assumptions about the proportion of variants that are associated with the phenotype of interest or the magnitude and direction of their effect. The method is flexible and can be applied to both dichotomous and quantitative traits and allows for the inclusion of covariates in the underlying regression model. The RAML method performed well compared to the other methods over a wide range of scenarios. Generally power was moderate in most of the scenarios, underlying the need for large sample sizes in any form of association testing.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

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

Using PHREEQC to model cement hydration

This paper presents the steps involved in undertaking an analysis of hydrating cements with different levels of limestone powder using the PHREEQC geochemical software with the Notepad++ editor. The analysis begins with determining which solid phases are thermodynamically predicted to precipitate and form using the oxide compositions of commercial CEM I and CEM II/A-L cements. When the phases are known, PHREEQC is programmed to provide predictions of the phase dissolution and phase assemblage over time (here, 1000 days of hydration) as well as the pore solution chemistry. Thermodynamics has been successfully applied to the field of cement hydration to predict phase assemblages and pore solution changes. With an appropriate cement-based thermodynamic database, PHREEQC has the potential to be a very powerful tool in the ongoing development of sustainable cements into the future. The paper also discusses the ongoing work to couple PHREEQC with the HYDCEM model to provide users with an all-in-one platform to undertake a complete simulation of cement hydration

Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

Background Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. Methods Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types. Results We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (P-EOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR](HGSOC) = 5.74 del), and BRCA2 (P-HGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. Conclusions CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.Peer reviewe

Future engineers: the intrinsic technology motivation of secondary school pupils

The supply of students motivated to study engineering in higher education is critical to the sector. Results are presented from the ‘Mindsets STEM Enhancement Project’. Fifty-seven new resources packs, designed to improve STEM education in Design and Technology, were given to schools across London. A modified Intrinsic Motivation Inventory questionnaire measured pupils’ (n = 458) motivation towards technology. The results show that although pupils have positive reactions to the technology content within Design and Technology lessons, the type of STEM resources and lessons created through the project had made no significant difference on pupils’ interest/enjoyment towards technology. This suggests standalone resources do not improve pupil motivation. The impact of this work to engineering higher education is that the existing levels and the inability to improve pupil motivation in technology at school could be a factor affecting the pursuit of a technology or engineering related education or career