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Purpose: There is growing evidence supporting the use of third-wave psychological therapies, such as mindfulness-based interventions (MBIs) and acceptance and commitment therapy (ACT), for people with long-term or chronic physical health conditions. We conducted a systematic review and meta-analysis to critically evaluate the effectiveness of third-wave interventions for improving hearing-related distress and psychological well-being in people with audiological problems. Method: We searched online bibliographic databases and assessed study quality. We conducted random-effects meta-analyses if at least two randomized controlled trials (RCTs) examined hearing-related distress, depression, anxiety, or quality of life in people with audiological problems. Findings of pre–post studies were summarized narratively. Results: We identified 15 studies: six RCTs and nine pre–post studies. The methodological quality of studies was mostly poor to moderate, and sample sizes were typically small (overall n = 750). Most studies focused on tinnitus ( n = 12), MBIs ( n = 8), and ACT ( n = 6). Statistically significant improvements in hearing-related distress were found with ACT and MBIs versus controls and other treatments at post-intervention in people with tinnitus, while improvements in depression and anxiety were only found for ACT versus controls at post-intervention. However, gains were either not maintained or not examined at follow-up, and there was no evidence for improvements in quality of life. Conclusions: At present, there is insufficient evidence to recommend the use of third-wave interventions for improving hearing-related distress or psychological well-being in people with audiological problems. There is some evidence that ACT and MBIs may be useful in addressing hearing-related distress in people with tinnitus, but only in the short term. However, findings should be interpreted with caution given the small number of studies with generally small sample sizes and mostly poor-to-moderate methodological quality. More high-quality, adequately powered, double-blind RCTs, particularly in audiological problems other than tinnitus, are needed to draw firm conclusions and meaningful clinical recommendations. Supplemental Material: https://doi.org/10.23641/asha.19735975

There are increasing concerns about university students’ mental health with mindfulness-based interventions (MBIs) showing promising results. The effect of MBIs delivered digitally to a broad range of university students and study attrition rates remain unclear. This review aimed to explore the effectiveness of online MBIs on university students’ mental health, academic performance and attrition rate of online MBIs. Four databases were searched; both randomised and non-randomised controlled trials were included. Outcomes included mental health-related outcomes and academic performance. Twenty-six studies were identified with outcomes related to mental health. When compared with non-active controls, small to medium statistically significant effect sizes in favour of online MBIs were found for depression, stress, anxiety, psychological distress and psychological well-being at post-intervention. However, these benefits were not seen when online MBIs were compared to active controls and other treatments at post-intervention or follow-up. University students in online MBI arms were more likely to drop out compared to non-active controls and active controls, but no differences were found compared to other treatments. Generally, the included studies’ risk of bias was moderate to high. Online MBIs appear beneficial for improving university students’ mental health when compared to non-active controls post-intervention, but not active controls or other treatments. Findings related to active controls and other treatments should be interpreted with caution due to the small number of studies, the small number of participants in included studies and the degree of heterogeneity in effect sizes.

Background Generalised anxiety disorder (GAD) is the most common anxiety disorder in older people. First-line management includes pharmacological and psychological therapies, but many do not find these effective or acceptable. Little is known about how to manage treatment-resistant generalised anxiety disorder (TR-GAD) in older people. Objectives To examine the acceptability, feasibility and preliminary estimates of the effectiveness of acceptance and commitment therapy (ACT) for older people with TR-GAD. Participants People aged ≥65 years with TR-GAD (defined as not responding to GAD treatment, tolerate it or refused treatment) recruited from primary and secondary care services and the community. Intervention Participants received up to 16 one-to-one sessions of ACT, developed specifically for older people with TR-GAD, in addition to usual care. Measurements Co-primary outcomes were feasibility (defined as recruitment of ≥32 participants and retention of ≥60% at follow-up) and acceptability (defined as participants attending ≥10 sessions and scoring ≥21/30 on the satisfaction with therapy subscale). Secondary outcomes included measures of anxiety, worry, depression and psychological flexibility (assessed at 0 and 20 weeks). Results Thirty-seven participants were recruited, 30 (81%) were retained and 26 (70%) attended ≥10 sessions. A total of 18/30 (60%) participants scored ≥21/30 on the satisfaction with therapy subscale. There was preliminary evidence suggesting that ACT may improve anxiety, depression and psychological flexibility. Conclusions There was evidence of good feasibility and acceptability, although satisfaction with therapy scores suggested that further refinement of the intervention may be necessary. Results indicate that a larger-scale randomised controlled trial of ACT for TR-GAD is feasible and warranted.

Made available in DSpace on 2021-06-25T10:11:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Agricultural Research Service Supplementation of broiler diets with feed additives such as chemotherapeutic drugs and antibiotics has side effects, meat residues, and antibiotics resistance complications. Plant-derived natural compounds could be safe and easy substitutes for chemical additives. One of the natural compounds is curcumin, the extract from herbal plant Curcuma longa, known for its antioxidant and antimicrobial properties which may be effective in reducing coccidia infection in poultry. The objective of this study was to evaluate the effects of curcumin on Eimeria challenged (C) and nonchallenged (NC) Cobb 500 broilers. A total of 360 12-day-old male chicks were housed in 36 cages in a completely randomized design with 6 replicates per treatment of 10 birds each cage. The six corn–soybean meal–based treatment diets were fed from day 12 to 20 to C and NC birds in 3-by-two factorial arrangement: nonchallenged control (NCC), NC + 100 mg/kg curcumin, NC + 200 mg/kg curcumin, challenged control (CC), C + 100 mg/kg curcumin, and C + 200 mg/kg curcumin. Broilers in C groups were inoculated orally with 50,000 oocysts of Eimeria maxima, 50,000 oocysts of Eimeria tenella, and 250,000 oocysts of Eimeria acervulina on day 14. The intestinal permeability (day 19), growth performance parameters, and intestinal lesion scoring were measured and recorded on day 20. The means were subjected to two-way ANOVA, and main factors effect and their interactions were considered. The growth performance and permeability were higher (P < 0.001) in the NC and C groups, respectively. However, no interaction was observed between curcumin dose and cocci challenge on both of these parameters. Results from lesion scores and oocyst shedding showed reduction (P < 0.050) in birds fed C + 200 mg/kg curcumin compared with those fed C + 100 mg/kg curcumin or CC. Curcumin treatment showed higher production of GSH (P = 0.002) and total glutathione (GSH+2GSSG) (P = 0.002) but lower GSH/GSSG ratio (P < 0.001) than the NCC group. Curcumin exhibited some positive responses on antioxidant capacity, lesion score, and oocyst shedding in the present study, suggesting that curcumin alone or a combination with other feed additives could be a dietary strategy to improve gut health in broilers. Department of Poultry Science University of Georgia Department of Foods and Nutrition University of Georgia Department of Breeding and Animal Nutrition São Paulo State University (UNESP) Department of Breeding and Animal Nutrition São Paulo State University (UNESP)

Place attachment to both physical and virtual places was investigated in an online survey of massively multiplayer online gamers. Participants (N=740) completed a place attachment inventory once for the place in the physical world which they considered home, and once for a place in a virtual world they felt attached to. In addition, measures of personality, gaming motivation, life satisfaction, attachment style, and identification with online avatars were taken. Results suggested that place identity, place uniqueness, and place social bonding were higher for physical places than for virtual places, but that place affect was higher for virtual places. A small number of participants (N=55, 7%) identified virtual ‘homes’, which participants felt were more special and which they identified more strongly with than other virtual places, and that were as unique and associated with an equal sense of belonging to physical homes. Results are interpreted through the lens of migration theory, and recommendations made for future research into digital domiciles and migration.

ObjectivesDepression and anxiety are common in frail older people and are associated with high levels of morbidity and mortality, yet they typically face greater barriers to accessing mental health treatments than younger people and express preferences for self-managing their symptoms. This study aims to explore frail older adults’ experiences of self-managing symptoms of depression and/or anxiety.DesignQualitative semi-structured interviews, exploring experiences of depression and/or anxiety, ways participants self-managed these and the contexts within which this took place. Interviews were audio-recorded and transcribed verbatim.Participants28 frail older adults in the United Kingdom, purposively sampled for neighbourhood, frailty and symptoms of anxiety/depression.AnalysisThematic analysis to inductively derive themes from the data.ResultsOur findings suggest that frail older adults find maintaining routines, engaging in meaningful and creative activities and socialising important to self-manage depression and anxiety. These could all be adapted to the level of frailty experienced. Stoicism, acceptance, faith or addressing the perceived cause were helpful in some situations and for some personalities. Distraction and avoidance were helpful for more severe symptoms or where the causes of symptoms could not be resolved. Self-management strategies were less well-established for anxiety symptoms, especially when linked to newer health fears and worries about the future.ConclusionsDeveloping services and sources of information that support and facilitate key therapeutic components of self-management, which align with older adults’ preferred coping styles and take into account levels of frailty, may be a way of supporting frail older people waiting for mental health treatments or those who prefer not to access these. Greater awareness of anxiety and how it can be self-managed in frail older people is needed.

The Covid-19 pandemic has impacted healthcare. Our aim was to identify how amyotrophic lateral sclerosis (ALS) care in the UK has been affected by the pandemic by exploring the experiences of people living with ALS (plwALS), healthcare professionals (HCPs) working with plwALS, and ALS care centers. Three surveys were carried out to explore the experiences of plwALS, HCPs and ALS care centers during the pandemic. Quantitative data were analyzed using descriptive and inferential statistics and triangulated with the qualitative data which were analyzed thematically. Responses from 53 plwALS, 73 HCPs and 23 ALS care centers were analyzed. Five main themes were identified: keeping safe, losses, negative emotions, delivering care and alternative care delivery in a pandemic. PlwALS and HCPs felt that care was sub-optimal as a result of the pandemic. Changes to care included longer waiting times and face-to-face appointments being canceled or replaced by virtual consultations. While benefits of virtual consultations were reported, concerns were raised about incomplete clinical assessments and the disruption of provision of testing and interventions. ALS care has changed as a result of the pandemic. Patients have had a lack of face-to-face contact with HCPs and have experienced delays to investigations and treatments. PlwALS and HCPs were concerned about the impact of this change, but the long-term implications remain unclear. We propose recommendations for HCPs caring for plwALS, that will promote continuity of evidenced based care in the context of a pandemic.

This study aimed to explore therapists’ perceptions and acceptability of providing internet-delivered, therapist-guided, self-help acceptance and commitment therapy (ACT) for family carers of people with dementia (iACT4CARERS). To achieve this, a qualitative approach with semi-structured interviews was employed with eight novice therapists recruited from primary and secondary care services taking part in a feasibility study of iACT4CARERS. The interviews were audio-recorded, transcribed, and analysed using thematic analysis. Four over-arching themes were identified: (1) positive attitudes towards the intervention, (2) therapists’ workload, (3) therapists’ confidence to perform their role, and (4) connecting with family carers in a virtual context. Theme 1 included seeing their involvement as an opportunity for personal growth and perceiving benefits to the family carers, which contributed to greater acceptability. Theme 2 reflected that while workload and the user-friendliness of the online platform were highly acceptable among the therapists, there were also time-consuming cases that increased therapists’ burden. Theme 3 revealed that practical resources provided during the training, continued supervision, and opportunities to learn from other therapists, increased therapist confidence and facilitated greater acceptability. Finally, Theme 4 highlighted that improving the connection between therapists and carers was critical in a virtual context and strategies to improve the therapist–carer relationship were recommended. The implementation of iACT4CARERS was largely acceptable for the therapists involved in the trial. Ways to strengthen the therapeutic relationship in the virtual context and practical strategies to deal with common problems may enhance therapist experience and delivery in a full-scale effectiveness trial. Key learning aims (1) To understand which factors facilitated therapists’ positive perceptions and acceptability of providing internet-delivered guided self-help ACT (iACT4CARERS). (2) To understand what challenges acted as barriers to therapists’ positive perceptions and acceptability of providing iACT4CARERS. (3) To learn what aspects of the training and the intervention can be refined to improve the acceptability to therapists in trials involving internet-delivered guided self-help interventions for family carers.

The tripeptide glutathione (GSH) is instrumental to antioxidant protection and xenobiotic metabolism, and the ratio of its reduced and oxidized forms (GSH/GSSG) indicates the cellular redox environment and maintains key aspects of cellular signaling. Disruptions in GSH levels and GSH/GSSG have long been tied to various chronic diseases, and many studies have examined whether variant alleles in genes responsible for GSH synthesis and metabolism are associated with increased disease risk. However, past studies have been limited to established, canonical GSH genes, though emerging evidence suggests that novel loci and genes influence the GSH redox system in specific tissues. The present study marks the most comprehensive effort to date to directly identify genetic loci associated with the GSH redox system. We employed the Diversity Outbred (DO) mouse population, a model of human genetics, and measured GSH and the essential redox cofactor NADPH in liver, the organ with the highest levels of GSH in the body. Under normal physiological conditions, we observed substantial variation in hepatic GSH and NADPH levels and their redox balances, and discovered a novel, significant quantitative trait locus (QTL) on murine chromosome 16 underlying GSH/GSSG; bioinformatics analyses revealed Socs1 to be the most likely candidate gene. We also discovered novel QTL associated with hepatic NADP+ levels and NADP+/NADPH, as well as unique candidate genes behind each trait. Overall, these findings transform our understanding of the GSH redox system, revealing genetic loci that govern it and proposing new candidate genes to investigate in future mechanistic endeavors., Graphical abstract Image 1, Highlights • A novel locus on murine chromosome 16 was associated with hepatic GSH/GSSG. • Bioinformatics analyses suggested Socs1 as the gene underlying hepatic GSH/GSSG. • Discrete QTL were associated with hepatic NADP + levels and NADP+/NADPH. • Hepatic levels of GSH, GSSG, and GSH/GSSG varied from 5- to 16-fold in outbred mice.

Generalised anxiety disorder, characterised by excessive anxiety and worry, is the most common anxiety disorder among older people. It is a condition that may persist for decades and is associated with numerous negative outcomes. Front-line treatments include pharmacological and psychological therapy, but many older people do not find these treatments effective. Guidance on managing treatment-resistant generalised anxiety disorder in older people is lacking.To assess whether or not a study to examine the clinical effectiveness and cost-effectiveness of acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder is feasible, we developed an intervention based on acceptance and commitment therapy for this population, assessed its acceptability and feasibility in an uncontrolled feasibility study and clarified key study design parameters.Phase 1 involved qualitative interviews to develop and optimise an intervention as well as a survey of service users and clinicians to clarify usual care. Phase 2 involved an uncontrolled feasibility study and qualitative interviews to refine the intervention.Participants were recruited from general practices, Improving Access to Psychological Therapies services, Community Mental Health Teams and the community.Participants were people aged ≥ 65 years with treatment-resistant generalised anxiety disorder.Participants received up to 16 one-to-one sessions of acceptance and commitment therapy, adapted for older people with treatment-resistant generalised anxiety disorder, in addition to usual care. Sessions were delivered by therapists based in primary and secondary care services, either in the clinic or at participants' homes. Sessions were weekly for the first 14 sessions and fortnightly thereafter.The co-primary outcome measures for phase 2 were acceptability (session attendance and satisfaction with therapy) and feasibility (recruitment and retention). Secondary outcome measures included additional measures of acceptability and feasibility and self-reported measures of anxiety, worry, depression and psychological flexibility. Self-reported outcomes were assessed at 0 weeks (baseline) and 20 weeks (follow-up). Health economic outcomes included intervention and resource use costs and health-related quality of life.Fifteen older people with treatment-resistant generalised anxiety disorder participated in phase 1 and 37 participated in phase 2. A high level of feasibility was demonstrated by a recruitment rate of 93% and a retention rate of 81%. A high level of acceptability was found with respect to session attendance (70% of participants attended ≥ 10 sessions) and satisfaction with therapy was adequate (60% of participants scored ≥ 21 out of 30 points on the Satisfaction with Therapy subscale of the Satisfaction with Therapy and Therapist Scale-Revised, although 80% of participants had not finished receiving therapy at the time of rating). Secondary outcome measures and qualitative data further supported the feasibility and acceptability of the intervention. Health economic data supported the feasibility of examining cost-effectiveness in a future randomised controlled trial. Although the study was not powered to examine clinical effectiveness, there was indicative evidence of improvements in scores for anxiety, depression and psychological flexibility.Non-specific therapeutic factors were not controlled for, and recruitment in phase 2 was limited to London.There was evidence of high levels of feasibility and acceptability and indicative evidence of improvements in symptoms of anxiety, depression and psychological flexibility. The results of this study suggest that a larger-scale randomised controlled trial would be feasible to conduct and is warranted.Current Controlled Trials ISRCTN12268776.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inGeneralised anxiety disorder, characterised by a tendency to worry, is the most common anxiety disorder among older people. Those with this condition may experience other difficulties, including increased distress and disability, poorer coping and reduced quality of life. Medication and talking therapy are usually offered as forms of treatment, but many do not find them helpful. Guidance is lacking on how to help older people manage generalised anxiety disorder when it does not respond to such treatments. We developed a 16-session intervention specifically for older people with treatment-resistant generalised anxiety disorder. This was based on acceptance and commitment therapy: a form of talking therapy that helps people to learn how to best live with distressing experiences while still doing things that really matter to them. It may be particularly suited to older people because many older people experience difficulties with chronic ill health and other problems that cannot be easily improved with conventional talking therapies. We developed our intervention by asking 15 older people about their experiences of treatment-resistant generalised anxiety disorder and treatments they have received for it, as well as what might help or hinder their engagement with talking therapy. We combined their guidance with advice from 36 clinicians to ensure that our intervention was tailored to the needs of this population. We then asked the same 15 older people, our Service User Advisory Group and academic clinicians about how we could optimise our intervention. We also conducted an online survey of service users and clinicians to clarify what care older people with generalised anxiety disorder are typically offered and receive. We tested how acceptable our intervention was to 37 older people with treatment-resistant generalised anxiety disorder, and how feasible it was to deliver within the NHS. We found evidence that it was acceptable to participants, that it could be delivered within the NHS and that its value for money could be tested in a larger study. We also found evidence suggestive of improvements in anxiety, depression and coping. There were some limitations of our study. However, overall, our results suggest that we should conduct a larger study to find out whether or not our intervention is helpful for older people with treatment-resistant generalised anxiety disorder.

Engaging in meaningful and enjoyable activities is an important contributor to well-being and maintaining good quality of life. There is a paucity of randomized controlled trials of interventions supporting people with mild dementia to engage in meaningful and purposeful activity. The aim of this study was to assess whether Behavioral Activation (BA) is an acceptable psychological intervention for people with mild dementia and whether a large-scale trial is feasible. Participants were randomly assigned to BA (n = 42) or treatment as usual (TAU) (n = 21). BA aimed at increasing engagement in enjoyable and meaningful activity, and preventing low mood. Follow-up was at 3 and 6 months. Assessors were blind to treatment allocation (trial registration number: ISRCTN75503960). Retention rate was above 80% at both assessment time points. Treatment acceptability and credibility were high. Depressive symptoms remained unchanged in both groups. There was evidence of improvement associated with BA for every day function (–3.92, 95% Confidence Interval (CI) –6.87 to –0.97), and engagement in meaningful and enjoyable activity (5.08, 95% CI 0.99 to 9.16) post-treatment (3 months) in comparison to TAU. Both carer-rated patient health-related quality of life (0.16, 95% CI 0.04 to 0.28) and physical health (11.31, 95% CI 2.03 to 20.59) showed evidence of improvement at 3 months. Improvements in meaningful and enjoyable activity were maintained at 6 months. BA for people with mild dementia is feasible and acceptable and may be associated with clinically significant changes in function and quality of life. A full scale randomized controlled trial of clinical effectiveness is now needed.

Background generalised anxiety disorder (GAD) is common in later life with a prevalence of 3–12%. Many only partially respond to cognitive behavioural therapy or pharmacotherapy and can be classified as treatment resistant. These patients experience poor quality of life, and are at increased risk of comorbid depression, falls and loneliness. Acceptance and commitment therapy (ACT) is an emerging therapy, which may be particularly suited to this population, but has not been tailored to their needs. Objectives to optimise the acceptability and feasibility of ACT for older adults with treatment-resistant GAD. Design a person-based approach to ground the adapted ACT intervention in the perspectives and lives of those who will use it. Methods first, we conducted qualitative interviews with 15 older adults with GAD and 36 healthcare professionals to develop guiding principles to inform the intervention. Second, we consulted service users and clinical experts and interviewed the same 15 older adults using ‘think aloud’ techniques to enhance its acceptability and feasibility. Results in Stage 1, older adults’ concerns and needs were categorised in four themes: ‘Expert in one’s own condition’, ‘Deep seated coping strategies’, ‘Expert in therapy’ and ‘Support with implementation’. In Stage 2, implications for therapy were identified that included an early focus on values and ACT as a collaborative partnership, examining beliefs around ‘self as worrier’ and the role of avoidance, validating and accommodating individuals’ knowledge and experience and compensating for age-related cognitive changes. Discussion Our systematic approach combined rigour and transparency to develop a therapeutic intervention tailored to the specific needs of older adults with treatment-resistant GAD.

Glutathione (GSH) is a critical cellular antioxidant that protects against byproducts of aerobic metabolism and other reactive electrophiles to prevent oxidative stress and cell death. Proper maintenance of its reduced form, GSH, in excess of its oxidized form, GSSG, prevents oxidative stress in the kidney and protects against the development of chronic kidney disease. Evidence has indicated that renal concentrations of GSH and GSSG, as well as their ratio GSH/GSSG, are moderately heritable, and past research has identified polymorphisms and candidate genes associated with these phenotypes in mice. Yet those discoveries were made with in silico mapping methods that are prone to false positives and power limitations, so the true loci and candidate genes that control renal glutathione remain unknown. The present study utilized high-resolution gene mapping with the Diversity Outbred mouse stock to identify causal loci underlying variation in renal GSH levels and redox status. Mapping output identified a suggestive locus associated with renal GSH on murine chromosome X at 51.602 Mbp, and bioinformatic analyses identified apoptosis-inducing factor mitochondria-associated 1 (Aifm1) as the most plausible candidate. Then, mapping outputs were compiled and compared against the genetic architecture of the hepatic GSH system, and we discovered a locus on murine chromosome 14 that overlaps between hepatic GSH concentrations and renal GSH redox potential. Overall, the results support our previously proposed model that the GSH redox system is regulated by both global and tissue-specific loci, vastly improving our understanding of GSH and its regulation and proposing new candidate genes for future mechanistic studies.

OBJECTIVES Substantial construct overlap exists between indicators of frailty and symptoms of some psychiatric disorders. This study aimed to gain consensus of expert academic opinion on the potential impact of psychiatric illness on frailty assessment and how best to conceptualise and measure frailty indicators in the context of psychiatric symptoms. DESIGN A classic Delphi approach was employed across two studies to achieve consensus: The first-round questionnaire consisted of open-ended questions, analysed through content analysis. The results informed the development of statements for participants to rate their agreement with in subsequent Delphi rounds. Statements with ≥66% agreement were accepted. Delphi Study 1 recruited experts in frailty assessment (n = 13) and Delphi Study 2 recruited experts in frailty and psychiatric disorder (n = 8). Experts were recruited globally. RESULTS Overall, 40% of Delphi Study 1 statements and 43% of Delphi Study 2 statements were accepted. Primarily, consensus was reached for statements concerning the influence of depression/anxiety on frailty assessment and potential methods of conceptualising and measuring frailty indicators in the context of psychiatric symptoms. Little consensus was reached concerning the ease and importance of differentiating between frailty indicators and psychiatric assessment criteria with substantial overlap. CONCLUSIONS The Delphi studies provide a novel exploration and consensus of expert academic opinions concerning the assessment of frailty indicators in the context of psychiatric symptoms. The results will inform future research into the adaptation or development of a frailty assessment tool specifically for use in older adult psychiatric populations.

ObjectiveTo adapt and optimize problem adaptation therapy for depression in dementia by grounding it in the lives of people with dementia, caregivers and clinicians.MethodsA person-centered qualitative approach was taken to elicit the unique cognitive, psychological and social needs of people with dementia relevant to the adaptation of the intervention. A two-stage design was used: the first involved interviews and focus groups to identify priorities and concerns surrounding depression in dementia, the second trialling of the adapted intervention.ParticipantsTen people with dementia and nine caregivers participated in individual interviews, 35 healthcare practitioners and clinical academics with experience of working with dementia participated in focus groups.ResultsThe findings highlight the importance of addressing key themes that typified the experience of depression among people with dementia including: a profound sense of isolation and role loss, the feeling of being both a burden and poorly understood, polarized thinking, interpersonal tensions, diverging views among carers and people with dementia about their capabilities, and changeability in cognitive ability and mood. These themes were used to inform adaptation of the intervention manual, ensuring that its content and delivery addressed the concerns of both people with depression and dementia and those who support them.ConclusionImplications for PATH included a focus on facilitating open communication, supporting the continuation of valued roles, and improving confidence.

Objective: The feasibility of research into internet-delivered guided self-help Acceptance and Commitment Therapy (ACT) for family carers of people with dementia is not known. This study assessed this in an uncontrolled feasibility study. Methods: Family carers of people with dementia with mild to moderate anxiety or depression were recruited from primary and secondary healthcare services in the UK. Participants were offered eight, guided, self-help online ACT sessions adapted for the needs of family carers of people with dementia with optional online peer support groups. Pre-defined primary indicators of success included recruitment of 30 eligible carers over six months and ≥70% completing at least two online sessions. Results: Thirty-three participants (110% of the target sample) were recruited over six months and 30 participants (91%) completed two or more sessions, and thus both indicators of success were met. Further, 70% of participants completed seven or all eight sessions, and 27% of participants were lost to follow-up, but none of the reasons for early withdrawal were related to the intervention. Conclusion: This study supports the feasibility, including recruitment and treatment completion. A full-scale trial to assess the clinical- and cost-effectiveness of the intervention including its long-term effects is warranted. Registration: ISRCTN trial registration 18956412

The quality of porcine oocytes for use in IVF is commonly graded according to the number of layers of cumulus cells (CCs) surrounding the oocyte; together these form the cumulus oocyte complex (COC). At least three compact layers of CCs is regarded as important for efficient IVP. To test this, oocytes were scored according to cumulus investment, with grade A representing COCs with three or more cumulus layers including granulosa cell‐cumulus oocyte complexes, grade B those with an intact corona radiata surrounded by another layer of cumulus cells and grades C and D representing COCs with lower CC investment. These oocytes were then monitored for in vitro maturation (IVM), as assessed by tubulin immunostaining for meiotic progression, the development of a cortical granule ring, and by glutathione levels. Results indicate that grading correlates closely with nuclear maturation and cytoplasmic maturation, suggesting that grading oocytes by cumulus investment is a reliable method to predict IVM success. Importantly, Grade A and B oocytes showed no significant differences in any measure and hence using a cut‐off of two or more CC layers may be optimal. We also determined the effect of assisted aspiration for oocyte retrieval, comparing the effect of needle size and applied pressure on the retrieval rate. These data indicated that both variables affected oocyte recovery rates and the quality of recovered oocytes. In combination, these experiments indicate that grade A and B oocytes have a similar developmental potential and that the recovery of oocytes of these grades is maximised by use of an 18‐gauge needle and 50 mmHg aspiration pressure., The global population is expected to rise dramatically over the next few decades. This means that the demand for meat, including pig derived products will also increase, and that a more sustainable way to produce such products is necessary. The establishment of production scale pig embryo in vitro production (IVP) could be one answer to this problem, however some challenges still exist, one of which is that pig IVP requires the consistent isolation of large numbers of high‐quality oocytes. Here, ways of maximising both the yield and the developmental potential of oocytes from abattoir derived ovaries has been investigated.

Background Compassion is an important component of nursing care, but public enquiries into care failures have noted that it is not always evident. Mindfulness interventions have the potential to support compassion. However, the feasibility of delivering a mindfulness intervention at scale to nursing students has not been established. Objectives To develop and test the feasibility and acceptability of a tailored mindfulness based online intervention to foster compassion in nursing students within clinical practice. Design A randomised feasibility study with a waiting list control. Setting A UK nursing faculty within a large university. Participants Post-graduate, post-registration and pre-registration nursing students (N = 77). Methods An online five module mindfulness based intervention (Mindful Nursing Online) was developed and tailored to support compassion in clinical nursing. The feasibility study comprised 77 participants randomised in a 2:1 ratio into an immediate access group (intervention, n = 50) or a delayed access group (waiting list control, n = 27). Data on feasibility through completion, attrition and practice rates, were collected through follow-up questionnaires at post-intervention, and 14 and 20 weeks after baseline. Acceptability data was collected through semi-structured interviews with 12 participants. Results Non-completion rates were high with all five modules completed by only 28% (n = 14) of participants, and three modules completed by only 46% (n = 23). The most commonly cited reason for non-completion was lack of time. However, the interview data suggested those who completed the intervention were using mindfulness techniques in practice. They described feeling less stressed on the ward, having an increased focus on patients and a greater appreciation of the importance of self-care. Evaluative feedback therefore showed that the intervention was perceived to be effective at promoting mindfulness skills and was relevant to nursing work. Conclusion Minimising attrition and enhancing engagement with the intervention should be the key objectives of a future study. Feedback from participants who completed the intervention indicates that a brief mindfulness intervention delivered online may support the delivery of compassionate nursing care.

Made available in DSpace on 2020-12-12T02:05:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-28 An experiment was conducted to evaluate the effect of different levels of inorganic copper and zinc on growth performance, intestinal permeability, intestinal lesion scores, oocyst shedding, antioxidant properties and bone quality in broilers challenged with Eimeria spp. A total of 360 d-old male Cobb broiler chickens were housed in floor cages for 12 days at the Poultry Research Center. At 12 days of age, birds were placed in grower Petersime batteries and distributed in a completely randomized design with 10 birds per cage, six replicates per treatment, and six treatments. There were six corn-soybean meal-based dietary treatments: non-challenged control (NC), challenged control (CC), 100 ppm Cu (100 Cu), 150 ppm Cu (150 Cu), 80 ppm Zn (80 Zn), and 100 ppm Zn (100 Zn). Broilers received the treatment diets for 9 days (12–20d). Birds, except NC, were challenged with Eimeria maxima (50,000 oocysts/bird), Eimeria tenella (50,000 oocysts/bird), and Eimeria acervulina (250,000 oocysts/bird) on 14d. On 20d, the growth performance was recorded, and one bird/cage was used for analysis of intestinal permeability, antioxidant properties and bone quality. Lesion score was recorded at 20 days of age in eight birds/cage. The means were subjected to ANOVA and, when significant, compared by Duncan's test. Intestinal permeability was significantly improved when birds received the 100 Zn diet (P < 0.05). In addition, lesion scores on duodenum were reduced when broilers received diets 150 Cu as compared to CC diet (P < 0.05). However, growth performance was not positively influenced by inclusion of inorganic minerals as compared to the NC diet. Furthermore, activity of superoxide dismutase and bone quality were not affected, whereas glutathione status was improved with mineral supplementation in all groups. This study showed that Cu and Zn supplementation improves intestinal integrity during the Eimeria spp. infection, suggesting that Cu and Zn supplementation would be a potential strategy to reduce detrimental effects of Eimeria infection in broilers. Department of Breeding and Animal Nutrition School of Veterinary Medicine and Animal Science São Paulo State University (UNESP) Department of Poultry Science University of Georgia (UGA) Department of Foods and Nutrition University of Georgia (UGA) Department of Breeding and Animal Nutrition School of Veterinary Medicine and Animal Science São Paulo State University (UNESP)

This study aimed to review the neurobiological and neuropsychological correlates of paranoid (persecutory delusions) and misidentification (misidentification delusions and/or hallucinations) subtypes of psychosis in dementia, to establish if they represent distinct subphenotypes. Nine studies were eligible, all included patients with Alzheimer’s disease. Greater global cognitive deficits and an accelerated global cognitive decline were observed in the misidentification subtype. Neuroimaging studies showed more marked volume loss in multiple regions in patients with the misidentification subtype, including those involved in object recognition and the processing of information on spatial and temporal context. A single study found greater impairment in visual sustained attention and object recognition in the misidentification subtype. The small number of studies and methodological heterogeneity limit interpretation of the findings. Nevertheless, these findings would tentatively suggest that there may be additional or accelerated pathological change in functional networks involved in visuoperceptual processing in the misidentification subtype. This should be further explored in prospective studies and the investigation extended to other forms of dementia, to gain a transdiagnostic perspective.

Objectives The objective of this study was to evaluate the effect of tumour necrosis factor‐alpha inhibitors (TNF‐αI) on Alzheimer's disease‐associated pathology. Design A literature search of PubMed, Embase, PsychINFO, Web of Science, Scopus, and the Cochrane Library databases for human and animal studies that evaluated the use of TNF‐αI was performed on 26 October 2016. Results The main outcomes assessed were cognition and behaviour, reduction in brain tissue mass, presence of plaques and tangles, and synaptic function. Risk of bias was assessed regarding blinding, statistical model, outcome reporting, and other biases. Sixteen studies were included, 13 of which were animal studies and 3 of which were human. All animal studies found that treatment with TNF‐αI leads to an improvement in cognition and behaviour. None of the studies measured change in brain tissue mass. The majority of studies documented a beneficial effect in other areas, including the presence of plaques and tangles and synaptic function. The amount of data from human studies was limited. Two out of 3 studies concluded that TNF‐αI are beneficial in Alzheimer's disease patients, with one being an observational study and the latter being a small pilot study, with a high risk of bias. Conclusion It was concluded that a large‐scale randomized controlled trial assessing the effectiveness of TNF‐αI on humans is warranted.

Depression and anxiety are common in later life, particularly when people are frail. This leads to reduced quality of life, faster decline in physical health and increased health/social care use. Available treatments are commonly not tailored to people with frailty. We explored frail older peoples' experiences of depression and/or anxiety and how services could be adapted to their needs.Semi-structured interviews with 28 older people in the UK purposively sampled for practice location and severity of frailty and anxiety/depression. We asked about symptoms, interactions with physical health, help-seeking, treatments and what might help in future. We audio-recorded and transcribed interviews, using thematic analysis to inductively derive themes.Frail older people had low expectations of their wellbeing at this point in life due to multiple physical health issues and so anxiety and mild depressive symptoms were normalised. There was a particular reluctance and uncertainty regarding help-seeking for anxiety. Treatments were considered appropriate where they aligned with coping skills developed over their lifetime, and facilitated independence and problem-solving skills. Most older people felt their knowledge of mental health was limited and relied upon information about and endorsement of therapies from an expert. This was usually their GP, but access was often problematic. Online methods of accessing information and therapies were not popular.Mental health support for frail older people needs to address late-life anxieties as well as depression, account for physical health issues, align with older people's need for independence and facilitate coping skills.

Background: There is a lack of knowledge about what factors may impede or facilitate engagement in psychological interventions in people with motor neuron disease (pwMND) and how such interventions can be adapted to best meet the needs of this population. Objectives: To explore the needs and preferences of pwMND with respect to psychological interventions, and how best to adapt such interventions for pwMND. Methods: A series of semi-structured interviews (n = 22) and workshops (n = 3) were conducted with pwMND (n = 15), informal caregivers of pwMND (n = 10), and MND healthcare professionals (n = 12). These explored preferences and concerns that would need to be considered when delivering a psychological intervention for pwMND. Three areas were explored: (i) perceived factors that may hinder or facilitate pwMND engaging with psychological interventions; (ii) ways in which such interventions could be adapted to meet the individual needs of pwMND; and (iii) views regarding the main psychological issues that would need to be addressed. Workshops and interviews were audio recorded and transcribed and thematic analysis was used to inductively derive themes. Findings: Data could be classified within four overarching themes: unfamiliar territory; a series of losses; variability and difficulty meeting individual needs; and informal support. Conclusions: Flexibility, tailoring interventions to the individual needs of pwMND, and encouraging autonomy are key attributes for psychological interventions with pwMND. Psychological interventions such as Acceptance and Commitment Therapy (ACT) could be acceptable for pwMND if adapted to their specific needs.

ObjectiveTo review evidence evaluating the use of multicomponent frailty assessment tools in assessing frailty in older adults with psychiatric disorders.MethodsA systematic literature review was conducted to identify all multicomponent frailty assessment tools (ie, a tool that assesses two or more indicators of frailty). The items of each frailty assessment tool were compared with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM‐5) diagnostic criteria for psychiatric disorders to assess construct overlap. Studies conducted in community, inpatient, and outpatient clinical settings were considered for inclusion.ParticipantsAdults aged 60 years or older.ResultsA total of 5639 records were identified following the removal of duplicates, from which 95 studies were included for review. Of the 48 multicomponent frailty assessment tools identified, no tool had been developed for, or validated in, older adult populations with a psychiatric disorder. Overall, 20 of 48 frailty assessment tools contained a psychological assessment domain, with 17 of 48 tools citing the presence of depressed mood and/or anxiety as a frailty indicator. Common areas of construct overlap in frailty assessment tools and DSM‐5 diagnostic criteria included weight loss (29 of 48) and fatigue (21 of 48).ConclusionsSignificant construct overlap exists between the indicators of frailty as conceptualized in existing frailty assessment tools and DSM‐5 diagnostic criteria for common psychiatric disorders including major depressive episode and generalized anxiety disorder that has the potential to confound frailty assessment results. Further research is necessary to establish a reliable and valid tool to assess frailty in this population. J Am Geriatr Soc, 1–11, 2018.

Glutathione (GSH) is a critical endogenous antioxidant found in all eukaryotic cells. Higher GSH concentrations protect against cellular damage, tissue degeneration, and disease progression in various models, so there is considerable interest in developing interventions that augment GSH biosynthesis. Oral GSH supplementation is not the most efficient option due to the enzymatic degradation of ingested GSH within the intestine by γ-glutamyltransferase, but supplementation of its component amino acids—cysteine, glycine, and glutamate—enhances tissue GSH synthesis. Furthermore, supplementation with some non-precursor amino acids and micronutrients appears to influence the redox status of GSH and related antioxidants, such as vitamins C and E, lowering systemic oxidative stress and slowing the rate of tissue deterioration. In this review, the effects of oral supplementation of amino acids and micronutrients on GSH metabolism are evaluated. And since specific dietary patterns and diets are being prescribed as first-line therapeutics for conditions such as hypertension and diabetes, the impact of overall diets on GSH homeostasis is also assessed.

Background and Objective: Current treatments for Alzheimer's Disease (AD) do not affect the course of the illness and brain stimulation techniques are increasingly promoted as potential therapeutic inter-ventions for AD. This study reviews the effects of electromagnetic field (EMF) exposure versus sham exposure on working memory (WM) performance of healthy human participants. Method: Online literature databases and previous systematic reviews were searched for studies of EMF and WM in participants without reported memory problems. Two thousand eight hundred and fifty seven studies were identified, and 10 studies met the inclusion criteria. An assessment of study quality was completed, and separate, random effects meta-analyses were conducted for each of the three WM tasks included: n-back, substitution and digit span forward. Results: No differences were found between participants exposed to active EMF versus sham conditions in any of the three working memory tasks examined. Conclusion: Results indicate that EMF does not affect WM during the n-back, substitution and digit-span tasks. Future studies should focus on the possible effects of chronic exposure to EMF in older adults with AD using a battery of comparable WM and attention tasks, before EMF can be seriously considered as a potential modulator of WM in AD.

Potential differences between relationships formed in online versus offline venues were explored using an online survey of massively multiplayer online gamers. Participants (N = 1654) provided information about two or more relationships (kin, friends, and romantic relationships), indicating whether these had originated in online or offline venues. Attachment, attraction and communication were assessed for each relationship. Relationship security was predicted by attraction, but the effects of venue were limited to avoidance towards online romantic relationships. Personality, gaming motivation, age and sex all made negligible contributions to relationship security. Limitations, including the correlational nature of the data and the high proportion of male participants, as well as suggestions for how relationship research might proceed in an increasingly online world, are discussed.

Glutathione is a ubiquitous antioxidant that protects cells against reactive oxygen species and other chemical stressors. Despite its functional importance, the impact of genetics on the glutathione system has yet to be fully appreciated. Here, we investigated the heritability of glutathione levels and redox status in a disease-relevant condition: advanced age. We assembled a panel of 18-21-month-old mice representing 19 inbred strains and quantified the levels of reduced and oxidized glutathione, and their sums and ratios, in liver, kidney, heart, pancreas, cerebral cortex, and striatum. Heritability values were calculated for each phenotype and the results varied by tissue of origin. Cardiac glutathione phenotypes exhibited the highest heritabilities (G2 = 0.44-0.67), while striatal glutathione was least heritable (G2 = 0.11-0.29). Statistical relationships between tissues were evaluated, and the emergence of significant correlations suggested that despite tissue-specific heritabilities, at least some shared regulatory mechanisms may exist. Overall, these data highlight another mechanism by which genetic background determines antioxidant protection and stress resistance.

To systematically review the characteristics, validity and outcome measures of tasks that have been described in the literature as assessing pattern separation and pattern completion in humans. Electronic databases were searched for articles. Parameters for task validity were obtained from two reviews that described optimal task design factors to evaluate pattern separation and pattern completion processes. These were that pattern separation should be tested during an encoding task using abstract, never-before-seen visual stimuli, and pattern completion during a retrieval task using partial cues; parametric alteration of the degree of interference of stimuli or degradation of cues should be used to generate a corresponding gradient in behavioral output; studies should explicitly identify the specific memory domain under investigation (sensory/perceptual, temporal, spatial, affect, response, or language) and account for the contribution of other potential attributes involved in performance of the task. A systematic, qualitative assessment of validity in relation to these parameters was performed, along with a review of general validity and task outcome measures. Sixty-two studies were included. The majority of studies investigated pattern separation and most tasks were performed on young, healthy adults. Pattern separation and pattern completion were most frequently tested during a retrieval task using familiar or recognizable visual stimuli and cues. Not all studies parametrically altered the degree of stimulus interference or cue degradation, or controlled for potential confounding factors. This review found evidence that some of the parameters for task validity have been followed in some human studies of pattern separation and pattern completion, but no study was judged to have adequately met all the parameters for task validity. The contribution of these parameters and other task design factors towards an optimal behavioral paradigm is discussed and recommendations for future research are made. © 2015 Wiley Periodicals, Inc.

Background Establishing the cognitive phenotype of psychotic symptoms in Alzheimer's disease (AD) could localise discrete pathology and target symptomatic treatment. This study aimed to establish whether psychotic symptoms would be associated with poorer performance on neuropsychological tests known to correlate with striatal dopaminergic function and to investigate whether these differences would be attributed to the paranoid (persecutory delusions) or misidentification (misidentification phenomena +/− hallucinations) subtype. Methods Seventy patients with probable AD (34 psychotic and 36 nonpsychotic) were recruited to the study. Analysis of covariance was used to compare motor speed and the rapid visual processing test of sustained visual attention, after adjusting for potential confounding factors. Multivariate analyses were used to compare performance across other cognitive domains. Significant findings were explored by separating patients on the basis of subtype. Results Rapid visual processing performance accuracy was reduced in patients with psychotic symptoms (F1,58 = 5.94, p = 0.02) and differed significantly across subtypes (F2,51 = 3.94, p = 0.03), largely because of poorer performance in the misidentification compared with nonpsychotic group. Multivariate analyses (corrected for multiple comparisons) showed poorer performance on the incomplete letters task in psychotic patients (F1,63 = 8.77, p = 0.004) and across subtypes (F2,55 = 10.90, p

ObjectiveDepressive symptoms are common among people with dementia, impacting quality of life and cognitive and functional decline. Currently, little is known about the acceptability and feasibility of psychological interventions for people with mild dementia, with recent reviews identifying the need for further evidence. Developing and evaluating psychological interventions to prevent and treat these symptoms is, therefore, an important clinical and research priority. This protocol describes a study testing the acceptability and feasibility of a manual-based behavioural activation (BA) intervention for preventing and treating depressive symptoms in people with mild dementia. The aim of this study is to explore the feasibility of conducting a pragmatic multicentre randomised controlled trial of clinical effectiveness of an eight-session intervention. The Intervention to prevent Depressive symptoms and promote well-being in EArly-stage dementia (IDEA) programme supports people with dementia and their family carers in identifying and scheduling enjoyable and meaningful activities.Methods and analysisSixty people who have received a diagnosis of dementia of any type in the last 6 months will be recruited via memory clinics. Further criteria are a Mini-Mental State Examination score of ≥20, and a family carer who can assist with the intervention. Consenting participants will be randomised in a ratio of 2:1 to BA or to treatment as usual. Analyses will estimate parameters such as rates of recruitment, retention and number of sessions completed. Questionnaires measuring depressive symptoms and quality of life for both the person with dementia and their carer will be completed at baseline, 3 and 6 months. Qualitative interviews will explore acceptability of the intervention, study procedures and experiences of the sessions.Ethics and disseminationThis study received a favourable ethical opinion from the London Camberwell St Giles Research Ethics Committee (16/LO/0540). We will disseminate findings at key conferences, the Alzheimer’s Society and University College London websites and local stakeholder events.Trial registration numberISRCTN75503960; Pre-results.

Background Predictor analyses of late-life depression can be used to identify variables associated with outcomes of treatments, and hence ways of tailoring specific treatments to patients. The aim of this review was to systematically identify, review and meta-analyse predictors of outcomes of any type of treatment for late-life depression.Methods Pubmed, Embase, CINAHL, Web of Science and PsycINFO were searched for studies published up to December 2016. Primary and secondary studies reported treatment predictors from randomised controlled trials of any treatment for patients with major depressive disorder aged over 60 were included. Treatment outcomes included response, remission and change in depression score.ResultsSixty-seven studies met the inclusion criteria. Of 65 identified statistically significant predictors, only 7 were reported in at least 3 studies. Of these, 5 were included in meta-analyses, and only 3 were statistically significant. Most studies were rated as being of moderate to strong quality and satisfied key quality criteria for predictor analyses.LimitationsThe searches were limited to randomised controlled trials and most of the included studies were secondary analyses.ConclusionsBaseline depression severity, co-morbid anxiety, executive dysfunction, current episode duration, early improvement, physical illnesses and age were reported as statistically significant predictors of treatment outcomes. Only the first three were significant in meta-analyses. Subgroup analyses showed differences in predictor effect between biological and psychosocial treatment. However, high heterogeneity and small study numbers suggest a cautious interpretation of results. These predictors were associated with various mechanisms including brain pathophysiology, perceived social support and proposed distinct types of depressive disorder. Further investigation of the clinical utility of these predictors is suggested.

In this article, the authors discuss the light and dark side of attachments and attachment style in physical and digital worlds. They argue that many games offer opportunities for the generation of new and meaningful attachments to both physical and digital others. They discuss two ‘fundamental attachment errors’ and show how these can lead to both ‘light’ outcomes, in terms of opportunities to learn more secure attachment patterns, and ‘dark’ outcomes, where existing dysfunctional behaviours become more pronounced. The authors argue that the avatars which children adopt online have important consequences for their psychosocial development, and that these are mediated through the degree to which the real self is differentiated from the avatar. It is proposed that attachment is a key force in understanding play, and that studying its manifestations and effects in digital playscapes may contribute to understanding the effects of life online, and how insecure attachments may become secure.

Introduction: Preimplantation genetic diagnosis and screening (PGD/PGS) has been applied clinically for >25 years however inherent drawbacks include the necessity to tailor each case to the trait in question, and that technology to detect monogenic and chromosomal disorders respectively is fundamentally different.\ud \ud Areas Covered: The area of preimplantation genetics has evolved over the last 25 years, adapting to changes in technology and the need for more efficient, streamlined diagnoses. Karyomapping allows the determination of inheritance from the (grand)parental haplobocks through assembly of inherited chromosomal segments. The output displays homologous chromosomes, crossovers and the genetic status of the embryos by linkage comparison, as well as chromosomal disorders. It also allows for determination of heterozygous SNP calls, avoiding the risks of allele dropout, a common problem with other PGD techniques. Manuscripts documenting the evolution of preimplantation genetics, especially those investigating technologies that would simultaneously detect monogenic and chromosomal disorders, were selected for review.\ud \ud Expert Commentary: Karyomapping is currently available for detection of single gene disorders; ~1000 clinics worldwide offer it (via ~20 diagnostic laboratories) and ~2500 cases have been performed. Due an inability to detect post-zygotic trisomy reliably however and confounding problems of embryo mosaicism, karyomapping has yet to be applied clinically for detection of chromosome disorders.

ObjectiveInflammation has been implicated in the aetiology of mental illness. We conducted the first systematic review and meta-analysis of the association between peripheral markers of inflammation and generalised anxiety disorder (GAD).DesignSystematic review and meta-analysis of studies measuring peripheral cytokine levels in people with GAD compared with controls.Data sourcesMEDLINE (1950–), EMBASE (1947–), PsycINFO (1872–) and Web of Science (1945–) databases up until January 2018.Eligibility criteriaPrimary, quantitative research studies of people with a diagnosis of GAD assessed using a standardised clinical interview that measured peripheral inflammatory markers.Data extraction and synthesisTwo independent reviewers extracted data and assessed study quality. Meta-analysis using a random-effects model was conducted for individual cytokines where data from three or more studies were available.Results14 of 1718 identified studies met the inclusion criteria, comprising 1188 patients with GAD and 10 623 controls. In total 16 cytokines were evaluated. Significantly raised levels of C reactive protein (CRP), interferon-γ and tumour necrosis factor-α were reported in patients with GAD compared with controls in two or more studies. Ten further proinflammatory cytokines were reported to be significantly raised in GAD in at least one study. However, 5 of 14 studies found no difference in the levels of at least one cytokine. Only CRP studies reported sufficient data for meta-analysis. CRP was significantly higher in people with GAD compared with controls, with a small effect size (Cohen’s d=0.38, 0.06–0.69), comparable with that reported in schizophrenia. However, heterogeneity was high (I2=75%), in keeping with meta-analyses of inflammation in other psychiatric conditions and reflecting differences in participant medication use, comorbid depression and cytokine sampling methodology.ConclusionThere is preliminary evidence to suggest an inflammatory response in GAD, but it remains unclear whether inflammatory cytokines play a role in the aetiology. GAD remains a poorly studied area of neuroinflammation compared with other mental disorders, and further longitudinal studies are required.

BackgroundThe use of benzodiazepines has been advised against in older people, but prevalence rates remain high.AimsTo review the evidence for interventions aimed at reducing benzodiazepine use in older people.MethodWe conducted a systematic review, assessment of risk of bias and meta-analyses of randomised controlled trials of benzodiazepine withdrawal and prescribing interventions.ResultsTen withdrawal and eight prescribing studies met the inclusion criteria. At post-intervention, significantly higher odds of not using benzodiazepines were found with supervised withdrawal with psychotherapy (odds ratio (OR) = 5.06, 95% CI 2.68–9.57,PP=0.04) in comparison with the control interventions treatment as usual (TAU), education placebo, withdrawal with or without drug placebo, or psychotherapy alone. Significantly higher odds of not using benzodiazepines were also found for multifaceted prescribing interventions (OR = 1.37, 95% CI 1.10–1.72,P= 0.006) in comparison with control interventions (TAU and prescribing placebo).ConclusionsSupervised benzodiazepine withdrawal augmented with psychotherapy should be considered in older people, although pragmatic reasons may necessitate consideration of other strategies such as medication review.

The first application of preimplantation genetic diagnosis (PGD) recently celebrated its 25th birthday. Aside from the very early days when chromosomal diagnoses were used (by sexing) for the selective implantation of embryos unaffected by sex linked disorders, the paths of chromosomal and monogenic PGD have diverged. For monogenic disorders, progress has been impeded by the need to tailor each diagnosis to the mutation in question. For chromosomal diagnoses, fluorescent in situ hybridization (FISH) technology was replaced by array comparative genomic hybridization (aCGH), and then next generation sequencing (NGS). Karyomapping is a novel approach that allows the detection of the inheritance of (grand) parental haploblocks through the identification of inherited chromosomal segments. It involves genome-wide single nucleotide polymorphism (SNP) analysis of parental DNA, a reference from a related individual of known disease status (typically an affected child) and amplified DNA form biopsied cells of the (usually blastocyst) embryos in question. Identification of informative loci for each of four parental haplotypes is followed by direct comparison to the reference, ultimately creating a Karyomap. The Karyomapping programme (Illumina) displays homologous chromosomes, points of crossing over and the haplotype of each of the embryos. It also detects meiotic trisomy, monosomy, triploidy and uniparental heterodisomy (some of which NGS and aCGH will not). Inherent in the design is the analysis of “key SNPs” (heterozygous informative calls) thereby avoiding the risk of misdiagnoses caused by the phenomenon of allele drop out (ADO). Karyomapping is currently in use for the detection of monogenic disorders and around 1000 clinics offer it worldwide making use of about 20 diagnostic laboratories. At the time of writing, over two and a half thousand clinical cases have been performed. Because of the limited detection of some post-zygotic errors such as post-zygotic trisomy which can also lead to mosaicism, Karyomapping has not yet been fully applied clinically for aneuploidy screening. The diagnostic potential of the technique will be fully recognised with the application of this technology on clinical cases.