UK clinicians' attitudes towards the application of molecular diagnostics to guide antibiotic use in ICU patients with pneumonias: a quantitative study.

BACKGROUND: Molecular diagnostic tests may improve antibiotic prescribing by enabling earlier tailoring of antimicrobial therapy. However, clinicians' trust and acceptance of these tests will determine their application in practice. OBJECTIVES: To examine ICU prescribers' views on the application of molecular diagnostics in patients with suspected hospital-acquired and ventilator-associated pneumonia (HAP/VAP). METHODS: Sixty-three ICU clinicians from five UK hospitals completed a cross-sectional questionnaire between May 2020 and July 2020 assessing attitudes towards using molecular diagnostics to inform initial agent choice and to help stop broad-spectrum antibiotics early. RESULTS: Attitudes towards using molecular diagnostics to inform initial treatment choices and to stop broad-spectrum antibiotics early were nuanced. Most (83%) were positive about molecular diagnostics, agreeing that using results to inform broad-spectrum antibiotic prescribing is good practice. However, many (58%) believed sick patients are often too unstable to risk stopping broad-spectrum antibiotics based on a negative result. CONCLUSIONS: Positive attitudes towards the application of molecular diagnostics to improve antibiotic stewardship were juxtapositioned against the perceived need to initiate and maintain broad-spectrum antibiotics to protect unstable patients.

Reliability and validity of the Turkish version of the medication practical barriers to adherence questionnaire in patients with chronic diseases.

PURPOSE: The aim of this study was to evaluate the validity and reliability of the Turkish version of the Medication Practical Barriers to Adherence Questionnaire (MPRAQ-TR). METHODS: This is a validation study conducted between August 2022 and March 2023 in the ambulatory services of a secondary care private hospital located in Istanbul, Türkiye, among patients (18 years of age and older) with chronic diseases. After the Turkish translation and cultural adaptation of the MPRAQ, and a pilot think-aloud study, the following psychometric properties were assessed: internal consistency by calculating the Cronbach's alpha coefficient, 2-week test-retest reliability, convergent validity by calculating Spearman's rank correlation between the MPRAQ-TR and the Turkish version of Medication Adherence Report Scale (MARS), and predictive validity by evaluating the association between the MPRAQ-TR score and nonadherence to medications. RESULTS: Among the 380 patients (response rate = 89.6%), 72.1% were nonadherent to their medications. The intraclass correlation coefficient was 0.99 for MPRAQ-TR scores (95% CI, 0.98-0.99; p < 0.001). The Cronbach's alpha of the MPRAQ-TR was 0.853. There was a moderate negative correlation between the scores on the MARS and the MPRAQ-TR (Spearman's rho = - 0.525; p < 0.01), supporting the convergent validity of the MPRAQ-TR. In the univariate analysis, the total score of MPRAQ-TR was associated with increased odds of nonadherence to medications (p < 0.01). CONCLUSION: MPRAQ-TR shows good psychometric properties and can be used to evaluate the practical adherence barriers of patients with chronic diseases.

Redefining Beauty: A Qualitative Study Exploring Adult Women's Motivations for Lip Filler Resulting in Anatomical Distortion.

BACKGROUND: Lip filler enhancement has fast become one of the most popular minimally invasive cosmetic procedures. Motivations for "overtreatment" with lip fillers are poorly understood. OBJECTIVES: The aim of this study was to explore female motivations for and experiences of procedures that achieve an aesthetic of distorted lip anatomy. METHODS: Twenty-four females who had undergone lip filler procedures resulting in strikingly distorted lip anatomy, determined by the Harris classification of filler spread, took part in semistructured interviews about their motivations, experiences, and perceptions related to lip fillers. A qualitative thematic analysis was carried out. RESULTS: Four major themes are discussed: (1) the normalization of lip fillers, (2) perceptual drift which is mediated by exposure to repetitive images of larger lips on social media, (3) perceived financial and social benefits of larger lips, and (4) the relation between mental health and seeking repeated lip filler procedures. CONCLUSIONS: Motivations for seeking lip fillers vary, but most subjects described social media impacting perceived aesthetic norms. A process of perceptual drift occurs whereby mental schema encoding expectations of "natural" facial anatomy can adapt through repeated exposure to enhanced images. The results can inform aesthetic practitioners and policymakers seeking to understand and support those seeking minimally invasive cosmetic procedures.

An Evidence-Based Theory of Psychological Adjustment to Long-Term Physical Health Conditions: Applications in Clinical Practice.

OBJECTIVE: Around 30% of people with long-term physical health conditions (LTCs) experience comorbid anxiety and depression. For many, comorbid distress is linked to difficulties adjusting to the challenges of the LTC. The aims of this article are to present a transdiagnostic theoretical model of adjustment to LTCs (TMA-LTC), demonstrate the application of this model in clinical practice, and highlight the distinguishing features of treating LTC-related distress compared with treating primary anxiety and/or depression. METHODS: A systematic review (k = 21) was conducted to collate preexisting evidence-based models of adjustment across LTCs. Models of adjustment for a range of LTCs were extracted and synthesized into a new preliminary TMA-LTC. Two expert consensus meetings were held, where experts rated the relevance and importance of all concepts within the models. RESULTS: The TMA-LTC proposes that acute critical events or ongoing illness stressors can disrupt emotional equilibrium, and that whether a person returns to equilibrium and achieves good psychological adjustment depends on a number of cognitive and behavioral factors, as well as their interpersonal, intrapersonal, environmental, and illness-specific contexts. A case study is presented to demonstrate the clinical application of this model in treating illness-related distress, highlighting how it overcomes roadblocks that may be encountered when working primarily within traditional mental health paradigms. CONCLUSIONS: As an empirically and clinically informed model, TMA-LTC provides a useful guide for assessment, formulation, and treatment in the context of psychological adjustment to LTCs. Future studies are needed to test treatments that have been developed based on TMA-LTC.

Disparities in access to mobile devices and e-health literacy among breast cancer survivors.

BACKGROUND: The number of e-health interventions developed for breast cancer survivors continues to increase. However, issues with engagement and retention are common. This study aimed to explore e-health literacy rates and access to smartphones and tablets in a large sample of breast cancer survivors. METHODS: In study 1, women were recruited from outpatient breast clinics across England and Wales. Eligible women were asked to complete a questionnaire pack to assess their access to devices and their e-health literacy. Multiple regression analyses were run to assess the relationship between technology access and e-health literacy with sociodemographic variables such as age, social deprivation, and education. Study 2 presents a smaller sample recruited through social media who answered a questionnaire relating to use of mobile devices and e-health, and apps. RESULTS: Two thousand nine women participated in the study. Seventy-one percent had access to a smartphone, 54% had access to a tablet, and 20% did not have access to either device. Multiple logistic regressions showed that women who were younger, had higher levels of education, and who were from less deprived areas were more likely to have access to either device. Poorer e-health literacy was associated with being older, having less education, and not having access to a mobile device. CONCLUSIONS: Whilst the results show relatively widespread access to mobile devices, there is evidence of a digital divide across some groups. Online interventions should be developed with consideration of individuals who are less e-health-literate and less technologically adept in order to increase the likelihood of engagement.

Adherence to adjuvant endocrine therapy among White British and ethnic minority breast cancer survivors in the United Kingdom.

OBJECTIVE: Around half of women do not take adjuvant endocrine therapy (AET) as prescribed. Research suggests that adherence rates vary across ethnic groups. This study compared AET adherences rates in White British women and women from minority ethnic groups in the United Kingdom. METHODS: This is an observational study with 2001 breast cancer survivors recruited from outpatient clinics. Eligible women were diagnosed with primary breast cancer and prescribed AET within the last 3 years. Adherence was measured using the Medication Adherence Rating Scale. Eligible women were asked to complete a questionnaire pack that collected sociodemographic data such as age, relationship status and ethnicity. Independent samples t tests and χ2 tests were used to compare White British women and women from minority ethnic groups on self-reported adherence to AET. RESULTS: Of White British women, 27.8% were classed as non-adherent, compared to 44.4% of women from minority ethnic groups. A logistic regression controlling for relevant demographics indicated that women from minority ethnic groups had a significantly higher risk of non-adherence than women who were White British (odds ratio = 1.50, p = 0.03) CONCLUSION: Rates of non-adherence to AET are higher in women from minority ethnic groups, which may contribute towards racial disparities in breast cancer outcomes. Research with larger and more diverse samples is needed to explore this further and to investigate the psychosocial factors driving differences in adherence.

Development of a self-management intervention to improve tamoxifen adherence in breast cancer survivors using an Intervention Mapping framework.

OBJECTIVE: Up to 50% of women prescribed tamoxifen do not take it as prescribed for the full duration, which increases risk of recurrence and mortality. The current paper describes the development of a self-management intervention aiming to improve adherence in breast cancer survivors taking tamoxifen. METHODS: The intervention was developed following an Intervention Mapping approach. The content of the intervention was determined by theories of health behaviour and empirical evidence. Development was an iterative process involving input from expert researchers, clinicians and patient representatives. RESULTS: The intervention was designed to improve both intentional and unintentional non-adherence. Key features included modifying unhelpful illness and treatment beliefs, improving confidence for coping with side effects and developing strategies for remembering to take tamoxifen. CONCLUSION: Intervention Mapping proved a useful tool for developing an intervention which is grounded in theory and empirical evidence. The intervention has the potential to improve adherence in breast cancer survivors but needs to be trialled before the effectiveness of the intervention can be determined.

Using the 5-Item Medication Adherence Report Scale (MARS-5) to Screen for Non-adherence to Vitamin and Mineral Supplementation After Bariatric Surgery.

INTRODUCTION: Poor adherence to recommended vitamin and mineral supplementation after bariatric surgery is common and challenging for healthcare professionals to identify. There are several questionnaires for self-reporting of adherence to chronic medication, but none has so far been evaluated for assessment of adherence to vitamin and mineral supplementation after bariatric surgery. The aim of this study was to assess the accuracy of the 5-item Medication Adherence Report Scale (MARS-5) in measuring adherence to vitamin and mineral supplementation post bariatric surgery (gastric bypass or sleeve gastrectomy). METHOD: The psychometric properties of MARS-5 for vitamin and mineral supplementation were validated in two cohorts: one at 1 year post bariatric surgery (n = 120) and the other at 2 years post-surgery (n = 211). MARS-5 was compared to pharmacy refill data for vitamin B12 and combined calcium/vitamin D as reference. RESULTS: Correlation analyses demonstrated that the MARS-5 had acceptable validity compared to objectively measured adherence rates from pharmacy refill data (calculated as continuous, multiple-interval measures of medication availability/gaps-coefficient ranged from 0.49 to 0.54). Internal reliability (Cronbach's α) was high: 0.81 and 0.95, respectively. There was a clear ceiling effect where one out of three had a maximum score on MARS-5. CONCLUSION: MARS-5 demonstrated acceptable psychometric properties for assessment of adherence to vitamin and mineral supplementation post bariatric surgery.

Identifying determinants of adherence to adjuvant endocrine therapy following breast cancer: A systematic review of reviews.

BACKGROUND: In oestrogen-receptor positive breast cancer, daily oral adjuvant endocrine therapy (ET) for at least 5 years significantly reduces risks of recurrence and breast cancer-specific mortality. However, many women are poorly adherent to ET. Development of effective adherence support requires comprehensive understanding of influences on adherence. We undertook an umbrella review to identify determinants of ET adherence. METHODS: We searched PubMed, Embase, CINAHL, PsycINFO, Cochrane and PROSPERO (inception to 08/2022) to identify systematic reviews on factors influencing ET adherence. Abstracted determinants were mapped to the World Health Organization's dimensions of adherence. Reviews were quality appraised and overlap assessed. RESULTS: Of 5732 citations screened, 17 reviews were eligible (9 quantitative primary studies; 4 qualitative primary studies; 4 qualitative or quantitative studies) including 215 primary papers. All five WHO dimensions influenced ET non-adherence: The most consistently identified non-adherence determinants were patient-related factors (e.g. lower perceived ET necessity, more treatment concerns, perceptions of ET 'cons' vs. 'pros'). Healthcare system/healthcare professional-related factors (e.g. perceived lower quality health professional interaction/relationship) were also important and, to a somewhat lesser extent, socio-economic factors (e.g. lower levels of social/economic/material support). Evidence was more mixed for medication-related and condition-related factors, but several may be relevant (e.g. experiencing side-effects, cost). Potentially modifiable factors are more influential than non-modifiable/fixed factors (e.g. patient characteristics). CONCLUSIONS: The evidence-base on ET adherence determinants is extensive. Future empirical studies should focus on less well-researched areas and settings. The determinants themselves are numerous and complex in indicating that adherence support should be multifaceted, addressing multiple determinants.

Health and illness beliefs in adults with tuberculosis infection during the COVID-19 pandemic in the UK.

Background: COVID-19 disrupted the TB prevention programme in the UK, especially for TB infection (TBI) care. We explore whether experience of the COVID-19 pandemic impacted on patients' perceptions of TBI and its treatment. Methods: Semi-structured interviews were conducted as part of the Research to Improve Detection and Treatment of TBI (RID-TB) programme, exploring perceptual and practical barriers to TBI treatment. Nineteen people diagnosed with TBI were interviewed between August 2020 and April 2021. Recordings were transcribed and analysed using a constant comparative approach, allowing for a dynamic and iterative exploration of themes. Themes are organised using the Perceptions and Practicalities Approach. Findings: Some participants perceived TBI as a risk factor for increased susceptibility to COVID-19, while some thought that treatment for TBI might protect against COVID-19 or mitigate its effects. Adaptations to TB services (e.g., remote follow-up) and integrated practices during the COVID-19 restrictions (e.g., medication being posted) addressed some practical barriers to TBI treatment. However, we identified beliefs about TBI and COVID-19 that are likely to act as barriers to engagement with TBI treatment, including: interpreting service delays as an indication of TBI not being serious enough for treatment and concerns about contracting COVID-19 in TB clinics. Interpretation: COVID-19 and TBI service delays influence people's perceptions and practical barriers to TBI treatment adherence. Failure to address these beliefs may lead to people's concerns about their treatment not being fully addressed. Utilised service adaptations like remote consultations to address practical barriers may be relevant beyond COVID-19. Funding: NIHR RID-TB Program (RP-PG-0217-20009).

Medication nonadherence: health impact, prevalence, correlates and interventions.

Nonadherence to medicines is a global problem compromising health and economic outcomes for individuals and society. This article outlines how adherence is defined and measured, and examines the impact, prevalence and determinants of nonadherence. It also discusses how a psychosocial perspective can inform the development of interventions to optimise adherence and presents a series of recommendations for future research to overcome common limitations associated with the medication nonadherence literature. Nonadherence is best understood in terms of the interactions between an individual and a specific disease/treatment, within a social and environmental context. Adherence is a product of motivation and ability. Motivation comprises conscious decision-making processes but also from more 'instinctive', intuitive and habitual processes. Ability comprises the physical and psychological skills needed to adhere. Both motivation and ability are influenced by environmental and social factors which influence the opportunity to adhere as well as triggers or cues to actions which may be internal (e.g. experiencing symptoms) or external (e.g. receiving a reminder). Systematic reviews of adherence interventions show that effective solutions are elusive, partly because few have a strong theoretical basis. Adherence support targeted at the level of individuals will be more effective if it is tailored to address the specific perceptions (e.g. beliefs about illness and treatment) and practicalities (e.g. capability and resources) influencing individuals' motivation and ability to adhere.

Acceptance and commitment therapy processes and their association with distress in cancer: a systematic review and meta-analysis.

Around 42% of individuals with cancer experience distress. Acceptance and commitment therapy (ACT) can reduce distress, but effects are small, and mechanisms unclear. This review aimed to identify associations between ACT processes and distress in cancer. Search terms included cancer, ACT processes, self-compassion, and distress. Six online databases and grey literature were searched until March 2022. Of 6555 papers screened, 108 studies were included with 17,195 participants. Five meta-analyses of 77 studies were conducted. Random effects meta-analyses of correlations revealed higher scores on flexible processes (acceptance, present moment awareness, self-compassion) were associated with lower distress (rpooled = -0.24, -0.39, -0.48, respectively); whilst higher scores on inflexible processes (experiential avoidance, cognitive fusion) were associated with higher distress (rpooled = 0.58, 0.57, respectively). Meta-analyses displayed moderate-to-high heterogeneity with most studies assessed as low risk of bias. Meta-regressions revealed no significant moderators (stage, time since diagnosis, gender and age). This review provides a theoretically aligned evidence base for associations between ACT processes and distress in cancer, supporting elements of ACT theory and providing targeted directions for intervention development. Due to limited evidence, future research should focus on self-as-context, values and committed action and conduct mediation analysis in controlled trials of ACT processes on distress in cancer.

Development of the HT&Me intervention to support women with breast cancer to adhere to adjuvant endocrine therapy and improve quality of life.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Approximately 80% of breast cancers are oestrogen receptor positive (ER+). Patients treated surgically are usually recommended adjuvant endocrine therapy (AET) for 5-10 years. AET significantly reduces recurrence, but up to 50% of women do not take it as prescribed. OBJECTIVE: To co-design and develop an intervention to support AET adherence and improve health-related quality-of-life (QoL) in women with breast cancer. METHODS: Design and development of the HT&Me intervention took a person-based approach and was guided by the Medical Research Council framework for complex interventions, based on evidence and underpinned by theory. Literature reviews, behavioural analysis, and extensive key stakeholder involvement informed 'guiding principles' and the intervention logic model. Using co-design principles, a prototype intervention was developed and refined. RESULTS: The blended tailored HT&Me intervention supports women to self-manage their AET. It comprises initial and follow-up consultations with a trained nurse, supported with an animation video, a web-app and ongoing motivational 'nudge' messages. It addresses perceptual (e.g. doubts about necessity, treatment concerns) and practical (e.g. forgetting) barriers to adherence and provides information, support and behaviour change techniques to improve QoL. Iterative patient feedback maximised feasibility, acceptability, and likelihood of maintaining adherence; health professional feedback maximised likelihood of scalability. CONCLUSIONS: HT&Me has been systematically and rigorously developed to promote AET adherence and improve QoL, and is complemented with a logic model documenting hypothesized mechanisms of action. An ongoing feasibility trial will inform a future randomised control trial of effectiveness and cost-effectiveness.

Optimized immunosuppression to prevent graft failure in renal transplant recipients with HLA antibodies (OuTSMART): a randomised controlled trial.

Background: 3% of kidney transplant recipients return to dialysis annually upon allograft failure. Development of antibodies (Ab) against human leukocyte antigens (HLA) is a validated prognostic biomarker of allograft failure. We tested whether screening for HLA Ab, combined with an intervention to improve adherence and optimization of immunosuppression could prevent allograft failure. Methods: Prospective, open-labelled randomised biomarker-based strategy (hybrid) trial in 13 UK transplant centres [EudraCT (2012-004308-36) and ISRCTN (46157828)]. Patients were randomly allocated (1:1) to unblinded or double-blinded arms and screened every 8 months. Unblinded HLA Ab+ patients were interviewed to encourage medication adherence and had tailored optimisation of Tacrolimus, Mycophenolate mofetil and Prednisolone. The primary outcome was time to graft failure in an intention to treat analysis. The trial had 80% power to detect a hazard ratio of 0.49 in donor specific antibody (DSA)+ patients. Findings: From 11/9/13 to 27/10/16, 5519 were screened for eligibility and 2037 randomised (1028 to unblinded care and 1009 to double blinded care). We identified 198 with DSA and 818 with non-DSA. Development of DSA, but not non-DSA was predictive of graft failure. HRs for graft failure in unblinded DSA+ and non-DSA+ groups were 1.54 (95% CI: 0.72 to 3.30) and 0.97 (0.54-1.74) respectively, providing no evidence of an intervention effect. Non-inferiority for the overall unblinded versus blinded comparison was not demonstrated as the upper confidence limit of the HR for graft failure exceeded 1.4 (1.02, 95% CI: 0.72 to 1.44). The only secondary endpoint reduced in the unblinded arm was biopsy-proven rejection. Interpretation: Intervention to improve adherence and optimize immunosuppression does not delay failure of renal transplants after development of DSA. Whilst DSA predicts increased risk of allograft failure, novel interventions are needed before screening can be used to direct therapy. Funding: The National Institute for Health Research Efficacy and Mechanism Evaluation programme grant (ref 11/100/34).

Patients' Experience of Medication Brand Changes during Hormone Therapy for Breast Cancer-An Interpretative Phenomenological Analysis.

Medication adherence to hormone therapy (HT) in breast cancer survivors is often suboptimal and is affected by a range of factors. Patients are usually prescribed different generic formulations of HT drugs and their impact on side effects and on adherence and persistence is poorly understood. This study aimed to explore women's lived experience of HT medication brand changes (generic substitution) and its impact on side effects, quality of life and medication-taking behaviors, as well as on adherence and persistence. Nine female breast cancer survivors who had previous experience of HT medication brand changes participated in the study. Individual, online, semi-structured interviews were conducted and analyzed using interpretative phenomenological analysis. The findings identified three superordinate themes and nine subordinate themes that influenced the lived experience of medication brand changes for these patients: (i) experiencing brand changes, (ii) responsiveness of health care providers and (iii) future expectations. Women reported negative physical and emotional experiences of brand changes, which is often compounded by healthcare professionals' lack of information and reassurances, disbelief in the worsening of side effects and inconsistent advice regarding generics. These have implications for women's self-efficacy for medication-taking behaviors, ability to manage side effects and HT adherence and persistence.

Qualitative Analysis of Interviews and Focus Groups Exploring Factors Contributing to Adherence to GnRH Agonists in Men with Prostate Cancer.

OBJECTIVES: Side effects from the prolonged use of gonadotropin-releasing hormone (GnRH) agonists may lead to nonadherence to the treatment in men with advanced prostate cancer (PCa). We investigated the reasons contributing to nonadherence to GnRH agonists through interviews with men with PCa and focus groups with their health care professionals. DATA SOURCES: The three stages of the study were validation of themes, interviews with men on GnRH agonists, and focus groups with oncology specialists and clinical nurse specialists. An experienced oncologist validated factors contributing to nonadherence identified from the literature. A total of 10 men with PCa were recruited from a large teaching hospital and were interviewed on a one-to-one basis using a topic guide. In stage three, two separate focus groups were held with oncology specialists and clinical nurse specialists treating men with PCa. The interviews and focus groups were audio recorded and transcribed verbatim. Initial codes identified from stage three were grouped into themes and thematically analyzed. CONCLUSION: Themes identified from the interviews and focus groups influencing adherence to treatment were side effects of treatment, patient belief system, benefits outweigh harm, quality of life over quantity of life, social support, and patient-clinician relationship. Although side effects such as hot flushes and loss of libido were sometimes overwhelming for many, these men felt that treatment benefits outweighed harm. IMPLICATIONS FOR NURSING PRACTICE: Reasons leading to nonadherence can be multifactorial and unique to each patient. Employing different strategies by health care professionals may lead to the eventual acceptance of treatment, while also acknowledging their reasons for nonadherence.

Extending Adjuvant Endocrine Therapy for 10 Years: A Mixed-Methods Analysis of Women's Decision Making in an Online Breast Cancer Forum.

An additional 5 years of treatment with adjuvant hormonal therapy, to complete 10 years of medication, is recommended to reduce the risk of breast cancer recurrence. Yet professionals and patients should balance this benefit against side effects and toxicities. Little is known about women's decision making regarding persistence with extended endocrine therapy. In this study, we collected data from a UK online breast cancer forum to analyse patterns of persistence and its associated factors. A mixed-methods exploratory sequential design was used, with a qualitative analysis of text (n = 61 individuals) informing the development of a quantitative instrument to statistically analyse the prevalence of the findings (n = 130). Our findings identified three different groups of women who had to make decisions regarding persistence with treatment: those about to complete 5 years of therapy, those who decided to extend treatment, and those who were initially prescribed 10 years. Factors affecting persistence were, lack of self-efficacy in managing side effects, lack of reassurance about individual risk of recurrence, and impact on quality of life. Interventions such as training of healthcare professionals including risk communication, medication reviews by clinical pharmacists, and re-planning of services in follow-up care, should better support women's needs in extended hormonal therapy.

Serine 396 of PDK1 is required for maximal PKB activation.

Protein kinase B (PKB; also known as Akt) is important for mediating survival and proliferation signals. Following activation, PKB shuttles to various compartments of the cell, including the nucleus, where it phosphorylates an array of targets. PKB is phosphorylated at T308 by its activator PDK1. PDK1 is normally excluded from the nucleus via a nuclear exclusion sequence (NES), and our previous work suggested that nuclear exclusion can be attenuated by IGF-1-induced phosphorylation of S396 proximal to the NES. No studies have been done to test the significance of S396 phosphorylation or the impact of nuclear accumulation of PDK1 on PKB activation. To address these questions, we created isogenic embryonic stem cell (ESC) lines expressing various alleles of PDK1 within a PDK1-/- background. Disruption of the NES domain of PDK1 correlated with elevated PKB phosphorylation at both T308 and S473. In contrast, mutation of S396 to alanine reduced PDK1 nuclear localization and reduced PKB phosphorylation and activation. The loss of phosphorylation of PKB by S396A mutation was rescued by forcing nuclear PDK1 or by conversion of S396 to an aspartic acid. The phosphorylation of the PKB substrate FOXO3alpha was reduced in S396A PDK1 ESC. Other known and suspected PKB substrates, including GSK3 and Raf1, were unaffected. This study therefore reveals that S396 plays a role in the activation of PKB leading to the regulated phosphorylation of some PKB substrates including FOXO3alpha.

Nonadherence to tamoxifen in breast cancer survivors: A 12 month longitudinal analysis.

OBJECTIVE: Previous research has shown that up to 50% of breast cancer survivors prescribed tamoxifen do not take it as recommended, which is associated with increased risk of recurrence and mortality. Little research has attempted to identify modifiable psychosocial factors associated with tamoxifen nonadherence. This study aimed to examine how tamoxifen adherence rates change over a year and to identify modifiable predictors of nonadherence. METHOD: Three hundred and forty-five breast cancer survivors who were in their first year of tamoxifen prescription were sent questionnaires at 4 points over a 12-month period. Questionnaires assessed demographic and clinical factors, side effects, beliefs about the illness and medication, social support, distress and tamoxifen adherence. Adherence was assessed using the Medication Adherence Rating Scale. Latent Growth Modeling was used to identify predictors of tamoxifen nonadherence. RESULTS: Reported rates of nonadherence increased over time (37-48%). Several demographic, clinical, and psychosocial variables were associated with nonadherence. Women who were nonadherent were more likely to be from a minority ethnic group, to have more negative medication beliefs and to have lower confidence in their ability to take tamoxifen. CONCLUSIONS: These demographic and clinical variables can be used to identify women at higher risk of nonadherence. The modifiable psychosocial variables can be used as the basis for psychological interventions to improve adherence in this population. Interventions should focus on both intentional and unintentional nonadherence. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Factors related to the experience of menopausal symptoms in women prescribed tamoxifen.

INTRODUCTION: Menopausal symptoms are frequent and severe in breast cancer survivors taking tamoxifen; however, treatment options are limited for these patients as hormonal replacement therapy is contraindicated. This study aimed to explore the experience and attribution of menopausal symptoms and identify factors related to the experience of menopausal symptoms in women taking tamoxifen. METHODS: Women who had been prescribed tamoxifen for a diagnosis of primary breast cancer were recruited from oncology clinics across England and from online advertisements. Seven hundred and forty women completed questionnaires assessing illness perceptions, social support, mood and symptom duration/severity. RESULTS: Eighty-four percent of women had experienced hot flushes and 80% experienced night sweats; of these, 60% experienced severe symptoms. Symptoms persisted throughout 5 years of treatment and were mainly attributed to tamoxifen. Logistic regressions showed that depressive symptoms, previous chemotherapy and being employed were associated with increased odds of hot flush or night sweat prevalence. Symptom severity was associated with depression, being employed and attributing symptoms to tamoxifen. DISCUSSION: These findings have clinical implications in terms of targeting women who are more at risk and offering non-hormonal treatment options, such as cognitive behavioural therapy, to help women to develop self-management strategies for coping with menopausal symptoms.