Shaping research for people living with co-existing mental and physical health conditions: A research priority setting initiative from the United Kingdom.

INTRODUCTION: Those with severe and enduring mental ill health are at greater risk of long-term physical health conditions and have a reduced life expectancy as a result. Multiple factors compound this health inequality, and the need for setting research priorities in this area is highlighted with physical and mental healthcare services being separate, and limited multimorbidity research. METHODS: The aim of this exercise was to work in partnership with healthcare professionals and carers, family, friends and individuals with lived experience of both mental and physical health conditions, to set research priorities to help people with mental health conditions to look after their physical health. The exercise was guided by the James Lind Alliance approach. For this, a steering group was set up, two surveys were completed and a final priority workshop was conducted. RESULTS: This priority setting exercise guided by people's needs and lived experience has produced a set of well-defined research topics. Initially, 555 research questions were suggested in the first survey, which were refined to 54 questions for the second survey. A priority setting workshop was then conducted to get the final 10 priorities. CONCLUSIONS: Taking these topics forward to improve services and treatment for both mental and physical ill health may in turn improve physical health and lessen the reduced life expectancy of those living with mental ill health. PATIENT OR PUBLIC CONTRIBUTION: This work was completed in collaboration with people who have lived experience of mental ill health and physical health conditions, as well as carers, family and friends. Their contribution has been significant for this work from piloting surveys, amending language used and educating the researchers and contributing to this paper. The initial work was completed with a steering group and continued with surveys and workshops.

Comparison of Racial and Ethnic Mortality Disparities among Post-9/11 Veterans with and without Traumatic Brain Injury to the Total U.S. Adult Population.

INTRODUCTION: The extent of racial/ethnic disparities and whether they are attenuated in the Veteran population compared to the total US population is not well understood. We aimed to assess racial/ethnic mortality disparities from all-cause, cardiovascular (CVD) and cancer among post-9/11 military Veterans with and without exposure to TBI, compared to the total US population. METHODS: This cohort study included 2,502,101 US military Veterans (18,932,083 person-years) who served after 09/11/2001 with 3 or more years of care in the Military Health System (MHS); or had 3 or more years of care in the MHS and 2 or more years of care in the Veterans Health Administration. Mortality follow-up occurred from 01/01/2002 to 12/31/2020. Mortality rate ratios (MRR) from negative binomial regression models were reported for racial/ethnic groups compared to White non-Hispanic Veterans for all-cause, CVD and cancer mortality. Veteran MRR were compared to the total US population. RESULTS: Mortality rates for Black Non-Hispanic Veterans were higher for all-cause (MRR = 1.21;95%CI: 1.13-1.29; p < 0.001), CVD (MRR = 1.78;95%CI: 1.62-1.96; p < 0.001) and cancer (MRR = 1.17;95%CI: 1.10-1.25; p < 0.001) than in White Non-Hispanic Veterans. Among Veterans with TBI, only Black Non-Hispanics had higher mortality than White Non-Hispanics and only for CVD (MRR = 1.32;95%CI: 1.12-1.54; p < 0.001), while CVD mortality was higher among Veterans without TBI (MRR = 1.77;95%CI: 1.63-1.93;p < 0.001). MRR for Black Non-Hispanics in the total US population, were consistently higher than those in the Veteran population for all-cause (MRR = 1.52;95%CI: 1.46-1.58; p < 0.001), CVD (MRR = 2.03;95%CI: 1.95-2.13; p < 0.001) and cancer (MRR = 1.26;95%CI: 1.22-1.30; p < 0.001). CONCLUSION: This Veteran cohort experienced less racial/ethnic disparity in mortality than the total US population, especially among Veterans with TBI.

Patient Reported Sexual Adaptation Following Prostate Cancer Treatment: An Analysis of Related Variables and Sexual Outcomes Associated with Sexual Adaptation Styles.

Sexual concerns after prostate cancer (PCa) treatment are high. Flexible coping is a crucial element to maintaining sexual activity after PCa and improves adaptation outcomes. We aimed to identify potential sexual adaptation styles reported by men following PCa treatment, and to assess relationships among associated variables and outcomes. Individuals (n = 223) with PCa treatment history (e.g., radical prostatectomy [n = 165, 74.0%], external beam radiation [n = 83, 37.2%], hormone/androgen deprivation therapy [n = 83, 37.2%]), completed an online survey assessing sexual variables and processes of sexual adaptation. Using a combination of inductive and deductive coding, open-ended responses were thematically analyzed and grouped into sexual adaptation styles. Factors potentially associated with sexual adaptation styles (e.g., age, perceived partner involvement, co-morbidities, relationship duration, time since PCa treatment, desire for physical affection, depression, relationship adjustment) were tested using multinomial logistic regression. Outcomes of sexual well-being (sexual distress, sexual bother, sexual satisfaction) and relationship adjustment were compared against each sexual adaptation style using a multivariate analysis of variance. Sexual activity status and satisfaction with the adaptation process was assessed across the sexual adaptation styles using a chi-square analysis and post-hoc tests. Two distinct categories were identified: those who had Adapted (n = 185) and those who had Not Adapted (n = 38). Four sexual adaptation styles emerged in the adapted category: Relationship Renegotiation (n = 53) and Sexual Renegotiation (n = 47), which were couples-focused styles, and Acceptance/Resignation (n = 34) and Masturbation/Erection (n = 48), which were individual-focused styles. Participants who could not be categorized as one style, but rather met several, were identified as Mixed (n = 3). Higher rates of depression, lower relationship adjustment, lack of sexual activity, and greater dissatisfaction with the adaptation process were observed for Not Adapted participants. Participants engaged in any type of adaptation style fared better than those who had Not Adapted. Couples-focused styles tended to emphasize renegotiation, including a changed perspective on the expression of the relationship. Perceived direct engagement of the partner facilitated adaptation and emphasized engagement with flexible coping, either through redefining priorities or ways of being sexual. Individual-focused styles emphasized pre-cancer erectile function, and either aimed to return to capacity for penetrative sexual activity or accepted its inaccessibility and largely an abandonment of partnered sexual activity.

What is the association of polypharmacy with frailty in heart failure? A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to explore the differences in the number of prescribed medications and polypharmacy risk between patients with heart failure (HF) and frailty vs. those with HF but without frailty. Eligible studies included observational or experimental studies in patients aged ≥50 years. Thirteen studies met the criteria and were included in the final analysis. Patients with frailty and HF exhibited a higher risk of polypharmacy (OR: 1.87, 95% CI 1.72 - 2.04, I2 = 0%, P < 0.01) compared to those without frailty. Results remained significant after adjusting for comorbidity status. Additionally, patients with frailty and HF were prescribed more medications compared to those without (k = 6; MD: 1.43, 95% CI 0.31 - 2.55, I2 = 94%, P = 0.01), with a high degree of heterogeneity. However, results were non-significant after adjustment for comorbidity status. Patients with HF and frailty have a higher need of polypharmacy compared to those without frailty, which may increase the risk of potentially inappropriate medications (PIM). Investigating the real-world prevalence of PIM may support clinicians in their routine assessment as part of a comprehensive management strategy in patients with HF and frailty.

Addressing the gaps in evaluation of new drugs for older adults: Strategies from the International Union of Basic and Clinical Pharmacology (IUPHAR) Geriatric Committee.

The International Union of Basic and Clinical Pharmacology (IUPHAR) Geriatric Committee aims to improve the use of drugs in older adults and develop new therapeutic approaches for the syndromes and diseases of old age through advocacy, education, and research. In the present paper, we propose strategies relevant to drug development and evaluation, spanning preclinical and the full range of clinical studies. Drugs for older adults need to consider not only age, but also other characteristics common in geriatric patients, such as multimorbidity, polypharmacy, falls, cognitive impairment, and frailty. The IUPHAR Geriatric Committee's position statement on 'Measurement of Frailty in Drug Development and Evaluation' is included, highlighting 12 key principles that cover the spectrum of translational research. We propose that where older adults are likely to be major users of a drug, that frailty is measured at baseline and as an outcome. Preclinical models that replicate the age, frailty, duration of exposure, comorbidities, and co-medications of the proposed patients may improve translation. We highlight the potential application of recent technologies, such as physiologically based pharmacokinetic-pharmacodynamic modeling informed by frailty biology, and Artificial Intelligence, to inform personalized medicine for older patients. Considerations for the rapidly aging populations in low- and middle-income countries related to health-care and clinical trials are outlined. Involving older adults, their caregivers and health-care providers in all phases of research should improve drug development, evaluation, and outcomes for older adults internationally.

A randomized comparison of online mindfulness-based group sex therapy vs supportive group sex education to address sexual dysfunction in breast cancer survivors.

BACKGROUND: Sexual difficulties and vaginal pain are common following treatment for breast cancer. AIM: The goal of this study was to evaluate an online mindfulness-based group sex therapy vs an online supportive sex education group therapy to address these sexual difficulties. METHODS: Breast cancer survivors (n = 118) were randomized to 1 of the 2 arms; 116 provided informed consent and completed the time 1 assessment. Treatment included 8 weekly 2-hour online group sessions. Those randomized to the mindfulness group completed daily mindfulness exercises, and those in the comparison arm read and completed exercises pertaining to sex education. OUTCOMES: Assessments were repeated at posttreatment and 6 months after the completion of the group. RESULTS: There was a main effect of treatment on primary endpoints of sexual desire, sexual distress, and vaginal pain, with all outcomes showing significant improvements, with no differential impact by treatment arm. Secondary endpoints of interoceptive awareness, mindfulness, and rumination about sex also significantly improved with both treatments, with no group-by-time interaction. CONCLUSION: Both mindfulness-based sex therapy and supportive sex education delivered in group format online are effective for improving many facets of sexual function, vaginal pain, rumination, mindfulness, and interoceptive awareness in breast cancer survivors. STRENGTHS AND LIMITATIONS: We used a randomized methodology. Future studies should seek to diversify participants. CLINICAL IMPLICATIONS: These findings highlight the need to offer similar treatments to more breast cancer survivors immediately after and in the years following cancer treatment as a means of improving survivorship quality of life.

The status of drug evaluation in older adults in the United Kingdom: Bridging the representation gap.

Older adults are persistently underrepresented in clinical drug trials worldwide, despite increasing multiple long-term conditions and significant prescribing in this demographic. We discuss systemic challenges such as the exclusion of people with comorbid conditions and the lack of assessment for comorbidities as modifiers of treatment effects and highlight the rising trend of polypharmacy, especially among the oldest age groups, which is linked to a significant percentage of unplanned hospitalizations and medication errors. The consequences of these trends prompted the United Kingdom National Overprescribing review, culminating in a set of recommendations for drug development tailored to older adults. Building on this, two critical reports released in April 2023 by the International Longevity Centre (ILC) and the Nuffield Council on Bioethics (NCOB) are discussed. These reports emphasize the importance of diversity and inclusion in clinical trials, advocating for ethical frameworks and methodologies that cater to the complex needs of older adults. The development of inclusive criteria, innovative statistical methodologies, and the integration of patient-reported outcomes are needed to address the persistent barriers to older adult participation in research, suggesting that pragmatic trials, exemplified by the UK's RECOVERY trial during the COVID-19 pandemic, could pave the way for more inclusive research practices.

Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars.

Importance: While brain cancer is rare, it has a very poor prognosis and few established risk factors. To date, epidemiologic work examining the potential association of traumatic brain injury (TBI) with the subsequent risk of brain cancer is conflicting. Further data may be useful. Objective: To examine whether a history of TBI exposure is associated with the subsequent development of brain cancer. Design, Setting, and Participants: A retrospective cohort study was conducted from October 1, 2004, to September 20, 2019, and data analysis was performed between January 1 and June 26, 2023. The median follow-up for the cohort was 7.2 (IQR, 4.1-10.1) years. Veterans Affairs (VA) and Department of Defense (DoD) administrative data on 1 919 740 veterans from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium were included. Exposure: The main exposure of interest was TBI severity (categorized as mild, moderate or severe [moderate/severe], and penetrating). Main Outcomes and Measures: The outcome of interest was the development of brain cancer based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes in either the DoD/VA medical records or from the National Death Index. Results: After 611 107 exclusions (predominately for no encounter during the study period), a cohort including 1 919 740 veterans was included, most of whom were male (80.25%) and non-Hispanic White (63.11%). Median age at index date was 31 (IQR, 25-42) years. The cohort included 449 880 individuals with TBI (mild, 385 848; moderate/severe, 46 859; and penetrating, 17 173). Brain cancer occurred in 318 individuals without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (≤0.06%). After adjustment, moderate/severe TBI (adjusted hazard ratio [AHR], 1.90; 95% CI, 1.16-3.12) and penetrating TBI (AHR, 3.33; 95% CI, 1.71-6.49), but not mild TBI (AHR, 1.14; 95% CI, 0.88-1.47), were associated with the subsequent development of brain cancer. Conclusions and Relevance: In this cohort study of veterans of the Iraq and Afghanistan wars, moderate/severe TBI and penetrating TBI, but not mild TBI, were associated with the subsequent development of brain cancer.

Understanding perceptions of the public and key stakeholders toward a localised cancer screening promotion campaign.

The aim of this study was to explore perceptions of members of the public and key stakeholders of a localised campaign to increase engagement with cervical cancer screening. Whilst numerous interventions have been trialled to increase engagement with cancer screening, the evidence for their effectiveness is somewhat mixed. In addition, few studies have explored the perceptions of members of the public targeted by such campaigns nor the perceptions of healthcare professionals who may be involved in delivering such campaigns in the United Kingdom. Members of the public who had potentially been exposed to the campaign in the North-East of England were approached to take part in individual interviews whilst stakeholders were invited to take part in a focus group. A total of 25 participants (13 members of the public, 12 stakeholders) took part. All interviews were audio recorded, transcribed verbatim and analysed using applied thematic analysis. Four themes were identified, two of which were cross-cutting (barriers to screening and factors promoting screening), with one theme identified as specific to the public interviews (knowledge of and attitudes toward awareness campaigns) and one theme specific to the focus group (keeping campaigns relevant. Awareness of the localised campaign was limited; however, when made aware, participants were mostly positive towards the approach, although mixed responses were noted in relation to financial incentives. Members of the public and stakeholders identified some common barriers to screening although differed in their perceptions of promotional factors. This study highlights the importance of multiple strategies to promote cervical screening as one size fits all approach may limit engagement.

A Proposal for the Comprehensive Care of Men on Androgen Deprivation Therapy: Recommendations From the Multidisciplinary Prostate Cancer 360 Working Group.

INTRODUCTION: To promote comprehensive care of patients throughout the androgen deprivation therapy (ADT) prescribing process, the Prostate Cancer 360 (PC360) Working Group developed monitoring and management recommendations intended to mitigate or prevent ADT-associated adverse events. METHODS: The PC360 Working Group included 14 interdisciplinary experts with a dedicated clinical interest in prostate cancer and ADT management. The working group defined challenges associated with ADT adverse event management and then collaboratively developed comprehensive care recommendations intended to be practical for ADT prescribers. RESULTS: The PC360 Working Group developed both overarching recommendations for ADT adverse event management and specific recommendations across 5 domains (cardiometabolic, bone, sexual, psychological, and lifestyle). The working group recommends an interdisciplinary, team-based approach wherein the ADT prescriber retains an oversight role for ADT management while empowering patients and their primary and specialty care providers to manage risk factors. The PC360 recommendations also emphasize the importance of proactive patient education that involves partners or other support providers. Recommended monitoring and assessment tools, risk factor management, and patient counseling points are also included for the 5 identified domains, with an emphasis on lifestyle and behavioral interventions that can improve quality of life and reduce the risk for ADT-associated complications. CONCLUSIONS: Comprehensive care of patients receiving ADT requires early and ongoing coordinated management of a variety of health domains, including cardiometabolic, bone, sexual, psychological health. Patient education and primary care provider involvement should begin prior to ADT initiation and continue throughout treatment to improve patient and partner quality of life.

Placental BCRP transporter reduces cadmium accumulation and toxicity in immortalized human trophoblasts.

Cadmium (Cd) is a ubiquitous environmental metal detectable in most pregnant women. Animal and human studies demonstrate that in utero exposure to Cd reduces birth weight and impairs perinatal growth due to placental toxicity. BCRP is a prominent transporter that can efflux xenobiotics from the placenta. This study sought to investigate Cd transport and toxicity in cultured human BeWo trophoblasts with reduced expression and function of the placental barrier transporter BCRP. Knockdown (KD) of BCRP protein expression and function in BeWo trophoblasts increased the intracellular accumulation of Cd by 100% following treatment with 1 µM CdCl2. No change in the expression of Cd uptake transporters was observed between control and BCRP-KD cells. Reduced BCRP expression impaired viability of BeWo cells exposed to CdCl2 for 48 hr (BCRP-KD IC50: 11 µM, control cells IC50: 18 µM). Moreover, BCRP-KD cells were more sensitive to CdCl2-induced cytotoxicity compared to control BeWo cells. CdCl2 treatment strongly induced the expression of the metal-binding protein metallothionein (MT) in both control and BCRP-KD cells, with significantly greater MT upregulation in Cd-treated BCRP-KD cells. These data suggest that the BCRP transporter reduces Cd accumulation in syncytiotrophoblasts, which may be one mechanism to reduce subsequent toxicity to the placenta and developing fetus.

Sexual satisfaction in prostate cancer: a multi-group comparison study of treated patients, patients under active surveillance, patients with negative biopsy, and controls.

PURPOSE: Erectile function changes after prostate cancer (PCa) treatment are well documented, but less understood is the relative impact of prostate biopsy and active surveillance on sexual well-being. It is unknown whether potential negative impacts are exclusive to patients who have been treated for PCa, or whether the diagnosis itself or the experience of biopsy may also impact sexual well-being. Sexual satisfaction is an important yet understudied indicator of sexual well-being in this population. This study examines sexual satisfaction and its predictors across several comparison groups to explore relative impact. METHODS: At baseline and 12 months, questionnaire data was collected in four samples: (1) following PCa treatment, (2) active surveillance, (3) negative prostate biopsy result, and (4) controls receiving no biopsy or treatment. Predictors assessed included group, erectile function, communication style, and partner involvement. RESULTS: Sexual satisfaction declined in the active treatment group, no changes were observed in active surveillance or non-PCa control, and improvements were observed in the biopsy group. Predictors of sexual satisfaction over and above erectile function included restrictive communication (i.e. protective buffering) and perceived partner involvement. For higher levels of erectile function, a higher perceived degree of partner involvement was protective of sexual satisfaction. CONCLUSION: Sexual satisfaction is an important indicator of sexual well-being and is negatively impacted following PCa treatment, but not active surveillance or prostate biopsy. IMPLICATIONS FOR CANCER SURVIVORS: Communication and partner involvement are potentially modifiable factors to be considered for intervention and may promote sexual satisfaction following PCa treatment. Patients experiencing negative biopsy, who note lower sexual satisfaction may experience improved satisfaction with time, and those under active surveillance who worry about sexual satisfaction may find reassurance from these results.

Increasing trend in hospitalisation due to adverse drug reactions: can we stem the tide?

Living with multiple long-term health conditions (multimorbidity) is increasingly common in older age. The more long-term conditions that an individual has, the more medicines they are likely to take. Hospitalisation as a consequence of medication-related harm is increasing and a concerted effort is needed to reduce the burden of harm caused by medication. However, making decisions about the balance between benefit and harm for an older person with multimorbidity and polypharmacy is very complex. There are various clinical tools that can help to identify patients at higher risk of harm and numerous strategies, including medicines optimisation reviews that incorporate personalised health information, to try to reduce risk. Further education and training of the healthcare professionals is needed to equip the multidisciplinary workforce with the skills and knowledge to address these challenges. This article discusses some of the changes that can be implemented now and highlights areas that will require more research before they can be introduced, in order to help patients to get the best out of their medicines.

Combinations of medicines in patients with polypharmacy aged 65-100 in primary care: Large variability in risks of adverse drug related and emergency hospital admissions.

BACKGROUND: Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes. METHODS: We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions. RESULTS: In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities. CONCLUSIONS: Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.

Implementation of individually tailored treatment plans in a group-based intervention for women with mixed vulvo-vaginal and sexual health concerns following cancer treatment: A feasibility study.

PURPOSE: This study evaluated a professionally-led, group-based vulvo-vaginal and sexual health (VSH) workshop for women diagnosed with cancer. The study goals were to: (1) implement and assess a novel group intervention for diverse VSH concerns; (2) explore post-workshop changes in symptom bother, motivation to use VSH treatments, and frequency of VSH treatment use; (3) examine post-workshop changes in sexual well-being. METHODS: A group-based educational workshop to address a variety of VSH concerns was developed and implemented. During the workshop, participants created an individualized treatment plan by selecting from various VSH treatment options presented. Treatment plan follow-ups were administered online at one-, two-, and three-months post-workshop. At baseline and three-month follow-up, participants completed online questionnaires to assess self-reported vulvo-vaginal symptoms, sexual function, sexual distress, and use of VSH strategies. RESULTS: 195 participants (age 20-81) attended workshops over a 2.5-year period. Individualized treatment plans were effectively completed by most participants (92%). Preliminary results show decreases in bother severity associated with VSH concerns post-workshop, stabilizing after 2 months. At three-month follow-up, participants reported increased use of VSH treatment strategies. Sexual satisfaction, sexual distress, and emotional impact of vulvovaginal symptoms also improved. CONCLUSIONS: Workshop attendance was associated with increased uptake of VSH treatment strategies and improvements in several parameters of sexual well-being. Findings indicate that individualized treatment plans can be implemented effectively in a group setting and that a one-time, group-based educational workshop can meaningfully impact VSH-related behavior change, reduce vulvo-vaginal symptom bother and promote sexual well-being in patients with diverse VSH concerns.

Health-risk behaviours among people with severe mental ill health: understanding modifiable risk in the Closing the Gap Health Study.

BACKGROUND: People with severe mental ill health (SMI) experience some of the largest health inequalities of any sector within society. For these inequalities to be reduced, an understanding of the behavioural determinants of health in this population is needed. AIMS: Utilising data from the Closing the Gap Health Study, we aimed to assess the extent to which people with SMI report health-risk factors and behaviours, their interest in modifying them, and the factors associated with being motivated to modify these behaviours. METHOD: Adult (≥18 years old) participants were recruited via primary and secondary care in the English National Health Service. To be eligible, participants needed to have a documented diagnosis of schizophrenia, psychotic disorders or bipolar disorder. Data were collected by survey on demographics, general physical health, diet, physical activity, alcohol, smoking and body mass index. RESULTS: Between April 2016 and March 2020, n = 9914 participants were recruited. Among people with SMI, high rates of obesity (37.5%), infrequent physical activity (62.0%), not meeting current guidelines (≥5) for the consumption of fruit and vegetables (85.0%) and smoking (42.2%) were observed. However, most participants were motivated to reduce health-risk behaviours. Perceiving the importance of health-promoting behaviours, being of poorer general health and being female were significantly associated with being motivated to modify health-risk behaviours. CONCLUSIONS: Despite experiencing poor physical and mental health outcomes compared with the general population, and contrary to popular misconceptions, people with SMI perceive health as important and are motivated to make behavioural changes to improve health.

Feasibility and Acceptability of a Group-Based Mindfulness Intervention for Sexual Interest/Arousal Disorder Following Breast Cancer Treatment.

This study aimed to assess feasibility and preliminary efficacy of an 8-week Mindfulness-Based Cognitive Therapy (MBCT) group program to treat Sexual Interest/Arousal Disorder (SIAD) in women following breast cancer (BrCa) treatment. Thirty women participated, of whom 67% (n = 20) attended at least 6 of 8 group sessions. Feedback indicated the program was relevant and valuable; minor modifications were suggested to further address survivorship concerns. Results of pre-post questionnaires demonstrated significant improvements in sexual distress and sexual interest/desire, with large effect sizes. Results support the feasibility and preliminary efficacy of an 8-week MBCT program among women following breast cancer treatment.

Sidestream Smoke Extracts from Harm-Reduction and Conventional Camel Cigarettes Inhibit Osteogenic Differentiation via Oxidative Stress and Differential Activation of intrinsic Apoptotic Pathways.

Epidemiological studies suggest cigarette smoking as a probable environmental factor for a variety of congenital anomalies, including low bone mass, increased fracture risk and poor skeletal health. Human and animal in vitro models have confirmed hypomineralization of differentiating cell lines with sidestream smoke being more harmful to developing cells than mainstream smoke. Furthermore, first reports are emerging to suggest a differential impact of conventional versus harm-reduction tobacco products on bone tissue as it develops in the embryo or in vitro. To gather first insight into the molecular mechanism of such differences, we assessed the effect of sidestream smoke solutions from Camel (conventional) and Camel Blue (harm-reduction) cigarettes using a human embryonic stem cell osteogenic differentiation model. Sidestream smoke from the conventional Camel cigarettes concentration-dependently inhibited in vitro calcification triggered by high levels of mitochondrially generated oxidative stress, loss of mitochondrial membrane potential, and reduced ATP production. Camel sidestream smoke also induced DNA damage and caspase 9-dependent apoptosis. Camel Blue-exposed cells, in contrast, invoked only intermediate levels of reactive oxygen species insufficient to activate caspase 3/7. Despite the absence of apoptotic gene activation, damage to the mitochondrial phenotype was still noted concomitant with activation of an anti-inflammatory gene signature and inhibited mineralization. Collectively, the presented findings in differentiating pluripotent stem cells imply that embryos may exhibit low bone mineral density if exposed to environmental smoke during development.

The DynAIRx Project Protocol: Artificial Intelligence for dynamic prescribing optimisation and care integration in multimorbidity.

Background: Structured Medication Reviews (SMRs) are intended to help deliver the NHS Long Term Plan for medicines optimisation in people living with multiple long-term conditions and polypharmacy. It is challenging to gather the information needed for these reviews due to poor integration of health records across providers and there is little guidance on how to identify those patients most urgently requiring review. Objective: To extract information from scattered clinical records on how health and medications change over time, apply interpretable artificial intelligence (AI) approaches to predict risks of poor outcomes and overlay this information on care records to inform SMRs. We will pilot this approach in primary care prescribing audit and feedback systems, and co-design future medicines optimisation decision support systems. Design: DynAIRx will target potentially problematic polypharmacy in three key multimorbidity groups, namely, people with (a) mental and physical health problems, (b) four or more long-term conditions taking ten or more drugs and (c) older age and frailty. Structured clinical data will be drawn from integrated care records (general practice, hospital, and social care) covering an ∼11m population supplemented with Natural Language Processing (NLP) of unstructured clinical text. AI systems will be trained to identify patterns of conditions, medications, tests, and clinical contacts preceding adverse events in order to identify individuals who might benefit most from an SMR. Discussion: By implementing and evaluating an AI-augmented visualisation of care records in an existing prescribing audit and feedback system we will create a learning system for medicines optimisation, co-designed throughout with end-users and patients.