Chorus wave power at the strong diffusion limit overcomes electron losses due to strong diffusion.

Earth's radiation belts consist of high-energy charged particles trapped by Earth's magnetic field. Strong pitch angle diffusion of electrons caused by wave-particle interaction in Earth's radiation belts has primarily been considered as a loss process, as trapped electrons are rapidly diffused into the loss cone and lost to the atmosphere. However, the wave power necessary to produce strong diffusion should also produce rapid energy diffusion, and has not been considered in this context. Here we provide evidence of strong diffusion using satellite data. We use two-dimensional Fokker-Planck simulations of electron diffusion in pitch angle and energy to show that scaling up chorus wave power to the strong diffusion limit produces rapid acceleration of electrons, sufficient to outweigh the losses due to strong diffusion. The rate of losses saturates at the strong diffusion limit, whilst the rate of acceleration does not. This leads to the surprising result of an increase, not a decrease in the trapped electron population during strong diffusion due to chorus waves as expected when treating strong diffusion as a loss process. Our results suggest there is a tipping point in chorus wave power between net loss and net acceleration that global radiation belt models need to capture to better forecast hazardous radiation levels that damage satellites.

Prediction of obstructive sleep apnoea in children and adolescents with Down syndrome.

BACKGROUND: Obstructive sleep apnoea (OSA) is common in children and adolescents with Down syndrome (DS). Clinical guidelines recommend that all children with DS have polysomnography (PSG) for assessment of OSA by the age of 4 years, but access is limited and testing may be burdensome for children and families. METHODS: The purpose of this prospective cross-sectional cohort study was to identify a model to predict OSA in this group that could be tested in an external population to triage children and adolescents with DS for PSG. These models were based on a comprehensive set of potential predictive demographic, anthropometric, quality of life and sleep-related variables. RESULTS: The results of this study show the predictive power of a model based on the sleep disordered breathing subscale of the Pediatric Sleep Survey Instrument and sleep fragmentation quantified using actigraphy in determining moderate-severe OSA in children and adolescents with DS. This model exhibits high sensitivity (82%), specificity (80%), positive predictive value (75%) and negative predictive value (86%). CONCLUSIONS: We demonstrate the utility of a tool containing the sleep disordered breathing subscale of the Pediatric Sleep Survey Instrument and sleep fragmentation quantified using actigraphy in identifying children and adolescents with DS who have moderate/severe OSA.

Acceleration of Electrons by Whistler-Mode Hiss Waves at Saturn.

Plasmaspheric hiss waves at the Earth are well known for causing losses of electrons from the radiation belts through wave particle interactions. At Saturn, however, we show that the different plasma density environment leads to acceleration of the electrons rather than loss. The ratio of plasma frequency to electron gyrofrequency frequently falls below one creating conditions for hiss to accelerate electrons. The location of hiss at high latitudes (>25°) coincides very well with this region of very low density. The interaction between electrons and hiss only occurs at these higher latitudes, therefore the acceleration is limited to mid to low pitch angles leading to butterfly pitch angle distributions. The hiss is typically an order of magnitude stronger than chorus at Saturn and the resulting acceleration is rapid, approaching steady state in one day at 0.4 MeV at L = 7 and the effect is stronger with increasing L-shell.

Supporting patients to get the best from their osteoporosis treatment: a rapid realist review of what works, for whom, and in what circumstance.

Systematic reviews that examine effectiveness of interventions to improve medicines optimisation do not explain how or why they work. This realist review identified that interventions which effectively optimise medicines use in osteoporosis include opportunities to address patients' perceptions of illness and treatment and/or support primary care clinician decision making. INTRODUCTION: In people with osteoporosis, adherence to medicines is poorer than other diseases and patients report follow-up is lacking, and multiple unmet information needs. We conducted a rapid realist review to understand what contextual conditions and mechanisms enable interventions to support osteoporosis medication optimisation. METHODS: A primary search identified observational or interventional studies which aimed to improve medicines adherence or optimisation; a supplementary second search identified research of any design to gain additional insights on emerging findings. Extracted data was interrogated for patterns of context-mechanism-outcome configurations, further discussed in team meetings, informed by background literature and the Practicalities and Perception Approach as an underpinning conceptual framework. RESULTS: We identified 5 contextual timepoints for the person with osteoporosis (identifying a problem; starting medicine; continuing medicine) and the practitioner and healthcare system (making a diagnosis and giving a treatment recommendation; reviewing medicine). Interventions which support patient-informed decision making appear to influence long-term commitment to treatment. Supporting patients' practical ability to adhere (e.g. by lowering treatment burden and issuing reminders) only appears to be helpful, when combined with other approaches to address patient beliefs and concerns. However, few studies explicitly addressed patients' perceptions of illness and treatment. Supporting primary care clinician decision making and integration of primary and secondary care services also appears to be important, in improving rates of treatment initiation and adherence. CONCLUSIONS: We identified a need for further research to identify a sustainable, integrated, patient-centred, and cost- and clinically effective model of long-term care for people with osteoporosis.

Determinants of non-adherence to anti-TB treatment in high income, low TB incidence settings: a scoping review.

BACKGROUND: Improving adherence to anti-TB treatment is a public health priority in high-income, low incidence (HILI) regions. We conducted a scoping review to identify reported determinants of non-adherence in HILI settings.METHODS: Key terms related to TB, treatment and adherence were used to search MEDLINE, EMBASE, Web of Science, PsycINFO and CINAHL in June 2019. Quantitative studies examining determinants (demographic, clinical, health systems or psychosocial) of non-adherence to anti-TB treatment in HILI settings were included.RESULTS: From 10,801 results, we identified 24 relevant studies from 10 countries. Definitions and methods of assessing adherence were highly variable, as were documented levels of non-adherence (0.9-89%). Demographic factors were assessed in all studies and clinical factors were frequently assessed (23/24). Determinants commonly associated with non-adherence were homelessness, incarceration, and alcohol or drug misuse. Health system (8/24) and psychosocial factors (6/24) were less commonly evaluated.CONCLUSION: Our review identified some key factors associated with non-adherence to anti-TB treatment in HILI settings. Modifiable determinants such as psychosocial factors are under-evidenced and should be further explored, as these may be better targeted by adherence support. There is an urgent need to standardise definitions and measurement of adherence to more accurately identify the strongest determinants.

Effects and moderators of coping skills training on symptoms of depression and anxiety in patients with cancer: Aggregate data and individual patient data meta-analyses.

PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects. METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs. RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (ß = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (ß = -0.16,95%CI = -0.25;-0.07) and anxiety (ß = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05). CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.

Quantum Rotation Sensing with Dual Sagnac Interferometers in an Atom-Optical Waveguide.

We describe a Sagnac interferometer suitable for rotation sensing, implemented using an atomic Bose-Einstein condensate confined in a harmonic magnetic trap. The atom wave packets are split and recombined by standing-wave Bragg lasers, and the trapping potential steers the packets along circular trajectories with a radius of 0.2 mm. Two conjugate interferometers are implemented simultaneously to provide common-mode rejection of noise and to isolate the rotation signal. With interference visibilities of about 50%, we achieve a rotation sensitivity comparable to Earth's rate in about 10 min of operation. Gyroscope operation was demonstrated by rotating the optical table on which the experiment was performed.

Rapid Electron Acceleration in Low-Density Regions of Saturn's Radiation Belt by Whistler Mode Chorus Waves.

Electron acceleration at Saturn due to whistler mode chorus waves has previously been assumed to be ineffective; new data closer to the planet show it can be very rapid (factor of 104 flux increase at 1 MeV in 10 days compared to factor of 2). A full survey of chorus waves at Saturn is combined with an improved plasma density model to show that where the plasma frequency falls below the gyrofrequency additional strong resonances are observed favoring electron acceleration. This results in strong chorus acceleration between approximately 2.5 R S and 5.5 R S outside which adiabatic transport may dominate. Strong pitch angle dependence results in butterfly pitch angle distributions that flatten over a few days at 100s keV, tens of days at MeV energies which may explain observations of butterfly distributions of MeV electrons near L=3. Including cross terms in the simulations increases the tendency toward butterfly distributions.

Protocol of a two arm randomised, multi-centre, 12-month controlled trial: evaluating the impact of a Cognitive Behavioural Therapy (CBT)-based intervention Supporting UPtake and Adherence to antiretrovirals (SUPA) in adults with HIV.

BACKGROUND: Delay to start antiretroviral therapy (ART) and nonadherence compromise the health and wellbeing of people living with HIV (PLWH), raise the cost of care and increase risk of transmission to sexual partners. To date, interventions to improve adherence to ART have had limited success, perhaps because they have failed to systematically elicit and address both perceptual and practical barriers to adherence. The primary aim of this study is to determine the efficacy of the Supporting UPtake and Adherence (SUPA) intervention. METHODS: This study comprises 2 phases. Phase 1 is an observational cohort study, in which PLWH who are ART naïve and recommended to take ART by their clinician complete a questionnaire assessing their beliefs about ART over 12 months. Phase 2 is a randomised controlled trial (RCT) nested within the observational cohort study to investigate the effectiveness of the SUPA intervention on adherence to ART. PLWH at risk of nonadherence (based on their beliefs about ART) will be recruited and randomised 1:1 to the intervention (SUPA intervention + usual care) and control (usual care) arms. The SUPA intervention involves 4 tailored treatment support sessions delivered by a Research Nurse utilising a collaborative Cognitive Behavioural Therapy (CBT) and Motivational Interviewing (MI) approach. Sessions are tailored to individual needs and preferences based on the individual patient's perceptions and practical barriers to ART. An animation series and intervention manual have been developed to communicate a rationale for the personal necessity for ART and illustrate concerns and potential solutions. The primary outcome is adherence to ART measured using Medication Event Monitoring System (MEMS). Three hundred seventy-two patients will be sufficient to detect a 15% difference in adherence with 80% power and an alpha of 0.05. Costs will be compared between intervention and control groups. Costs will be combined with the primary outcome in cost-effectiveness analyses. Quality adjusted life-years (QALYs) will also be estimated over the follow-up period and used in the analyses. DISCUSSION: The findings will enable patients, healthcare providers and policy makers to make informed decisions about the value of the SUPA intervention. TRIAL REGISTRATION: The trial was retrospectively registered 21/02/2014, ISRCTN35514212 .

Exploring organizational support for the provision of structured self-management education for people with Type 2 diabetes: findings from a qualitative study.

AIM: To explore the organizational context in which Type 2 diabetes structured group education is provided. METHODS: Four Clinical Commissioning Groups in England providing Type 2 diabetes structured self-management education participated in a qualitative study exploring the context for provision of that education. Using UK National Diabetes Audit returns, two Clinical Commissioning Groups were selected that had non-attendance rates of ≤25%, and two that had non-attendance rates of ≥50%. Between May 2016 and August 2017, 20 interviews were conducted with Clinical Commissioning Group staff including: commissioners, healthcare professionals, managers, general practitioners and diabetes educators. Data gathering was prolonged as it proved challenging to engage with healthcare staff as a result of frequent local restructuring and service disruption. RESULTS: Local audits revealed discrepancies in basic data such as referral and attendance numbers compared with national audit data. There was a commonality in the themes identified from interviews: diabetes education was rarely embedded in service structure; where education uptake was poor, a lack of central support to delivery teams was noticeable; and where education uptake was positive, delivery teams were actively engaged, sometimes relying on enthusiastic individuals. Both situations put the local sustainability of diabetes education at risk. CONCLUSIONS: There appears to be a link between attendance rates and organizational issues, therefore, when considering how to increase attendance rates, the state of the diabetes education infrastructure should be reviewed. Good uptake of diabetes education can be too reliant on the enthusiastic commitment of small teams or individuals delivering the education.

Formation of electron radiation belts at Saturn by Z-mode wave acceleration.

At Saturn electrons are trapped in the planet's magnetic field and accelerated to relativistic energies to form the radiation belts, but how this dramatic increase in electron energy occurs is still unknown. Until now the mechanism of radial diffusion has been assumed but we show here that in-situ acceleration through wave particle interactions, which initial studies dismissed as ineffectual at Saturn, is in fact a vital part of the energetic particle dynamics there. We present evidence from numerical simulations based on Cassini spacecraft data that a particular plasma wave, known as Z-mode, accelerates electrons to MeV energies inside 4 RS (1 RS = 60,330 km) through a Doppler shifted cyclotron resonant interaction. Our results show that the Z-mode waves observed are not oblique as previously assumed and are much better accelerators than O-mode waves, resulting in an electron energy spectrum that closely approaches observed values without any transport effects included.

Strong whistler mode waves observed in the vicinity of Jupiter's moons.

Understanding of wave environments is critical for the understanding of how particles are accelerated and lost in space. This study shows that in the vicinity of Europa and Ganymede, that respectively have induced and internal magnetic fields, chorus wave power is significantly increased. The observed enhancements are persistent and exceed median values of wave activity by up to 6 orders of magnitude for Ganymede. Produced waves may have a pronounced effect on the acceleration and loss of particles in the Jovian magnetosphere and other astrophysical objects. The generated waves are capable of significantly modifying the energetic particle environment, accelerating particles to very high energies, or producing depletions in phase space density. Observations of Jupiter's magnetosphere provide a unique opportunity to observe how objects with an internal magnetic field can interact with particles trapped in magnetic fields of larger scale objects.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

A cylindrically symmetric magnetic trap for compact Bose-Einstein condensate atom interferometer gyroscopes.

We present a variant of the time-orbiting potential trap suitable for Bose-Einstein condensate atom interferometers, which provides weak, cylindrically symmetric confinement as well as support for the atoms against gravity. This trapping configuration is well-suited for the implementation of a compact atom interferometer based gyroscope. The trap is made up of six coils, which were produced using photolithographic techniques and take up a modest volume of approximately 1 cubic inch inside a vacuum chamber. The trapping frequencies and thermal characteristics of the trap are presented, showing cylindrical symmetry and scalability of the trapping frequencies from 1 Hz to 8 Hz in the symmetry plane.

International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates.

Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug. INTRODUCTION: Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients. METHODS: The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis. RESULTS: Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3 months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%. CONCLUSIONS: If a significant decrease is observed, the treatment can continue, but if no decrease occurs, the clinician should reassess to identify problems with the treatment, mainly low adherence.

The 'molecularly unstratified' patient: a focus for moral, psycho-social and societal research.

The biomedical paradigm of personalised precision medicine - identification of specific molecular targets for treatment of an individual patient - offers great potential for treatment of many diseases including cancer. This article provides a critical analysis of the promise, the hype and the pitfalls attending this approach. In particular, we focus on 'molecularly unstratified' patients - those who, for various reasons, are not eligible for a targeted therapy. For these patients, hope-laden therapeutic options are closed down, leaving them left out, and left behind, bobbing untidily about in the wake of technological and scientific 'advance'. This process creates a distinction between groups of patients on the basis of biomarkers and challenges our ability to provide equitable access to care for all patients. In broadening our consideration of these patients to include the research ecosystem that shapes their experience, we hypothesise that the combination of immense promise with significant complexity creates particular individual and organisational challenges for researchers. The novelty and complexity of their research consumes high levels of resource, possibly in parallel with undervaluing other 'low hanging fruit', and may be challenging current regulatory thinking. We outline future research to consider the societal, psycho-social and moral issues relating to 'molecularly unstratified' patients, and the impact of the drive towards personalisation on the research, funding, and regulatory ecosystem.

Fast phase stabilization of a low frequency beat note for atom interferometry.

Atom interferometry experiments rely on the ability to obtain a stable signal that corresponds to an atomic phase. For interferometers that use laser beams to manipulate the atoms, noise in the lasers can lead to errors in the atomic measurement. In particular, it is often necessary to actively stabilize the optical phase between two frequency components of the beams. Typically this is achieved using a time-domain measurement of a beat note between the two frequencies. This becomes challenging when the frequency difference is small and the phase measurement must be made quickly. The method presented here instead uses a spatial interference detection to rapidly measure the optical phase for arbitrary frequency differences. A feedback system operating at a bandwidth of about 10 MHz could then correct the phase in about 3 µs. This time is short enough that the phase correction could be applied at the start of a laser pulse without appreciably degrading the fidelity of the atom interferometer operation. The phase stabilization system was demonstrated in a simple atom interferometer measurement of the (87)Rb recoil frequency.

Glucocorticoid therapy for adrenal insufficiency: nonadherence, concerns and dissatisfaction with information.

OBJECTIVE: Appropriate self-management of glucocorticoid therapy (GC) is crucial for patients with adrenal insufficiency (AI). We aimed to describe patients' self-reported nonadherence to GC, evaluate perceived doubts about need for GC, concerns about adverse effects, and dissatisfaction with information received about GC. DESIGN: Cross-sectional survey. PATIENTS: Patients prescribed GC for AI (n = 81) from five European countries. MEASUREMENTS: Online survey including the Medication Adherence Report Scale (MARS), Beliefs about Medicines Questionnaire(©) (BMQ Specific, adapted for AI) and Satisfaction with Information about Medicines Scale(©) (Prof Rob Horne; SIMS). RESULTS: Most patients (85·2%) reported a degree of nonadherence to GC. The most frequent types of nonadherence concerned changing the timing of GC doses, for example taking a dose later in the day than advised (37·0%). Few patients doubted their personal need for daily GC, but most reported high concerns about GC including potential weight gain (50·6%), osteoporosis (53·6%) and the continuing risk of adrenal crisis (50·6%). Dissatisfaction with information about GC was frequent, with participants particularly dissatisfied with the amount of information they had received about potential problems with GC. People who expressed dissatisfaction with information about GC, and concerns about its adverse effects were also more likely to report nonadherence (P < 0·05). CONCLUSIONS: Nonadherence to treatment, concerns about potential adverse effects and dissatisfaction with the information provided about treatment were frequently reported by this European sample of AI patients. Many AI patients may need additional information about their GC and support to address concerns about GC and facilitate adherence.

Natural history, reasons for, and impact of low/non-adherence to medications for osteoporosis in a cohort of community-dwelling older women already established on medication: a 2-year follow-up study.

UNLABELLED: Approximately 15 % of older women on oral medications for osteoporosis could be considered for alternatives including parenteral therapies. Collection of data on socio-demographic/clinical variables is unlikely to be helpful in predicting low/non-adherence. Alternative approaches are needed to identify individuals at risk of low/non-adherence. INTRODUCTION: This study aims to identify individual patient reasons for stopping medications for osteoporosis, and to investigate whether this can be predicted from knowledge about socio-demographic/clinical data, or whether alternative approaches need to be used. METHODS: The Cohort for Skeletal Health in Bristol and Avon (COSHIBA) recruited 3200 older women from South West UK, of whom a proportion were on medications for osteoporosis at baseline. Information on self-reported adherence and reasons for low/non-adherence were collected at 6-monthly intervals over a 2-year period. Data was also collected on potential predictors of and impact of low/non-adherence. RESULTS: Two hundred thirty-three of 3200 (7.3 %) women were on medications for osteoporosis at baseline. Mean length of time on treatment prior to enrolment was 46 months. Of those on osteoporosis medications, 94.9 % were on bisphosphonates; 8.5 % reported low adherence and 21.6 % stopped their medication completely over the 2-year follow-up period. Length of time on medication at baseline did not influence rates of low/non-adherence. Reasons for low/non-adherence to bisphosphonates included side effects (53.9 %), practical reasons such as forgetting to take them (18.0 %) and beliefs about medications (20.5 %). No convincing predictors of low/non-adherence were identified. CONCLUSIONS: Approximately 15 % of older women on oral medications for osteoporosis could be considered for alternatives including parenteral therapies. This has important implications for healthcare provision. Collection of data on socio-demographic/clinical variables is unlikely to be helpful in predicting low/non-adherence. Alternative approaches are needed to identify individuals at risk of low/non-adherence to osteoporosis medications.

Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis.

BACKGROUND: Preventive therapy is a risk reduction option for women who have an increased risk of breast cancer. The effectiveness of preventive therapy to reduce breast cancer incidence depends on adequate levels of uptake and adherence to therapy. We aimed to systematically review articles reporting uptake and adherence to therapeutic agents to prevent breast cancer among women at increased risk, and identify the psychological, clinical and demographic factors affecting these outcomes. DESIGN: Searches were carried out in PubMed, CINAHL, EMBASE and PsychInfo, yielding 3851 unique articles. Title, abstract and full text screening left 53 articles, and a further 4 studies were identified from reference lists, giving a total of 57. This review was prospectively registered with PROSPERO (CRD42014014957). RESULTS: Twenty-four articles reporting 26 studies of uptake in 21 423 women were included in a meta-analysis. The pooled uptake estimate was 16.3% [95% confidence interval (CI) 13.6-19.0], with high heterogeneity (I(2) = 98.9%, P < 0.001). Uptake was unaffected by study location or agent, but was significantly higher in trials [25.2% (95% CI 18.3-32.2)] than in non-trial settings [8.7% (95% CI 6.8-10.9)] (P < 0.001). Factors associated with higher uptake included having an abnormal biopsy, a physician recommendation, higher objective risk, fewer side-effect or trial concerns, and older age. Adherence (day-to-day use or persistence) over the first year was adequate. However, only one study reported a persistence of ≥ 80% by 5 years. Factors associated with lower adherence included allocation to tamoxifen (versus placebo or raloxifene), depression, smoking and older age. Risk of breast cancer was discussed in all qualitative studies. CONCLUSION: Uptake of therapeutic agents for the prevention of breast cancer is low, and long-term persistence is often insufficient for women to experience the full preventive effect. Uptake is higher in trials, suggesting further work should focus on implementing preventive therapy within routine care.