A pilot randomised controlled trial of acceptance and commitment therapy for medication decision-making and quality of life in women with breast cancer: The ACTION trial.

OBJECTIVE: Non-adherence to adjuvant endocrine therapy (AET) in women with breast cancer is common and associated with medication side-effects and distress. We co-designed an Acceptance and Commitment Therapy intervention (ACTION) to enhance medication decision-making and quality of life (QoL). We undertook a pilot trial of ACTION to inform the feasibility of a phase III trial, and to examine intervention acceptability. METHODS: This was a multi-site, exploratory, two-arm, individually randomised external pilot trial. Women with early breast cancer prescribed AET were randomised (1:1) to receive usual care (UC) or UC + ACTION. The ACTION intervention comprised a remotely delivered one-to-one ACT session followed by three group sessions delivered by clinical psychologists, alongside a website containing ideas for the self-management of side effects. RESULTS: Of the 480 women screened for eligibility, 260 (54.2%) were approached and 79 (30.4%) randomised. 71 (89.9%) women provided data at 3-month and 70 (88.6%) at 6-month 40 women were randomised to receive UC + ACTION and 32 (80.0%) completed the intervention. Most (75.0%) accessed the website at least once. ACTION was acceptable to participants (Borkovec & Nau Scale: mean = 7.8 [SD = 2.7] out of 10). Signals of effectiveness in favour of the UC + ACTION arm were observed for medication adherence (Adherence Starts with Knowledge questionnaire-12), QoL (work and social adjustment scale), health-related QoL (functional assessment of cancer therapy[FACT] general and FACT-ES-19/23), distress (generalised anxiety disorder -7, patient health questionnaire-9) and psychological flexibility (valuing questionnaire). CONCLUSIONS: The ACTION intervention was acceptable to patients. There were promising signals for effectiveness on primary and secondary outcomes. A phase III randomised controlled trial is feasible. TRIAL REGISTRATION: ISRCTN12027752.

Acceptability of aspirin for cancer preventive therapy: a survey and qualitative study exploring the views of the UK general population.

OBJECTIVES: Aspirin could be offered for colorectal cancer prevention for the UK general population. To ensure the views of the general population are considered in future guidance, we explored public perceptions of aspirin for preventive therapy. DESIGN: We conducted an online survey to investigate aspirin use, and awareness of aspirin for cancer prevention among the UK general population. We conducted semistructured interviews with a subsample of survey respondents to explore participants' acceptability towards aspirin for cancer preventive therapy. We analysed the interview data using reflexive thematic analysis and mapped the themes onto the Theoretical Domains Framework, and the Necessity and Concerns Framework. SETTING: Online survey and remote interviews. PARTICIPANTS: We recruited 400 UK respondents aged 50-70 years through a market research company to the survey. We purposefully sampled, recruited and interviewed 20 survey respondents. RESULTS: In the survey, 19.0% (76/400) of respondents were aware that aspirin can be used to prevent cancer. Among those who had previously taken aspirin, 1.9% (4/216) had taken it for cancer prevention. The interviews generated three themes: (1) perceived necessity of aspirin; (2) concerns about side effects; and (3) preferred information sources. Participants with a personal or family history of cancer were more likely to perceive aspirin as necessary for cancer prevention. Concerns about taking aspirin at higher doses and its side effects, such as gastrointestinal bleeding, were common. Many described wanting guidance and advice on aspirin to be communicated from sources perceived as trustworthy, such as healthcare professionals. CONCLUSIONS: Among the general population, those with a personal or family history of cancer may be more receptive towards taking aspirin for preventive therapy. Future policies and campaigns recommending aspirin may be of particular interest to these groups. Multiple considerations about the benefits and risks of aspirin highlight the need to support informed decisions on the medication.

Acceptability, fidelity and trial experience of four intervention components to support medication adherence in women with breast cancer: A process evaluation protocol for a pilot fractional factorial trial.

Background: The Refining and Optimising a behavioural intervention to Support Endocrine Therapy Adherence (ROSETA) programme has developed four intervention components aiming to improve medication adherence in women with early-stage breast cancer. These are (a) text messages, (b) information leaflet, (c) Acceptance and Commitment Therapy-based guided self-help (ACT), (d) side-effect management website. Guided by the Multiphase Optimisation Strategy, our pilot trial will use a fractional factorial design to evaluate the feasibility of undertaking a larger optimisation trial. The pilot will include a process evaluation to maximise learning regarding the fidelity and acceptability of the intervention components before proceeding with a larger trial. The trial process evaluation has three aims: to assess the (1) fidelity and (2) acceptability of the intervention components; and (3) to understand participant's trial experience, and barriers and facilitators to recruitment and retention. Methods: The process evaluation will use multiple methods. Fidelity of the intervention components will be assessed using self-reported questionnaire data, trial data on intervention component adherence, and observations of the ACT sessions. Acceptability of the intervention components and trial experience will be explored using an acceptability questionnaire and interviews with patients and trial therapists. Trial experience will be assessed using a questionnaire and interviews with participants, while barriers and facilitators to recruitment and retention will be assessed using a questionnaire completed by research nurses and participant interviews. The pilot trial opened for recruitment on 20th May 2022 and was open at the time of submission. Conclusions: This process evaluation will provide information regarding whether the intervention components can be delivered with fidelity within a national healthcare setting and are acceptable to participants. We will also better understand participant experience in a pilot trial with a fractional factorial design, and any barriers and facilitators to recruitment and retention. Registration: ISRCTN registry ( ISRCTN10487576, 16/12/2021).

BACKGROUND: The majority of women with early-stage breast cancer are recommended adjuvant endocrine therapy (AET) to reduce the chances of their cancer coming back. Many women given this medication don't take it every day or stop taking it earlier than they should. We have developed four different interventions to help women take AET. These are; text messages reminding women to take AET; an information leaflet explaining how AET works and its benefits and side-effects; a therapy programme to reduce distress, consisting of five support sessions and four module booklets; and a website with strategies to manage AET side-effects. We are now testing whether these interventions can be delivered within the NHS in different combinations, in a small trial. STUDY METHODS: We have three aims: 1. To find out if the interventions can be given and are received in the way they were supposed to (fidelity).2. To find out if the support received as part of the trial was acceptable to women with breast cancer (acceptability).3. To find out what women's experience was of taking part in the trial overall (trial experience). To do this we will: 1. Interview participants to ask them how acceptable they found the interventions, what they understood, whether they used the interventions, and how they found participating in the trial.2. Interview therapists who delivered the therapy programme to see if they delivered it as they were supposed to, and how they found delivering the intervention.3. Ask participants to complete questionnaires about how acceptable the interventions were, and whether they read and used them.4. Ask the staff involved in finding participants for the trial about challenges and improvements. We will use what we find to make improvements in a future trial where we will test whether the interventions help women to take AET.

Optimization of an Information Leaflet to Influence Medication Beliefs in Women With Breast Cancer: A Randomized Factorial Experiment.

BACKGROUND: Adherence to adjuvant endocrine therapy (AET) is low in women with breast cancer. Negative beliefs about the necessity of AET and high concerns are barriers to adherence. PURPOSE: To use the multiphase optimization strategy to optimize the content of an information leaflet intervention, to change AET beliefs. METHODS: We conducted an online screening experiment using a 25 factorial design to optimize the leaflet. The leaflet had five components, each with two levels: (i) diagrams about AET mechanisms (on/off); (ii) infographics displaying AET benefits (enhanced/basic); (iii) AET side effects (enhanced/basic); (iv) answers to AET concerns (on/off); (v) breast cancer survivor (patient) input: quotes and photographs (on/off). Healthy adult women (n = 1,604), recruited via a market research company, were randomized to 1 of 32 experimental conditions, which determined the levels of components received. Participants completed the Beliefs about Medicines Questionnaire before and after viewing the leaflet. RESULTS: There was a significant main effect of patient input on beliefs about medication (ß = 0.063, p < .001). There was one significant synergistic two-way interaction between diagrams and benefits (ß = 0.047, p = .006), and one antagonistic two-way interaction between diagrams and side effects (ß = -0.029, p = .093). There was a synergistic three-way interaction between diagrams, concerns, and patient input (ß = 0.029, p = .085), and an antagonistic four-way interaction between diagrams, benefits, side effects, and concerns (ß = -0.038, p = .024). In a stepped approach, we screened in four components and screened out the side effects component. CONCLUSIONS: The optimized leaflet did not contain enhanced AET side effect information. Factorial experiments are efficient and effective for refining the content of information leaflet interventions.

Adjuvant endocrine therapy (AET) is a medication given to women to stop breast cancer from returning. Many women do not take AET every day or stop taking it before they should. Some women do not take AET because they do not believe it will help them, or they have concerns about the side effects. We ran an online study aiming to create the best information leaflet to help women understand how AET is helpful and to reduce their concerns. The leaflet had five sections; diagrams explaining how AET works, visual pictures of the benefits of AET, information about the side effects, answers to common concerns, and quotes from other women with breast cancer. 1,604 healthy women filled in a questionnaire before and after looking at an information leaflet about AET. Women received different combinations of the five sections of the information leaflet. We found quotes from other women with breast cancer led to more positive beliefs about AET. Some sections of the leaflet worked better in combination, while other sections were worse in combination. Our results led us to remove the detailed side effect information from the leaflet, as in combination with the other sections this negatively affected women's beliefs about AET.

Awareness of symptoms, anticipated barriers and delays to help-seeking among women at higher risk of breast cancer: A UK multicentre study.

Women with a family history of breast cancer have an increased lifetime risk of the disease. Delay in symptom presentation can lead to poorer outcomes. Low awareness of breast cancer symptoms and help-seeking barriers have been associated with delay in presentation in the general population. Symptom awareness and help-seeking barriers among women at increased risk of breast cancer are unknown. We conducted analysis of survey data which included women with moderate and high risk of breast cancer from 20 secondary and tertiary care clinics in England (n = 408). Women completed a validated survey assessing breast cancer symptom awareness, barriers to help-seeking and anticipated delay in help-seeking. Women recognised an average of 9.1/11 breast cancer symptoms (SD = 2.1). Nipple rash was the least recognised symptom (51.0%). Women educated to at least degree level had higher awareness than those with lower education (ß = 0.14, 95% CI 0.13, 0.99, p = 0.011). Women at lower socioeconomic status (SES) had lower awareness than those at higher SES (ß = -0.13, 95% CI -1.09, -0.07, p = 0.027). Women reported several anticipated help-seeking barriers (mean = 4.0/11, SD = 2.8). Waiting to see if a symptom will pass was the most commonly reported barrier to help-seeking (71.5%). Most women (376/408; 92.2%) reported that they would seek medical help within 2 weeks of discovering a breast cancer symptom. Interventions to increase awareness of non-lump breast cancer symptoms and reduce help-seeking barriers are needed, with considerations of appropriate reading levels and modalities for women with lower education and SES.

Codevelopment of a Text Messaging Intervention to Support Adherence to Adjuvant Endocrine Therapy in Women With Breast Cancer: Mixed Methods Approach.

BACKGROUND: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence and mortality in women with early-stage breast cancer. Unintentional nonadherence to AET is common (eg, forgetting to take medication). Forming habits surrounding medication taking could reduce reliance on memory and improve AET adherence. SMS text messaging interventions may offer a low-cost approach for promoting medication-taking habits. To optimize the likely effectiveness of such SMS text messages, the content should be developed using a transparent approach to ensure fidelity to relevant psychological theory and with user input to increase acceptability. OBJECTIVE: This study aimed to develop a pool of brief SMS text messages promoting habit formation to support AET adherence, which are acceptable to women with breast cancer and show fidelity to theory-based behavior change techniques (BCTs). METHODS: According to published literature, we selected 6 BCTs derived from the habit formation model: action planning, habit formation, restructuring the physical environment, adding objects to the environment, prompts/cues, and self-monitoring of behavior. In study 1, behavior change experts (n=10) created messages, each based on 1 of the 6 BCTs, in a web-based workshop and rated the fidelity of the messages to the intended BCT. In study 2, women with experience of taking AET discussed the acceptability of the messages in a focus group (n=5), and the messages were refined following this. In study 3, women with breast cancer rated the acceptability of each message in a web-based survey (n=60). In study 4, additional behavior change experts rated the fidelity of the remaining messages to the intended BCT in a web-based survey (n=12). Finally, a consultant pharmacist reviewed a selection of messages to ensure that they did not contradict general medical advice. RESULTS: In study 1, 189 messages were created targeting the 6 BCTs. In total, 92 messages were removed because they were repetitious, unsuitable, or >160 characters, and 3 were removed because of low fidelity (scoring <5.5/10 on a fidelity rating scale). Following study 2, we removed 13 messages considered unacceptable to our target population. In study 3, all remaining messages scored above the midpoint on an acceptability scale (1-5); therefore, no messages were removed (mean 3.9/5, SD 0.9). Following study 4, we removed 13 messages owing to low fidelity (scoring <5.5/10 on a fidelity rating scale). All the remaining messages showed fidelity to the intended BCTs (mean 7.9/10, SD 1.3). Following the pharmacist review, 2 messages were removed, and 3 were amended. CONCLUSIONS: We developed a pool of 66 brief SMS text messages targeting habit formation BCTs to support AET adherence. These showed acceptability to women with breast cancer and fidelity to the intended BCTs. The delivery of the messages will be further evaluated to assess their effect on medication adherence.

Refining and optimising a behavioural intervention to support endocrine therapy adherence (ROSETA) in UK women with breast cancer: protocol for a pilot fractional factorial trial.

INTRODUCTION: Women with breast cancer who do not adhere to adjuvant endocrine therapy (AET) have increased risks of mortality and recurrence. There are multiple barriers to AET adherence, including medication side-effects, beliefs about medication, memory and psychological distress. We developed four intervention components, each targeting a different barrier. This pilot trial is part of the preparation phase of the Multiphase Optimisation Strategy, and aims to establish key trial parameters, establish intervention component adherence, establish availability and feasibility of outcome and process data, estimate variability in planned outcome measures and estimate cost of developing and delivering each intervention component. METHODS AND ANALYSIS: The four intervention components are as follows: short message service text reminders (target: memory); a written information leaflet (target: medication beliefs); a guided self-help Acceptance and Commitment Therapy programme (target: psychological flexibility to reduce distress) and a self-management website (target: side-effect management). To evaluate the feasibility of recruitment, acceptability of the intervention components and the availability of outcome data, we will conduct a multisite, exploratory pilot trial using a 24-1 fractional factorial design, with a nested process evaluation. We will randomise 80 women with early-stage breast cancer who have been prescribed AET to one of eight experimental conditions. This will determine the combination of intervention components they receive, ranging from zero to four, with all conditions receiving usual care. Key outcomes of interest include medication adherence and quality of life. Progression to the optimisation phase will be based on predefined criteria for consent rates, patient adherence to intervention components and availability of medication adherence data. ETHICS AND DISSEMINATION: The study was reviewed by the Wales Research Authority Research Ethics Committee 3 (21/WA/0322). Written informed consent will be obtained from all patients before randomisation. The results of this trial will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRTCN10487576.

One size does not fit all: Impact of hand size on ease of use of instruments for minimally invasive surgery.

BACKGROUND: Consideration of ergonomic factors is important for the practice of safe and efficient minimally invasive surgery (MIS). Surgeons with smaller glove sizes have previously been reported to have increased difficulties with some minimally invasive instruments. We aim to investigate hand anthropometrics and their relationship to surgeon comfort when using MIS instruments. METHODS: Male and female surgeons from two centres were surveyed on their experience of handling MIS instruments and images obtained of the dorsal and palmar aspects of their dominant hand. Photographs of hands were transformed to calibrated coordinates to enable anthropometric measurements of finger length and width as well as palm width and hand span photogrammetrically. Surgeon-perceived discomfort, fatigue, pressure points and techniques to mitigate difficulty handling instruments were compared to hand measurements. RESULTS: Questionnaires were completed by 58 surgeons; 20 (34%) were consultants, 17 (29%) were women. Glove size ranged from 6 to 8 (median 7.5). Male participants had significantly larger hands than females in all measured dimensions. Female surgeons and those with smaller finger and hand dimensions were significantly more likely to experience difficulty or discomfort across a range of variables when using MIS instruments. CONCLUSIONS: Surgeons with smaller hands reported increased problems handling MIS instruments. This represents an issue of equity in surgery, with women being more significantly affected than men. Hand size varies greatly between surgeons and anthropometric variability should be considered in design of MIS instruments.

Clinical significance of intermittent absent end-diastolic flow of the umbilical artery in fetal growth restriction.

BACKGROUND: Fetal growth restriction can result from a variety of maternal, fetal, and placental conditions. Umbilical artery Doppler assesses the impedance to blood flow along the fetal component of the placental unit. An abnormal umbilical artery waveform reflects the presence of placental insufficiency and can help differentiate a growth-restricted fetus from the constitutionally small, thus guiding further management. The presence of persistently absent end-diastolic flow and reversed end-diastolic flow is an indication for inpatient antenatal surveillance and preterm delivery. There is no consensus on the optimal management of intermittent absent end-diastolic flow owing to a lack of data to support the ideal delivery timing for growth-restricted fetuses with this finding. OBJECTIVE: This study aimed to estimate the risks of adverse perinatal outcomes among growth-restricted pregnancies with persistently elevated, intermittently absent, and persistently absent end-diastolic flow. Fetal growth restriction is a common condition that is associated with an increased risk of fetal morbidity and mortality. Intermittently absent umbilical artery end-diastolic flow may be identified among pregnancies with fetal growth restriction. The fetal risks associated with persistently absent end-diastolic flow have been described. However, the risks associated with intermittent absent end-diastolic flow are not as well-known. STUDY DESIGN: We performed a retrospective cohort study including nonanomalous, singleton, growth-restricted pregnancies that received umbilical artery Doppler assessment at our institution from 2009 to 2020. Fetuses were classified into the following 3 categories: elevated umbilical artery Doppler, intermittent absent end-diastolic flow, and persistently absent end-diastolic flow. The Doppler categories were classified by the most severe in the pregnancy. The primary outcome was a composite of neonatal morbidity. RESULTS: Total 233 fetuses met the criteria. Of which 78 (33.0%) had elevated umbilical artery Doppler waveforms, 37 (16.0%) had intermittent absent end-diastolic flow, and 119 (51.0%) had absent end-diastolic flow. The composite outcome was statistically different between the groups, occurring in 16.9% with elevated umbilical artery Doppler waveforms (13/77), 35.1% (12/39) with intermittent absent end-diastolic flow, and 56.3% (65/127) with absent end-diastolic flow (P<.001). The odds ratio for the composite outcome was significantly increased in absent end-diastolic flow (odds ratio, 6.15; 95% confidence interval, 3.14-12.80) and was not significantly increased for intermittently absent end-diastolic flow (odds ratio, 2.46; 95% confidence interval, 0.98-6.19) when compared with elevated umbilical artery Doppler waveforms. When adjusted for gestational age at delivery and antenatal steroids, no difference was seen in the primary outcome for intermittent absent end-diastolic flow (adjusted odds ratio, 0.73; 95% confidence interval, 0.20-2.68) and absent end-diastolic flow (adjusted odds ratio, 1.44; 95% confidence interval, 0.51-4.07). CONCLUSION: Among growth-restricted pregnancies, intermittent absent end-diastolic flow is associated with a similar rate of composite neonatal morbidity as persistently elevated Doppler waveforms. In addition, there is no difference in composite neonatal morbidity between the 3 groups when corrected for gestational age at delivery and antenatal steroid administration. These similar outcomes should be considered when creating an antenatal surveillance plan and discussing the potential for outpatient management.

Barriers and facilitators to using aspirin for preventive therapy: a qualitative study exploring the views and experiences of people with Lynch syndrome and healthcare providers.

BACKGROUND: The National Institute for Health and Care Excellence (NG151) recommends considering daily aspirin for people with Lynch syndrome to reduce colorectal cancer risk. However, deciding whether to initiate aspirin could be a complex decision for patients and their healthcare providers, as both the potential benefits and harms need to be considered. METHODS: We conducted semi-structured interviews to explore the barriers and facilitators to using aspirin for preventive therapy. We recruited 15 people with Lynch syndrome, and 23 healthcare providers across multiple professions in primary, and specialist care (e.g. clinical genetics) in the United Kingdom. Interview schedules were informed by the Theoretical Domains Framework. RESULTS: There were three themes: 1) Considering potential harms and benefits; 2) Healthcare pathway; 3) Patients' level of interest in aspirin. All healthcare providers, across primary and specialist care, viewed general practitioners (GPs) as being responsible for prescribing and overseeing the use of aspirin. However, GPs were unfamiliar with aspirin for preventive therapy, and concerned about prescribing at higher doses (300-600 mg). To support decision-making, GPs wanted clarification from specialist clinicians on the evidence and dose to prescribe. Not all participants with Lynch syndrome received information on aspirin from their healthcare provider, and several were unsure who to discuss aspirin with. GPs were more inclined to prescribe aspirin for patients with expressed preferences for the medication, however several patients were uncertain and wanted further guidance. CONCLUSIONS: Coordinated and multilevel strategies are needed, addressing the needs of both GPs and people with Lynch syndrome, to ensure consistent implementation of national guidance on aspirin for preventive therapy.

Supporting adjuvant endocrine therapy adherence in women with breast cancer: the development of a complex behavioural intervention using Intervention Mapping guided by the Multiphase Optimisation Strategy.

BACKGROUND: Adjuvant endocrine therapy (AET) reduces the risk of breast cancer recurrence and mortality. However, up to three-quarters of women with breast cancer do not take AET as prescribed. Existing interventions to support adherence to AET have largely been unsuccessful, and have not focused on the most salient barriers to adherence. This paper describes the process of developing four theory-based intervention components to support adherence to AET. Our aim is to provide an exemplar of intervention development using Intervention Mapping (IM) with guidance from the Multiphase Optimisation Strategy (MOST). METHODS: Iterative development followed the six-stage IM framework with stakeholder involvement. Stage 1 involved a literature review of barriers to adherence and existing interventions, which informed the intervention objectives outlined in Stage 2. Stage 3 identified relevant theoretical considerations and practical strategies for supporting adherence. Stage 4 used information from Stages 1-3 to develop the intervention components. Stages 1-4 informed a conceptual model for the intervention package. Stages 5 and 6 detailed implementation considerations and evaluation plans for the intervention package, respectively. RESULTS: The final intervention package comprised four individual intervention components: Short Message Service to encourage habitual behaviours surrounding medication taking; an information leaflet to target unhelpful beliefs about AET; remotely delivered Acceptance and Commitment Therapy-based guided self-help to reduce psychological distress; and a website to support self-management of AET side-effects. Considerations for implementation within the NHS, including cost, timing and mode of delivery were outlined, with explanation as to how using MOST can aid this. We detail our plans for the final stage of IM which involve feasibility testing. This involved planning an external exploratory pilot trial using a 24-1 fractional factorial design, and a process evaluation to assess acceptability and fidelity of intervention components. CONCLUSIONS: We have described a systematic and logical approach for developing a theoretically informed intervention package to support medication adherence in women with breast cancer using AET. Further research to optimise the intervention package, guided by MOST, has the potential to lead to more effective, efficient and scalable interventions.

Does decentralisation of surgical management improve outcomes for paediatric testicular torsion?

INTRODUCTION: In testicular torsion (TT), delayed emergency scrotal exploration (ESE) increases the risk of orchidectomy. Transfer of a patient with suspected TT from a district general hospital (DGH) to a paediatric surgical centre (PSC) delays ESE and potentially puts them at increased risk of testicular loss. Prior to 1st January 2017, all boys under aged <16 years presenting to a DGH within the East Midlands Clinical Network (EMCN) would be referred to the PSC. From this date, it was agreed within the EMCN that boys aged ≥5 years with suspected TT presenting to a network DGH would be managed locally, barring exceptional circumstances. Boys aged <5 years would be referred to the PSC for management. AIM: This study aimed to assess the impact of decentralisation of ESE for suspected TT on orchidectomy rates in the EMCN. METHODS: All patients who underwent ESE under the care of paediatric surgery in the PSC, and all patients <16 years old who underwent ESE in 4 EMCN DGHs between January 2017 and December 2019 were identified. Neonatal cases and inpatient referrals were excluded. Comparison was made with published data on ESE performed in the PSC over the 9 years 2008-2016 prior to decentralisation. RESULTS: In the 9 years prior to decentralisation, there were 110 cases of TT in the PSC. In the subsequent 3 years, there were 40 in the PSC and 37 in the DGHs. The orchidectomy rate of boys with TT presenting to DGHs and undergoing exploration locally (16%, 6/37) contrasts with the rate in those transferred from DGHs to the PSC for exploration (58%, 15/26). The difference is highly significant (p = 0.00059, RR 0.28 [95% CI 0.13-0.63]) and indicates that in the EMCN, avoiding hospital transfer and performing ESE at the presenting DGH reduces the risk of orchidectomy by 72%. CONCLUSION: Decentralisation of the provision of ESE in boys with TT has resulted in a significantly lower orchidectomy rate in boys undergoing ESE in the presenting hospital than when transferred to the PSC. This study reinforces existing literature that demonstrates the effect of delayed ESE on orchidectomy rate, and supports the recommendations of national guidelines in the UK that transfer of boys to a PSC for ESE should only occur in exceptional circumstances.

Strategies to self-manage side-effects of adjuvant endocrine therapy among breast cancer survivors: an umbrella review of empirical evidence and clinical guidelines.

PURPOSE: Side-effects of adjuvant endocrine therapy (AET) are common in breast cancer survivors, and can affect adherence to treatment. We synthesised the evidence for strategies to self-manage these side-effects. METHODS: We searched for systematic reviews and clinical guidelines on self-management strategies for AET side-effects (arthralgia, fatigue, hot flashes, gastrointestinal discomfort, nausea, vulvovaginal symptoms, and sleep disturbance). We searched oncology organisation's websites and eight databases (Inception-November 2020). Screening, data extraction and quality assessment were completed independently in duplicate. PROSPERO: 2019CRD4201914001. RESULTS: We identified 33 systematic reviews and 18 clinical guidelines. 21% of reviews were high quality, and the average quality score for guidelines was 44%. Evidence for most strategies was absent or weak. There was consensus from a low-quality review and multiple guidelines to recommend moisturisers, gels and lubricants for vulvovaginal symptoms. Evidence was weak for physical activity for self-managing most symptoms, although two high-quality reviews indicated yoga and aerobic exercise could reduce fatigue. Primary research was often biased by weak and underpowered study designs. Eleven reviews did not report information on adverse events. CONCLUSIONS: Most self-management strategies for breast cancer survivors experiencing side-effects from AET lack evidence. Primary research is needed using high-quality well-powered designs focusing on implementable strategies. IMPLICATIONS FOR CANCER SURVIVORS: Patients and clinicians should be aware that although the risk of harm is low for these self-management strategies, the likelihood of benefit is often unclear. Women should consider moisturisers, gels or lubricants for self-managing vulvovaginal symptoms, and yoga or aerobic exercise for alleviating fatigue.

Is the use of augmented reality-assisted surgery beneficial in urological education? A systematic review.

BACKGROUND: Google Glass is an optical head-mounted display that has been used in multiple medical and surgical settings to enhance delivery of education and training. This systematic review focuses solely on the use of this technology in urology operating theaters for the purpose of surgical education. MATERIALS AND METHODS: A systematic search strategy was employed using EMBASE (1996-2019), Medline (1946-2019) and PubMed. Search terms included optical head-mounted displays, Google Glass and urological surgical training. Use of this technology in a nonurological setting, nonteaching sessions, case reports, reviews, editorials, abstracts, and articles not in English were rejected. Three studies were identified following the exclusion criteria. RESULTS: All 3 studies received positive feedback from trainees regarding this technology in relation to enhanced surgical education. In addition, in all studies the trainees felt the technology had a place for educational training in the future. All studies described disadvantages to the technology as well including battery life, comfort, and cost. CONCLUSIONS: Studies describe a big potential for Google Glass and similar head-mounted devices for the role of surgical training in urology, however, larger studies looking at more varied operations can help reinforce this viewpoint.

Myogenic autoregulation in bone marrow arterioles and in vivo intramedullary pressure in femora of conscious, female Long Evans rats.

OBJECTIVES: The ability to regulate skeletal blood flow is critical for the maintenance of bone. The myogenic response is essential for regulating tissue blood flow. Myogenic responsiveness in bone marrow arterioles has not yet been determined. Furthermore, the literature is disparate regarding intramedullary pressures (IMP) within bone. The purposes of this study were to (1) determine whether bone marrow arterioles have myogenic activity and (2) assess if the autoregulatory zone corresponds with IMP. Also, this study provides detailed methodology on dissecting and isolating bone marrow arterioles for functional assessment. METHODS: Experiment 1: Femoral shafts of female Long Evans rats were catheterized to assess in vivo IMP. Experiment 2: Bone marrow arterioles from female Long Evans rats were cannulated. Active and passive myogenic responses were determined. RESULTS: In vivo intramedullary pressure averaged 32 ± 3 mmHg, intramedullary pulse pressure averaged 5.28 ± 0.03 mmHg, and the mean maximal diameter and wall thickness of the bone marrow arterioles were 96 ± 7 µm and 18 ± 2 µm, respectively. An active myogenic response was observed and differed (p < .001) from the passive curve. CONCLUSION: Bone marrow arterioles have myogenic responsiveness and the autoregulatory zone corresponded with the range of IMP (15-51 mmHg) within the femoral diaphysis of conscious animals.

Human activity vs. climate change: Distinguishing dominant drivers on LAI dynamics in karst region of southwest China.

Understanding the impacts of climate change and human activities on vegetation is of great significance to the sustainable development of terrestrial ecosystems. However, most studies focused on the overall impact over a period and rarely examined the time-lag effect of vegetation's response to climatic factors when exploring the driving mechanisms of vegetation dynamics. In this study, we identified key areas driven by either positive or negative human activities and climate change. Taking the three karst provinces of southwest China as the case study area, a Leaf Area Index (LAI)-climate model was constructed by quantifying the time-lag effect. Then the associated residual threshold was calculated to identify the vegetation change areas dominated by human activities and climate change. The results showed that, during the implementation period of ecological restoration projects from 1999 to 2015, positive impact areas of human activities were mainly distributed among the implementation areas of ecological restoration projects, accounting for 5.61% of the total area. For another, the negative impact areas were mainly distributed across the mountainous area of Yunnan Province, accounting for 1.30% of the total area. Karst landform had the greatest influence on the areas dominated by positive human activities, whereas both topography and karst landform significantly affected the areas dominated by negative human activities. Urban development level had the greatest impact on the areas dominated by climate change. The outcomes of this study provided scientific supports for the sustainable development of ecological restoration projects in China's karst region.

Contribution of soil microbial necromass to SOC stocks during vegetation recovery in a subtropical karst ecosystem.

Carbon sequestration is a key soil function, and an increase in soil organic carbon (SOC) is an indicator of ecosystem recovery because it underpins other ecosystem services by acting as a substrate for the soil microbial community. The soil microbial community constitutes the active pool of SOC, and its necromass (microbial residue carbon, MRC) contributes strongly to the stable SOC pool. Therefore, we propose that the potential for restoration of degraded karst ecosystems lies in the abundance of soil microbial community and the persistence of its necromass, and may be measured by changes in its contribution to the active and stable SOC pools during recovery. We investigated changes in SOC stocks using an established space-for-time chronosequence along a perturbation gradient in the subtropical karst ecosystem: sloping cropland < abandoned cropland < shrubland < secondary forest < primary forest. Microbial biomarkers were extracted from soil profiles from surface to bedrock and used to measure the contributions of the soil microbial community composition (using phospholipid fatty acids, PLFAs) and MRC (using amino sugars) to SOC stocks at each recovery stage. The results showed that the SOC stocks ranged from 10.53 to 31.77 kg m-2 and increased with recovery stage, with total MRC accounting for 17-28% of SOC. Increasing PLFAs and MRC abundances were positively correlated with improved soil structure (decreased bulk density) and organic carbon, nitrogen and phosphorus nutrient. Bacterial MRC contributes more to SOC stocks than fungal residue carbon during vegetation recovery. The PLFA analysis indicated that Gram positive bacteria were the largest microbial group and were relatively more abundant in deeper soils, and biomarkers for saprophytic and ectomycorrhizal fungi were more abundant in soils under woody vegetation. In conclusion, this study suggests that the soil microbial community in karst soils have the potential to adapt to changing soil conditions and contribute substantially to building SOC stocks after abandonment of agriculture in degraded karst landscapes.

Drought-modulated allometric patterns of trees in semi-arid forests.

Tree allometry in semi-arid forests is characterized by short height but large canopy. This pattern may be important for maintaining water-use efficiency and carbon sequestration simultaneously, but still lacks quantification. Here we use terrestrial laser scanning to quantify allometry variations of Quercus mongolica in semi-arid forests. With tree height (Height) declining, canopy area (CA) decreases with substantial variations. The theoretical CA-Height relationship in dynamic global vegetation models (DGVMs) matches only the 5th percentile of our results because of CA underestimation and Height overestimation by breast height diameter (DBH). Water supply determines Height variation (P = 0.000) but not CA (P = 0.2 in partial correlation). The decoupled functions of stem, hydraulic conductance and leaf spatial arrangement, may explain the inconsistency, which may further ensure hydraulic safety and carbon assimilation, avoiding forest dieback. Works on tree allometry pattern and determinant will effectively supply tree drought tolerance studying and support DGVM improvements.

Probing the hydrothermal system of the Chicxulub impact crater.

The ~180-km-diameter Chicxulub peak-ring crater and ~240-km multiring basin, produced by the impact that terminated the Cretaceous, is the largest remaining intact impact basin on Earth. International Ocean Discovery Program (IODP) and International Continental Scientific Drilling Program (ICDP) Expedition 364 drilled to a depth of 1335 m below the sea floor into the peak ring, providing a unique opportunity to study the thermal and chemical modification of Earth's crust caused by the impact. The recovered core shows the crater hosted a spatially extensive hydrothermal system that chemically and mineralogically modified ~1.4 × 105 km3 of Earth's crust, a volume more than nine times that of the Yellowstone Caldera system. Initially, high temperatures of 300° to 400°C and an independent geomagnetic polarity clock indicate the hydrothermal system was long lived, in excess of 106 years.