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INTRODUCTION: Idiopathic mastalgia (benign breast pain of unknown origin) is often poorly managed because of its subjective nature and unclear aetiology. Mastalgia is a reason for up to 50% of breast outpatient referrals. Existing systematic reviews discuss dated treatment options that provide limited symptomatic relief.METHODS: A systematic review was conducted for aetiology and treatment of idiopathic mastalgia in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance. Databases such as PubMed, MEDLINE, Cochrane Database and the Clinical Trial Registry were searched (February 2016).RESULTS: Reassurance plus bra-fitting advice provides relief for most women. If symptoms persist, addition of topical non-steroidal anti-inflammatory drugs (NSAIDs) provides relief in 70–92% of women. There is some benefit in reducing dietary coffee and fat intake. Medical treatments have serious side-effects (often androgenic or menopausal) and should be considered only in cases resistant to simpler measures. Dopamine agonists are useful, but less effective than endocrine treatments such as Danazol or Tamoxifen. Of the Selective Oestrogen Receptor Modulator drugs, Ormeloxifene appears most effective, but is not licenced in the United Kingdom. Relaxation therapy, acupuncture and kinesiology may be useful but currently lack good evidence of effectiveness.DISCUSSION: First-line management of breast pain should be explanation, reassurance and a bra-fitting advice. Subsequent drug therapy should be balanced against its side-effects; topical NSAIDs and Ormeloxifene show greatest benefit with least side-effects. Newer agents (Ormeloxifene) currently being used for mastalgia in India could be considered in the developed world.

Key Points Axillary micrometastases require no further axillary treatment after SNB for patients with early stage breast cancer After positive sentinel node biopsy, axillary irradiation provides equivalent regional control to nodal clearance in early breast cancer Less morbidity (especially lymphoedema) is seen after axillary radiotherapy Axillary dissection can be safely omitted in patients with more than two positive sentinel nodes after breast-conserving surgery, provided whole-breast radiation therapy is planned Although most patients with breast cancer have clinically negative axillary nodes at preoperative assessment, 15–20% of these women will have metastatic disease within the lymph nodes at operative sentinel node biopsy. The authors discuss the evidence base for management of the axilla after detection of a positive sentinel node, discuss why micrometastatic disease requires systemic but not axillary therapy, and describe data indicating that axillary irradiation gives equivalent control to axillary node clearance, with less morbidity. Although the majority of patients with breast cancer have clinically negative axillary nodes at preoperative assessment, around 15–20% of these women will have metastatic disease within the lymph nodes at operative sentinel node biopsy, and additional selective treatment to the axilla might be required. Local treatment to the axilla can include axillary node clearance or axillary radiotherapy. The recent results of the American College of Surgeons Oncology Group Z0011 trial suggested that some women would be safe from recurrence without further axillary treatment if they have less than three involved sentinel nodes, with no extracapsular spread. We review the evidence base for management of the axilla after detection of a positive sentinel node, discuss the evidence for why micrometastatic disease requires systemic but not axillary therapy, and present data suggesting that axillary irradiation for macrometastases gives equivalent control to axillary node clearance, but causes less morbidity such as lymphoedema. Ongoing trials will confirm whether any further therapy can be omitted for all patients with low volume, sentinel-node macrometastases.

Background Systemic sclerosis (SSc) is a rare connective tissue disorder with heterogeneous manifestations. Two predominant subtypes, limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), are distinguished based on skin involvement distribution. A comprehensive conceptual SSc model is needed to support measurement strategies for outcome studies. This qualitative study aimed to explore key SSc disease concepts and develop a conceptual disease model capturing the heterogeneous lived experiences of patients with SSc. Methods Patient- and clinician-reported concepts specific to dcSSc (more severe and faster-progressing than lcSSc) were identified via a targeted literature review and used to develop a preliminary dcSSc symptom model and a semi-structured qualitative interview guide. The guide was used in concept elicitation interviews with adults with lcSSc and dcSSc. A final conceptual SSc symptoms model was refined based on interview results. Results Disease concepts were retrieved from 35 peer-reviewed articles and 17 clinical trials focusing on patients with dcSSc. The preliminary dcSSc symptom model included skin, hand, gastrointestinal, pain, joint, muscle, mouth, sexual, lung, cardiovascular, cognitive, ocular, and other symptoms. During concept elicitation interviews, participants (n = 44) reported 112 unique symptoms (within 13 domains). Twenty-six symptoms had not previously been identified in pertinent literature. Hand and skin symptoms were reported by all participants. Over 95% of participants reported at least one gastrointestinal and pain symptom, around 80% reported joint and mouth symptoms, 70% reported muscle symptoms, and over 50% reported ocular symptoms. Cognitive, lung, sexual, and cardiac symptoms were reported by fewer than half of participants. Participants with dcSSc reported a broader variety of symptoms than those with lcSSc. However, concepts relevant to patients with dcSSc and lcSSc strongly overlapped, suggesting that a single conceptual model is appropriate to map symptoms for both subtypes. The overlap was further reflected in the most bothersome symptoms, which included skin fibrosis and hand symptoms for both populations. Conclusions The final conceptual model captures the heterogeneous symptoms of SSc and reflects the lived experience of patients with SSc. It covers both clinical SSc subtypes and can support the choice and/or development of instruments to measure patient experiences in clinical trials.

Background End stage renal disease (ESRD) is the irreversible decline in an individual’s kidney function. In severe cases it can be fatal if dialysis or transplantation is not sought. Renal transplantation is associated with longer life expectancies and improved quality of life and is often the preferred treatment over chronic dialysis for those with ESRD. After kidney transplant, patients are at risk of infections, and complications such as allograft rejection. Antibody mediated rejection (AMR) is one of the most common causes of allograft failure. There is currently no approved medication for the prevention or treatment of AMR after transplantation. Whereas the patient-reported symptoms and impacts of ESRD and of kidney transplant have been widely documented, a paucity of these data specific to the population at high risk of or with active AMR is evident. Methods We conducted qualitative interviews and analysis with 14 patients with ESRD on the waiting list for a kidney transplant, and 19 patients who had received a kidney transplant (patients post-transplant without AMR ( n  = 12), and patients post-transplant at high risk of or with active AMR ( n  = 7)). Results A total of 52 symptoms and 69 impacts were reported across the populations with ESRD and post-transplant. New concepts emerged from the interviews that had not been reported in previous literature. The patients with AMR in our study reported mostly negative symptoms but continued to experience many benefits of transplant such as increased energy, an absence of dry or itching skin, an absence of urological and neuropathic symptoms and fewer symptoms overall. Negative impacts were most often related to emotional, physical, and social functioning, and positive impacts most frequently reported for overall health, activities of daily living and quality of life. Patients post-transplant both with and without AMR reported improvements in quality of life compared to before their transplant. However, although patients with AMR reported a number of positive impacts, fewer were mentioned, and less frequently than by patients post-transplant without AMR; a return to normalcy, increased social interaction, and improved diet and lifestyle are all examples of this. Our research allowed the development of a conceptual disease model specific to patients with AMR. Conclusion The qualitative exploration of patient experience of symptoms and impacts carried out in our study underlines the heterogeneity of experience and the burden of disease and treatment experienced by patients at all stages of disease and treatment, from ESRD, to AMR of the kidney transplant. Eliciting these data directly from patients, analyzing and presenting these concepts in conceptual disease models is an essential step towards relevant and accurate measurement of patient experience in these populations.

Contralateral risk-reducing mastectomy (CRRM) rates have tripled over the last 2 decades. Reasons for this are multi-factorial, with those harbouring a pathogenic variant in the BRCA1 / 2 gene having the greatest survival benefit. On May 14th, 2013, Angelina Jolie shared the news of her bilateral risk-reducing mastectomy (BRRM), on the basis of her BRCA1 pathogenic variant status. We evaluated the impact of this news on rates of CRRM in women with increased risk for developing breast cancer after being diagnosed with unilateral breast cancer. The prospective cohort study included all women with at least a moderate lifetime risk of developing breast cancer who attended our family history clinic (1987–2019) and were subsequently diagnosed with unilateral breast cancer. Rates of CRRM were then compared between patients diagnosed with breast cancer before and after Angelina Jolie’s announcement (pre- vs. post-AJ). Of 386 breast cancer patients, with a mean age at diagnosis of 48 ± 8 years, 268 (69.4%) were diagnosed in the pre-AJ period, and 118 (30.6%) in the post-AJ period. Of these, 123 (31.9%) underwent CRRM, a median 42 (interquartile range: 11–54) days after the index cancer surgery. Rates of CRRM doubled following AJ’s news, from 23.9% pre-AJ to 50.0% post AJ ( p  < 0.001). Rates of CRRM were found to decrease with increasing age at breast cancer ( p  < 0.001) and tumour TNM stage ( p  = 0.040), and to increase with the estimated lifetime risk of breast cancer ( p  < 0.001) and tumour grade ( p  = 0.015) on univariable analysis. After adjusting for these factors, the step-change increase in CRRM rates post-AJ remained significant (odds ratio: 9.61, p  < 0.001). The AJ effect appears to have been associated with higher rates of CRRM amongst breast cancer patients with increased cancer risk. CRRM rates were highest amongst younger women and those with the highest lifetime risk profile. Clinicians need to be aware of how media news can impact on the delivery of cancer related services. Communicating objective assessment of risk is important when counselling women on the merits of risk-reducing surgery.

SUMMARY POINTS Ductal carcinoma in situ (DOS) is a preinvasive breast cancer—malignant cells are confined within an intact ductal basement membrane Most cases (90%) are asymptomatic and detected at screening, but it can present as Paget's disease of the nipple, nipple discharge, or a lump Treatment aims to prevent invasive disease Oestrogen receptor status tends to be preserved in recurrences or disease progression; this has implications for adjuvant treatment and reducing risk of recurrence The optimum treatment is unclear, and urgent clarification is needed Women with DCIS should have the option of entering high quality randomised controlled trials

We used a combination of field studies and laboratory experiments to characterize key ecological aspects of the seed biology and soil seed bank dynamics of annual plant communities in chenopod shrublands of South Australia. A sequential study of the soil seed bank demonstrated seasonal and between-year variability in numbers and composition of the soil seed bank. Soil samples incubated under different temperature and watering regimes produced different communities, indicating that species respond differentially to various environmental combinations. Emergence was extremely low at low water availability and at high temperatures, even in trays with ample water. A high percentage of seeds of four out of five species buried in the field remained viable for two years, while the fifth, Carrichtera annua, showed a sharp decline in seed viability, reaching nearly zero survivorship. Our results indicate that, in this system, annual plant communities result from germination of a fraction of seeds present in the soil seed bank, when autumn or winter rainfalls occur. Because different species have different responses to various combinations of environmental conditions, the community composition varies from year to year. This variability is likely to be a component of coexistence through the storage effect.

Introduction Cabotegravir plus rilpivirine (CAB + RPV) is the first complete long‐acting (LA) regimen recommended for maintaining HIV‐1 virological suppression. Cabotegravir And Rilpivirine Implementation Study in European Locations (CARISEL) is an implementation–effectiveness study examining the implementation of CAB+RPV LA administered every 2 months (Q2M) in European HIV centres. We present staff study participant (SSP) perspectives on the administration of CAB+RPV LA over 12 months. Methods Eighteen clinics were randomized to one of two implementation support packages: standard arm (Arm‐S) or enhanced arm (Arm‐E). Arm‐S included video injection training and provider/patient toolkits. Additionally, Arm‐E included skilled wrap‐around team meetings, face‐to‐face injection training and continuous quality improvement (CQI) calls. SSPs completed surveys on the acceptability, appropriateness and feasibility of CAB+RPV LA as an intervention and its implementation into their clinics, as well as barriers and facilitators to implementation. All surveys were completed at Month (M)1 (baseline), M5 and M12; data collection was completed by February 2022. Qualitative data were obtained from semi‐structured interviews at M1, M5 and M12. The primary objective was assessed via formal statistical comparisons between study arms of the Acceptability of Implementation Measure, Implementation Appropriateness Measure and Feasibility of Implementation Measure surveys (1–5 Likert scale ranging from 1 = “completely disagree” to 5 = “completely agree”). Equivalent measures anchored to CAB+RPV LA as a therapy were also assessed. Results Seventy SSPs completed surveys and interviews at M1, 68 at M5 and 62 at M12. Mean acceptability/appropriateness/feasibility scores were ≥3.8 (out of 5) at M12 for implementation‐ and intervention‐based measures. An analysis of covariance showed no significant differences between study arms for these outcomes. Although barriers were noted, most SSPs were not overly concerned that these would impact implementation; concern about these anticipated barriers also decreased over time. At M12, 90.3% (n = 56/62) of SSPs held a positive opinion about CAB+RPV LA implementation. Qualitative interviews and CQI calls highlighted three top practices that supported implementation: implementation planning; education about CAB+RPV LA clinical efficacy; and education around administering injections and managing pain/discomfort after injections. Conclusions CARISEL demonstrated that CAB+RPV LA dosed Q2M was successfully implemented across a range of European locations, with SSPs finding implementation highly acceptable, appropriate and feasible. ClinicalTrials.gov number NCT04399551

Background Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure in the UK. The introduction of techniques to augment the subpectoral pocket has revolutionised the procedure, but there is a lack of high-quality outcome data to describe the safety or effectiveness of these techniques. Randomised controlled trials (RCTs) are the best way of comparing treatments, but surgical RCTs are challenging. The iBRA (implant breast reconstruction evaluation) study aims to determine the feasibility, design and conduct of a pragmatic RCT to examine the effectiveness of approaches to IBBR. Methods/design The iBRA study is a trainee-led research collaborative project with four phases: Phase 1 – a national practice questionnaire (NPQ) to survey current practice Phase 2 – a multi-centre prospective cohort study of patients undergoing IBBR to evaluate the clinical and patient-reported outcomes Phase 3– an IBBR-RCT acceptability survey and qualitative work to explore patients’ and surgeons’ views of proposed trial designs and candidate outcomes. Phase 4 – phases 1 to 3 will inform the design and conduct of the future RCT All centres offering IBBR will be encouraged to participate by the breast and plastic surgical professional associations (Association of Breast Surgery and British Association of Plastic Reconstructive and Aesthetic Surgeons). Data collected will inform the feasibility of undertaking an RCT by defining current practice and exploring issues surrounding recruitment, selection of comparator arms, choice of primary outcome, sample size, selection criteria, trial conduct, methods of data collection and feasibility of using the trainee collaborative model to recruit patients and collect data. Discussion The preliminary work undertaken within the iBRA study will determine the feasibility, design and conduct of a definitive RCT in IBBR. It will work with the trainee collaborative to build capacity by creating an infrastructure of research-active breast and plastic surgeons which will facilitate future high-quality research that will ultimately improve outcomes for all women seeking reconstructive surgery. Trial registration ISRCTN37664281

Introduction CARISEL is an implementation–effectiveness “hybrid” study examining the perspectives of people living with HIV-1 (patient study participants [PSPs]) on cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) dosed every 2 months (Q2M) across 5 European countries. Methods PSPs completed questionnaires on acceptability (Acceptability of Intervention Measure), appropriateness (Intervention Appropriateness Measure), and feasibility (Feasibility of Intervention Measure) at their first (Month [M] 1), third (M4), and seventh (M12) injection visits. Semistructured qualitative interviews were also conducted. Results Overall, 437 PSPs were enrolled, of whom 430 received treatment. Median (interquartile range) age was 44 (37-51) years, 25.3% (n = 109/430) were female (sex at birth), and 21.9% (n = 94/430) were persons of color. Across time points, PSPs found CAB + RPV LA highly acceptable, appropriate, and feasible (mean scores ≥4.47/5). Qualitative data supported these observations. Conclusions PSPs found CAB + RPV LA Q2M to be an acceptable, appropriate, and feasible treatment option.