A Qualitative Concept Elicitation Study to Understand Patient-Reported Symptoms and Impacts of Neisseria gonorrhoeae Infections in the United States.

BACKGROUND: Gonorrhea is the second most common bacterial sexually transmitted infection in the United States, with rising rates. Emerging antimicrobial resistance threatens public health, and vaccines are in development. This study documents patient-reported gonorrhea symptoms and health-related quality-of-life (HRQoL) impact in women who have sex with men (WSM), men who have sex with women (MSW), and men who have sex with men (MSM). METHODS: Semistructured qualitative interviews were conducted (April 2021-March 2022) among US adults with recent (≤6 months) confirmed gonorrhea. Concept saturation was achieved, confirming adequate participant numbers to meet objectives. Elicited symptom and HRQoL impacts were used to develop a conceptual disease model. Common patient-reported outcome measure (PROM) items were compared with elicited concepts. RESULTS: Thirty-two participants (15 WSM, 8 MSW, and 9 MSM) were included. Eight were asymptomatic, 6 had repeat infections, and 5 women and 4 men had complications (i.e., infertility or pelvic inflammatory disease, and urethritis, respectively).The most frequently reported symptoms were vaginal discharge (n = 11 of 12), dysuria (n = 10 of 12), and abdominal/vaginal pain (n = 9 of 12) for symptomatic WSM; dysuria (n = 5 of 6) and penile discharge (n = 4 of 6) for symptomatic MSW; and throat, testicular, or rectal pain (n = 4 of 6) for symptomatic MSM. All (symptomatic and asymptomatic) participants reported HRQoL impacts including negative emotional experiences (n = 31 of 32), and interference with sexual activity (n = 30 of 32), relationships (n = 24 of 32), and social life (n = 17 of 32). Concepts were poorly represented in existing PROMs. CONCLUSIONS: Participants reported a diverse range of symptoms and HRQoL impacts, to help inform the value of new treatment and prevention options. More research is needed to quantify patient burden and develop PROMs.

Facilitating self-care through community pharmacy in England.

In England, almost all the population are within a short walk of a community pharmacy. This network of pharmacies provides a range of services, most of which are commissioned and remunerated through a nationally agreed contract with the National Health Service (NHS). Over time this contract has seen funding move from the traditional core service of dispensing medicines, toward patient-facing clinical services. All of these services have elements of self-care built in to the service specification, which pharmacists are mandated to deliver. These services significantly expand the role of the community pharmacist beyond facilitating self-care by supplying "over the counter" (OTC) medication. The increased public health role, where promotion of healthy living and prevention of disease is now seen as an essential activity by and for pharmacists. Changes to UK health policy, where the focus has been on delivering care closer to the patients' home, means community pharmacists have an increasing role in the effective management of acute and long-term conditions. The most recent contract afforded to pharmacy has now started to integrate pharmacy services with medical services, in both primary and secondary care, in attempt to provide greater continuity for the patient. It is very likely that self-care activities provided by community pharmacy will expand further, especially around the management of long-term conditions as the pharmacy workforce transitions in to having prescribing rights for medicines other than non-prescription medicines.

Accuracy of robot-assisted stereotactic MRI-guided laser ablation in children with epilepsy.

OBJECTIVE: Robot-assisted (RA) stereotactic MRI-guided laser ablation has been reported to be a safe and effective technique for the treatment of epileptogenic foci in children and adults. In this study the authors aimed to assess the accuracy of RA stereotactic MRI-guided laser fiber placement in children and to identify factors that might increase the risk of misplacement. METHODS: A retrospective single-institution review of all children from 2019 to 2022 who underwent RA stereotactic MRI-guided laser ablation for epilepsy was undertaken. Placement error was calculated at the target by measuring the Euclidean distance between the implanted laser fiber position and the preoperatively planned position. Collected data included age at surgery, sex, pathology, date of robot calibration, number of catheters, entry position, entry angle, extracranial soft-tissue thickness, bone thickness, and intracranial catheter length. A systematic review of the literature was also performed using Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. RESULTS: In 28 children with epilepsy, the authors assessed 35 RA stereotactic MRI-guided laser ablation fiber placements. Twenty (71.4%) children had undergone ablation for hypothalamic hamartoma, 7 children (25.0%) for presumed insular focal cortical dysplasia, and 1 patient (3.6%) for periventricular nodular heterotopia. Nineteen children were male (67.9.%) and 9 were female (32.1%). The median age at the time of the procedure was 7.67 years (IQR 4.58-12.26 years). The median target point localization error (TPLE) was 1.27 mm (IQR 0.76-1.71 mm). The median offset error between the planned and actual trajectories was 1.04° (IQR 0.73°-1.46°). Patient age, sex, pathology and the time interval between date of surgery and robot calibration, entry position, entry angle, soft-tissue thickness, bone thickness, and intracranial length were not associated with the placement accuracy of the implanted laser fibers. However, the number of catheters placed did correlate with the offset angle error on univariate analysis (ρ = 0.387, p = 0.022). There were no immediate surgical complications. Meta-analysis indicated that the overall pooled mean TPLE was 1.46 mm (95% CI -0.58 to 3.49 mm). CONCLUSIONS: RA stereotactic MRI-guided laser ablation for epilepsy in children is highly accurate. These data will aid surgical planning.

Results of shared learning of a new magnetic seed localisation device - A UK iBRA-NET breast cancer localisation study.

INTRODUCTION: Shared learning is imperative in the assessment and safe implementation of new healthcare interventions. Magnetic seeds (Magseed®) potentially offer logistical benefit over wire localisation for non-palpable breast lesions but few data exist on outcomes comparing these techniques. A national registration study (iBRA-NET) was conducted to collate device outcomes. In order to share learning, thematic analysis was conducted to ascertain early clinical experiences of Magseed® and wire guided localisation and explore how learning events may be applied to improve clinical outcomes. METHODS: A qualitative study of 27 oncoplastic surgeons, radiologists and physicians was conducted in January 2020 to ascertain the feasibility and challenges associated with Magseed® versus wire breast localisation surgery. Four focus groups were asked to discuss experiences, concerns and shared learning outcomes which were tabulated and analysed thematically. RESULTS: Three key themes were identified comparing Magseed® and wire localisation of breast lesions relating to preoperative, intraoperative and postoperative learning outcomes. Percutaneous Magseed® detection, instrument interference and potential seed or wire dislodgement were the most common issues identified. Clinician experience suggested Magseed® index lesion identification was non-inferior to wire placement and improved the patient pathway in terms of scheduling and multi-site insertion. CONCLUSIONS: Prospective shared learning suggested Magseed® offered additional non-clinical benefits over wire localisation, improving the efficiency of the patient pathway. Recommendations for improving breast localisation technique, appropriate patient selection and clinical practice through shared learning are discussed that may aid other surgeons in the adoption of this relatively new technique.

Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for IBD: a retrospective cohort study.

BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used to treat rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Blood-test safety monitoring is mainly undertaken in primary care. Normal blood results are common. AIM: To determine the frequency and associations of persistently normal blood tests in patients with RA prescribed methotrexate, and patients with IBD prescribed azathioprine. DESIGN AND SETTING: Two-year retrospective study of a cohort taken from an electronic pseudonymised primary care/laboratory database covering >1.4 million patients across Hampshire, UK. METHOD: Patients with RA and IBD, and associated methotrexate and azathioprine prescriptions, respectively, were identified. Tests and test thresholds recommended by the National Institute for Health and Care Excellence were applied. Persistent normality was defined as no abnormalities of any tests nor alanine aminotransferase (ALT), white blood count (WBC), neutrophils, and estimated glomerular filtration rate (eGFR) individually. Logistic regression was used to identify associations with test normality. RESULTS: Of 702 265 adults, 7102 had RA and 8597 had IBD. In total, 3001 (42.3%) patients with RA were prescribed methotrexate and 1162 (13.5%) patients with IBD were prescribed azathioprine; persistently normal tests occurred in 1585 (52.8%) and 657 (56.5%) of the populations, respectively. In patients with RA on methotrexate, 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In patients with IBD on azathioprine, 138 (11.9%) had WBC, 88 (7.6%) eGFR, 72 (6.2%) ALT, and 65 (5.6%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities. CONCLUSION: Persistent test normality is common when monitoring these DMARDs, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored.

Wire- and magnetic-seed-guided localization of impalpable breast lesions: iBRA-NET localisation study.

BACKGROUND: Wire localization is historically the most common method for guiding excision of non-palpable breast lesions, but there are limitations to the technique. Newer technologies such as magnetic seeds may allow some of these challenges to be overcome. The aim was to compare safety and effectiveness of wire and magnetic seed localization techniques. METHODS: Women undergoing standard wire or magnetic seed localization for non-palpable lesions between August 2018 and August 2020 were recruited prospectively to this IDEAL stage 2a/2b platform cohort study. The primary outcome was effectiveness defined as accurate localization and removal of the index lesion. Secondary endpoints included safety, specimen weight and reoperation rate for positive margins. RESULTS: Data were accrued from 2300 patients in 35 units; 2116 having unifocal, unilateral breast lesion localization. Identification of the index lesion in magnetic-seed-guided (946 patients) and wire-guided excisions (1170 patients) was 99.8 versus 99.1 per cent (P = 0.048). There was no difference in overall complication rate. For a subset of patients having a single lumpectomy only for lesions less than 50 mm (1746 patients), there was no difference in median closest margin (2 mm versus 2 mm, P = 0.342), re-excision rate (12 versus 13 per cent, P = 0.574) and specimen weight in relation to lesion size (0.15 g/mm2versus 0.138 g/mm2, P = 0.453). CONCLUSION: Magnetic seed localization demonstrated similar safety and effectiveness to those of wire localization. This study has established a robust platform for the comparative evaluation of new localization devices.

No association between breast pain and breast cancer: a prospective cohort study of 10 830 symptomatic women presenting to a breast cancer diagnostic clinic.

BACKGROUND: Women with breast pain constitute >20% of breast clinic attendees. AIM: To investigate breast cancer incidence in women presenting with breast pain and establish the health economics of referring women with breast pain to secondary care. DESIGN AND SETTING: A prospective cohort study of all consecutive women referred to a breast diagnostic clinic over 12 months. METHOD: Women were categorised by presentation into four distinct clinical groups and cancer incidence investigated. RESULTS: Of 10 830 women, 1972 (18%) were referred with breast pain, 6708 (62%) with lumps, 480 (4%) with nipple symptoms, 1670 (15%) with 'other' symptoms. Mammography, performed in 1112 women with breast pain, identified cancer in eight (0.7%). Of the 1972 women with breast pain, breast cancer incidence was 0.4% compared with ∼5% in each of the three other clinical groups. Using 'breast lump' as reference, the odds ratio (OR) of women referred with breast pain having breast cancer was 0.05 (95% confidence interval = 0.02 to 0.09, P<0.001). Compared with reassurance in primary care, referral was more costly (net cost £262) without additional health benefits (net quality-adjusted life-year [QALY] loss -0.012). The greatest impact on the incremental cost-effectiveness ratio (ICER) was when QALY loss because of referral-associated anxiety was excluded. Primary care reassurance no longer dominated, but the ICER remained greater (£45 528/QALY) than typical UK National Health Service cost-effectiveness thresholds. CONCLUSION: This study shows that referring women with breast pain to a breast diagnostic clinic is an inefficient use of limited resources. Alternative management pathways could improve capacity and reduce financial burden.

The Impact of Radiotherapy on Patient-reported Outcomes of Immediate Implant-based Breast Reconstruction With and Without Mesh.

OBJECTIVE: To explore the impact of PMRT on PROs of IBBR performed with and without mesh. SUMMARY OF BACKGROUND DATA: PMRT is increasingly given to improve breast cancer outcomes but can adversely impact complications after IBBR.Little; however, is known about the impact of PMRT on the PROs of IBBR, especially when mesh is used. METHODS: The implant Breast Reconstruction evAluation prospective cohort study recruited consecutive women undergoing immediate IBBR from 81 UK breast and plastic surgical units. Demographic, operative, oncological, and 3-month complication data were collected, and patients consented to receive validated PRO questionnaires at 18-months. The association between IBBR, PMRT, and PROs were investigated using mixed-effects regression models adjusted for clinically-relevant confounders and including a random-effect to account for potential clustering by center. RESULTS: A total of 1163 women consented to receive 18-month questionnaires of whom 730 (63%) completed it. Patients undergoing PMRT (214 patients) reported worse PROs in 3 BREAST-Q domains: satisfaction with breasts [-6.27 points, P = 0.008, 95% confidence interval (CI) (-10.91, -1.63)], satisfaction with outcome [-7.53 points, P = 0.002, CI (-12.20, -2.85)] and physical well-being [-6.55 points, P < 0.001, CI (-9.43, -3.67)]. Overall satisfaction was worse in the PMRT group [OR 0.497, P = 0.002, CI (0.32, 0.77)]. These effects were not ameliorated by mesh use. CONCLUSIONS: PMRT may adversely affect PROs after IBBR irrespective of whether mesh is used. These findings should be discussed with all patients considering IBBR and when indications for PMRT are borderline to enable informed decision-making regarding oncological and reconstructive treatment options. TRIAL REGISTRATION: ISRCTN37664281.

Characterising risk of non-steroidal anti-inflammatory drug-related acute kidney injury: a retrospective cohort study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAID complications include acute kidney injury (AKI), causing burden to patients and health services through increased morbidity, mortality, and hospital admissions. AIM: To measure the extent of NSAID prescribing in an adult population, the degree to which patients with potential higher risk of AKI were exposed to NSAIDs, and to quantify their risk of AKI. DESIGN & SETTING: Retrospective 2-year closed-cohort study. METHOD: A retrospective cohort of adults was identified from a pseudonymised electronic primary care database in Hampshire, UK. The cohort had clinical information, prescribing data, and complete GP- and hospital-ordered biochemistry data. NSAID exposure (minimum one prescription in a 2-month period) was categorised as never, intermittent, and continuous, and first AKI using the national AKI e-alert algorithm. Descriptive statistics and logistic regression were used to explore NSAID prescribing patterns and AKI risk. RESULTS: The baseline population was 702 265. NSAID prescription fell from 19 364 (2.8%) to 16 251 (2.4%) over 2 years. NSAID prescribing was positively associated with older age, female sex, greater socioeconomic deprivation, and certain comorbidities (diabetes, hypertension, osteoarthritis, and rheumatoid arthritis) and negatively with cardiovascular disease (CVD) and heart failure. Among those prescribed NSAIDs, AKI was associated with older age, greater deprivation, chronic kidney disease (CKD), CVD, heart failure, diabetes, and hypertension. CONCLUSION: Despite generally good prescribing practice, NSAID prescribing was identified in some people at higher risk of AKI (for example, patients with CKD and older) for whom medication review and NSAID deprescribing should be considered.

A Novel Mixed-Methods Platform Study Protocol for Investigating New Surgical Devices, with Embedded Shared Learning: Ibra-net Breast Lesion Localisation Study.

INTRODUCTION: New medical devices must have adequate research, such that outcomes are known, enabling patients to be consented with knowledge of the safety and efficacy of the device to be implanted. Device trials are challenging due to the learning curve and iterative assessment of best practice. This study is designed to pilot a national collaborative approach to medical device introduction by breast surgeons in the UK, using breast localisation devices as an exemplar. The aim is to develop an effective and transferable surgical device platform protocol design, with embedded shared learning. METHODS AND ANALYSIS: The iBRA-net localisation study is a UK based prospective, multi-centre platform study, comparing the safety and efficacy of novel localisation devices with wire-guided breast lesion localisation for wide local excision, using Magseed® as the pilot intervention group. Centres performing breast lesion localisation for wide local excision or excision biopsy will be eligible to participate if using one of the included devices. Further intervention arms will be added as new devices are CE marked. Outcomes will be collected via an online database. The primary outcome measure will be identification of the index lesion. Participating surgeons will be asked to record shared learning events via online questionnaires and focus group interviews to inform future study arms. ETHICS AND DISSEMINATION: The study will aim to collect data on 950 procedures for each intervention (Magseed® and wire localisation) from UK breast centres over an 18-month period. Shared learning will be prospectively evaluated via thematic analysis to refine breast localisation technique and to promote early identification of potential pitfalls and problems. Results will be presented at national and international conferences and published in peer reviewed journals. REGISTRATION: This is a UK national audit registered with Manchester University NHS Foundation Trust. HIGHLIGHTS: This protocol outlines a novel methodology for a collaborative national platform study to collate safety and efficacy data on new medical devices. Improved registration and audit of new medical devices is a major theme of the Cumberlege report of the Independent Medicines and Medical Devices Safety Review.We outline a protocol for a UK based multi-centre prospective audit to investigate the safety and efficacy of new surgical devices for breast lesion localisation. The study will run as a platform study using wire localisation as a control group and Magseed® as the first intervention arm.The protocol is designed for additional bolt-on intervention arms for other localisation devices, such as Hologic Localizer™ and Savi Scout®, when they become available to the European market. This will enable comparison of these devices to datasets already collected on wire and Magseed® localisation.The study includes a novel shared learning methodology using iterative online database reporting and surgical interviews to centrally distribute information on learning events, critical governance issues and recommended protocols for future use.

The Angelina Jolie effect: Contralateral risk-reducing mastectomy trends in patients at increased risk of breast cancer.

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.

Feasibility of Using Strength Measures, Including Peak Inspiratory Flow, for Routine Monitoring in Case Management Patients Aged 65 and Over.

Peak inspiratory flow (PIF) is a portable, relatively new method for measuring respiratory function and indirect muscle strength; the feasibility of its routine clinical measurement is unknown. To investigate the acceptability, reliability and short-term stability of PIF, alongside the established measures of peak expiratory flow (PEF) and grip strength in community dwelling case management patients. Patients were tested in a sitting position, initially on two occasions, one week apart; seven patients having repeated measures taken on a further four occasions over a seven-week period. The best of three attempts for all measures were recorded. Reliability was tested using intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimal detectable change (MDC) and Bland-Altman analysis. Eight patients aged 69-91 years (mean age 81.5 ± 7.7 years; 5 males) participated. For between-day reliability using the first two time points, one week apart the ICCs (3,1) were 0.97, 0.98 and 0.99 for PIF, PEF and grip strength respectively; using all five time points resulted in ICCs of 0.92, 0.99 and 0.99 respectively. Bland-Altman plots also illustrated a good level of agreement across days. Feedback on the acceptability of the measures was gathered from patients. PIF, PEF and grip strength showed excellent reliability and acceptability. Whilst excellent reliability was observed over the seven-week period, the occurrence of clinically significant symptoms and adverse events in the presence of unchanging PIF, PEF and grip strength, suggests that the measures may not be suitable to identify patients with multiple health conditions entering a period of acute decline.

Do surgical margins matter after mastectomy? A systematic review.

BACKGROUND: No consensus exists regarding adequacy of margins after mastectomy. To determine if pathological margin proximity is associated with local (LR) or distant recurrence after mastectomy for early invasive breast cancer or ductal carcinoma in situ. METHODS: A systematic review of literature published from 1980 to 2019 and meta-analysis was conducted. Unpublished data were sought from authors (PROSPERO (CRD42019127541)). Thirty-four studies comprising 34,833 breast cancer patients were included in the quantitative synthesis. Eligible studies reported on patients undergoing curative mastectomy for cancer allowing estimation of outcomes in relation to margin status/width. The association between pathological margin status and local (LR) and distant recurrence was considered using random effects modelling. PRISMA guidelines were followed. RESULTS: Positive margins were associated with increased LR on multivariable analyses (HR, 2·64, (95%CI 2·01-3·46)) and LR was higher regardless of the distance of tumour from the margin defined as positive. After skin-sparing mastectomy, positive margins were associated with increased LR (HR 3·40, (95%CI 1·9-6·2)). In the 4 studies reporting distant recurrence, patients with involved margins had a higher risk (HR 1·53, (95%CI 1·03-2·25)). CONCLUSIONS: Failure to achieve clear margins after mastectomy may increase the risks of local and distant recurrence. Adequate margin clearance should be recommended to minimize recurrence after mastectomy in National and International Guidelines.

Provision of Bilingual Dispensing Labels to Non-Native English Speakers: An Exploratory Study.

Patients with limited English proficiency living in the U.K. receive prescribed medication labels in English. These patients are at risk of worse health outcomes compared with the general population. This article describes a service evaluation of the use of bilingual dispensing labels to facilitate patient understanding of medicine administration instructions. Recruited patients answered two questionnaires to assess engagement with and understanding of their medicine labels. The first was completed at the point of dispensing, and the second within six weeks. Questionnaires were either self-completed or via facilitation over the telephone. A total of 151 participants completed the first questionnaire, and 130 completed the follow-up. Key findings highlighted the lack of engagement by participants with English-language labels and their reliance on asking for help from pharmacy staff, friends, or family to understand the information. However, when provided with information in their preferred language, they reported high levels of understanding and sought help less frequently from a third party. This study has shown that this service has improved understanding of labelling information in this target group.

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study.

BACKGROUND: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. METHODS: Consecutive women undergoing mastectomy ± IBR for breast cancer July-December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. RESULTS: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. CONCLUSIONS: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients.

Short-term safety outcomes of mastectomy and immediate implant-based breast reconstruction with and without mesh (iBRA): a multicentre, prospective cohort study.

BACKGROUND: Use of biological or synthetic mesh might improve outcomes of immediate implant-based breast reconstruction-breast reconstruction with implants or expanders at the time of mastectomy-but there is a lack of high-quality evidence to support the safety or effectiveness of the technique. We aimed to establish the short-term safety of immediate implant-based breast reconstruction performed with and without mesh, to inform the feasibility of undertaking a future randomised clinical trial comparing different breast reconstruction techniques. METHODS: In this prospective, multicentre cohort study, we consecutively recruited women aged 16 years or older who had any type of immediate implant-based breast reconstruction for malignancy or risk reduction, with any technique, at 81 participating breast and plastic surgical units in the UK. Data about patient demographics and operative, oncological, and complication details were collected before and after surgery. Outcomes of interest were implant loss (defined as unplanned removal of the expander or implant), infection requiring treatment with antibiotics or surgery, unplanned return to theatre, and unplanned re-admission to hospital for complications of reconstructive surgery, up to 3 months after reconstruction and assessed by clinical review or patient self-report. Follow-up is complete. The study is registered with the ISRCTN Registry, number ISRCTN37664281. FINDINGS: Between Feb 1, 2014, and June 30, 2016, 2108 patients had 2655 mastectomies with immediate implant-based breast reconstruction at 81 units across the UK. 1650 (78%) patients had planned single-stage reconstructions (including 12 patients who had a different technique per breast). 1376 (65%) patients had reconstruction with biological (1133 [54%]) or synthetic (243 [12%]) mesh, 181 (9%) had non-mesh submuscular or subfascial implants, 440 (21%) had dermal sling implants, 42 (2%) had pre-pectoral implants, and 79 (4%) had other or a combination of implants. 3-month outcome data were available for 2081 (99%) patients. Of these patients, 182 (9%, 95% CI 8-10) experienced implant loss, 372 (18%, 16-20) required re-admission to hospital, and 370 (18%, 16-20) required return to theatre for complications within 3 months of their initial surgery. 522 (25%, 95% CI 23-27) patients required treatment for an infection. The rates of all of these complications are higher than those in the National Quality Standards (<5% for re-operation, re-admission, and implant loss, and <10% for infection). INTERPRETATION: Complications after immediate implant-based breast reconstruction are higher than recommended by national standards. A randomised clinical trial is needed to establish the optimal approach to immediate implant-based breast reconstruction. FUNDING: National Institute for Health Research, Association of Breast Surgery, and British Association of Plastic, Reconstructive and Aesthetic Surgeons.

The Near-Term Viability and Benefits of eLabels for Patients, Clinical Sites, and Sponsors.

BACKGROUND: Current clinical trial labels are designed primarily to meet regulatory requirements. These labels have low patient and site utility, few are opened, and they have limited space and small fonts. As our world transitions from paper to electronic, an opportunity exists to provide patients with information about their investigational clinical trial product in a way that is more easily accessible, meets Health Authority requirements, and provides valuable additional information for the patient and caregiver. METHODS: A TransCelerate initiative was launched to understand the current regulatory and technology landscape for the potential use an electronic label (eLabel) for investigational medicinal products (IMPs). Concepts and an example proof of concept were developed intended to show the "art of the possible" for a foundational eLabel and a "universal printed label." In addition, possible patient-centric enhancements were captured in the eLabel proof of concept. These concepts were shared with Health Authorities as well as patient and site advisory groups to gather feedback and subsequently enhance the concepts. RESULTS: Feedback indicated that the concept of an eLabel provides value and concepts should continue to be pursued. While the Health Authorities engaged with did not express issues with the use of an eLabel per se, the reduction in the content on the paper label is not possible in some geographic locations due to existing regulations. CONCLUSIONS: There is nothing that prevents transmitting the label electronically in conjunction with current conventional labeling. While there are still some regulatory barriers that need to be addressed for reducing what is on the paper label, advancement toward a more patient-centric approach benefits stakeholders and will enable a fully connected patient-centric experience. The industry must start now to build the foundation.

Adherence to best practice consensus guidelines for implant-based breast reconstruction: Results from the iBRA national practice questionnaire survey.

INTRODUCTION: The 2008 National Mastectomy and Breast Reconstruction Audit demonstrated marked variation in the practice and outcomes of breast reconstruction in the UK. To standardise practice and improve outcomes for patients, the British professional associations developed best-practice guidelines with specific guidance for newer mesh-assisted implant-based techniques. We explored the degree of uptake of best-practice guidelines within units performing implant-based reconstruction (IBBR) as the first phase of the implant Breast Reconstruction Evaluation (iBRA) study. METHODS: A questionnaire developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Simple summary statistics were calculated for each survey item to assess compliance with current best-practice guidelines. RESULTS: 81 units from 79 NHS Trusts completed the questionnaire. Marked variation was observed in adherence to guidelines, especially those relating to clinical governance and infection prevention strategies. Less than half (n = 28, 47%) of units obtained local clinical governance board approval prior to offering new mesh-based techniques and prospective audit of the clinical, cosmetic and patient-reported outcomes of surgery was infrequent. Most units screened for methicillin-resistant staphylococcus aureus prior to surgery but fewer than 1 in 3 screened for methicillin-sensitive strains. Laminar-flow theatres (recommended for IBBR) were not widely-available with less than 1 in 5 units having regular access. Peri-operative antibiotics were widely-used, but the type and duration were highly-variable. CONCLUSIONS: The iBRA national practice questionnaire has demonstrated variation in reported practice and adherence to IBBR guidelines. High-quality evidence is urgently required to inform best practice.

Clinical management of idiopathic mastalgia: a systematic review.

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.

Seizure and cognitive outcomes after resection of glioneuronal tumors in children.

OBJECTIVE: Glioneuronal tumors (GNTs) are well-recognized causes of chronic drug-resistant focal epilepsy in children. Our practice involves an initial period of radiological surveillance and antiepileptic medications, with surgery being reserved for those with radiological progression or refractory seizures. We planned to analyze the group of patients with low-grade GNTs, aiming to identify factors affecting seizure and cognitive outcomes. METHODS: We retrospectively reviewed the medical records of 150 children presenting to Great Ormond Street Hospital with seizures secondary to GNTs. Analysis of clinical, neuroimaging, neuropsychological, and surgical factors was performed to determine predictors of outcome. Seizure outcome at final follow-up was classified as either seizure-free (group A) or not seizure-free (group B) for patients with at least 12-months follow-up postsurgery. Full-scale intelligence quotient (FSIQ) was used as a measure of cognitive outcome. RESULTS: Eighty-six males and 64 females were identified. Median presurgical FSIQ was 81. One hundred twenty-one patients (80.5%) underwent surgery. Median follow-up after surgery was 2 years, with 92 patients (76%) having at least 12 months of follow-up after surgery. Seventy-four patients (80%) were seizure-free, and 18 (20%) continued to have seizures. Radiologically demonstrated complete tumor resection was associated with higher rates of seizure freedom (P = .026). Higher presurgical FSIQ was related to shorter epilepsy duration until surgery (P = .012) and to older age at seizure onset (P = .043). SIGNIFICANCE: A high proportion of children who present with epilepsy and GNTs go on to have surgical tumor resection with excellent postoperative seizure control. Complete resection is associated with a higher chance of seizure freedom. Higher presurgical cognitive functioning is associated with shorter duration of epilepsy prior to surgery and with older age at seizure onset. Given the high rate of eventual surgery, early surgical intervention should be considered in children with continuing seizures associated with GNTs.