Recent Submissions

  • Cohort profile of the Sloane Project: methodology for a prospective UK cohort study of >15 000 women with screen-detected non-invasive breast neoplasia.

    Stevens-Harris, I; Sibbering, Mark
    PURPOSE: The introduction of breast screening in the UK led to an increase in the detection of non-invasive breast neoplasia, predominantly ductal carcinoma in situ (DCIS), a non-obligatory precursor of invasive breast cancer. The Sloane Project, a UK prospective cohort study of screen-detected non-invasive breast neoplasia, commenced in 2003 to evaluate the radiological assessment, surgical management, pathology, adjuvant therapy and outcomes for non-invasive breast neoplasia. Long-term follow-up and accurate data collection are essential to examine the clinical impact. Here, we describe the establishment, development and analytical processes for this large UK cohort study. PARTICIPANTS: Women diagnosed with non-invasive breast neoplasia via the UK National Health Service Breast Screening Programme (NHSBSP) from 01 April 2003 are eligible, with a minimum age of 46 years. Diagnostic, therapeutic and follow-up data collected via proformas, complement date and cause of death from national data sources. Accrual for patients with DCIS ceased in 2012 but is ongoing for patients with epithelial atypia/in situ neoplasia, while follow-up for all continues long term. FINDINGS TO DATE: To date, patients within the Sloane cohort comprise one-third of those diagnosed with DCIS within the NHSBSP and are representative of UK practice. DCIS has a variable outcome and confirms the need for longer-term follow-up for screen-detected DCIS. However, the radiology and pathology features of DCIS can be used to inform patient management. We demonstrate validation of follow-up information collected from national datasets against traditional, manual methods. FUTURE PLANS: Conclusions derived from the Sloane Project are generalisable to women in the UK with screen-detected DCIS. The follow-up methodology may be extended to other UK cohort studies and routine clinical follow-up. Data from English patients entered into the Sloane Project are available on request to researchers under data sharing agreement. Annual follow-up data collection will continue for a minimum of 20 years.
  • A systematic review and meta-analysis on delaying surgery for urothelial carcinoma of bladder and upper tract urothelial carcinoma: Implications for the COVID19 pandemic and beyond.

    Chan, VW
    PURPOSE: The COVID-19 pandemic has led to competing strains on hospital resources and healthcare personnel. Patients with newly diagnosed invasive urothelial carcinomas of bladder (UCB) upper tract (UTUC) may experience delays to definitive radical cystectomy (RC) or radical nephro-ureterectomy (RNU) respectively. We evaluate the impact of delaying definitive surgery on survival outcomes for invasive UCB and UTUC. METHODS: We searched for all studies investigating delayed urologic cancer surgery in Medline and Embase up to June 2020. A systematic review and meta-analysis was performed. RESULTS: We identified a total of 30 studies with 32,591 patients. Across 13 studies (n = 12,201), a delay from diagnosis of bladder cancer/TURBT to RC was associated with poorer overall survival (HR 1.25, 95% CI: 1.09-1.45, p = 0.002). For patients who underwent neoadjuvant chemotherapy before RC, across the 5 studies (n = 4,316 patients), a delay between neoadjuvant chemotherapy and radical cystectomy was not found to be significantly associated with overall survival (pooled HR 1.37, 95% CI: 0.96-1.94, p = 0.08). For UTUC, 6 studies (n = 4,629) found that delay between diagnosis of UTUC to RNU was associated with poorer overall survival (pooled HR 1.55, 95% CI: 1.19-2.02, p = 0.001) and cancer-specific survival (pooled HR of 2.56, 95% CI: 1.50-4.37, p = 0.001). Limitations included between-study heterogeneity, particularly in the definitions of delay cut-off periods between diagnosis to surgery. CONCLUSIONS: A delay from diagnosis of UCB or UTUC to definitive RC or RNU was associated with poorer survival outcomes. This was not the case for patients who received neoadjuvant chemotherapy.
  • Reporting of Surgically Removed Lymph Nodes for Breast Tumors: Recommendations From the International Collaboration on Cancer Reporting.

    Deb, Rahul
    CONTEXT.—: The International Collaboration on Cancer Reporting (ICCR), supported by major pathology and cancer organizations, aims at the standardization of evidence-based pathology reporting of different types of cancers, with the inclusion of all parameters deemed to be relevant for best patient care and future data collection. Lymph node metastasis is one of the most important prognostic factors in breast cancer. OBJECTIVE.—: To produce a histopathology reporting guide by a panel of recognized experts from the fields of pathology and surgery with elements deemed to be core (required) and noncore (recommended) to report when assessing regional lymph nodes of patients with breast cancer. DATA SOURCES.—: Published literature, previous guidelines/recommendations, and current cancer staging principles were the basis of the data set drafted by the expert panel. This was discussed in a series of teleconferences and email communications. The draft data set was then made available for public consultation through the ICCR Web site. After this consultation and ICCR ratification, the data set was finalized. CONCLUSIONS.—: The ICCR has published a data set for the reporting of surgically removed lymph nodes (including sentinel lymph node biopsy, axillary lymph node dissection, targeted axillary surgery, and lymph node sampling specimens) for breast tumors. This is part of a series of 4 ICCR breast cancer-related data sets. It includes 10 core elements along with 2 noncore elements. This should allow for synoptic reporting, which is more precise, uniform, and complete than nonsynoptic reporting, and leads to improved patient outcomes.
  • Effectiveness of telemedicine in outpatient parenteral antimicrobial therapy (Tele-OPAT): A systematic review.

    Durojaiye, OC
    INTRODUCTION: Telemedicine is increasingly used to deliver healthcare in many clinical specialities. However, the adoption of telemedicine in the delivery of outpatient parenteral antimicrobial therapy (OPAT) has been relatively slow and limited. This study aims to collate current evidence for telemedicine in OPAT regarding clinical efficacy, safety, acceptability and cost-effectiveness. METHODS: We systematically searched the Cochrane Library, CINAHL, EMCARE, EMBASE and MEDLINE databases through 24 July 2022, for relevant studies published in English. Research articles and conference abstracts were included if they involved any form of telephone or video consultation in delivering parenteral antibiotics in the home or outpatient setting. Study findings were synthesised into three main themes: patient outcomes and safety, patient and provider satisfaction and cost-effectiveness. The mixed methods appraisal tool was used to review the methodological quality of the studies. PROSPERO CRD42022342874. RESULTS: The literature search yielded 311 articles, of which 12 (five full-length articles and seven conference abstracts) reporting over 1245 telemedicine interventions were reviewed. The reported outcomes were heterogeneous. Telemedicine was cost-effective and associated with high patient satisfaction and comparable complication rates compared to conventional OPAT. Considering six comparative studies, rehospitalisation risk was lower for telemedicine than conventional OPAT (risk ratio, 0.58; 95% confidence interval, 0.38-0.88; I2  =  31%). DISCUSSION: The results of this review demonstrate that telemedicine has a role in delivering safe and cost-effective OPAT care, especially for patients residing in remote and geographically isolated locations. Nevertheless, high-quality studies and publication of existing data and experiences are needed to further validate this model of care delivery.
  • The BAC recommended code of practice for cytology laboratories participating in the United Kingdom cervical screening programmes (2022) - a new edition for a new decade.

    Cropper, Alison
    The last update of the British Association for Cytopathology (BAC) code of practice (CoP) was published in 2017, since when there have been such significant changes to the UK cervical screening programmes (CSPs) in, most notably the implementation of primary screening for high-risk Human Papilloma Virus (hrHPV), that a major revision is required. Previous versions of the CoP have provided a valuable resource for cytology laboratories and other key stakeholders, and it is hoped that this latest edition will continue to do so.
  • The correlation between pre-treatment symptoms, acute and late toxicity and patient-reported health-related quality of life in non-small cell lung cancer patients: Results of the REQUITE study.

    Ennis, Dawn
    BACKGROUND AND PURPOSE: To investigate the association between clinician-scored toxicities and patient-reported health-related quality of life (HRQoL), in early-stage (ES-) and locally-advanced (LA-) non-small cell lung cancer (NSCLC) patients receiving loco-regional radiotherapy, included in the international real-world REQUITE study. MATERIALS AND METHODS: Clinicians scored eleven radiotherapy-related toxicities (and baseline symptoms) with the Common Terminology Criteria for Adverse Events version 4. HRQoL was assessed with the European Organization for Research and Treatment of Cancer core HRQoL questionnaire (EORTC-QLQ-C30). Statistical analyses used the mixed-model method; statistical significance was set at p=0.01. Analyses were performed for baseline and subsequent time points up to 2 years after radiotherapy and per treatment modality, radiotherapy technique and disease stage. RESULTS: Data of 435 patients were analysed. Pre-treatment, overall symptoms, dyspnea, chest wall pain, dysphagia and cough impacted overall HRQoL and specific domains. At subsequent time points, cough and dysphagia were overtaken by pericarditis in affecting HRQoL. Toxicities during concurrent chemo-radiotherapy and 3-dimensional radiotherapy had the most impact on HRQoL. Conversely, toxicities in sequential chemo-radiotherapy and SBRT had limited impact on patients' HRQoL. Stage impacts the correlations: LA-NSCLC patients are more adversely affected by toxicity than ES-NSCLC patients, mimicking the results of radiotherapy technique and treatment modality. CONCLUSION: Pre-treatment symptoms and acute/late toxicities variously impact HRQoL of ES- and LA-NSCLC patients undergoing different treatment approaches and radiotherapy techniques. Throughout the disease, dyspnea seems crucial in this association, highlighting the additional effect of co-existing comorbidities. Our data call for optimized radiotherapy limiting toxicities that may affect patients' HRQoL.
  • Does the character of the hospital of primary management influence outcomes in patients treated for presumed early stage endometrial cancer and atypical endometrial hyperplasia: a comparison of outcomes from a cancer unit and cancer centre.

    McGowan, Mark; Addley, Susan; Davies, Jason; Shaikh, Abdul; Asher, Viren; Bali, Anish; Phillips, A
    A retrospective study from 2015 to 2020 comparing overall survival (OS) outcomes of a cancer unit and centre for presumed early stage endometrial cancers is presented. Cancer centres manage these presumed early endometrial cancer (EC) in situations of complex co-morbidities, surgical challenges as well as their own local unit patients. Our analysis compares 138 patients at KMH (unit) and 282 patients at RDH (centre) on OS, patient demographics, grading histology and final histology. Patients with presumed early stage EC can be reassured regarding no difference in OS between the cancer unit and centre management (p = .05). However, rates of minimal access surgery were higher at the cancer centre compared to the unit (93.2% versus 68.1%). The rates of upstaged disease were 4% and 8.8% at the cancer unit and centre respectively (p = .096). Sentinel node biopsy and genomic assessment may change future thresholds for centre-level management due to rates of upstaged disease.Impact StatementWhat is already known on this subject? Presumed lower risk endometrial cancers (endometrioid grades 1 and 2) have a rate of occult nodal involvement of only 1.4%. The BGCS does not recommend lymphadenectomy for low-risk endometrial cancers. These low-risk endometrial cancers should be managed with a hysterectomy and bilateral salpingo-ophrectomy via minimal access surgery. In view of the low rates of occult nodal involvement in low-risk endometrial cancer, surgery can be offered at a cancer unit.What do the results of this study add? Our study demonstrates there is no disadvantage in overall survival in the surgical management of presumed low-risk endometrial cancers at cancer units and centres. However, cancer centres have higher rates of minimal access to surgery despite managing a more elderly population. Our rates of upstaged disease of 4% and 8.8% at the cancer unit and centre indicate a potential benefit of pelvic lymph node assessment.What are the implications of these findings for clinical practice and/or further research? Sentinel lymph node biopsy does not have the surgical morbidity associated with systematic lymph node dissection. Therefore, when applied to presumed early stage endometrial cancer, there are potential changes in the threshold for centre-level management to improve overall survival.
  • Cancer multidisciplinary team meetings: impact of logistical challenges on communication and decision-making.

    Bali, Anish; Asher, Viren
    BACKGROUND: Multidisciplinary teams (MDTs) are widely used in cancer care. Recent research points to logistical challenges impeding MDT decision-making and dissatisfaction among members. This study sought to identify different types of logistical issues and how they impacted team processes. METHODS: This was a secondary analysis of a cross-sectional observational study. Three cancer MDTs (breast, colorectal, and gynaecological) were recruited from UK hospitals. Validated observational instruments were used to measure decision-making (Metrics of Observational Decision-making, MDT-MODe), communication (Bales' Interaction Process Analysis, Bales' IPA), and case complexity (Measure of Case Discussion Complexity, MeDiC), including logistical challenges (Measure of Case Discussion Complexity, MeDiC), across 822 case discussions from 30 videoed meetings. Descriptive analysis and paired samples t tests were used to identify and compare frequency of different types of logistical challenges, along with partial correlations, controlling for clinical complexity of cases, to understand how such issues related to the MDT decision-making and communication. RESULTS: A significantly higher frequency of administrative and process issues (affecting 30 per cent of cases) was seen compared with the frequency of equipment issues (affecting 5 per cent of cases; P < 0.001) and the frequency of the attendance issues (affecting 16 per cent of cases; P < 0.001). The frequency of the attendance issues was significantly higher than the frequency of equipment issues (P < 0.001). Partial correlation analysis revealed that administrative and process issues, including attendance, were negatively correlated with quality of information (r = -0.15, P < 0.001; r = -0.11, P < 0.001), and equipment issues with the quality of contribution to meeting discussion (r = -0.14, P < 0.001). More questioning and answering by MDT members was evident with the administrative and process issues (r = 0.21, P < 0.001; r = 0.19, P < 0.001). Some differences were observed in teams' socioemotional reactions to the administrative and process issues with the gynaecological MDT showing positive correlation with positive socioemotional reactions (r = 0.20, P < 0.001), and the breast cancer MDT with negative socioemotional reactions (r = 0.17, P < 0.001). CONCLUSION: Administrative and process issues were the most frequent logistical challenges for the studied teams. Where diagnostic results were unavailable, and inadequate patient details provided, the quality of decision-making was reduced.
  • Fibroepithelial lesions of the breast: Improving the accuracy of imaging diagnosis and reducing unnecessary biopsy.

    Evans, Andrew; Jethwa, K
    Fibroadenomas and phyllodes tumours are fibroepithelial lesions of the breast. Fibroadenomas are common benign breast masses encountered both symptomatically and incidentally. Phyllodes tumours are uncommon and usually present symptomatically. Management of fibroadenomas focuses on reducing biopsies without missing cancers while radiological management of phyllodes tumours should focus on predicting the need for surgical excision with or without margins.
  • What Is the Most Effective Management of the Primary Tumor in Men with Invasive Penile Cancer: A Systematic Review of the Available Treatment Options and Their Outcomes.

    Kailavasan, Mithun
    CONTEXT: The primary lesion in penile cancer is managed by surgery or radiation. Surgical options include penile-sparing surgery, amputative surgery, laser excision, and Moh's micrographic surgery. Radiation is applied as external beam radiotherapy (EBRT) and brachytherapy. The treatment aims to completely remove the primary lesion and preserve a sufficient functional penile stump. OBJECTIVE: To assess whether the 5-yr recurrence-free rate and other outcomes, such as sexual function, quality of life, urination, and penile preserving length, vary between various treatment options. EVIDENCE ACQUISITION: The EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane HTA, DARE, HEED), Google Scholar, and ClinicalTrials.gov were searched for publications from 1990 through May 2021. Randomized controlled trials, nonrandomized comparative studies (NRCSs), and case series (CSs) were included. EVIDENCE SYNTHESIS: The systematic review included 88 studies, involving 9578 men from 16 NRCSs and 72 CSs. The cumulative mean 5-yr recurrence-free rates were 82.0% for penile-sparing surgery, 83.9% for amputative surgery, 78.6% for brachytherapy, 55.2% for EBRT, 69.4% for lasers, and 88.2% for Moh's micrographic surgery, as reported from CSs, and 76.7% for penile-sparing surgery and 93.3% for amputative surgery, as reported from NRCSs. Penile surgery affects sexual function, but amputative surgery causes more appearance concerns. After brachytherapy, 25% of patients reported sexual dysfunction. Both penile-sparing surgery and amputative surgery affect all aspects of psychosocial well-being. CONCLUSIONS: Despite the poor quality of evidence, data suggest that penile-sparing surgery is not inferior to amputative surgery in terms of recurrence rates in selected patients. Based on the available information, however, broadly applicable recommendations cannot be made; appropriate patient selection accounts for the relative success of all the available methods. PATIENT SUMMARY: We reviewed the evidence of various techniques to treat penile tumor and assessed their effectiveness in oncologic control and their functional outcomes. Penile-sparing as well as amputative surgery is an effective treatment option, but amputative surgery has a negative impact on sexual function. Penile-sparing surgery and radiotherapy are associated with a higher risk of local recurrence, but preserve sexual function and quality of life better. Laser and Moh's micrographic surgery could be used for smaller lesions.
  • Retrospective analysis of outcomes of outpatient parenteral antimicrobial therapy (OPAT) for necrotising otitis externa.

    Slucka, A
    Necrotising otitis externa (NOE) is an uncommon but life-threatening infection that requires prolonged systemic antimicrobial therapy. This study aims to identify factors associated with treatment response and outcome in patients with NOE treated through outpatient parenteral antimicrobial therapy (OPAT). We performed a retrospective analysis of patients with NOE treated over a 4-year period (January 2018-January 2022) at a tertiary referral hospital in Derbyshire, UK. We defined OPAT failure as unplanned readmission within 30 days of discontinuation of OPAT. Prolonged duration of therapy was defined as length of parenteral antimicrobial treatment of more than 8 weeks. A total of 46 cases of NOE were reviewed. OPAT failure and prolonged therapy were recorded in 9 (19.6%) and 23 (50.0%) episodes respectively. Facial nerve involvement (odds ratio [OR], 14.54; 95% confidence interval [CI], 2.76-76.60; p = 0.002), dementia (OR, 7.65; 95% CI, 1.23-47.46; p = 0.029), Charlson comorbidity score (OR, 1.41 per unit increase; 95% CI, 1.00-2.00; p = 0.049) and peak CRP level (OR, 1.03 per unit increase; 95% CI, 1.00-1.06; p = 0.027) were associated with increased risk of treatment failure. Facial nerve involvement (OR, 16.30; 95% CI, 2.60-102.31; p = 0.003) and peak CRP level (OR, 1.04; 95% CI, 1.01-1.07; p = 0.016) were also associated with an increased need for prolonged antimicrobial therapy. In addition, extent of disease (based on imaging findings) was linked to prolonged therapy (OR, 22.89; 95% CI, 3.62-144.76; p = 0.001). NOE could be effectively managed as outpatient via OPAT. However, vigorous antimicrobial treatment and close monitoring of patients with pre-existing comorbidities, facial nerve paralysis, extensive disease and markedly elevated inflammatory markers are essential to optimise clinical outcomes.
  • Lactate Is a Reliable Predictor of ICU Length of Stay Following Ultra-radical Ovarian Cancer Surgery.

    Addley, Susan; McGowan, Mark; Asher, Viren; Bali, Anish; Abdul, Summi; Cullimore, Victoria; Crossland, Harriet; Phillips, Andrew
    BACKGROUND/AIM: With a greater proportion of women with advanced ovarian cancer (AOC) successfully undergoing radical cytoreductive surgery, the demand on peri-operative resources - including intensive care (ICU) beds - is also on the rise. Extended post-operative ICU length of stay (LOS) confers increased patient morbidity and mortality. Several variables associated with prolonged ICU LOS following AOC surgery have been identified. We aimed to evaluate the predictive value of serum lactate levels. PATIENTS AND METHODS: All patients undergoing ultra-radical surgery for AOC in a large cancer centre over a 34-month period between 2018-2021 were identified via the institution tumour registry. Data were collected retrospectively via electronic care and operating records; biochemistry, radiology, and histopathology databases. RESULTS: In total, 63 patients were identified. Elevated intra-operative serum lactate levels were associated with significantly longer length of ICU post-operative stay. Longer time for hyperlactaemia to normalise following surgery also conferred significantly longer ICU, high dependency and total hospital LOS. Greater blood loss, higher surgical complexity and peritoneal carcinomatosis score, and longer operating time were associated with higher - and persistently elevated - peri-operative lactate levels. CONCLUSION: Serum lactate in the context of ultra-radical surgery for AOC represents an accessible and inexpensive marker with potential to not only reliably predict LOS, but also to serve as a dynamic prompt for early targeted intervention. Early recognition and correction of hyperlactaemia following AOC may reduce ICU LOS limiting both the resource pressure and patient morbidity/mortality sequelae.
  • Safety Learning in Anxiety, Pavlovian Conditioned Inhibition and COVID Concerns.

    Thurston, Meghan
    Experimental studies of fear conditioning have identified the effectiveness of safety signals in inhibiting fear and maintaining fear-motivated behaviors. In fear conditioning procedures, the presence of safety signals means that the otherwise expected feared outcome will not now occur. Differences in the inhibitory learning processes needed to learn safety are being identified in various psychological and psychiatric conditions. However, despite early theoretical interest, the role of conditioned inhibitors as safety signals in anxiety has been under-investigated to date, in part because of the stringent test procedures required to confirm the demonstration of conditioned inhibition as such. Nonetheless, the theoretical implications of an inhibitory learning perspective continue to influence clinical practice. Moreover, our understanding of safety signals is of additional importance in the context of the increased health anxiety and safety behaviors generated by the COVID-19 pandemic.
  • International physical therapists consensus on clinical descriptors for diagnosing rotator cuff related shoulder pain: A Delphi study

    Bateman, Marcus
    BACKGROUND: There is a lack of standardized criteria for diagnosing rotator cuff related shoulder pain (RCRSP). OBJECTIVE: To identify the most relevant clinical descriptors for diagnosing RCRSP. METHODS: A Delphi study was conducted through use of an international physical therapists expert panel. A 3-round Delphi survey involving an international panel of physical therapists experts with extensive clinical, teaching, and research experience was conducted. A search query was performed in Web of Science, along with a manual search, to find the experts. The first round was composed of items obtained from a previous pilot Delphi study along with new items proposed by the experts. Participants were asked to rate items across six clinical domains using a five-point Likert scale. An Aiken's Validity Index ≥ 0.7 was considered indicative of group consensus. RESULTS: Fifteen experts participated in the Delphi survey. After the three rounds, consensus was reached on 18 clinical descriptors: 10 items were included in the "subjective examination" domain, 1 item was included in the "patient-reported outcome measures" domain, 3 items in the "diagnostic examination" domain, 2 items in the "physical examination" domain", and 2 items in the "functional tests" domain. No items reached consensus within the "special tests" domain. The reproduction of symptoms in relation to the application of load, the performance of overhead activities, and the need of active and resisted movement assessment were some of the results with greatest consensus. CONCLUSION: In this Delphi study, a total of 18 clinical descriptors across six clinical domains were agreed upon for diagnosing RCRSP.
  • Overview of health-related quality of life and toxicity of non-small cell lung cancer patients receiving curative-intent radiotherapy in a real-life setting (the REQUITE study).

    Ennis, Dawn
    OBJECTIVES: Radiotherapy-induced toxicity may negatively impact health-related quality of life (HRQoL). This report investigates the impact of curative-intent radiotherapy on HRQoL and toxicity in early stage and locally-advanced non-small cell lung cancer patients treated with radiotherapy or chemo-radiotherapy enrolled in the observational prospective REQUITE study. MATERIALS AND METHODS: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire up to 2 years post radiotherapy. Eleven toxicities were scored by clinicians using the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Toxicity scores were calculated by subtracting baseline values. Mixed model analyses were applied to determine statistical significance (p ≤ 0.01). Meaningful clinical important differences (MCID) were determined for changes in HRQoL. Analysis was performed on the overall data, different radiotherapy techniques, multimodality treatments and disease stages. RESULTS: Data of 510 patients were analysed. There was no significant change in HRQoL or its domains, except for deterioration in cognitive functioning (p = 0.01). Radiotherapy technique had no significant impact on HRQoL. The addition of chemotherapy was significantly associated with HRQoL over time (p <.001). Overall toxicity did not significantly change over time. Acute toxicities of radiation-dermatitis (p =.003), dysphagia (p =.002) and esophagitis (p <.001) peaked at 3 months and decreased thereafter. Pneumonitis initially deteriorated but improved significantly after 12 months (p =.011). A proportion of patients experienced meaningful clinically important improvements and deteriorations in overall HRQoL and its domains. In some patients, pre-treatment symptoms improved gradually. CONCLUSIONS: While overall HRQoL and toxicity did not change over time, some patients improved, whereas others experienced acute radiotherapy-induced toxicities and deteriorated HRQoL, especially physical and cognitive functioning. Patient characteristics, more so than radiotherapy technique and treatment modality, impact post-radiotherapy toxicity and HRQoL outcomes. This stresses the importance of considering the potential impact of radiotherapy on individuals' HRQoL, symptoms and toxicity in treatment decision-making.
  • Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.

    Das, P
    BACKGROUND: Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS: These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial]
  • Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts.

    Keeley, Vaughan (2021-12)
    BACKGROUND: Primary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, 'WILD syndrome' (Warts, Immunodeficiency, Lymphoedema and anogenital Dysplasia), have previously depended on a single case report. METHODS AND RESULTS: We present 21 patients (including the first described case) with similar clinical and immunological phenotypes. All had PL affecting multiple segments, with systemic involvement (intestinal lymphangiectasia/pleural or pericardial effusions) in 70% (n=14/20). Most (n=20, 95%) had a distinctive cutaneous lymphovascular malformation on the upper anterior chest wall. Some (n=10, 48%) also had hyperpigmented lesions resembling epidermal naevi (but probably lymphatic in origin). Warts were common (n=17, 81%) and often refractory. In contrast to the previous case report, anogenital dysplasia was uncommon-only found in two further cases (total n=3, 14%). Low CD4 counts and CD4:CD8 ratios typified the syndrome (17 of 19, 89%), but monocyte counts were universally normal, unlike GATA2 deficiency. CONCLUSION: WILD syndrome is a previously unrecognised, underdiagnosed generalised PL syndrome. Based on this case series, we redefine WILD as 'Warts, Immunodeficiency, andLymphatic Dysplasia' and suggest specific diagnostic criteria. The essential criterion is congenital multisegmental PL in a 'mosaic' distribution. The major diagnostic features are recurrent warts, cutaneous lymphovascular malformations, systemic involvement (lymphatic dysplasia), genital swelling and CD4 lymphopaenia with normal monocyte counts. The absence of family history suggests a sporadic condition, and the random distribution of swelling
  • Pet Ownership and Multiple Sclerosis during COVID-19

    Edwards, Laura (2021)
    Background: Multiple sclerosis (MS) is associated with lower quality of life, reduced social participation, and decreased self-efficacy. The COVID-19 pandemic has had documented effects on the health and wellbeing of people with and without MS. Previous research has demonstrated the positive impact pets can have for people living with long-term conditions. Objectives: To explore the rates of pet ownership and pet attachment in people living with MS and pet ownership associations with quality of life, satisfaction with social roles, and self-efficacy scores; and to explore the effects of the COVID-19 outbreak on people's perceived relationships with their pets. Materials and Methods: A postal questionnaire was distributed to members of a local MS Register and a control group of people without MS. The questionnaire assessed quality of life, satisfaction with social roles, self-efficacy, the perceived roles of pets, and pet-related concerns experienced during the COVID-19 pandemic. Results: No apparent difference in attachment to pets was found between the patient and control groups. Pet ownership and level of attachment were not associated with differences in quality of life or self-efficacy scores in people living with MS. Using multiple regression analysis, pet ownership was associated with a decrease in satisfaction with participation in social roles, but with the estimated effect being small compared to having a diagnosis of MS or being unemployed. Most participants reported that pets had positive roles during the pandemic, and the most reported pet-related concern was access to veterinary treatment. Conclusion: Pet owners both with and without MS reported subjective benefits to their wellbeing from pet ownership during COVID-19, although analysis suggested that pet ownership was associated with a reduction in satisfaction with social roles. The study had several limitations and suggestions are made for future work.

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