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Approach to screening for Familial Adenomatous Polyposis (FAP) in a cohort of 226 patients with Desmoid-type Fibromatosis (DF): experience of a specialist center in the UK.
No full textINTRODUCTION
Desmoid-type fibromatosis (DF) are locally infiltrative, non-metastasizing tumours associated with significant morbidity and mortality if located intra-abdominally, retroperitoneally or in head and neck localisation. They are mostly sporadic, due to somatic CTNNB1 mutations. Alternatively, they can be associated with germline pathogenic variants in APC causing Familial Adenomatous Polyposis (FAP). Germline APC variants and somatic CTNNB1 mutations are mutually exclusive.
AIMS AND METHODS
We conducted a retrospective descriptive analysis of patients with DF seen at the Royal Marsden NHS Foundation Trust Sarcoma Unit in London. We aimed to describe the methods of screening for FAP in patients with DF from a specialist unit. Patients diagnosed between 1992 and 2020 were selected from the prospectively maintained Sarcoma Unit database.
RESULTS
226 patients were identified and 67% (n = 152) were female. Median age at diagnosis was 37.5 (range 2-81) years. Tumour localisation was limbs/pelvis in 30.9% (N = 70), intra-abdominal 16.8% (N = 38), abdominal wall 23.5% (N = 53), thorax 18.6% (N = 42), head and neck 3.1% (N = 7) and vertebral/paravertebral 7.1% (N = 16). Colonoscopy was requested in 65 patients (28.8% of all cases) and was completed in forty-six (20.4%). Molecular testing of CTNNB1 testing was requested in 35 cases (15.5%). APC germline test was requested in 12 cases. Four patients in our cohort had an FAP-associated DF.
CONCLUSIONS
CTNNB1 ± APC testing and colonoscopy are useful tools for the screening of patients with DF. CTNNB1 molecular testing should be performed in all cases of newly diagnosed DF. Negative CTNNB1 results, alongside clinical assessment, should prompt APC testing and/or colonoscopy
Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma.
No full textBACKGROUND
In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis.
PATIENTS AND METHODS
Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/m, Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/m (TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancer-specific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status.
RESULTS
Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (≥10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6-35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms.
CONCLUSIONS
Depatux-M had no impact on HRQoL and NDFS in patients with EGFR-amplified recurrent glioblastoma, except for more visual disorders, an expected side-effect of the study drug.
CLINICAL TRIAL REGISTRATION
NCT02343406
ERS International Congress 2020 Virtual: highlights from the Allied Respiratory Professionals Assembly.
No full textThis article provides an overview of outstanding sessions that were (co)organised by the Allied Respiratory Professionals Assembly during the European Respiratory Society International Congress 2020, which this year assumed a virtual format. The content of the sessions was mainly targeted at allied respiratory professionals, including respiratory function technologists and scientists, physiotherapists, and nurses. Short take-home messages related to spirometry and exercise testing are provided, highlighting the importance of quality control. The need for quality improvement in sleep interventions is underlined as it may enhance patient outcomes and the working capacity of healthcare services. The promising role of digital health in chronic disease management is discussed, with emphasis on the value of end-user participation in the development of these technologies. Evidence on the effectiveness of airway clearance techniques in chronic respiratory conditions is provided along with the rationale for its use and challenges to be addressed in future research. The importance of assessing, preventing and reversing frailty in respiratory patients is discussed, with a clear focus on exercise-based interventions. Research on the impact of disease-specific fear and anxiety on patient outcomes draws attention to the need for early assessment and intervention. Finally, advances in nursing care related to treatment adherence, self-management and patients' perspectives in asthma and chronic obstructive pulmonary disease are provided, highlighting the need for patient engagement and shared decision making. This highlights article provides readers with valuable insight into the latest scientific data and emerging areas affecting clinical practice of allied respiratory professionals
Peptide allergen-specific immunotherapy for allergic airway diseases-State of the art.
No full textAllergen-specific immunotherapy (AIT) is the only means of altering the natural immunological course of allergic diseases and achieving long-term remission. Pharmacological measures are able to suppress the immune response and/or ameliorate the symptoms but there is a risk of relapse soon after these measures are withdrawn. Current AIT approaches depend on the administration of intact allergens, often comprising crude extracts of the allergen. We propose that the challenges arising from current approaches, including the risk of serious side-effects, burdensome duration of treatment, poor compliance and high cost, are overcome by application of peptides based on CD4 T cell epitopes rather than whole allergens. Here we describe evolving approaches, summarize clinical trials involving peptide AIT in allergic rhinitis and asthma, discuss the putative mechanisms involved in their action, address gaps in evidence and propose future directions for research and clinical development
Tunnelled peritoneal drainage catheter placement for the palliative management of refractory ascites in patients with liver cirrhosis.
No full textObjective
Refractory ascites is an established indication for liver transplantation. While transplantation is regarded as the definitive therapy for this condition, many patients are unsuitable due to comorbidity or frailty. Alternatives such as transjugular intrahepatic portosystemic shunt (TIPSS) and large-volume paracentesis can lead to complications, including encephalopathy, circulatory and renal dysfunction, and protein-calorie deficiency that may accelerate sarcopenia. Cost and complication rates limit therapies such as alfapump. While there are data to support the use of indwelling catheters in the management of patients with malignant ascites, there is limited evidence to support their routine use in the context of end-stage liver cirrhosis. Here we describe our centres' experience using indwelling tunnelled ascitic drains over a 6-year period.
Methods
A retrospective review of data (January 2012-May 2018) was undertaken for all patients with refractory ascites who underwent a tunnelled ascitic drain. Demographics, disease aetiology, procedure data and follow-up data were obtained through interrogation of electronic records and reports.
Results
Twenty-five drains were placed. All procedures were technically successful with no immediate complications. Six patients were readmitted following their index admission with abdominal pain and suspected infected ascites (although only two had a positive ascitic fluid culture). There were three cases of abdominal wall cellulitis and three of leakage around the tunnel site; all managed conservatively.
Conclusion
Indwelling drains appear an effective strategy for palliative management of select patients with liver cirrhosis complicated by refractory ascites who are not amenable to undergo TIPSS or transplantation. While complications can occur, these are most usually minor and can be managed on an outpatient basis
Downstream testing after CT coronary angiography: time for a rethink?
No full textOBJECTIVE
We surveyed UK practice and compliance with the National Institute for Health and Care Excellence (NICE) 'recent-onset chest pain' guidance (Clinical Guideline 95, 2016) as a service quality initiative. We aimed to evaluate the diagnostic utility and efficacy of CT coronary angiography (CTCA), NICE-guided investigation compliance, invasive coronary angiography (ICA) use and revascularisation.
METHODS
A prospective analysis was conducted in nine UK centres between January 2018 and March 2020. The reporter decided whether the CTCA was diagnostic. Coronary artery disease was recorded with the Coronary Artery Disease-Reporting and Data System (CAD-RADS). Local electronic records and picture archiving/communication systems were used to collect data regarding functional testing, ICA and revascularisation. Duplication of coronary angiography without revascularisation was taken as a surrogate for ICA overuse.
RESULTS
5293 patients (mean age, 57±12 years; body mass index, 29±6 kg/m²; 50% men) underwent CTCA, with a 96% diagnostic scan rate. 618 (12%) underwent ICA, of which 48% (298/618) did not receive revascularisation. 3886 (73%) had CAD-RADS 0-2, with 1% (35/3886) undergoing ICA, of which 94% (33/35) received ICA as a second-line test. 547 (10%) had CAD-RADS 3, with 23% (125/547) undergoing ICA, of which 88% (110/125) chose ICA as a second-line test, with 26% (33/125) leading to revascularisation. For 552 (10%) CAD-RADS 4 and 91 (2%) CAD-RADS 5 patients, ICA revascularisation rates were 64% (221/345) and 74% (46/62), respectively.
CONCLUSIONS
While CTCA for recent-onset chest pain assessment has been shown to be a robust test, which negates the need for further investigation in three-quarters of patients, subsequent ICA overuse remains with almost half of these procedures not leading to revascularisation
Intramedullary Headless Screw Fixation of Distal Metacarpal Fractures - the Birmingham Experience.
No full textSurgical fixation using intramedullary headless screws (IHS) is a relatively new technique for metacarpal fracture repair. However, there are very few studies investigating the outcomes of this procedure. We present the surgical and functional outcomes of a consecutive series of 30 metacarpal fractures treated by a single surgeon over a 2.5-year period using IHS. We retrospectively reviewed the records of 30 metacarpal fractures in 27 patients who underwent IHS fixation from March 2016 to October 2018. There were 29 fractures of the metacarpal neck and 1 was to the metacarpal head. All fractures underwent the procedure by a single operating surgeon. Individual joint movements along with total active movement (TAM) was measured at postoperative follow-up appointments 4-8 weeks after surgery. Fracture healing was confirmed with plain radio-graphs. Patients were also recalled in March 2019 for their latest functional measurements. A QuickDASH (disabilities of the arm, shoulder and hand) questionnaire was used to assess for any residual functional disability. All fractures healed within acceptable radiological parameters with no mal-unions or rotational deformities. The average TAM at initial follow-up was 245°, which improved to 264° at the March 2019 review. All patients returned to work in an average of 6 weeks. The final functional QuickDASH score was an average of 2.9/100 (range 0-18.2). 2/27 patients required further surgery for stiffness before regaining excellent TAM. No patient required metalwork removal. There were no other complications. Our findings suggest that IHS fixation is an effective alternative technique for the treatment of metacarpal fractures. It is a relatively simple procedure, which provides good stable fixation, allowing for early mobilisation. It has few complications and does not routinely require removal of the implant
A Position Statement on the Utility of Interval Imaging in Standard of Care Brain Tumour Management: Defining the Evidence Gap and Opportunities for Future Research.
No full textObjectiv e
To summarise current evidence for the utility of interval imaging in monitoring disease in adult brain tumours, and to develop a position for future evidence gathering while incorporating the application of data science and health economics.
Methods
Experts in 'interval imaging' (imaging at pre-planned time-points to assess tumour status); data science; health economics, trial management of adult brain tumours, and patient representatives convened in London, UK. The current evidence on the use of interval imaging for monitoring brain tumours was reviewed. To improve the evidence that interval imaging has a role in disease management, we discussed specific themes of data science, health economics, statistical considerations, patient and carer perspectives, and multi-centre study design. Suggestions for future studies aimed at filling knowledge gaps were discussed.
Results
Meningioma and glioma were identified as priorities for interval imaging utility analysis. The "monitoring biomarkers" most commonly used in adult brain tumour patients were standard structural MRI features. Interval imaging was commonly scheduled to provide reported imaging prior to planned, regular clinic visits. There is limited evidence relating interval imaging in the absence of clinical deterioration to management change that alters morbidity, mortality, quality of life, or resource use. Progression-free survival is confounded as an outcome measure when using structural MRI in glioma. Uncertainty from imaging causes distress for some patients and their caregivers, while for others it provides an important indicator of disease activity. Any study design that changes imaging regimens should consider the potential for influencing current or planned therapeutic trials, ensure that opportunity costs are measured, and capture indirect benefits and added value.
Conclusion
Evidence for the value, and therefore utility, of regular interval imaging is currently lacking. Ongoing collaborative efforts will improve trial design and generate the evidence to optimise monitoring imaging biomarkers in standard of care brain tumour management
Direct oral anticoagulant-related medication incidents and pharmacists' interventions in hospital in-patients: evaluation using reason's accident causation theory.
No full textBackground Direct oral anticoagulants (DOACs) have revolutionised anticoagulant pharmacotherapy. However, DOAC-related medication incidents are known to be common. Objective To assess medication incidents associated with DOACs using an error theory and to analyse pharmacists' contributions in minimising medication incidents in hospital in-patients. Setting A large University academic hospital in the West Midlands of England. Methods Medication incident data from the incident reporting system (48-months period) and pharmacists' interventions data from the prescribing system (26-month period) relating to hospital in-patients were extracted. Reason's Accident Causation Model was used to identify potential causality of the incidents. Pharmacists' intervention data were thematically analysed. Main outcome measure (a) Frequency, type and potential causality of DOAC-related incidents; (b) nature of pharmacists' interventions. Results A total of 812 reports were included in the study (124 medication incidents and 688 intervention reports). Missing drug/omission was the most common incident type (26.6%, n = 33) followed by wrong drug (16.1%, n = 20) and wrong dose/strength (11.3%, n = 14). A high majority (89.5%, n = 111) of medication incidents were caused by active failures. Patient discharge without anticoagulation supply and failure to restart DOACs post procedure/scan were commonly recurring themes. Pharmacists' interventions most frequently related to changes in pharmacological strategy, including drug or dose changes (38.1%, n = 262). Impaired renal function was the most common reason for dose adjustments. Conclusion Prescribers' active failure rather than system errors (i.e. latent failures) contributed to the majority of DOAC-related incidents. Reinforcement of guideline adherence, prescriber education, harnessing pharmacists' roles and mandating renal function information in prescriptions are likely to improve patient safety
The Clinical Assessment of MicroRNA Diagnostic, Prognostic, and Theranostic Value in Colorectal Cancer.
No full textMiRNAs have recently become a subject of great interest within cancers and especially colorectal cancers in diagnosis, prognosis, and therapy decisions; herein we review the current literature focusing on miRNAs in colorectal cancers, and we discuss future challenges to use this tool on a daily clinical basis. In liquid biopsies, miRNAs seem easily accessible and can give important information toward each step of the management of colorectal cancers. However, it is now necessary to highlight the most sensitive and specific miRNAs for each goal thanks to multicentric prospective studies. Conclusions: by their diversity and the feasibility of their use, miRNAs are getting part of the armamentarium of healthcare management of colorectal cancers