2021

GLP-1 receptor agonists in type 2 diabetes: An underused asset? Updated January 2021 (2021)

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Type of publication:
Journal article

Author(s):
*Morris, David

Citation:
Journal of Diabetes Nursing; Jan 2021; vol. 25 (no. 1); p. 1-13

Abstract:
As our understanding of the incretin hormones has increased, a number of drugs targeting this system have been developed. The realisation of this potential has developed rapidly, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now a standard feature in management guidelines for type 2 diabetes. This article reviews the operation of the incretin system and the mechanism by which GLP-1 RAs act to provide benefit in type 2 diabetes. The availability and indications for use of the GLP-1 RAs, and their clinical benefits and disadvantages, are summarised. The position of GLP-1 RAs in the management of type 2 diabetes is discussed pragmatically, with reference to various key guidelines. This article has been updated in January 2021 to incorporate recent guideline changes and the launch in the UK of an oral formulation of semaglutide.

BSE and BCOS Guideline for Transthoracic Echocardiographic Assessment of Adult Cancer Patients Receiving Anthracyclines and/or Trastuzumab (2021)

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Type of publication:
Journal article

Author(s):
Dobson R.; Ghosh A.K.; Manisty C.; Ky B.; Marwick T.; Stout M.; Pearce K.; Harkness A.; Steeds R.; Robinson S.; Oxborough D.; Adlam D.; Stanway S.; Rana B.; *Ingram T.; Ring L.; Rosen S.; Lyon A.R.; Plummer C.; Harbinson M.; Sharma V.; Augustine D.X.

Citation:
JACC: CardioOncology; Mar 2021; vol. 3 (no. 1); p. 1-16

Abstract:
The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor receptor (HER) 2-positive targeted treatment (e.g., trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented.

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Digital mammographic interpretation by UK radiographer mammographers: A JAFROC analysis of observer performance (2021)

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Type of publication:
Journal article

Author(s):
*Williams S.; *Aksoy U.; *Cielecki L.; Reed W.; Woznitza N.

Citation:
Radiography; Aug 2021; vol. 27 (no. 3); p. 915-919

Abstract:
Introduction: Radiologists utilise mammography test sets to bench mark their performance against recognised standards. Using a validated test set, this study compares the performance of radiographer readers against previous test results for radiologists. Method(s): Under similar test conditions radiographer readers were given an established test set of 60 mammograms and tasked to identify breast cancer, they were measured against their ability to identify, locate and give a confidence level for cancer being present on a standard set of mammographic images. The results were then compared to previously published results for radiologists for similar or the same test sets. Result(s): The 10 radiographer readers demonstrated similar results to radiologists and for lesion sensitivity were the highest scoring group. The study group score a sensitivity of 83; a specificity of 69.3 and lesion sensitivity of 74.8 with ROC and JAFROC scores of 0.86 and 0.74 respectively. Conclusion(s): Under test conditions radiographers are able to identify and accurately locate breast cancer in a range of complex mammographic backgrounds. Implications for practice: The study was performed under experimental conditions with results comparable to breast radiologists under similar conditions, translation of these findings into clinical practice will help address access and capacity issues in the timely identification and diagnosis of breast cancer.

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Can existing routine clinical data be used to predict hypoxaemia for mnd patients undertaking commercial flight? (2021)

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Type of publication:
Conference abstract

Author(s):
Cliff I.J.; Mustfa N.; Stone H.; Hurst C.; *Crawford E.

Citation:
Thorax; Feb 2021; vol. 76

Abstract:
Introduction: Pre-COVID-19, the total number of passengers traveling by commercial airlines rose to 4.3 billion, with Europe amounting to a 7.2% increase. The risks of respiratory compromised patients developing hypoxaemia during flight is well documented. Assessment of these patients is time consuming and often requires specialised equipment. Furthermore, the majority of evidence is based on research into patients with Chronic Obstructive Pulmonary Disease (COPD). The aim of this study is to investigate potential predictive biomarkers relating to the development of hypoxaemia during flight in patients with Motor Neurone Disease (MND). Method(s): 118 MND patients referred into a fitness to fly service (n=118) completed baseline lung function and a Hypoxic Challenge Test (HCT) as part of a risk stratification for (Table presented) planned air travel (77 male). Data from patients requiring inflight oxygen was compared to patients who did not, in accordance with the British Thoracic Society recommendations 2011: Managing passengers with stable respiratory disease planning air travel. Statistical analysis was performed using one-way ANOVA, Kruskal-Wallis, and Chi-Squared tests, as appropriate. Result(s): There was no significant difference between the pass (n=94) and fail (n=24) groups for age, gender, smoking history or BMI. There was a significant difference for all spirometry data (FEV1, FVC and FEV1/FVC ratio – absolute, percent predicted and standardised residuals). Moreover, the resting blood gases (FiO221%) data showed significant difference for all parameters with the exception of pH (<0.001). The Regression analysis showed limited predictive value of spirometry and/or resting blood gas data with the exception of PaCO2 and base excess (BE). Conclusion(s): The predictive value of spirometic paraments and resting blood gases are limited in assessing hypoxaemia during commercial flight in MND patients, with the exception of parameters relating to respiratory failure. Despite the significant difference between the two groups, routine physiological data was limited in the predictive regression equations. We recommend that the safest approach in managing this group of patients is to perform an HCT in all patients intending to use air travel until more evidence-based data is available.

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Can historical assumptions be used to assess fitness to fly for MND and ILD patients? An evaluation of physiological parameters to risk stratify patients planning air travel (2021)

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Type of publication:
Conference abstract

Author(s):
Cliff I.J.; Mustfa N.; Stone H.; Hurst C.; Allen M.B.; *Crawford E.

Citation:
Thorax; Feb 2021; vol. 76

Abstract:
Introduction: The risk associated with commercial flight for respiratory compromised patients is well known. Many of the assumptions are based on studies that have included patients with Chronic Obstructive Pulmonary Disease (COPD) and have often been extended to other respiratory and non-respiratory disorders. This study aimed to examine differences in physiological parameters and Hypoxic Challenge Test (HCT) outcome in patients with Motor Neurone Disease (MND), Interstitial Lung Disease (ILD) and COPD. Method(s): Respiratory patients who were referred into a fitness to fly service (n=225) with COPD (n=51), MND (n=118) and ILD (n=56) completed baseline lung function and a HCT as part of a risk stratification for planned air travel. Statistical analysis was performed using one-way ANOVA, Kruskal-Wallis, and Chi-Squared tests, as appropriate. Result(s): Demographic data relating to age, smoking history and BMI were significantly different between the patient groups. Spirometric data showed significant differences in Forced Expiratory Volume in one second (FEV1) absolute, percent predicted and standardised residuals, however there was no significant difference in Forced Vital Capacity (FVC) absolute or percent predicted. Resting capillary blood gases (CBGs) (FiO221%) showed significant differences between patient groups in all parameters with the exception of pH. Responses to the hypoxic mix during the HCT (FiO215%) showed differences in all CBG values with the exception of pH. This was also mirrored in the corrective values (FiO228%). The difference between the PaO2 at rest (21%) and during the HCT (15%) is higher in the MND and ILD groups (2.66and 2.74 kPa respectively) versus the COPD group (2.2kPa). The HCT fail rate was greatest for the COPD group (table 1). Conclusion(s): In this retrospective, exploratory examination, the physiological data supports significant differences between the disorders for the majority of data. The assumptions and algorithms based on the study of COPD patients cannot be assumed for MND or ILD, and these groups need to be (Table presented) specifically studied to better understand their response to the commercial cabin environment.

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MRI of the Achilles tendon-A comprehensive pictorial review. Part one (2021)

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Type of publication:
Journal article

Author(s):
Szaro P.; Nilsson-Helander K.; *Carmont M.

Citation:
European Journal of Radiology Open; Jan 2021; vol. 8

Abstract:
The normal Achilles tendon is composed of twisted subtendons separated by thin high signal septae, which are a potential pitfall on MRI because they mimic a tendon tear. Tendinopathy and full thickness tears may be assessed effectively both on MRI and ultrasound. MRI is superior to ultrasound in detection of partial tears and for postoperative assessment. The use of fat suppression sequences allows the ability to detect focal lesions. Sagittal and coronal sections are useful for assessing the distance between stumps of a ruptured tendon. Sequences with contrast are indicated in postoperative investigations and suspicion of infection, arthritis or tumor. MRI may reveal inflammatory changes with minor symptoms long before the clinical manifestations of seronegative spondyloarthropathy. The most common non-traumatic focal lesion of the Achilles tendon is Achilles tendon xanthoma, which is manifested by intermediate or slightly higher signal on T1- and T2-weighted images compared to that in the normal Achilles tendon. Other tumors of the Achilles tendon are very rare, whereas the involvement of the tendon from tumor in adjacent structures is more frequent. The novel MRI sequences may help to detect disorders of the Achilles tendon more specifically before clinical manifestation. Regeneration or remodeling of the Achilles tendon can be non-invasively detected and monitored in diffusion tensor imaging. Assessment of healing is possible using T2-mapping while evaluating the tendon vascularization in intravoxel incoherent motion MRI.

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Postpartum haemorrhage and risk of mental ill health: A population-based longitudinal study using linked primary and secondary care databases (2021)

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Type of publication:
Journal article

Author(s):
*Parry-Smith W.; Coomarasamy A.; Nirantharakumar K.; Okoth K.; Subramanian A.; Gokhale K.M.; Chandan J.S.; Sumilo D.; Humpston C.

Citation:
Journal of Psychiatric Research; May 2021; vol. 137 ; p. 419-425

Abstract:
There is a gap in the literature investigating the impact of obstetric complications on subsequent mental ill health outcomes. The aim of this study was to establish the association between post-partum haemorrhage (PPH) and mental ill health. We conducted a retrospective open cohort study utilizing linked primary care (The Health Improvement Network (THIN)) and English secondary care (Hospital Episode Statistics (HES)) databases, from January 1, 1990 to January 31, 2018. A total of 42,327 women were included: 14,109 of them were exposed to PPH during the study period and 28,218 unexposed controls were matched for age and date of delivery. Hazard ratios (HRs) for mental illness among women with and without exposure to PPH were estimated after controlling for covariates. Women who had had PPH were at an increased risk of developing postnatal depression (adjusted HR: 1.10, 95%CI: 1.01-1.21) and post-traumatic stress disorder (PTSD) (adjusted HR: 1.17, 95%CI: 0.73-1.89) compared to women unexposed to PPH. When restricting the follow-up to the first year after childbirth, the adjusted HR for PTSD was 3.44 (95% CI 1.31-9.03). No increase in the overall risk was observed for other mental illnesses, including depression (adjusted HR: 0.94, 95%CI: 0.87-1.01), severe mental illness (adjusted HR: 0.65, 95%CI: 0.40-1.08, p = 0.239) and anxiety (adjusted HR: 0.99, 95%CI: 0.90-1.09). PPH is associated with a significant increase in the risk of developing postnatal depression and PTSD in the first year after delivery. Active monitoring for mental illness should form an integral part of the follow-up in women who suffered a PPH.

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Continuous positive airway pressure (CPAP) as a ceiling of care treatment for hypoxemic respiratory failure due to COVID-19 (2021)

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Type of publication:
Journal article

Author(s):
Patrick Bradley , *Jennifer Nixon , James Wilson , James Redfern , Tarek Saba , Emily Nuttall, Thomas Bongers

Citation:
Journal of the Intensive Care Society 2021, Vol. 0(0), 1–3 [epub ahead of print]

Abstract:
Among patients admitted to hospital with COVID-19 in the UK, 10% develop severe hypoxemic respiratory failure managed with invasive mechanical ventilation (IMV). Much interest has focused on non-invasive strategies to avert progression to IMV. UK guidelines recommend the use of continuous positive airway pressure (CPAP), including in patients for whom IMV is not appropriate. However, other nations have recommended against the use of CPAP, and within the UK, CPAP use has varied widely (personal communication). The greatest burden of COVID-19 disease is carried by older patients with comorbidities, many of whom are deemed unsuitable for IMV and critical care. However, it is unclear whether they might benefit from CPAP. The RECOVERY-RS trial is investigating the efficacy of CPAP and high-flow nasal oxygen (HFNO) in severely hypoxic patients with COVID-19, but will not complete until late 2021, and excludes patients unsuitable for IMV. Current evidence is limited to cohort studies of heterogeneous patient groups, with no published data focussing on patients for whom CPAP is the ceiling-of-care. Physicians caring for such patients, and those involved in planning the delivery of CPAP services, must balance any potential benefits of CPAP against its burden on patients, families, staff, and services. Therefore data in this patient population are urgently needed.

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Objective responses to first-line neoadjuvant carboplatin-paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial (2021)

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Type of publication:
Journal article

Author(s):
Morgan R.D.; Jayson G.C.; Clamp A.R.; McNeish I.A.; Krell J.; Cook A.D.; James E.C.; Lord R.; Dark G.; Glasspool R.M.; Parkinson C.; Poole C.J.; Hall M.; Gallardo-Rincon D.; Lockley M.; Essapen S.; Summers J.; Anand A.; *Zachariah A.; Williams S.; Jones R.; Scatchard K.; Walther A.; Kim J.-W.; Sundar S.; Ledermann J.A.

Citation:
The Lancet Oncology; Feb 2021; vol. 22 (no. 2); p. 277-288

Abstract:
Background: Platinum-based neoadjuvant chemotherapy followed by delayed primary surgery (DPS) is an established strategy for women with newly diagnosed, advanced-stage epithelial ovarian cancer. Although this therapeutic approach has been validated in randomised, phase 3 trials, evaluation of response to neoadjuvant chemotherapy using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and cancer antigen 125 (CA125) has not been reported. We describe RECIST and Gynecologic Cancer InterGroup (GCIG) CA125 responses in patients receiving platinum-based neoadjuvant chemotherapy followed by DPS in the ICON8 trial. Method(s): ICON8 was an international, multicentre, randomised, phase 3 trial done across 117 hospitals in the UK, Australia, New Zealand, Mexico, South Korea, and Ireland. The trial included women aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, life expectancy of more than 12 weeks, and newly diagnosed International Federation of Gynecology and Obstetrics (FIGO; 1988) stage IC-IIA high-grade serous, clear cell, or any poorly differentiated or grade 3 histological subtype, or any FIGO (1988) stage IIB-IV epithelial cancer of the ovary, fallopian tube, or primary peritoneum. Patients were randomly assigned (1:1:1) to receive intravenous carboplatin (area under the curve [AUC]5 or AUC6) and intravenous paclitaxel (175 mg/m2 by body surface area) on day 1 of every 21-day cycle (control group; group 1); intravenous carboplatin (AUC5 or AUC6) on day 1 and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 2); or intravenous dose-fractionated carboplatin (AUC2) and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 3). The maximum number of cycles of chemotherapy permitted was six. Randomisation was done with a minimisation method, and patients were stratified according to GCIG group, disease stage, and timing and outcome of cytoreductive surgery. Patients and clinicians were not masked to group allocation. The scheduling of surgery and use of neoadjuvant chemotherapy were determined by local multidisciplinary case review. In this post-hoc exploratory analysis of ICON8, progression-free survival was analysed using the landmark method and defined as the time interval between the date of pre-surgical planning radiological tumour assessment to the date of investigator-assessed clinical or radiological progression or death, whichever occurred first. This definition is different from the intention-to-treat primary progression-free survival analysis of ICON8, which defined progression-free survival as the time from randomisation to the date of first clinical or radiological progression or death, whichever occurred first. We also compared the extent of surgical cytoreduction with RECIST and GCIG CA125 responses. This post-hoc exploratory analysis includes only women recruited to ICON8 who were planned for neoadjuvant chemotherapy followed by DPS and had RECIST and/or GCIG CA125-evaluable disease. ICON8 is closed for enrolment and follow-up, and registered with ClinicalTrials.gov, NCT01654146. Finding(s): Between June 6, 2011, and Nov 28, 2014, 1566 women were enrolled in ICON8, of whom 779 (50%) were planned for neoadjuvant chemotherapy followed by DPS. Median follow-up was 29.5 months (IQR 15.6-54.3) for the neoadjuvant chemotherapy followed by DPS population. Of 564 women who had RECIST-evaluable disease at trial entry, 348 (62%) had a complete or partial response. Of 727 women who were evaluable by GCIG CA125 criteria at the time of diagnosis, 610 (84%) had a CA125 response. Median progression-free survival was 14.4 months (95% CI 9.2-28.0; 297 events) for patients with a RECIST complete or partial response and 13.3 months (8.1-20.1; 171 events) for those with RECIST stable disease. Median progression-free survival for women with a GCIG CA125 response was 13.8 months (95% CI 8.8-23.4; 544 events) and 9.7 months (5.8-14.5; 111 events) for those without a GCIG CA125 response. Complete cytoreduction (R0) was achieved in 187 (56%) of 335 women with a RECIST complete or partial response and 73 (42%) of 172 women with RECIST stable disease. Complete cytoreduction was achieved in 290 (50%) of 576 women with a GCIG CA125 response and 30 (30%) of 101 women without a GCIG CA125 response. Interpretation(s): The RECIST-defined radiological response rate was lower than that frequently quoted to patients in the clinic. RECIST and GCIG CA125 responses to neoadjuvant chemotherapy for epithelial ovarian cancer should not be used as individual predictive markers to stratify patients who are likely to benefit from DPS, but instead used in conjunction with the patient's clinical capacity to undergo cytoreductive surgery. A patient should not be denied surgery based solely on the lack of a RECIST or GCIG CA125 response. Funding(s): Cancer Research UK, UK Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.

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