2020

Nutritional status and predictors of weight loss in patients with systemic sclerosis (2020)

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Type of publication:
Journal article

Author(s):
Hvas C.L.; Eriksen M.K.; *Harrison E.; Herrick A.L.; McLaughlin J.T.; Lal S.

Citation:
Clinical Nutrition ESPEN; Volume 40, December 2020, Pages 164-170

Abstract:
Background & aims: Systemic sclerosis (SSc) commonly affects the gastrointestinal (GI) tract and predisposes to malnutrition. Few studies assessed body composition in outpatients with SSc or used more than one method for comparison over time. The aim of this study was to describe markers of nutrition and body composition in patients with SSc and to identify predictors of unintentional weight loss. Method(s): We consecutively included outpatients with SSc and performed a one-year follow-up. Gastrointestinal (GI) involvement was evaluated from clinical investigations. Patients completed questionnaires for organ involvement and functional status. Clinical assessment included body mass index (BMI), the malnutrition universal screening tool (MUST), inter-incisor distance, anthropometry, and bio-electrical impedance analysis (BIA). Result(s): In total, 168 consecutive patients with SSc were included, and 127 (76%) completed one-year follow-up. Thirteen (8%) died before follow-up. Based on MUST scores, 12% of patients were at high and 14% at medium risk of malnutrition. A low BMI was associated with small intestinal involvement (p < 0.0001). Percentage body fat correlated with BMI, both when using four-site anthropometry (r = 0.65, p < 0.01) and BIA (r = 0.49, p < 0.01). Nine (7%) patients had >5% unintentional weight loss at follow-up. Independent baseline predictors of unintentional weight loss included upper GI involvement and disease severity estimated by Health Assessment Questionnaire Disability Index score. Conclusion(s): Nutritional risk and GI involvement are frequent and closely correlated in patients with SSc. BIA and four-site anthropometry are comparable in the clinical assessment of patients with SSc. Unintentional weight loss is discrete and related to disease-specific characteristics.

Impact of coronavirus disease 2019 on urgent referrals to secondary care otolaryngology: a prospective case series (2020)

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Type of publication:
Journal article

Author(s):
Osborne M.S.; Bentley E.; Farrow A.; Murphy J.; *Chan J.

Citation:
Journal of Laryngology and Otology; 2020 [epub ahead of print]

Abstract:
Objective. As the novel coronavirus disease 2019 changed patient presentation, this study aimed to prospectively identify these changes in a single ENT centre. Design. A seven-week prospective case series was conducted of urgently referred patients from primary care and accident and emergency department. Results. There was a total of 133 referrals. Referral rates fell by 93 per cent over seven weeks, from a mean of 5.4 to 0.4 per day. Reductions were seen in referrals from both primary care (89 per cent) and the accident and emergency department (93 per cent). Presentations of otitis externa and epistaxis fell by 83 per cent, and presentations of glandular fever, tonsillitis and peritonsillar abscess fell by 67 per cent. Conclusion. Coronavirus disease 2019 has greatly reduced the number of referrals into secondary care ENT. The cause for this reduction is likely to be due to patients' increased perceived risk of the virus presence in a medical setting. The impact of this reduction is yet to be ascertained, but will likely result in a substantial increase in emergency pressures once the lockdown is lifted and the general public's perception of the coronavirus disease 2019 risk reduces.

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Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: An expert panel position statement from HEART UK (2020)

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Type of publication:
Journal article

Author(s):
Iqbal Z.; Ho J.H.; France M.; Schofield J.; Nicholson K.; Soran H.; Adam S.; Durrington P.; Syed A.; Neely D.; Rees A.; Payne J.; Khatib R.; Cegla J.; Byrne C.; Qureshi N.; *Capps N.; Ferns G.; Datta D.; Pottle A.; Halcox J.; Krentz A.

Citation:
Atherosclerosis; Nov 2020; vol. 313 ; p. 126-136

Abstract:
The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes Coronavirus Disease 2019 (COVID-19) has resulted in a pandemic. SARS-CoV-2 is highly contagious and its severity highly variable. The fatality rate is unpredictable but is amplified by several factors including advancing age, atherosclerotic cardiovascular disease, diabetes mellitus, hypertension and obesity. A large proportion of patients with these conditions are treated with lipid lowering medication and questions regarding the safety of continuing lipid-lowering medication in patients infected with COVID-19 have arisen. Some have suggested they may exacerbate their condition. It is important to consider known interactions with lipid-lowering agents and with specific therapies for COVID-19. This statement aims to collate current evidence surrounding the safety of lipid-lowering medications in patients who have COVID-19. We offer a consensus view based on current knowledge and we rated the strength and level of evidence for these recommendations. Pubmed, Google scholar and Web of Science were searched extensively for articles using search terms: SARS-CoV-2, COVID-19, coronavirus, Lipids, Statin, Fibrates, Ezetimibe, PCSK9 monoclonal antibodies, nicotinic acid, bile acid sequestrants, nutraceuticals, red yeast rice, Omega-3-Fatty acids, Lomitapide, hypercholesterolaemia, dyslipidaemia and Volanesorsen. There is no evidence currently that lipid lowering therapy is unsafe in patients with COVID-19 infection. Lipid-lowering therapy should not be interrupted because of the pandemic or in patients at increased risk of COVID-19 infection. In patients with confirmed COVID-19, care should be taken to avoid drug interactions, between lipid-lowering medications and drugs that may be used to treat COVID-19, especially in patients with abnormalities in liver function tests.

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Using the Glasgow Benefit Inventory questionnaire to quantify the health benefits of lymphoedema treatment in patients with head and neck cancer (2020)

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Type of publication:
Journal article

Author(s):
*Halliday E.; *Ahsan S.F.; Gittins J.

Citation:
Applied Cancer Research; Dec 2020; vol. 40 (no. 1)

Abstract:
Background: Lymphoedema is a common side effect after treatment for head and neck cancer. Our treatment protocol involves staging the degree of lymphoedema and then offering treatment comprising skin care, manual lymphatic drainage, simple lymphatic drainage, compression and elastic therapeutic tape. The Glasgow Benefit Inventory is a validated post-interventional questionnaire applicable to otorhinolaryngology interventions which measures changes in health status. The aim of this study was to quantify the health benefits of lymphoedema treatment using the Glasgow Inventory Benefit questionnaire, in patients with a history of treated head and neck cancer. Method(s): Any patient who had undergone treatment with curative intent of a primary head and neck malignancy who had been referred for lymphoedema treatment within a 6 month period was eligible for inclusion. Patients completed a questionnaire after finishing the course of lymphoedema treatment. Result(s): A total of 15 patients completed the questionnaire. Ten patients (67%) demonstrated some level of improvement in quality of life, while two (13%) reported no benefit and three (20%) reported negative improvements. The average score for the total Glasgow Benefit Inventory scale was + 7.2. The greatest benefit was demonstrated with the physical benefit subscale (+ 13.1). The average general benefit score was + 9.0. Conclusion(s): Lymphoedema treatment involves techniques which can fairly easily be taught to patients to complete at home. In this study, there were mild improvements in patient reported quality of life using the Glasgow Benefit Inventory in the majority of patients. Clinical interest has increased in lymphoedema recently, but there is still limited information about the effectiveness of treatments and future research should look to address these issues.

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Selection of endogenous control genes for normalising gene expression data derived from formalin-fixed paraffin-embedded tumour tissue (2020)

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Type of publication:
Journal article

Author(s):
Smith T.A.D.; AbdelKarem O.A.; Irlam-Jones J.J.; Lane B.; Valentine H.; Bibby B.A.S.; Choudhury A.; West C.M.L.; *Denley H.

Citation:
Scientific reports; Oct 2020; vol. 10 (no. 1)

Abstract:
Quantitative real time polymerase chain reaction (qPCR) data are normalised using endogenous control genes. We aimed to: (1) demonstrate a pathway to identify endogenous control genes for qPCR analysis of formalinfixed paraffin-embedded (FFPE) tissue using bladder cancer as an exemplar; and (2) examine the influence of probe length and sample age on PCR amplification and co-expression of candidate genes on apparent expression stability. RNA was extracted from prospective and retrospective samples and subject to qPCR using TaqMan human endogenous control arrays or single tube assays. Gene stability ranking was assessed using coefficient of variation (CoV), GeNorm and NormFinder. Co-expressed genes were identified from The Cancer Genome Atlas (TCGA) using the on-line gene regression analysis tool GRACE. Cycle threshold (Ct) values were lower for prospective (19.49+/-2.53) vs retrospective (23.8+/-3.32) tissues (p<0.001) and shorter vs longer probes. Co-expressed genes ranked as the most stable genes in the TCGA cohort by GeNorm when analysed together but ranked lower when analysed individually omitting co-expressed genes indicating bias. Stability values were<1.5 for the 20 candidate genes in the prospective cohort. As they consistently ranked in the top ten by CoV, GeNorm and Normfinder, UBC, RPLP0, HMBS, GUSB, and TBP are the most suitable endogenous control genes for bladder cancer qPCR.

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Results of a randomized phase III study of dysphagia-optimized intensity modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT) in head and neck cancer (2020)

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Type of publication:
Conference abstract

Author(s):
Nutting C.; Rooney K.; Foran B.; *Pettit L.; Beasley M.; Finneran L.; Roe J.; Tyler J.; Roques T.; Cook A.; Petkar I.; Bhide S.; Srinivasan D.; Boon C.; De Winton E.; Frogley R.; Mertens K.; Emson M.; Hall E.

Citation:
Journal of Clinical Oncology; 2020; vol. 38 (no. 15)

Abstract:
Background: Most newly diagnosed oro-& hypopharngeal cancers (OPC, HPC) are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. CRUK/14/014 investigated if using Do-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Method(s): Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary&nodal tumour; 54Gy/30f to remaining pharyngeal subsite&nodal areas at risk of microscopic disease) or Do-IMRT. The volume of the superior∣dle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in Do-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site&AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT with 102 patients needed to detect a 10 point improvement (assuming S-IMRT score of 72, standard deviation (SD) 13.8; 90% power, 2-sided 5% alpha). Patients were blind to treatment allocation. Secondary endpoints included local control. Result(s): 112 patients (56 S-IMRT, 56 Do-IMRT) were randomised from 22 UK centres from 06/2016 to 04/2018. Mean age was 57 years; 80% were male; 97% had OPC; 90% had AJCC stage 3&4 disease; 86% had concomitant chemotherapy only, 4% induction&concomitant and 10% no chemotherapy. 111/112 had RT doses as prescribed (1 patient died before RT). Median of the mean inferior PCM dose was S-IMRT 49.8Gy (IQR 47.1-52.4) vs. Do-IMRT 28.4Gy (21.3-37.4), p < 0.0001; superior∣dle PCM dose was S-IMRT 57.2Gy (56.3-58.3) vs. Do-IMRT 49.7Gy (49.4-49.9), p < 0.0001. Do-IMRT had significantly higher MDADI scores: S-IMRT 70.3 (SD 17.3) vs. Do-IMRT 77.7 (16.1), p = 0.016. 3 local recurrences (1 S-IMRT, 2 Do-IMRT) have been reported. Conclusion(s): Do-IMRT reduced RT dose to the DARS and improved patient reported swallowing function compared with S-IMRT. This is the first randomised study to demonstrate functional benefit of swallow-sparing IMRT in OPC.

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Management of mid-urethral tape complications: a retrospective study (2020)

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Type of publication:
Journal article

Author(s):
Offiah I.; *Rachaneni S.; Dua A.

Citation:
Journal of Obstetrics and Gynecology of India; Apr 2020; vol. 70 (no. 2); p. 152-157

Abstract:
Background/purpose of the study: Following mid-urethral tape insertion, for stress urinary incontinence (SUI), a proportion of women experience complications such as voiding dysfunction or tape erosion which fail to respond to conservative management approaches. These women thus require further surgical treatment. Our objective was to describe the outcomes of the surgical management of complications in these women. Method(s): This retrospective study describes the results obtained following the surgical management of mid-urethral tape complications. Twenty-nine consecutive women who required mid-urethral tape lysis, loosening or excision for tape-related complications in the period 2007-2017 were included. Primary outcomes were improvement in voiding dysfunction and resolution of pain, while secondary outcomes were evaluation of the recurrence of stress urinary incontinence and patient satisfaction. Patient outcomes were measured using the Patient Global Impression of Improvement questionnaire. Result(s): There were 1459 mid-urethral tape procedures performed in the study period. Twenty-nine women (1.99%) who had revision surgery for tape complication were identified. Interventions included tape loosening or lysis in 19 women and tape excision in ten women. Twenty-three of the 29 patients reported a significant improvement in their symptoms postoperatively. Two women had a recurrence of SUI in the tape excision cohort; all patients following tape loosening or lysis remained continent. Conclusion(s): Tape revision surgery is a safe and effective treatment for mid-urethral tape complications with the majority of women maintaining continence following revision. Early intervention and proactive management of complications, by the appropriate specialist, will improve outcomes.

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The Cortical Basal ganglia Functional Scale (CBFS): Development and preliminary validation (2020)

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Type of publication:
Journal article

Author(s):
Lang A.E.; Stebbins G.T.; Wang P.; Boxer A.L.; Jabbari E.; Morris H.; Lamb R.; Boxer (PI) A.; Boeve B.; Dickerson B.; Grossman M.; Litvan I.; Ljubenkov P.; Rojas-Martinez J.; Pantelyat A.; Tartaglia M.-C.; Wills A.-M.; Morris (PI) H.; Amar K.; *Capps E.; Carey G.; Church A.; Critchley P.; Ghosh B.; Houlden H.; Hu M.; Kobylecki C.; Massey L.; Molloy S.; Nath U.; Pavese N.; Rowe J.B.

Citation:
Parkinsonism and Related Disorders; Oct 2020; vol. 79 ; p. 121-126

Abstract:
Objective: To develop a patient/care-giver reported scale capable of easily and reliably assessing functional disability in 4 repeat tauopathies (4RTs). Background(s): 4R tauopathies including progressive supranuclear palsy, corticobasal degeneration and a subset of frontotemporal dementias manifest a range of overlapping clinical phenotypes. No available rating scale is capable of evaluating the functional impact of these complex disorders. Method(s): A multi-staged modified Delphi process was used to propose, evaluate and rank potential scale items providing content validity ratios. Staged cognitive pretesting involving input from examiners, patients and caregivers was followed by validation testing in patients participating in the 4R Tauopathy Neuroimaging Initiative or the PROgressive Supranuclear Palsy CorTico-Basal Syndrome MSA Longitudinal Study. Clinimetric properties were examined using classical test theory and item response methods, assessing data quality, reliability, construct validity, convergent validity and known-group validity. Result(s): The resultant Cortical Basal ganglia Functional Scale (CBFS) included questions on Motor Experiences in Daily Living (14 items) and Non-Motor Experiences of Daily Living (17 items). Reliability was acceptable for internal consistency, test-retest stability, item discrimination, item-scaling thresholds and item-fit. Examination of construct validity revealed a parsimonious two-factor solution, and concurrent validity demonstrated significant correlations between the CBFS and other measures of disease severity and functional impairment. The CBFS significantly discriminated between all diagnostic groups and controls (all AUCs>90). The CBFS scores demonstrated sensitivity to change over a 12 month follow-up in patients with probable 4RTs. Conclusion(s): The CBFS is a patient/care-giver reported outcome measure with excellent clinimetric properties that captures disability correlated with motor, cognitive and psychiatric impairments.

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Expansile Endocervical Crypt Involvement by CIN2-3 as a Risk Factor for High Grade Cytology Recurrence after Cold Coagulation Cervical Treatment (2020)

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Type of publication:
Journal article

Author(s):
*Papoutsis D.; *Underwood M.; *Parry-Smith W.; *Panikkar J.; *Williams J.

Citation:
Geburtshilfe und Frauenheilkunde; Sep 2020; vol. 80 (no. 9); p. 891-895

Abstract:
Introduction: To determine whether expansile endocervical crypt involvement (ECI) on pretreatment cervical punch biopsies is a risk factor for high grade cytology recurrence in women following cold coagulation for cervical intraepithelial neoplasia (CIN).Materials and Methods: This was a secondary analysis on the results of an observational study of women who had a single cold coagulation cervical treatment between 2001–2011 and who were followed up for cytology recurrence. Women with a previous cervical treatment were excluded.
Results: 559 women were identified with a mean age of 28.7 ± 6.2 years. Expansile and non-expansile ECI were identified in 5.4 and 4.3% of women, respectively. The proportion of women with high grade cytology recurrence was 10% for those with expansile ECI and 2.3% for those without. Multivariate analysis showed that women with expansile ECI when compared to those without, had a four-fold greater risk for high grade cytology recurrence (HR = 4.22; 95% CI: 1.10–16.29, p = 0.036). There was no significant association found between non-expansile ECI and overall or high grade cytology recurrence. The increased biopsy depth and the CIN3 grade of pretreatment cervical punch biopsies were significantly associated with greater odds for the detection of expansile ECI. We calculated that the optimal-cut off of pretreatment cervical punch biopsy depth for the detection of expansile ECI was 4 mm (sensitivity: 73.3%; specificity: 55.1%).
Conclusions: Expansile ECI is a risk factor that increases the likelihood of high grade cytology recurrence following cold coagulation. Deeper pretreatment cervical punch biopsies need to be taken so as not to miss expansile ECI prior to ablative treatment.

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Effective echo screening and inter modality agreement in the assessment of ascending thoracic aorta dimension (2020)

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Type of publication:
Conference abstract

Author(s):
*Botley S.; *Challinor E.; *Ingram T.; *Lee E.; *Pakala V.

Citation:
Heart; Jul 2020; vol. 106

Abstract:
Introduction: Accurate measurement and interval monitoring of the ascending aorta for at risk individuals are crucial for prevention of life-threatening complications. Echocardiography (echo) is the first line screening test. Positive results are referred for computed tomography (CT) or magnetic resonance imaging (MRI), both are considered gold standard methods for imaging the whole aorta. These tests involve radiation (CT) and contrast (CT & MRI) exposure. An effective screening echo streamlines subsequent referrals to CT and MRI. Several published references (1,2,3) are in clinical use. Measurements are normalised to body surface area (1,3), height (2), gender (2,3) and age (3). The aims of this study were: Assess the inter-modality agreement of ascending aorta measurements between echo and CT. Compare the rate of 'dilated aorta' using the existing references (1,2,3). Methods Between Sep 2018 and Sep 2019, 107 patients underwent gated CT thoracic aorta at our institute as per clinically indicated. We retrospectively examined these records. We used Bland Altman plot to assess inter-modality agreement (echo & CT) of ascending aorta measurements. We reported inter and intra-observer variability for echo measurements as coefficient of variation. Echo aorta measurements were coded into 'dilated' or 'normal' after normalising for age, sex, height and weight as per the existing references (1,2,3). The rates of 'dilated aorta' using the three reference methods (1,2,3) were compared using Chi-squared test with Bonferroni adjustment. Statistical analysis was performed using SPSS 25 (IBM). Results Data were excluded from analysis due to incomplete biometrics (9), poor echo images (27). 71 subjects were included for analysis (age 68 +/- 14 years, BSA 1.9 +/- 0.2 m2, 52.1% male). 16 had bicuspid aortic valves. Intra- and interobserver variability for echo measurements were 1.2% and 1.4% respectively. Figure 1 shows the inter-modality agreement of ascending aorta measurements. Echo underestimated ascending aorta dimensions by a mean of 1.4 +/- 2.7 mm (95% CI 0.7-2.0 mm). There was a significant difference in the rates of 'dilated aorta' using the existing reference ranges (1,2,3): 59% (1), 27% (3) and 59% (2) of subjects had 'dilated aorta', c2 = 15.3, p=0.00. Conclusion Echo is an effective screening test for detecting ascending aorta dilatation. In our department, it has excellent intra- and inter- observer variability and good measurement agreement with CT. Normalising aortic dimension (3) resulted in the fewest 'positive test' requiring further imaging; potentially improving clinical efficacy of the service and avoiding contrast and radiation exposure for the patients.

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