Open access

Folic Acid Supplementation in Postmenopausal Women with Hot Flushes: Phase III Randomised Double-Blind Placebo-Controlled Trial (2021)

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Type of publication:
Randomised controlled trial

Author(s):
Ayman Ewies, Ikhlaq Ahmed, Farook Alazzawi, Joan Pitkin, Pratima Gupta, Mojca Persic, *Banchhita Sahu, Alaa El-Ghobashy, Lisa Barraclough, Jacqueline Woodman, Jaspreet Babrah, Sarah Bowdem, Deborah Stocken, Lucinda Billingham, Sudha Sundar, Daniel Rea

Citation:
BJOG; November 2021; Volume128, Issue12, Pages 2024-2033

Abstract:
Objective: To assess whether folic acid supplementation ameliorates hot flushes. Design: Double-blind, placebo-controlled randomised trial. Setting: Nine hospitals in England. Population: Postmenopausal women experiencing ≥50 hot flushes weekly. Methods: Women (n=164) were randomly assigned in a 1:1 ratio to receive folic acid 5mg tablet or placebo daily for 12 weeks. Participants recorded frequency and severity of hot flushes in Sloan Diary daily and completed Greene Climacteric and Utian Quality of Life (UQoL) Scales at 4-weekly intervals. Main Outcome Measures: The change in daily Hot Flush Score at week-12 from randomisation based on Sloan Diary Composite Score B calculation. Results: Data of 143 (87%) women was available for the primary outcome. The mean change (SD) in Hot Flush Score at week-12 was -6.98 (10.30) and -4.57 (9.46) for folic acid and placebo group, respectively. The difference between groups in the mean change was -2.41 (95% CI: -5.68, 0.87), p=0.149 and in the adjusted mean change was -2.61 (95% CI: -5.72, 0.49) with p=0.098. There was an increased benefit in the folic acid group regarding changes in total and emotional UQoL scores at week-8 when compared with placebo. The difference in the mean change from baseline was 5.22 (95% CI: 1.16, 9.28) and 1.88 (95% CI: 0.23, 3.52) for total and emotional score, respectively. Conclusions: Folic acid had a greater benefit in reducing Hot Flush Score over 12 weeks in postmenopausal women when compared with placebo; however, the difference did not reach statistical significance. Definitive evidence of benefit requires a larger study.

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Using clinical guidelines to assess the potential value of laboratory medicine in clinical decision-making (2021)

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Type of publication:
Journal article

Author(s):
Hicks A.J.; Carwardine Z.L.; *Hallworth M.J.; Kilpatrick E.S.

Citation:
Biochemia Medica; Feb 2021; vol. 31 (no. 1); p. 10703

Abstract:
Introduction: It is often quoted that 70% of clinical decisions are based on laboratory results, but the evidence to substantiate this claim is lacking. Since clinical guidelines aim to document best-practice decision making for specific disease conditions, inclusion of any laboratory test means that the best available evidence is recommending clinicians use it. Cardiovascular disease (CVD) is the world's most common cause of mortality, so this study reviewed all CVD guidelines published by five national/international authorities to determine what proportion of them recommended laboratory testing. Material(s) and Method(s): Five leading CVD guidelines were examined, namely the European Society of Cardiology (ESC), the UK National Institute for Health and Clinical Excellence (NICE), the American College of Cardiology (ACC), the Australian Heart Foundation (AHF) and the Cardiac Society of Australia and New Zealand (CSANZ). Result(s): A total of 101 guidelines were reviewed. Of the 33 individual ESC guidelines relating to CVD, 24/33 made a direct reference to the use of clinical laboratory tests in either diagnosis or follow-up treatment. The same applied to 15/20 of NICE guidelines, 24/32 from the ACC and 15/16 from the AHF/CSANZ. Renal function and blood count testing were the most recommended (39 and 26 times), with lipid, troponin and natriuretic peptide measurement advocated 25, 19 and 19 times respectively. Conclusion(s): This study has shown that laboratory testing is advocated by between 73% and 94% of individual CVD guideline recommendations from five national/international authorities. This provides an index to assess the potential value of laboratory medicine to healthcare.

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Emotional distress and adjustment in patients with end-stage kidney disease: A qualitative exploration of patient experience in four hospital trusts in the West Midlands, UK (2020)

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Type of publication:
Journal article

Author(s):
Sein K.; Damery S.; Combes G.; Baharani J.; *Nicholas J.

Citation:
PLoS ONE; Nov 2020; vol. 15 (no. 11)

Abstract:
Objectives To explore patient perceptions and experiences of mild-to-moderate emotional distress and the support offered by kidney units to patients with end-stage kidney disease. Methods In-depth, semi-structured qualitative interviews with patients (n = 46) being treated for endstage kidney disease in four hospital Trusts, with data analysed thematically. Results Patients described multiple sources of distress and talked about the substantial burden that emotional challenges raised for their ability to manage their condition and develop coping strategies. Many patients did not feel it appropriate to disclose their emotional issues to staff on the kidney unit, due to a perceived lack of time for staff to deal with such issues, or a perception that staff lacked the necessary skills to provide resolution. Five themes were identified from the patient interviews, broadly related to patients' experience of distress, and the support offered by the kidney unit: I) the emotional burden that distress placed on patients; ii) patients' relationship with the treatment for their condition; iii) strategies for coping and adjustment; iv) patient-staff interactions and the support offered by the kidney unit, and v) the mediating impact of the treatment environment on patient experience of distress and their ability to raise emotional issues with staff. Conclusions Many patients felt unprepared for the likelihood of experiencing emotional issues as part of their condition, for which pre-dialysis education could help in managing expectations, along with support to help patients to develop appropriate coping strategies and adjustments. These findings demonstrate the importance of recognising patient distress and ensuring that talking about distress becomes normalised for patients with end-stage kidney disease.

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Sex differences in cardiovascular morbidity associated with familial hypercholesterolaemia: A retrospective cohort study of the UK Simon Broome register linked to national hospital records (2020)

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Type of publication:
Journal article

Author(s):
Barbara Iyen, Nadeem Qureshi, Stephen Weng, Paul Roderick, Joe Kai, *Nigel Capps, Paul N. Durrington, Ian FW. McDowell, Handrean Soran, Andrew Neil, Steve E. Humphries

Citation:
Atherosclerosis, 2020 Dec;315:131-137

Abstract:
Background and aims: The UK Simon Broome (SB) familial hypercholesterolaemia (FH) register previously reported 3-fold higher standardised mortality ratio for cardiovascular disease (CVD) in women compared to men from 2009 to 2015. Here we examined sex differences in CVD morbidity in FH by national linkage of the SB register with Hospital Episode Statistics (HES).
Methods: Of 3553 FH individuals in the SB register (aged 20–79 years at registration), 2988 (52.5% women) had linked HES records. Standardised Morbidity Ratios (SMbR) compared to an age and sex-matched UK general practice population were calculated [95% confidence intervals] for first CVD hospitalisation in HES (a composite of coronary heart disease (CHD), myocardial infarction (MI), stable or unstable angina, stroke, TIA, peripheral vascular disease (PVD), heart failure, coronary revascularisation interventions).
Results: At registration, men had significantly (p < 0.001) higher prevalence of previous CHD (24.8% vs 17.6%), previous MI (13.2% vs 6.3%), and were commenced on lipid-lowering treatment at a younger age than women (37.5 years vs 42.3 years). The SMbR for composite CVD was 6.83 (6.33–7.37) in men and 7.55 (6.99–8.15) in women. In individuals aged 30–50 years, SMbR in women was 50% higher than in men (15.04 [12.98–17.42] vs 10.03 [9.01–11.17]). In individuals >50 years, SMbR was 33% higher in women than men (6.11 [5.57–6.70] vs 4.59 [4.08–5.15]).
Conclusions: Excess CVD morbidity due to FH remains markedly elevated in women at all ages, but especially those aged 30–50 years. This highlights the need for earlier diagnosis and optimisation of lipid-lowering risk factor management for all FH patients, with particular attention to young women with FH.

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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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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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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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A minimum dataset for a level 1 echocardiogram: A guideline protocol from the british society of echocardiography (2020)

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Type of publication:
Journal article

Author(s):
Hindocha R.; Garry D.; Short N.; *Ingram T.E.; Steeds R.P.; Colebourn C.L.; Pearce K.; Sharma V.

Citation:
Echo Research and Practice; Jun 2020; vol. 7 (no. 2)

Abstract:
The British Society of Echocardiography has previously outlined a minimum dataset for a standard transthoracic echocardiogram, and this remains the basis on which an echocardiographic study should be performed. The importance of ultrasound in excluding critical conditions that may require urgent treatment is well known. Several point-of-care echo protocols have been developed for use by non-echocardiography specialists. However, these protocols are often only used in specific circumstances and are usually limited to 2D echocardiography. Furthermore, although the uptake in training for these protocols has been reasonable, there is little in the way of structured support available from accredited sonographers in the ongoing training and reaccreditation of those undertaking these point-of-care scans. In addition, it is well recognised that the provision of echocardiography on a 24/7 basis is extremely challenging, particularly outside of tertiary cardiac centres. Consequently, following discussions with NHS England, the British Society of Echocardiography has developed the Level 1 echocardiogram in order to support the rapid identification of critical cardiac pathology that may require emergency treatment. It is intended that these scans will be performed by non-specialists in echocardiography and crucially are not designed to replace a full standard transthoracic echocardiogram. Indeed, it is expected that a significant number of patients, in whom a Level 1 echocardiogram is required, will need to have a full echocardiogram performed as soon as is practically possible. This document outlines the minimum dataset for a Level 1 echocardiogram. The accreditation process for Level 1 echo is described separately.

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Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial (2020)

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Type of publication:
Randomised controlled trial

Author(s):
Chu, Justin J; Devall, Adam J; Beeson, Leanne E; Hardy, Pollyanna; Cheed, Versha; Sun, Yongzhong; Roberts, Tracy E; Ogwulu, C Okeke; Williams, Eleanor; Jones, Laura L; La Fontaine Papadopoulos, Jenny H; Bender-Atik, Ruth; Brewin, Jane; Hinshaw, Kim; Choudhary, Meenakshi; Ahmed, Amna; Naftalin, Joel; Nunes, Natalie; Oliver, Abigail; Izzat, Feras; Bhatia, Kalsang; Hassan, Ismail; Jeve, Yadava; Hamilton, Judith; Deb, Shilpa; Bottomley, Cecilia; Ross, Jackie; Watkins, Linda; *Underwood, Martyn; Cheong, Ying; Kumar, Chitra S; Gupta, Pratima; Small, Rachel; Pringle, Stewart; Hodge, Frances; Shahid, Anupama; Gallos, Ioannis D; Horne, Andrew W; Quenby, Siobhan; Coomarasamy, Arri

Citation:
Lancet; Sep 2020; vol. 396 (no. 10253); p. 770-778

Abstract:
BACKGROUND The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone. METHODS MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/m2vs ≥35 kg/m2), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024. FINDINGS Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups. INTERPRETATION Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery. FUNDING UK National Institute for Health Research Health Technology Assessment Programme.

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