• Biochemical assessment of patients following ketogenic diets for epilepsy: current practice in the UK and Ireland

      Schoeler, Natasha; Simpson, Zoe; Whiteley, Victoria; Nguyen, Patty; Meskell, Rachel; Lightfoot, Kathryn; Martin-McGill, Kirsty; Olpin, Simon; Ivison, Fiona
      Objective: Biochemical assessment is recommended for patients prior to initiating and following a ketogenic diet (KD). There is no published literature regarding current practice in the UK and Ireland. We aimed to explore practice in comparison to international guidelines, determine approximate costs of biochemical testing in KD patients across the UK and Ireland, and promote greater consistency in KD services nationally. Methods: A survey was designed to determine the biochemical tests requested for patients at baseline, 3-, 6-, 12-, 18- and 24-months+ on KD. The survey was circulated to 39 centres across the UK and Ireland. Results: 16 centres completed the survey. Full blood count, electrolytes, calcium, liver function tests (LFTs), lipid profile and vitamin D were requested at all centres at baseline, in keeping with international guidelines. Bicarbonate, total protein and urinalysis were less consistently requested. Magnesium and zinc were requested by all centres, despite not being specifically recommended for pre-diet evaluation in guidelines. Urea and electrolyte profiles and some LFTs were consistently requested at follow-up, in accordance with guidelines. Other LFTs and renal tests, full blood count, lipid profile, acylcarnitine profile, selenium, vitamin D and urinalysis were less consistently requested at follow-up. The mean costs of the lowest and highest number of tests requested at baseline in our participating centres was £167.54 and £501.93; the mean costs of the lowest and highest number of tests requested at 3-month follow-up was £19.17 and £450.06. Significance: Biochemical monitoring of KD patients varies widely across the UK and Ireland and does not fully correspond to international best practice guidelines. With an ongoing drive for cost-effectiveness within healthcare, further work is needed to streamline practice whilst ensuring patient safety.
    • Clobazam add-on therapy for drug-resistant epilepsy

      Bresnahan, Rebecca; Williamson, John; Martin-McGill, Kirsty J.; Michael, Benedict D.; Marson, Anthony G. (Wiley, 2019-10-22)
    • Dietary approaches for patients with heart failure and diabetes

      Butler, Thomas; Georgousopoulou, Ekavi N; Mellor, Duane (Wiley, 2018-08-20)
    • The low-risk perception of developing type 2 diabetes among women with a previous history of gestational diabetes: a qualitative study

      Sharma, Manisha; Purewal, Tejpal Singh; Fallows, Stephen; Kennedy, Lynne; Edge Hill University; Royal Liverpool Hospital; University of Chester (Wiley, 2019-02-12)
      We conducted a qualitative study to explore the risk perceptions, health beliefs and behaviours of women with a previous history of gestational diabetes mellitus (GDM). Women aged between 18 to 40 years (at the time of pregnancy) with a previous history of GDM, registered at The Royal Liverpool University Hospital, United Kingdom, participated in individual, semi-structured, face-to-face interviews. Qualitative data from seven participants were collected until data saturation and were analysed by thematic analysis. Participants had a low-risk perception of the future risk of developing diabetes. Some believed that their risk was the same as that of any other woman without a history of GDM, and some other participants were not aware of the risk at all and perceived GDM as a temporary health condition with no long-term risks. Participants showed some understanding of a healthy lifestyle in general. However, most of the information was self-acquired by participants and not linked to the future risk of developing diabetes. The findings of this research also indicated a contrast between the high perception of the immediate risks of complications during the pregnancy and low long-term risk of developing diabetes after pregnancy associated with GDM. Participants received healthy lifestyle advice during their pregnancy, but none of them reported involvement in any postnatal health education, intervention or counselling as recommended by 2008 and 2014 NICE guidelines. The low-risk perception impedes positive health behaviour required to overcome the barriers against a healthy lifestyle. This was a small research project but the findings warrant scope for more research in this field. A larger study might promote the development of a well-structured, long-term follow-up health intervention programme, incorporating a reminder system for annual diabetes screenings to improve the risk perception and reduce the risk for the development of type 2 diabetes in this population.
    • Modulation of Innate and Adaptive Immune Responses by Arabinoxylans

      Fadel, Abdulmannan; Plunkett, Andrew; Li, Weili; Ashworth, Jason J.; Manchester Metropolitan University; University of Chester; Al-Baha University; Al-Ahliyya Amman University; Universiti Putra Malaysia; Istanbul Universitesi (Wiley, 2017-11-30)
      Humans are exposed to harmful pathogens and a wide range of noxious substances every day.The immune system reacts to, and destroys, these pathogens and harmful substances. The immunesystem is composed of innate and adaptive immunity, which liaise to protect the host and maintainhealth. Foods, especially cereals, have been reported to modulate the immune response.Arabinoxylans are nonstarch polysaccharides that have been shown to possess immune-modulatory activities. This review article discusses the fundamentals of the immune system andprovides an overview of the immunomodulatory potential of arabinoxylans in conjunction withtheir structural characteristics and proposed similarities with lipopolysaccharides
    • Nice to know: impact of NICE guidelines on ketogenic diet services nationwide

      Whiteley, Victoria; Carroll, Jennifer; Taylor, Hannah; Schoeler, Natasha; Martin-McGill, Kirsty J.; Royal Manchester Childrens Hospital; University of Salford; University of Chester; University of Liverpool; University of Plymouth; Sheffield Childrens Hospital; UCL Great Ormond Street Institute of Child Health (Wiley, 2019-08-20)
      Background In 2012, the National Institute for Health and Care Excellence (NICE) Clinical Guidelines for Epilepsies: Diagnosis and Management (CG137) included, for the first time, ketogenic diets (KDs) as a treatment option for drug‐resistant paediatric epilepsy. The recommendation was made to refer children and young people with epilepsy whose seizures have not responded to appropriate anti‐epileptic drugs to a tertiary paediatric epilepsy specialist for consideration of the use of KDs. We aimed to assess the impact of this change in guidance on the numbers of ketogenic centres and patients following KDs for epilepsy in the UK and Ireland. Methods An online survey was circulated to ketogenic dietitians from the UK and Ireland. The results were compared with similar surveys published in 2000 and 2010. Results The number of centres offering KDs for treatment of epilepsy has risen from 22 in 2000, to 28 in 2010, and to 39 in 2017 (77% overall increase). Seven of these centres accept adult referrals, in comparison to only two centres in 2010. Patient numbers have increased from 101 in 2000 to 754 in 2017. In total, 267 patients are waiting to commence KD at 31 centres. Conclusions Over the last 7 years, the number of patients treated with a KD for epilepsy in the UK and Ireland has increased by 647%, with a 77% increase in the number of centres offering KDs. Despite this rapid growth, there is ongoing demand for patients to be considered for dietary therapy, highlighting the need for continued expansion of KD services nationally.
    • Numerical simulation of non-Newtonian polymer film flow on a rotating spoked annulus

      Hossain, Mohammad Sayeed; Ashraf, Muhammad Arif; Al-Assaf, Saphwan; McMillan, Alison (Wiley, 2017-03-03)
    • Regulation of Inducible Nitric Oxide Synthase by Arabinoxylans with molecular characterization from Wheat Flour in Cultured Human Monocytes

      Zhengxiao, Zhang; Christopher, Smith; Jason, Ashworth; Weili, Li; Manchester Metropolitan University; University of Chester (Wiley, 2018-01-08)
      The immunomodulatory activity of the arabinoxylans (AXs) extracts from cereal sources has been reported to impart health benefits in terms of immune enhancement. This study investigated the effect of enzymatic extraction on extraction yield and structure of AXs from wheat flour pentosan fraction. Under the optimised conditions, the extraction yield of AXs reached up to 81.25%. Furthermore, the study determined whether water-extracted AXs (WEAXs) and enzyme-extracted AXs (E-WEAXs) from wheat flour were able to differentially stimulate nitric oxide (NO) secretion through increased levels of inducible nitric oxide synthase (iNOS) in human U937 monocytes. The results indicated that AXs concomitantly induced (P < 0.05) both NO and iNOS productions in U937 monocytes compared to untreated cells. Compared with WEAXs, E-WEAXs resulted in a higher proportion of low Mw (1–10 KDa) AXs (49.51% vs. 19.11% in WEAXs), a higher A/X ratio (0.83 vs. 0.48 in WEAXs) and a higher yield (12.83 ± 0.35% vs. 7.54 ± 0.47% in WEAXs). Moreover, E-WEAXs induced significantly (P < 0.05) greater NO and iNOS production per million viable cells (61.8 ± 2.7 μm and 42.41 ± 3.83 ng respectively) than WEAXs (51.6 ± 2.6 μm and 33.46 ± 1.48 ng, respectively). The findings suggest AXs may heighten innate immune activity in the absence of infection or disease through an iNOS-mediated stimulation of NO production. The immunomodulatory activity of the wheat-derived AXs was enhanced by enzyme treatment, with low Mw and high A/X ratio associated with elevated NO/iNOS levels in human monocytes compared to water extraction.
    • Regulation of Nitric Oxide Synthase Expression by Structure Modified Arabinoxylans from Wheat Flour in Cultured Human Monocytes

      Zhang, Zhengxiao; Smith, Christopher J.; Ashworth, Jason J.; Li, Weili; Manchester Metropolitan University; University of Chester (Wiley, 2018-01-08)
      The immunomodulatory activity of the arabinoxylans (AXs) extracts from cereal sources has been reported to impart health benefits in terms of immune enhancement. This study investigated the effect of enzymatic extraction on extraction yield and structure of AXs from wheat flour pentosan fraction. Under the optimised conditions, the extraction yield of AXs reached up to 81.25%. Furthermore, the study determined whether water-extracted AXs (WEAXs) and enzyme-extracted AXs (E-WEAXs) from wheat flour were able to differentially stimulate nitric oxide (NO) secretion through increased levels of inducible nitric oxide synthase (iNOS) in human U937 monocytes. The results indicated that AXs concomitantly induced (P < 0.05) both NO and iNOS productions in U937 monocytes compared to untreated cells. Compared with WEAXs, E-WEAXs resulted in a higher proportion of low Mw (1–10 KDa) AXs (49.51% vs. 19.11% in WEAXs), a higher A/X ratio (0.83 vs. 0.48 in WEAXs) and a higher yield (12.83 ± 0.35% vs. 7.54 ± 0.47% in WEAXs). Moreover, E-WEAXs induced significantly (P < 0.05) greater NO and iNOS production per million viable cells (61.8 ± 2.7 μm and 42.41 ± 3.83 ng respectively) than WEAXs (51.6 ± 2.6 μm and 33.46 ± 1.48 ng, respectively). The findings suggest AXs may heighten innate immune activity in the absence of infection or disease through an iNOS-mediated stimulation of NO production. The immunomodulatory activity of the wheat-derived AXs was enhanced by enzyme treatment, with low Mw and high A/X ratio associated with elevated NO/iNOS levels in human monocytes compared to water extraction.
    • Sulthiame add-on therapy for epilepsy

      Bresnahan, Rebecca; Milburn-McNulty, Philip; Powell, Graham; Sills, Graeme; Marson, Anthony G.; Martin-McGill, Kirsty J.; University of Chester; University of Liverpool; The Walton Centre NHS Foundation Trust; University of Glasgow; Liverpool Health Partners (Wiley, 2019-08-27)
      Background This is an updated version of the Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2015, Issue 10. Epilepsy is a common neurological condition, characterised by recurrent seizures. Most people respond to conventional antiepileptic drugs, however, around 30% will continue to experience seizures, despite treatment with multiple antiepileptic drugs. Sulthiame, also known as sultiame, is a widely used antiepileptic drug in Europe and Israel. We present a summary of the evidence for the use of sulthiame as add-on therapy in epilepsy. Objectives To assess the efficacy and tolerability of sulthiame as add-on therapy for people with epilepsy of any aetiology compared with placebo or another antiepileptic drug. Search methods For the latest update, we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group’s Specialized Register and CENTRAL (17 January 2019), MEDLINE Ovid (1946 to January 16, 2019), ClinicalTrials.gov and the WHO ICTRP Search Portal (17 January 2019). We imposed no language restrictions. We contacted the manufacturers of sulthiame, and researchers in the field to seek any ongoing or unpublished studies. Selection criteria Randomised controlled trials of add-on sulthiame, with any level of blinding (single, double or unblinded) in people of any age, with epilepsy of any aetiology. Data collection and analysis Two review authors independently selected trials for inclusion, and extracted relevant data. We assessed these outcomes: (1) 50% or greater reduction in seizure frequency between baseline and end of follow-up; (2) complete cessation of seizures during follow-up; (3) mean seizure frequency; (4) time-to-treatment withdrawal; (5) adverse effects; and (6) quality of life. We used intention-to-treat for primary analyses. We presented results as risk ratios (RR) with 95% confidence intervals (CIs). However, due to the paucity of trials, we mainly conducted a narrative analysis. Sulthiame add-on therapy for epilepsy (Review) 1 Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. For Preview Only Main results We included one placebo-controlled trial that recruited 37 infants with newly diagnosed West syndrome. This trial was funded by DESITIN Pharma, Germany. During the study, sulthiame was given as an add-on therapy to pyridoxine. No data were reported for the outcomes: 50% or greater reduction in seizure frequency between baseline and end of follow-up; mean seizure frequency; or quality of life. For complete cessation of seizures during a nine-day follow-up period for add-on sulthiame versus placebo, the RR was 11.14 (95% CI 0.67 to 184.47; very low-certainty evidence), however, this difference was not shown to be statistically significant (P = 0.09). The number of infants experiencing one or more adverse events was not significantly different between the two treatment groups (RR 0.85, 95% CI 0.44 to 1.64; very low-certainty evidence; P = 0.63). Somnolence was more prevalent amongst infants randomised to add-on sulthiame compared to placebo, but again, the difference was not statistically significant (RR 3.40, 95% CI 0.42 to 27.59; very low-certainty evidence; P = 0.25). We were unable to conduct meaningful analysis of time-to-treatment withdrawal and adverse effects due to incomplete data. Authors’ conclusions Sulthiame may lead to a cessation of seizures when used as an add-on therapy to pyridoxine in infants with West syndrome, however, we are very uncertain about the reliability of this finding. The included study was small and had a significant risk of bias, largely due to the lack of details regarding blinding and the incomplete reporting of outcomes. Both issues negatively impacted the certainty of the evidence. No conclusions can be drawn about the occurrence of adverse effects, change in quality of life, or mean reduction in seizure frequency. No evidence exists for the use of sulthiame as an add-on therapy in people with epilepsy outside West syndrome. Large, multi-centre randomised controlled trials are needed to inform clinical practice, if sulthiame is to be used as an add-on therapy for epilepsy
    • Tiagabine add-on therapy for drug-resistant focal epilepsy

      Bresnahan, Rebecca; Martin-McGill, Kirsty J.; Hutton, Jane L.; Marson, Anthony G. (Wiley, 2019-10-14)
    • Understanding mothers' engagement with antenatal parent education services: A critical analysis of a local Sure Start Service

      Pearson, Charlotte; Thurston, Miranda; University of Chester (Wiley, 2006-03-17)
      This article discusses the findings of a local evaluation of a Sure Start parent education programme designed to improve parental engagement with antenatal services.