Staff Publication

Does arbitration work? (2021)

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Type of publication:
Conference abstract

Author(s):
*Williams S.; *Deane L.; *Burley S.; *Cielecki L.; *Aksoy U.; *Metelko M.

Citation:
Breast Cancer Research 2021, 23(Suppl 1):P63

Abstract:
Introduction: To improve cancer detection rates, personal performance and as part of our routine service improvement programme, an audit was undertaken of discordant cases returned directly to routine recall between 1/4/15 and 31/3/17 inclusive. These were reviewed against the results of the subsequent screening round to determine if the correct judgement had been made at the previous screening round or if there were any opportunities to learn from misinterpretation.
Method(s): All cases arbitrated and directly returned to routine screening between 2015/16 and 2016/17 were identified and crossreferenced with the results for the subsequent screening episode. All screen detected cancers previously arbitrated on the same side were reviewed by the same routine method and criteria as all interval cancers within our unit and each was given an 'interval' category. All of the screen detected cancers previously arbitrated on the same side were included in the annual interval cancer review session to discuss learn opportunities and improved outcomes.
Result(s): There were 829 cases arbitrated and returned to routine screening at the original screening episode 2015/16 or 2016/17. 11 cases were diagnosed with a same side screen detected cancer at the subsequent screening round and 2 cases presented as a same side interval cancer. Neither interval cancers detected at the case review. 1 of the 11 same side screen detected cancers classified as minimal signs.
Conclusion(s): In our unit arbitration cases returned to routine recall is the correct decision in the vast majority.

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Survey of Foundation Year 1 doctors in managing and preparing patients for anaesthesia (2021)

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Type of publication:
Conference abstract

Author(s):
Cheng Y.; *Noakes A.

Citation:
Anaesthesia; Jul 2021; vol. 76 ; p. 95

Abstract:
Introduction Good management of surgical patients on the ward before surgery has a significant impact on postoperative outcome. Foundation Year 1 (FY1) doctors are fundamental in ensuring all patients are managed and prepared for anaesthesia and surgery appropriately. Our initial survey showed FY1 doctors lacked confidence in managing patients pre-operatively and preparing them for anaesthesia. Therefore, a teaching session was organised, which all FY1 doctors found useful. Methods An online survey was sent to all FY1 doctors in Royal Shrewsbury and Telford hospital asking about their confidence level in managing pre-operative conditions using five scales ranging from no confidence to very confident. After the teaching session, feedback was collected to assess the usefulness of the teaching. Results In our survey, 22 responses were collected. Only 31.8% of respondents were confident in fasting guidelines and pre-procedure cessation regime for warfarin, anticoagulants and anti-platelets and bridging therapy for anticoagulants. Of the respondents, 18.2% were confident in managing peri-operative medications (e.g. withholding certain medications), 27.3% of respondents were confident in managing pre-operative anaemia and 72.7% of respondents had little or no confidence in preparing patients with cardiac implantable electronic devices for surgery. In feedback that was collected after the teaching (n = 25), 90% of attendees found it extremely and very useful. Discussion The survey results showed low confidence in FY1 doctors in preparing patients for surgery and anaesthesia. This led to a teaching session facilitated by anaesthetic registrars and consultants. They were introduced to local hospital guidelines, which all of them found useful. Topics covered in the teaching session included fasting guidelines, management of perioperative medications, management of pre-operative anaemia, pre-procedure cessation for anticoagulants and bridging therapies and pre-operative management of diabetic, hypertensive, cardiac and renal patients. With good feedback, this teaching will be incorporated into their weekly teaching and will be taught yearly to all FY1 doctors. Feedback was also collected to improve our delivery of the teaching sessions

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Environmental impact of anaesthetic gases at a tertiary hospital: A comparison of subspecialties and analysis of anaesthetic choices (2021)

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Type of publication:
Conference abstract

Author(s):
Ito Y.; Takacs R.; Mittal R.; *Damm E.; Daley H.

Citation:
Anaesthesia; Jul 2021; vol. 76 ; p. 103

Abstract:
The Anthropocene has already caused warming exceeding 1.2degreeC compared to pre-industrial levels, resulting in profound, immediate and rapidly worsening health effects. The climate crisis will continue to worsen without meaningful intervention [1]. Five per cent of the total carbon footprint (CF) of the NHS is due to inhalational anaesthesia [2]. Anaesthetists therefore have a unique opportunity and obligation to intervene [2]. Methods: Data of inhaled anaesthesia during maintenance phase were collected in 13 theatres in a tertiary hospital over a 9-day period. Data were extracted from Maquet Flow-i anaesthetic machines and the Bluerspier theatre information system. Case categories included emergency, elective and trauma; covering most surgical specialties. The 'Anaesthetic Impact Calculator' application was used to calculate the equivalent of CO2 kg.h-1 produced, cost, and km.h-1 for a car (efficiency 122 g.km-1). End tidal (ET) sevoflurane of 2.1, flow of 0.3 l.min-1, was used to calculate a benchmark of ideal volatile use. Results One hundred and seventy-three cases with complete datasets were included. Eighty-six per cent were performed under general anaesthesia (GA). Sixty-six per cent of cases used sevoflurane, 16% isoflurane, and 4% desflurane. Desflurane increased the cost and CF significantly, whereas N2O increased CF only. Fifty per cent of desflurane usage was in neurosurgery, followed by general and thoracic surgery. N2O was used in 20% of cases, of which 64% were trauma. Thirty per cent of paediatric cases used N2O, compared to 18% in adults. The highest CO2 kg.h-1 was recorded for emergency work (17.6), followed by elective (7.7), then trauma (4.7). Our data suggest this was mostly due to excessive gas flow. General surgery was first at (19.7), followed by neuro (16), and thirdly thoracic surgery (9.4). If using ET sevoflurane of 2.1 with 0.3 l.h-1 O2, a total of 2916 kg of CO2 could have been saved; equivalent to driving 24,065 km, or saving 1284. Discussion Sixty-six per cent of cases used sevoflurane, with few at low-flow rates. An alarming 20% used N2O. Only 14% of cases used techniques that avoided GA. There was a significant variation of CF between specialties. Our project is likely to under-represent the CF/anaesthetic as induction was not included. Every effort should be taken to use anaesthetic techniques avoiding use of inhalational anaesthesia. If required, lower carbon alternatives should be used at low flow, avoiding N2O. This is in line with the NHS Long Term Plan committed to lowering the 2% of the NHS' CF from anaesthetic gases by 40% [2].

Link to full-text [no password required]

Intrauterine contraception (2021)

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Type of publication:
Journal article

Author(s):
*Ritchie J.; Phelan N.; Briggs P.

Citation:
Obstetrician and Gynaecologist; Jul 2021; vol. 23 (no. 3); p. 187-195

Abstract:
Key content: An intrauterine device (IUD), also known as intrauterine contraceptive device (IUCD) or intrauterine contraception (IUC) offers reliable long-acting reversible contraception; however, some patients can be hesitant to choose this option because of misconceptions about side effects and perceived complications. A comprehensive knowledge of IUC is required to allow adequate counselling and to dispel myths. There are many different methods of IUC, including four different levonorgestrel-containing intrauterine systems (LNG-IUS) and multiple different copper intrauterine devices, with different insertion techniques. Considering contraception is important at several life stages, including post-delivery, post-termination of pregnancy and around the menopause; these will require different counselling. The use of IUC can have noncontraceptive benefits, including relief of heavy menstrual bleeding, management of menopause and premenstrual syndrome and reducing gynaecological cancer risk. Learning objectives: To learn the different types of IUC, including the different indications and possible complications. To understand the noncontraceptive benefits of IUC. To understand the challenges faced when a patient is hesitant to consider IUC

Link to full-text [NHS OpenAthens account required]

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs (2021)

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Type of publication:
Systematic Review

Author(s):
Cordell H.J.; Fryett J.J.; Darlay R.; Ueno K.; Khor S.-S.; Kawai Y.; Tokunaga K.; Aiba Y.; Nakamura M.; Hitomi Y.; Kawashima M.; Nishida N.; Gervais O.; Nagasaki M.; Tang R.; Ma X.; Shi Y.; Li Z.; Juran B.D.; Cheung A.; Lazaridis K.N.; Atkinson E.J.; de Andrade M.; Gerussi A.; Carbone M.; Invernizzi P.; Cristoferi L.; D'Amato D.; Malinverno F.; Mancuso C.; Massironi S.; Milani C.; Ronca V.; Asselta R.; Baras A.; Horowitz J.; Ferreira M.A.R.; Sun D.; Jones D.E.; Flack S.; Spicer A.; Mulcahy V.L.; Sandford R.N.; Mells G.F.; Byan J.; Han Y.; Amos C.I.; Hirschfield G.M.; Seldin M.F.; Siminovitch K.A.; Mason A.; Vincent C.; Xie G.; Zhang J.; Affronti A.; Almasio P.L.; Alvaro D.; Andreone P.; Andriulli A.; Azzaroli F.; Battezzati P.M.; Benedetti A.; Bragazzi M.; Brunetto M.; Bruno S.; Calvaruso V.; Cardinale V.; Casella G.; Cazzagon N.; Ciaccio A.; Coco B.; Colli A.; Colloredo G.; Colombo M.; Colombo S.; Cursaro C.; Croce L.S.; Crosignani A.; Donato F.; Elia G.; Ferrari C.; Fabris L.; Fagiuoli S.; Floreani A.; Galli A.; Marra F.; Giannini E.; Grattagliano I.; Lampertico P.; Lleo A.; Marzioni M.; Mattalia A.; Miele L.; Morini L.; Morisco F.; Muratori L.; Muratori P.; Niro G.A.; O'Donnell S.; Picciotto A.; Portincasa P.; Rigamonti C.; Rosina F.; Spinzi G.; Strazzabosco M.; Tarocchi M.; Tiribelli C.; Toniutto P.; Valenti L.; Vinci M.; Zuin M.; Nakamura H.; Abiru S.; Nagaoka S.; Komori A.; Yatsuhashi H.; Ishibashi H.; Ito M.; Migita K.; Ohira H.; Katsushima S.; Naganuma A.; Sugi K.; Komatsu T.; Mannami T.; Matsushita K.; Yoshizawa K.; Makita F.; Nikami T.; Nishimura H.; Kouno H.; Ota H.; Komura T.; Nakamura Y.; Shimada M.; Hirashima N.; Komeda T.; Ario K.; Nakamuta M.; Yamashita T.; Furuta K.; Kikuchi M.; Naeshiro N.; Takahashi H.; Mano Y.; Tsunematsu S.; Yabuuchi I.; Shimada Y.; Yamauchi K.; Sugimoto R.; Sakai H.; Mita E.; Koda M.; Tsuruta S.; Kamitsukasa H.; Sato T.; Masaki N.; Kobata T.; Fukushima N.; Ohara Y.; Muro T.; Takesaki E.; Takaki H.; Yamamoto T.; Kato M.; Nagaoki Y.; Hayashi S.; Ishida J.; Watanabe Y.; Kobayashi M.; Koga M.; Saoshiro T.; Yagura M.; Hirata K.; Tanaka A.; Takikawa H.; Zeniya M.; Abe M.; Onji M.; Kaneko S.; Honda M.; Arai K.; Arinaga-Hino T.; Hashimoto E.; Taniai M.; Umemura T.; Joshita S.; Nakao K.; Ichikawa T.; Shibata H.; Yamagiwa S.; Seike M.; Honda K.; Sakisaka S.; Takeyama Y.; Harada M.; Senju M.; Yokosuka O.; Kanda T.; Ueno Y.; Kikuchi K.; Ebinuma H.; Himoto T.; Yasunami M.; Murata K.; Mizokami M.; Kawata K.; Shimoda S.; Miyake Y.; Takaki A.; Yamamoto K.; Hirano K.; Ichida T.; Ido A.; Tsubouchi H.; Chayama K.; Harada K.; Nakanuma Y.; Maehara Y.; Taketomi A.; Shirabe K.; Soejima Y.; Mori A.; Yagi S.; Uemoto S.; H E.; Tanaka T.; Yamashiki N.; Tamura S.; Sugawara Y.; Kokudo N.; Chalasani N.; Luketic V.; Odin J.; Chopra K.; Abecasis G.; Cantor M.; Coppola G.; Economides A.; Lotta L.A.; Overton J.D.; Reid J.G.; Shuldiner A.; Beechert C.; Forsythe C.; Fuller E.D.; Gu Z.; Lattari M.; Lopez A.; Schleicher T.D.; Padilla M.S.; Toledo K.; Widom L.; Wolf S.E.; Pradhan M.; Manoochehri K.; Ulloa R.H.; Bai X.; Balasubramanian S.; Barnard L.; Blumenfeld A.; Eom G.; Habegger L.; Hawes A.; Khalid S.; Maxwell E.K.; Salerno W.; Staples J.C.; Jones M.B.; Mitnaul L.J.; Sturgess R.; Healey C.; Yeoman A.; Gunasekera A.V.; Kooner P.; Kapur K.; Sathyanarayana V.; Kallis Y.; Subhani J.; Harvey R.; McCorry R.; Rooney P.; Ramanaden D.; Evans R.; Mathialahan T.; Gasem J.; Shorrock C.; Bhalme M.; Southern P.; Tibble J.A.; Gorard D.A.; Jones S.; Mells G.; Mulcahy V.; Srivastava B.; Foxton M.R.; Collins C.E.; Elphick D.; Karmo M.; Porras-Perez F.; Mendall M.; Yapp T.; Patel M.; Ede R.; Sayer J.; Jupp J.; Fisher N.; Carter M.J.; Koss K.; Shah J.; Piotrowicz A.; Scott G.; Grimley C.; Gooding I.R.; Williams S.; Tidbury J.; Lim G.; Cheent K.; Levi S.; Mansour D.; Beckley M.; Hollywood C.; Wong T.; Marley R.; Ramage J.; Gordon H.M.; Ridpath J.; Ngatchu T.; Bob Grover V.P.; Shidrawi R.G.; Abouda G.; Corless L.; Narain M.; Rees I.; Brown A.; Taylor-Robinson S.; Wilkins J.; Grellier L.; Banim P.; Das D.; Heneghan M.A.; Curtis H.; Matthews H.C.; Mohammed F.; Aldersley M.; Srirajaskanthan R.; Walker G.; McNair A.; Sharif A.; Sen S.; Bird G.; Prince M.I.; Prasad G.; Kitchen P.; Barnardo A.; Oza C.; Sivaramakrishnan N.N.; Gupta P.; Shah A.; Evans C.D.; Saha S.; Pollock K.; Bramley P.; Mukhopadhya A.; Barclay S.T.; McDonald N.; Bathgate A.J.; Palmer K.; Dillon J.F.; Rushbrook S.M.; Przemioslo R.; McDonald C.; Millar A.; Tai C.; Mitchell S.; Metcalf J.; Shaukat S.; Ninkovic M.; Shmueli U.; Davis A.; Naqvi A.; Lee T.J.; Ryder S.; Collier J.; Klass H.; Cramp M.E.; Sharer N.; Aspinall R.; Ghosh D.; Douds A.C.; Booth J.; Williams E.; Hussaini H.; Christie J.; Mann S.; Thorburn D.; Marshall A.; Patanwala I.; Ala A.; Maltby J.; Matthew R.; Corbett C.; Vyas S.; Singhal S.; Gleeson D.; Misra S.; *Butterworth J.; George K.; Harding T.; Douglass A.; Mitchison H.; Panter S.; Shearman J.; Bray G.; Roberts M.; Butcher G.; Forton D.; Mahmood Z.; Cowan M.; Ch'ng C.L.; Rahman M.; Whatley G.C.A.; Wesley E.; Mandal A.; Jain S.; Pereira S.P.; Wright M.; Trivedi P.; Gordon F.H.; Unitt E.; Palejwala A.; Austin A.; Vemala V.; Grant A.; Higham A.D.; Brind A.; Mathew R.; Cox M.; Ramakrishnan S.; King A.; Whalley S.; Fraser J.; Thomson S.J.; Bell A.; Wong V.S.; Kia R.; Gee I.; Keld R.; Ransford R.; Gotto J.; Millson C.

Citation:
Journal of Hepatology; 2021

Abstract:
Backgrounds & Aims: Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.
Method(s): We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.
Result(s): We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (TH)1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune
disorders.
Conclusion(s): This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. Lay summary: Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these
'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.

Improving outcomes for older people with diabetes (2021)

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Type of publication:
Journal article

Author(s):
*Morris, David

Citation:
Practice Nursing; Jul 2021; vol. 32 (no. 7); p. 270-276

Abstract:
Older people with diabetes have unique challenges. David Morris discusses the importance of individualising care for this group of people An individualised approach aiming to maximise safety, preserve autonomy and improve quality of life is needed when helping an older person to manage their diabetes. It is important to interpret the older person's diabetes in the context of their overall health concerns, including reference to co-morbidities, cognitive function, lifestyle, social setting, and life expectancy, and practice nurses are well placed to work in partnership with people with diabetes to achieve this. Pharmacological treatment goals must be realistic, acknowledging the metabolic consequences of old age, the risks of hypoglycaemia and the dangers of
polypharmacy.

A UK Expert Consensus Approach for Managing Symptomatic Arteriovenous Fistula (AVF) Stenosis in Haemodialysis Patients (2021)

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Type of publication:
Journal article

Author(s):
Jaffer, Ounali; Gibbs, Paul; Gibson, Matthew; Gilbert, James; Hanko, Jennifer; Jeevaratnam, Praveen; Jones, Robert; *Nicholas, Johann; Ramnarine, Raymond; Sivaprakasam, Rajesh; Steiner, Kate; Tippett, Richard; Wilkins, Jason

Citation:
Cardiovascular and interventional radiology; Nov 2021; vol. 44 (no. 11); p. 1736-1746

Abstract:
PURPOSE Stenoses in mature arteriovenous fistulas (AVFs) are common and can negatively impact on the quality of haemodialysis, the longevity of the AVF and lead to debilitating symptoms. Multiple treatment options exist; however, management can vary between different centres. We aimed to establish multidisciplinary consensus on the optimal stepwise application of interventions based on evidence and consensus. METHODS A modified Delphi process was conducted with 13 participants from hospitals across the UK, all of whom have high-volume dialysis access practice. RESULTS The usual intervention to rectify de novo stenoses of mature AVFs is fistuloplasty, although surgery for inflow segment stenoses is also clinically acceptable. Appropriate first-line interventions include plain old balloon angioplasty or high-pressure balloon angioplasty; if these fail during the fistuloplasty, consider upsizing the balloon, prolonged balloon inflation or using alternative interventions, such as cutting or scoring balloons and ultra-high-pressure balloons. Alternative or subsequent interventions vary by anatomical site and may require additional multidisciplinary team input. For a stenoses recurring between 3 and 12 months, it is appropriate to consider interventions used de novo, but with a lower threshold for using drug-coated balloons (DCBs) in all regions and for using stent grafts in all regions but inflow segment. Recurrence after 12 months should be treated as a de novo lesion, with DCBs considered if they have been used successfully during previous interventions. CONCLUSIONS These recommendations aim to provide a practical guide to multidisciplinary teams in order to optimise the use of multiple interventions for rectifying AVF stenoses and provide unified evidence-based practice guidelines.

Requirement of interventional treatment in a patient being conservatively managed for persistent pneumothorax over a prolonged period (2021)

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Type of publication:
Journal article

Author(s):
*Brenac, Sophia

Citation:
BMJ case reports; Jul 2021; vol. 14 (no. 7)

Abstract:
An 85-year-old ex-smoker being managed conservatively over 2 years for a small right apical pneumothorax presented to the respiratory clinic with suddenly worsening shortness of breath and chest pain. A chest radiograph demonstrated sudden deterioration in the size of his pneumothorax. Previous CT scans had found emphysematous cystic changes within the lungs, and his new presentation warranted definitive surgical intervention with a right bullectomy and talc pleurodesis through a video-assisted thoracoscopic surgery procedure. The patient made a good recovery and was discharged from clinic a year later. This case demonstrates the importance of follow-up in patients with unresolved pneumothoraces due to the potential for sudden deterioration, and highlights the significance of respecting patient involvement and autonomy in the decision-making process.

Link to full-text [NHS OpenAthens account required]

Non-drug therapies for the management of chronic constipation in adults: the CapaCiTY research programme including three RCTs (2021)

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Type of publication:
Journal article

Author(s):
Knowles, Charles H; Booth, Lesley; Brown, Steve R; Cross, Samantha; Eldridge, Sandra; Emmett, Christopher; Grossi, Ugo; Jordan, Mary; *Lacy-Colson, Jon; Mason, James; McLaughlin, John; Moss-Morris, Rona; Norton, Christine; Scott, S Mark; Stevens, Natasha; Taheri, Shiva; Yiannakou, Yan.

Citation:
NIHR Journals Library. Programme Grants for Applied Research 2021 Vol 9(14).

Abstract:
BACKGROUND: Chronic constipation affects 1-2% of adults and significantly affects quality of life. Beyond the use of laxatives and other basic measures, there is uncertainty about management, including the value of specialist investigations, equipment-intensive therapies using biofeedback, transanal irrigation and surgery. OBJECTIVES: (1) To determine whether or not standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback is more clinically effective than standardised specialist-led habit training alone, and whether or not outcomes of such specialist-led interventions are improved by stratification to habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or habit training alone based on prior knowledge of anorectal and colonic pathophysiology using standardised radiophysiological investigations; (2) to compare the impact of transanal irrigation initiated with low-volume and high-volume systems on patient disease-specific quality of life; and (3) to determine the clinical efficacy of laparoscopic ventral mesh rectopexy compared with controls at short-term follow-up. DESIGN: The Chronic Constipation Treatment Pathway (CapaCiTY) research programme was a programme of national recruitment with a standardised methodological framework (i.e. eligibility, baseline phenotyping and standardised outcomes) for three randomised trials: a parallel three-group trial, permitting two randomised comparisons (CapaCiTY trial 1), a parallel two-group trial (CapaCiTY trial 2) and a stepped-wedge (individual-level) three-group trial (CapaCiTY trial 3). SETTING: Specialist hospital centres across England, with a mix of urban and rural referral bases. PARTICIPANTS: The main inclusion criteria were as follows: age 18-70 years, participant self-reported problematic constipation, symptom onset > 6 months before recruitment, symptoms meeting the American College of Gastroenterology's constipation definition and constipation that failed treatment to a minimum basic standard. The main exclusion criteria were secondary constipation and previous experience of study interventions. INTERVENTIONS: CapaCiTY trial 1: group 1 – standardised specialist-led habit training alone (n = 68); group 2 – standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback (n = 68); and group 3 – standardised radiophysiological investigations-guided treatment (n = 46) (allocation ratio 3 : 3 : 2, respectively). CapaCiTY trial 2: transanal irrigation initiated with low-volume (group 1, n = 30) or high-volume (group 2, n = 35) systems (allocation ratio 1 : 1). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy performed immediately (n = 9) and after 12 weeks' (n = 10) and after 24 weeks' (n = 9) waiting time (allocation ratio 1 : 1 : 1, respectively). MAIN OUTCOME MEASURES: The main outcome measures were standardised outcomes for all three trials. The primary clinical outcome was mean change in Patient Assessment of Constipation Quality of Life score at the 6-month, 3-month or 24-week follow-up. The secondary clinical outcomes were a range of validated disease-specific and psychological scoring instrument scores. For cost-effectiveness, quality-adjusted life-year estimates were determined from individual participant-level cost data and EuroQol-5 Dimensions, five-level version, data. Participant experience was investigated through interviews and qualitative analysis. RESULTS: A total of 275 participants were recruited. Baseline phenotyping demonstrated high levels of symptom burden and psychological morbidity. CapaCiTY trial 1: all interventions (standardised specialist-led habit training alone, standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback and standardised radiophysiological investigations-guided habit training alone or habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback) led to similar reductions in the Patient Assessment of Constipation Quality of Life score (approximately -0.8 points), with no statistically significant difference between habit training alone and habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback (-0.03 points, 95% confidence interval -0.33 to 0.27 points; p = 0.8445) or between standardised radiophysiological investigations and no standardised radiophysiological investigations (0.22 points, 95% confidence interval -0.11 to 0.55 points; p = 0.1871). Secondary outcomes reflected similar levels of benefit for all interventions. There was no evidence of greater cost-effectiveness of habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or stratification by standardised radiophysiological investigations compared with habit training alone (with the probability that habit training alone is cost-effective at a willingness-to-pay threshold of 30,000 per quality-adjusted life-year gain; p = 0.83). Participants reported mixed experiences and similar satisfaction in all groups in the qualitative interviews. CapaCiTY trial 2: at 3 months, there was a modest reduction in the Patient Assessment of Constipation Quality of Life score, from a mean of 2.4 to 2.2 points (i.e. a reduction of 0.2 points), in the low-volume transanal irrigation group compared with a larger mean reduction of 0.6 points in the high-volume transanal irrigation group (difference -0.37 points, 95% confidence interval -0.89 to 0.15 points). The majority of participants preferred high-volume transanal irrigation, with substantial crossover to high-volume transanal irrigation during follow-up. Compared with low-volume transanal irrigation, high-volume transanal irrigation had similar costs (median difference -8, 95% confidence interval -240 to 221) and resulted in significantly higher quality of life (0.093 quality-adjusted life-years, 95% confidence interval 0.016 to 0.175 quality-adjusted life-years). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy resulted in a substantial short-term mean reduction in the Patient Assessment of Constipation Quality of Life score (-1.09 points, 95% confidence interval -1.76 to -0.41 points) and beneficial changes in all other outcomes; however, significant increases in cost (5012, 95% confidence interval 4446 to 5322) resulted in only modest increases in quality of life (0.043 quality-adjusted life-years, 95% confidence interval -0.005 to 0.093 quality-adjusted life-years), with an incremental cost-effectiveness ratio of 115,512 per quality-adjusted life-year. CONCLUSIONS: Excluding poor recruitment and underpowering of clinical effectiveness analyses, several themes emerge: (1) all interventions studied have beneficial effects on symptoms and disease-specific quality of life in the short term; (2) a simpler, cheaper approach to nurse-led behavioural interventions appears to be at least as clinically effective as and more cost-effective than more complex and invasive approaches (including prior investigation); (3) high-volume transanal irrigation is preferred by participants and has better clinical effectiveness than low-volume transanal irrigation systems; and (4) laparoscopic ventral mesh rectopexy in highly selected participants confers a very significant short-term reduction in symptoms, with low levels of harm but little effect on general quality of life. LIMITATIONS: All three trials significantly under-recruited [CapaCiTY trial 1, n = 182 (target 394); CapaCiTY trial 2, n = 65 (target 300); and CapaCiTY trial 3, n = 28 (target 114)]. The numbers analysed were further limited by loss before primary outcome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11791740,
ISRCTN11093872 and ISRCTN11747152.

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Evidence-based use of newer agents in type 2 diabetes (2021)

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Type of publication:
Journal article

Author(s):
*Morris, D.

Citation:
Journal of Prescribing Practice; Jun 2021; vol. 3 (no. 6); p. 224-234

Abstract:
The DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors are newer agents for glycaemic control in type 2 diabetes that can offer additional health benefits. All three treatments carry a low risk of hypoglycaemia. GLP-1 RAs and SGLT-2 inhibitors are associated with weight loss and DPP-4 inhibitors are weight neutral. The GLP-1 RAs and SGLT-2 inhibitors offer protection against cardiovascular events. SGLT-2 inhibitors are the agents of choice to add on to metformin for glycaemic control in chronic kidney disease and heart failure, with GLP-1 RAs an alternative to be considered if SGLT-2 inhibitors are poorly tolerated or contraindicated. DPP-4 inhibitors are very well tolerated. Gastrointestinal side-effects can be problematic with GLP-1 RAs though frequently these settle with time. Genital thrush is a common side-effect with SGLT-2 inhibitors and diabetic ketoacidosis is a rare but serious side-effect. It is important that healthcare professionals with responsibility in diabetes familiarise themselves with these treatments in order to know when and how to safely and effectively deploy them. The selection of newer agents should be based on careful assessment of individual circumstances. Overall, the standpoint has shifted from a largely glucocentric approach to one considering the impact of treatments on weight, risk of hypoglycaemia, and co-morbidities (notably atherosclerotic cardiovascular disease, heart failure and chronic kidney disease). Case histories are used in the article to illustrate the pragmatic use of these agents.