Author: Jason Curtis

Diabetic nephropathy and type 2 diabetes (2021)

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Type of publication:Interactive case study

Author(s):*Morris, David

Citation:Diabetes and Primary Care; 2021; 23(1)

Abstract:This interactive case study, presented by Diabetes & Primary Care, takes you through the necessary considerations in managing diabetic nephropathy in an individual with type 2 diabetes. The scenario is not unusual and is one that, as a primary healthcare worker, you could easily be confronted with. By actively engaging with this case history, you should feel more confident and empowered to manage effectively such a problem in the future.

Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study (2021)

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Type of publication:Journal article

Author(s):Harvey P.R.; McKay S.C.; Wilkin R.J.W.; Layton G.R.; Powell-Brett S.; Okoth K.; Trudgill N.; Roberts K.J.; Baker G.; Brom M.K.; Brown Z.; Farrugia A.; Haldar D.; Kalisvaart M.; Marley A.; Pande R.; Patel R.; Stephenson B.T.F.; Baillie C.; Croitoru C.; Eddowes P.J.; Elshaer M.; Farhan-Alanie M.M.; Laing R.; Mann K.; Materacki L.; Nandi S.; Pericleous S.; Prasad P.; Rinkoff S.; Selvaraj E.; Shah J.; Sheel A.R.G.; Szatmary P.; Williams P.; Milburn J.; Bekheit M.; Ghazanfar M.; Curry H.; Persson P.; Rollo A.; Thomson R.; Harper S.; Varghese S.; Collins J.; Stupalkowska W.; Afzal Z.; Badran A.; Barker J.; Hakeem A.; Kader R.; Saji S.; Sheikh S.; Smith A.C.D.; Stasinos K.; Steinitz H.; Malik H.; Burston C.; Carrion-Alvarez L.; Shiwani M.; Ahmad G.; Allen T.; Darley E.; Patil S.; Brooks C.; Cresswell B.; Welsh F.; Cook C.; Smyth R.; Booth R.; West M.; King A.; Tucker O.; Phelan L.; Burahee A.; Devogel C.; Javed A.; Kay R.; Khan S.; Leet F.; Troth T.; Ward A.; Young J.; Murray E.; Gray T.; Johnson R.; Lockwood S.; Young R.; Zhou G.; Portal J.; Rees J.; Arnold B.; Scroggie D.; Abeysekera K.W.M.; Asif A.; Hay F.; Maccabe T.; Pathak S.; Robertson H.; Sandberg C.; Woodland H.; Charalabopoulos A.; Kordzadeh A.; Anderson J.; Napier D.; Hodges P.; Jones G.; Sheiybani G.; Archer T.; Khan A.; Kirk S.; Walker N.; Hassam U.; Wong I.; Silva M.; Jones K.; Allen J.; Abbas S.H.; Harborne M.; Majid Z.; Eardley N.; Reilly I.; Wadsworth P.; Bell C.; Holloway K.; Stockton W.; Thomas R.; Williams K.J.; Canelo R.; Tay Y.; Adnan M.; Aroori S.; Rajaretnam N.; Rekhraj S.; Wilkins A.; Nelapatia R.; Verebcean M.; Braithwaite S.; Apollos J.; Robertson N.; Belgaumkar A.; Brant A.; Shahdoost A.; French J.J.; Sen G.; Thakkar R.; Kanwar A.; Klaptocz J.; Rodham P.; O'Riordan B.; Maharaj G.; Davies M.; Higgs S.; Cutting J.; Joseph M.; Backhouse L.; Butler J.; Cooper J.; O'nions T.; Shaukat S.; Kumar A.; George V.; Ingmire J.; Saha A.; Coe P.; Noor R.; Lykoudis P.; Elshaer A.; Andreou A.; Clarke T.; Davies O.; Rimmer P.; Kanakala V.; Mitra V.; Akol G.; Burgess M.; Elzubier M.; Jones R.; Majumdar D.; Wescott H.; Bailey A.; Gomez M.; Herman O.; Deguara J.; Whitehead-Clarke T.; Gorard L.; Law R.; Leung L.Y.; Whitelaw D.; Adil M.; Krivan S.; Waters J.; Fernandes R.; Mealey L.; Merh R.; Okaro A.; Shepherd J.; O'Reilly D.; Pilkington J.; Hussain Z.; Ingram S.; Stott M.C.; Abbott S.; Bhamra N.; Hirri F.; Lee K.; Murrell J.; Resool S.; Taylor M.; King M.; Madhotra R.; Ayubi H.; Ali J.; Chander N.; Mckune G.; Wothers T.; Shingler G.; Mortimer M.; Dykes K.; Edwards H.; Menon S.; Gautham A.; Ali I.; Anjum R.; Brookes M.; Wilkinson B.; Tait I.; Noaman I.; Wilson M.; Mogan S.; Rushbrook S.; Hyde S.; Baker S.; Hall P.; Lucas H.; Pease J.; Millar A.; Tariq Z.; Blad W.; Cunningham M.; Hall M.; Luthra P.; Seymour K.; Aawsaj Y.; Jones M.; Elliott D.; Finch J.G.; Rajjoub Y.; Gupta A.; Molloy P.; Mykoniatis I.; Atallah E.; Albraba E.; Asimba V.; Baxter A.; Chin A.; Vojtekova K.; Ong L.; Modi H.N.; Muscara F.; Perry M.; Katz C.; Shaban N.; Dichmont L.; Dissanayake T.; Mostafa W.; Ghosh D.; Hwang S.; Bajomo O.; Lloyd T.; Wye J.; Holt A.; Pathanki A.; Townsend S.; Babar N.; Giovinazzo F.; Kennedy L.; Kandathil M.; King D.; Pillai M.; Glen P.; Holroyd D.; Drozdzik S.; Kourounis G.; Thompson J.; McNally S.; Thomas I.; Reddy Y.; Subar D.; Heywood N.; Khoo E.; Austin A.; Awan A.; Tan H.; Kasi M.; Prasad S.; Baqai M.; Abd Alkoddus M.; Al-Allaf O.; Mitchell K.; Mole S.; Yoong A.; Fusai G.; Brown S.; Bulathsinhala S.; Gilliland J.; Boyce T.; Al-Ardah M.; Matthews E.; Wakefield C.; Hou D.; Thomasset S.; Guest R.; Falconer S.; Hughes M.; Johnston C.; Kung J.W.C.; Lee E.; McNally E.; Sherif A.E.; Stutchfield B.; Baron R.D.; Dunne D.F.J.; Dickerson L.D.; Exarchou K.E.; Knight E.; Whelan P.; Hutchins R.; Wilson P.; Phillpotts S.; Badrulhisham F.; Dawes A.; Derwa Y.; Rajagopal S.; Ramoutar S.; Vaik T.; Bhogal R.H.; McLaren N.; Policastro T.; *Butterworth J.; *Riera M.; *Ismail A.; *Ahmed A.; *Alame R.; *Alford K.; *Banerjee S.; *Bull C.; *Kirby G.; Athwal T.; Hebbar S.; Ishtiaq J.; Kamran U.; Abbasi A.; Kamarul-bahrin M.; Banks A.; Khalil A.; Karanjia N.; Trivedi D.; Chakravaratty S.; Frampton A.; Gabriella J.; Pinn G.; Colleypriest B.; Betteridge F.; Murugiah D.; Rossiter A.; Yong K.; Sellahewa C.; Chui K.; Ehsan A.; Fisher N.; Iyer S.; McMurtry H.; Garbutt G.; Mahgoub S.; Alleyne L.; Harvey J.; Johnson K.; Richards E.; Palaniyappan N.; Bowler C.; Inumerable R.; Abu M.; Suhool A.; Talbot T.; Westwood J.; Zumbo G.; Osborne A.; Botes A.; Dyer S.; Thomas-Jones I.; Merker L.; Przemioslo R.; Roderick M.; Valverde J.; Zerafa A.; Barker S.; Wan A.; Lalani R.; Barrett C.; Kapirial N.; McCarthney K.; Ramamoorthy R.; Yalchin M.; Huggett M.; Macutkiewicz C.; Smith A.; Buchanan A.; Burke J.; Goodchild G.; Keane M.G.; Potts J.; Disney B.; McFarlane M.; Baker E.; Bullock S.; Coleman S.; Mcardle C.; Morgan J.; Mozdiak E.; Obisesan A.; O'Flynn L.; Mowbray N.; de Berker H.T.; Driscoll P.; Alberts J.C.; Sadien I.D.; Webb K.; Khalil H.; Parmar C.; Sadigh D.; Seyed-Safi P.; Shala L.; Somasundaram M.; Bryce G.; McCormack K.; Jamieson W.; Mitchell L.; Cheung D.; Hicken B.; Abbas N.; Kurian A.; Tahir I.; Spearman J.; Johnston T.; Jones C.

Citation:Pancreatology; Sep 2021; vol. 21 (no. 6); p. 1127-1134

Abstract:Objective: UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design(s): RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Result(s): Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5-7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion(s): Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required.

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CORONA (COre ultRasOund of covid in iNtensive care and Acute medicine) study: National service evaluation of lung and heart ultrasound in intensive care patients with suspected or proven COVID-19 (2022)

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Type of publication:Journal article

Author(s):Parulekar P.; Powys-Lybbe J.; Aron J.; Knight T.; Lasserson D.; Smallwood N.; Rudge G.; *Miller A.; Peck M.

Citation:Journal of the Intensive Care Society; 2022 [epub ahead of print]

Abstract:Background: Combined Lung Ultrasound (LUS) and Focused UltraSound for Intensive Care heart (FUSIC Heart – formerly Focused Intensive Care Echocardiography, FICE) can aid diagnosis, risk stratification and management in COVID-19. However, data on its application and results are limited to small studies in varying countries and hospitals. This United Kingdom (UK) national service evaluation study assessed how combined LUS and FUSIC Heart were used in COVID-19 Intensive Care Unit (ICU) patients during the first wave of the pandemic. Method(s): Twelve trusts across the UK registered for this prospective study. LUS and FUSIC Heart data were obtained, using a standardised data set including scoring of abnormalities, between 1st February 2020 to 30th July 2020. The scans were performed by intensivists with FUSIC Lung and Heart competency as a minimum standard. Data was anonymised locally prior to transfer to a central database. Result(s): 372 studies were performed on 265 patients. There was a small but significant relationship between LUS score >8 and 30-day mortality (OR 1.8). Progression of score was associated with an increase in 30-day mortality (OR 1.2). 30-day mortality was increased in patients with right ventricular (RV) dysfunction (49.4% vs 29.2%). Severity of LUS score correlated with RV dysfunction (p < 0.05). Change in management occurred in 65% of patients following a combined scan. Conclusion(s): In COVID-19 patients, there is an association between lung ultrasound score severity, RV dysfunction and mortality identifiable by combined LUS and FUSIC Heart. The use of 12-point LUS scanning resulted in similar risk score to 6-point imaging in the majority of cases. Our findings suggest that serial combined LUS and FUSIC Heart on COVID-19 ICU patients may aid in clinical decision making and prognostication.

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Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: The MifeMiso RCT (2021)

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Type of publication:Journal article

Author(s):Devall A.; Chu J.; Gallos I.; Coomarasamy A.; Beeson L.; Cheed V.; Sun Y.; Roberts T.; Ogwulu C.O.; Williams E.; Jones L.; La Fontaine Papadopoulos J.; Hardy P.; Bender-Atik R.; Brewin J.; Hinshaw K.; Ahmed A.; Choudhary M.; Naftalin J.; Nunes N.; Oliver A.; Izzat F.; Bhatia K.; Hassan I.; Jeve Y.; Hamilton J.; Deb S.; Bottomley C.; Ross J.; Watkins L.; *Underwood M.; Cheong Y.; Kumar C.; Gupta P.; Small R.; Pringle S.; Hodge F.; Shahid A.; Horne A.; Quenby S.

Citation:Health Technology Assessment; 2021; vol. 25 (no. 68), p. 1-114

Abstract:Background Miscarriage is the most common complication of pregnancy. As many as 15-25% of pregnancies end in a miscarriage, and the number of miscarriages in England is estimated to be approximately 125,000 per year. Management of miscarriage can be expectant (i.e. waiting for natural miscarriage), medical (i.e. with drugs) or surgical. About 25% of women opt for medical management; however, there is uncertainty about the optimal drug regimens for medical management. Before National Institute for Health and Care Excellence (NICE) guideline CG154 was published in 2012, it was common practice to use a combination of mifepristone (Mifegyne, Exelgyn, Paris, France) and misoprostol. The 2012 guideline, however, recommended that misoprostol alone should be given to women having medical management. This recommendation was based on very limited evidence, from one study of 115 women, which found no difference between a combination of mifepristone and misoprostol and misoprostol alone. Recognising the limited available evidence, NICE and the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) called for a trial. Objectives The primary objective was to test the hypothesis that treatment with mifepristone plus misoprostol is superior to treatment with misoprostol alone for the resolution of miscarriage within 7 days in women diagnosed by pelvic ultrasound scan with a missed miscarriage in the first 14 weeks of pregnancy. The key secondary objective aimed to test the hypothesis that the addition of mifepristone reduces the need for surgical intervention to resolve the miscarriage. Other secondary objectives aimed to evaluate if the addition of mifepristone reduces the need for further doses of misoprostol, to evaluate if the addition of mifepristone improves other clinical outcomes [including surgical intervention up to and including 7 days post randomisation and after 7 days post randomisation, duration of bleeding, infection, negative pregnancy test at 21 days post randomisation, time from randomisation to discharge from early pregnancy unit (EPU) care, side effects and complications], to evaluate if the addition of mifepristone improves patient satisfaction and acceptability of management and to assess the cost-effectiveness of the combination of mifepristone and misoprostol in the medical management of missed miscarriage. Methods Participants were randomised online in a 1: 1 ratio via a secure internet facility through an Integrated Trial Management System. Minimisation was implemented for maternal age (< 30 or >= 30 years), body mass index (< 35 or >= 35 kg/m2), previous parity (nulliparous or parous women), gestational age (< 70 or >= 70 days), amount of bleeding (Pictorial Blood loss Assessment Chart score; <= 2 or >= 3) and randomising centre. Clinical data were collected up to discharge from EPU care. Participants who agreed to participate in the qualitative study were interviewed by telephone or videoconference or face to face within approximately 6 weeks of their discharge date. The primary analysis was by intention to treat. A withintrial cost-effectiveness study and a nested qualitative study were also conducted as part of the trial. Results A total of 711 women, from 28 hospitals in the UK, received either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group [risk ratio (RR) 0.73, 95% confidence interval (CI) 0.54 to 0.98; p = 0.04]. Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (RR 0.70, 95% CI 0.52 to 0.94; p = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview.Women appeared to have a preference for active management of their miscarriage, to help bring a timely resolution to the physical process. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The within-trial cost-effectiveness analysis found that the use of mifepristone and misoprostol resulted in an absolute effect difference of 6.6% (95% CI 0.7% to 12.5%). The average cost per woman was lower in the mifepristone and misoprostol (MifeMiso) group than in the placebo and misoprostol group, with a cost saving of 182 (95% CI 26 to 338). Hence the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone. The modelbased analysis, that compared the trial intervention with other existing possible interventions for the management of miscarriage not analysed in the trial, showed that the MifeMiso intervention is dominant when compared with expectant management and the current medical management strategy. However, the intervention is a less effective, although less costly, strategy than surgical management. Conclusions Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again.

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Healing pattern of the cervical stroma following cold coagulation treatment for cervical intraepithelial neoplasia: A case report (2022)

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Type of publication:
Journal article

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

Citation:
Oncology letters; 2022 Mar; Vol. 23 (3), pp. 81

Abstract:
Cold coagulation of the cervix for cervical intraepithelial neoplasia (CIN), when compared with cervical excision, has previously demonstrated comparable cure rates and a reduction in the rate of spontaneous preterm birth. In the present report the healing pattern in the cervices of two women after cold coagulation is described. Both women underwent cold coagulation due to CIN3, which was found on pre-treatment cervical punch biopsies. They were followed up after cold coagulation and at 7 and 18 months, respectively, they underwent cervical excision. The histopathological slides from the excised specimen were reviewed, which represents the healed cervix after cold coagulation. A clear boundary of collagenisation was noted in the superficial stroma, which appeared to stop at the junction with the healthy muscular stroma. The collagenised superficial stroma depth, which represents the area that was thermally ablated and has now healed, measured 1.6 and 1.5 mm for the two women, respectively, which is less compared with that typically removed by cervical excision. Observations from these two cases indicate that cold coagulation does not appear to disrupt the deep tissue architecture of the cervix and could therefore explain the reduced levels of adverse obstetric morbidity in patients who underwent cold coagulation ablative treatment of the cervix, which has been previously reported.

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Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol (2022)

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Type of publication:
Systematic Review

Author(s):
Attard, Gerhardt; Murphy, Laura; Clarke, Noel W; Cross, William; Jones, Robert J; Parker, Christopher C; Gillessen, Silke; Cook, Adrian; Brawley, Chris; Amos, Claire L; Atako, Nafisah; Pugh, Cheryl; Buckner, Michelle; Chowdhury, Simon; Malik, Zafar; Russell, J Martin; Gilson, Clare; Rush, Hannah; Bowen, Jo; Lydon, Anna; Pedley, Ian; O'Sullivan, Joe M; Birtle, Alison; Gale, Joanna; *Srihari, Narayanan; Thomas, Carys; Tanguay, Jacob; Wagstaff, John; Das, Prantik; Gray, Emma; Alzoueb, Mymoona; Parikh, Omi; Robinson, Angus; Syndikus, Isabel; Wylie, James; Zarkar, Anjali; Thalmann, George; de Bono, Johann S; Dearnaley, David P; Mason, Malcolm D; Gilbert, Duncan; Langley, Ruth E; Millman, Robin; Matheson, David; Sydes, Matthew R; Brown, Louise C; Parmar, Mahesh K B; James, Nicholas D; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators

Citation:
Lancet; Dec 2021 [epub ahead of print]

Abstract:
BACKGROUND Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial with no overlapping controls, the combination-therapy group also received enzalutamide (160 mg daily orally). ADT was given for 3 years and combination therapy for 2 years, except if local radiotherapy was omitted when treatment could be delivered until progression. In this primary analysis, we used meta-analysis methods to pool events from both trials. The primary endpoint of this meta-analysis was metastasis-free survival. Secondary endpoints were overall survival, prostate cancer-specific survival, biochemical failure-free survival, progression-free survival, and toxicity and adverse events. For 90% power and a one-sided type 1 error rate set to 1·25% to detect a target hazard ratio for improvement in metastasis-free survival of 0·75, approximately 315 metastasis-free survival events in the control groups was required. Efficacy was assessed in the intention-to-treat population and safety according to the treatment started within randomised allocation. STAMPEDE is registered with ClinicalTrials.gov, NCT00268476, and with the ISRCTN registry, ISRCTN78818544. FINDINGS Between Nov 15, 2011, and March 31, 2016, 1974 patients were randomly assigned to treatment. The first trial allocated 455 to the control group and 459 to combination therapy, and the second trial, which included enzalutamide, allocated 533 to the control group and 527 to combination therapy. Median age across all groups was 68 years (IQR 63-73) and median PSA 34 ng/ml (14·7-47); 774 (39%) of 1974 patients were node positive, and 1684 (85%) were planned to receive radiotherapy. With median follow-up of 72 months (60-84), there were 180 metastasis-free survival events in the combination-therapy groups and 306 in the control groups. Metastasis-free survival was significantly longer in the combination-therapy groups (median not reached, IQR not evaluable [NE]-NE) than in the control groups (not reached, 97-NE; hazard ratio [HR] 0·53, 95% CI 0·44-0·64, p<0·0001). 6-year metastasis-free survival was 82% (95% CI 79-85) in the combination-therapy group and 69% (66-72) in the control group. There was no evidence of a difference in metatasis-free survival when enzalutamide and abiraterone acetate were administered concurrently compared with abiraterone acetate alone (interaction HR 1·02, 0·70-1·50, p=0·91) and no evidence of between-trial heterogeneity (I2 p=0·90). Overall survival (median not reached [IQR NE-NE] in the combination-therapy groups vs not reached [103-NE] in the control groups; HR 0·60, 95% CI 0·48-0·73, p<0·0001), prostate cancer-specific survival (not reached [NE-NE] vs not reached [NE-NE]; 0·49, 0·37-0·65, p<0·0001), biochemical failure-free-survival (not reached [NE-NE] vs 86 months [83-NE]; 0·39, 0·33-0·47, p<0·0001), and progression-free-survival (not reached [NE-NE] vs not reached [103-NE]; 0·44, 0·36-0·54, p<0·0001) were also significantly longer in the combination-therapy groups than in the control groups. Adverse events grade 3 or higher during the first 24 months were, respectively, reported in 169 (37%) of 451 patients and 130 (29%) of 455 patients in the combination-therapy and control groups of the abiraterone trial, respectively, and 298 (58%) of 513 patients and 172 (32%) of 533 patients of the combination-therapy and control groups of the abiraterone and enzalutamide trial, respectively. The two most common events more frequent in the combination-therapy groups were hypertension (abiraterone trial: 23 (5%) in the combination-therapy group and six (1%) in control group; abiraterone and enzalutamide trial: 73 (14%) and eight (2%), respectively) and alanine transaminitis (abiraterone trial: 25 (6%) in the combination-therapy group and one (<1%) in control group; abiraterone and enzalutamide trial: 69 (13%) and four (1%), respectively). Seven grade 5 adverse events were reported: none in the control groups, three in the abiraterone acetate and prednisolone group (one event each of rectal adenocarcinoma, pulmonary haemorrhage, and a respiratory disorder), and four in the abiraterone acetate and prednisolone with enzalutamide group (two events each of septic shock and sudden death). INTERPRETATION Among men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population. FUNDING Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

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Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial (2021)

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Type of publication:
Randomised controlled trial

Author(s):
Devall A.; Chu J.; Beeson L.; Hardy P.; Cheed V.; Sun Y.; Roberts T.; Ogwulu C.O.; Williams E.; Jones L.; Papadopoulos J.F.; Bender-Atik R.; Brewin J.; Hinshaw K.; Choudhary M.; Ahmed A.; Naftalin J.; Nunes N.; Oliver A.; Izzat F.; Bhatia K.; Hassan I.; Jeve Y.; Hamilton J.; Deb S.; Bottomley C.; Ross J.; Watkins L.; *Underwood M.; Cheong Y.; Kumar C.; Gupta P.; Small R.; Pringle S.; Hodge F.; Shahid A.; Gallos I.; Horne A.; Quenby S.; Coomarasamy A.

Citation:

Health Technology Assessment, November 2021, 25(68) (pp 1-114)

Abstract:
TRIAL DESIGN: A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne, Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage. METHOD(S): Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1:1 ratio) to receive 200mg of oral mifepristone or matched placebo, followed by 800mug of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage. RESULT(S): A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98; p=0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94; p=0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of 182 (95% confidence interval 26 to 338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone. LIMITATIONS: The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage. FUTURE WORK: Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage. CONCLUSION(S): Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone.

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Myomectomy during cesarean section or non-caesarean myomectomy in reproductive surgery: This is the dilemma. (2021)

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Type of publication:
Journal article

Author(s):
Tinelli A.; Nezhat C.H.; Likic-Ladjevic I.; Andjic M.; Tomasevic D.; *Papoutsis D.; Stefanovic R.; Sparic R.

Citation:
Clinical and Experimental Obstetrics and Gynecology. December 2021, 48(6) (pp 1250-1258)

Abstract:
Nowadays it is quite common to encounter pregnants over 35 years with uterine fibroids (UFs), requiring cesarean section (CS). Large UFs may cause severe complications during delivery, as bleeding and hemorrhage, during vaginal or cesarean delivery. Frequently, the caesarean myomectomy (CM) is recommended, but generally obstetricians are reluctant to perform CM, since literature data do not agree on its surgical recommendation. CM is jet particularly controversial, due to increased risk of perioperative hemorrhage and cesarean hysterectomy, and UFs are often left in situ during cesarean section (CS). CM investigations are generally directed to myomectomy associated issues, whereas CS complications without CM are largely underreported. The risks of leaving UF for an interval myomectomy is underestimated and large UFs, left in uterus during CS, might cause significant early and late postoperative complications, even necessitating a relaparotomy and/or a subsequent hysterectomy. CM would be mandatory in some instances, whatever the UF diameter, to avoid further damage or complications. UFs management prior to CS should include a full counselling on pro and cons on the possible consequences of surgical decisioning. To illustrate what was discussed above, authors performed a narrative review with an expert opinion, reporting a case of a 31-year-old woman with a large UF who underwent a CS without myomectomy. Nine hours after CS, puerpera was submitted, for a massive postoperative hemorrhage and hemorrhagic shock, to an emergency relaparotomy with total hysterectomy without salpingo-oophorectomy

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Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study (2021)

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Type of publication:
Journal article

Author(s):
COVIDSurg Collaborative; GlobalSurg Collaborative (COVIDSurg Collaborative includes *Yen Nee Jenny Bo, *Mohammad Iqbal, *Aarti Lakhiani, *Guleed Mohamed, *William Parry-Smith, *Banchhita Sahu of Shrewsbury and Telford Hospital NHS Trust)

Citation:
Anaesthesia, June 2021, Volume 76, Issue 6, Pages 748-758

Abstract:
Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3–4.8), 3.9 (2.6–5.1) and 3.6 (2.0–5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9–2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2–8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

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