2019

Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial (2019)

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Type of publication:
Journal article

Author(s):
Clarke, N W; Ali, A; Ingleby, F C; Hoyle, A; Amos, C L; Attard, G; Brawley, C D; Calvert, J; Chowdhury, S; Cook, A; Cross, W; Dearnaley, D P; Douis, H; Gilbert, D; Gillessen, S; Jones, R J; Langley, R E; MacNair, A; Malik, Z; Mason, M D; Matheson, D; Millman, R; Parker, C C; Ritchie, A W S; Rush, H; Russell, J M; Brown, J; Beesley, S; Birtle, A; Capaldi, L; Gale, J; Gibbs, S; Lydon, A; Nikapota, A; Omlin, A; O'Sullivan, J M; Parikh, O; Protheroe, A; Rudman, S; *Srihari, N N; Simms, M; Tanguay, J S; Tolan, S; Wagstaff, J; Wallace, J; Wylie, J; Zarkar, A; Sydes, M R; Parmar, M K B; James, N D

Citation:
Annals of Oncology; Dec 2019 30(12) p. 1992-2003

Abstract:
BACKGROUND STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.
METHODS We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.
RESULTS Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).
CONCLUSIONS The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

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See Erratum - The authors regret that Fig.2F has been incorrectly titled. The correct title is “Failure-free survival high burden M1”.

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Management of mid-urethral tape complications: a retrospective study (2019)

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Type of publication:
Journal article

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

Citation:
Journal of Obstetrics and Gynecology of India; 2019 [epub ahead of print]

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

Best supportive care (BSC) with or without lowdose chemotherapy (chemo) in frail elderly patients with advanced gastroesophageal cancer (aGOAC): The uncertain randomization of the GO2 phase III trial (2019)

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Type of publication:
Conference abstract

Author(s):
Swinson D.; Hingorani M.; Stokes Z.; Dent J.; Guptal K.; *Chatterjee A.; Kamposioras K.; Grumett S.A.; Khan M.; Marshall H.; Ruddock S.; Allmark C.; Katona E.; Howard H.C.; Velikova G.; Lord S.; Hall P.S.; Seymour M.T.

Citation:
Journal of Clinical Oncology; May 2019; vol. 37

Abstract:
Background: Before 2000, trials comparing BSC +/chemo for aGOAC showed overall survival (OS) benefit, but in predominantly fit patients (pts). We have revisited this question in a modern context, using lowdose chemo in a frail population, with comprehensive baseline health and frailty assessment.
Method(s): In the GO2 trial, elderly and/or frail aGOAC pts with a ?certain? indication for chemo were randomised between 3 chemo doses. In this GO2 sub-study, pts with an ?uncertain? indication for chemo were instead randomised to BSC +/- the lowest dose chemo. Pts were eligible if clinician and pt agreed the indication for chemo was uncertain. There was no PS threshold, but eGFR >=30 and bili < 2xULN were required. Baseline assessment included global QL, symptom & functional scales, frailty and comorbidity. Randomisation was 1:1 to BSC alone, or with oxaliplatin 78 mg/m2 d1, capecitabine 375 mg/m2 bd d121 (modified if eGFR 3050 ml/min or bili 1.52.0 xULN), q21d. QL was reassessed after 9 and 18 wks. The primary endpoint analysis was OS, adjusted for baseline factors. The sample size for this exploratory sub-study was not preset, but around 60 pts were anticipated.
Result(s): 558 pts entered GO2 at 61 centres 201417, of whom only 45 pts (8%) at 21 centres entered this uncertain randomisation. This would provide 80% power at p = 0.05 (2tailed) to detect an OS HR of 0.3. OS was shorter in pts with worse baseline PS (p<0.01) or distant mets (p<0.05). OS was not significantly improved with chemo; however we cannot exclude HR >0.32. QL deteriorated less with BSC+chemo than with BSC alone.
Conclusion(s): In this frail, poor PS population, we observed a small survival benefit with chemo but this did not reach statistical significance. Clinicians should carefully consider BSC alone as a valid treatment option for aGOAC pts with poor PS and/or frailty.

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Childbirth-related pelvic floor trauma in women at-risk: A survey of the current obstetric management of short stature primigravid women (2019)

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Type of publication:
Conference abstract

Author(s):
*Rachaneni S.; Freeman R.

Citation:
Female Pelvic Medicine and Reconstructive Surgery; 2019; vol. 25 (no. 5)

Abstract:
Objective: To assess the antenatal and intrapartum management of short statured primigravid women in relation to the awareness of the increased risk of long-term pelvic floor morbidity from childbirth, by Obstetricians and Gynaecologists in the UK.
Method(s): We carried out a questionnaire survey with 15 questions about the antenatal and intrapartum management of short statured primigravid women with a clinically large fetus, their timing and mode of delivery and discussion with the women about their risk of long-term pelvic floor morbidity following spontaneous and instrumental vaginal deliveries, their choice of instruments and episiotomy.
Result(s): The survey was completed by 424 Members and Fellows of Royal College of Obstetricians and Gynaecologists (UK). We created a scenario of a short stature primigravid woman who presented with a clinically large baby around 38 weeks gestation. Sixty five percent of the responders stated that they would scan for estimated fetal weight, 48% would offer induction of labo-r at 40 weeks gestation and 13% would offer an elective caesarean section at 39-40 weeks. Only 59% of the responders said that would discuss the risks of obstructed labo-r, shoulder dystocia, instrumental delivery and Obstetric anal sphincter injury. Seventy percent of the responders said they would not discuss the long term risks of urinary, fecal incontinence and prolapse during antenatal or intrapartum management. For intrapartum management with failure to progress in the second stage of labo-r, 69% would attempt a rotational instrumental delivery, and only 5% would offer an emergency caesarean section. Manual rotation followed by 'straight' forceps application (59%) was the most frequent rotational delivery offered followed by Ventouse (40%) and Keillands forceps rotation. Thirty four percent stated that do not routinely perform an episiotomy in this scenario. The choice of instrument was not based on the long-term risk of pelvic floor dysfunction in 73% of the responses.
Conclusion(s): The survey reveals a poor level of counselling of primigravid women of short stature who are known to be at higher risk of long- term pelvic floor trauma and consequent incontinence and prolapse.

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Current management of children and young people with heterozygous familial hypercholesterolaemia - HEART UK statement of care (2019)

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Type of publication:
Journal article

Author(s):
Ramaswami U.; Humphries S.E.; Priestley-Barnham L.; Green P.; Wald D.S.; *Capps N.; Anderson M.; Dale P.; Morris A.A.

Citation:
Atherosclerosis; Nov 2019; vol. 290 ; p. 1-8 [epub ahead of print]

Abstract:
This consensus statement on the management of children and young people with heterozygous familial hypercholesterolaemia (FH) addresses management of paediatric FH in the UK, identified by cascade testing when a parent is diagnosed with FH and for those diagnosed following incidental lipid tests. Lifestyle and dietary advice appropriate for children with FH; suggested low density lipoprotein cholesterol (LDL-C) targets and the most appropriate lipid-lowering therapies to achieve these are discussed in this statement of care. Based on the population prevalence of FH as ~1/250 and the UK paediatric population, there are approximately 50,000 FH children under 18 years. Currently only about 550 of these children and young people have been identified and are under paediatric care.

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Biological Mesh Repair of Paraesophageal Hernia: An Analysis of Our Outcomes (2019)

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Type of publication:
Journal article

Author(s):
*Korwar V.; *Adjepong S.; *Pattar J.; *Sigurdsson A.

Citation:
Journal of Laparoendoscopic and Advanced Surgical Techniques. Part A; Nov 2019; vol. 29 (no. 11); p. 1446-1450

Abstract:
Introduction: Symptomatic paraesophageal hernia (PEH) is an indication for surgical repair. Laparoscopic suture repair has high recurrence rates. Many surgeons prefer mesh repair to reduce PEH recurrence. Several types of mesh, synthetic and biological, are in use. Synthetic mesh has a risk of erosion and stricture, hence we preferred biological mesh repair. Our aim in this study is to assess medium-term outcomes of PEH repair with the use of biological mesh reinforcement over the cruroplasty. We also aimed to correlate clinical recurrences with
radiological recurrences.
Material(s) and Method(s): This is a retrospective study of 154 consecutive patients from a single centre who underwent a standardized laparoscopic suture repair of the hiatus reinforced with an on-lay patch of Surgisis (porcine small intestine submucosa) and fundoplication. The mean age of the patients was 65 years. All patients were called for regular clinical follow-up and a barium study. Modified GERD-HRQL symptom severity
instrument was used to assess postoperative symptoms and satisfaction.
Result(s): The mean follow-up for barium swallow and clinical assessment were 28.42+/-21.2 and 33.69+/-23.46 months. The mean patient satisfaction score after surgery was 4.43+/-1.09 (0-5). Follow-up barium swallow was performed in 122 (79.22%), 87 (56.49%) patients completed clinical follow-up questionnaire, and 77 (50%) had both. Symptomatic recurrence was noted in 25 (28.73%), recurrence on barium swallow 25(20.4%), and 10 (12.98%) had both. The reoperation rate was 3.25%. Mann-Whitney U test showed no statistical significance in reflux-related score between radiological recurrence group compared with no radiological recurrence (P=.06).
Conclusion(s): Biological mesh repair of PEH is safe and well accepted by patients. There is significantly high PEH recurrence rate in long-term follow-up, even with mesh repair. Majority of these recurrences are small, asymptomatic, and the reoperation rate is very low.

Speech and language therapy referrals following Bayley-III developmental assessment on ex-preterms (2019)

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Type of publication:
Journal article

Author(s):
*Ray, Sagarika

Citation:
Infant; Sep 2019; vol. 15 (no. 5); p. 192-194

Abstract:
National Institute for Health and Care Excellence (NICE) guidance recommends multidisciplinary team input during enhanced developmental surveillance for up to two years corrected age in ex-preterm children. However, achieving this may be challenging because of resource constraints. There is a lack of nationally comparable data on neonatal follow-up programmes and outcomes. This article describes a service evaluation of a local neonatal follow-up programme and the role of quality assurance while aspiring to meet NICE recommendations.

External rotation bracing for first-time anterior dislocation of the shoulder: A discontinued randomised controlled trial comparing external rotation bracing with conventional sling (2019)

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Type of publication:
Journal article

Author(s):
Chan, Samuel Kl; *Bentick, Kieran R; Kuiper, Jan H; Kelly, Cormac P

Citation:
Shoulder & elbow; Aug 2019; vol. 11 (no. 4); p. 256-264

Abstract:
Introduction: Itoi et al. introduced the concept of bracing in abduction and external rotation to treat traumatic anterior shoulder dislocations. However, controversy remains as studies have reported variable results. Our study investigates whether there is a difference in outcomes between treatment with a conventional sling or external rotation brace.
Methods: A prospective, multi-centre randomised control trial was conducted between 2006 and 2010. The study was discontinued early with 72 (36 cases in each group) first-time anterior shoulder dislocations recruited.
Results: The re-dislocation rate over 24 months was comparable 30% (95% CI: 17-47) sling vs. 24% (95% CI: 13-41) external rotation bracing. Sixteen percent (95% CI: 7-32) of sling patients and 12% (95% CI: 5-27) of external rotation-bracing patients had shoulder stabilisation surgery within 24 months of the initial dislocation (p > 0.05). There was no difference in OSI scores at 24 months between the two treatment groups and intolerability of the external rotation brace was high.
Conclusion: Recruitment to this study was difficult, and lost-to-follow-up rates were high leading to early discontinuation of the study. The results suggest that ER bracing is unlikely to provide clinical benefit in traumatic first-time anterior shoulder dislocation.

SGLT2 inhibitors - moving on with the evidence (2019)

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Type of publication:
Journal article

Author(s):
*Morris, David

Citation:
Journal of Diabetes Nursing; Jun 2019; vol. 23 (no. 4); p. 1-9

Abstract:
The evidence base on the benefits and risks of using sodium-glucose cotransporter 2 (SGLT2) inhibitors for the management of hyperglycaemia has grown in recent years, with data showing potential cardiovascular and renal benefits, along with safety concerns that warrant cautious use and monitoring in certain users. This article reviews the benefits and difficulties associated with the use of SGLT2 inhibitors in people with type 2 diabetes and, potentially, type 1 diabetes.

Chaperons for child protection medical examinations: A missing link? (2019)

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Type of publication:
Conference abstract

Author(s):
*Saran S.; Ganesh M.; Yousif E.

Citation:
Archives of Disease in Childhood; Jun 2019; vol. 104

Abstract:
Background: Child protection medical examinations should be undertaken in the presence of a chaperone. This as a good practice recommendation is clearly stated in the Child Protection companion. Aim(s): We undertook an audit of Child Protection medical examination reports to see if our practice meets the standards set by RCPCH in Child Protection companion. Method Child protection companion's model report was chosen as the standard to compare our practices. Hospital-based electronic patient records system (clinical portal) was used to review the reports by a single auditor. Twenty-eight reports were randomly selected. These children undertook Child Protection medical examination at a District General Hospital over a period of 14 months from January'2017 to February'2018. Demographics Three-fourth were boys & one-fourth were girls. Fifteen percent were under 1 year old, sixty percent were between 1 & 5 years old and twenty-five percent were over 5 years old. Timeliness Three-fourth of the reports were typed within 72 hours of CP medical examination. Quality All (100%) the reports stated the source of information and recommendations made after assessment. Over three-fourth reports stated informed consent was taken; included a brief introduction of the author and information about the growth centiles. Two-third reports established that child's concerns were recorded. Reference to the evidence-based literature was made in fifteen percent of the reports. Only seven percent of the reports stated use of Chaperones and amendments in the report after peer review meeting. Three percent of the reports stated both the time and date of referral. Recommendations Our audit highlighted that Chaperons is an underused entity in child protection medical examinations. Chaperons are not only supposed to provide assurance to the child and family but also offers clinicians with an extra layer of protection in case of a complaint. Thus we strongly advocate using Chaperon's in all cases of Child Protection Medicals unless declined by the child/family. In that case, this should be clearly documented. There is also a pressing need to improve the quality of overall documentation.

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