Systematic review

A Systematic Review of Long-Distance Triathlon Musculoskeletal Injuries (2022)

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Type of publication:Journal article

Author(s):Rhind JH; Dass D; Barnett A; *Carmont M

Citation:Journal of Human Kinetics 2022 Feb 10; Vol. 81, pp. 123-134.

Abstract:The distribution of injuries affecting long-distance triathletes is yet to be fully understood. A systematic review was performed of the clinical literature to determine the epidemiology of musculoskeletal injuries affecting long-distance triathletes. Searched databases in Feb 2020 were PubMed, Medline, EMBASE, EMCARE, and CINHAL databases. Published observational research articles related to the incidence or prevalence of musculoskeletal injuries in long-distance triathletes (competing at "Ironman" full distance or greater), written in the English language and not restricted by age or gender or date were eligible. Of the 975 studies identified on the initial search, six studies met the inclusion criteria for analysis. The mean age (SD) of the long-distance triathletes in these studies was 35.1 (2.7) and the range was 21-68 years. Overuse injuries were most frequent with the incidence range of 37-91%, and acute injury incidence range was 24-27%. The knee and spine were the most frequent location of injury. Running and cycling were the most frequently affected disciplines. Elite athletes had a lower incidence of overuse injury (37%). The highest acute injury incidence (27%) was recorded in non-elite athletes. The quality of the studies was relatively poor with only one study satisfying >50% of the quality assessment tool questions and only two studies were prospective, the rest were retrospective cross-sectional studies. Overall, there is a lack of literature reporting on musculoskeletal injuries in long-distance triathletes. Overuse injuries, particularly in the knee, are the most frequently reported, running and cycling are the most frequent disciplines associated. Long-distance triathletes may have a lower incidence of both overuse and acute injuries.

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Learning curves in minimally invasive pancreatic surgery: a systematic review (2022)

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Type of publication:Systematic Review

Author(s):Fung, Gayle; Sha, Menazir; Kunduzi, Basir; Froghi, Farid; *Rehman, Saad; Froghi, Saied

Citation:
Langenbeck's Archives of Surgery. 407(6) (pp 2217-2232), 2022. Date of Publication: September 2022.

Abstract:BACKGROUND The learning curve of new surgical procedures has implications for the education, evaluation and subsequent adoption. There is currently no standardised surgical training for those willing to make their first attempts at minimally invasive pancreatic surgery. This study aims to ascertain the learning curve in minimally invasive pancreatic surgery.
METHODS A systematic search of PubMed, Embase and Web of Science was performed up to March 2021. Studies investigating the number of cases needed to achieve author-declared competency in minimally invasive pancreatic surgery were included.
RESULTS In total, 31 original studies fulfilled the inclusion criteria with 2682 patient outcomes being analysed. From these studies, the median learning curve for distal pancreatectomy was reported to have been achieved in 17 cases (10-30) and 23.5 cases (7-40) for laparoscopic and robotic approach respectively. The median learning curve for pancreaticoduodenectomy was reported to have been achieved at 30 cases (4-60) and 36.5 cases (20-80) for a laparoscopic and robotic approach respectively. Mean operative times and estimated blood loss improved in all four surgical procedural groups. Heterogeneity was demonstrated when factoring in the level of surgeon's experience and patient's demographic.
CONCLUSIONS There is currently no gold standard in the evaluation of a learning curve. As a result, derivations are difficult to utilise clinically. Existing literature can serve as a guide for current trainees. More work needs to be done to standardise learning curve assessment in a patient-centred manner.

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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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Fascial defect closure in laparoscopic incisional/ventral hernia: A systematic review and meta-analysis of published randomized, controlled trials (2021)

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Type of publication:Conference abstract

Author(s):Rehman S.; *Akhtar M.S.; Khan M.; Sains P.; Sajid M.S.

Citation:British Journal of Surgery; Oct 2021; vol. 108, Supplement 7

Abstract:Aims: Closure of fascial defect (CFD) during laparoscopic incisional/ ventral hernia repair (LIVHR) remains a controversial issue which requires further investigations to reach a solid conclusion. The objective of this study is to present a systematic review comparing the outcomes of randomized controlled trials evaluating the defect closure versus no-defect closure in patients undergoing LIVHR. Method(s): A systematic review of randomized, controlled trials reporting the fascial defect closure in patients undergoing LIVHR until January 2021 published in Embase, Medline, PubMed, PubMed Central and Cochrane databases was performed using the principles of metaanalysis. Result(s): A total of four RCTs involving 443 patients were included. In the random effects model analysis, using the statistical software Review Manager, defect closure during LIVHR showed no difference in hernia recurrence (risk ratio (RR), 0.89; 95% CI, 0.31, 2.57; z=0.21; P=0.84). In addition, the post-operative complications (RR, 0.69; 95% CI, 0.41, 1.16; z=1.41; P=0.16), duration of operation (Standardized mean difference (SMD), -0.04; 95% CI, -0.52, 0.43; z=0.18; P=0.86) and hospital stay (SMD, 0.27; 95% CI, -0.02, 0.56; z=1.80; P=0.07) were also statistically similar in both groups. CFD was associated with an increased post-operative pain score (SMD, 1.82; 95% CI, 0.61, 3.03; z=2.95; P=0.003). Conclusion(s): Fascial defect closure in patients undergoing LIVHR does not demonstrate any superiority over no-defect closure in terms of recurrence, post-operative morbidity, post-operative pain duration of operation and length of hospital stay.

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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.

Myocardial bridges: A meta-analysis (2021)

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Type of publication:
Systematic Review

Author(s):
*Roberts W.; Ang C.; Charles S.M.; Tubbs R.S.; Loukas M.; Holda M.K.; Walocha J.; Lachman N.

Citation:
Clinical Anatomy; Jul 2021; vol. 34 (no. 5); p. 685-709

Abstract:
Myocardial bridges are anatomical entities characterized by myocardium covering segments of coronary arteries. In some patients, the presence of a myocardial bridge is benign and is only incidentally found on autopsy. In other patients, however, myocardial bridges can lead to compression of the coronary artery during systolic contraction and delayed diastolic relaxation, resulting in myocardial ischemia. This ischemia in turn can lead to myocardial infarction, ventricular arrhythmias and sudden cardiac death. Myocardial bridges have also been linked to an increased incidence of atherosclerosis, which has been attributed to increased shear stress and the presence of vasoactive factors. Other studies however, demonstrated the protective roles of
myocardial bridges. In this study, using systematic review and a meta-analytical approach we investigate the prevalence and morphology of myocardial bridges in both clinical imaging and cadaveric dissections. We also discuss the pathophysiology, clinical significance, and management of these anatomical entities.

Systematic review and metanalyses of prognostic value of circulating tumour cells in early breast cancer (2021)

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Type of publication:
Conference abstract

Author(s):
*Mahmood N.

Citation:
European Journal of Surgical Oncology; May 2021; vol. 47 (no. 5)

Abstract:
Background: Prognostic value of circulating tumour cells (CTC) in breast cancer is currently under investigation. This systematic review with Meta-analysis measures the evidence on prognostic relevance of CTC in early breast cancer presented in recent published studies. Method(s): A detailed search was made for published primary studies, those assessed prognostic value of CTC in early breast cancer. Review and quality assessment of 22 included studies were performed and data on CTC status and disease recurrence and death were extracted. Primary outcomes analysed were hazard ratios for disease-free survival (DFS) and overall survival (OS) between the patient groups with positive and negative detection of CTC. Meta-analysis calculated the pooled hazard ratio (HR) with 95% confidence intervals (CIs) as the overall effect measure on DFS and OS using the fixed and random effects models. Result(s): 22 studies enrolling total of 5724 patients were eligible for the systematic review and meta-analysis. Pooled HR for DFS: 2.81 (CI: 2.20-3, 61) and for OS: 2.74 (CI: 2.20-3.41) was found with CTC positive status. Conclusion(s): This systematic review and meta-analysis finds that positive detection of CTC in early breast cancer is a poor prognostic index for disease recurrence and mortality by nearly 3 times.

Uterotonic agents for first-line treatment of postpartum haemorrhage: a network meta-analysis (2020)

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Type of publication:
Systematic Review

Author(s):
*Parry Smith, William R; Papadopoulou, Argyro; Thomas, Eleanor; Tobias, Aurelio; Price, Malcolm J; Meher, Shireen; Alfirevic, Zarko; Weeks, Andrew D; Hofmeyr, G Justus; Gülmezoglu, Ahmet Metin; Widmer, Mariana; Oladapo, Olufemi T; Vogel, Joshua P; Althabe, Fernando; Coomarasamy, Arri; Gallos, Ioannis D

Citation:
The Cochrane Database of Systematic Reviews; Nov 2020; vol. 11 ; p. CD012754

Abstract:
BACKGROUND Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH. OBJECTIVES To identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile.SEARCH METHODSWe searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies. SELECTION CRITERIA All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion.DATA COLLECTION AND ANALYSIS Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence.MAIN RESULTS Seven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty). AUTHORS' CONCLUSIONS The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.

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Can adjuncts to bowel preparation for colonoscopy improve patient experience and result in superior bowel cleanliness? A systematic review and meta-analysis (2020)

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Type of publication:
Systematic Review

Author(s):
Kamran, Umair; *Abbasi, Abdullah; Tahir, Imran; Hodson, James; Siau, Keith

Citation:
United European gastroenterology journal; Aug 2020 [epub ahead of print]

Abstract:
BACKGROUND Bowel preparation for colonoscopy is often poorly tolerated due to poor palatability and adverse effects. This can negatively impact on the patient experience and on the quality of bowel preparation. This systematic review and meta-analysis was carried out to assess whether adjuncts to bowel preparation affected palatability, tolerability and quality of bowel preparation (bowel cleanliness).METHODS A systematic search strategy was conducted on PubMed, MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to identify studies evaluating adjunct use for colonoscopic bowel preparation. Studies comparing different regimens and volumes were excluded. Specific outcomes studied included palatability (taste), willingness to repeat bowel preparation, gastrointestinal adverse events and the quality of bowel preparation. Data across studies were pooled using a random-effects model and heterogeneity assessed using I2-statistics.RESULTS Of 467 studies screened, six were included for analysis (all single-blind randomised trials; n = 1187 patients). Adjuncts comprised citrus reticulata peel, orange juice, menthol candy drops, simethicone, Coke Zero and sugar-free chewing gum. Overall, adjunct use was associated with improved palatability (mean difference 0.62, 95% confidence interval 0.29-0.96, p < 0.001) on a scale of 0-5, acceptability of taste (odds ratio 2.75, 95% confidence interval: 1.52-4.95, p < 0.001) and willingness to repeat bowel preparation (odds ratio 2.92, 95% confidence interval: 1.97-4.35, p < 0.001). Patients in the adjunct group reported lower rates of bloating (odds ratio 0.48, 95% confidence interval: 0.29-0.77, p = 0.003) and vomiting (odds ratio 0.47, 95% confidence interval 0.27-0.81, p = 0.007), but no difference in nausea (p = 0.10) or abdominal pain (p = 0.62). Adjunct use resulted in superior bowel cleanliness (odds ratio 2.52, 95% confidence interval: 1.31-4.85, p = 0.006). Heterogeneity varied across outcomes, ranging from 0% (vomiting) to 81% (palatability), without evidence of publication bias. The overall quality of evidence was rated moderate.CONCLUSION In this meta-analysis, the use of adjuncts was associated with better palatability, less vomiting and bloating, willingness to repeat bowel preparation and superior quality of bowel preparation. The addition of adjuncts to bowel preparation may improve outcomes of colonoscopy and the overall patient experience.

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Three-dimensional versus two-dimensional imaging during laparoscopic cholecystectomy: a systematic review and meta-analysis of randomised controlled trials (2020)

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Type of publication:
Systematic Review

Author(s):
*Davies S.; Ghallab M.; Hajibandeh S.; Hajibandeh S.; Addison S.

Citation:
Langenbeck's Archives of Surgery; Aug 2020; vol. 405 (no. 5); p. 563-572

Abstract:
Objectives: To evaluate the comparative outcomes of three-dimensional (3D) versus two-dimensional (2D) imaging during laparoscopic cholecystectomy.
Method(s): We conducted a systematic search of electronic information sources and bibliographic reference lists and applied a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits. Procedure time, Calot's triangle dissection time, gallbladder removal time, gallbladder perforation, intraoperative bleeding, postoperative complications, conversion to open and intraoperative errors were the evaluated outcome parameters.
Result(s): We identified 6 randomised controlled trials (RCT) reporting a total of 577 patients who underwent laparoscopic cholecystectomy using 3D (n = 282) or 2D (n = 295) imaging. The 3D imaging was associated with significantly shorter procedure time (MD – 4.23, 95% CI – 8.14 to – 0.32, p = 0.03), Calot's triangle dissection time (MD – 4.19, 95% CI – 6.52 to – 1.86, p = 0.0004) and significantly lower risk of gallbladder perforation (RR 0.50, 95% CI 0.28-0.88, p = 0.02) compared to the 2D approach. No significant difference was found in gallbladder removal time (MD – 0.79, 95% CI – 2.24 to 0.66, p = 0.28), intraoperative bleeding (RR 1.14, 95% CI 0.68-1.90, p = 0.61), postoperative complications (RD – 0.01, 95% CI – 0.06 to 0.05, p = 0.85), conversion to open (RD 0.00, 95% CI – 0.02 to 0.03, p = 0.70) or intraoperative errors (RR 0.96, 95% CI 0.79-1.17, p = 0.70) between the two groups.
Conclusion(s): Although our findings suggest that the use of 3D imaging during laparoscopic cholecystectomy may be associated with significantly shorter procedure time, Calot's triangle dissection time and gallbladder injury compared to the 2D imaging, the differences seem to be clinically insignificant. Moreover, both approaches carry s similar risk of postoperative morbidities. The impact of the surgeon's level of experience and difficulty of the procedure on the outcomes of each imaging modality remains unknown.