Reproducibility of malaria sporozoite challenge model in humans for evaluating efficacy of vaccines and drugs: a systematic review

Abstract Background The development of novel malaria vaccines and antimalarial drugs is limited partly by emerging challenges to conduct field trials in malaria endemic areas, including unknown effects of existing immunity and a reported fall in malaria incidence. As a result, Controlled Human Malaria Infection (CHMI) has become an important approach for accelerated development of malarial vaccines and drugs. We conducted a systematic review of the literature to establish aggregate evidence on the reproducibility of a malaria sporozoite challenge model. Methods A systematic review of research articles published between 1990 and 2018 on efficacy testing of malaria vaccines and drugs using sporozoite challenge and sporozoite infectivity studies was conducted using Pubmed, Scopus, Embase and Cochrane Library, ClinicalTrials.gov and Trialtrove. The inclusion criteria were randomized and non-randomized, controlled or open-label trials using P. falciparum or P. vivax sporozoite challenges. The data were extracted from articles using standardized data extraction forms and descriptive analysis was performed for evidence synthesis. The endpoints considered were infectivity, prepatent period, parasitemia and safety of sporozoite challenge. Results Seventy CHMI trials conducted with a total of 2329 adult healthy volunteers were used for analysis. CHMI was induced by bites of mosquitoes infected with P. falciparum or P. vivax in 52 trials and by direct venous inoculation of P. falciparum sporozoites (PfSPZ challenge) in 18 trials. Inoculation with P. falciparum-infected mosquitoes produced 100% infectivity in 40 studies and the mean/median prepatent period assessed by thick blood smear (TBS) microscopy was ≤ 12 days in 24 studies. On the other hand, out of 12 infectivity studies conducted using PfSPZ challenge, 100% infection rate was reproduced in 9 studies with a mean or median prepatent period of 11 to 15.3 days as assessed by TBS and 6.8 to 12.6 days by PCR. The safety profile of P. falciparum and P.vivax CHMI was characterized by consistent features of malaria infection. Conclusion There is ample evidence on consistency of P. falciparum CHMI models in terms of infectivity and safety endpoints, which supports applicability of CHMI in vaccine and drug development. PfSPZ challenge appears more feasible for African trials based on current evidence of safety and efficacy.

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Hypertensive disorders of pregnancy and cardiometabolic outcomes in childhood: A systematic review

European Journal of Preventive Cardiology ◽

10.1177/2047487319852716 ◽

2019 ◽

Vol 26 (16) ◽

pp. 1718-1747 ◽

Cited By ~ 6

Author(s):

Maria AC Jansen ◽

Linda PM Pluymen ◽

Geertje W Dalmeijer ◽

T Katrien J Groenhof ◽

Cuno SPM Uiterwaal ◽

...

Keyword(s):

Systematic Review ◽

Blood Pressure ◽

Evidence Synthesis ◽

Current Evidence ◽

Cochrane Library ◽

Pregnancy Induced Hypertension ◽

Hypertensive Disorders Of Pregnancy ◽

Hypertensive Disorders ◽

Induced Hypertension ◽

Cardiometabolic Markers

Background Hypertensive disorders of pregnancy (HDPs) are among the leading causes of maternal and perinatal morbidity and mortality worldwide and have been suggested to increase long-term cardiovascular disease risk in the offspring. Objective The objective of this study was to investigate whether HDPs are associated with cardiometabolic markers in childhood. Search strategy PubMed, The Cochrane Library and reference lists of included studies up to January 2019. Selection criteria Studies comparing cardiometabolic markers in 2–18-year-old children of mothers with HDP in utero, to children of mothers without HDP. Data collection and analysis Sixteen studies reported in 25 publications were included in this systematic review, of which three were considered as having high risk of bias. Thus 13 studies were included in the evidence synthesis: respectively two and eight reported pregnancy induced hypertension and preeclampsia, and three studies reported on both HDPs. Main results Most studies ( n = 4/5) found a higher blood pressure in children exposed to pregnancy induced hypertension. Most studies ( n = 7/10) found no statistically significantly higher blood pressure in children exposed to preeclampsia. No association was found between exposure to HDP and levels of cholesterol, triglycerides or glucose ( n = 5/5). No studies investigated an association with (carotid) intima-media thickness, glycated haemoglobin or diabetes mellitus type 2. Conclusions Most studies showed that exposure to pregnancy induced hypertension is associated with a higher offspring blood pressure. There is no convincing evidence for an association between exposure to preeclampsia and blood pressure in childhood. Based on current evidence, exposure to HDP is not associated with blood levels of cholesterol, triglycerides and glucose in childhood.

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Appraisal of systematic reviews on interventions for postpartum depression: systematic review

BMC Pregnancy and Childbirth ◽

10.1186/s12884-020-03496-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ryan Chow ◽

Eileen Huang ◽

Allen Li ◽

Sophie Li ◽

Sarah Y. Fu ◽

...

Keyword(s):

Systematic Review ◽

Postpartum Depression ◽

Systematic Reviews ◽

Methodological Quality ◽

A Priori ◽

Behavioural Therapy ◽

Therapeutic Interventions ◽

Current Evidence ◽

Cochrane Library ◽

Measurement Tool

Abstract Background Postpartum depression (PPD) is a highly prevalent mental health problem that affects parental health with implications for child health in infancy, childhood, adolescence and beyond. The primary aim of this study was to critically appraise available systematic reviews describing interventions for PPD. The secondary aim was to evaluate the methodological quality of the included systematic reviews and their conclusions. Methods An electronic database search of MEDLINE, Embase, and the Cochrane Library from 2000 to 2020 was conducted to identify systematic reviews that examined an intervention for PPD. A Measurement Tool to Assess Systematic Reviews was utilized to independently score each included systematic review which was then critically appraised to better define the most effective therapeutic options for PPD. Results Of the 842 studies identified, 83 met the a priori criteria for inclusion. Based on the systematic reviews with the highest methodological quality, we found that use of antidepressants and telemedicine were the most effective treatments for PPD. Symptoms of PPD were also improved by traditional herbal medicine and aromatherapy. Current evidence for physical exercise and cognitive behavioural therapy in treating PPD remains equivocal. A significant, but weak relationship between AMSTAR score and journal impact factor was observed (p = 0.03, r = 0.24; 95% CI, 0.02 to 0.43) whilst no relationship was found between the number of total citations (p = 0.27, r = 0.12; 95% CI, − 0.09 to 0.34), or source of funding (p = 0.19). Conclusion Overall the systematic reviews on interventions for PPD are of low-moderate quality and are not improving over time. Antidepressants and telemedicine were the most effective therapeutic interventions for PPD treatment.

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COVID-19 and myocarditis: a systematic review and overview of current challenges

Heart Failure Reviews ◽

10.1007/s10741-021-10087-9 ◽

2021 ◽

Author(s):

Teresa Castiello ◽

Georgios Georgiopoulos ◽

Gherardo Finocchiaro ◽

Monaco Claudia ◽

Andrea Gianatti ◽

...

Keyword(s):

Systematic Review ◽

Systolic Function ◽

Imaging Modality ◽

Current Evidence ◽

Cochrane Library ◽

Myocardial Inflammation ◽

Prognostic Impact ◽

Direct Role ◽

Potential Implication ◽

Histological Data

AbstractMyocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19–30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further.

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Kinesio Taping for Balance Function after Stroke: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/8470235 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 4

Author(s):

Yijuan Hu ◽

Dongling Zhong ◽

Qiwei Xiao ◽

Qiang Chen ◽

Juan Li ◽

...

Keyword(s):

Systematic Review ◽

Treatment Duration ◽

Meta Analysis ◽

Current Evidence ◽

Cochrane Library ◽

Clinical Effects ◽

Balance Function ◽

Balance Impairment ◽

Kinesio Taping ◽

Significant Difference

Objective. With the increasing social and economic burdens of balance impairment after stroke, the treatment for balance impairment after stroke becomes a major public health problem worldwide. Kinesio taping (KT) as a part of clinical practice has been used widely in the treatment of balance impairment after stroke. However, the clinical effects of KT for balance function have not been confirmed. The objective of this study is to investigate the effects and safety of KT for balance impairment after stroke. Methods. We conducted a systematic review (SR) and meta-analysis of randomized controlled trials (RCTs) on the effects of KT for balance impairment after stroke. We searched the following databases: (1) English databases: EMBASE (via Ovid), MEDLINE (via Ovid), the Cochrane library, PubMed, and PEDro; (2) Chinese databases: China Biology Medicine (CBM), Wan Fang database, China National Knowledge Infrastructure (CNKI), and VIP. Besides, hand searches of relevant references were also conducted. We systematically searched from the inception to December 2018, using the keywords (Kinesio, Kinesio Tape, tape, or Orthotic Tape) and (stroke, hemiplegia, or hemiplegic paralysis) and (balance or stability). The search strategies were adjusted for each database. The reference lists of included articles were reviewed for relevant trials. For missing data, we contacted the authors to get additional information. Results. 22 RCTs involved 1331 patients, among which 667 patients in the experimental group and 664 patients in the control group were included. Results of meta-analysis showed that, compared with conventional rehabilitation (CR), there was significant difference in Berg Balance Scale (BBS) (MD=4.46, 95%CI 1.72 to 7.19, P=0.001), Time Up and Go Test (TUGT) (MD=-4.62, 95%CI -5.48 to -3.79, P < 0.00001), functional ambulation category scale (FAC) (MD=0.53, 95%CI 0.38 to 0.68, P < 0.00001), Fugl-Meyer assessment (FMA-L) (MD=4.20, 95%CI 3.17 to 5.24, P < 0.00001), and Modified Ashworth Scale (MAS) (MD=-0.38, 95%CI -0.49 to -0.27, P < 0.00001). The results of subgroup analysis showed that there was no significant difference between KT and CR with ≤4 weeks treatment duration (< 4 weeks: MD=5.03, 95%CI -1.80 to 11.85, P=0.15; =4 weeks: MD=4.33, 95%CI -1.50 to 10.15, P=0.15), while there was significant difference with more than 4-week treatment duration (MD=4.77, 95%CI 2.58 to 6.97, P < 0.0001). Conclusions. Based on current evidence, KT was more effective than CR for balance function, lower limb function, and walking function in poststroke patients. Longer treatment duration may be associated with better effects. However, more well-conducted RCTs are required in the future.

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Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽

10.3390/vaccines9080939 ◽

2021 ◽

Vol 9 (8) ◽

pp. 939

Author(s):

Jiaxin Chen ◽

Yuangui Cai ◽

Yicong Chen ◽

Anthony P. Williams ◽

Yifang Gao ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Fixed Effects ◽

Meta Analysis ◽

Phase 1 ◽

Cochrane Library ◽

Categorical Variables ◽

Control Group ◽

Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

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Methods of conduct and reporting of living systematic reviews: a protocol for a living methodological survey

F1000Research ◽

10.12688/f1000research.18005.2 ◽

2019 ◽

Vol 8 ◽

pp. 221 ◽

Cited By ~ 3

Author(s):

Assem M. Khamis ◽

Lara A. Kahale ◽

Hector Pardo-Hernandez ◽

Holger J. Schünemann ◽

Elie A. Akl

Keyword(s):

Systematic Review ◽

Systematic Reviews ◽

Evidence Synthesis ◽

Cochrane Library ◽

Cross Sectional Survey ◽

Systematic Review Methodology ◽

Cross Sectional ◽

Prospective Longitudinal ◽

Over Time

Background: The living systematic review (LSR) is an emerging approach for improved evidence synthesis that uses continual updating to include relevant new evidence as soon as it is published. The objectives of this study are to: 1) assess the methods of conduct and reporting of living systematic reviews using a living study approach; and 2) describe the life cycle of living systematic reviews, i.e., describe the changes over time to their methods and findings. Methods: For objective 1, we will begin by conducting a cross-sectional survey and then update its findings every 6 months by including newly published LSRs. For objective 2, we will conduct a prospective longitudinal follow-up of the cohort of included LSRs. To identify LSRs, we will continually search the following electronic databases: Medline, EMBASE and the Cochrane library. We will also contact groups conducting LSRs to identify eligible studies that we might have missed. We will follow the standard systematic review methodology for study selection and data abstraction. For each LSR update, we will abstract information on the following: 1) general characteristics, 2) systematic review methodology, 3) living approach methodology, 4) results, and 5) editorial and publication processes. We will update the findings of both the surveys and the longitudinal follow-up of included LSRs every 6 months. In addition, we will identify articles addressing LSR methods to be included in an ‘LSR methods repository’. Conclusion: The proposed living methodological survey will allow us to monitor how the methods of conduct, and reporting as well as the findings of LSRs change over time. Ultimately this should help with ensuring the quality and transparency of LSRs.

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Efficacy and safety of microbiota transfer therapy for the management of autism spectrum disorder in children: a systematic review

F1000Research ◽

10.12688/f1000research.21525.1 ◽

2020 ◽

Vol 9 ◽

pp. 48

Author(s):

Pablo Daniel Estrella Porter ◽

Luis Eduardo Guzmán Freire ◽

Joseth Paulina Adatty Molina ◽

María Verónica Burneo Raza ◽

Henry Alejandro Carrión Celi ◽

...

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Intervention Group ◽

Autism Spectrum ◽

Nervous System Development ◽

Spectrum Disorder ◽

Current Evidence ◽

Cochrane Library ◽

Efficacy And Safety ◽

Level Of Evidence

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with an unclear etiologic mechanism. Following suggestions in the literature of a close relation between the gut microbiota and the central nervous system development, neuroimmune and neuroendocrine systems, new theories and strategies of the management of ASD in children focus on the brain-gut axis via microbiota transfer therapy. Despite the regular appearance in the news, the level of evidence supporting this intervention is unclear and to this date, no systematic review on this issue has been published. Methods: We conducted a systematic literature review of the efficacy and safety of microbiota transfer therapy for the management of ASD in children. MEDLINE via PubMed, LILACS IBECS via BVS, EMBASE via Ovid, Scopus and Cochrane Library were searched on 19th April 2018. Results: One single study published in 2017 was identified. The intervention group included 18 patients and showed significant clinical improvements in the gastrointestinal and ASD-related symptoms. The clinical procedure was reported as safe and well-tolerated with some transitory adverse effects. Conclusions: The causality and correlation of the intervention and the expected outcomes cannot be assumed with current evidence. In addition, recommendations about the effectiveness or safety of microbiota transfer therapy in children with ASD cannot be currently issued. Randomized controlled trials and clinical protocols for the intervention are needed.

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Systematic review of health economic studies in cranial neurosurgery

Neurosurgical FOCUS ◽

10.3171/2018.2.focus17792 ◽

2018 ◽

Vol 44 (5) ◽

pp. E2 ◽

Cited By ~ 1

Author(s):

Won Hyung A. Ryu ◽

Michael M. H. Yang ◽

Sandeep Muram ◽

W. Bradley Jacobs ◽

Steven Casha ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Cost Effectiveness ◽

Acute Ischemic Stroke ◽

Cost Effective ◽

Current Evidence ◽

Cochrane Library ◽

Endovascular Thrombectomy ◽

Life Years ◽

The Cost

OBJECTIVEAs the cost of health care continues to increase, there is a growing emphasis on evaluating the relative economic value of treatment options to guide resource allocation. The objective of this systematic review was to evaluate the current evidence regarding the cost-effectiveness of cranial neurosurgery procedures.METHODSThe authors performed a systematic review of the literature using PubMed, EMBASE, and the Cochrane Library, focusing on themes of economic evaluation and cranial neurosurgery following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Included studies were publications of cost-effectiveness analysis or cost-utility analysis between 1995 and 2017 in which health utility outcomes in life years (LYs), quality-adjusted life years (QALYs), or disability-adjusted life years (DALYs) were used. Three independent reviewers conducted the study appraisal, data abstraction, and quality assessment, with differences resolved by consensus discussion.RESULTSIn total, 3485 citations were reviewed, with 53 studies meeting the inclusion criteria. Of those, 34 studies were published in the last 5 years. The most common subspecialty focus was cerebrovascular (32%), followed by neurooncology (26%) and functional neurosurgery (24%). Twenty-eight (53%) studies, using a willingness to pay threshold of US$50,000 per QALY or LY, found a specific surgical treatment to be cost-effective. In addition, there were 11 (21%) studies that found a specific surgical option to be economically dominant (both cost saving and having superior outcome), including endovascular thrombectomy for acute ischemic stroke, epilepsy surgery for drug-refractory epilepsy, and endoscopic pituitary tumor resection.CONCLUSIONSThere is an increasing number of cost-effectiveness studies in cranial neurosurgery, especially within the last 5 years. Although there are numerous procedures, such as endovascular thrombectomy for acute ischemic stroke, that have been conclusively proven to be cost-effective, there remain promising interventions in current practice that have yet to meet cost-effectiveness thresholds.

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A SYSTEMATIC REVIEW OF CLINICAL OUTCOMES IN THE TREATMENT OF TEMPOROMANDIBULAR JOINT DYSFUNCTION USING ULTRASOUND GUIDED ARTHROCENTESIS AND CONVENTIONAL THERAPY

10.36106/ijsr/9303653 ◽

2021 ◽

pp. 19-22

Author(s):

Chirag Bhatia ◽

Hirkani Attarde

Keyword(s):

Systematic Review ◽

Temporomandibular Joint ◽

Operating Time ◽

Mouth Opening ◽

Risk Of Bias ◽

Temporomandibular Joint Disorders ◽

Current Evidence ◽

Cochrane Library ◽

Review Protocol ◽

Reported Data

Objective: This systematic review aimed to compare outcomes between ultrasound (US)-guided arthrocentesis and conventional arthrocentesis for the management of temporomandibular joint disorders (TMDs). Methods: PubMed, MEDLINE, Cochrane Library, Google Scholar and th EBSCOhost databases were searched up to 30 September 2020 for randomized control trials (RCTs) comparing US-guided and conventional arthrocentesis. The review protocol followed the PRISMA guidelines and was registered in PROSPERO (CRD42020211942). The risk of bias of the studies was independently evaluated using Cochrane Risk of Bias tool. Results: Four RCTs were included. It did not demonstrate any statistically signicant difference in pain or maximal mouth opening (MMO) scores after 1 week and 1 month of follow-up between US-guided and conventional arthrocentesis. Studies also reported data on intra-operative needle relocations and operating time but with conicting results. Conclusion: This study indicates that the use of US during arthrocentesis may not improve postoperative pain and MMO in the short term. Further high-quality adequately powered RCTs are required to strengthen current evidence.

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Effectiveness and safety of inpatient versus extended venous thromboembolism (VTE) prophylaxis with heparin following major pelvic surgery for malignancy: protocol for a systematic review

Systematic Reviews ◽

10.1186/s13643-019-1179-1 ◽

2019 ◽

Vol 8 (1) ◽

Author(s):

Bridget Heijkoop ◽

Natalie Parker ◽

George Kiroff ◽

Daniel Spernat

Keyword(s):

Systematic Review ◽

Venous Thromboembolism ◽

Systematic Reviews ◽

Pelvic Surgery ◽

Current Evidence ◽

Cochrane Library ◽

Vte Prophylaxis ◽

Optimum Duration ◽

Number Of Patients ◽

Increased Risk

Abstract Background Venous thromboembolism (VTE) is a common postoperative complication associated with significant morbidity and mortality. The use of prophylactic heparin postoperatively reduces this risk, and the use of extended duration prophylaxis is becoming increasingly common. Malignancy and pelvic surgery both independently further increase the risk of postoperative VTE and patients undergoing major pelvic surgery for malignancy are at particularly high risk of VTE. However, the optimum duration of prophylaxis specifically in this population currently remains unclear. Methods We will conduct a systematic review of literature in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.,2011) to evaluate current evidence of the effectiveness and safety of inpatient versus extended VTE prophylaxis with heparin (all forms) following major pelvic surgery for malignancy. We will search PubMed, EMBASE, and the Cochrane Library. Regarding safety, Food and Drug Administration (FDA), and Therapeutic Goods Administration (TGA) websites will be searched, including all levels of evidence. Results will be the postoperative timeframe in which a VTE event can be considered to have been provoked by the surgery, and the number of patients needed to treat with both inpatient and extended prophylaxis to prevent a VTE event in this timeframe, comparing these to determine if there is a significant benefit from extended prophylaxis. Discussion This systematic review will aim to identify the postoperative period in which patients undergoing major pelvic surgery for malignancy are at further increased risk of VTE as a result of their surgery and the optimum duration of heparin VTE prophylaxis with heparin to reduce this risk. Determining this will allow evidence-based recommendations to be made for the optimum duration of heparin VTE prophylaxis post major pelvic surgery for malignancy, leading to improved standards of care that are consistent between different providers and institutions. Systematic review registration In accordance with guidelines, our systematic review was submitted to PROSPERO for consideration of registration on 16/12/17 and was registered on 12/1/18 with the registration number CRD42018068961, and it was last updated on December 1, 2018.

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