Search

Abdelhamid M Attia,1 Magdy M Ibrahim,1 Ahmed M Abou-Setta21Department of Obstetrics and Gynecology, Cairo University, Cairo, Egypt; 2George and Fay Yee Centre for Healthcare Innovation, University of Manitoba/Winnipeg Regional Health Authority, Winnipeg, MB, CanadaAbstract: Norgestrel, a synthetic progestin chemically derived from 19-nortestosterone, is six times more potent than progesterone, with variable binding affinity to various steroid receptors. The levonorgestrel-releasing intrauterine system (LNG IUS) provides a long-acting, highly effective, and reversible form of contraception, with a pearl index of 0.18 per 100 women-years. The locally released hormone leads to endometrial concentrations that are 200–800 times those found after daily oral use and a plasma level that is lower than that with other forms of levonorgestrel-containing contraception. The contraceptive effect of the LNG IUS is achieved mainly through its local suppressive effect on the endometrium, leading to endometrial thinning, glandular atrophy, and stromal decidualization without affecting ovulation. The LNG IUS is generally well tolerated. The main side effects are related to its androgenic activity, which is usually mild and transient, resolving after the first few months. Menstrual abnormalities are also common but well tolerated, and even become desirable (eg, amenorrhea, hypomenorrhea, and oligomenorrhea) with proper counseling of the patient during the choice of the method of contraception. The satisfaction rates after 3 years of insertion are high, reaching between 77% and 94%. The local effect of the LNG IUS on the endometrium and low rates of systemic adverse effects have led to its use in other conditions rather than contraception, as for the treatment of endometrial hyperplasia, benign menorrhagia, endometriosis, adenomyosis, and uterine fibroids.Keywords: levonorgestrel, intrauterine device, contraception, family planning, Mirena, Skyla

Jaro Wex, Ahmed M Abou-Setta PharmArchitecture, London, UK Abstract: Gonadotropin-releasing hormone-analog type, fertilization method, and number of embryos available for cryopreservation should be incorporated into economic evaluations of highly purified human menopausal gonadotropin (HP-hMG) and recombinant human follicle-stimulating hormone (r-hFSH), as they may affect treatment costs. We searched for randomized trials and meta-analyses comparing HP-hMG and r-hFSH. Meta-analysis showed no significant difference in live births (odds ratio 0.82, 95% confidence interval [CI] 0.66–1.01), but a greater number of oocytes with r-hFSH (mean difference [MD] 1.96, 95% CI 1.02–2.90). Using a cost-minimization model for Sweden, accounting for embryo availability, survival following thawing, and patient dropout, we simulated patients individually for up to three cycles. R-hFSH was found to be cost-saving, at 2,767 kr (95% CI 1,580–4,057) per patient (€315 or $411); baseline savings were 6.43% of the total HP-hMG cost. In fresh cycles only, the savings for r-hFSH were 1,752 kr (95% CI 48–3,658) per patient (€200 or $260). In univariate sensitivity analyses, savings were obtained until the price of r-hFSH increased by 30% or the dosage of HP-hMG decreased by 38%–62% of baseline value. In probabilistic sensitivity analysis, r-hFSH was cost-saving in 100% of the simulated cohort per patient and in 85% per live birth; the respective percentages for fresh cycles only were 97.3% and 73.1%. In conclusion, a greater number of oocytes with r-hFSH allows for more frozen embryo transfers, thereby reducing overall treatment cost. Keywords: recombinant human FSH, highly purified menopausal gonadotropin, meta-analysis, economic analysis, in vitro fertilization, cryopreservation

Jaro Wex,1 Manpreet Sidhu,2 Isaac Odeyemi,2 Ahmed M Abou-Setta,1 Peny Retsa,2 Bertrand Tombal31PharmArchitecture Limited, London, UK; 2Astellas Pharma Europe Ltd, Chertsey, UK; 3Cliniques Universitaires Saint-Luc, Brussels, BelgiumObjective: Leuprolide is an established luteinizing hormone–releasing hormone (LHRH) agonist used as first-line treatment in advanced prostate cancer. As different formulations and dosing schedules are likely to have economic implications, we aimed to evaluate their efficacy, safety, and costs in nine European countries: Austria, Belgium, Czech Republic, Hungary, Italy, Latvia, Netherlands, Poland, and Portugal.Methods: Database searches identified 13 clinical trials of leuprolide 1- (1 M), 3- (3 M) and 6-monthly (6 M). Only data on leuprolide with Atrigel were compared for all three formulations, which had the same efficacy, safety, and adherence. Cost-minimization analysis accounting for cost of Eligard®, specialist consultations, and diagnostics during up to 12 months follow-up was conducted. The perspective was that of public payers.Results: No significant differences were observed in the percentages of intention-to-treat patients achieving testosterone levels ≤ 50 ng/dL following treatment with Eligard® 1 M (93.3%), 3 M (98.3%), and 6 M (97.3%) (P > 0.05), and adverse event profiles of the three formulations were comparable. Overall, 6 M was the least expensive, with average total annual costs from €788 (Belgium) to €1839 (Portugal). The 3 M option was between 2.5% (Hungary) and 37.6% (Belgium) more expensive than 6 M; 1 M formulation was the most expensive, with costs 15.5% and 151.6% more expensive than 6 M for those countries, respectively. The 3 M option was 11.2%–45.3% less expensive than 1 M. Total costs were associated with frequency of visits for injection and monitoring. The 1 M required twelve visits, 3 M 4.4–4.8 visits, and 6 M 2.1–2.3 visits. Up to 50% additional visits could be funded with the savings resulting from switching eligible patients from 1 M and 3 M to 6 M. Results were stable in univariate and probabilistic sensitivity analyses.Conclusion: Eligard® formulations offer comparable efficacy and safety, but different dosing schedules require different number of visits. The 6 M formulation offers the greatest cost savings and should be considered the treatment of choice in eligible patients in Europe.Keywords: prostate, cancer, androgen, leuprolide, Eligard, cost-effectiveness

Background: Community-acquired pneumonia (CAP) triggers inflammatory and thrombotic host responses driving morbidity and mortality. Antiplatelet agents may favorably modulate these pathways; however, their role in non–COVID-19 CAP remains uncertain. Objectives: To evaluate the association of antiplatelet agents with mortality in hospitalized patients with non–COVID-19 CAP. Methods: We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) of adult patients hospitalized for non–COVID-19 CAP exposed to antiplatelet agents (acetylsalicylic acid or P2Y12 inhibitors). We searched MEDLINE, Embase, and CENTRAL from inception to August 2023. Our primary outcome was all-cause mortality: meta-analyzed (random-effects models) separately for observational studies and RCTs. For observational studies, we used adjusted mortality estimates. Results: We included 13 observational studies (123,012 patients; 6 reported adjusted mortality estimates) and 2 RCTs (225 patients; both high risk of bias). In observational studies reporting hazard ratio, antiplatelet agents were associated with lower mortality (hazard ratio, 0.65; 95% CI, 0.46-0.91; I2 = 85%; 4 studies, 91,430 patients). In studies reporting adjusted odds ratio, antiplatelet agent exposure was associated with reduced odds of mortality (odds ratio, 0.67; 95% CI, 0.45-1.00; I2 = 0%; 2 studies, 24,889 patients). Among RCTs, there was a nonsignificant association with mortality (risk ratio, 0.66; 95% CI, 0.20-2.25; I2 = 54%; 2 studies, 225 patients). By the Grading of Recommendations, Assessment, Development, and Evaluation criteria, the certainty of the evidence was low, primarily due to risk of bias. Conclusion: In hospitalized patients with non–COVID-19 CAP, antiplatelet agents may be associated with reduced mortality compared with usual care or placebo, but the certainty of evidence is low.

Abstract Background It has long been believed that the patulous eustachian tube is a unique but uncommon condition, with an estimated incidence ranging from 0.3 to 6.6% in the general population. Hearing one’s own voice and breathing, or autophony and aerophony, are the most common symptoms of PET, along with frequent auditory fullness. Aim This study is to establish a standardized protocol for the audiological evaluation of patulous Eustachian tube using acoustic reflex decay test during different breathing tasks. Methods Between January 2022 and December 2022, the ENT department at Suez Canal University Hospitals undertook an observational case-control study. Fifty-two adult patients who present to the Suez Canal University ENT department with complaints of autophony, auditory fullness, or aerophony are diagnosed with patulous eustachian tube dysfunction through endoscopic examination of the tympanic membrane’s synchronized movement with respiration. Results The incidence rate of PET among adults was approximately 3 patients/1000 patients/year. The age of the whole studied group ranged from 20 to 60 years with mean ± SD of 37.4 ± 12.6 years. They included 23 males (44.2%) and 29 females (55.8%). The most common symptom among the studied group was aural fullness (46%), while the least common symptom was aerophony (12%); the most common risk factor among the studied patients was allergy (46.2%), while the least common was radiotherapy (3.9%); 66.7% of the patients with GERD were males, while 66.7% of the patients who lost weight were females; 58.3% of the patients with allergies were females, and also 60% of the patients with thin built were females. In the case group, there is a significant higher change of middle ear compliance in ipsilateral nostril breathing than the mouth breathing and nasal breathing. The sensitivity of the acoustic reflex decay test to diagnose PET with reference to the gold standard test is 88.5% (23/26*100), the specificity is 100% (26/26*100), and the positive predictive value is 100% (23/23*100). Conclusion The sensitivity of the acoustic reflex decay test to diagnose PET with reference to the gold standard test is high, and the specificity is very high with very good diagnostic accuracy.

Background: Preoperative treatment with oral neomycin combined with erythromycin or metronidazole is recommended to decrease the risk of surgical site infections (SSIs) in elective colorectal surgery. However, oral neomycin is not commercially available in Canada, and therefore it is not routinely used. Fluoroquinolones are widely available and have excellent activity against aerobic Gram-negative bacteria. The aim of this systematic review was to identify, critically appraise and summarize the evidence on the efficacy and safety of preoperative use of oral fluoroquinolone antibiotics for the prevention of SSIs in adult patients undergoing elective colorectal resection. Methods: Following Cochrane guidelines, we included English-language randomized controlled trials (RCTs) comparing oral fluoroquinolones plus routine preoperative intravenous antibiotics against intravenous antibiotics alone from MEDLINE (Ovid), Embase (Ovid), the Cochrane Central Register of Controlled Trials (Ovid) and ClinicalTrials.gov. Results: We included 3 RCTs (1136 patients). Risk of bias was uncertain in 2 trials and high in 1 trial. Preoperative oral fluoroquinolones led to significantly decreased total SSIs (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.32-0.57, [I.sup.2] = 0%), superficial incisional (RR 0.38, 95% CI 0.22-0.68, [I.sup.2] = 32%), deep incisional (RR 0.19, 95% CI 0.06-0.65, [I.sup.2] = 0%) and organ/space SSIs (RR 0.34, 95% CI 0.12-0.90, [I.sup.2] = 33%). There was also a significant reduction in anastomotic leaks (RR 0.22, 95% CI 0.06-0.87, [I.sup.2] = 0%). No antibiotic-related adverse events were reported. Conclusion: This review suggests that preoperative oral fluoroquinolones with intravenous antibiotics are superior to intravenous antibiotics alone for preventing SSIs after colorectal surgery. If neomycin is unavailable, oral fluoroquinolones should be considered as a reasonable alternative. Future trials are required to further compare the relative efficacy of oral antibiotic regimens. Contexte : Un traitement préopératoire par néomycine orale associée à de l'érythromycine ou du métronidazole est recommandé pour réduire le risque d'infection du site opératoire (ISO) lors de la chirurgie colorectale non urgente. Or, la néomycine orale n'est pas disponible sur le marché au Canada et par conséquent, n'est pas utilisée. Les fluoroquinolones sont facilement accessibles et exercent une excellente activité contre les bactéries aérobies à Gram négatif. Le but de cette revue systématique était d'identifier, d'évaluer de façon critique et de résumer les données probantes sur l'efficacité et l'innocuité de l'administration préopératoire de fluoroquinolones orales pour la prévention des ISO chez des adultes soumis à une résection colorectale élective. Méthodes : Conformément aux lignes directrices Cochrane, nous avons inclus les essais randomisés et contrôlés (ERC) de langue anglaise ayant comparé des fluoroquinolones orales en association avec les antibiotiques intraveineux préopératoires habituels et aux antibiotiques intraveineux seuls, recensés dans les bases de données MEDLINE (Ovid), Embase (Ovid), le Registre central Cochrane des essais contrôlés (Ovid) et ClinicalTrials.gov. Résultats : Nous avons inclus 3 ERC (1136 patients). Le risque de biais était incertain pour 2 essais et élevé pour 1 essai. Les fluoroquinolones orales préopératoires ont donné lieu à une diminution significative du nombre total d'ISO (risque relatif [RR] 0,43, intervalle de confiance [IC] de 95 % 0,32-0,7, [I.sup.2] = 0 %), superficielles (RR 0,38, IC de 95 % 0,22-0,68, [I.sup.2] =32 %), profondes (RR 0,19, IC de 95 % 0,06-0,65, [I.sup.2] = 0 %) et des cavités/organes (RR 0,34, IC de 95 % 0,12-0,90, [I.sup.2] = 33 %). On a aussi noté une réduction significative des fuites anastomotiques (RR 0,22, IC de 95 % 0,06-0,87, [I.sup.2] = 0 %). Aucun effet indésirable lié à l'antibiothérapie n'a été signalé. Conclusion : Selon cette revue, les fluoroquinolones orales préopératoires avec antibiothérapie intraveineuse sont supérieures aux antibiotiques intraveineux seuls pour la prévention des ISO après la chirurgie colorectale. En l'absence de néomycine, les fluoroquinolones orales représentent une solution de rechange acceptable. Il faudra procéder à d'autres essais pour mieux comparer l'efficacité relative des différents schémas d'antibiothérapie orale., Colorectal surgical procedures are associated with some of the highest rates of surgical site infections (SSIs) of any intra-abdominal procedures, which are frequently caused by anaerobic bacterial flora and Gram-negative [...]

Abstract Purpose To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for prostate cancer in adults aged 18 years and older in primary care. This protocol outlines the planned scope and methods for a series of systematic reviews. Methods Updates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with a prostate-specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false-positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. The quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding the choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomized, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, gray literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome. Discussion The series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older. Systematic review registration This review has been registered with PROSPERO (CRD42022314407) and is available on the Open Science Framework (osf.io/dm32k).

This is the introductory paper in a collection of four papers on the Strategy for Patient-Oriented Research (SPOR) Evidence Alliance, a pan-Canadian research initiative that was funded by the Canadian Institutes of Health Research in September of 2017. Here, we introduce the SPOR enterprise in Canada, provide a rationale for the creation of the SPOR Evidence Alliance, provide information on the mandate and approach, and describe how the SPOR Evidence Alliance adds to the health research ecosystem in Canada and beyond.

Background: COVID-19 has proven to be challenging to manage for many reasons, including its high infection rate. One of the potential ways to limit its spread is by limiting international travel. The objective of this systematic review was to identify, critically appraise and summarise evidence on international air travel-related control measures for COVID-19. Methods: This review is based on the Cochrane review: International travel-related control measures to contain the COVID-19 pandemic and followed the same methods. In brief, we searched for clinical and modelling studies in general health and COVID-19-specific bibliographic databases. The primary outcome categories were (i) cases avoided, (ii) a shift in epidemic development and, (iii) cases detected. Results: From 6,202 citations identified by the search strategy, we included 22 new studies (modelling = 9, observational = 13) in addition to the 62 studies identified in the Cochrane review. Studies suggest that quarantine or microbial detection or a combination may avoid further cases. Similarly, these interventions may produce a positive shift in epidemic development and case detection may improve. Most studies were evaluated as having a moderate to critical risk of bias. The studies did not change the main conclusions of the Cochrane review nor the quality of the evidence (very low certainty); however, they added to the evidence base for most outcomes. Conclusions: Weak evidence supports the use of international air travel-related control measures to limit the spread of COVID-19 via air travel. More real-world studies are required to support these conclusions.

Abstract Background Obesity has become a major driver in the burden of chronic diseases. The Canadian Clinical Practice Guidelines recommend a lifestyle intervention for the management and prevention of obesity. This includes behavior modification, dietary counseling, and physical activity. With the market overwhelmed with weight loss programs, the majority are focused on low-calorie diets and general recommendations for exercise. Most are not personalized and are not administered by healthcare professionals. An interdisciplinary team of highly trained healthcare professionals has the ability to provide medically sound and safe advice in all aspects of an individuals’ life, such as lifestyle, sleep, mental health, and behaviors. A clinically managed weight loss program is defined as a team including a dietitian, exercise professional, psychologist, and/or physician or nurse practitioner oversight. With limiting results in the literature regarding clinically managed weight loss programs, it is difficult to conclude whether it may be effective. Therefore, the objective of this systematic review is to assess clinically managed weight loss programs, with a physician or nurse practitioner oversight in comparison with non-clinically managed weight loss programs with no physician oversight or nurse practitioner oversight in adults who are living with overweight or obesity. Methods A literature search will be executed by a knowledge synthesis librarian on MEDLINE, Cochrane Central, Embase, PsycINFO, and CINAHL. The data collected will be extracted, stored, and managed in MS Excel 2016. The extraction of the data will include study details, study population details, health team details, intervention details, and outcome details. Discussion The prevalence of obesity has been increasing throughout the decades. The results from this systematic review may aid in recommending a more clinically safe weight loss program for those who struggle with overweight or obesity. Systematic review registration PROSPERO CRD42020170014

Abstract Background Papaya (Carica papaya Linn.) is well known for its nutritional as well as medicinal value. Different parts of the plant including leaves have been used as therapeutic remedies for various diseases. The objective of the present study is to determine the impact of different extraction methods; microwave-assisted, ultrasonic-assisted and conventional maceration on extract yield, polyphenols, flavonoids composition and subsequently, the anti-hyperlipidemic potential of papaya leaves (Carica papaya Linn.). Results Innovative extraction methods represented in microwave assisted extraction (MAE) and ultrasonic assisted extraction (UAE) have significant impact on the extract yield and total phenolic and flavonoids content than conventional maceration extraction (CME) of the prepared aqueous ethanol extracts. HPLC assay showed the highest content of bioactive polyphenols characterized extract from the MAE (29.99 mg/g), followed by UAE (24.75 mg/g) and the lowest content was that obtained from CME. The aqueous ethanol extract of the leaves obtained by MAE induced significant hypolipidemic activity (P

Abstract Published protocols have the potential to reduce bias in the conduct and reporting of systematic reviews (SR). When reporting the results of a completed SR, the question might arise whether text used in the protocol can also be used in the completed SR? Does this constitute text recycling, plagiarism, or even copyright infringement? In theory, no major changes to the protocol will be expected for the introduction and methods sections if the SR is completed in time. The benefits of maintaining the introduction and methods section of a protocol in the published SR are straightforward. Authors will require less time for writing up the completed SR. Potential benefits can also be expected for peer reviewers and editors. However, reusing text can be described as self-plagiarism. The question to be answered is whether this type of self-plagiarism is acceptable when copying text used previously (as would be the case when copying text from the protocol and pasting it into the subsequent completed SR)? The “traditional answer” to this question is “yes” because authors should not get credit for one piece of work for more than one time unless the work is cited appropriately. In contrast, we propose that in this context, it seems to be fully acceptable from a scientific and ethical perspective. As such, authors should not be accused of plagiarism in this case, but rather be encouraged to be efficient. However, legal issues need to be taken into consideration (e.g., copyright). We hope to stimulate a discussion on this topic among authors, readers, editors, and publishers.

Abstract Background Behavior change is not simple, and the introduction of guidelines or protocols does not mean that they will be followed. As such, implementation strategies are vital for the uptake and sustainability of changes in medical protocols. Medical or mental emergencies may be life-threatening, especially in children due to their unique physiological needs. In emergency departments (EDs), where timely decisions are often made, practice change requires thoughtful considerations regarding the best approaches to implementation. As there are many studies reporting on a wide variety of implementation strategies in the emergency management of children in EDs, we aim to identify and map the characteristics of these studies. Methods We will conduct a scoping review to identify various implementation strategies in the emergency management of children using the Arksey and O’Malley framework. We will search MEDLINE (Ovid), Embase (Ovid), Cochrane Central (Wiley), and CINAHL (Ebsco), from inception to May 29, 2019, for implementation studies among the pediatric population (≤ 21 years) in a pediatric emergency setting. Two pairs of reviewers will independently select studies for inclusion and extract the data. We will perform a descriptive, narrative analysis of the characteristics of the identified implementation strategies. Discussion We will present specific characteristics and outcome measures of all included studies in a tabular form. The results of this review are expected to help identify and characterize successful implementation strategies in the emergency management of children in EDs. Systematic review registration Open Science Framework https://osf.io/h6jv2

Abstract Background A new tool, “risk of bias (ROB) instrument for non-randomized studies of exposures (ROB-NRSE),” was recently developed. It is important to establish consistency in its application and interpretation across review teams. In addition, it is important to understand if specialized training and guidance will improve the reliability in the results of the assessments. Therefore, the objective of this cross-sectional study is to establish the inter-rater reliability (IRR), inter-consensus reliability (ICR), and concurrent validity of the new ROB-NRSE tool. Furthermore, as this is a relatively new tool, it is important to understand the barriers to using this tool (e.g., time to conduct assessments and reach consensus—evaluator burden). Methods Reviewers from four participating centers will apprise the ROB of a sample of NRSE publications using ROB-NRSE tool in two stages. For IRR and ICR, two pairs of reviewers will assess the ROB for each NRSE publication. In the first stage, reviewers will assess the ROB without any formal guidance. In the second stage, reviewers will be provided customized training and guidance. At each stage, each pair of reviewers will resolve conflicts and arrive at a consensus. To calculate the IRR and ICR, we will use Gwet’s AC1 statistic. For concurrent validity, reviewers will appraise a sample of NRSE publications using both the Newcastle-Ottawa Scale (NOS) and ROB-NRSE tool. We will analyze the concordance between the two tools for similar domains and for the overall judgments using Kendall’s tau coefficient. To measure evaluator burden, we will assess the time taken to apply ROB-NRSE tool (without and with guidance), and the NOS. To assess the impact of customized training and guidance on the evaluator burden, we will use the generalized linear models. We will use Microsoft Excel and SAS 9.4, to manage and analyze study data, respectively. Discussion The quality of evidence from systematic reviews that include NRSE depends partly on the study-level ROB assessments. The findings of this study will contribute to an improved understanding of ROB-NRSE and how best to use it.

Abstract Background The Cochrane Bias Methods Group recently developed the “Risk of Bias (ROB) in Non-randomized Studies of Interventions” (ROBINS-I) tool to assess ROB for non-randomized studies of interventions (NRSI). It is important to establish consistency in its application and interpretation across review teams. In addition, it is important to understand if specialized training and guidance will improve the reliability of the results of the assessments. Therefore, the objective of this cross-sectional study is to establish the inter-rater reliability (IRR), inter-consensus reliability (ICR), and concurrent validity of ROBINS-I. Furthermore, as this is a relatively new tool, it is important to understand the barriers to using this tool (e.g., time to conduct assessments and reach consensus—evaluator burden). Methods Reviewers from four participating centers will appraise the ROB of a sample of NRSI publications using the ROBINS-I tool in two stages. For IRR and ICR, two pairs of reviewers will assess the ROB for each NRSI publication. In the first stage, reviewers will assess the ROB without any formal guidance. In the second stage, reviewers will be provided customized training and guidance. At each stage, each pair of reviewers will resolve conflicts and arrive at a consensus. To calculate the IRR and ICR, we will use Gwet’s AC1 statistic. For concurrent validity, reviewers will appraise a sample of NRSI publications using both the New-castle Ottawa Scale (NOS) and ROBINS-I. We will analyze the concordance between the two tools for similar domains and for the overall judgments using Kendall’s tau coefficient. To measure the evaluator burden, we will assess the time taken to apply the ROBINS-I (without and with guidance), and the NOS. To assess the impact of customized training and guidance on the evaluator burden, we will use the generalized linear models. We will use Microsoft Excel and SAS 9.4 to manage and analyze study data, respectively. Discussion The quality of evidence from systematic reviews that include NRS depends partly on the study-level ROB assessments. The findings of this study will contribute to an improved understanding of the ROBINS-I tool and how best to use it.