Fragility Index Research Articles

The Continuous Fragility Index of Statistically Significant Findings in Studies Based on High Levels of Evidence Comparing Interventions for Femoroacetabular Impingement Syndrome.

Critical analysis of studies with high level of evidence has relied on the significance set by the reported P values. However, this strategy steers readers toward categorical interpretation of the data; therefore, a more comprehensive approach of data analysis is warranted. The continuous fragility index (CFI) allows for frailty interpretation of any given study's continuous outcome results. To calculate the CFI of high-level quality studies reporting significant continuous outcomes on comparison of treatment modalities for management of femoroacetabular impingement syndrome. Meta-analysis; Level of evidence, 2. Three databases (PubMed, Embase, Cochrane) were queried from inception to February 2024 utilizing Boolean operators to combine variations of the following search terms: "femoroacetabular impingement, randomized controlled trials or prospective cohort." Studies were included if level of evidence 1 or 2, and a statistically significant outcome was reported for any continuous outcome. CFI calculation was performed for all significant outcomes to obtain a study-specific mean CFI and also for the primary outcome of each study. Mean CFI was also calculated for outcomes reported to be significant in >3 studies. Additionally, multivariable linear regression was utilized for assessment of variables associated with achievement of a higher CFI. Thirteen studies totaling 1316 patients were included for analysis: 11 level of evidence 1 and 2 level of evidence 2 studies. A total of 48 outcomes reaching significance were extracted, with 8 representing primary outcomes. Study-specific mean (SD) CFI was 8 (9.3), whereas primary outcome mean CFI was 12.5 (12). In 4 of the 13 studies, the number of hips lost to follow-up was greater than the study CFI. Outcome-specific mean CFI was obtained for 5 outcomes reported in >3 studies. Multivariable linear regression revealed that larger sample size and greater journal impact factor had a significant positive association with a higher overall CFI value (P < .05). The mean (SD) number of patient outcome events needed to reverse the significance of a continuous outcome (ie, CFI) was 8.0 (9.3). Nearly one-third of studies had a CFI less than the reported loss to follow-up, reflecting the need for better patient compliance to attain less fragile statistical results. Larger sample size and greater journal impact factor were both predictive of a higher CFI.

Bleeding disorders, longer operative time, and nongeneral anesthesia increase are associated with overnight admission after hip arthroscopy

Abstract Overnight admission is a rare but major complication after hip arthroscopy (HA), and the paucity of data surrounding its causes limits patient education and quality of care. The purpose of this study was to identify risk factors for an unanticipated overnight admission after HA and assess for associated complications. This analysis queried the American College of Surgeons National Surgical Quality Improvement Program database using Current Procedural Terminology codes to identify hip arthroscopies from 2005 to 2017. Patient demographics, perioperative variables, and comorbidities were compared between ambulatory and nonambulatory patients [length of stay (LOS) ≥ 1] using bivariate analysis. Multivariate stepwise logistic regression then identified independent risk factors of adverse outcomes. Linear regression analyzed correlation of LOS with age, operative time, modified fragility index (mFI-5), and year of operation. A total of 2420 cases were included in this study with 400 (16.5%) overnight admissions. The mean subject age was 40 ± 13.9 years old (58.1% female). Admitted patients generally had higher American Society of Anesthesiologists (ASA) scores and a higher mFI-5 index. Multivariate logistic regression showed that mFI-5 &amp;gt; 0, bleeding disorders, operative time &amp;gt;1.5 h, and nongeneral anesthesia were independent risk factors for prolonged hospital stay. Patients aged 31–40 years had decreased risk of LOS ≥1. Nonambulatory surgery was associated with significantly increased risk for any complication, readmission, wound complication, and venous thromboembolism. This analysis demonstrates that operations &amp;gt;1.5 h and increased medical comorbidities predispose patients to greater risk of being admitted to the hospital after HA. Surgeons should consider these data to optimize controllable factors and patient selection to reduce the risk of postoperative admission.

Lupus nephritis randomised controlled trials: evidence gaps and under-represented groups

ObjectiveWe performed a scoping review of randomised clinical trials (RCTs) assessing pharmacological therapies for the initial management of lupus nephritis (LN), focusing on study design, included populations and outcome definitions,...

Beyond the Usual Significance: Fragility Indices of Randomized Controlled Trials in Top General Orthopaedic Journals.

Understanding the reliability of outcomes in randomized controlled trials (RCTs) is crucial, as standard metrics, such as P-value do not fully capture result fragility. This led to the adoption of specific indices: the fragility index (FI), which measures the strength of trial through significant results by calculating the minimum number of patient status changes from nonevent to event required to make the results statistically insignificant; reverse fragility index (RFI), used for insignificant results; and continuous fragility index (CFI), which acts similar to FI for significant continuous outcomes. The objective is to assess the robustness of orthopaedics RCTs using these indices across leading orthopaedic journals. A systematic review of RCTs published between 2019 and 2023 in the top five general orthopaedic journals, identified through Scientific Journal Rankings, was done. Data extraction focused on FI, RFI, and CFI and related measures for 160 RCTs. The indices were calculated using established methodologies, with sample size adjustments. 22 RCTs had statistically significant dichotomous primary outcomes and 17 studies had notable dichotomous secondary outcomes. Twenty-nine had negligible (insignificant) dichotomous primary outcomes, and 92 reported notable continuous outcomes. Only one RCT reported a FI in the article. The median FI was 5 with a median sample size of 142 for dichotomous outcomes. The median RFI was 3 with a median sample size of 100 for negligible outcomes, and the median CFI was 13 with a median sample size of 86.5 for continuous outcomes, showing dichotomous outcomes to be more fragile than continuous ones. Continuous outcomes are less fragile than dichotomous outcomes, with negligible dichotomous outcomes being particularly more fragile. This fragility stems from small sample sizes and limited outcome events. Using these indices, especially when considering patient loss to follow-up, can improve the reliability of findings. I.

Time to Amputation After Traumatic Digital Injury Does Not Affect Complication Rates: A Retrospective Multi-Institutional Analysis.

Revisionary digital amputations are often performed after partial or full traumatic digital amputation to minimize complications while preserving as much length and functionality as possible. Many surgeons attempt revisionary procedures swiftly after initial injury. The aim of this study was to investigate the effects of time from injury to surgery on rate of complications and reoperation in revisionary traumatic digital amputations. This was a retrospective chart review of all patients undergoing revisionary digital amputation for initial traumatic amputation at a single hospital from January 1, 2007 to December 31, 2021. Demographics, comorbidities, surgical details, complications, and time from injury to surgery were collected. Five-factor modified fragility index scores were also computed for each patient. Primary outcomes of interest included complications and need for additional procedures. Secondary outcomes of interest included development of neuroma, phantom limb, and referral to a long-term pain specialist. A total of 97 patients were identified as meeting all inclusion criteria. The average time to surgery was 14.4 days. Body mass index, comorbidities, and time to surgery were not associated with increased risk of complication. Increasing time to surgery was not significantly associated with increased risk of complications, development of neuroma, phantom limb, or a referral to long-term pain service. The only factors which were significantly associated with reoperation were absence of diabetes and hypertension. Increasing time to surgery after initial injury was not significantly associated with increased risk of complications or reoperation. Surgeons should consider this when assessing urgency of surgery in patients after traumatic digital amputation.

Letter to the Editor: The Frailty of Fragility Index, Orthopaedic Paradigms and Practice.

Letter to the Editor: The Frailty of Fragility Index, Orthopaedic Paradigms and Practice.

Navigating sociopolitical waters: exploring the influence of key factors on global supply base concentration

PurposeVarious economic, strategic and sociopolitical factors drive the decisions related to the location of global supply chain partners. Yet, research on how sociopolitical factors affect these decisions is not that prevalent. We contribute to this line of research by evaluating the changes in global supply base concentration accounted for by three key sociopolitical factors – populism, state fragility and political constraints – that magnify or attenuate the effects of institutional risks, uncertainties and volatility.Design/methodology/approachApart from hypothesizing the negative effects of populism and state fragility, political constraints are conjectured to significantly attenuate these negative effects. The proposed hypotheses were motivated using the tenets of institutional economics theory and tested using a comprehensive dataset compiled from six widely used secondary data sources. The panel data spanning 2003–2018 focused on a sample of global US-listed companies with worldwide suppliers.FindingsOur results supported three of the four hypotheses. Specifically, the direct effects of populism and state fragility were found to be significant, suggesting that they reduced the number of suppliers in the country. However, political constraints did not moderate the effect of populism on global supply base concentration, while they negatively moderated the effect of the state fragility index. This result showcases the overpowering effect of populism on a country’s market environment.Originality/valueSupply chain scholars resoundingly acknowledge the need for more research on the effect of broader sociopolitical factors on global supply chain management. Responding to this call, we evaluate the direct and contingent effects of populism, state fragility and political constraints on global supply base concentration. Our choice of these factors was based on their representation of most of the critical institutional environments prevalent in various countries. One surprising result we found was that populism was found to be pervasive even in countries with strong checks and balances, suggesting its paramount importance to practicing management. Overall, by unraveling the interesting effects of these multidimensional sociopolitical factors, our study makes a valuable contribution to not only theory but also practice.

Fragility in cardiovascular randomized controlled trials with primary continuous outcomes (2018–2022) from multi-perspectives assessment: a cross-sectional survey

Objective This study aims to assess the robustness of cardiovascular disease randomized controlled trials (RCTs) with primary continuous outcomes from a clinical perspective, utilizing the concepts of continuous fragility index (CFI), reverse continuous fragility index (RCFI) and their corresponding quotients (CFQ, RCFQ). Methods A cross-sectional study was conducted, searching PubMed for cardiovascular RCTs published between January 1, 2018, to December 31, 2022, in eight high-impact journals. Inclusion criteria were phase III or IV trials with 1:1 randomization, reporting at least one primary continuous outcome. Data analysis involved altering each outcome until achieving the reversal of significance (ɑ = 0.05) to determine the CFI or RCFI. The fragility quotients were then calculated by dividing the CFI or RCFI by the sample size, and Spearman’s correlation assessed correlation analyses. Results Of 3983 records were screened, and 64 RCTs (76 outcomes) were included. The fragility index was analysed with 72 outcomes. The overall median CFI was 7, with an associated median CFQ of 0.032. Nonsignificant P values exhibited greater statistical instability (median RCFI = 5, RCFQ = 0.023) than significant P values (median CFI = 14, CFQ = 0.062). Interestingly, “fragile” values were found in 36% (9/25) of CFI or 46.7% (7/15) of RCFI. Additionally, fragility index showed a significant association with several variables. Conclusions The findings suggest that changing only a small number of interventions (median of 7) could alter outcome significance. Reporting the fragility index alongside P values is recommended to provide a clearer understanding of statistical findings’ robustness. Highlights The continuous fragility index (CFI) represents the minimum patient count needed to modify significance by altering their intervention. Among 72 primary continuous outcomes in 64 cardiovascular RCTs, the overall median CFI was 7, with a corresponding CFQ of 0.032. CFI demonstrated moderate to strong correlations with sample size, total dropouts, and patient numbers analyzed.

Statistical Fragility of Findings From Randomized Phase 3 Trials in Pediatric Oncology.

The fragility index (FI) is an adjunctive metric to facilitate the interpretation of p-values in clinical trials. The FI has not been studied in phase 3 trials in pediatric oncology. PubMed was used to identify phase 3 pediatric oncology trials published between 1980 and 2020. We report trial characteristics and calculate the FI for trials with a binary outcome and survival-inferred fragility index (SIFI) for trials with a time-to-event outcome. FI/SIFI is the number of patients from one arm of a trial who would need to change groups for the statistical conclusion to change. We also report fragility quotients (FQ and SFQ) to normalize FI and SIFI relative to trial size. One hundred and thirteen trials included sufficient data for analysis. The median FI for trials with a binary outcome (n = 40) was 4.5 (range: 1-33). The median SIFI for trials with a time-to-event outcome (n = 73) was 13 (range: 0-61). The FI or SIFI was less than the number of patients lost to follow-up in 25% of 36 trials. Median FQ and SFQ were 0.026 and 0.03, respectively, and did not significantly vary according to trial characteristics. While sample sizes increased over time, the FQ and SFQ remained stable. The statistical conclusions of pediatric oncology phase 3 trials hinge on a relatively small number and proportion of patients. Despite the sample size limitations of low prevalence diseases, pediatric cancer trials are similarly or less fragile than adult oncology trials. Smaller trials do not appear more statistically fragile than larger trials. Statistical fragility appears to have remained constant over the four decades evaluated. We recommend reporting FI or SIFI, in conjunction with p-values, for all phase 3 pediatric oncology trials.

Understanding progress and challenges in women's health and wellbeing in exemplar countries: a time-series study identifying positive outliers

Women's health and wellbeing (WHW) forms a multidimensional continuum across the life course, with intersecting power dynamics including socioeconomic and ethnic positioning. The WHW Exemplars project uses robust quantitative approaches to identify best-performing low-income and middle-income countries (LMICs) in improving WHW across the entire life course. Using the life course approach, we created a list of 32 cross-sectional indicators belonging to nine dimensions based on a conceptual framework to assess progress in WHW. Small population countries (<5 million people), high-income countries, and those among the top ten in the fragility index were excluded. We calculated the average annual rates of change (AARC; 2000-19) for each indicator, which were then standardised around the regional mean for comparability. The standardised values were aggregated into a final score for each country (the lower the score, the worse the country's performance). We assessed the performance of countries from a regression of the aggregated scores and the AARC of gross domestic product. We evaluated the performance of each country relative to regional peers across life course stages and dimensions based on data availability and improved performance. The final standardised score ranged from -11·0 in Costa Rica to 14·8 in Cambodia (measure of dispersion of the standarised score: 1·0 [SD 5·9]). Cambodia, Ethiopia, Peru, and Türkiye ranked highest in the life course and dimension assessment in their regions. After triangulation of results, the best-performing countries in WHW were Bangladesh, Cambodia, and India in south Asia and east Asia and the Pacific; Congo (Brazzaville), Ethiopia, Rwanda, and Sierra Leone in sub-Saharan Africa; Peru, Bolivia, and Colombia in Latin America and the Caribbean; and Morocco, Türkiye, Kazakhstan, and Azerbaijan in Europe and central Asia and the Middle East and north Africa. This study quantified the performance of WHW across the life course among LMICs over the past two decades and identified good performers that might be selected as exemplars. The study also highlights low data availability and quality relating to this topic. Children's Investment Fund Foundation and Gates Ventures. For the French, Spanish, Portuguese, Chinese and Arabic translations of the abstract see Supplementary Materials section.

Does the Application of Topical Vancomycin Reduce Surgical Site Infections in Spine Surgery? A Meta-analysis of Randomized Controlled Trials.

Surgical site infections (SSIs) represent a major challenge in spine surgery, leading to severe morbidity, mortality, and increased costs. The local application of antibiotics, particularly vancomycin, has emerged as a potential strategy. Individual randomized controlled trials (RCTs) have disagreed about the efficacy of topical vancomycin in preventing SSIs after spine surgery, and so a meta-analysis that pools data from those RCTs might be helpful to inform clinicians' decisions on the topic. This meta-analysis of RCTs asked: Does intrawound topical vancomycin reduce the risk of (1) SSIs, (2) deep SSIs, and (3) superficial SSIs in patients undergoing spine surgery? PubMed, Cochrane, and Google Scholar (pages 1-20) were searched up through March 13, 2024 (search performed on March 13, 2024). Inclusion criteria consisted of English or non-English-language RCTs comparing the implementation of topical vancomycin in spine surgery to its nonuse and assessing its efficacy in preventing SSI, while exclusion criteria consisted of nonrandomized comparative studies, single-arm noncomparative studies, comparative studies based on national databases or from the same center as other included studies, studies posted to preprint servers, studies reporting incomplete/nonrelevant outcomes, and studies adding another SSI preventive measure. The studies were assessed using the Cochrane Risk of Bias tool. Heterogeneity was evaluated by Q tests and I 2 statistics. We used a random-effects model when considerable heterogeneity was observed (all SSIs, deep SSIs); otherwise, a fixed-effects model was used (all SSIs subanalysis, superficial SSIs). Furthermore, the fragility index was calculated for each of the assessed outcomes when there was no difference between the two groups to assess how many patients were needed to experience the outcomes for a difference to become present. The studied outcomes were the risks of SSIs, deep SSIs, and superficial SSIs. Deep SSIs were defined by the included trials as SSIs underneath the fascia, otherwise they were considered superficial. Six RCTs representing a total of 2140 patients were included, with 1053 patients in the vancomycin group and 1087 in the control group. Using an alpha of 0.05, our meta-analysis had 80% power to detect a risk difference of 1.5% for the primary outcome between patients who did and did not receive vancomycin. The age of the patients in the vancomycin group ranged from 37 to 52 years, while the age in the control group ranged from 34 to 52 years. The surgical procedures consisted of both instrumented and noninstrumented spinal procedures. Overall, the risk of bias in the included studies was either low or unclear, with none of the studies having a high risk of bias in any of the assessed categories (selection bias, performance bias, detection bias, attrition bias, and reporting bias). We found no difference in the risk of SSI between the vancomycin and control groups (3.0% [32 of 1053] versus 3.9% [42 of 1087], relative risk 0.74 [95% CI 0.35 to 1.57]; p = 0.43). Ten additional patients (4.8% infection risk) in the control group would need to experience an SSI for a difference to be observed between the two groups. We found no difference in the risk of deep SSI between the vancomycin and control groups (1.8% [15 of 812] versus 2.7% [23 of 860], relative risk 0.69 [95% CI 0.24 to 2.00]; p = 0.50). Seven additional patients (3.5% infection risk) in the control group would need to experience a deep SSI for a difference to be observed between the two groups. We found no difference in the risk of superficial SSI between the vancomycin and control groups (1.0% [6 of 620] versus 1.4% [9 of 662], relative risk 0.68 [95% CI 0.25 to 1.89]; p = 0.46). Seven additional patients (2.4% infection risk) in the control group would need to experience a superficial SSI for a difference to be observed between the two groups. This meta-analysis of randomized trials examining use of topical vancomycin in spine surgery failed to show efficacy in reducing infection, and thus we do not recommend routine use of topical vancomycin for this indication. Future large-scale trials would be needed if surgeons believe that between-group differences smaller than those for which we were powered here (this meta-analysis had 80% power to detect a between-group difference of 1.5% in infection risk) are clinically important, and large database surveys may be informative in terms of assessing for postoperative adverse events associated with the use of vancomycin powder. Level I, therapeutic study.

Randomized controlled trials - The what, when, how and why.

Randomized controlled trials (RCTs) are at the top of the pyramid of evidence as they offer the best answer on the efficacy of a new treatment. RCTs are true experiments in which participants are randomly allocated to receive a certain intervention (experimental group) or a different intervention (comparison group), or no treatment at all (control or placebo group). Randomization, along with other methodological features such as blinding and allocation concealment, safeguard against biases. This review will focus on parallel group RCT design as it is the most common design in the field of Pediatric Urology. RCTs can be designed using a superiority, equivalency, or non-inferiority hypothesis, and are usually preceded by a pilot, where the trial protocol is implemented in a small number of patients, mimicking the larger, definitive study. Even though regarded as the best available option to bring out scientific data, RCTs might be prone to mislead. If RCTs are small and underpowered, a difference of even one single event between groups, may completely change the trial results. To safeguard against RCTs weakness, a fragility concept of statistical significance was developed and called the Fragility Index (FI). RCTs may not be appropriate, ethical, or feasible for all surgical interventions. They may have limitations such as prohibitive cost and unrealistic large sample sizes. Nearly 60% of surgical research questions cannot be answered by RCTs. Therefore, clinical practice should be based on the best available evidence on a given topic, regardless of the study design. However, even in these situations, conclusions drawn from observational studies must be interpreted with caution.

The Continuous Fragility Index of Outcomes in Rotator Cuff Repair Augmentation Randomized Trials: A Systematic Review

The Continuous Fragility Index of Outcomes in Rotator Cuff Repair Augmentation Randomized Trials: A Systematic Review

Beyond the Fragility Index.

The results of randomized clinical trials (RCTs) are frequently assessed with the fragility index (FI). Although the information provided by FI may supplement the p value, this indicator presents intrinsic weaknesses and shortcomings. In this article, we establish an analysis of fragility within a broader framework so that it can reliably complement the information provided by the p value. This perspective is named the analysis of strength. We first propose a new strength index (SI), which can be adopted in normal distribution settings. This measure can be obtained for both significance and nonsignificance and is straightforward to calculate, thus presenting compelling advantages over FI, starting from the presence of a threshold. The case of time-to-event outcomes is also addressed. Then, beyond the p value, we develop the analysis of strength using likelihood ratios from Royall's statistical evidence viewpoint. A new R package is provided for performing strength calculations, and a simulation study is conducted to explore the behavior of SI and the likelihood-based indicator empirically across different settings. The newly proposed analysis of strength is applied in the assessment of the results of three recent trials involving the treatment of COVID-19.

Cooperative and Local Molecular Motion of High-Density Water in Glycerol Aqueous Solutions.

The glass-to-liquid transition of water, particularly in high-density water (HDW), has long been a controversial topic due to challenges posed by inevitable crystallization. In this study, we addressed this issue by creating homogeneous high-density glass from a dilute glycerol aqueous solution under high pressure. Using dielectric spectroscopy, we explored the glass transition of HDW in glycerol solutions across the full concentration range under high pressures. HDW was found to exhibit two distinct relaxation modes: one linked to cooperative motion and the other to noncooperative local motion. The fragility index classification of HDW, derived from the cooperative motion of water, suggests that HDW behaves as a "fragile" liquid, contradicting previous suggestions. Extrapolation to pure HDW indicates that the dielectric relaxation observed in pure HDW originates from noncooperative local water motion.

Heated Environment, Armed People: Between “Climate Change Conflict” and “Fragility Conflict” in the Sahel

The Sahel is a classic example of a region inundated by climate change and conflicts. The region is an ecological hotspot that is on the brink of collapse, as countries in the area are trapped in a vicious cycle of conflict, resource scarcity, and environmental threats, which increase the chances of political instability and civil unrest. Noting that there is a divergent scholarly viewpoint on the relationship between climate change and conflict, this study evaluates the climate change-conflict thesis vis-à-vis the fragility-conflict thesis. It argues that armed conflicts in the Sahel are not exclusively attributable to climate change; rather, other conventional drivers exacerbate the impact of climate change on conflicts. These conventional drivers, framed as fragility indices, play a more significant role in conflict escalation in the Sahel. To this end, this study provides a holistic perspective on conflict dynamics and underscores the intricate interplay between fragility and conflict proliferation. This study adopts a qualitative approach and analyzes secondary data, particularly journal articles, reports, briefs, and developmental indices. The findings show that conditions symptomatic of a fragile state increase the incidence and proliferation of armed conflict in the region. Thus, conflict in the Sahel is a product of amplified pre-existing socioeconomic vulnerabilities and governance challenges.

How statistically fragile are randomized controlled trials comparing quadriceps tendon autografts with hamstring or bone-patellar tendon-bone autografts in anterior cruciate ligament reconstruction?

To determine the statistical fragility of randomized controlled trials (RCTs) which compare the use of quadriceps tendon (QT) autografts to either hamstring tendon (HT) or bone-patellar tendon-bone (BPTB) autografts in anterior cruciate ligament reconstruction (ACLR). A search was conducted across PubMed, MEDLINE and EMBASE databases for RCTs comparing QT autografts to HT or BPTB autografts in ACLR from inception to 21 April 2024. Studies that reported ≥1 statistically significant continuous outcome, statistically significant dichotomous outcome and/or nonsignificant dichotomous outcome were included for analysis. The fragility index (FI), continuous fragility index (CFI) and reverse fragility index (RFI) were calculated for significant dichotomous outcomes, significant continuous outcomes and nonsignificant dichotomous outcomes, respectively. A total of 11 RCTs comprising 716 patients were included. The mean sample size was 65.8 patients. The median FI among nine outcomes from four studies was 1.0 (interquartile range [IQR], 0.5; 95% confidence interval [CI], 0.6-1.4; range 0.5-1.5). The number of patients lost to follow-up at the final follow-up period was more than the study-specific FI in three (75%) studies. The median CFI among 30 outcomes from six studies was 4.9 (IQR, 10.1, 95% CI, 3.9-8.2; range 0-18.2). The number of patients lost to follow-up at the final follow-up period was more than the study-specific CFI in four (66.7%) studies. The median RFI among 10 outcomes from five studies was 5.0 (IQR, 3.5; 95% CI, 3.4-6.6; range 1.0-9.0). The number of patients lost to follow-up at the final follow-up period was more than the study-specific RFI in four (80%) studies. This systematic review revealed that regardless of the metric used, RCTs comparing QT autografts to HT or BPTB autograft options in ACLR are statistically fragile. While the indices of statistical fragility evaluated in this study are important metrics of robustness to consider, their application in research and clinical practice needs to be further elucidated. Level I.

Exploring the fragility of meta-analyses in ophthalmology: a systematic review.

The fragility index (FI) of a meta-analysis evaluates the extent that the statistical significance can be changed by modifying the event status of individuals from included trials. Understanding the FI improves the interpretation of the results of meta-analyses and can help to inform changes to clinical practice. This review determined the fragility of ophthalmology-related meta-analyses. Meta-analyses of randomized controlled trials with binary outcomes published in a journal classified as 'Ophthalmology' according to the Journal Citation Report or an Ophthalmology-related Cochrane Review were included. An iterative process determined the FI of each meta-analysis. Multivariable linear regression modeling evaluated the relationship between the FI and potential predictive factors in statistically significant and non-significant meta-analyses. 175 meta-analyses were included. The median FI was 6 (Q1-Q3: 3-12). This meant that moving 6 outcomes from one group to another would reverse the study's findings. The FI was 1 for 18 (10.2%) of the included meta-analyses and was ≤5 for 75 (42.4%) of the included meta-analyses. The number of events (p < 0.001) and the p-value (p < 0.001) were the best predictors of the FI in both significant and non-significant meta-analyses. The statistical significance of meta-analyses in ophthalmology often hinges on the outcome of a few patients. The number of events and the p-value are the most important factors in determining the fragility of the evidence. The FI is an easily interpretable measure that can supplement the reader's understanding of the strength of the evidence being presented. CRD42022377589.

The Fragility of Statistical Significance in the Use of Aspirin in Prevention of Venous Thromboembolism Events Following Total Joint Arthroplasty: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background/Objectives: Comparative studies often use the p value to convey statistical significance, but fragility indices (FI) and fragility quotients (FQ) may better signify statistical strength. The use of aspirin as venous thromboembolism (VTE) chemoprophylaxis following elective arthroplasty has been debated between the orthopedic and cardiac fields. The purpose of this study was to apply both the FI and FQ to evaluate the degree of statistical fragility in the total joint arthroplasty (TJA) literature regarding aspirin (ASA) use for VTE prevention. Methods: We performed a systematic search for TJA clinical trials from 2004 to 2023 reporting comparisons between ASA and other chemoprophylaxis methods for VTE. The FI of each outcome was calculated through reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by study sample size and interquartile range (IQR) was calculated. SPSS Meta-analysis function was used to calculate the Mean Effect Size Estimate and 95% Confidence Intervals for each outcome. Results: Of 245 articles screened, 39 met search criteria, with 10 RCTs included for analysis (n = 11,481 patients). There were 38 outcome events reported, with three significant (p < 0.05) outcomes and 35 non-significant (p > 0.05) outcomes identified. The overall FI and FQ for all 38 outcomes were 6 (IQR: 5-7) and 0.059 (IQR: 0.044-0.064), respectively. Seven studies (70%) reported a loss-to-follow-up (LTF) greater than the overall FI. There was no increased risk of DVT, PE, or mortality with use of ASA (all p > 0.2). Conclusions: Despite showing non-inferiority in preventing venous thromboembolic events in TJA overall, the highest-level peer-reviewed literature concerning aspirin use following total joint arthroplasty is considered statistically fragile due to high loss-to-follow-up. In addition to the reporting of the p value, the fragility index and quotient can further provide insight into the strength and trustworthiness of outcome measures.

Evaluation of the robustness of randomized controlled trials for the treatment modalities of esophageal cancer using the fragility index - a systematic review.

Esophageal cancer remains a significant global health challenge. Several treatment modalities were explored in randomized controlled trials (RCTs) in recent decades. This study evaluates the robustness of RCTs focusing on esophageal cancer treatment using the fragility index (FI) and reverse fragility index (RFI). A systematic review of RCTs studying different treatment modalities for esophageal cancer from 2000 to 2023 was conducted. The FI and RFI were utilized to gauge the robustness of statistically significant and non-significant outcomes, respectively. The FI represents the minimal number of patient outcomes that would need to alter to overturn a trial's statistical significance, while RFI indicates the minimal changes required to achieve significance in non-significant results. Out of 4028 studies retrieved, 21 RCTs were included for final analysis. The studies spanned 2001 to 2023 with a mean followup of 66 months (range, 29-108 months) and median number of patients of 194 (range, 45-802). The most common treatment modalities examined in these studies were neoadjuvant chemoradiotherapy (n = 7, 33.3%), neoadjuvant chemotherapy (n = 4, 19.0%), and neoadjuvant immunotherapy (n = 2, 9.5%). Only 5 studies (23.8%) had a statistically significant primary outcome result with a median FI of 6 (IQR, 2.5-8.5). Non-significant primary outcomes were seen in 16 studies (76.2%) with a median RFI of 4 (IQR 1-11) and lost to followup of 0 (IQR 0-4). In the study with the highest FI (10), the FI was lower than the number of patients lost to followup (13). Our findings demonstrate that most RCTs on esophageal cancer treatments did not report significant primary outcomes. The few studies that reported significant results had a low fragility index, suggesting a vulnerability in their findings.