Composite Outcomes at OMERACT: Multi-Outcome Domains and Composite Outcome Domains

2021 ◽  
Author(s):  
George A Wells ◽  
Peter Tugwell ◽  
Gunnar Tomasson ◽  
Francis Guillemin ◽  
Lara J Maxwell ◽  
...  
Keyword(s):  
Composite Outcome ◽  
Composite Outcomes

scholarly journals Bias Attributable to Composite Outcome

2020 ◽  
Author(s):  
Fredi Alexander Diaz-Quijano
Keyword(s):  
Clinical Trials ◽  
Delta Method ◽  
List Type ◽  
Composite Outcome ◽  
Critical Component ◽  
Association Measures ◽  
Composite Outcomes ◽  
Critical Components ◽  
Relevant Component ◽  
Positive Controls

AbstractBackgroundLittle guidance is available on how composite outcomes should be interpreted, especially in situations of varied direction in the association across the event subtypes. I proposed an index to evaluate the bias attributable to composite outcomes (BACO) and applied it in recently published clinical trials.MethodsI defined the BACO index as the ratio between logarithms of the association measures of both a composite outcome and its most relevant component (e.g., any-cause mortality). By using the non-linear combination of parameters, based on the delta method, I calculated the confidence intervals and performed Wald-type tests for the null hypotheses (BACO index = 1). I applied this method in systematically selected clinical trials, and in two other preselected trials which I considered “positive controls”. These last trials have been recognized as examples of primary composite outcomes that were disregarded because of inconsistency with the treatment effect on mortality.ResultsBACO index values different from one were classified according to whether the use of composite outcomes overestimated (BACO index >1), underestimated (BACO index between zero and <1), or inverted (BACO index <0) the association between exposure and prognosis. In three of 23 clinical trials and the two positive controls, the BACO indices were significantly lower than one (using p <0.005 as a preset cutoff).ConclusionBased on the BACO index testing, researchers could predefined rules to make impartial decisions about maintaining a composite outcome as the primary endpoint or to state cautions regarding its interpretation.Key MessagesDiscrepancies between the effects on composite outcomes and those on their most critical components make the interpretation of research results a challenge.An index based on the ratio of association measures can be used to evaluate the correspondence between the composite outcome and its most critical component.This index could help to preset rules to make decisions for interpretation of clinical studies.

scholarly journals Comparing low-molecular-weight heparin dosing for treatment of venous thromboembolism in patients with obesity (RIETE registry)

2020 ◽  
Vol 4 (11) ◽  
pp. 2460-2467
Author(s):  
Reza Mirza ◽  
Robby Nieuwlaat ◽  
Juan J. López-Núñez ◽  
Raquel Barba ◽  
Arnav Agarwal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Low Molecular Weight Heparin ◽  
Multivariable Analysis ◽  
Multivariable Logistic Regression Analysis ◽  
Low Molecular Weight ◽  
Composite Outcome ◽  
Bleeding Episodes ◽  
Composite Outcomes

Abstract Because of the absence of comparative evidence, current guidelines and product monographs diverge in the dosing of low-molecular-weight heparin (LMWH) for obese patients with venous thromboembolism (VTE). We used the RIETE registry to compare the primary composite outcomes (VTE recurrence, major bleeding, or death) in patients with VTE who weighed &gt;100 kg during LMWH therapy with capped doses of LMWH (18 000 IU/d) vs uncapped doses (&gt;18 000 IU/d). Multivariable logistic regression analysis was used to account for possible confounders. A total of 2846 patients who weighed &gt;100 kg were included: 454 (16%) received capped doses of LMWH, and the remaining 2392 received uncapped doses. Mean (standard deviation) LMWH treatment duration was 14.8 (20.6) and 14.3 (32.3) days, respectively. Thirty-one patients (1.9%) had VTE recurrences, 38 (1.3%) had bleeding episodes, 65 (2.3%) died, and 122 (4.3%) had at least 1 of the composite outcomes. Unadjusted outcome rates revealed that capped dosing was associated with a decrease in the composite outcome (rate ratio, 0.22; 95% confidence interval [CI], 0.04-0.75). Multivariable analysis confirmed that patients who received capped doses had significantly lower rates of the composite outcome (odds ratio, 0.16; 95% CI, 0.04-0.68) while receiving LMWH. These retrospective observational data suggest that capped dosing of LMWH is an acceptable alternative to uncapped dosing based on body weight, given the significantly lower composite event rate of VTE recurrence, major bleeding, and all-cause death.

scholarly journals A more comprehensive evaluation of quality of care after total hip and knee arthroplasty: combining 4 indicators in an ordered composite outcome

2021 ◽  
Author(s):  
Peter Van Schie ◽  
Leti Van Bodegom-Vos ◽  
Liza N Van Steenbergen ◽  
Rob G H H Nelissen ◽  
Perla J Marang-van de Mheen ◽  
...  
Keyword(s):  
Quality Of Care ◽  
Comprehensive Evaluation ◽  
Composite Outcome ◽  
Comprehensive Overview ◽  
Random Effects Models ◽  
Total Hip ◽  
Hospital Variation ◽  
Specific Feedback ◽  
Composite Outcomes

Background and purpose — Most arthroplasty registers give hospital-specific feedback on revision rates after total hip and knee arthroplasties (THA/TKA). However, due to the low number of events per hospital, multiple years of data are required to reliably detect worsening performance, and any single indicator provides only part of the quality of care delivered. Therefore, we developed an ordered composite outcome including revision, readmission, complications, and long length-of-stay (LOS) for a more comprehensive view on quality of care and assessed the ability to reliably differentiate between hospitals in their performance (rankability)with fewer years of data. Methods — All THA and TKA performed between 2017 and 2019 in 20 Dutch hospitals were included. All combinations of the 4 indicators were ranked from best to worst to create the ordinal composite outcome for THA and TKA separately. Between-hospital variation for the composite outcome was compared with individual indicators standardized for case-mix differences, and we calculated the statistical rankability using fixed and random effects models. Results — 22,908 THA and 20,423 TKA were included. Between-hospital variation for the THA and TKA composite outcomes was larger when compared with revision, readmission, and complications, and similar to long LOS. Rankabilities for the composite outcomes were above 80% even with 1 year of data, meaning that largely true hospital differences were detected rather than random variation. Interpretation — The ordinal composite outcome gives a more comprehensive overview of quality of delivered care and can reliably differentiate between hospitals in their performance using 1 year of data, thereby allowing earlier introduction of quality improvement initiatives.

Association and treatment of diabetes in patients affected by Covid-19

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1198-1201
Author(s):  
Syed Yasir Afaque
Keyword(s):  
Diabetes Mellitus ◽  
Prognostic Value ◽  
Heart Diseases ◽  
The Novel ◽  
The World ◽  
Treatment Of Diabetes ◽  
Coronavirus Infection ◽  
Composite Outcomes ◽  
Novel Coronavirus ◽  
The Impact

In December 2019, a unique coronavirus infection, SARS-CoV-2, was first identified in the province of Wuhan in China. Since then, it spread rapidly all over the world and has been responsible for a large number of morbidity and mortality among humans. According to a latest study, Diabetes mellitus, heart diseases, Hypertension etc. are being considered important risk factors for the development of this infection and is also associated with unfavorable outcomes in these patients. There is little evidence concerning the trail back of these patients possibly because of a small number of participants and people who experienced primary composite outcomes (such as admission in the ICU, usage of machine-driven ventilation or even fatality of these patients). Until now, there are no academic findings that have proven independent prognostic value of diabetes on death in the novel Coronavirus patients. However, there are several conjectures linking Diabetes with the impact as well as progression of COVID-19 in these patients. The aim of this review is to acknowledge about the association amongst Diabetes and the novel Coronavirus and the result of the infection in such patients.

scholarly journals Sex disparity in long-term stroke recurrence and mortality in a rural population in the United States

2020 ◽  
Vol 13 ◽  
pp. 175628642097189
Author(s):  
Clare Lambert ◽  
Durgesh Chaudhary ◽  
Oluwaseyi Olulana ◽  
Shima Shahjouei ◽  
Venkatesh Avula ◽  
...  
Keyword(s):  
United States ◽  
Ischemic Stroke ◽  
Rural Population ◽  
The United States ◽  
Competing Risk ◽  
Stroke Recurrence ◽  
Composite Outcome ◽  
Stroke Patients ◽  
Central Pennsylvania ◽  
All Cause Mortality

Background: Several studies suggest women may be disproportionately affected by poorer stroke outcomes than men. This study aims to investigate whether women have a higher risk of all-cause mortality and recurrence after an ischemic stroke than men in a rural population in central Pennsylvania, United States. Methods: We analyzed consecutive ischemic stroke patients captured in the Geisinger NeuroScience Ischemic Stroke research database from 2004 to 2019. Kaplan–Meier (KM) estimator curves stratified by gender and age were used to plot survival probabilities and Cox Proportional Hazards Ratios were used to analyze outcomes of all-cause mortality and the composite outcome of ischemic stroke recurrence or death. Fine–Gray Competing Risk models were used for the outcome of recurrent ischemic stroke, with death as the competing risk. Two models were generated; Model 1 was adjusted by data-driven associated health factors, and Model 2 was adjusted by traditional vascular risk factors. Results: Among 8900 adult ischemic stroke patients [median age of 71.6 (interquartile range: 61.1–81.2) years and 48% women], women had a higher crude all-cause mortality. The KM curves demonstrated a 63.3% survival in women compared with a 65.7% survival in men ( p = 0.003) at 5 years; however, the survival difference was not present after controlling for covariates, including age, atrial fibrillation or flutter, myocardial infarction, diabetes mellitus, dyslipidemia, heart failure, chronic lung diseases, rheumatic disease, chronic kidney disease, neoplasm, peripheral vascular disease, past ischemic stroke, past hemorrhagic stroke, and depression. There was no adjusted or unadjusted sex difference in terms of recurrent ischemic stroke or composite outcome. Conclusion: Sex was not an independent risk factor for all-cause mortality and ischemic stroke recurrence in the rural population in central Pennsylvania.

scholarly journals Differences in effectiveness and use of laparoscopic surgery in locally advanced colon cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Schootman ◽  
Matthew Mutch ◽  
T. Loux ◽  
J. M. Eberth ◽  
N. O. Davidson
Keyword(s):  
Colon Cancer ◽  
Length Of Stay ◽  
Cancer Patients ◽  
Postoperative Ileus ◽  
Locally Advanced ◽  
Composite Outcome ◽  
Improvement Program ◽  
Advanced Colon Cancer ◽  
Outcome Score ◽  
T4 Colon Cancer

AbstractPatients with locally advanced colon cancer have worse outcomes. Guidelines of various organizations are conflicting about the use of laparoscopic colectomy (LC) in locally advanced colon cancer. We determined whether patient outcomes of LC and open colectomy (OC) for locally advanced (T4) colon cancer are comparable in all colon cancer patients, T4a versus T4b patients, obese versus non-obese patients, and tumors located in the ascending, descending, and transverse colon. We used data from the 2013–2015 American College of Surgeons’ National Surgical Quality Improvement Program. Patients were diagnosed with nonmetastatic pT4 colon cancer, with or without obstruction, and underwent LC (n = 563) or OC (n = 807). We used a composite outcome score (mortality, readmission, re-operation, wound infection, bleeding transfusion, and prolonged postoperative ileus); length of stay; and length of operation. Patients undergoing LC exhibited a composite outcome score that was 9.5% lower (95% CI − 15.4; − 3.5) versus those undergoing OC. LC patients experienced a 11.3% reduction in postoperative ileus (95% CI − 16.0; − 6.5) and an average of 2 days shorter length of stay (95% CI − 2.9; − 1.0). Patients undergoing LC were in the operating room an average of 13.5 min longer (95% CI 1.5; 25.6). We found no evidence for treatment heterogeneity across subgroups (p > 0.05). Patients with locally advanced colon cancer who receive LC had better overall outcomes and shorter lengths of stay compared with OC patients. LC was equally effective in obese/nonobese patients, in T4a/T4b patients, and regardless of the location of the tumor.

scholarly journals Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial

Diabetologia ◽  
2021 ◽  
Author(s):  
David Z. I. Cherney ◽  
◽  
Bernard Charbonnel ◽  
Francesco Cosentino ◽  
Samuel Dagogo-Jack ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Renal Dialysis ◽  
Composite Endpoint ◽  
Composite Outcome ◽  
The Impact

Abstract Aims/hypothesis In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Methods Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed. Results A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups. Conclusions/interpretation Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR. Trial registration ClinicalTrials.gov NCT01986881 Graphical abstract

Gastrostomy Tubes Placed in Children With Neurologic Impairment: Associated Morbidity and Mortality

2021 ◽  
pp. 088307382110001
Author(s):  
Jody L. Lin ◽  
Joseph Rigdon ◽  
Keith Van Haren ◽  
MyMy Buu ◽  
Olga Saynina ◽  
...  
Keyword(s):  
Severe Pneumonia ◽  
Sensitivity Analyses ◽  
Tube Placement ◽  
Composite Outcome ◽  
Eligibility Criteria ◽  
Risk Of Death ◽  
Cox Proportional Hazard ◽  
Neurologic Impairment ◽  
Increased Risk ◽  
The Impact

Background: Gastrostomy tube (G-tube) placement for children with neurologic impairment with dysphagia has been suggested for pneumonia prevention. However, prior studies demonstrated an association between G-tube placement and increased risk of pneumonia. We evaluate the association between timing of G-tube placement and death or severe pneumonia in children with neurologic impairment. Methods: We included all children enrolled in California Children’s Services between July 1, 2009, and June 30, 2014, with neurologic impairment and 1 pneumonia hospitalization. Prior to analysis, children with new G-tubes and those without were 1:2 propensity score matched on sociodemographics, medical complexity, and severity of index hospitalization. We used a time-varying Cox proportional hazard model for subsequent death or composite outcome of death or severe pneumonia to compare those with new G-tubes vs those without, adjusting for covariates described above. Results: A total of 2490 children met eligibility criteria, of whom 219 (9%) died and 789 (32%) had severe pneumonia. Compared to children without G-tubes, children with new G-tubes had decreased risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.39-0.55) but increased risk of the composite outcome (HR 1.21, CI 1.14-1.27). Sensitivity analyses using varied time criteria for definitions of G-tube and outcome found that more recent G-tube placement had greater associated risk reduction for death but increased risk of severe pneumonia. Conclusion: Recent G-tube placement is associated with reduced risk of death but increased risk of severe pneumonia. Decisions to place G-tubes for pulmonary indications in children with neurologic impairment should weigh the impact of severe pneumonia on quality of life.

scholarly journals FRI0421 RATES OF PROGRESSION DIFFER BETWEEN STRUCTURAL PHENOTYPES OF KNEE OSTEOARTHRITIS: A SECONDARY ANALYSIS FROM THE FNIH COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 808.1-809
Author(s):  
F. Roemer ◽  
J. Collins ◽  
T. Neogi ◽  
M. Crema ◽  
A. Guermazi
Keyword(s):  
Subchondral Bone ◽  
Radiographic Progression ◽  
Conditional Logistic Regression ◽  
Secondary Analysis ◽  
Sensitivity Analyses ◽  
Case Group ◽  
Composite Outcome ◽  
Bone Phenotype ◽  
Increased Risk ◽  
Inflammatory Phenotype

Background:Imaging plays an important role in determining structural disease severity and potential suitability of patients recruited to disease-modifying osteoarthritis drug (DMOAD) trials. It has been suggested that there may be three main structural phenotypes in OA, i.e., inflammation, meniscus/cartilage and subchondral bone. These may progress differently and may represent distinct tissue targets for DMOAD approaches.Objectives:To stratify the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort, a well-defined subsample of the larger Osteoarthritis Initiative (OAI) study, into distinct structural phenotypes based on semiquantitative MRI assessment and to determine their risk for progression over 48 months.Methods:The FNIH was designed as a case-control study with knees showing either 1) radiographic and pain progression (i.e., “composite” cases), 2) radiographic progression only (“JSL”), 3) pain progression only, and 4) neither radiographic nor pain progression. MRI of both knees was performed on 3 T systems at the four OAI clinical sites. Two musculoskeletal radiologists read the baseline MRIs according to the MOAKS scoring system. Knees were stratified into subchondral bone, meniscus/cartilage and inflammatory phenotypes1. A secondary, less stringent definition for inflammatory and meniscus/cartilage phenotype was used for sensitivity analyses. The relation of each phenotype to risk of being in the JSL or composite case group compared to those not having that phenotype was determined using conditional logistic regression. Only KL2 and 3 and those without root tears were included.Results:485 knees were included. 362 (75%) did not have any phenotype, while 95 (20%) had the bone phenotype, 22 (5%) the cartilage/meniscus phenotype and 19 (4%) the inflammatory phenotype. The bone phenotype was associated with a higher risk of the JSL and composite outcome (OR 1.81;[95%CI 1.14,2.85] and 1.65; 95%CI [1.04,2.61]) while the inflammatory (OR 0.96 [95%CI 0.38,2.42] and 1.25; 95%CI [0.48,3.25]) and the meniscus/cartilage phenotypes were not (OR 1.30 95%CI [0.55,3.07] and 0.99; 95%CI [0.40,2,49]).In sensitivity analyses, the bone phenotype and having two phenotypes (vs. none) were both associated with increased risk of experiencing the composite outcome (bone: OR 1.65; 95% CI 1.04, 2.61; 2 phenotypes: OR 1.87; 95% CI 1.11, 3.16.Conclusion:The bone phenotype was associated with increased risk of having both radiographic and pain progression together, or radiographic progression alone, whereas the inflammatory phenotype or meniscus/cartilage phenotype each individually were not associated with either outcome. Phenotypic stratification appears to provide insights into risk for structural or composite structure plus pain progression, and therefore may be useful to consider when selecting patients for inclusion in clinical trials.References:[1]Roemer FW, Collins J, Kwoh CK, et al. MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES). Osteoarthritis Cartilage 2020;28(1):71-81Disclosure of Interests:Frank Roemer: None declared, Jamie Collins Consultant of: Boston Imaging Core Lab (BICL), LLC., Tuhina Neogi Grant/research support from: Pfizer/Lilly, Consultant of: Pfizer/Lilly, EMD-Merck Serono, Novartis, Michel Crema: None declared, Ali Guermazi Consultant of: AventisGalapagos, Pfizer, Roche, AstraZeneca, Merck Serono, and TissuGene

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