Study Of Outcomes In Patients Research Articles

Early functional recovery outcomes and return to work after primary total hip arthroplasty: a novel patient reported outcomes questionnaire

PurposeClinical and patient reported outcomes are often collected before and after the procedure to benchmark and study outcomes for patients. These outcomes and scores are useful for tracking patient outcomes after surgery, however, the fact that these commonly used measures typically provide information about a patient’s level of pain and function at a single point in time is a limitation.MethodsWe present early functional recovery and return to work outcomes after primary THA from a novel questionnaire administered in a global, multi-center, prospective clinical study.ResultsBy 6 and 12 weeks post-op, a large proportion of study subjects were able to perform functional recovery outcomes after their THA: walk without an aid (74%; 94%); drive (76%; 97%); basic activities of daily living (94%; 99%); perform light household duties (91%; 96%); perform moderate-to-heavy household duties (54%; 86%); go up and down a flight of stairs (92%; 99%); put on socks/stockings (77%; 93%); bend down to pick up an object from the floor (87%; 97%); stand up from a chair (96%; 99%); perform leisure recreational activities (54%; 84%); perform primary goal identified pre-THA (69%; 86%). 60% were able to return to work by 12 weeks post-op. These questions showed strong association with the Forgotten Joint Score.ConclusionExcellent patient reported early functional recovery outcomes and satisfaction were observed at 6- and 12-weeks post-op in this cohort and is the first reported data using a novel PRO.Clinical trial registrationNCT03189303, registered June 14, 2017.

SGLT2 Inhibitors vs GLP-1 Receptor Agonists and Clinical Outcomes in Patients With Diabetes With/Without Atrial Fibrillation.

The coexistence of diabetes mellitus and atrial fibrillation (AF) is associated with substantial risks of adverse cardiovascular events. The relevant outcomes associated with the use of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) vs glucagon-like peptide-1 receptor agonists (GLP-1RAs) among patients with type 2 diabetes (T2D) with/without concomitant AF remain unknown. In this nationwide retrospective cohort study from the Taiwan National Health Insurance Research Database, there were 344 392 and 31 351 patients with T2D without AF, and 11 462 and 816 T2D patients with AF treated with SGLT2is and GLP-1RAs, respectively, from May 1, 2016, to December 31, 2019. Patients were followed from the drug index date until the occurrence of study events, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. We used propensity score-stabilized weight to balance covariates across the 2 medication groups. The incidence rate of all study outcomes in patients with concomitant AF was much higher than in those without concomitant AF. For the AF cohort, SGLT2i vs GLP-1RA was associated with a lower risk of hospitalization for heart failure (HF) (2.32 vs 4.74 events per 100 person-years; hazard ratio [HR] 0.48, 95% CI 0.36-0.66), with no benefit seen for the non-AF cohort (P for homogeneity < .01). SGLT2i vs GLP-1RA was associated with a lower risk of composite kidney outcomes both in the AF (0.38 vs 0.79 events per 100 person-years; HR 0.47; 95% CI 0.23-0.96) and the non-AF cohorts (0.09 vs 0.18 events per 100 person-years; HR 0.53; 95% CI 0.43-0.64). There were no significant differences in the risk of major adverse cardiovascular events and all-cause mortality in those who received SGLT2i compared with GLP-1RA for the AF or non-AF cohorts. Considering the high risk of developing HF and/or high prevalence of concomitant HF in patients with concomitant diabetes and AF, whether SGLT2is should be the preferred treatment to GLP-1RAs for such a high-risk population requires further investigation.

Serum creatinine to cystatin C ratio and clinical outcomes in adults with non-dialysis chronic kidney disease.

BackgroundStudies have suggested that the serum creatinine/cystatin C (Cr/CysC) ratio is a surrogate marker for muscle wasting is associated with adverse outcomes in several disease conditions. To clarify the utility of the Cr/CysC ratio as a prognostic marker in chronic kidney disease (CKD) we evaluated the association between the Cr/CysC ratio clinical outcomes in patients with non-dialysis CKD.MethodsThis prospective observational cohort study included 1,966 participants of the KoreaN cohort study Outcomes in patients With CKD (KNOW-CKD). We evaluated associated factors with the serum Cr/CysC ratio and association between the serum Cr/CysC ratio and composite outcomes of all-cause death and cardiovascular events (CVEs).ResultsThe mean age was 54 ± 12 (SD) years and 61% were men. The mean serum Cr/CysC ratio was 10.97 ± 1.94 in men and 9.10 ± 1.77 in women. The Cr/CysC ratio correlated positively with urinary creatinine excretion, a marker of muscle mass. In the fully adjusted Cox proportional hazard model, the Cr/CysC ratio was associated with the occurrence of adverse outcomes through a median follow-up of 5.9 years [hazard ratio (HR) = 0.92, 95% confidence interval (CI) = 0.85–0.99 for the composite outcomes, HR = 0.87, 95% CI, 0.78 − 0.97 for all-cause death, and HR = 0.93; 95% CI, 0.84–1.04 for CVEs]. In subgroup analyses, there were interactions of the Cr/CysC ratio with age and sex for risk of the clinical outcomes, but not eGFR group.ConclusionA higher Cr/CysC ratio is associated with a lower risk of the composite outcomes, especially all-cause mortality, even after adjusting for eGFR. These suggest that the Cr/CysC ratio is a useful prognostic marker in CKD.

Increased Distraction Magnitude Leads to Greater Reduction in the Apnea-Hypopnea Index in Infants With Robin Sequence

Upper airway obstruction seen in Robin Sequence (RS) is commonly treated with mandibular distraction osteogenesis (MDO). The purpose of this study is to evaluate the impact of distraction distance on sleep study outcomes in patients with obstructive sleep apnea (OSA) secondary to RS. A retrospective cohort study was conducted for patients with isolated RS who underwent MDO at Children's Hospital Los Angeles between January 2006-September 2021. The predictor variable was distraction distance (maximal distraction using a 30mm device vs sub-maximal distraction), and the primary outcome variable was OSA scores. Relationships between covariates, including demographic characteristics, preoperative sleep variables, and postoperative OSA outcomes using polysomnography, were also analyzed. Descriptive statistics and tests of statistical significance were performed using the Statistical Package for Social Sciences (SPSS) (version 28.0), including Student's t-test, proportions testing, multiple linear regression, and correlation analysis. Seventy-one patients met inclusion criteria (39.4% female, 60.6% male). Average age at MDO was 3.0±10.2months. Fifty-six patients were distracted maximally with a 30mm distractor, while the remaining 15 patients experienced shorter distraction due to distractor limitations (25mm distractor), persistent infection or family request. Looking at absolute values of postoperative sleep study variables, there were no significant differences between patients who were maximally and sub-maximally distracted across apnea-hypopnea index (AHI), highest carbon dioxide, lowest oxygen saturation, and oxygen requirement. However, both cohorts demonstrated significant improvements in lowest oxygen saturation, AHI, highest carbon dioxide level, and highest oxygen requirement compared to their pre-distraction levels. Compared with patients distracted <30mm, maximal distraction had a significantly greater improvement in AHI when controlling for preoperative sleep study variables (P=.047). Patients with isolated RS who have more severe OSA experienced greater improvements in AHI, oxygen requirement, and oxygen saturation after MDO. Two-thirds of patients no longer had oxygen requirements after MDO. Our results suggest that MDO is helpful in treating patients with RS regardless of distraction distance. However, our study provides evidence that increasing the distraction distance may further improve AHI, which is particularly beneficial to patients with a significant preoperative AHI.

Treatment-related toxicity and improved outcomes with immune checkpoint inhibitors in patients with hepatocellular carcinoma.

4085 Background: The development of treatment-related adverse events (trAE) correlates favorably with clinical outcomes in multiple studies of patients receiving immune checkpoint inhibitors (ICI), however, this relationship is undefined in patients with hepatocellular carcinoma (HCC). This retrospective multi-center study aimed to examine whether trAEs are prognostic in HCC. Methods: We established an international consortium of 10 tertiary-care referral centers located in Europe (n = 67), United States (US, n = 248) and Asia (n = 42) to test whether the development of clinically significant trAE (i.e. graded &gt;2, trAE2) predicted for improved overall (OS), progression-free survival (PFS), and overall response rates (ORR) following ICI, and subsequently validated this association in a separate cohort of 406 HCC patients receiving ICI therapy as part of international clinical trials submitted to the US Food and Drug Administration (FDA) in support of marketing applications. Results: In a multi-institutional cohort of 357 patients, 274 (77%) with Barcelona Clinic Liver Cancer (BCLC) stage C HCC mostly treated with ICI monotherapy (n = 304, 85%), trAE were reported in 146 patients (41%). Development of trAE2 were associated with longer OS (23.3 versus 12.2 months) and PFS (8.6 months versus 3.7 months). After adjusting for viral aetiology, gender, presence of cirrhosis, Child-Pugh class, BCLC stage, AFP levels, ECOG-PS, ICI regimen (mono/combination therapy) and receipt of corticosteroid therapy, trAE2 were confirmed predictors of improved OS (HR 0.55; 95%CI:0.34-0.88) and PFS (HR 0.51; 95%CI: 0.35-0.74). TrAE2 were associated with higher ORR (27% versus 16%) from ICI. The association between trAE2 and patients’ OS (HR 0.49; 95%CI:0.34-0.70) and PFS (HR 0.43; 95%CI:0.32-0.59) was also observed in the FDA dataset. After a 6-weeks landmark selection, trAE2 were confirmed to be associated with improved PFS (HR 0.59; 95%CI:0.39-0.87); the additional analysis adjusted for tumour response and duration of treatment within the FDA cohort further confirmed the association with longer PFS (HR 0.67; 95%CI: 0.47-0.94). Conclusions: Development of trAE2 may correlate with response and survival in patients with HCC receiving ICI, a clinical setting where the lack of biomarkers still represents an unmet need. Prospective studies aimed at understanding the underlying immunologic foundations of such relationship are warranted to identify predictive biomarkers of toxicity and response.

Dulaglutide is cardioprotective with or without background metformin in patients with diabetes and established or high risk for coronary vascular disease. A subgroup analysis of the REWIND Trial

Abstract Background The 2019 ESC/EASD European Guidelines for Diabetes, Prediabetes and Coronary Artery Disease introduced a paradigm shift in the management of patients with type 2 diabetes (T2D) at high risk for or already established cardiovascular (CV) disease by recommending a GLP-1 receptor agonist (GLP-1 RA) as initial glucose lowering therapy in patients without any previous antihyperglycaemic treatment. This recommendation has been questioned since outcome trials of GLP-1-RA were usually conducted with metformin as background therapy. Purpose The aim of this report is to determine whether the effect of dulaglutide on cardiovascular events varies according to baseline metformin therapy. It was tested by a subgroup analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. Methods REWIND, a multicentre, double-blind, placebo-controlled trial, comprised 9901 participants (women: 46.3%; mean age: 66.2 years) with T2D and either a previous CV event (31%) or a high CV risk (69%). They were randomised (1:1) to either sc. dulaglutide (1.5 mg/week) or placebo in addition to standard of care. The primary outcome was the first of a composite of non-fatal myocardial infarction or stroke or CV death. Secondary outcomes were a microvascular composite endpoint, all-cause death and heart failure. The effect of dulaglutide study outcomes in patients with and without baseline metformin was evaluated by means of a Cox regression hazard model with baseline metformin, dulaglutide assignment and the interaction between dulaglutide and metformin as independent variables. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using a Cox regression model with additional adjustments for factors that differed at baseline between people on vs. those not on baseline metformin selected by a backward regression model. A p&amp;lt;0.05 was considered significant (see Figure 1). Results Patients without metformin at baseline (n=1864; 19%) were older, leaner, more likely to be women and had a higher proportion of prior CV events, heart failure and renal disease than patients with metformin (n=8037; 81%). During a median follow-up of 5.4 years (IQR 5.1–5.9), the primary outcome occurred in 976 (12%) participants with baseline metformin and in 281 (15%) without metformin. There was no significant difference in the effect of dulaglutide on the primary outcome in the groups with vs. without metformin at baseline (HR 0.93 [CI 0.82–1.06] vs. 0.78 [CI 0.61–0.99]; p for interaction=0.16). The effect of dulaglutide on the secondary outcomes was also not modified by concomitant metformin use (all interaction p&amp;gt;0.1). Conclusion This exploratory analysis suggests that the cardioprotective effect of dulaglutide does not depend on baseline metformin therapy. This supports the recommendation of using agents with proven cardioprotective efficacy without metformin in patients with diabetes and additional cardiac risk factors. Figure 1. Forest plot Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Eli Lilly and Company

Prognostic impact of plasma volume estimated from hemoglobin and hematocrit in heart failure with preserved ejection fraction.

Plasma volume (PV) estimated from Duarte's formula (based on hemoglobin/hematocrit) has been associated with poor prognosis in patients with heart failure (HF). There are, however, limited data regarding the association of estimated PV status (ePVS) derived from hemoglobin/hematocrit with clinical profiles and study outcomes in patients with HF and preserved ejection fraction (HFpEF). Patients from North and South America enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) with available hemoglobin/hematocrit data were studied. The association between ePVS (Duarte formula and Hakim formula) and the composite of cardiovascular mortality, HF hospitalization, or aborted cardiac arrest was assessed. Among 1747 patients (age 71.6years; males 50.1%), mean ePVS derived from Duarte formula was 4.9 ± 1.0mL/g. Higher Duarte-derived ePVS was associated with prior HF admission, diabetes, more severe congestion, poor renal function, higher natriuretic peptide level, and E/e'. After adjustment for potential covariates including natriuretic peptide, higher Duarte-derived ePVS was associated with an increased rate of the primary outcome [highest vs. lowest ePVS quartile: adjusted-HR (95%CI) = 1.79 (1.28-2.50), p < 0.001]. Duarte-derived ePVS improved prognostic performance on top of clinical and routine variables (including natriuretic peptides) (NRI = 11, p < 0.001), whereas Hakim-derived ePVS did not (p = 0.59). The prognostic value of Duarte-derived ePVS was not modified by renal function (P interaction > 0.10 for all outcomes). ePVS from Duarte's formula was associated with congestion status and improved risk stratification regardless of renal function. Our findings suggest that Duarte-derived ePVS is a useful congestion variable in patients with HFpEF.

Clinical determinants and prognostic implications of renin and aldosterone in patients with symptomatic heart failure.

AimsActivation of the renin–angiotensin–aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF.Methods and resultsWe analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT‐CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all‐cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT‐CHF study, median renin and aldosterone levels were 85.3 (percentile25–75 = 28–247) μIU/mL and 9.4 (percentile25–75 = 4.4–19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted‐HR (95% CI) = 1.47 (1.16–1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted‐HR (95% CI) = 1.16 (0.93–1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT‐CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies.ConclusionsCirculating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the “point” measurement of renin and aldosterone in HF is of limited clinical utility.

720. Efficacy of Fosfomycin for Injection (FOS) vs. Piperacillin–Tazobactam (PIP-TAZ) in Adults with Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP): ZEUS Study Outcomes in Patients With Reduced Study Drug Susceptibility

BackgroundFOS is being pursued for US registration in cUTI/AP. Safety and efficacy of FOS vs. PIP-TAZ were demonstrated in the noninferiority ZEUS trial in hospitalized patients with cUTI/AP. Although FOS resistance has been observed in several in vitro studies, resistance rates in clinical settings have remained relatively stable despite >40 years of clinical use of FOS outside of the United States. Here we report outcomes in patients who developed reduced susceptibility to study drug (FOS or PIP-TAZ) after enrollment in ZEUS.MethodsPatients received IV FOS 6g q8h or PIP-TAZ 4.5g q8h for 7 days (no oral switch allowed). The primary endpoint was overall success (clinical cure + microbiologic eradication) in microbiologic modified intent-to-treat (m-MITT) population at test-of-cure (TOC; Day 19–21). Reduced susceptibility to FOS or PIP-TAZ was defined as a ≥4-fold increase from baseline in minimum inhibitory concentration (MIC) at Day 5, end of treatment (EOT; Day 7–8), TOC, or late follow-up (LFU; Day 26 ± 2). Microbiologic eradication/persistence of baseline and postbaseline pathogens was confirmed post hoc by pulsed-field gel electrophoresis (PFGE).ResultsIn all m-MITT patients, overall success/clinical cure/microbiologic eradication rates (with PFGE) at TOC were 69.0/90.8/70.7% (FOS) and 57.3/91.6/60.1% (PIP-TAZ). Reduced study drug susceptibility was identified in 7/184 (3.8%) FOS and 8/178 (4.5%) PIP-TAZ patients; all had monomicrobial infections (Table 1). Of these patients, almost all were aged ≥50 years (93%), male (73%), white (100%), and had a screening diagnosis of cUTI (93%). At TOC, 7/7 FOS patients and 7/8 PIP-TAZ patients had microbiologic persistence but all patients were clinical cures; these responses were all sustained through LFU (Table 1).ConclusionIn the ZEUS study, few patients had urine isolates with reduced postbaseline susceptibility to either FOS or PIP-TAZ. No trend was observed in isolate species associated with decreased susceptibility to FOS or PIP-TAZ, including various Enterobacteriaceae species and Pseudomonas aeruginosa. Despite microbiologic persistence at TOC in a small number of patients, all of these patients were clinical cures at TOC and sustained cures at LFU. Disclosures All authors: No reported disclosures.

An Update on the Use of Disease-Modifying Therapy in Pregnant Patients with Multiple Sclerosis.

The active management of multiple sclerosis (MS) has been made possible during the last two decades with the advent of disease-modifying therapies (DMTs), leading to improved clinical outcomes for many patients. Furthermore, with the realization that MS does not adversely affect pregnancy outcome and that pregnancy does not have an overall negative impact on the long-term disease course of MS, the importance of appropriate counseling and discussion of future pregnancy plans with women of childbearing age is greater than ever. Although several DMTs are licensed for the treatment of MS, none are specifically approved for use during pregnancy or breastfeeding and the use of DMTs during these periods frequently gives rise to concerns regarding potential risks to the fetus. The outcomes of studies in patients with MS treated with DMTs during pregnancy and immediately postpartum have been the focus of several recently published papers. Given the high level of interest surrounding the prescribing of DMTs for MS patients of childbearing age, and the lack of clear guidance in this respect, the current review presents an up-to-date overview of new data, including observational data on real-world outcomes, that have been published during the last 2years, and could inform future prescribing decisions.

Head-to-Head Comparative Responsiveness of Patient-Reported Outcomes Before and After Anterior Cruciate Ligament Reconstruction

To compare in a head-to-head fashion the responsiveness of four PROMs commonly used to measure outcome in studies of patients undergoing anterior cruciate ligament (ACL) reconstruction.

The Reporting of Patient-reported Outcomes in Studies of Patients with Rheumatoid Arthritis: A Systematic Review of 250 Articles.

Patient-reported outcomes (PRO) in rheumatoid arthritis (RA) provide important information regarding disease effect. The study objective was to assess the frequency of PRO use in recent RA studies and compare results with a previous systematic review (SR) in 2005-2007. An SR was performed in PubMed MEDLINE (January 2015). Publications were identified using these MEdical Subject Headings terms: "arthritis, rheumatoid" with a limitation to "humans," "all adults: 19+ years," "English," "published in the last 2 years," and "clinical trials." All studies were assessed, whatever their designs. All PRO reported in publications were classified according to general domains of health by 2 authors. Statistics were descriptive. Two hundred fifty articles were analyzed. Of them, 113 (45.2%) were randomized controlled trials; 138 different PRO were reported. The most frequent PRO, similar to the 2007 SR, were function (68.0%), pain (40.0%), patient's global assessment (49.2%), and health-related quality of life (18.4%). Fatigue (14.4%), morning stiffness (10.0%), psychological status (9.6%), productivity losses (6.4%), utility (5.2%), sleep disturbance (2.4%), and coping (2.0%) were rarely reported. Although frequent domains were reported using well-validated questionnaires, the others were reported using heterogeneous questionnaires. The PRO collected and reported in RA studies are remarkably consistent with those seen in 2005-2007, and reflect the existing RA Core Set measures. Other domains of health prioritized by patients including fatigue, psychological status, productivity losses, sleep disturbance, and coping remain rarely reported. Further, heterogeneity in outcome measures used presents challenges in interpreting true disease effect and response to therapy.

Endovascular treatment for M2 occlusions in the era of stentrievers: a descriptive multicenter experience

BackgroundPatients with M2 middle cerebral artery (MCA) occlusions are not always considered for endovascular treatment.ObjectiveTo study outcomes in patients with M2 occlusion treated with endovascular procedures in the era of...

Survival in esophageal high-grade dysplasia/adenocarcinoma post endoscopic resection

Endoscopic resection followed by ablative therapy is frequently used to treat esophageal high-grade dysplasia or early esophageal adenocarcinoma. To study outcomes in patients with high-grade dysplasia compared to those with esophageal adenocarcinoma after endoscopic resection. Retrospective, observational, descriptive, single-centre study from a prospective database. We extracted data from 116 endoscopic resections. Survival was plotted using Kaplan-Meier curves multivariable Cox-proportional hazard assess for possible predictors of survival post-endoscopic resection was performed. 116 patients (64 esophageal adenocarcinoma, 52 high-grade dysplasia) underwent endoscopic resection from May 2003 to June 2010. Mean age was 71 ± 11 years for high-grade dysplasia and 72 ± 10 years for esophageal adenocarcinoma. Median follow-up was 17 months. Eighty-five patients had negative margins on endoscopic resection. Five-year survivals for high-grade dysplasia and esophageal adenocarcinoma were 86% (range 68-100%) and 78% (59-96%), respectively. Survival was not significantly different between groups (p=0.20). Overall mortality rate was 10.6% (9/85). At multivariable Cox regression increased Barrett's oesophagus length was associated with worse survival (HR 1.18 [1.06-1.33], p=0.0039). Survival was not affected by the pathology before resection: HR 2.4 [95%CI, 0.70-8.4], p=0.16. Survival in patients with high-grade dysplasia of the oesophagus is similar to those with esophageal adenocarcinoma. Longer Barrett's oesophagus segments are associated with decreased survival.

The Identifiable Virtual Patient Model: Comparison of Simulation and Clinical Closed-Loop Study Results

Optimizing a closed-loop insulin delivery algorithm for individuals with type 1 diabetes can be potentially facilitated by a mathematical model of the patient. However, model simulation studies that evaluate changes to the control algorithm need to produce conclusions similar to those that would be obtained from a clinical study evaluating the same modification. We evaluated the ability of a low-order identifiable virtual patient (IVP) model to achieve this goal. Ten adult subjects (42.5 ± 11.5 years of age; 18.0 ± 13.5 years diabetes; 6.9 ± 0.8% hemoglobin A1c) previously characterized with the IVP model were studied following the procedures independently reported in a pediatric study assessing proportional-integral-derivative control with and without a 50% meal insulin bolus. Peak postprandial glucose levels with and without the meal bolus and use of supplemental carbohydrate to treat hypoglycemia were compared using two-way analysis of variance and chi-square tests, respectively. The meal bolus decreased the peak postprandial glucose levels in both the adult-simulation and pediatricclinical study (231 ± 38 standard deviation to 205 ± 33 mg/dl and 226 ± 51 to 194 ± 47 mg/dl, respectively; p = .0472). No differences were observed between the peak postprandial levels obtained in the two studies (clinical and simulation study not different, p = .57; interaction p = .83) or in the use of supplemental carbohydrate (3 occurrences in 17 patient days of closed-loop control in the clinical-pediatric study; 7 occurrences over 20 patient days in the adult-simulation study, p = .29). Closed-loop simulations using an IVP model can predict clinical study outcomes in patients studied independently from those used to develop the model.

Use of US Veterans Affairs Administrative Databases to Study Outcomes in Patients with Rheumatoid Arthritis

To the Editor: In a recent issue of The Journal , Khurana, et al 1 report on the increased risk of lung cancer in patients with rheumatoid arthritis (RA) using administrative data from the Veterans Integrated Service Networks (VISN). The methodology and conclusions of the study raise several issues. The first is the definition of the diagnoses of RA and lung cancer used in the study. The authors state that the diagnosis of RA was based on International Classification of Diseases (ICD-9) coding of 714.0 in the computerized records without any other qualifying criteria. Published data show that an ICD-9 code for RA when combined with the receipt of a disease-modifying agent (DMARD) in the Veterans Affairs (VA) administrative databases has a sensitivity of 76%–88% and a specificity of 83%–97%2. Thus, use … Address reprint requests to Dr. P. Ranganathan, Division of Rheumatology, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8045, St. Louis, MO 63110. E-mail: prangana{at}im.wustl.edu

Combined Aspirin–Oral Anticoagulant Therapy Compared With Oral Anticoagulant Therapy Alone Among Patients at Risk for Cardiovascular Disease

For patients receiving oral anticoagulant (OAC) therapy, deciding whether to add aspirin to their treatment is a common clinical scenario with no clear guidelines to aid practice. We performed a systematic review and meta-analysis of randomized controlled trials comparing these 2 treatment strategies (combined aspirin-OAC therapy vs OAC therapy alone) to assess the therapeutic benefits and risks. Randomized controlled trials published up to June 2005 in MEDLINE, EMBASE, and Cochrane Library databases. Randomized controlled trials with at least 3 months of follow-up that compared aspirin-OAC therapy with OAC therapy alone, in which OAC was administered to achieve the same target international normalized ratio or was given at the same fixed dose in both treatment arms. Two reviewers independently extracted data on study characteristics and outcomes. Pooled odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated for study outcomes in patients receiving aspirin-OAC therapy and OAC therapy alone. Ten studies were included, totaling 4180 patients. The risk for arterial thromboembolism was lower in patients receiving combined aspirin-OAC therapy compared with OAC therapy alone (OR, 0.66; 95% CI, 0.52-0.84). However, these benefits were limited to patients with a mechanical heart valve (OR, 0.27; 95% CI, 0.15-0.49). There was no difference in the risk for arterial thromboembolism with these treatments in patients with atrial fibrillation (OR, 0.99; 95% CI, 0.47-2.07) or coronary artery disease (OR, 0.69; 95% CI, 0.35-1.36). There was no difference in all-cause mortality with either treatment (OR, 0.98; 95% CI, 0.77-1.25). The risk for major bleeding was higher in patients receiving aspirin-OAC therapy compared with OAC therapy alone (OR, 1.43; 95% CI, 1.00-2.02). Our findings question the current practice of using combined aspirin-OAC therapy except in patients with a mechanical heart valve, given the questionable benefits in reducing thromboembolic events and the increased risk of major bleeding.