Adjustment For Baseline Patient Characteristics Research Articles

Abstract WP149: Duration of Lead-In Parenteral Therapy and Outcomes in Individuals Treated With DOAC for Cerebral Venous Thrombosis: The ACTION-CVT Study

Background: Direct oral anticoagulants (DOACs) are suitable for some patients with cerebral venous thrombosis (CVT). The optimal transition strategy from parenteral anticoagulation (PA) to DOAC is not known. We examined duration of PA prior to DOAC initiation and outcomes in ACTION-CVT, an international retrospective study. Methods: We compared three groups: no lead-in PA, 1-4 days (d) of PA, and 5-21d of PA. The primary outcome at day 90 (D90) was a composite of CVT recurrence/extension and symptomatic intracranial hemorrhage (sICH). Secondary outcomes (D90) were complete venous recanalization and mRS of 0-2. We evaluated outcomes using descriptive statistics and crude and adjusted logistic regression modeling. Results: Of 231 patients treated with DOAC, 11.7% had no lead-in PA, 64.5% 1-4d, 23.8% 5-21d. Compared to those with <5d, those with 5-21d had worse clinical-radiological presentations at baseline, including more focal deficits, encephalopathy, and ICH (Table 1). Primary outcome events were low overall; all 6 occurred in the <5d group. Odds of complete recanalization were lower in the <5d group, although this difference attenuated with adjustment for baseline characteristics. There were no differences in odds of mRS 0-2. (Table 2) Conclusions: Individuals treated with DOAC for CVT who received 5-21d of PA had more severe clinical and radiological presentations compared to those with <5d. Rates of CVT extension, recurrence and sICH were too low to reach conclusions regarding safety of one strategy over another. Odds of complete recanalization were higher in those with 5-21d PA, but these differences attenuated after adjustment for baseline patient characteristics.

Arthroscopic Versus Open Ankle Arthrodesis: A 5-Year Follow Up.

End-stage ankle arthritis has long been managed surgically with open ankle arthrodesis (OAA). Since the first published report in 1983, arthroscopic ankle arthrodesis (AAA) has been thought to be associated with improved patient-reported outcome measures (PROMs) and fewer complications. The purpose of the present study was to compare the long-term PROMs, major complications, and reoperations for these 2 approaches at up to 15 years of follow-up. This longitudinal cohort study included patients at our institution who underwent primary ankle arthrodesis for the treatment of end-stage arthritis. Demographic data and preoperative COFAS (Canadian Orthopaedic Foot and Ankle Society) ankle arthritis type were collected for all patients. PROMs were completed preoperatively, at 6 months, and annually thereafter to 5 years. PROMs were compared at all time points with use of a mixed-effects regression model that adjusted for preoperative variables and scores. Major complications and reoperations at the site of the ankle arthrodesis were also compared. Of 1,294 patients who were screened for inclusion, 351 who had undergone ankle arthrodesis between 2003 and 2019 were eligible for the study. Of those, 223 had undergone AAA and 128 had undergone OAA. The 2 groups were similar preoperatively with respect to demographics, but COFAS Type-4 arthritis was relatively more common in the OAA group and Type-1 arthritis was relatively more common in the AAA group. In addition, the Ankle Osteoarthritis Scale (AOS) score and Ankle Arthritis Score (AAS) were better in the AAA group. In the mixed-effects model analysis, the differences in postoperative outcome scores between the groups were not significant. The risk of revision due to malunion or nonunion was similar in both groups (6% in the AAA group, compared with 4% in the OAA group). Deep infection and wound complications did not occur in the arthroscopic group but occurred in 4% of the patients in the OAA group. After adjustment for baseline patient characteristics, there were no differences in PROMs between the 2 techniques. Ankle arthrodeses done arthroscopically had a similar revision rate but lower infection rate compared with those done with the open technique. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Graft failure is more frequent after hamstring than patellar tendon autograft

The risk of graft failure after anterior cruciate ligament (ACL) reconstructions with hamstring or patellar tendon was evaluated in a French population of athletes. Athletes who had undergone ACL autograft reconstruction and who received rehabilitation care at the European Center for Sports Rehabilitation (CERS; Capbreton, France) were screened for this prospective cohort study. Eligibility criteria included a simple hamstring autograft or patellar tendon autograft surgical technique. Patients were contacted by phone to participate in follow-up during the second year after surgery. The primary endpoint was the graft failure frequency, evaluated with a multivariate logistic model with adjustment for baseline patient characteristics. The secondary endpoint was time to graft failure, analyzed by an adjusted Cox model. A total of 2424 athletes were included after having a hamstring autograft (semitendinosus and gracilis) or a patellar tendon autograft between 2011 and 2014. Of the 988 athletes who responded to a follow-up phone call (40.7% response rate), 33 were excluded for new contralateral ACL rupture (3.3%), with 955 included for analysis (713 hamstring autografts; 242 patellar-tendon autografts). There were no significant differences between the baseline characteristics of the patients analyzed and the population which did not respond to the questionnaire. A significant difference in the frequency of graft failure was seen, 6.5% for hamstring autografts vs 2.1% for patellar-tendon autografts [adjusted odds ratio (OR) = 3.64, 95% CI (1.55; 10.67); p = 0.007]. Mean time to graft failure was 10.7 vs 17.4months for hamstring and patellar-tendon autografts respectively [adjusted hazard ratio (HR) = 3.50, 95% CI (1.53; 10.11); p = 0.008]. Age less than 25years significantly increased the frequency of graft failure [adjusted OR = 3.85 (1.89; 8.72); p < 0.001]. The rate of patients returning to competitive sport after the first graft was not significantly different for the two techniques: 70.8% for hamstring and 77.8% for patellar tendon [adjusted OR = 0.718; 95% CI (0.50; 1.02)]. Graft failure is significantly more frequent after hamstring than patellar tendon autografts in a French population, despite similar rates of return to competition. Athletes aged less than 25years have a higher risk of failure than those aged ≥ 25years. Our results are in accordance with recent Scandinavian studies. II.

The Identification of Calcified Coronary Plaque Is Associated With Initiation and Continuation of Pharmacological and Lifestyle Preventive Therapies: A Systematic Review and Meta-Analysis

ObjectivesThe aim of this study was to assess the odds of initiation or continuation of pharmacological and lifestyle preventive therapies in patients with nonzero versus zero coronary artery calcium (CAC) score detected on cardiac computed tomography. BackgroundDetection of calcified coronary plaque could serve as a motivational tool for physicians and patients to intensify preventive therapies. MethodsWe searched PubMed, EMBASE (Excerpta Medica database), Web of Science, Cochrane CENTRAL (Cochrane central register of controlled trials), ClinicalTrials.gov, and the International Clinical Trials Registry Platform for studies evaluating the association of CAC scores with downstream pharmacological or lifestyle interventions for prevention of cardiovascular disease. Pooled odds ratios (ORs) of downstream interventions were obtained using the DerSimonian and Laird random effects model. ResultsAfter a review of 6,256 citations and 54 full-text papers, 6 studies (11,256 participants, mean follow-up time: 1.6 to 6.0 years) were included. Pooled estimates of the odds of aspirin initiation (OR: 2.6; 95% confidence interval [CI]: 1.8 to 3.8), lipid-lowering medication initiation (OR: 2.9; 95% CI: 1.9 to 4.4), blood pressure–lowering medication initiation (OR: 1.9; 95% CI: 1.6 to 2.3), lipid-lowering medication continuation (OR: 2.3; 95% CI: 1.6 to 3.3), increase in exercise (OR: 1.8; 95% CI: 1.4 to 2.4), and dietary change (OR: 1.9; 95% CI: 1.5 to 2.5) were higher in individuals with nonzero CAC versus zero CAC scores, but not for aspirin or blood pressure–lowering medication continuation. When assessed within individual studies, these findings remained significant after adjustment for baseline patient characteristics and cardiovascular risk factors. ConclusionsThis systematic review and meta-analysis suggests that nonzero CAC score, identifying calcified coronary plaque, significantly increases the likelihood of initiation or continuation of pharmacological and lifestyle therapies for the prevention of cardiovascular disease.

Impact of clinic follow-up visits on body weight control in people with prediabetes or diabetes mellitus: Japanese nonelderly cohort study.

Body weight control is considered essential for the management of diabetes mellitus. Clinicians have an important role in educating and guiding patients with diabetes to control their body weight. The aim of the present study was to clarify if clinic visits influenced body weight control of people with prediabetes or diabetes mellitus. To examine whether individuals with diabetes mellitus who visit clinics show better weight control. We used a large Japanese database (Japan Medical Data Center, Tokyo, Japan) of screening for lifestyle disease linked with administrative claim data to retrospectively identify people with prediabetes or diabetes mellitus based on their fasting plasma glucose and glycated haemoglobin (HbA1c) concentration. We collected data on their baseline characteristics (including age, sex, body mass index and disease history) and their lifestyles. We used propensity-score inverse probability of treatment weighted generalized estimating equations to examine the association between clinic visits and change in body mass index. Between 2013 and 2014, we identified 11004 individuals with prediabetes or diabetes. The proportions visiting clinics after the first diagnosis made at screening was 27.8%. Clinic visit was significantly associated with lower body mass index after adjustment for baseline patient characteristics a year after first screening (-0.17 kg/m2; 95% confidence interval, -0.22 to -0.12). In Japanese people found to have prediabetes or diabetes during an annual health screen, those who visited clinics after their first diagnosis were likely to have better body weight control.

Intensive care units with low versus high volume of myocardial infarction: clinical outcomes, resource utilization, and quality metrics.

BackgroundThe volume-outcome relationship associated with intensive care unit (ICU) experience with managing acute myocardial infarction (AMI) remains inadequately understood.Methods and ResultsWithin a multicenter clinical ICU database, we identified patients with a primary ICU admission diagnosis of AMI between 2008 and 2010 to evaluate whether annual AMI volume of an individual ICU is associated with mortality, length-of-stay, or quality indicators. Patients were categorized into those treated in ICUs with low-annual-AMI volume (≤50th percentile, <2 AMI patients/month, n=569 patients) versus high-annual-AMI volume (≥90th percentile, ≥8 AMI patients/month, n=17 553 patients). Poisson regression and generalized estimating equation with negative binomial regression were used to calculate the relative risk (95% CI) for mortality and length-of-stay, respectively, associated with admission to a low-AMI-volume ICU. When compared with high-AMI-volume, patients admitted to low-AMI-volume ICUs had substantially more medical comorbidities, higher in-hospital mortality (11% versus 4%, P<0.001), longer hospitalizations (6.9±7.0 versus 5.0±5.0 days, P<0.001), and fewer evidence-based therapies for AMI (reperfusion therapy, antiplatelets, β-blockers, and statins). However, after adjustment for baseline patient characteristics, low-AMI-volume ICU was no longer an independent predictor of in-hospital mortality (relative risk 1.17 [0.87 to 1.56]) or hospital length-of-stay (relative risk 1.01 [0.94 to 1.08]). Similar findings were noted in secondary analyses of ICU mortality and ICU length-of-stay.ConclusionsAdmission to an ICU with lower annual AMI volume is associated with higher in-hospital mortality, longer hospitalization, and lower use of evidence-based therapies for AMI. However, the relationship between low-AMI-volume and outcomes is no longer present after accounting for the higher-risk medical comorbidities and clinical characteristics of patients admitted to these ICUs.

Chlorhexidine daily bathing: Impact on health care–associated infections caused by gram-negative bacteria

Health care-associated infections (HAIs) are a major cause of morbidity and mortality in intensive care unit (ICU) patients. Our objective was to evaluate the impact of daily bathing with chlorhexidine gluconate (CHG) on the incidence rates of HAIs, with a focus on their causative bacteria, in a French ICU. From March 2012-May 2013, we enrolled 325 patients with at least 1 episode of suspected sepsis in the ICU, during two 6-month periods. The intervention group was subjected daily to skin cleansing with 2% CHG-impregnated cloths, whereas the control group was bathed daily with soap and water. HAI included bloodstream infections, ventilator-associated pneumonia, and urinary tract infections. Incidence rates corresponded to the number of infections per 1,000 patient days. Incidence of HAI was significantly decreased in the intervention group (29 vs 56; P = .01). After adjustment for baseline patient characteristics, the increased risk of HAI in the water and soap group was significant (odds ratio = 1.993; 95% confidence interval [CI], 1.132-3.508; P = .017). The incidence rate of clinical cultures positive for gram-negative bacteria, including Enterobacteriaceae and nonfermenting bacilli, decreased in the intervention group (risk ratio = 0.588; 95% CI, 0.346-0.978; P = .04). CHG daily cleansing reduced the incidence rate of HAI caused by gram-negative bacteria, highlighting the role of the transient gram-negative bacteria skin colonization in the pathogenesis of HAI.

Preoperative blood glucose concentrations and postoperative outcomes after elective non-cardiac surgery: an observational study

BackgroundThe association between preoperative blood glucose (BG) concentration and outcomes after non-cardiac surgery and the impact of the diabetes diagnosis status remain unclear. We tested two hypotheses: that preoperative BG is related to surgical outcomes; and that this relationship depends on the diabetes diagnosis status of the patient. MethodsWe retrospectively analysed data on 61 536 consecutive elective non-cardiac surgery patients treated at our tertiary care facility. Logistic regression models were used to test the hypotheses before and after adjustment for baseline patient characteristics. Our primary outcome was a composite of in-hospital serious complications and mortality. A second primary outcome was 1 yr mortality. ResultsThe crude incidence of the composite in-hospital outcome was significantly related to preoperative BG (P<0.001), but not after covariable adjustment (P=0.40). This relationship did not significantly differ between patients with and without diagnosed diabetes (P=0.09). One year mortality was significantly related to preoperative BG, both univariably (P<0.001) and after covariable-adjustment (P<0.001). Patients with diagnosed diabetes and preoperative euglycaemia generally had worse 1 yr mortality than those without diabetes at the same BG {e.g. odds ratio (OR) [95% confidence interval (CI)] of 1.27 (1.06, 1.53) at 6 mmol litre−1 (108 mg dl−1), P=0.003}. Conversely, hyperglycaemic patients with diagnosed diabetes displayed a significantly lower 1 yr mortality than hyperglycaemic patients without diabetes [OR (95% CI) of 0.58 (0.44, 0.77) at 12 mmol litre−1 (216 mg dl−1), P<0.001]. ConclusionsFor elective non-cardiac surgery, preoperative hyperglycaemia should be given greater consideration in patients without diabetes than in those with diagnosed diabetes.

Reducing tuberculosis-associated early mortality in antiretroviral treatment programmes in sub-Saharan Africa

Between 8% and 26% of patients starting antiretroviral therapy (ART) in programmes in sub-Saharan Africa die during the first year of ART, with the majority of deaths occurring in the first few months [1]. There is a critical need for effective interventions to reduce this [2]. In this patient group

Underpowered trials in critical care medicine: how to deal with them?

In their recently published article, Dr Aberegg and colleagues described interesting results of a literature search for randomized controlled trials comparing mortality of therapies for critically ill adults in fi ve high impact journals over a 10 year period [1]. Th e authors show that the predicted delta (the eff ect size of a therapy compared to control) used for power calculations was substantially larger than the observed delta in the majority of the included studies. Th ey conclude that this fi nding, referred to as ‘delta infl ation’, led to underpowered trials in the fi eld of critical care medicine. We agree that treatment eff ects are small in this fi eld of medicine and that many critical care trials have been underpowered. Th is problem is particularly relevant to the fi eld of neurocritical care after traumatic brain injury [2]. Th e IMPACT (International Mission on Prognosis and Clinical Trial Design in Traumatic Brain Injury) Study Group extensively investigated possible causes and solutions and recently reported recommendations for improving the design and analysis of future clinical trials in traumatic brain injury to increase statistical power [3]. Th ese include the use of relatively broad enrolment criteria instead of strict patient selection [4], covariate adjustment for baseline patient characteristics [5], and ordinal rather than dichotomous outcome analysis [6]. In our opinion these recommendations are also applicable to other fi elds of critical care research characterized by heterogeneous patient populations. We submit that adopting these recommendations in future trials will increase the chance of detecting small but clinically relevant treatment eff ects in critical care medicine. Competing interests All authors are members of the IMPACT Study Group. The work of the IMPACT Study Group is funded by a grant of the US National Institutes of Health (NS-042691). Author details 1

Exploring Relative Mortality and Epoetin Alfa Dose Among Hemodialysis Patients

Confounding-by-indication is a bias in nonexperimental studies that occurs when outcomes are compared for treated and untreated patients and the treatment or medication dose is related to predictors of the outcome. Two recent publications reported that greater epoetin alfa (EPO) doses were associated with increased mortality rates. We assessed whether confounding-by-indication might account for these results. We used a retrospective cohort study design. Hemodialysis patients were randomly selected from a large dialysis organization from July 2000 to June 2002 and were required to have completed a 9-month baseline period. EPO dose assessed during months 7 to 9 of the baseline period and monthly throughout the follow-up period. Hemoglobin (Hb) was assessed as average value during months 4 to 6 of the baseline period and monthly throughout the follow-up period. All other covariates were assessed during months 1 to 6 of the baseline period. All-cause mortality during the 1 year of follow-up. Baseline Cox models were fitted with log EPO and Hb with and without adjustment for baseline patient characteristics. Time-dependent models were fitted with time-varying log EPO and Hb and, separately, lagged log EPO and Hb, with adjustment for baseline patient characteristics. 22,955 patients met our inclusion criteria. In the unadjusted model, we observed increased mortality risk with increasing EPO dose (hazard ratio [HR], 1.31 per log unit increase; 95% confidence interval [CI], 1.26 to 1.36). Adjustment for baseline patient characteristics resulted in an appreciably decreased HR (HR, 1.21; 95% CI, 1.15 to 1.28). In the lagged time-dependent analyses, estimates ranged from HR of 0.93 (95% CI, 0.92 to 0.95) to HR of 1.01 (95% CI, 0.99 to 1.03) for the 1- and 2-month lagged models, respectively. This analysis was limited to prevalent hemodialysis patients, and inhospital EPO dosing information was unavailable. The observed mortality risk estimates associated with EPO dose in nonexperimental studies in dialysis patients may be highly sensitive to the analytic method used. This highlights the complexity of evaluating the association between EPO dose, Hb level, and mortality in these studies.

Evaluation of Risk-Adjusted Hospital Mortality After Coronary Artery Bypass Graft Surgery in the Catalan Public Healthcare System. Influence of Hospital Management Type (ARCA Study)

Previous studies suggest that the effectiveness of coronary surgery is influenced by the type of management at the healthcare centre where the intervention is performed. The present study assessed the risk-adjusted hospital mortality of coronary surgery in the Catalan healthcare system in hospitals under either private or public management. We carried out a prospective study of all consecutive patients receiving a first coronary artery bypass graft, with public financial support, in a period of 2 years at 5 hospitals under either public or private management. Preoperative risk was assessed using the EuroSCORE and Catalan Agency for Health Technology Assessment (CAHTA) predictive models. Overall, 1605 patients underwent interventions, 21% of which were at private hospitals. The percentage of patients undergoing non-elective surgery was higher at private hospitals (64% vs 50%), as was the percentage needing intravenous nitrates (17% vs 11%) and the percentage in functional class IV (20% vs 11%). The odds ratio for in-hospital mortality in private compared with public hospitals was 0.56 (95% CI, 0.29-1.06) when adjusted for EuroSCORE, 0.56 (95% CI, 0.29-1.07) when adjusted for CAHTA score, and 0.43 (95% CI, 0.21-0.87) when adjusted for patient characteristics. The mortality observed, 4.8% (95% CI 3.8-5.6), was not significantly higher than that predicted. a) Hospital mortality was equivalent to or lower than that expected after adjustment for the 2 risk scores; b) after adjustment for baseline patient characteristics, the results favored privately managed centers; and c) comparison with previous results suggests that coronary surgery effectiveness has improved in recent years.

International differences in in-hospital revascularization and outcomes following acute myocardial infarction A multilevel analysis of patients in ASSENT-2

Revascularization rates vary substantially between countries in patients with acute ST-elevation myocardial infarction (STEMI). The impact of early revascularization on clinical outcomes in such patients remains uncertain. The ASSENT-2 fibrinolytic trial provides the opportunity to compare revascularization rates following STEMI in patients across 29 countries, and to explore the relationship between revascularization and clinical outcome. Countries participating in ASSENT-2 were grouped into tertiles according to their in-hospital revascularization rates (<15%, 15-39%, >39%). Baseline characteristics, medication and procedure use, and clinical outcomes of the 16949 patients enrolled were compared. Multiple Cox regressions were used to assess the relationship between the tertiles and 30-day mortality, the primary endpoint of the ASSENT-2 trial. Multilevel logistic regression models were developed to validate and further extend the findings from the single-level analyses. Patients in highest tertile countries were younger, heavier, and more often diabetic or hypertensive. They were more likely to have had a previous myocardial infarction or revascularization procedure. Time to treatment and hospital length of stay were shorter in the highest tertile, and beta-blocker use was more frequent. Stroke rates were low and similar across tertiles, with no statistically significant difference in rates of intracranial haemorrhage. Recurrent ischaemia and reinfarction were less common in the highest tertile. Mortality rates at 30 days were lower for countries with the highest revascularization rates (5.1% vs 6.9% vs 6.5% for the lower two tertiles, P<0.001). At 1 year, mortality remained significantly lower in the highest tertile countries (8.4% vs 10.6% vs 9.9%, P=0.001). Following adjustment for baseline patient characteristics, Cox regression analysis confirmed an excess of 30-day and 1-year mortality in the lowest and intermediate tertiles compared to the highest tertile. The multilevel analyses validated these findings, and demonstrated that a country's life expectancy and the hospital volume were inversely related to both 30-day and 1-year mortality. The highest rate of in-hospital revascularization following fibrinolytic therapy for acute myocardial infarction in this international study was associated with a reduction in recurrent ischaemia, reinfarction, and improved survival at both 30 days and at 1 year. The optimal rates of revascularization in this setting remain to be determined.