scholarly journals Analytical challenges in estimating the effect of exposures that are bounded by follow-up time: experiences from the Blood Stream Infection—Focus on Outcomes study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rebecca Evans ◽  
Katie Pike ◽  
Alasdair MacGowan ◽  
Chris A. Rogers
Keyword(s):  
Risk Factors ◽  
Missing Data ◽  
Blood Stream Infection ◽  
Modifiable Risk Factors ◽  
Time Varying ◽  
Primary Analysis ◽  
Immortal Time Bias ◽  
Time To Initiation ◽  
Time Varying Covariates

Abstract Objective To illustrate the challenges of estimating the effect of an exposure that is bounded by duration of follow-up on all-cause 28-day mortality, whilst simultaneously addressing missing data and time-varying covariates. Study design and methods BSI-FOO is a multicentre cohort study with the primary aim of quantifying the effect of modifiable risk factors, including time to initiation of therapy, on all-cause 28-day mortality in patients with bloodstream infection. The primary analysis involved two Cox proportional hazard models, first one for non-modifiable risk factors and second one for modifiable risk factors, with a risk score calculated from the first model included as a covariate in the second model. Modifiable risk factors considered in this study were recorded daily for a maximum of 28 days after infection. Follow-up was split at daily intervals from day 0 to 28 with values of daily collected data updated at each interval (i.e., one row per patient per day). Analytical challenges Estimating the effect of time to initiation of treatment on survival is analytically challenging since only those who survive to time t can wait until time t to start treatment, introducing immortal time bias. Time-varying covariates representing cumulative counts were used for variables bounded by survival time e.g. the cumulative count of days before first receipt of treatment. Multiple imputation using chained equations was used to impute missing data, using conditional imputation to avoid imputing non-applicable data e.g. ward data after discharge. Conclusion Using time-varying covariates represented by cumulative counts within a one row per day per patient framework can reduce the risk of bias in effect estimates. The approach followed uses established methodology and is easily implemented in standard statistical packages.

Abstract P111: Changes in Burden of Peripheral Artery Disease Following a Hypothetical Change in the Population Distribution of Adiposity: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Kapuaola S Gellert ◽  
Alexander P Keil ◽  
Donglin Zeng ◽  
Ronald E Aubert ◽  
Christy L Avery ◽  
...  
Keyword(s):  
Risk Factors ◽  
African American ◽  
Peripheral Artery Disease ◽  
Cumulative Incidence ◽  
Population Distribution ◽  
Time Varying ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Time Varying Covariates

Introduction: Shifting the population distribution of common risk factors has considerable potential to reduce disease burden. Peripheral artery disease (PAD) is a disabling, often life-threatening condition affecting 8.5 million U.S. adults, yet the potential impact of feasible shifts in the population distribution of adiposity on the associated burden of PAD has not been reported. Methods: From the population-based, biracial ARIC cohort, 13,604 individuals (54% female; 27% African American; and mean age: 54 years) were examined after excluding 969 participants who at baseline had chronic conditions associated with weight change and 632 with prevalent PAD. Exposure [body mass index (BMI)] and covariates (smoking, hypertension, and diabetes) were ascertained at each of 4 triennial study visits. Incident PAD events were identified from active surveillance of hospitalizations and ICD-9-CM discharge codes. Diabetes and hypertension are time-varying covariates that may lie on the causal pathway between BMI and PAD, and are in turn affected by previous BMI. Using the parametric g-formula, we assessed the hypothesis that a reduction in the cumulative incidence of PAD would be observed following a hypothetical 5% yearly BMI reduction down to 24 kg/m2 for all individuals under 65 years of age with a BMI> 24 kg/m2. This approach allows for control of time-varying confounding by covariates that may act as both mediators and confounders, provided that we have longitudinal measures of those covariates. Participants were followed until the first incident PAD event (2%), study dropout (27%), death (7%), or end of follow-up (64%). Results: During a median 12 years of follow-up, we identified 231 participants with incident PAD (31% female; 17% African American; 51% smokers; 45% with diabetes; and 77% with hypertension). The 12-year cumulative incidence of PAD was 1.89% (95%CI: 1.62, 2.17%) under the natural course, and 1.72% (95%CI: 1.46, 2.08%) following a 5% yearly reduction in BMI. Thus, we predicted a -0.17% (95%CI: -0.38, 0.13) change in the risk of PAD. The cumulative incidence of PAD following hypothetical shifts of various magnitude down to a BMI of 24 kg/m2 followed an expected dose response curve, although all estimates were within the 95% confidence limits of our study’s estimated cumulative incidence. Conclusion: We observed an estimated reduction of small magnitude in the risk of PAD attributed to a feasible shift in the population distribution of BMI, consistent with the larger impact of PAD risk factors that are not influenced by BMI, such as cigarette smoking and age. There is need for characterization of the effect of reducing mid-life BMI on PAD with extended follow-up time, and to older ages when PAD risk is highest. Our results suggest that 9% of PAD cases occurring in this study population over the 12 years of follow-up could have been prevented by a 5% shift in the population distribution of BMI.

scholarly journals Competing Risk of Death and Time-Varying Covariates in Cardiovascular Epidemiologic Research: Modeling the Hazards of Coronary Heart Disease in the First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study

2019 ◽  
Vol 3 (1) ◽  
pp. 20
Author(s):  
Rodrigue Pierre ◽  
C. Perry Brown ◽  
Charlotte Baker ◽  
Matthew Dutton ◽  
Oghenekome Onokpise ◽  
...  
Keyword(s):  
Risk Factors ◽  
Competing Risk ◽  
Time Varying ◽  
Nutrition Examination Survey ◽  
Coefficient Estimates ◽  
Risk Of Death ◽  
Follow Up Study ◽  
Health And Nutrition ◽  
Time Varying Covariates

<p><em>Competing risk of death and time-varying covariates, often overlooked during statistical analyses of longitudinal studies, can alter the magnitude of estimates of the effect of covariates on the hazards of health outcomes. This study aimed to investigate whether estimates obtained when modeling the effect of risk factors on the hazards of coronary heart disease (CHD) varied significantly while accounting for the presence of competing risk of death and time-varying covariates. We used data from the First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study (n=6346) to model estimates of the effect of risk factors on the hazards of CHD using Cox proportional hazards model, Cox extension with time-varying covariates, and the Fine Gray approach. We used a chi-square test to compare coefficient estimates obtained from the three modeling techniques. We obtained a P-value &gt; 0.05 when comparing coefficient estimates for body mass index, age, cholesterol, smoking, and diabetes after fitting the three models. Coefficient estimates obtained when modeling the effect of risk factors on the hazards of CHD did not vary significantly in the presence of competing risk of death and time-varying covariates. Researchers should consider exploring these concepts more systematically in cohort studies with cardiovascular outcomes.</em><em></em></p>

Antithrombotic Treatment and Outcomes of Splanchnic Vein Thrombosis in an International Prospective Registry: Results of 2-Year Follow-up

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 592-592
Author(s):  
Walter Ageno ◽  
Nicoletta Riva ◽  
Sam Schulman ◽  
Jan Beyer-Westendorf ◽  
Soo-Mee Bang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Major Bleeding ◽  
Research Funding ◽  
Bleeding Events ◽  
Primary Analysis ◽  
Vascular Events ◽  
Vein Thrombosis ◽  
Cirrhotic Patients

Abstract Background: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT). We aimed to assess incidence rates of bleeding, recurrence, and mortality in a large prospective cohort of SVT patients after a 2-year follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Information was gathered on baseline characteristics, risk factors and therapeutic strategies. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis, and mortality) during follow-up were collected and reviewed by a Central Adjudication Committee. Major bleeding was defined using the ISTH definition plus the need for hospitalization. The primary analysis was performed up to the first adjudicated major bleeding or thrombotic event. Results: 604 patients from 31 centers were enrolled in this study, 21 (3.5%) were lost to follow-up. Median follow-up duration was 2 years (IQR 1-2). Median age was 54 years (range 16-85); 62.6% were males. Most common risk factors were liver cirrhosis in 27.8% of patients and solid cancer in 22.3%. Portal vein was the most common site of thrombosis. 139 patients were not anticoagulated; 175 received parenteral anticoagulants only (median duration 5.8 months, IQR 3-12) and 290 were started on vitamin K antagonists (median duration 24 months, IQR 7-24). According to the primary analysis, 103 events occurred during follow-up: 35 major bleeding events (3.8/100 patient-years [pt-y]; 95%CI, 2.7-5.2), 2 of which were fatal bleeding, and 68 thrombotic events (7.3/100 pt-y; 95%CI 5.8-9.3), 9 of which were vascular deaths. All-cause mortality occurred in 106 patients (10.3/100 pt-y; 95% CI 8.5-12.5). The incidence of major bleeding events was 4.0/100 pt-y in patients on anticoagulant drugs and 3.4/100 pt-y in patients not receiving anticoagulants. The incidence of vascular events was 5.6/100 pt-y and 9.7/100 pt-y, respectively. Major bleeding and vascular event rates were highest in cirrhotic patients (10.0/100 pt-y and 11.3/100 pt-y, respectively), and lowest in the subgroup of non-malignant non-cirrhotic patients (1.8/100 pt-y and 5.6/100 pt-y, respectively). Conclusions: SVT patients have a non-negligible long-term risk of both bleeding and thrombotic events, but this risk varies according to the pathogenesis of SVT. Anticoagulant treatment is associated with a reduced incidence of thrombotic events without apparently resulting in an increased risk of bleeding. Funding: The study was funded by a grant from Pfizer Canada to ISTH Disclosures Ageno: Bayer Healthcare: Research Funding. Schulman:Bayer HealthCare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding. Beyer-Westendorf:Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Boehringer: Honoraria, Research Funding.

Effect of a lifestyle-focused electronic patient support application on risk factor management in post-myocardial infarction patients – a randomized controlled trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Ogmundsdottir Michelsen ◽  
I Sjolin ◽  
M Back ◽  
M Gonzalez ◽  
A Olsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Exercise Capacity ◽  
Mobile Device ◽  
Controlled Trial ◽  
Modifiable Risk Factors ◽  
Funding Source ◽  
Lifestyle Advice ◽  
Device Application ◽  
Randomized Controlled

Abstract Background Cardiac rehabilitation (CR) is central in reducing morbidity and mortality after myocardial infarction (MI). However, the fulfillment of guideline recommended CR targets is unsatisfactory. eHealth offers new possibilities to improve clinical care. Purpose The aim of this study was to assess the efficacy of a mobile device application to support adherence to lifestyle advice and self-control of risk factors as a complement to traditional CR after MI. Method This unblinded multi-centre randomized controlled trial included 150 patients with MI (81% men, 60.4±8.8 years). All patients in the intervention (INT) and control (CON) groups participated in a 1-year CR program. Additionally, INT patients (n=101) received access to the mobile device application for 25 weeks post-MI where information about lifestyle (i.e., diet, physical activity, smoking), modifiable risk factors (i.e., weight, blood pressure (BP)), and symptoms could be registered. The software provided direct positive feedback and lifestyle advice. Data was reviewed twice weekly by the CR nurse. The primary outcome was change in sub-maximal exercise capacity (W) between an exercise test 2-weeks post MI and at follow-up 4 month later. Secondary outcomes included changes in lifestyle and modifiable risk factors including body mass index, waist circumference, blood-lipids, fasting glucose and HbA1c, between baseline and 2-week, 2-month and 1-year follow-up visits. Regression analysis was used, adjusting for relevant baseline variables. Results Participation in CR was high, with 96% of INT patients and 98% of the CON patients attending the 1-year follow-up visit. Forty-six percent of the INT patients and 57% of the CON patients attended centre-based exercise training (p=0.1). In the INT group 86% logged data in the application at least once. Adherence, defined as logging data at least twice per week, was 92% in week 1 and 57% in week 25. There was a numerical trend toward better exercise capacity improvement in the INT group (INT +14.4±19.0 vs. CON +10.3±16.1 W, p=0.2) although differences were non-significant. INT patients achieved larger BP reduction at 2-weeks (systolic) and 2-months (systolic and diastolic) (Figure). At 2-months 70% vs. 46% of smokers in the INT vs CON groups had quit smoking, and at 1-year the respective percentages were 57% vs. 36%. The number of smokers in the study was however low (n=33) and the differences non-significant. For other secondary endpoints no differences were observed. Conclusion Complementing CR with a mobile device application improved BP during the first months after MI, and non-significant trends towards better exercise capacity and higher smoking cessation rates were observed. Even though the differences were non-significant in our small study sample, they indicate that using eHealth in the form of a mobile device application could clinically benefit post-MI patients participating in CR. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Governmental funding of clinical research within the National Health Services in Sweden.

scholarly journals Complications of Percutaneous Renal Biopsy

2019 ◽  
Vol 36 (02) ◽  
pp. 097-103
Author(s):  
Kenaz Bakdash ◽  
Kristofer M. Schramm ◽  
Aparna Annam ◽  
Matthew Brown ◽  
Kimi Kondo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Biopsy ◽  
Bleeding Complications ◽  
Modifiable Risk Factors ◽  
Delayed Presentation ◽  
Histologic Diagnosis ◽  
Poor Renal Function ◽  
Percutaneous Renal Biopsy ◽  
Risk Patients

AbstractPercutaneous renal biopsy is widely used for diagnosis, prognosis, and management of nephropathies. Complications may arise after renal biopsy, most commonly in the form of bleeding. Efforts should be taken to optimize modifiable risk factors such as hypertension, thrombocytopenia, and coagulopathy prior to the procedure. Unmodifiable risk factors such as poor renal function, gender, and underlying histologic diagnosis may be used to identify high-risk patients. Delayed presentation of bleeding complications is common, and close clinical follow-up is crucial.

scholarly journals Risk Factors for Patient–Ventilator Asynchrony and Its Impact on Clinical Outcomes: Analytics Based on Deep Learning Algorithm

2020 ◽  
Vol 7 ◽  
Author(s):  
Huiqing Ge ◽  
Kailiang Duan ◽  
Jimei Wang ◽  
Liuqing Jiang ◽  
Lingwei Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Tidal Volume ◽  
Clinical Outcomes ◽  
Regression Models ◽  
Negative Binomial ◽  
Cox Regression ◽  
Plateau Pressure ◽  
Care Hospital ◽  
Time Varying ◽  
Time Varying Covariates

Background and objectives: Patient–ventilator asynchronies (PVAs) are common in mechanically ventilated patients. However, the epidemiology of PVAs and its impact on clinical outcome remains controversial. The current study aims to evaluate the epidemiology and risk factors of PVAs and their impact on clinical outcomes using big data analytics.Methods: The study was conducted in a tertiary care hospital; all patients with mechanical ventilation from June to December 2019 were included for analysis. Negative binomial regression and distributed lag non-linear models (DLNM) were used to explore risk factors for PVAs. PVAs were included as a time-varying covariate into Cox regression models to investigate its influence on the hazard of mortality and ventilator-associated events (VAEs).Results: A total of 146 patients involving 50,124 h and 51,451,138 respiratory cycles were analyzed. The overall mortality rate was 15.6%. Double triggering was less likely to occur during day hours (RR: 0.88; 95% CI: 0.85–0.90; p &lt; 0.001) and occurred most frequently in pressure control ventilation (PCV) mode (median: 3; IQR: 1–9 per hour). Ineffective effort was more likely to occur during day time (RR: 1.09; 95% CI: 1.05–1.13; p &lt; 0.001), and occurred most frequently in PSV mode (median: 8; IQR: 2–29 per hour). The effect of sedatives and analgesics showed temporal patterns in DLNM. PVAs were not associated mortality and VAE in Cox regression models with time-varying covariates.Conclusions: Our study showed that counts of PVAs were significantly influenced by time of the day, ventilation mode, ventilation settings (e.g., tidal volume and plateau pressure), and sedatives and analgesics. However, PVAs were not associated with the hazard of VAE or mortality after adjusting for protective ventilation strategies such as tidal volume, plateau pressure, and positive end expiratory pressure (PEEP).

Association of Graft-Versus-Host Disease and Immunosuppressive Treatment with Risks of Recurrent Malignancy and Mortality After Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 218-218
Author(s):  
Yoshihiro Inamoto ◽  
Mary E.D. Flowers ◽  
Stephanie J. Lee ◽  
Paul A. Carpenter ◽  
Edus H. Warren ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Time Varying ◽  
Graft Versus Host ◽  
Recurrent Malignancy ◽  
Time Varying Covariates

Abstract Abstract 218 Background: Graft-versus-leukemia (GVL) effects are closely associated with graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). In a reexamination of GVL effects, we evaluated acute and chronic GVHD defined by NIH consensus criteria and immunosuppressive treatment (IST) as risk factors for recurrent malignancy after HCT. Patients and methods: We analyzed a cohort of 2656 consecutive patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN) who received allogeneic HCT after high-intensity conditioning between 1992 and 2005. The onset of NIH chronic GVHD was ascertained by retrospective chart review using follow-up information obtained by our Long Term Follow Up clinic. Rates and hazards of recurrent malignancy and mortality were analyzed according to GVHD and IST as time-varying covariates. To illustrate the effect of time-varying covariates, we calculated the rate of recurrent malignancy per patient-year according to prior GVHD within sequential 90-day intervals after HCT. Cox proportional hazard models were adjusted for potential factors affecting outcomes. Results: The median patient age at HCT was 39 years (range, 0 to 71 years). Donors were HLA-identical relatives (n=1088), HLA-matched unrelated volunteers (n=912), HLA-mismatched relatives (n=243), and HLA-mismatched unrelated volunteers (n=413). GVHD prophylaxis was mostly cyclosporine and methotrexate (n=1885, 71%). Relapse rates per patient-year declined from 3 months until at least 36 months after HCT for patients with prior acute GVHD or NIH chronic GVHD (Figure). Patients without prior GVHD showed a much less pronounced decline between 12 and 30 months after HCT. Adjusted Cox analysis showed that acute GVHD and NIH chronic GVHD were associated with statistically similar reductions in risk of late recurrent malignancy beyond 18 months after HCT, with no incremental effect of chronic GVHD in patients with prior acute GVHD (Table 1). GVL effects were demonstrable in patients with CML or AML but not in those with ALL or MDS/MPN. Discontinuation of IST was associated with a decreased risk of recurrent malignancy among patients without prior GVHD but not among those with prior GVHD (Table 2). Grades III–IV acute GVHD and NIH chronic GVHD with prior acute GVHD were associated with a statistically significant increase in risk of early mortality between 3 and 18 months, but grade II acute GVHD and NIH chronic GVHD without prior acute GVHD were not. Conclusion: Both acute and NIH chronic GVHD are associated with potent GVL effects, but NIH chronic GVHD does not confer any incremental benefit after acute GVHD. Withdrawal of IST was associated with a reduction in risk of recurrent malignancy in patients without prior GVHD. Analyses of GVL effects should account for time from HCT, the history of GVHD, type of malignancy and IST. Immune manipulations such as prophylactic donor lymphocyte infusion or early withdrawal of IST may represent reasonable approaches to decrease the risk of recurrent malignancy in patients without prior GVHD, if the risk of GVHD could be minimized. Disclosures: No relevant conflicts of interest to declare.

Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion

Rheumatology ◽  
2020 ◽  
Author(s):  
Margherita Zen ◽  
Marta Loredo Martinez ◽  
Francesco Benvenuti ◽  
Mariele Gatto ◽  
Francesca Saccon ◽  
...  
Keyword(s):  
Risk Factors ◽  
Oral Anticoagulation ◽  
Odds Ratio ◽  
Lupus Anticoagulant ◽  
Thrombotic Event ◽  
Modifiable Risk Factors ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Thrombotic Risk

Abstract Objective The withdrawal of oral anticoagulation (OAC) in patients with SLE and secondary aPL syndrome (SAPS) who become seronegative has not been clearly investigated to date. Our aim was to evaluate the prevalence of aPL seroconversion and the prognosis of SLE patients with SAPS who withdrew OAC after aPL negativization. Methods We retrospectively analysed data of all SLE patients (ACR criteria) with SAPS (Sydney criteria) prospectively followed-up in our clinic. aPL seroconversion was defined as negativization of lupus anticoagulant, aCL, and anti-β2glycoprotein-1 antibodies on two or more consecutive measurements, at least 12 weeks apart. OAC discontinuation was defined as the definitive withdrawal of all anticoagulants. Results Fifty-five out of 513 (10.7%) SLE patients had vascular SAPS. Sixteen patients (29.1%) became aPL seronegative during follow-up. Immunosuppressive therapy predicted aPL negativization (odds ratio 5.211, 95%CI 1.341, 20.243), whereas APS diagnosis prior to that of SLE (odds ratio 0.078, 95%CI 0.008, 0.799) and triple-positive profile (odds ratio 0.264, 95%CI 0.115, 0.609) were negative predictors of aPL negativization. OAC was discontinued in 13/55 patients (23.6%), after a median follow-up of 45 months (range 1–276) from aPL seroconversion. SLE-related modifiable risk factors for thrombosis were observed in 10/13 patients (77%) at the time of the thrombotic event. No thrombotic recurrences were observed during a mean follow-up time of 44 (19) months from OAC discontinuation. Conclusions Our results suggest that OAC can be safely discontinued in SLE patients who became persistently seronegative for aPL, at least when aPL-related thrombotic events occurred in presence of other thrombotic risk factors.

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