Association between sinusitis and relapse and changes in the myeloperoxidase–antineutrophil cytoplasmic antibody in microscopic polyangiitis

Previous studies have evaluated the risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the biomarkers of AAV for predicting relapse. However, little is known about the association between the presence of sinusitis and relapse and changes in the ANCA levels in AAV. This single-center, retrospective cohort study included 104 consecutive patients who were newly diagnosed with myeloperoxidase (MPO)-ANCA-positive microscopic polyangiitis (MPA) between 2006 and 2018 and were treated at the Aichi Medical University Hospital in Japan. The relationships between sinusitis and relapse of vasculitis and elevated MPO-ANCA levels were assessed using multivariate Cox proportional hazards models that were adjusted for clinically relevant factors. During the entire follow-up period (median, 24 months; interquartile range, 7–54 months), 93 (89.4%) patients achieved remission. After achieving remission, 38 (40.9%) patients experienced at least one relapse (13 [65.0%] in the sinusitis group; 25 [34.3%] in the non-sinusitis group). Sinusitis was identified as a significant predictor of relapse (adjusted hazard ratio: 2.41, 95% confidence interval [CI]: 1.19–4.88; P = 0.015). Furthermore, sinusitis was more likely to be associated with elevated MPO-ANCA levels (adjusted hazard ratio: 2.59, 95% CI: 1.14–5.92; P = 0.024). In conclusion, sinusitis was associated with a higher risk of relapse and elevated MPO-ANCA levels in MPA patients, suggesting that careful management may be required to reduce the risk of relapse in patients with sinusitis. Further studies are needed to elucidate the optimal treatment strategy for these patients.

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Confounding by indication of the safety of de-escalation in community-acquired pneumonia: a simulation study embedded in a prospective cohort

10.1101/652610 ◽

2019 ◽

Author(s):

Inger van Heijl ◽

Valentijn A. Schweitzer ◽

C.H. Edwin Boel ◽

Jan Jelrik Oosterheert ◽

Susanne M. Huijts ◽

...

Keyword(s):

Propensity Scores ◽

Proportional Hazards ◽

Community Acquired Pneumonia ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Confounding By Indication ◽

Potential Impact ◽

Using Data ◽

Clinical Stability

BackgroundObservational studies have demonstrated that de-escalation of antimicrobial therapy is independently associated with lower mortality. This most probably results from confounding by indication. Reaching clinical stability is associated with the decision to de-escalate and with survival. However, studies rarely adjust for this confounder. We quantified the potential confounding effect of clinical stability on the estimated impact of de-escalation on mortality in patients with community-acquired pneumonia.MethodsData were used from the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA). The primary outcome was 30-day mortality. We performed Cox proportional-hazards regression with de-escalation as time-dependent variable and adjusted for baseline characteristics using propensity scores. The potential impact of unmeasured confounding was quantified through simulating a variable representing clinical stability on day three, using data on prevalence and associations with mortality from the literature.ResultsOf 1,536 included patients, 257 (16.7%) were de-escalated, 123 (8.0%) were escalated and in 1156 (75.3%) the antibiotic spectrum remained unchanged. The adjusted hazard ratio of de-escalation for 30-day mortality (compared to patients with unchanged coverage), without adjustment for clinical stability, was 0.36 (95%CI: 0.18-0.73). If 90% to 100% of de-escalated patients were clinically stable on day three, the fully adjusted hazard ratio would be 0.53 (95%CI: 0.26-1.08) to 0.90 (95%CI: 0.42-1.91), respectively. The simulated confounder was substantially stronger than any of the baseline confounders in our dataset.ConclusionsWith plausible, literature-based assumptions, clinical stability is a very strong confounder for the effects of de-escalation. Quantification of effects of de-escalation on patient outcomes without proper adjustment for clinical stability results in strong negative bias. As a result, the safety of de-escalation remains to be determined.

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Prognostic indicators of secondary progression in a paediatric-onset multiple sclerosis cohort in Kuwait

Multiple Sclerosis Journal ◽

10.1177/1352458515608960 ◽

2015 ◽

Vol 22 (8) ◽

pp. 1086-1093 ◽

Cited By ~ 4

Author(s):

Saeed Akhtar ◽

Raed Alroughani ◽

Samar F Ahmed ◽

Jasem Y Al-Hashel

Keyword(s):

Multiple Sclerosis ◽

Confidence Interval ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Cox Proportional Hazards Model ◽

Adjusted Hazard Ratio ◽

Secondary Progressive ◽

Hazards Model

Background: The frequency of paediatric-onset multiple sclerosis (POMS) and the precise risk of secondary progression of disease are largely unknown in the Middle East. This cross-sectional cohort study assessed the risk and examined prognostic factors for time to onset of secondary progressive multiple sclerosis (SPMS) in a cohort of POMS patients. Methods: The Kuwait National MS Registry database was used to identify a cohort of POMS cases (diagnosed at age <18 years) from 1994 to 2013. Data were abstracted from patients’ records. A Cox proportional hazards model was used to evaluate the prognostic significance of the variables considered. Results: Of 808 multiple sclerosis (MS) patients, 127 (15.7%) were POMS cases. The median age (years) at disease onset was 16.0 (range 6.5–17.9). Of 127 POMS cases, 20 (15.8%) developed SPMS. A multivariable Cox proportional hazards model showed that at MS onset, brainstem involvement (adjusted hazard ratio 5.71; 95% confidence interval 1.53–21.30; P=0.010), and POMS patient age at MS onset (adjusted hazard ratio 1.38; 95% confidence interval 1.01–1.88; P=0.042) were significantly associated with the increased risk of a secondary progressive disease course. Conclusions: This study showed that POMS patients with brainstem/cerebellar presentation and a relatively higher age at MS onset had disposition for SPMS and warrant an aggressive therapeutic approach.

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Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes

Neurology ◽

10.1212/wnl.0000000000004586 ◽

2017 ◽

Vol 89 (18) ◽

pp. 1877-1885 ◽

Cited By ~ 41

Author(s):

Ariela R. Orkaby ◽

Kelly Cho ◽

Jean Cormack ◽

David R. Gagnon ◽

Jane A. Driver

Keyword(s):

Lower Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Confounding By Indication ◽

Cox Proportional Hazards Models ◽

Incident Dementia ◽

Us Veterans

Objective:To determine whether metformin is associated with a lower incidence of dementia than sulfonylureas.Methods:This was a retrospective cohort study of US veterans ≥65 years of age with type 2 diabetes who were new users of metformin or a sulfonylurea and had no dementia. Follow-up began after 2 years of therapy. To account for confounding by indication, we developed a propensity score (PS) and used inverse probability of treatment weighting (IPTW) methods. Cox proportional hazards models estimated the hazard ratio (HR) of incident dementia.Results:We identified 17,200 new users of metformin and 11,440 new users of sulfonylureas. Mean age was 73.5 years and mean HbA1c was 6.8%. Over an average follow-up of 5 years, 4,906 cases of dementia were diagnosed. Due to effect modification by age, all analyses were conducted using a piecewise model for age. Crude hazard ratio [HR] for any dementia in metformin vs sulfonylurea users was 0.67 (95% confidence interval [CI] 0.61–0.73) and 0.78 (95% CI 0.72–0.83) for those <75 years of age and ≥75 years of age, respectively. After PS IPTW adjustment, results remained significant in veterans <75 years of age (HR 0.89; 95% CI 0.79–0.99), but not for those ≥75 years of age (HR 0.96; 95% CI 0.87–1.05). A lower risk of dementia was also seen in the subset of younger veterans who had HbA1C values ≥7% (HR 0.76; 95% CI 0.63–0.91), had good renal function (HR 0.86; 95% CI 0.76–0.97), and were white (HR 0.87; 95% CI 0.77–0.99).Conclusions:After accounting for confounding by indication, metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans <75 years of age. Further work is needed to identify which patients may benefit from metformin for the prevention of dementia.

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Phospholipid Levels at Seroconversion are Associated with Resolution of Persistent Islet Autoimmunity: The Diabetes Autoimmunity Study in the Young

10.2337/figshare.14414342 ◽

2021 ◽

Author(s):

Patrick M. Carry ◽

Lauren A. Vanderlinden ◽

Randi K. Johnson ◽

Teresa Buckner ◽

Oliver Fiehn ◽

...

Keyword(s):

Proportional Hazards ◽

Principal Component ◽

Enrichment Analysis ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Islet Autoimmunity ◽

Potential Influence ◽

Serum Samples ◽

Sugar Intake ◽

Cox Proportional Hazards Models

Reversion of islet autoimmunity (IA) may point to mechanisms that prevent IA progression. We followed 199 individuals who developed IA during the Diabetes Autoimmunity Study in the Young. Untargeted metabolomics was performed in serum samples following IA. Cox-proportional hazards models were used to test if the metabolites (2,487) predicted IA reversion, two or more consecutive visits negative for all autoantibodies. We conducted a principal component analysis (PCA) of the top metabolites, |hazard ratio (HR) >1.25| and nominal p<0.01. Phosphatidylcholine (16:0_18:1(9Z) was the strongest individual metabolite (hazard ratio (HR) per 1 standard deviation: 2.16, FDR adjusted p=0.0037). Enrichment analysis identified four clusters (FDR p<0.10) characterized by an overabundance of sphingomyelin (d40:0), phosphatidylcholine (16:0_18:1(9Z)), phosphatidylcholine (30:0), and L-decanoylcarnitine. Overall, 63 metabolites met the criteria for inclusion in the PCA. PC1 (HR: 1.4, p<0.0001), PC2 (HR: 0.85, p=0.0185), and PC4 (HR: 1.28, p=0.0103) were associated with IA reversion. Given the potential influence of diet on the metabolome, we investigated whether nutrients were correlated with PCs. We identified 20 nutrients that were correlated with the PCs (p<0.05). Total sugar intake was the top nutrient. Overall, we identified an association between phosphatidylcholine, sphingomyelin, and carnitine levels and reversion of IA.

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The Association of Prenatal Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Vaccination With Attention-Deficit/Hyperactivity Disorder

American Journal of Epidemiology ◽

10.1093/aje/kwaa074 ◽

2020 ◽

Vol 189 (10) ◽

pp. 1163-1172

Author(s):

Tracy A Becerra-Culqui ◽

Darios Getahun ◽

Vicki Chiu ◽

Lina S Sy ◽

Hung Fu Tseng

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Confidence Interval ◽

Attention Deficit ◽

Proportional Hazards ◽

International Classification Of Diseases ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Kaiser Permanente ◽

Hyperactivity Disorder ◽

Cox Proportional Hazards Models

Abstract As prenatal vaccinations become more prevalent, it is important to assess potential safety events. In a retrospective cohort study of Kaiser Permanente Southern California (Pasadena, California) mother-child pairs with birth dates during January 1, 2011–December 31, 2014, we investigated the association between prenatal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Information on Tdap vaccination during pregnancy was obtained from electronic medical records. ADHD was defined by International Classification of Diseases codes (Ninth or Tenth Revision) and dispensed ADHD medication after age 3 years. Children were followed to the date of their first ADHD diagnosis, the end of Kaiser Permanente membership, or the end of follow-up (December 31, 2018). In Cox proportional hazards models, we estimated unadjusted and adjusted hazard ratios for the association between maternal Tdap vaccination and ADHD, with inverse probability of treatment weighting (IPTW) used to adjust for confounding. Of 128,756 eligible mother-child pairs, 85,607 were included in the final sample. The ADHD incidence rate was 3.41 per 1,000 person-years in the Tdap-vaccinated women and 3.93 per 1,000 person-years in the unvaccinated (hazard ratio = 1.01, 95% confidence interval: 0.88, 1.16). The IPTW-adjusted analyses showed no association between prenatal Tdap vaccination and ADHD in offspring (hazard ratio = 1.00, 95% confidence interval: 0.88, 1.14). In this study, prenatal Tdap vaccination was not associated with ADHD risk in offspring, supporting recommendations to vaccinate pregnant women.

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Prognostic value of leukemia inhibitory factor and its receptor in pancreatic adenocarcinoma

Future Oncology ◽

10.2217/fon-2019-0684 ◽

2020 ◽

Vol 16 (3) ◽

pp. 4461-4473 ◽

Cited By ~ 3

Author(s):

Dong Wang ◽

Kun Liu ◽

Yingchi Yang ◽

Tingting Wang ◽

Quan Rao ◽

...

Keyword(s):

Overall Survival ◽

Pancreatic Adenocarcinoma ◽

Leukemia Inhibitory Factor ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Inhibitory Factor ◽

Normal Tissues ◽

Kaplan Meier

Currently, the prognostic effects of leukemia inhibitory factor (LIF) and LIF receptor (LIFR) in pancreatic adenocarcinoma (PAAD) are not clear. In the present study, we utilized the large datasets from four public databases to investigate the expression of LIF and LIFR and their clinical significance in PAAD. Eight cohorts containing 1278 cases with PAAD were identified and the analysis results suggested that LIF was highly expressed while LIFR was lowly expressed in PAAD tissues compared with adjacent or normal tissues. Kaplan–Meier plot curves and univariate and multivariate Cox proportional hazards regression analyses indicated high LIF expression was associated with shorter overall survival (adjusted hazard ratio = 1.641, 95% CI: 1.399–1.925, p < 0.001) whereas high LIFR expression was associated with longer overall survival (adjusted hazard ratio = 0.653, 95% CI: 0.517–0.826, p < 0.001).

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Renal-function change after transjugular intra-hepatic portosystemic shunt placement and its relationship with survival: a single-center experience

Gastroenterology Report ◽

10.1093/gastro/goaa081 ◽

2020 ◽

Author(s):

Min Lang ◽

Angela L Lang ◽

Brian Q Tsui ◽

Weiping Wang ◽

Brian K Erly ◽

...

Keyword(s):

Renal Function ◽

Mortality Risk ◽

Proportional Hazards ◽

De Novo ◽

Strong Predictor ◽

Cox Proportional Hazards ◽

Portosystemic Shunt ◽

Hazard Ratio ◽

Single Center Experience ◽

Cox Proportional Hazards Models

Abstract Background The effect of transjugular intra-hepatic portosystemic shunt (TIPS) placement on renal function and the correlation of post-TIPS Cr with mortality remain unclear. This study aimed to assess the effect of TIPS placement on renal function and to examine the relationship between post-TIPS Cr and mortality risk. Methods A total of 593 patients who underwent de novo TIPS placement between 2004 and 2017 at a single institution were included in the study. The pre-TIPS Cr level (T0; within 7 days before TIPS placement) and post-TIPS Cr levels, at 1–2 days (T1), 5–12 days (T2), and 15–40 days (T3), were collected. Predictors of Cr change after TIPS placement and the 1-year mortality rate were analysed using multivariable linear-regression and Cox proportional-hazards models, respectively. Results Overall, 21.4% of patients (n = 127) had elevated baseline Cr (≥1.5 mg/dL; mean, 2.51 ± 1.49 mg/dL) and 78.6% (n = 466) had normal baseline Cr (<1.5 mg/dL; mean, 0.92 ± 0.26 mg/dL). Patients with elevated pre-TIPS Cr demonstrated a decrease in post-TIPS Cr (difference, −0.60 mg/dL), whereas patients with normal baseline Cr exhibited no change (difference, <0.01 mg/dL). The 30-day, 90-day, and 1-year mortality rates were 13%, 20%, and 32%, respectively. Variceal bleeding as a TIPS-placement indication (hazard ratio = 1.731; P = 0.036), higher T0 Cr (hazard ratio = 1.834; P = 0.012), and higher T3 Cr (hazard ratio = 3.524; P < 0.001) were associated with higher 1-year mortality risk. Conclusion TIPS placement improved renal function in patients with baseline renal dysfunction and the post-TIPS Cr level was a strong predictor of 1-year mortality risk.

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Informal Caregiver Support Policies Change Use of Vocational Assistance Services for Individuals With Disabilities

Medical Care Research and Review ◽

10.1177/10775587211018548 ◽

2021 ◽

pp. 107755872110185

Author(s):

Megan Shepherd-Banigan ◽

Valerie A. Smith ◽

Karen M. Stechuchak ◽

Courtney H. Van Houtven

Keyword(s):

Confidence Interval ◽

Supported Employment ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Care Recipient ◽

Gi Bill ◽

Individuals With Disabilities ◽

Caregiver Support ◽

Cox Proportional Hazards Models

Support policies for caregivers improves care-recipient access to care and effects may generalize to nonhealth services. Using administrative data from the U.S. Department of Veterans Affairs (VA) for veterans <55 years, we assessed the association between enrollment in a VA caregiver support program and veteran use of vocational assistance services: the post-9/11 GI Bill, VA vocational rehabilitation and employment (VR&E), and supported employment. We applied instrumental variables to Cox proportional hazards models. Caregiver enrollment in the program increased veteran supported employment use (hazard ratio = 1.35, 95% confidence interval [1.14, 1.53]), decreased VR&E use (hazard ratio = 0.84, 95% confidence interval [0.76, 0.92]), and had no effect on the post-9/11 GI Bill. Caregiver support policies could increase access to some vocational assistance for individuals with disabilities, particularly supported employment, which is integrated into health care. Limited coordination between health and employment sectors and misaligned incentives may have inhibited effects for the post-9/11 GI Bill and VR&E.

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IGF-Binding Proteins, Adiponectin, and Survival in Metastatic Colorectal Cancer: Results From CALGB (Alliance)/SWOG 80405

JNCI Cancer Spectrum ◽

10.1093/jncics/pkaa074 ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Brendan J Guercio ◽

Sui Zhang ◽

Fang-Shu Ou ◽

Alan P Venook ◽

Donna Niedzwiecki ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Igf Binding Proteins ◽

C Peptide ◽

Igf Binding ◽

Igfbp 3

Abstract Background Energy balance-related biomarkers are associated with risk and prognosis of various malignancies. Their relationship to survival in metastatic colorectal cancer (mCRC) requires further study. Methods Baseline plasma insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGFBP-7, C-peptide, and adiponectin were measured at time of trial registration in a prospective cohort of patients with mCRC participating in a National Cancer Institute–sponsored trial of first-line systemic therapy. We used Cox proportional hazards regression to adjust for confounders and examine associations of each biomarker with overall survival (OS) and progression-free survival (PFS). P values are 2-sided. Results Median follow-up for 1086 patients was 6.2 years. Compared with patients in the lowest IGFBP-3 quintile, patients in the highest IGFBP-3 quintile experienced an adjusted hazard ratio (HR) for OS of 0.57 (95% confidence interval [CI] = 0.42 to 0.78; Pnonlinearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; Ptrend = .003). Compared with patients in the lowest IGFBP-7 quintile, patients in the highest IGFBP-7 quintile experienced an adjusted hazard ratio for OS of 1.60 (95% CI = 1.30 to 1.97; Ptrend < .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; Ptrend < .001). Plasma C-peptide and IGF-1 were not associated with patient outcomes. Adiponectin was not associated with OS; there was a nonlinear U-shaped association between adiponectin and PFS (Pnonlinearity = .03). Conclusions Among patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with longer OS and PFS. Extreme levels of adiponectin were associated with shorter PFS. These findings suggest potential avenues for prognostic and therapeutic innovation.

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Diagonal Earlobe Crease and Long-Term Survival After Myocardial Infarction

10.21203/rs.3.rs-820579/v1 ◽

2021 ◽

Author(s):

Christian Thilo ◽

Christine Meisinger ◽

Margit Heier ◽

Wolfgang Scheidt ◽

Inge Kirchberger

Keyword(s):

Myocardial Infarction ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Term Survival ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Artery Disease ◽

Adjusted Model

Abstract Background: The association between the presence of a diagonal earlobe crease (DEC) and coronary artery disease (CAD) has been prescribed earlier. However, it is unclear whether patients with acute myocardial infarction (AMI) and DEC have a higher risk of dying. Methods: Study participants were persons with AMI who were included in the KORA Myocardial Infarction Registry Augsburg from August 2015 to December 2016. After taking pictures of both earlobes, two employees independently assessed the severity of DEC in 4 degrees. For analysis, the expression of the DEC was dichotomized. Information on risk factors, severity and therapy of the AMI was collected by interview and from the medical record. Vital status post AMI was obtained by population registries in 2019. The relationship between DEC and survival time was determined using Cox proportional hazards models. Results: Out of 655 participants, 442 (67.5%) showed DEC grade 2/3 and 213 (32.5%) DEC grade 0/1. Median observation period was 3.06 years (5-1577 days). During this period, 26 patients (12.2%) with DEC grade 0/1 and 92 patients (20.8%) with grade 2/3 died (hazard ratio 1.91, 95% confidence interval (CI) 1.23 - 2.96, p = 0.0037). In the fully adjusted model, patients with DEC grade 2/3 had a 1.48-fold increased risk of death compared to the DEC grade 0/1 patient group (CI 0.94 - 2.34, p = 0.0897). The fully adjusted model applied for 1-year survival revealed a significant, 2.57-fold hazard ratio of death (CI 1.07 - 6.17, p = 0.0347) for the patients with DEC grade 2/3.Conclusions: Our results indicate that DEC is independently associated with 1-year AMI survival.

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