Statins Are Associated With Reduced Mortality in Multiple Myeloma

Purpose The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have activity in one of the pathways influenced by nitrogen-containing bisphosphonates, which are associated with improved survival in multiple myeloma (MM). To understand the benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of patients with MM. Patients and Methods From the Veterans Administration Central Cancer Registry, we identified patients diagnosed with MM between 1999 and 2013. We defined statin use as the presence of any prescription for a statin within 3 months before or any time after MM diagnosis. Cox proportional hazards regression assessed the association of statin use with mortality, while controlling for known MM prognostic factors. Results We identified a cohort of 4,957 patients, of whom 2,294 received statin therapy. Statin use was associated with a 21% decrease in all-cause mortality (adjusted hazard ratio, 0.79; 95% CI, 0.73 to 0.86; P < .001) as well as a 24% decrease in MM-specific mortality (adjusted hazard ratio, 0.76; 95% CI, 0.67 to 0.86; P < .001). This association remained significant across all sensitivity analyses. In addition to reductions in mortality, statin use was associated with a 31% decreased risk of developing a skeletal-related event. Conclusion In this cohort study of US veterans with MM, statin therapy was associated with a reduced risk of both all-cause and MM-specific mortality. Our findings suggest a potential role for statin therapy in patients with MM. The putative benefit of statin therapy in MM should be corroborated in prospective studies.

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Theoretical substitutions between dairy products and all-cause and cause-specific mortality. Results from the Danish diet, cancer and health cohort

British Journal Of Nutrition ◽

10.1017/s0007114521002464 ◽

2021 ◽

pp. 1-10

Author(s):

Anne Sofie D. Laursen ◽

Anne L. Thomsen ◽

Anne Beck ◽

Kim Overvad ◽

Marianne U. Jakobsen

Keyword(s):

Cancer Mortality ◽

Dairy Products ◽

Proportional Hazards ◽

Dairy Product ◽

Daily Intake ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Low Fat ◽

Specific Mortality ◽

Optimal Health

Abstract A daily intake of dairy products is recommended in many countries in order to maintain optimal health throughout life. However, evidence regarding the association between intake of individual dairy products and mortality is limited. We therfore, explored associations between intake of different dairy products and all-cause and cause-specific mortality using specified theoretical substitution analyses. We analysed data from 55 775 Danish men and women aged 50–64 years between 1993 and 1997. Information about dairy product intake at baseline was collected using a validated food frequency questionnaire. Information about vital status and causes of death was obtained through national registers. Measures of associations were calculated using Cox proportional hazards regression. During a median follow-up of 19·0 years, 11 586 participants died. For all-cause mortality, we observed that the intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese was associated with a higher rate of death (hazard ratios between 1·03 and 1·12 per serving/d substituted). The same pattern was present for CVD mortality. For cancer mortality, whole-fat milk and low-fat yogurt products in place of cheese were also associated with a higher rate of death for men while for women, whole-fat milk in place of buttermilk was associated with a higher cancer mortality rate. The results appeared robust in several sensitivity analyses. Our results suggest that intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese is associated with a higher rate of all-cause and cause-specific mortality.

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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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Impact of Cognitive Dysfunction on Survival in Patients With and Without Statin Use Following Carotid Endarterectomy

Neurosurgery ◽

10.1227/neu.0000000000000904 ◽

2015 ◽

Vol 77 (6) ◽

pp. 880-887 ◽

Cited By ~ 12

Author(s):

Eric J. Heyer ◽

Joanna L. Mergeche ◽

Shuang Wang ◽

John G. Gaudet ◽

E. Sander Connolly

Keyword(s):

Confidence Interval ◽

Carotid Endarterectomy ◽

Cognitive Dysfunction ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Rank Test ◽

Term Survival ◽

Asymptomatic Patients ◽

Statin Use

BACKGROUND: Early cognitive dysfunction (eCD) is a subtle form of neurological injury observed in ∼25% of carotid endarterectomy (CEA) patients. Statin use is associated with a lower incidence of eCD in asymptomatic patients having CEA. OBJECTIVE: To determine whether eCD status is associated with worse long-term survival in patients taking and not taking statins. METHODS: This is a post hoc analysis of a prospective observational study of 585 CEA patients. Patients were evaluated with a battery of neuropsychometric tests before and after surgery. Survival was compared for patients with and without eCD stratifying by statin use. At enrollment, 366 patients were on statins and 219 were not. Survival was assessed by using Kaplan-Meier methods and multivariable Cox proportional hazards models. RESULTS: Age ≥75 years (P = .003), diabetes mellitus (P < .001), cardiac disease (P = .02), and statin use (P = .014) are significantly associated with survival univariately (P < .05) by use of the log-rank test. By Cox proportional hazards model, eCD status and survival adjusting for univariate factors within statin and nonstatin use groups suggested a significant effect by association of eCD on survival within patients not taking statin (hazard ratio, 1.61; 95% confidence interval, 1.09–2.40; P = .018), and no significant effect of eCD on survival within patients taking statin (hazard ratio, 0.98; 95% confidence interval, 0.59–1.66; P = .95). CONCLUSION: eCD is associated with shorter survival in patients not taking statins. This finding validates eCD as an important neurological outcome and suggests that eCD is a surrogate measure for overall health, comorbidity, and vulnerability to neurological insult.

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

PLoS ONE ◽

10.1371/journal.pone.0243572 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243572

Author(s):

Hiroya Tanaka ◽

Makoto Yamaguchi ◽

Takayuki Katsuno ◽

Hirokazu Sugiyama ◽

Shiho Iwagaitsu ◽

...

Keyword(s):

Proportional Hazards ◽

Microscopic Polyangiitis ◽

Antineutrophil Cytoplasmic Antibody ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

University Hospital ◽

Cox Proportional Hazards Models ◽

Medical University ◽

Risk Of Relapse

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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Lower carbohydrate diets and all-cause and cause-specific mortality: a population-based cohort study and pooling of prospective studies

European Heart Journal ◽

10.1093/eurheartj/ehz174 ◽

2019 ◽

Vol 40 (34) ◽

pp. 2870-2879 ◽

Cited By ~ 30

Author(s):

Mohsen Mazidi ◽

Niki Katsiki ◽

Dimitri P Mikhailidis ◽

Naveed Sattar ◽

Maciej Banach

Keyword(s):

Cohort Studies ◽

Prospective Studies ◽

Proportional Hazards ◽

Cox Regression ◽

Positive Association ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Pooled Data ◽

Specific Mortality

Abstract Aims Little is known about the long-term association between low-carbohydrate diets (LCDs) and mortality. We evaluated the link between LCD and overall or cause-specific mortality using both individual data and pooled prospective studies. Methods and results Data on diets from the National Health and Nutrition Examination Survey (NHANES; 1999–2010) were analysed. Multivariable Cox proportional hazards were applied to determine the hazard ratios and 95% confidence intervals (CIs) for mortality for each quartile of the LCD score, with the lowest quartile (Q1—with the highest carbohydrates intake) used as reference. We used adjusted Cox regression to determine the risk ratio (RR) and 95% CI, as well as random effects models and generic inverse variance methods to synthesize quantitative and pooled data, followed by a leave-one-out method for sensitivity analysis. Overall, 24 825 participants from NHANES study were included (mean follow-up 6.4 years). After adjustment, participants with the lowest carbohydrates intake (quartile 4 of LCD) had the highest risk of overall (32%), cardiovascular disease (CVD) (50%), cerebrovascular (51%), and cancer (36%) mortality. In the same model, the association between LCD and overall mortality was stronger in the non-obese (48%) than in the obese (19%) participants. Findings on pooled data of nine prospective cohort studies with 462 934 participants (mean follow-up 16.1 years) indicated a positive association between LCD and overall (RR 1.22, 95% CI 1.06–1.39, P < 0.001, I2 = 8.6), CVD (RR 1.13, 95% CI 1.02–1.24, P < 0.001, I2 = 11.2), and cancer mortality (RR 1.08, 95% CI 1.01–1.14, P = 0.02, I2 = 10.3). These findings were robust in sensitivity analyses. Conclusion Our study suggests a potentially unfavourable association of LCD with overall and cause-specific mortality, based on both new analyses of an established cohort and by pooling previous cohort studies. Given the nature of the study, causality cannot be proven; we cannot rule out residual bias. Nevertheless, further studies are needed to extend these important findings, which if confirmed, may suggest a need to rethink recommendations for LCD in clinical practice.

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Early Changes in Serum Albumin Predict Clinical and Endoscopic Outcomes in Patients With Ulcerative Colitis Starting Anti-TNF Treatment

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa309 ◽

2020 ◽

Author(s):

Sun-Ho Lee ◽

Margaret Walshe ◽

Eun Hye Oh ◽

Sung Wook Hwang ◽

Sang Hyoung Park ◽

...

Keyword(s):

Ulcerative Colitis ◽

Serum Albumin ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Interquartile Range ◽

Adjusted Hazard Ratio ◽

Protein Levels ◽

Patient Status ◽

Timely Access

Abstract Background Up to 60% of patients with ulcerative colitis (UC) ultimately fail anti-tumor necrosis factor (TNF) treatment. We aimed to investigate early predictive markers of clinical and endoscopic outcomes in patients with UC who were anti-TNF-naïve commencing anti-TNF treatment, with particular focus on changes in albumin and C-reactive protein levels in the first 2 weeks of treatment. Methods We retrospectively investigated 210 patients with UC who started infliximab or adalimumab between 2009 and 2016 (male, 62.4%; median age at diagnosis, 37.9 years [interquartile range, 25.5–48.9 years]; median follow-up duration, 3.3 years [1.9–5.0 years]). Logistic and Cox proportional-hazards regressions were performed to identify variables associated with primary nonresponse (PNR), endoscopic outcomes, time-to-colectomy, and anti-TNF failure. Results Forty-one patients (19.5%) experienced PNR; week 0/week 2 ratio serum albumin was associated with PNR (adjusted odds ratio [aOR], 1.8; 95% confidence interval [CI], 1.1–2.9, per interquartile range increase). Week 0/week 2 ratio albumin was also associated with endoscopic response (aOR, 0.28; 95% CI, 0.31–0.82) and endoscopic remission (aOR, 0.61; 95% CI, 0.39–0.96) at weeks 8 to 14, time-to-colectomy (adjusted hazard ratio, 2.12; 95% CI, 1.29–3.49) and time-to-anti-TNF failure (adjusted hazard ratio, 1.54; 95% CI, 1.22–1.96), regardless of age, disease severity, or in-patient status. Association with time-to-colectomy and anti-TNF failure was externally validated in an independent cohort of inpatients with UC starting infliximab. Conclusions Change in serum albumin within the first 2 weeks of anti-TNF treatment is predictive of PNR, endoscopic outcomes, time-to-colectomy, and anti-TNF failure in patients with UC. Timely access to this biomarker enables early identification of patients with UC at risk of anti-TNF failure and may guide early optimization of anti-TNF treatment to improve disease outcomes.

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Improved survival with continuation of statins in bacteremic patients

SAGE Open Medicine ◽

10.1177/2050312118801707 ◽

2018 ◽

Vol 6 ◽

pp. 205031211880170

Author(s):

Ajinkya M Pawar ◽

Kerry L LaPlante ◽

Tristan T Timbrook ◽

Aisling R Caffrey

Keyword(s):

Statin Therapy ◽

Proportional Hazards ◽

Primary Diagnosis ◽

Cox Proportional Hazards ◽

Inpatient Mortality ◽

Hospital Data ◽

Continuous Therapy ◽

Proportional Hazards Regression ◽

The Impact ◽

Statin Use

Objectives: Varying statin exposures in bacteremic patients have different impacts on mortality. Among patients with adherent statin use, we sought to evaluate the impact of statin continuation on inpatient mortality in bacteremic patients. Methods: A retrospective cohort study was conducted using Optum ClinformaticsTM with matched Premier Hospital data (October 2009–March 2013). Patients with a primary diagnosis of bacteremia and 6 months of continuous enrollment prior to the admission, receiving antibiotics at least 2 days of antibiotics during the first 3 days of admission, were selected for inclusion. Furthermore, patients demonstrating adherent statin use based on 90 days of continuous therapy prior to admission were included. We then compared those continuing statin therapy for at least the first 5 days after admission and those not continuing during the admission. Results: Simvastatin (53.2%) and atorvastatin (33.8%) were the most commonly used statins among the 633 patients who met our inclusion and exclusion criteria. Propensity score adjusted Cox proportional hazards regression models demonstrated significantly lower inpatient mortality among those continuing statin therapy compared with those not continuing (n = 232 vs 401, adjusted hazard ratio 0.25, 95% confidence interval 0.08–0.79). Conclusion: Among patients adherent to their statin therapy prior to a bacteremia hospitalization, continued statin use after admission increased survival by 75% compared with those not continuing.

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