Multiple Cox Proportional Hazards Models Research Articles

Increased Dose and Duration of Statin Use Is Associated with Decreased Asthma-Related Emergency Department Visits and Hospitalizations

Statins have pleiotropic anti-inflammatory and immunomodulatory effects, yet the effect of statin use on asthma-related emergency department (ED) visits and hospitalizations has remained unclear, especially in Asian populations. We sought to examine the effect of statin therapy on asthma-related ED visits and/or hospitalizations. A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2013. A total of 117,595 adult patients with asthma were included. The outcomes were defined as asthma-related ED visits and/or hospitalizations. Multiple Cox proportional hazards models were applied to determine the effect of statin use on asthma-related ED visits and/or hospitalizations. There were 3,417 asthma-related ED visits and/or hospitalizations among 117,595 subjects with asthma. Statin users were significantly less likely to experience asthma-related ED visits and/or hospitalizations (adjusted hazard ratio: 0.81; 95% confidence interval: 0.74-0.89) compared with nonstatin users. The risks of asthma-related ED visits and/or hospitalizations were decreased among those with a higher cumulative defined daily dose (DDD), greater average DDD, and longer cumulative-day users than the counterparts. Our study suggests that statin use is associated with the decreased risk of asthma-related ED visits and/or hospitalizations in patients with asthma. A dose-response effect of statin use is also observed in this study. Therefore, future randomized clinical trials would be warranted to further evaluate the association.

Abstracts of the 10th International Conference on Cachexia, Sarcopenia and Muscle Wasting, Rome, Italy, 8-10 December 2017 (Part 1)

Abstracts of the 10th International Conference on Cachexia, Sarcopenia and Muscle Wasting, Rome, Italy, 8-10 December 2017 (Part 1)

Increased risk of periodontitis in patients with psoriatic disease: a nationwide population-based retrospective cohort study.

AimsPeriodontitis and psoriatic disease, including psoriasis (PS) and psoriatic arthritis (PsA), share the common risk factors and co-morbidities. However, the risk of periodontitis in patients with psoriatic disease still needs further investigation. This study was a nationwide population-based retrospective cohort study assessing the risk of periodontitis from psoriatic disease exposure.Materials and MethodsPatients with newly diagnosed psoriatic disease from 2003 to 2012 were identified from the Taiwanese National Health Insurance Research Database. The 1:4 ratio propensity score matched controls were selected from no psoriatic disease participations. The subsequent risk of periodontitis was evaluated in exposure and comparison groups. Multiple Cox proportional hazard models were used for the estimation.ResultsA total of 3,487 psoriatic disease patients and 13,948 controls were identified. Incidence rate of periodontitis was higher in patients with PsA. The adjusted hazard ratio (aHRs) for moderate/severe periodontitis were 0.85 (95% CI [0.65–1.11]) in PS group and 1.66 (95% CI [0.99–2.78]) in PsA group. The aHRs of PsA were increased over time, aHRs was changed from 0.65 (0–11 months from index date) to 1.34 (≥12 months from index date) in all types of periodontitis and from 1.09 to 1.79 in moderate/severe periodontitis group, respectively.ConclusionsThe increased risk of periodontitis was observed, especially the association between PsA and moderate/severe periodontitis. The patients with psoriatic disease should receive regular periodontal evaluation.

471TiP - A multicentre, randomised, double-blind, parallel-group, placebo-controlled trial of apatinib in local progressive or metastatic radioactive iodine-refractory differentiated thyroid cancer

Background: Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a big challenge in the management of thyroid cancer. Sorafenib and lenvatinib are the 2 FDA-approved tyrosine kinase inhibitors (TKIs), which might not be affordable for most of the Chinese patients (pts). Apatinib is an oral TKI targeting VEGFR-2, with a patient assistance program available in China. It achieved a quick Tg decline of 21% 2 weeks later and an objective response rate (ORR) of 90%, showing promising efficacy in RAIR-DTC (Lin et al, ATA 2016, Short Call Poster 65; Lin et al, Oncotarget, Epub Feb. 02, 2017). Thus, this study aimed to further evaluate the efficacy and safety of apatinib in treating RAIR-DTC. Trial design: This study is a multicentre, randomised, double-blind, parallel-group, placebo-controlled, phase III trial in China. Adult pts with locally advanced or metastatic RAIR-DTC are eligible. The inclusion criteria include at least one measurable lesion; disease progression within the past 12 months; and ECOG PS 0–2. Pts are defined as RAIR-DTC if they have target lesion(s) without iodine uptake, received one RAI treatment (≥3.7 GBq [≥100 mCi]) but progressed within the past 12 months, received two RAI treatments or more with a time interval of less than 12 months and progressed at least 12 months later), or received cumulative RAI activity over 22.2 GBq (≥600 mCi). Previous targeted therapy is not allowed. Enrolled patients will be randomly assigned to receive apatinib (500 mg qd) and placebo, respectively. Four weeks is defined as one cycle. Dose increase to 750 mg and dose reduction to 250 mg are allowed. The primary endpoint is progression free survival. The secondary endpoints include disease control rate, ORR, duration of response, changes in serum Tg and TgAb concentration, quality of life, and safety. A multiple Cox proportional hazards model is used to evaluate the hazard ratios after adjusting iodine uptake, metastatic lesion site, gender, and age. 118 pts will be recruited assuming a 106.9% increase in median PFS in the apatinib arm compared with the placebo arm. As of 2nd May 2017, 3 eligible patients have been enrolled. Clinical trial identification: NCT03048877 (Release date: February 7, 2017) Legal entity responsible for the study: Yansong Lin Funding: None Disclosure: All authors have declared no conflicts of interest.

Vitamin D status is associated with treatment failure and duration of illness in Nepalese children with severe pneumonia

BackgroundThere is no consensus on optimal Vitamin D status. The objective of this study was to estimate the extent to which vitamin D status predicts illness duration and treatment failure in children with severe pneumonia by using different cutoffs for vitamin D concentration.MethodsWe measured the plasma concentration of 25(OH)D in 568 children hospitalized with World Health Organization-defined severe pneumonia. The associations between vitamin D status, using the most frequently used cutoffs for vitamin D insufficiency (25(OH)D<50 and <75 nmol/l), and risk for treatment failure and time until recovery were analyzed in multiple logistic regression and Cox proportional hazards models, respectively.ResultsOf the 568 children, 322 (56.7%) had plasma 25(OH)D levels ≥75 nmol/l, 179 (31.5%) had levels of 50–74.9 nmol/l, and 67 (%) had levels <50 nmol/l. Plasma 25(OH)D <50 nmol/l was associated with increased risk for treatment failure and longer time until recovery.ConclusionOur findings indicate that low vitamin D status (25(OH)D<50 nmol/l) is an independent risk factor for treatment failure and delayed recovery from severe lower respiratory infections in children.

Is aircraft noise exposure associated with cardiovascular disease and hypertension? Results from a cohort study in Athens, Greece

BackgroundWe followed up, in 2013, the subjects who lived near the Athens International Airport and had participated in the cross-sectional multicountry HYENA study in 2004–2006.ObjectiveTo evaluate the association of exposure...

Cirrhosis patients' stroke risks and adverse outcomes: Two nationwide studies

Background & aimsThe association between liver cirrhosis (LC) and stroke is not completely understood. Our purpose was to evaluate stroke risk and post-stroke outcomes in patients with LC. MethodsWe identified 6944 adults aged 20 years and older, newly diagnosed with LC, using the Taiwan's National Health Insurance Research Database from 2000 to 2005. The comparison cohort consisted of 27,776 adults without LC, randomly selected by frequency matching in age and sex. Events of new-onset stroke were identified from medical claims during the 2000–2013 follow-up period. Adjusted hazard ratios (HR) and 95% confidence intervals (CIs) of stroke associated with LC were calculated in the multiple Cox proportional hazard model. Another nested stroke cohort study of 21,267 hospitalized stroke patients analyzed adjusted odds ratios (ORs) and 95% CIs of adverse events after stroke, among patients with and without LC, between 2000 and 2009. ResultsThe incidences of stroke for people with and without LC were 6.1 and 4.3 per 1000 person-years, respectively. Compared with the non-cirrhotic cohort, the adjusted HR of stroke was 1.55 (95% CI 1.28–1.87) for LC patients. Previous LC was associated with risks of epilepsy (OR 1.30, 95% CI 1.09–1.56), admission to intensive care unit (OR 1.23, 95% CI (1.14–1.32) and in-hospital mortality (OR 1.83, 95% CI 1.63–2.05) after stroke. ConclusionsLC was associated with higher risk of stroke, and patients with LC had more complications and mortality after stroke. This susceptible population needs strategies to prevent stroke and post-stroke adverse events.

Clinical impact of high serum hepatocyte growth factor in advanced non-small cell lung cancer.

Activation of c-MET through hepatocyte growth factor (HGF) increases tumorigenesis, induces resistance, and is associated with poor prognosis in various solid tumors. However, the clinical value of serum HGF (sHGF) in patients with advanced non-small cell lung cancer (NSCLC), especially those receiving cytotoxic chemotherapy, remains unknown. Here, we show that sHGF may be useful to predict tumor response and progression-free survival (PFS) in patients with advanced NSCLC. A total of 81 patients with NSCLC were investigated. sHGF levels were evaluated using ELISA at 4 time-points: at pre-treatment, at response-evaluation (1–2 months after treatment initiation), at the best tumor response, and at disease progression. As a control biomarker, CEA was also evaluated in lung adenocarcinoma. Positive-sHGF at response-evaluation predicted poor PFS compared with Negative-sHGF in both first-line (median, 153.5 vs. 288.0; P < 0.05) and second-line treatment (87.0 vs. 219.5; P = 0.01). In 55 patients that received cytotoxic chemotherapy, multiple Cox proportional hazards models showed significant independent associations between poor PFS and Positive-sHGF at response-evaluation (hazard ratio, 4.24; 95% CI, 2.05 to 9.46; P < 0.01). Lung adenocarcinoma subgroup analysis showed that in patients receiving second cytotoxic chemotherapy, there were no significant differences in PFS between patients with low-CEA compared with those with high-CEA, but Positive-sHGF at pre-treatment or at response-evaluation predicted poor PFS (35.0 vs. 132.0; P < 0.01, 50.0 vs. 215.0; P < 0.01, respectively). These findings give a rationale for future research investigating the merit of sHGF as a potential clinical biomarker to evaluate HGF/c-MET activity, which would be useful to indicate administration of c-MET inhibitors.

Survival analysis of elderly patients in Intensive Care Units

Abstract Objective: Conduct a survival analysis of elderly patients hospitalized in an intensive care unit (ICU), identifying the predictors of mortality among this age group. Methods: A retrospective cohort study was performed with data from the medical records of 457 elderly patients hospitalized in an ICU located in the city of Natal in Brazil. Survival functions were estimated using the Kaplan-Meier estimator, and the Log-rank test was used for comparisons. In addition, a multiple Cox proportional hazards model was constructed to identify the independent effects of the predictors of survival. Results: It was found that the survival of elderly ICU patients declined due to factors such as increased hospitalization time, advancing years, unmarried (including common-law-marriage) status, the presence of shock, pneumonia, septicaemia, fractures, a reduced state of consciousness, hospitalization for clinical reasons, being bedridden prior to hospitalization, fever, bradycardia, hypotension, cardiac arrest and the need for mechanical ventilation. The multiple Cox proportional hazards model revealed that variables such as shock, longevity, bradycardia, fractures, fever, hospitalization in the public healthcare system and admission for clinical reasons remained significant as predictors of reduced survival in intensive care units. Conclusions: The survival rates of elderly persons in an ICU in the city of Natal in Brazil were affected by demographic and clinical predictors, and those related to the type of hospitalization and the health care network. This shows that any initiative aimed at increasing the survival of elderly ICU patients must look at individual and social issues and factors related to the health care network.

Delta neutrophil index is an independent predictor of mortality in septic acute kidney injury patients treated with continuous renal replacement therapy

BackgroundDelta neutrophil index (DNI), representing an elevated fraction of circulating immature granulocytes in acute infection, has been reported as a useful marker for predicting mortality in patients with sepsis. The aim of this study was to evaluate the prognostic value of DNI in predicting mortality in septic acute kidney injury (S-AKI) patients treated with continuous renal replacement therapy (CRRT).MethodThis is a retrospective analysis of consecutively CRRT treated patients. We enrolled 286 S-AKI patients who underwent CRRT and divided them into three groups based on the tertiles of DNI at CRRT initiation (high, DNI > 12.0%; intermediate, 3.6–12.0%; low, < 3.6%). Patient survival was estimated with the Kaplan-Meier method and Cox proportional hazards models to determine the effect of DNI on the mortality of S-AKI patients.ResultsPatients in the highest tertile of DNI showed higher Acute Physiology and Chronic Health Evaluation II score (highest tertile, 27.9 ± 7.0; lowest tertile, 24.6 ± 8.3; P = 0.003) and Sequential Organ Failure Assessment score (highest tertile, 14.1 ± 3.0; lowest tertile, 12.1 ± 4.0; P = 0.001). The 28-day mortality rate was significantly higher in the highest tertile group than in the lower two tertile groups (P < 0.001). In the multiple Cox proportional hazard model, DNI was an independent predictor for mortality after adjusting multiple confounding factors (hazard ratio, 1.010; 95% confidence interval, 1.001–1.019; P = 0.036).ConclusionThis study suggests that DNI is independently associated with mortality of S-AKI patients on CRRT.

Cumulative survival rate and associated risk factors of Implantium implants: A 10-year retrospective clinical study.

PURPOSEThe objective of this study was to determine the cumulative survival rate (CSR) and associated risk factors of Implantium implants by retrospective clinical study.MATERIALS AND METHODSPatients who received Implantium implants (Dentium Co., Seoul, Korea) at Korea University Guro Hospital from 2004 to 2011 were included. The period between the first surgery and the last hospital visit until December 2015 was set as the observation period for this study. Clinical and radiographic data were collected from patient records, including all complications observed during the follow-up period. Kaplan-Meier analysis was performed to examine CSR. Multiple Cox proportional hazard model was employed to assess the associations between potential risk factors and CSR.RESULTSA total of 370 implants were placed in 121 patients (mean age, 56.1 years; range, 19 to 75 years). Of the 370 implants, 13 failed, including 7 implants that were lost before loading. The 10-year cumulative survival rate of implants was 94.8%. The multiple Cox proportional hazard model revealed that significant risk factor of implant failure were smoking and maxillary implant (P<.05).CONCLUSIONThe 10-year CSR of Implantium implants was 94.8%. Risk factors of implant failure were smoking and maxillary implant.

Prognostic Value of C-Reactive Protein and Homocysteine in Large-Artery Atherosclerotic Stroke: a Prospective Observational Study

Our objective is to investigate whether C-reactive protein (CRP) and homocysteine (Hcy) levels in the acute phase of large-artery atherosclerotic stroke predict long-term functional disability and recurrent vascular events. Patients with first-ever large-artery atherosclerotic ischemic stroke were prospectively registered in the Nanjing Stroke Registry Program between January 2012 and June 2014. Venous blood samples were collected within 2 weeks after the index stroke. Patients were followed up for 1 year. The Kaplan-Meier method was performed in survival analysis. Multiple logistic regression analysis and Cox proportional hazard model were applied to identify predictors of functional disability and recurrent vascular events, respectively. A total of 625 eligible patients (458 males) were evaluated. During the 1-year follow-up period, 63 patients suffered recurrent vascular events. An elevated CRP level is an independent predictor of poor functional disability at 1 year (P for trend = .002), in both males (P for trend = .017) and females (P for trend = .042). Hcy showed no relationship with functional disability. No significant relationship between CRP and Hcy levels and recurrent vascular events was found in total patients in multiple models. Stratified by sex, high Hcy levels were associated with recurrent vascular events in females (P for trend = .036) but not in males. Elevated CRP levels are associated with poor functional disability in patients with large-artery atherosclerotic stroke at 1 year, and Hcy is a relatively moderate predictor of recurrent vascular events in female patients with large-artery atherosclerotic stroke at 1 year.

Cognitive abilities predict death during the next 15years in older Japanese adults.

The longitudinal relationship between cognitive abilities and subsequent death was investigated among community-dwelling older Japanese adults. Participants (n=1060; age range 60-79years) comprised the first-wave participants of the National Institute for Longevity Sciences-Longitudinal Study of Aging. Participants' cognitive abilities were measured at baseline using the Japanese Wechsler Adult Intelligence Scale-Revised Short Form, which includes the following tests: Information (general knowledge), Similarities (logical abstract thinking), Picture Completion (visual perception and long-term visual memory) and Digit Symbol (information processing speed). By each cognitive test score, participants were classified into three groups: the high-level group (≥ the mean+1SD), the low-level group (≤ the mean-1SD) and the middle-level group. Data on death and moving during the subsequent 15years were collected and analyzed using the multiple Cox proportional hazard model adjusted for physical and psychosocial covariates. During the follow-up period, 308 participants (29.06%) had died and 93 participants (8.77%) had moved. In the Similarities test, adjusted hazard ratios (HR) of the low-level group to the high-level group were significant (HR 1.49, 95% CI 1.02-2.17, P=0.038). Furthermore, in the Digit symbol test, the adjusted HR of the low-level group to the high-level group was significant (HR 1.62, 95% CI 1.03-2.58, P=0.038). Significant adjusted HR were not observed for the Information or Picture Completion tests. It is suggested that a lower level of logical abstract thinking and slower information processing speed are associated with shorter survival among older Japanese adults. Geriatr Gerontol Int 2017; 17: 1654-1660.

Mortality and readmissions in heart failure: an analysis of 36,824 elderly patients from the Slovenian national hospitalization database

In heart failure (HF), comorbidity burden and prognostic risks increase with age. Studies investigating outcome in elderly patients from large datasets are lacking, particularly in central and eastern European countries. We analyzed the Slovenian data on mortality and readmissions after first HF hospitalization in patients aged 65years or over. In this observational epidemiological study, the Slovenian national hospitalization database was searched for HF patients aged ≥65years with first HF hospitalization between 2008 and 2012. All-cause mortality and readmissions were compared in young-olds (65-74years), middle-olds (75-84years), and old-olds (≥85years) using cumulative probability plots and log rank test. The prognostic value of comorbidities on mortality and readmissions for age groups were assessed using multiple Cox proportional hazards models. Overall, 36,824 patients were included (median age 80years, 41 % men, 20 % in-hospital mortality). The proportions of young-olds, middle-olds, and old-olds were 26, 48, and 26 %, respectively. Arterial hypertension (60 %), pulmonary disease (44 %), and atrial fibrillation (38 %) were the most prevalent comorbidities, with little variation over age. While age group was associated with higher mortality (P< 0.001), no such associations were seen for readmissions at any time points (P> 0.1 for all). Importance of comorbidities as apredictor for mortality faded with increasing age while only small decrease in hazard ratios for readmissions were seen. Age is an independent predictor of mortality but not readmissions in elderly patients with first HF hospitalization. Comorbidities are important predictors for mortality and readmissions in elderly.

Frequency of Stroke After Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting (from an Eleven-Year Statewide Analysis)

We compared stroke rates associated with coronary artery bypass grafting (CABG), both on-pump and off-pump, and percutaneous coronary intervention (PCI) with both drug-eluting stent (DES) and bare-metal stent (BMS) and the impact on 30-day and 1-year all-cause mortality. The Myocardial Infarction Data Acquisition System database was used to study patients who had on-pump CABG (n= 47,254), off-pump CABG (n=19,118), and PCI with BMS (n= 46,641), and DES (n= 115,942) in New Jersey from 2002 to 2012. Multiple logistic and Cox proportional hazard models were used to compare the risk of stroke and mortality. Adjustments were made for demographics, year of hospitalization, and co-morbidities. The rate of postprocedural stroke was lowest with DES (0.5%), followed by BMS (0.6%), off-pump CABG (1.3%), and on-pump CABG (1.8%). After adjustment, on-pump CABG had a higher risk of stroke compared with off-pump (odds ratio 1.36, 95% CI 1.18 to 1.56, p <0.0001). DES had lower risk of stroke compared with off-pump CABG (odds ratio 0.64, 95% CI 0.55 to 0.74, p <0.0001). There was a significant excess risk of 1-year mortality due to the interaction between stroke and procedure type (on-pump vs off-pump CABG and PCI with DES vs BMS; p value for interaction= 0.02). In conclusion, in this retrospective analysis of nonrandomized data from a statewide database, PCI with DES was associated with the lowest rate of postprocedural stroke, and off-pump CABG had a lower rate of postprocedural stroke than on-pump CABG; there was an excess 1-year mortality risk with on-pump versus off-pump CABG and with DES versus BMS in patients with stroke.

Calcinosis is associated with digital ischaemia in systemic sclerosis-a longitudinal study.

To determine if ischaemia is a causal factor in the development of calcinosis in SSc. Patients with SSc were assessed yearly. Physicians reported the presence of calcinosis, digital ischaemia (digital ulcers, digital necrosis/gangrene, loss of digital pulp on any digits and/or auto- or surgical digital amputation) and nailfold capillary dropout assessed using a dermatoscope. The number of digits with digital ischaemia was used as an assessment of the severity of digital ischaemia. SSc specific antibodies were detected with a line immunoassay. Multiple logistic regression and Cox proportional hazards models were generated to determine associations between calcinosis, digital ischaemia and capillary dropout. One thousand three hundred and five patients were included in this study, of whom 300 (23.0%) had calcinosis at study entry. In a cross-sectional multivariate analysis, at baseline, calcinosis was associated with digital ischaemia (odds ratio (OR) = 2.37, 95% CI: 1.66, 3.39), severity of ischaemia (OR = 1.12, 95% CI: 1.06, 1.18), capillary dropout (OR = 1.41, 95% CI: 1.05, 1.89), ACAs (OR = 1.68, 95% CI: 1.17, 2.43) and anti-RNA polymerase III antibodies (OR = 1.77, 95% CI: 1.08, 2.89). Current use of calcium channel blockers was inversely associated with the presence of calcinosis (OR = 0.70, 95% CI: 0.52, 0.96). Of the 805 patients with no calcinosis at study entry and at least one follow-up visit, 215 (26.7%) developed calcinosis during follow-up. Significant baseline predictors of the development of calcinosis in follow-up were digital ischaemia (hazard ratio (HR) = 1.82, 95% CI: 1.30, 2.54), capillary dropout (HR = 1.46, 95% CI: 1.08, 1.99), dcSSc (HR = 1.57, 95% CI: 1.11, 2.21), ACA (HR = 2.18, 95% CI: 1.50, 3.17) and anti-RNA polymerase III antibodies (HR = 2.58, 95% CI: 1.65, 4.04). Ischaemia may play a role in the development of calcinosis in SSc.

Is aircraft noise exposure associated with cardiovascular disease and hypertension? Results from a cohort study in Athens Greece

Introduction: We followed up, in 2013, the subjects who lived near the Athens International Airport and had participated in the cross-sectional multi-country HYENA study in 2004-06. The objective was to evaluate the association of exposure to aircraft and road traffic noise with the incidence of hypertension and other cardiovascular outcomes. Methods: From the 780 individuals who participated in the cross-sectional study, 537 were still living in the same area and 420 accepted to participate in the follow-up. Aircraft and road traffic noise exposure was based on the estimations conducted in 2004-06, linking geo-coded residential addresses of the participants to noise levels. We applied multiple logistic regression and Cox proportional hazards models, adjusting for potential confounders. Results: The incidence of hypertension was significantly associated with higher aircraft noise exposure during the night. Specifically, the OR for hypertension per 10 dB increase in Lnight aircraft noise exposure was 2.63 (95% C.I. 1.21-5.71). Doctor diagnosed cardiac arrhythmia was significantly associated with Lnight, when all cases were considered with an OR of 2.09 (95% CI 1.07, 4.08). Stroke risk was also increased with increasing noise exposure but the association was not significant. The OR per 10 dB Lnight aircraft and the LAeq16hr noise exposure for incident doctor diagnosed hearing impairment events was 3.51 (95% C.I. 1.46-8.44) and 2.33 (95% C.I. 1.26-4.30), respectively. There were no clear association with twenty four hour road traffic noise. Conclusions: In conclusion, the present study suggests that long-term exposure to aircraft noise, particularly during the night, is associated with hypertension and possibly, also, cardiovascular effects.

Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. To create a prognostic model to estimate survival of patients with refractory coeliac disease. We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality=30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20year increase, hazard ratio=2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio=2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio=0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up.

Digoxin and short term mortality after acute STEMI: Results from the MAGIC trial

BackgroundThe safety of digoxin has been a subject of debate for decades, most recently among patients with atrial fibrillation (AF). Digoxin has been used during the acute phase of ST elevation myocardial infarction (STEMI) complicated with AF or heart failure. Data about digoxin in this setting are scarce. HypothesisWe hypothesize that digoxin maybe associated with increased mortality when used during the acute phase of ST segment myocardial infarction. MethodsWe investigated the association between digoxin and mortality in patients enrolled in the MAGnesium In Coronaries (MAGIC) study, which evaluated the efficacy of early magnesium administration in STEMI. Multiple Cox proportional hazards models were examined to assess the aforementioned association after correction for clinical characteristics and comorbidities. ResultsAfter excluding 639 (10.3%) patients for missing data, we analyzed the remaining 5574 patients. There were 852 (15.3%) deaths during the one month follow-up and 170 (3.0%) patients on digoxin concomitantly, among which 42 patients (24.7%) died. There was a statistically significant association between digoxin and increased mortality in the unadjusted statistical analysis; however, this association disappeared after correction for clinical characteristics and comorbidities in the primary multivariable analysis (estimated hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.62–1.19, p=0.372) and in three additional multivariable analyses. ConclusionDigoxin use as a new or preexisting medication during the acute phase of STEMI in the MAGIC trial was not associated with a significant increase in mortality after correcting for clinical characteristics and comorbidities.

Dipeptidyl peptidase-4 inhibitor use is not associated with elevated risk of severe joint pain in patients with type 2 diabetes: a population-based cohort study.

This is the first large longitudinal cohort study to investigate the putative association of severe joint pain (SJP) with dipeptidyl peptidase-4 inhibitor (DPP4i) use in patients with type 2 diabetes. The propensity score-matched population-based cohort study was performed between 2009 and 2013 in a group of type 2 diabetes patients with stable metformin use. In total, 4743 patients with type 2 diabetes used a DPP4i as the second-line antidiabetic drug (ie, DPP4i users), and the same number of matched non-DPP4i users was selected. The 2 study groups were followed up until SJP diagnosis (International Classification of Diseases, Ninth Reversion, Clinical Modification code 719.4), health insurance policy termination, or the end of 2013. The incidence rate of SJP was estimated under the Poisson assumption. Multiple Cox proportional hazard model was used to estimate the covariate-adjusted hazard ratio and 95% CI of SJP in association with DPP4i use. Over a maximum follow-up of 5 years, 679 DPP4i users and 767 non-DPP4i users were newly diagnosed with SJP, representing incidence rates of 47.20 and 50.66 per 1000 person-years, respectively. Cox proportional hazard model indicated that DPP4i use slightly but nonsignificantly reduced the risk of SJP (adjusted hazard ratio: 0.92 [95% CI: 0.83-1.02]). Such null results were also observed among all age and sex stratifications and in a sensitivity analysis using all nonspecific arthropathies as the study endpoint. This study provides no support for the putative risk of SJP related to DPP4i use in type 2 diabetes patients during a maximum follow-up of 5 years.