Higher fasting triglyceride predicts higher risks of diabetes mortality in US adults

Abstract Background It is unknown whether higher triglyceride results in higher mortality from diabetes, i.e., diabetes mortality. This study aimed to investigate the association of fasting triglyceride with diabetes mortality. Methods This study included 26,582 US adults from the National Health and Nutrition Examination Surveys from 1988 to 2014. Diabetes mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of triglyceride for diabetes mortality. Results Higher levels of fasting triglyceride were associated with higher levels of glucose, glycated hemoglobin, insulin, and homeostatic model assessment for insulin resistance at baseline. A 1-natural-log-unit increase in triglyceride (e.g., from 70 to 190 mg/dL) was associated with a 115% higher multivariate-adjusted risk of diabetes diagnosis (odds ratio, 2.15; 95% CI, 2.00–2.33). During 319,758 person-years of follow-up with a mean follow-up of 12.0 years, 582 diabetes deaths were documented. Compared with people with triglyceride in the lowest quintile, people with triglyceride in the highest quintile had an 85% higher risk of diabetes mortality (HR, 1.85; 95% CI, 1.25–2.73). A 1-natural-log-unit increase in triglyceride was associated with a 40% higher multivariate-adjusted risk of diabetes mortality. The positive association between triglyceride and diabetes mortality was also presented in sub-cohorts of participants with or without diabetes. Conclusions This study demonstrated that higher fasting triglyceride was associated with a higher diabetes mortality risk.

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Abstract WP218: Increased Systolic Blood Pressure Variability Among Diabetic Patients is Associated With Higher Risk of Incident Stroke: A Secondary Analysis of ACCORDION

Stroke ◽

10.1161/str.51.suppl_1.wp218 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Adam H de Havenon ◽

Ka-Ho Wong ◽

Eva Mistry ◽

Mohammad Anadani ◽

Shadi Yaghi ◽

...

Keyword(s):

Blood Pressure ◽

Blood Pressure Variability ◽

Proportional Hazards ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Diabetic Patients ◽

Adjusted Risk ◽

Cox Proportional Hazards Models ◽

Increased Risk

Background: Increased blood pressure variability (BPV) has been associated with stroke risk, but never specifically in patients with diabetes. Methods: This is a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Follow-On Study (ACCORDION), the long term follow-up extension of ACCORD. Visit-to-visit BPV was analyzed using all BP readings during the first 36 months. The primary outcome was incident ischemic or hemorrhagic stroke after 36 months. Differences in mean BPV was tested with Student’s t-test. We fit Cox proportional hazards models to estimate the adjusted risk of stroke across lowest vs. highest quintile of BPV and report hazard ratios along with 95% confidence intervals (CI). Results: Our analysis included 9,241 patients, with a mean (SD) age of 62.7 (6.6) years and 61.7% were male. Mean (SD) follow-up was 5.7 (2.4) years and number of BP readings per patient was 12.0 (4.3). Systolic, but not diastolic, BPV was higher in patients who developed stroke (Table 1). The highest quintile of SBP SD was associated with increased risk of incident stroke, independent of mean blood pressure or other potential confounders. (Table 2, Figure 1). There was no interaction between SBP SD and treatment arm assignment, although the interaction for glucose approached significance (Table 2). Conclusion: Higher systolic BPV was associated with incident stroke in a large cohort of diabetic patients. Future trials of stroke prevention may benefit from interventions targeting BPV reduction.

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Association of Urinary Cadmium with Cancer Mortality Is Influenced by Zinc Intake in Follow-up Study of NHANES 1988–1994 and 1999–2004 (P18-026-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz039.p18-026-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Kijoon Kim ◽

Melissa Melough ◽

Junichi Sakaki ◽

Hwayoung Noh ◽

Sung Koo ◽

...

Keyword(s):

Cancer Mortality ◽

Proportional Hazards ◽

Adult Population ◽

Positive Association ◽

Cox Proportional Hazards ◽

Toxic Heavy Metal ◽

Cox Proportional Hazards Models ◽

All Cause Mortality ◽

Risk Of Cancer

Abstract Objectives Exposure to cadmium (Cd), a toxic heavy metal, increases risk of numerous chronic diseases and overall mortality. However, little work has been conducted to examine the effect of Zn intake on the association between Cd burden and mortality. The aim of this study was to examine whether the association between urinary Cd concentration and all-cause and disease specific mortality differs by Zn intake level among a representative sample of the US adult population. Methods A total of 15,642 US adults aged 30 years and older in the National Health and Nutrition Examination Survey 1988–1994 and 1999–2004 were followed up through December 31, 2011. Participants’ Zn intake was assessed through 24-hour dietary recalls. The main outcomes included mortality from cardiovascular disease (CVD), cancer, and all causes. Using Cox proportional hazards models, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for quartiles of urinary Cd, quartiles of dietary Zn, and for quartiles of urinary Cd stratified by level of dietary Zn. Results Of 5367 total deaths that occurred over a mean follow-up of 15 years, 1194 were attributed to cancer and 1677 were attributed to CVD. After adjustment for potential confounders, positive relationships were observed between urinary Cd and all-cause mortality (HR for highest vs. lowest quartile (Q4 vs. Q1): 1.38; 95% CI: 1.14–1.68; P-trend < 0.0001) and cancer mortality (HR for Q4 vs. Q1: 1.54; 95% CI: 1.05–2.27; P-trend < 0.005), but not CVD mortality (HR for Q4 vs. Q1: 1.22; 95% CI: 0.95–1.57; P-trend = 0.0502). Negative associations were observed between dietary Zn and all-cause mortality (HR for Q4 vs. Q1: 0.88; 95% CI: 0.75–1.02; P-trend < 0.05) and cancer mortality (HR for Q4 vs. Q1: 0.82; 95% CI: 0.65–1.03, P-trend < 0.05). Among the lowest tertile of Zn consumers, there was a clear positive association between urinary Cd and cancer mortality (HR for Q4 vs. Q1: 1.79; 95% CI: 1.07–3.01), however, among the highest Zn consumers, this association was somewhat diminished (HR for Q4 vs. Q1: 1.66; 95% CI: 0.80–3.41). Conclusions These findings support existing evidence that Cd burden is associated with greater mortality, and also demonstrate that greater Zn consumption is associated with reduced risk of cancer death related to Cd. Funding Sources This study received no financial support.

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Association of poor sleep burden in middle age and older adults with risk for delirium during hospitalization

The Journals of Gerontology Series A ◽

10.1093/gerona/glab272 ◽

2021 ◽

Author(s):

Ma Cherrysse Ulsa ◽

Xi Zheng ◽

Peng Li ◽

Arlen Gaba ◽

Patricia M Wong ◽

...

Keyword(s):

Sleep Disturbances ◽

Proportional Hazards ◽

Time Lag ◽

Cox Proportional Hazards ◽

Poor Sleep ◽

Cardiovascular Risks ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

The Uk

Abstract Background Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization. Methods 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype–a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first. Results In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p<0.001) and 57% (1.57 [1.38-1.80], p<0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction <0.001). Conclusion Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.

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Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4578 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4578-4578

Author(s):

Bradley Alexander McGregor ◽

Daniel M. Geynisman ◽

Mauricio Burotto ◽

Camillo Porta ◽

Cristina Suarez Rodriguez ◽

...

Keyword(s):

Proportional Hazards ◽

Objective Response ◽

Indirect Comparison ◽

Progression Free Survival ◽

Wald Test ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Published Data ◽

Cox Proportional Hazards Models

4578 Background: Nivolumab in combination with cabozantinib (N+C) has demonstrated significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS), compared with sunitinib as a first-line (1L) treatment for aRCC in the phase 3 CheckMate (CM) 9ER trial. As there are no head-to-head trials comparing N+C with pembrolizumab in combination with axitinib (P+A), this study compared the efficacy of N+C with P+A as 1L treatment in aRCC. Methods: An MAIC was conducted using individual patient data on N+C (N = 323) from the CM 9ER trial (median follow-up: 23.5 months) and published data on P+A (N = 432) from the KEYNOTE (KN)-426 trialof P+A (median follow-up: 30.6 months). Individual patients within the CM 9ER trial population were reweighted to match the key patient characteristics published in KN-426 trial, including age, gender, previous nephrectomy, International Metastatic RCC Database Consortium risk score, and sites of metastasis. After weighting, hazards ratios (HR) of PFS, duration of response (DoR), and OS comparing N+C vs. P+A were estimated using weighted Cox proportional hazards models, and ORR was compared using a weighted Wald test. All comparisons were conducted using the corresponding sunitinib arms as an anchor. Results: After weighting, patient characteristics in the CM 9ER trial were comparable to those in the KN-426 trial. In the weighted population, N+C had a median PFS of 19.3 months (95% CI: 15.2, 22.4) compared to a median PFS of 15.7 months (95% CI: 13.7, 20.6) for P+A. Using sunitinib as an anchor arm, N+C was associated with a 30% reduction in risk of progression or death compared to P+A, (HR: 0.70, 95% CI: 0.53, 0.93; P = 0.015; table). In addition, N+C was associated with numerically, although not statistically, higher improvement in ORR vs sunitinib (difference: 8.4%, 95% CI: -1.7%, 18.4%; P = 0.105) and improved DoR (HR: 0.79; 95% CI: 0.47, 1.31; P = 0.359). Similar OS outcomes were observed for N+C and P+A (HR: 0.99; 95% CI: 0.67, 1.44; P = 0.940). Conclusions: After adjusting for cross-trial differences, N+C had a more favorable efficacy profile compared to P+A, including statistically significant PFS benefits, numerically improved ORR and DoR, and similar OS.[Table: see text]

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Gestational diabetes with diabetes and prediabetes risks: a large observational study

Acta Endocrinologica ◽

10.1530/eje-18-0130 ◽

2018 ◽

Vol 179 (1) ◽

pp. 51-58 ◽

Cited By ~ 11

Author(s):

Yun Shen ◽

Peng Wang ◽

Leishen Wang ◽

Shuang Zhang ◽

Huikun Liu ◽

...

Keyword(s):

Gestational Diabetes ◽

Observational Study ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

World Health ◽

Oral Glucose ◽

Adjusted Risk ◽

Postpartum Diabetes ◽

Incident Cases

Aims To compare risks of early postpartum diabetes and prediabetes in Chinese women with and without gestational diabetes mellitus (GDM) during pregnancy. Subjects and methods Tianjin GDM observational study included 1263 women with a history of GDM and 705 women without GDM who participated in the urban GDM universal screening survey by using World Health Organization’s criteria. Postpartum diabetes and prediabetes were identified after a standard oral glucose tolerance test. Cox proportional hazards regression was used to assess risks of postpartum diabetes and prediabetes between women with and without GDM. Results During a mean follow-up of 3.53 years postpartum, 90 incident cases of diabetes and 599 incident cases of prediabetes were identified. Multivariable-adjusted hazard ratios among women with prior GDM, compared with those without it, were 76.1 (95% CI: 23.6–246) for diabetes and 25.4 (95% CI: 18.2–35.3) for prediabetes. When the mean follow-up extended to 4.40 years, 121 diabetes and 616 prediabetes cases were identified. Women with prior GDM had a 13.0-fold multivariable-adjusted risk (95% CI: 5.54-30.6) for diabetes and 2.15-fold risk (95% CI: 1.76-2.62) for prediabetes compared with women without GDM. The positive associations between GDM and the risks of postpartum diabetes and prediabetes were significant and persistent when stratified by younger and older than 30 years at delivery and normal weight and overweight participants. Conclusions The present study indicated that women with prior GDM had significantly increased risks for postpartum diabetes and prediabetes, with the highest risk at the first 3–4 years after delivery, compared with those without GDM.

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Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality

RMD Open ◽

10.1136/rmdopen-2019-001015 ◽

2019 ◽

Vol 5 (2) ◽

pp. e001015 ◽

Cited By ~ 10

Author(s):

Fernando Pérez Ruiz ◽

Pascal Richette ◽

Austin G Stack ◽

Ravichandra Karra Gurunath ◽

Ma Jesus García de Yébenes ◽

...

Keyword(s):

Uric Acid ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

First Year ◽

Cox Proportional Hazards Models ◽

Crude Mortality ◽

Risk Patients ◽

The Impact ◽

Related Mortality

ObjectiveTo determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.MethodsProspective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs.ResultsOf 1193 patients, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45).ConclusionsFailure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.

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Long-term efficacy of mycophenolate mofetil in myelin oligodendrocyte glycoprotein antibody-associated disorders

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000705 ◽

2020 ◽

Vol 7 (3) ◽

pp. e705 ◽

Cited By ~ 9

Author(s):

Shengde Li ◽

Haitao Ren ◽

Yan Xu ◽

Tao Xu ◽

Yao Zhang ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Proportional Hazards ◽

Myelin Oligodendrocyte Glycoprotein ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

College Hospital ◽

Relapse Risk ◽

Medical College ◽

Cox Proportional Hazards Models

ObjectiveTo investigate whether the use of mycophenolate mofetil (MMF) could reduce the relapse risk in patients with myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG)-associated disorders (MOGADs).MethodsThis prospective observational cohort study included patients with MOGAD at Peking Union Medical College Hospital between January 1, 2017, and April 30, 2019. The patients were divided into 2 groups: those with (MMF+) or without (MMF−) MMF therapy. The primary outcome was relapse at follow-up. We used Cox proportional hazards models to calculate hazard ratios (HRs) for relapse.ResultsSeventy-nine patients were included in our MOG cohort. Fifty (63.3%) were adults at index date, and 47 (59.5%) were women. Fifty-four (68.4%) were in the MMF+ group, and 25 (31.6%) were in the MMF− group. Clinical and demographic factors, MOG-IgG titer, and follow-up time (median, 472.5 days for MMF+, 261.0 days for MMF−) were comparable between the groups. Relapse rates were 7.4% (4/54) in the MMF+ group and 44.0% (11/25) in the MMF− group. Of all potential confounders, only the use of MMF was associated with reduced risk of relapse. The HR for relapse among patients in the MMF+ group was 0.14 (95% CI, 0.05–0.45) and was 0.08 (95% CI, 0.02–0.28) in a model adjusted for age, sex, disease course, and MOG-IgG titer. MMF therapy also remained associated with a reduced relapse risk in sensitivity analyses. Only one patient (1.9%) discontinued MMF therapy because of adverse effect.ConclusionsThese findings provide a clinical evidence that MMF immunosuppression therapy may prevent relapse in patients with MOGAD.Classification of evidenceThis study provides class IV evidence that for patients with MOGAD, MMF reduces relapse risk.

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Childhood body mass index and multiple sclerosis risk: a long-term cohort study

Multiple Sclerosis Journal ◽

10.1177/1352458513483889 ◽

2013 ◽

Vol 19 (10) ◽

pp. 1323-1329 ◽

Cited By ~ 143

Author(s):

Kassandra L Munger ◽

Joan Bentzen ◽

Bjarne Laursen ◽

Egon Stenager ◽

Nils Koch-Henriksen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Body Mass Index ◽

Body Mass ◽

School Health ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Z Score ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Unit Increase

Background: Obesity in late adolescence has been associated with an increased risk of multiple sclerosis (MS); however, it is not known if body size in childhood is associated with MS risk. Methods: Using a prospective design we examined whether body mass index (BMI) at ages 7–13 years was associated with MS risk among 302,043 individuals in the Copenhagen School Health Records Register (CSHRR). Linking the CSHRR with the Danish MS registry yielded 774 MS cases (501 girls, 273 boys). We used Cox proportional hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among girls, at each age 7–13 years, a one-unit increase in BMI z-score was associated with an increased risk of MS (HRage 7=1.20, 95% CI: 1.10–1.30; HRage 13=1.18, 95% CI: 1.08–1.28). Girls who were ≥95th percentile for BMI had a 1.61–1.95-fold increased risk of MS as compared to girls <85th percentile. The associations were attenuated in boys. The pooled HR for a one-unit increase in BMI z-score at age 7 years was 1.17 (95% CI: 1.09–1.26) and at age 13 years was 1.15 (95% CI: 1.07–1.24). Conclusion: Having a high BMI in early life is a risk factor for MS, but the mechanisms underlying the association remain to be elucidated.

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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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A Combined Prospective and Retrospective Comparison of Long-Term Functional Outcomes Suggests Delayed Loss of Ambulation and Pulmonary Decline with Long-Term Eteplirsen Treatment

Journal of Neuromuscular Diseases ◽

10.3233/jnd-210665 ◽

2021 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Olga Mitelman ◽

Hoda Z. Abdel-Hamid ◽

Barry J. Byrne ◽

Anne M. Connolly ◽

Peter Heydemann ◽

...

Keyword(s):

Natural History ◽

Repeated Measures ◽

Proportional Hazards ◽

Clinical Care ◽

Standard Of Care ◽

Cox Proportional Hazards ◽

Kaplan Meier ◽

Cox Proportional Hazards Models

Background: Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care. Objective: To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls. Methods: Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures. Results: Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p < 0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: –3.3 vs. –6.0 percentage points annually, p < 0.0001). Conclusions: Study 405 highlights the functional benefits of eteplirsen on ambulatory and pulmonary function outcomes up to 7 years of follow-up in comparison to external controls.

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