All-cause and cause-specific mortality in ANCA-associated vasculitis: overall and according to ANCA type

Abstract Objective The objective of this study was to evaluate causes of death in a contemporary inception cohort of ANCA-associated vasculitis patients, stratifying the analysis according to ANCA type. Methods We identified a consecutive inception cohort of patients newly diagnosed with ANCA-associated vasculitis from 2002 to 2017 in the Partners HealthCare System and determined vital status through the National Death Index. We determined cumulative mortality incidence and standardized mortality ratios (SMRs) compared with the general population. We compared MPO- and PR3-ANCA+ cases using Cox regression models. Results The cohort included 484 patients with a mean diagnosis age of 58 years; 40% were male, 65% were MPO-ANCA+, and 65% had renal involvement. During 3385 person-years (PY) of follow-up, 130 patients died, yielding a mortality rate of 38.4/1000 PY and a SMR of 2.3 (95% CI: 1.9, 2.8). The most common causes of death were cardiovascular disease (CVD; cumulative incidence 7.1%), malignancy (5.9%) and infection (4.1%). The SMR for infection was greatest for both MPO- and PR3-ANCA+ patients (16.4 and 6.5). MPO-ANCA+ patients had an elevated SMR for CVD (3.0), respiratory disease (2.4) and renal disease (4.5). PR3- and MPO-ANCA+ patients had an elevated SMR for malignancy (3.7 and 2.7). Compared with PR3-ANCA+ patients, MPO-ANCA+ patients had a higher risk of CVD death [hazard ratio 5.0 (95% CI: 1.2, 21.2]; P = 0.03]. Conclusion Premature ANCA-associated vasculitis mortality is explained by CVD, infection, malignancy, and renal death. CVD is the most common cause of death, but the largest excess mortality risk in PR3- and MPO-ANCA+ patients is associated with infection. MPO-ANCA+ patients are at higher risk of CVD death than PR3-ANCA+ patients.

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Does Hospitalization Predict the Disease Course in Ulcerative Colitis? Prevalence and Predictors of Hospitalization and Re- Hospitalization in Ulcerative Colitis in a Population-based Inception Cohort (2000-2012)

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.243.pag ◽

2015 ◽

Vol 24 (3) ◽

pp. 287-292 ◽

Cited By ~ 5

Author(s):

Petra A. Golovics ◽

Laszlo Lakatos ◽

Michael D. Mandel ◽

Barbara D. Lovasz ◽

Zsuzsanna Vegh ◽

...

Keyword(s):

Ulcerative Colitis ◽

Cox Regression ◽

Diagnostic Procedures ◽

Population Based ◽

Disease Course ◽

Inception Cohort ◽

Disease Extent ◽

Cox Regression Analysis ◽

Hospitalization Rates

Background & Aims: Limited data are available on the hospitalization rates in population-based studies. Since this is a very important outcome measure, the aim of this study was to analyze prospectively if early hospitalization is associated with the later disease course as well as to determine the prevalence and predictors of hospitalization and re-hospitalization in the population-based ulcerative colitis (UC) inception cohort in the Veszprem province database between 2000 and 2012. Methods: Data of 347 incident UC patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (M/F: 200/147, median age at diagnosis: 36, IQR: 26-50 years, follow-up duration: 7, IQR 4-10 years). Both in- and outpatient records were collected and comprehensively reviewed. Results: Probabilities of first UC-related hospitalization were 28.6%, 53.7% and 66.2% and of first re-hospitalization were 23.7%, 55.8% and 74.6% after 1-, 5- and 10- years of follow-up, respectively. Main UC-related causes for first hospitalization were diagnostic procedures (26.7%), disease activity (22.4%) or UC-related surgery (4.8%), but a significant percentage was unrelated to IBD (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at diagnosis (HR extensive: 1.79, p=0.02) or at last follow-up (HR: 1.56, p=0.001), need for steroids (HR: 1.98, p<0.001), azathioprine (HR: 1.55, p=0.038) and anti-TNF (HR: 2.28, p<0.001) were associated with the risk of UC-related hospitalization. Early hospitalization was not associated with a specific disease phenotype or outcome; however, 46.2% of all colectomies were performed in the year of diagnosis. Conclusion: Hospitalization and re-hospitalization rates were relatively high in this population-based UC cohort. Early hospitalization was not predictive for the later disease course.

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POS0119 RENAL INVOLVEMENT AND NEED OF RENAL REPLACEMENT THERAPY IN ANCA ASSOCIATED VASCULITIS IN A SPANISH SINGLE-CENTER STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.345 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 270.2-271

Author(s):

J. Álvarez Troncoso ◽

J. C. Santacruz Mancheno ◽

A. Díez Vidal ◽

S. Afonso Ramos ◽

A. Noblejas Mozo ◽

...

Keyword(s):

Renal Replacement Therapy ◽

Replacement Therapy ◽

Granulomatosis With Polyangiitis ◽

Renal Involvement ◽

Age At Diagnosis ◽

Systemic Involvement ◽

Risk Of Death ◽

Anca Associated Vasculitis ◽

The Mean

Background:Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EPGA). Renal involvement is frequent in AAV and is an important factor for morbidity and mortality.Objectives:The main objective of this study was to analyze the demographic, clinical, histological and therapeutic characteristics of renal involvement in patients with AAV and the risk of renal replacement therapy (RRT) or death.Methods:Retrospective observational study of 56 patients with AAV fulfilling classificatory criteria and renal involvement diagnosed between 1995 and 2020 from a Spanish tertiary centre. We studied the histological involvement (according to the 2010 classification in focal, crescentic, mixed or sclerotic), immunofluorescence (IF) and the treatment received with the risk of RRT or death.Results:We included 56 patients diagnosed with AAV and renal involvement. The mean age was 61.08±4.05 years; 58.9% were women. The mean follow-up time of these patients was 16.14± 8.80 years. Only 57.1% of patients presented systemic involvement.Most frequent non-renal AAV manifestations were lung involvement (39.3%), central nervous system (30.4%), otorhinolaryngology (ORL) (14.3%), skin (8.9%) and cardiac involvement (8.9%). Main immunological findings were ANCA-MPO+ (69.6%), ANCA-PR3+ (23.2%), ANCA-negative (5.4%). Low C3 was found in 19.6% patients. Histologic classification (HC) and need of RRT is described in table 1. Main HC in renal AAV was crescentic, mixed, focal and sclerotic respectively. Eight patients had not biopsy performed. IF was positive for C3 deposits in 20 patients (35.7%). Half of the patients presented <50% normal glomeruli.The treatment of renal involvement in AAV in our cohort was as follows: 83.9% (47) corticosteroids (CS) and cyclophosphamide (of which 40 received intravenous and 7 oral cyclophosphamide; and 12 patients associated plasma exchange (PE) with this treatment), 5.36% CS alone, 2 patients received CS and mycophenolate; 1 CS and rituximab, 1 CS and PE, and 2 patients received no treatment. A total of 13 patients received PE and 18 RRT. The mean time to RRT was 65.44±32.72 months. Relapses were not uncommon, 33.93% of the patients presented ≥1 relapse and 10.71% presented ≥2.Infections were very frequent since they were present in 91.07% of the patients. Other frequent non-immunological complications observed in the follow-up of these patients were thrombosis in 31.14%, cardiovascular events in 28.57% and cancer in 19.64%.Patients with ANCA-PR3+ were younger at diagnosis (p<0.001), were more likely to present cardiac (p=0.045) and ORL involvement (p<0.001). However, neither ANCA-PR3+ nor ANCA-MPO+ were specifically associated with the need of RRT or higher risk of death in our cohort. Use of CS alone for the treatment of renal AAV was associated with higher mortality (p=0.006) but CS and cyclophosphamide with lower mortality (p=0.044). ANCA-negative patients were more likely to receive no treatment. Having <50% normal glomeruli and C3 deposits on IF were associated with an increased need for RRT. Presenting focal disease on HC was protective for the need of RRT. Older age at diagnosis, systemic involvement of AAV and need of RRT was associated with higher mortality.Conclusion:AAVs are complex vasculitides with frequent renal involvement. Increased C3 deposition, non-focal histological forms, and <50% normal glomeruli were related to the need for RRT. In turn, the need for RRT, a later age at diagnosis, and systemic involvement were associated with higher mortality. Holistic and multidisciplinary early management of AAVs in experience centers can help improve renal prognosis and decrease mortality.References:[1]Binda et al. ANCA-associated vasculitis with renal involvement. J Nephrol. 2018 Apr;31(2):197-208.[2]Kronbichler et al. Clinical associations of renal involvement in ANCA-associated vasculitis. Autoimmun Rev. 2020 Apr;19(4):102495.Disclosure of Interests:None declared

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Abstract 88: Social Inequalities in Stroke Mortality, Incidence and Case-fatality in Europe.

Stroke ◽

10.1161/str.47.suppl_1.88 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Marco M Ferrario ◽

Giovanni Veronesi ◽

Kari Kuulasmaa ◽

Martin Bobak ◽

Lloyd E Chambless ◽

...

Keyword(s):

Risk Factors ◽

Social Inequalities ◽

Cox Regression ◽

Case Fatality ◽

Stroke Mortality ◽

Stroke Incidence ◽

Low Education ◽

Mortality Incidence ◽

European Populations

Introduction and aim: There are limited comparative data on social inequalities in stroke morbidity across Europe. We aimed to assess the magnitude of educational class inequalities in stroke mortality, incidence and 1-year case-fatality in European populations. Methods: The MORGAM study comprised 45 cohorts from Finland, Denmark, Sweden, Northern Ireland, Scotland, France, Germany, Italy, Lithuania, Poland and Russia, mostly recruited in mid 1980s-early 90s. Baseline data collection and follow-up (median 12 years) for fatal and non-fatal strokes adhered to MONICA-like procedures. Stroke mortality was defined according to the underlying cause of death (ICD-IX codes 430-438 or ICD-X I60-I69). We derived 3 educational classes from population-, sex- and birth year-specific tertiles of years of schooling. We estimated the age-adjusted difference in event rates, and the age- and risk factor-adjusted hazard ratios (HRs), between the bottom and the top of the educational class distribution from sex- and population-specific Poisson and Cox regression models, respectively. The association between 1-year case-fatality and education was estimated through logistic models adjusted for risk factors. Results: Among the 91,563 CVD-free participants aged 35-74 at baseline, 1037 stroke deaths and 3902 incident strokes occurred during follow-up. Low education accounted for 26 additional stroke deaths per 100,000 person-years in men (95%CI: 9 to 42), and 19 (7 to 32) in women. In both genders, inequalities in fatal stroke rates were larger in the East EU and in the Nordic Countries populations. The age-adjusted pooled HRs of first stroke, fatal or non-fatal, for the least educated men and women were 1.52 (95%CI: 1.29-1.78) and 1.51 (1.25-1.81), respectively, consistently across populations. Adjustment for smoking, blood pressure, HDL-cholesterol and diabetes attenuated the pooled HRs to 1.34 (95%CI: 1.14-1.57) in men and 1.29 (1.07-1.55) in women. A significant association between low education and increased 1-year case-fatality was observed in Northern Sweden only. Conclusions: Social inequalities in stroke incidence are widespread in most European populations, and less than half of the gap is explained by major risk factors.

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Cause of Death After Surgical Aortic Valve Replacement: SWEDEHEART Observational Study

Journal of the American Heart Association ◽

10.1161/jaha.121.022627 ◽

2021 ◽

Author(s):

Natalie Glaser ◽

Michael Persson ◽

Anders Franco‐Cereceda ◽

Ulrik Sartipy

Keyword(s):

Aortic Valve ◽

General Population ◽

Life Expectancy ◽

Aortic Valve Replacement ◽

Valve Replacement ◽

Causes Of Death ◽

Study Cohort ◽

Surgical Aortic Valve Replacement ◽

Standardized Mortality Ratios

Background Prior studies showed that life expectancy in patients who underwent surgical aortic valve replacement (AVR) was lower than in the general population. Explanations for this shorter life expectancy are unknown. The aim of this nationwide, observational cohort study was to investigate the cause‐specific death following surgical AVR. Methods and Results We included 33 018 patients who underwent primary surgical AVR in Sweden between 1997 and 2018, with or without coronary artery bypass grafting. The SWEDEHEART (Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) register and other national health‐data registers were used to obtain and characterize the study cohort and to identify causes of death, categorized as cardiovascular mortality, cancer mortality, or other causes of death. The relative risks for cause‐specific mortality in patients who underwent AVR compared with the general population are presented as standardized mortality ratios. During a mean follow‐up period of 7.3 years (maximum 22.0 years), 14 237 (43%) patients died. The cumulative incidence of death from cardiovascular, cancer‐related, or other causes was 23.5%, 8.3%, and 11.6%, respectively, at 10 years, and 42.8%, 12.8%, and 23.8%, respectively, at 20 years. Standardized mortality ratios for cardiovascular, cancer‐related, and other causes of death were 1.79 (95% CI, 1.75–1.83), 1.00 (95% CI, 0.97–1.04), and 1.08 (95% CI, 1.05–1.12), respectively. Conclusions We found that life expectancy following AVR was lower than in the general population. Lower survival after AVR was explained by an increased relative risk of cardiovascular death. Future studies should focus on the role of earlier surgery in patients with asymptomatic aortic stenosis and on optimizing treatment and follow‐up after AVR. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02276950.

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P0471DIALYSIS TREATMENT AT THE TIME OF DIAGNOSIS PREDICTS OUTCOMES IN ANCA ASSOCIATED VASCULITIS PATIENTS - DATA FROM CROATIAN REFERRAL CENTER

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0471 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Matija Crnogorac ◽

Ana Brechelmacher ◽

Ivica Horvatić ◽

Patricia Kacinari ◽

Miroslav Tišljar ◽

...

Keyword(s):

Relapse Rate ◽

Strong Predictor ◽

Univariate Analysis ◽

Renal Involvement ◽

Tubular Damage ◽

Dialysis Treatment ◽

Acute Dialysis ◽

Anca Associated Vasculitis ◽

Time To Diagnosis

Abstract Background and Aims Dialysis dependence and ESRD are known complications of ANCA associated vasculitis (AAV) with renal involvement. What is not so often discussed is the role of dialysis treatment at the time of diagnosis and how it affects patient outcomes as well as characteristics of such patients. We present data showing the importance of dialysis treatment at the time of diagnosis as the predictor of clinical outcomes. Method This study included 106 consecutive AAV patients with renal involvement in the period from 2007-2017. We performed renal biopsy on patients using automatic 16 Gauge needle. Light, immunofluorescent and electronic microscopy were performed. Primary outcomes were combined outcome progression to end-stage renal disease, defined as persistent (more than three months) need for renal replacement therapy or permanent reduction of EGFR to <15ml/minute (according to CKD EPI formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Results Out of 106 patients (55,6% female, median age 61; IQR 51-70) there were 66 (61,1%) microscopic poliangitiis (MPA), 20 (18,5%) granulomatosis with angitiis and 20 (18,5%) with renal limited vasculitis (RLV). Out of those 14 (13%) were PR3-ANCA positive patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCA+MPO-ANCA positive and 32 (29,6%) ANCA negative patients. Average serum creatinine (SCr) levels was 316,5 μmol/l (IQR 207,0-548,5), 24-hour proteinuria median was 1,7g/24h (IQR 0,8-2,8). According to the Berden classification 43 (39,8%) patients had crescentic, 19 (17,6%) focal, 34 (31,5%) mixed and 12 (11,1%) sclerotic class. Follow up time ranged from 1 to 127 months. Median follow up time was 21 months (IQR = 7-44). Median time to diagnosis was 3 months (IQR 2,0-6,0). Patients requiring dialysis treatment at the time of diagnosis were more often MPO – (p=0,04), had more severe anemia (p=0,001), higher CRP (p=0,003), and more pronounced hypoalbuminemia (serums albumin <30g/l; p=0,006).Such patients were older than those not requiring dialysis (p=0,055) na had shorter time to diagnosis (p=0,001). Clinically such patient s presented more often with RPGN (p<0,001) which is in a way expected thus having higher SCr levels (p=<0,001). Histologically dialysis treated patients predominantly had crescentic class, while non-dialysis group had focal class (p<0,001). Of note dialysis group had more acute tubular damage (p=0,007). Interestingly enough there was slightly more positive C3 deposition in dialysis group (p=0,09). In univariate analysis the need for acute dialysis at the time of diagnosis of AAV was significant predictor for combined ESRDD, D, ESRD and relapse rate. In multivariate analysis the need for acute dialysis at the time of diagnosis of AAV remained significant predictor for ESRD (HR = 4,674, 95% CI =1,996-10,946; p = < 0,001) and relapse rate (HR = 59,545, 95% CI =3,467-1022,665; p = 0,005). Conclusion The need for dialysis at the time of AAV diagnosis is a strong predictor for ESRD and relapse rate. It is also interesting to further study differences between patients needing dialysis at the time of diagnosis and those who don’t need it.

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Outcome in biopsy-proven Lupus nephritis: Evaluation of biopsies from the Norwegian Kidney Biopsy Registry

Lupus ◽

10.1177/0961203316686700 ◽

2017 ◽

Vol 26 (8) ◽

pp. 881-885 ◽

Cited By ~ 14

Author(s):

G E Norby ◽

G Mjøen ◽

R Bjørneklett ◽

B E Vikse ◽

H Holdaas ◽

...

Keyword(s):

General Population ◽

Lupus Nephritis ◽

Confidence Interval ◽

Cardiovascular Events ◽

Causes Of Death ◽

Cox Regression ◽

Population Sample ◽

All Cause Mortality ◽

Class Iv

Objective To evaluate long-term mortality and end-stage renal disease (ESRD) in a cohort of Norwegian patients with biopsy-proven lupus nephritis (LN). Methods Renal biopsies were obtained from 178 patients with LN from 1988 until 2007. Mortality rate and death causes were provided by Statistics Norway and ESRD data were provided by the Norwegian Renal Registry. Risk factors for all-cause mortality were evaluated by Cox regression. Standardized mortality ratio (SMR) was compared to observed deaths in a matched general population sample. Results Mean age was 37.6 (±14.4) years, and median time of follow-up was 8.5 years (0–26.2). Thirty-six patients (20.2%) died during follow-up. The SMR for all-cause mortality was 5.6 (Confidence interval [CI] 3.7–7.5). In an adjusted multivariate analysis proliferative glomerulonephritis (LN class IV) was independently associated with all-cause mortality; hazard ratio (HR) 2.6 (Confidence interval [CI] 1.2–5.7 p = 0.017). Main causes of death were infections (47.2%) and cardiovascular events 8 (22.2%). Thirty-six patients (20.2%) reached ESRD. Conclusions Biopsy-proven LN is associated with increased mortality compared to the general population. LN class IV is associated with all-cause mortality. Infections and cardiovascular events were the most common causes of death. Patients with LN have a high incidence of ESRD.

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Prognostic Factors for Survival and Relapse in ANCA-Associated Vasculitis with Renal Involvement: A Clinical Long-Term Follow-Up Study

International Journal of Nephrology ◽

10.1155/2018/6369814 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Anna Salmela ◽

Tom Törnroth ◽

Tuija Poussa ◽

Agneta Ekstrand

Keyword(s):

Prognostic Factors ◽

Patient Survival ◽

Renal Involvement ◽

Multivariable Analysis ◽

Induction Treatment ◽

Renal Survival ◽

Histopathological Classification ◽

Anca Associated Vasculitis

Aim. We describe the clinical pattern of ANCA-associated vasculitis (AAV) and assess long-term prognostic factors of patients and renal survival and relapse. Methods. Data from 85 patients with renal biopsy-proven AAV at a single center with up to 20-year [median 16.2 years (95% CI 14.9-17.7)] follow-up were retrospectively collected. Results. Overall, 55% of the patients had microscopic polyangiitis (MPA) and 45% had granulomatosis with polyangiitis (GPA). The histopathological classes were focal in 35%, crescentic in 26%, mixed in 20%, and sclerotic glomerulonephritis in 19% of the patients. As induction treatment, a combination of cyclophosphamide and corticosteroids was given to 82%, while a combination of azathioprine and corticosteroids was maintenance therapy in 79%. The twenty-year patient survival was 45%. In a multivariable analysis, age ≥58 years [hazard ratio (HR) 7.64, 95% CI 3.44-16.95] and myeloperoxidase (MPO) ANCA (HR 2.12, 95% CI 1.08-4.17) were associated with shorter patient survival time. Renal survival was 68% overall: 88% in focal, 71% in crescentic, 56% in mixed, and 37% in sclerotic class (p=0.01). Female sex (HR 0.26, 95% CI 0.10-0.73) was a predictor of improved renal survival, whereas GFR <30 ml/min and MPO-ANCA were associated with worse renal survival (HR 4.10, 95% CI 1.35-12.49 and HR 3.10, 95% CI 1.21-7.95, respectively). Relapse-free survival at 20 years was 10%. MPA was associated with a lower risk for relapse (HR 0.48, 95% CI 0.28–0.82). Conclusion. We confirmed the improved patient and renal survival in AAV patients with glomerulonephritis, while relapse remained the primary challenge. Histopathological classification may be relevant for survival.

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Causes of death among crack cocaine users

Brazilian Journal of Psychiatry ◽

10.1590/s1516-44462006000300010 ◽

2006 ◽

Vol 28 (3) ◽

pp. 196-202 ◽

Cited By ~ 49

Author(s):

Marcelo Ribeiro ◽

John Dunn ◽

Ricardo Sesso ◽

Andréa Costa Dias ◽

Ronaldo Laranjeira

Keyword(s):

General Population ◽

Mortality Risk ◽

Causes Of Death ◽

Crack Cocaine ◽

Study Endpoint ◽

Intravenous Drug Use ◽

Common Causes ◽

History Of ◽

Cocaine Users

OBJECTIVE: The study accompanied 131 crack-cocaine users over a 5-year period, and examined mortality patterns, as well as the causes of death among them. METHOD: All patients admitted to a detoxification unit in Sao Paulo between 1992 and 1994 were interviewed during two follow-up periods: 1995-1996 and 1998-1999. RESULTS: After 5 years, 124 patients were localized (95%). By the study endpoint (1999), 23 patients (17.6%) had died. Homicide was the most prevalent cause of death (n = 13). Almost one third of the deaths were due to the HIV infection, especially among those with a history of intravenous drug use. Less than 10% died from overdose. CONCLUSIONS: The study suggests that the mortality risk among crack cocaine users is greater than that seen in the general population, being homicide and AIDS the most common causes of death among such individuals.

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Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile

American Journal of Epidemiology ◽

10.1093/aje/kwz086 ◽

2019 ◽

Vol 188 (8) ◽

pp. 1484-1492 ◽

Cited By ~ 2

Author(s):

Stella Koutros ◽

Jay H Lubin ◽

Barry I Graubard ◽

Aaron Blair ◽

Patricia A Stewart ◽

...

Keyword(s):

Bladder Cancer ◽

Proportional Hazards ◽

Cox Regression ◽

The United States ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Increased Risk ◽

Total Cancer ◽

Standardized Mortality Ratios

Abstract We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.

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Donepezil Adherence, Persistence and Time to First Discontinuation in a Three-Year Follow-Up of Older People

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000441894 ◽

2015 ◽

Vol 5 (3) ◽

pp. 482-491 ◽

Cited By ~ 3

Author(s):

Henry C. Ndukwe ◽

Prasad S. Nishtala

Keyword(s):

Cox Regression ◽

Cumulative Probability ◽

Inception Cohort ◽

Cox Regression Analysis ◽

Adjusted Risk ◽

Kaplan Meier ◽

Moderate Dementia ◽

The Mean ◽

Minimum Dataset

Background: Donepezil is indicated for the management of mild to moderate dementia, particularly in Alzheimer's disease. Several studies have described low adherence rates with donepezil. Aim: To examine and measure donepezil adherence, persistence and time to first discontinuation in older New Zealanders. Methods: An inception cohort of 1,999 new users of donepezil, aged 65 years or older, were identified from the Pharmaceutical Collections and National Minimum Dataset from 1 November 2010 to 31 December 2013. Kaplan-Meier curves and Cox regression analysis were used to estimate the cumulative probability and risk of time to first discontinuation of donepezil therapy. Results: The mean age of the cohort was 79.5 ± 6.4 years and included 42.7% females. Adherence was high (89.0%), while the proportion of donepezil dispensings (81.0-32.5%) declined between 6 and 36 months. Persistence between the 1st and 6th dispensing visit decreased by 19.0%, and 11.0% of the total cohort had a gap of 31 days or more. The adjusted risk of time to first discontinuation in the non-adherent group was 2.2 times (95% CI 1.9-2.6) that of the adherent group. Conclusions: The non-adherent new donepezil users, on average, discontinued faster than the adherent group. Time to first discontinuation in this study was higher compared to discontinuation rates observed in clinical trials.

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