Patterns of Cause-Specific Mortality Among 2053 Survivors of Retinoblastoma, 1914–2016

Abstract Background Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However, cause-specific mortality patterns for long-term hereditary and nonhereditary retinoblastoma survivors are poorly understood. Methods Among 2053 retinoblastoma patients diagnosed during 1914–2006 at two major US treatment centers and followed to 2016, we estimated cumulative mortality, standardized mortality ratios (SMRs), and absolute excess risks (AERs) compared with the US general population. Results Most deaths occurred in 1129 hereditary retinoblastoma patients (n = 518 deaths, cumulative mortality 70 years after retinoblastoma = 75.8%, 95% CI = 69.0% to 82.6%; SMR = 8.5, 95% CI = 7.7 to 9.2). Of these, 267 were due to subsequent cancers (SMR = 27.4, 95% CI = 24.2 to 30.9; AER = 72.3 deaths/10 000 person-years), for which SMRs were highest 15–29 years after diagnosis (n = 69, SMR = 89.9, 95% CI = 70.0 to 113.8) but remained statistically significantly elevated at 60 and more years (n = 14, SMR = 6.7, 95% CI = 3.6 to 11.2), whereas AERs increased with time (AER<15years = 38.0; AER60+years = 327.5). Increased risk of death due to cancers of pancreas, large intestines, and kidney were noted for the first time. Overall risk of subsequent cancers was greater for those treated with radiotherapy and chemotherapy compared to radiotherapy alone, although patterns varied by organ site. For 924 patients with nonhereditary retinoblastoma, we noted a modestly increased risk of death for subsequent cancers (n = 27, SMR = 1.8, 95% CI = 1.2 to 2.6) possibly due to treatment or misclassification of hereditary status. Risks of noncancer causes of death were not elevated for hereditary or nonhereditary patients. Conclusion Hereditary retinoblastoma survivors died mainly from an excess risk of subsequent cancers up to six decades later, highlighting the need to develop long-term clinical management guidelines for hereditary retinoblastoma survivors treated in the past.

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Long-term cause-specific mortality in hodgkin lymphoma patients

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djaa194 ◽

2020 ◽

Author(s):

Simone de Vries ◽

Michael Schaapveld ◽

Cécile P M Janus ◽

Laurien A Daniëls ◽

Eefke J Petersen ◽

...

Keyword(s):

General Population ◽

Hodgkin Lymphoma ◽

Primary Treatment ◽

Subdistribution Hazard ◽

Cumulative Mortality ◽

Risk Of Death ◽

Disease Mortality ◽

Specific Mortality ◽

The Impact

Abstract Background Few studies examined the impact of treatment-related morbidity on long-term cause-specific mortality in Hodgkin lymphoma (HL) patients. Methods This multicenter cohort included 4,919 HL patients, treated before age 51 between 1965–2000, with a median follow-up of 20.2 years. Standardized mortality ratios (SMRs), absolute excess mortality per 10,000 person-years (AEM) and cause-specific cumulative mortality by stage and primary treatment, accounting for competing risks were calculated. Results HL patients experienced 5.1-fold (AEM = 123 excess deaths per 10,000 person-years) higher risk of death due to causes other than HL. This risk remained increased in 40-year survivors (SMR = 5.2, 95% Confidence Interval (95%CI) = 4.2–6.5; AEM = 619). At age 54 years, HL survivors experienced similar cumulative mortality (20.0%) from causes other than HL as 71-year old individuals from the general population. While HL mortality statistically significantly decreased over calendar period (p < .001), solid tumor mortality did not change in the most recent treatment era. Patients treated in 1989–2000 had lower 25-year cardiovascular disease mortality than patients treated in 1965–1976 (4.3% vs. 5.7%; subdistribution Hazard Ratio (HR) = 0.65, 95%CI = 0.46–0.93). Infectious disease mortality was not only increased after splenectomy but also after spleen irradiation (HR = 2.81, 95%CI = 1.55–5.07). For stage I-II, primary treatment with chemotherapy alone was associated with statistically significantly higher HL mortality (p < .001 for CT vs. RT; p = .04 for CT vs. RT+CT), but lower 30-year mortality from causes other than HL (15.8%, 95%CI = 9.7%–23.3%), compared to radiotherapy alone (36.9%, 95%CI = 34.0%–39.8%; p = .001) and radiotherapy and chemotherapy combined (29.8%, 95%CI = 26.8%–32.9%; p = .02). Conclusion Compared to the general population, HL survivors have a substantially reduced life expectancy. Optimal selection of patients for primary CT is crucial, weighing risks of HL relapse and long-term toxicity.

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Long-Term Cause-Specific Mortality of Patients Treated for Hodgkin’s Disease

Journal of Clinical Oncology ◽

10.1200/jco.2003.07.131 ◽

2003 ◽

Vol 21 (18) ◽

pp. 3431-3439 ◽

Cited By ~ 488

Author(s):

Berthe M.P. Aleman ◽

Alexandra W. van den Belt-Dusebout ◽

Willem J. Klokman ◽

Mars B. van’t Veer ◽

Harry Bartelink ◽

...

Keyword(s):

General Population ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Initial Therapy ◽

Second Primary ◽

Risk Of Death ◽

Increased Risk ◽

Specific Mortality

Purpose: To assess long-term cause-specific mortality of young Hodgkin’s disease (HD) patients. Patients and Methods: The study population consisted of 1,261 patients treated for HD before age 41 between 1965 and 1987. Follow-up was complete until October 2000. For 95% of deaths, the cause was known. Long-term cause-specific mortality was compared with general population rates to assess relative risk (RR) and absolute excess risk (AER) of death. Results: After a median follow-up of 17.8 years, 534 patients had died (55% of HD). The RR of death from all causes other than HD was 6.8 times that of the general population, and still amounted to 5.1 after more than 30 years. RRs of death resulting from solid tumors (STs) and cardiovascular disease (CVD) were increased overall (RR = 6.6 and 6.3, respectively), but especially in patients treated before age 21 (RR = 14.8 and 13.6, respectively). When these patients grew older, this elevated mortality decreased. The overall AER of death from causes other than HD increased throughout follow-up. Patients receiving salvage chemotherapy had a significantly increased RR of death from STs, compared to patients receiving initial therapy only. Conclusion: The main cause of death among HD patients was lymphoma, but after 20 years, HD mortality was negligible. The RRs and AERs of death from second primary cancers (SCs) and CVDs continued to increase after 10 years. Even more than 30 years after diagnosis, HD patients experienced elevated risk of death from all causes other than HD. Increased risk of death from SCs and CVDs was found especially in patients treated before age 21, but these risks seemed to abate with age.

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Risk of death among people with rare autoimmune diseases compared to the general population in England during the 2020 COVID-19 pandemic

Rheumatology ◽

10.1093/rheumatology/keaa855 ◽

2020 ◽

Author(s):

Emily Peach ◽

Megan Rutter ◽

Peter Lanyon ◽

Matthew J Grainge ◽

Richard Hubbard ◽

...

Keyword(s):

General Population ◽

Healthcare Services ◽

Mortality Rates ◽

Published Data ◽

Risk Of Death ◽

Increased Risk ◽

Specific Mortality ◽

Population Mortality ◽

The Uk ◽

Recorded Diagnosis

Abstract Objectives To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared with the general population, and compared with their pre-COVID risk. Methods We conducted a cohort study in Hospital Episode Statistics for England 2003 onwards, and linked data from the NHS Personal Demographics Service. We used ONS published data for general population mortality rates. Results We included 168 691 people with a recorded diagnosis of RAIRD alive on 01/03/2020. Their median age was 61.7 (IQR 41.5–75.4) years, and 118 379 (70.2%) were female. Our case ascertainment methods had a positive predictive value of 85%. 1,815 (1.1%) participants died during March and April 2020. The age-standardised mortality rate (ASMR) among people with RAIRD (3669.3, 95% CI 3500.4–3838.1 per 100 000 person-years) was 1.44 (95% CI 1.42–1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Age-specific mortality rates in people with RAIRD compared with the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Women had a greater increase in mortality rates during COVID-19 compared with men. Conclusion The risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to healthcare services.

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Cause-specific mortality in survivors of lymphoplasmacytic lymphoma (LPL) and waldenstrom macroglobulinemia (WM).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e19056 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e19056-e19056

Author(s):

Nicole H. Dalal ◽

Graca Dores ◽

Rochelle E. Curtis ◽

Martha S. Linet ◽

Lindsay M. Morton

Keyword(s):

General Population ◽

Causes Of Death ◽

Age Groups ◽

Population Data ◽

Cancer Registries ◽

Population Based ◽

Cumulative Mortality ◽

Risk Of Death ◽

Specific Mortality ◽

Absolute Excess Risk

e19056 Background: LPL and WM are rare, indolent mature B-cell lymphomas. While recent studies reveal improving survival after LPL/WM, cause-specific mortality has not been comprehensively studied. Methods: We identified 6659 adults with first primary LPL (n = 2866) or WM (n = 3793) within 17 US population-based cancer registries from 2000 to 2015. Patients were followed for vital status (mean follow-up = 5.07 years), and causes of death were determined from death certificates. Standardized mortality ratios (SMRs) estimated relative risk of death compared to the general population. We estimated cumulative mortality and absolute excess risk (AER) per 10,000 person-years. Results: We observed 2826 deaths overall, of which 43%, 13%, and 42% were due to lymphoma, cancers excluding lymphoma, and non-malignant causes, respectively. There was a 20% higher risk of death due to non-malignant causes compared to the general population (n = 1194, SMR = 1.2, 95% confidence interval [CI] = 1.1 to 1.2). The most common non-malignant causes included infectious (n = 162, SMR = 1.8, 95% CI = 1.5 to 2.1, AER = 21.0), respiratory (n = 131, SMR = 1.2, 95% CI = 1.0 to 1.5, AER = 7.4), and digestive (n = 76, SMR = 1.9, 95% CI = 1.5 to 2.4, AER = 10.7) diseases. Cause-specific mortality varied by time since and age at LPL/WM diagnosis. Risks were highest in the first year after LPL/WM for non-malignant causes (SMR = 1.4, AER = 34.3), particularly infections (SMR = 2.4, AER = 34.4) and non-neoplastic hematologic diseases (SMR = 17.3, AER = 20.7). In contrast, risk of death due to cancers excluding lymphoma increased with time since diagnosis (SMR< 1y = 1.2, SMR≥5y = 1.7; AER< 1y = 15.1, AER≥5y = 60.0). Analyses by age, focused on AERs, showed generally similar risks across age groups (cancers excluding lymphoma: AER< 65= 26, AER65-75= 28, AER≥75= 31; non-malignant causes: AER< 65= 52, AER65-75= 66, AER≥75= 23). Cumulative mortality from non-malignant causes (23.7%) exceeded that from lymphoma (22.9%) beginning 9 years after LPL/WM diagnosis. Conclusions: Using population data, we identified areas to improve survivorship care of LPL/WM patients, particularly for non-malignant causes of death.

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Mortality in patients with systemic lupus erythematosus and neuropsychiatric involvement: A retrospective analysis from a tertiary referral center in the Netherlands

Lupus ◽

10.1177/0961203320963815 ◽

2020 ◽

Vol 29 (14) ◽

pp. 1892-1901

Author(s):

Rory C Monahan ◽

Rolf Fronczek ◽

Jeroen Eikenboom ◽

Huub A M Middelkoop ◽

Liesbeth J J Beaart-van de Voorde ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

General Population ◽

The Netherlands ◽

Lupus Erythematosus ◽

Current Status ◽

Systemic Lupus ◽

Tertiary Referral ◽

Risk Of Death ◽

Increased Risk ◽

Specific Mortality

Objective We aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007–2018. Methods Patients visiting the tertiary referral NPSLE clinic of the Leiden University Medical Center were included. NP symptoms were attributed to SLE requiring treatment (major NPSLE) or to other and mild causes (minor/non-NPSLE). Municipal registries were checked for current status (alive/deceased). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using data from the Dutch population. Rate ratio (RR) and 95% CI were calculated using direct standardization to compare mortality between major NPSLE and minor/non-NPSLE. Results 351 patients were included and 149 patients were classified as major NPSLE (42.5%). Compared with the general population, mortality was increased in major NPSLE (SMR 5.0 (95% CI: 2.6–8.5)) and minor/non-NPSLE patients (SMR 3.7 (95% CI: 2.2–6.0)). Compared with minor/non-NPSLE, mortality was similar in major NPSLE patients (RR: 1.0 (95% CI: 0.5–2.0)). Cause-specific mortality rates demonstrated an increased risk of death due to infections in both groups, whereas death due to cardiovascular disease was only increased in minor/non-NPSLE patients. Conclusion Mortality was increased in both major NPSLE and minor/non-NPSLE patients in comparison with the general population. There was no difference in mortality between major NPSLE and minor/non-NPSLE patients.

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POS0796 SURVIVAL OF GIANT CELL ARTERITIS PATIENTS IN SLOVENIA

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.321 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 650.1-650

Author(s):

A. Hočevar ◽

A. Viršček ◽

R. Jese ◽

M. Tomsic ◽

Z. Rotar

Keyword(s):

General Population ◽

Survival Curve ◽

Standardized Mortality Ratio ◽

First Year ◽

Risk Of Death ◽

Slovenian Population ◽

Kaplan Meier ◽

Increased Risk ◽

Standardized Mortality Ratios

Background:Recent meta-analysis reported no difference in the long-term mortality of GCA patients at a population level, but an increased mortality in hospital-based cohorts1.Objectives:The aim of our study was to evaluate for the first time the survival of GCA patients in Slovenia.Methods:We included patients with clinical diagnosis of GCA supported by histology or imaging diagnosed between September 2011 and December 2019 and prospectively followed at our secondary/tertiary rheumatology center. To evaluate mortality the censor date of 24. June 2020 was used. Kaplan–Meier analysis was used to analyze mortality. Standardized mortality ratio (SMR) was calculated using data of age matched Slovenian population as the reference.Results:Between September 2011 and December 2019 we identified 309 new GCA patients (203 (65.7%) females, median (IQR) age 74.9 (67.7–80.1.7), range 53.7 to 97.5 years). Patients were followed (until death or censor date) of a median (IQR) 33.3 (17.5-60.8) months. Until the censor date 51 (16.5%) GCA patients died (24 females, 27 males). We found no significant sex related differences in the net survival estimates during the first five years of follow up (p=0.68). Figure 1 shows the survival curve of GCA patients and general population as a comparator according to Kaplan–Meier analysis. In the first year following GCA diagnosis the mortality rate was 1.9 times higher compared to general Slovenian population (95% CI 1.19 - 2.88, p=0.03). For patients who survived the first year after diagnosis the mortality was comparable to the general population (Table 1).Figure 1.Survival curve according to Kaplan–Meier analysis in GCATable 1.Standardized mortality ratios of patients who survived the first year after diagnosing GCA (ie. were followed at least one year) compared to the general populationYearsof FUObserved deathsExpected deathsSMR (95%CI)P-value2119.71.14 (0.57-2.03)0.75331416.50.85 (0.46-1.43)0.62642121.60.97 (0.60-1.49)0.98752525.01.00 (0.65-1.48)0.92162627.60.94 (0.61-1.38)0.831Legend: FU follow up; SMR Standardized mortality ratios; CI confidence intervalConclusion:GCA patients had an increased risk of death in the first year from the GCA diagnosis.References:[1]Hill CL, et al. Semin Arthritis Rheum. 2017;46(4):513-9.Disclosure of Interests:None declared

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Long-Term Mortality in Children With Ischemic Stroke: A Nationwide Register-Based Cohort Study

Stroke ◽

10.1161/strokeaha.121.034797 ◽

2021 ◽

Author(s):

Heléne E.K. Sundelin ◽

Anna Walås ◽

Jonas Söderling ◽

Peter Bang ◽

Jonas F. Ludvigsson

Keyword(s):

Ischemic Stroke ◽

Cause Of Death ◽

Mortality Risk ◽

Neurological Diseases ◽

Risk Of Death ◽

First Degree Relatives ◽

Increased Risk ◽

Specific Mortality ◽

Long Term Mortality

Background and Purpose: Ischemic stroke is a common cause of death in adults, however, mortality after pediatric ischemic stroke is not well explored. We investigate long-term and cause-specific mortality in children with ischemic stroke and their first-degree relatives. Methods: Through nationwide Swedish registers, we identified 1606 individuals <18 years old with ischemic stroke between 1969 and 2016 and their first-degree relatives (n=5714). Each individual with ischemic stroke was compared with 10 reference individuals (controls) matched for age, sex, and county of residence. Our main analysis examined 1327 children with ischemic stroke still alive 1 week after the event. First-degree relatives to children with ischemic stroke were compared with first-degree relatives to the reference individuals. Using a Cox proportional hazard regression model, the risk of overall and cause-specific mortality was computed in individuals with pediatric ischemic stroke and their first-degree relatives. Results: The mortality rate in the first 6 months was 40.1 (95% CI, 24.7–55.6) per 1000 person-years compared with 1.1/1000 in controls (95% CI, 0.3–1.9). The overall mortality risk was hazard ratio (HR)=10.8 (95% CI, 8.1–14.3) and remained elevated beyond 20 years (HR=3.9 [95% CI, 2.1–7.1]). Children with ischemic stroke were at increased risk of death from neurological diseases (HR=29.9 [95% CI, 12.7–70.3]), cardiovascular diseases (HR=6.2 [95% CI, 1.8–22.2]), cancers (HR=6.5 [95% CI, 2.6–15.9]) and endocrine, nutritional and metabolic diseases (HR=49.2 [95% CI, 5.7–420.8]). First-degree relatives to children with ischemic stroke had an increased mortality risk (HR=1.21 [95% CI, 1.05–1.39]), with the highest risk among siblings (HR=1.52 [95% CI, 1.09–2.11]) and relatives to individuals with ischemic stroke >28 days of age (HR=1.23 [95% CI, 1.06–1.42]) compared with the relatives of the controls. Conclusions: Long-term mortality increased after pediatric ischemic stroke, even 20 years later, with neurological diseases as the most frequent cause of death.

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Mortality and causes of death among people suspected of driving under the influence and testing positive for multiple substances

Scandinavian Journal of Public Health ◽

10.1177/1403494819894166 ◽

2019 ◽

Vol 48 (8) ◽

pp. 809-816

Author(s):

Karoliina Karjalainen ◽

Jari Haukka ◽

Kristiina Kuussaari ◽

Sanna Hautala ◽

Pekka Hakkarainen

Keyword(s):

General Population ◽

Causes Of Death ◽

Social Background ◽

Reference Population ◽

Elevated Risk ◽

Driving Under The Influence ◽

Finnish Population ◽

Risk Of Death ◽

Increased Risk ◽

Specific Mortality

Aims: Understanding the mortality of drug users using multiple substances is helpful in preventing the harmful effects of polydrug use. We examined overall and cause-specific mortality and differences in mortality based on social background among people suspected of driving under the influence and testing positive for multiple substances (DUIMS) compared with the general Finnish population. Methods: Register data from 785 DUIMS during 2003–2006 were studied, with a reference population ( n = 25,381) drawn from the general Finnish population. The effect of DUIMS on all-cause and cause-specific mortality was estimated using a Poisson regression model. Results: DUIMS had an increased risk of death compared with the general population (MRR 5.3, 95% CI 4.2–6.6). The most common causes of death in DUIMS were poisonings (37.9%) and suicides (13.6%), whereas in the reference population these were cardiovascular diseases (30.8%) and cancer (26.6%). The cause-specific risk of death among DUIMS was higher in all observed causes of death, except for cancer. The effect of DUIMS on mortality was modified by age, employment status and marital status; DUIMS was associated with an elevated risk of death especially in younger age groups and in singles. Conclusions: DUIMS indicates higher mortality, and DUIMS’ profiles in causes of death differ from the general population. Elevated risk for, for instance, suicidal, accidental and violent death among those using multiple substances highlights the need to also pay attention to causes of death other than poisoning/overdose.

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Population-Based Study on the All-Cause and Cause-Specific Risks of Mortality among Long-Term Opioid Analgesics Users without Cancer in Taiwan

Healthcare ◽

10.3390/healthcare9111402 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1402

Author(s):

Po-Feng Lee ◽

Chung-Yi Li ◽

Yen-Chin Liu ◽

Chang-Ta Chiu ◽

Wen-Hsuan Hou

Keyword(s):

General Population ◽

Opioid Analgesics ◽

Population Based ◽

Opioid Use ◽

Data Set ◽

Risk Of Mortality ◽

Increased Risk ◽

Underlying Causes ◽

Standardized Mortality Ratios

(1) Background: The prevalence of opioid use in Taiwan increased by 41% between 2002 and 2014. However, little is known regarding the risk of mortality among long-term opioid analgesics users who do not have cancer. This study investigated this mortality risk with an emphasis on the calendar year and patients’ age and sex. (2) Methods: This retrospective cohort study included 12,990 adult individuals without cancer who were long-term users of opioid analgesics and were randomly selected from the data set of Taiwan’s National Health Insurance program from 2000 to 2012. They were then followed up through 2013. Information on the underlying causes of death was retrieved from the Taiwan Death Registry. Age, sex, and calendar year-standardized mortality ratios (SMRs) of all-cause and cause-specific mortality were calculated with reference to those of the general population. (3) Results: With up to 14 years of follow-up, 558 individuals had all-cause mortality in 48,020 person-years (cumulative mortality: 4.3%, mortality rate: 11.62 per 1000 person-years). Compared with the general population, the all-cause SMR of 4.30 (95% confidence interval (95% CI): 3.95–4.66) was significantly higher: it was higher in men than in women, declined with calendar year and age, and was significantly higher for both natural (4.15, 95% CI: 3.78–4.53) and unnatural (5.04, 95% CI: 3.88–6.45) causes. (4) Conclusions: Long-term opioid analgesics use among individuals without cancer in Taiwan was associated with a significantly increased risk of mortality. The notably increased mortality in younger adults warrants attention. Strategies to reduce long-term opioid analgesics use, especially their overuse or misuse, are in an urgent need.

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Survival in Restless Legs Syndrome: An 11-Year Surveillance, Community-Based Population Study

Neuroepidemiology ◽

10.1159/000508855 ◽

2020 ◽

Vol 54 (5) ◽

pp. 375-382

Author(s):

Esther Cubo ◽

Carla Collazo Riobo ◽

Cesar Gallego-Nieto ◽

Miren Elizari-Roncal ◽

Teresa Barroso-Pérez ◽

...

Keyword(s):

Regression Analysis ◽

General Population ◽

Restless Legs Syndrome ◽

Cox Regression ◽

Cox Regression Analysis ◽

Restless Legs ◽

Risk Of Mortality ◽

Increased Risk ◽

Standardized Mortality Ratios

Background: A growing body of evidence relates restless legs syndrome (RLS) to an increased risk of mortality attributable to both cerebrovascular and cardiovascular events. The aim was to investigate survival in patients with RLS. Methods: This was an observational, retrospective longitudinal study of a cohort of patients followed up for 11 years. RLS was diagnosed by a physician using the International RLS Study Group criteria. Mortality was analyzed using age-standardized mortality ratios (SMR: observed/expected deaths) and Cox regression analysis. Results: Vital status was studied in a cohort of 232 patients: 181 women (78%), 96 with RLS (41.4%) with a mean age at baseline of 49.8 ± 15.0 years and a mean RLS duration of 14.1 ± 1.9 years, and 136 non-RLS (58.6%) with a mean age of 51.3 ± 14.9 years. This RLS cohort was followed up for a period of 10.4 ± 2.0 years. As of September 2019, 17 (7.3%) patients died (6 with RLS, 6.3%), and the most frequent cause was oncological (66.7%). A total of 944 person-years of observations were available for survival analysis. RLS was not associated with increased mortality in adjusted Cox regression analysis (HR = 1.12, 95% CI: 0.40–3.15), and survival was similar to that expected for the general population (SMR = 0.61, 95% CI: 0.27–1.36). Conclusions: RLS seems not to be associated with increased mortality compared to the general population. Still, studies with prospective data collection with large samples are needed to study the long-term mortality risk factors in RLS cohorts.

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