525 A population-based study of phenoconversion to parkinsonism from REM sleep behavior: a Population-based Study in the CLSA

Abstract Introduction To date, studies have estimated the phenoconversion rate from sleep clinics, using polysomnography proven RBD. However, no population-based estimates have been reported, testing to what degree possible RBD, screened by questionnaire is associated with increased risk of neurodegeneration. Methods We included those aged 45–85 years, living in one of 10 Canadian provinces in between 2012–2015 (at the baseline), recruited via three population-based sampling methods. Dream enactment behavior/possible RBD was screened using the RBD1Q single question-questionnaire. De-novo parkinsonism was defined as free of pre-existing diagnosis at the baseline with a ‘new’ diagnosis at the follow-up (205–2019). Relative risk (log-binomial regression), hazard ratio (Cox regression), incidence rate (Poisson regression) between the affected group and the symptom naïve group were assessed, adjusting for age and sex (and total years of education and language). Results Overall, 58 participants phenoconverted into parkinsonism and 53 into dementia at the follow-up (mean intervals=3.06±0.37 years). Participants with dream enactment behavior had 2.75 times higher risk to phenoconvert into parkinsonism than the symptom-free. Similarly, those with dream enactment behavior at the baseline possessed higher risk to screening positive of parkinsonism. No difference in time to phenoconversion was found between groups, The results remained robust after excluding non-RBD related symptoms, such as apnea and non-REM sleep parasomnia. Conclusion Compared to symptom-free, those with pRBD had higher risk to developing parkinsonism in near future. Support (if any):

Download Full-text

Risk of Seizures in Patients with Organophosphate Poisoning: A Nationwide Population-Based Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16173147 ◽

2019 ◽

Vol 16 (17) ◽

pp. 3147 ◽

Cited By ~ 5

Author(s):

Chieh-Sen Chuang ◽

Kai-Wei Yang ◽

Chia-Ming Yen ◽

Cheng-Li Lin ◽

Chia-Hung Kao

Keyword(s):

General Population ◽

Cox Regression ◽

Population Based ◽

Organophosphate Poisoning ◽

Research Database ◽

Population Based Study ◽

Increased Risk ◽

Taiwan National Health Insurance ◽

History Of

Objective: Previous research has demonstrated that patients with a history of organophosphate poisoning tend to have a higher risk of neurological disorder. However, research on the rate of seizure development in patients after organophosphate poisoning is lacking. This study examined whether individuals with organophosphate poisoning have an increased risk of seizures through several years of follow-up. Patients and Methods: We conducted a retrospective study on a cohort of 45,060 individuals (9012 patients with a history of organophosphate poisoning and 36,048 controls) selected from the Taiwan National Health Insurance Research Database. The individuals were observed for a maximum of 12 years to determine the rate of new-onset seizure disorder. We selected a comparison cohort from the general population that was randomly frequency-matched by age, sex, and index year and further analyzed the risk of seizures using a Cox regression model adjusted for sex, age, and comorbidities. Results: During the study period, the risk of seizure development was 3.57 times greater in patients with organophosphate poisoning compared with individuals without, after adjustments for age, sex, and comorbidities. The absolute incidence of seizures was highest in individuals aged 20 to 34 years in both cohorts (adjusted hazard ratio = 13.0, 95% confidence interval = 5.40−31.4). A significantly higher seizure risk was also observed in patients with organophosphate poisoning and comorbidities other than cirrhosis. Conclusions: This nationwide retrospective cohort study demonstrates that seizure risk is significantly increased in patients with organophosphate poisoning compared with the general population.

Download Full-text

Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽

10.3390/cancers13112844 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2844

Author(s):

Christopher J. D. Wallis ◽

Bobby Shayegan ◽

Scott C. Morgan ◽

Robert J. Hamilton ◽

Ilias Cagiannos ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Clinical Decision Making ◽

Cox Regression ◽

De Novo ◽

Population Based ◽

Population Based Study ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Download Full-text

Dietary and lifestyle inflammatory scores are associated with increased risk of metabolic syndrome in Iranian adults

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00648-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Hossein Farhadnejad ◽

Karim Parastouei ◽

Hosein Rostami ◽

Parvin Mirmiran ◽

Fereidoun Azizi

Keyword(s):

Metabolic Syndrome ◽

Positive Association ◽

Population Based ◽

Population Based Study ◽

Logistic Regression Models ◽

Increased Risk ◽

Confounding Variables ◽

Adjusted Model ◽

Diet And Lifestyle

Abstract Background In the current study, we aimed to investigate the association of dietary inflammation scores (DIS) and lifestyle inflammation scores (LIS) with the risk of metabolic syndrome (MetS) in a prospective population-based study. Methods A total of 1625 participants without MetS were recruited from among participants of the Tehran Lipid and Glucose Study(2006–2008) and followed a mean of 6.1 years. Dietary data of subjects were collected using a food frequency questionnaire at baseline to determine LIS and DIS. Multivariable logistic regression models, were used to calculate the odds ratio (ORs) and 95 % confidence interval (CI) of MetS across tertiles of DIS and LIS. Results Mean ± SD age of individuals (45.8 % men) was 37.5 ± 13.4 years. Median (25–75 interquartile range) DIS and LIS for all participants was 0.80 (− 2.94, 3.64) and 0.48 (− 0.18, − 0.89), respectively. During the study follow-up, 291 (17.9 %) new cases of MetS were identified. Based on the age and sex-adjusted model, a positive association was found between LIS (OR = 7.56; 95% CI 5.10–11.22, P for trend < 0.001) and risk of MetS, however, the association of DIS and risk of MetS development was not statistically significant (OR = 1.30;95% CI 0.93–1.80, P for trend = 0.127). In the multivariable model, after adjustment for confounding variables, including age, sex, body mass index, physical activity, smoking, and energy intake, the risk of MetS is increased across tertiles of DIS (OR = 1.59; 95% CI 1.09–2.33, P for trend = 0.015) and LIS(OR = 8.38; 95% CI 5.51–12.7, P for trend < 0.001). Conclusions The findings of the current study showed that greater adherence to LIS and DIS, determined to indicate the inflammatory potential of diet and lifestyle, are associated with increased the risk of MetS.

Download Full-text

Abstract 1158: Sudden Death in Children with Cardiomyopathy: Long Term Follow-Up from a National Population-Based Study of Childhood Cardiomyopathy

Circulation ◽

10.1161/circ.118.suppl_18.s_651-b ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Tara Bharucha ◽

Andrew M Davis ◽

Christian Turner ◽

Robert Justo ◽

Terry Robertson ◽

...

Keyword(s):

Risk Factors ◽

Primary Prevention ◽

Sudden Death ◽

Systolic Dysfunction ◽

Population Based ◽

Z Score ◽

Icd Implantation ◽

Population Based Study ◽

Increased Risk

Introduction Better data regarding the incidence and risk factors for sudden cardiac death (SCD) in children with cardiomyopathy (CM) is critical in defining appropriate primary prevention strategies. Methods The National Australian Childhood Cardiomyopathy Study is a prospective cohort study, including all children in Australia with primary CM diagnosed at 0 – 10 years of age, between 1987–1997. SCD was defined as sudden and unexpected death in children who were not hospitalized and not in congestive heart failure at the time of death. Nine subjects with sudden death as presenting symptom were excluded. Indexed echocardiographic measurements at latest follow-up were compared between subjects with SCD and survivors. Results Study criteria were met by 291 children. Mean duration of follow-up was 9.2 years. The incidence of sudden death relative to each CM type, for all cases and as a proportion of deaths, is shown in the Table : Incidence of SCD by CM type. SCD incidence was significantly associated with CM type, for all cases ( p = 0.006) and when only those subjects who died were considered ( p = 0.005), with LVNC and RCM having up to 4 times the risk of other CM types. Children with familial DCM had a significantly higher rate of SCD than subjects with non-familial CM (12% vs 3%; p = 0.028), however, familial CM was not a risk factor in other CM types. DCM SCD subjects had larger LVEDd Z score than survivors (median 5.53 vs 1.16; p <0.0001) and lower FS Z score (median −9.23 vs −0.51; p = 0.0025). HCM SCD subjects had thicker LVPW dimension Z scores than survivors (median 4.63 vs 1.18; p = 0.007). Twelve subjects (2 DCM, 8 HCM and 2 LVNC) underwent ICD implantation (8/12 for primary prevention). Conclusions: This population based study defines new risk factors for sudden death in children with CM. RCM is well known to have a high incidence of SCD. In addition, children with LVNC and those with DCM who have severe dilatation, systolic dysfunction or familial DCM are at increased risk of sudden death.

Download Full-text

Headache as a risk factor for dementia: A prospective population-based study

Cephalalgia ◽

10.1177/0333102413513181 ◽

2013 ◽

Vol 34 (5) ◽

pp. 327-335 ◽

Cited By ~ 22

Author(s):

Knut Hagen ◽

Eystein Stordal ◽

Mattias Linde ◽

Timothy J Steiner ◽

John-Anker Zwart ◽

...

Keyword(s):

Risk Factor ◽

Cohort Study ◽

Cox Regression ◽

Subsequent Development ◽

Population Based ◽

Health Study ◽

Cox Regression Analysis ◽

Hazard Ratios ◽

Increased Risk

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.

Download Full-text

Impact of putative chemopreventative agents on prostate cancer diagnosis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.40 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 40-40

Author(s):

Hanan Goldberg ◽

Faizan Moshin ◽

Zachary William Abraham Klaassen ◽

Thenappan Chandrasekar ◽

Christopher Wallis ◽

...

Keyword(s):

Prostate Cancer ◽

Cox Regression ◽

Large Population ◽

Multivariable Analysis ◽

Population Based ◽

Cumulative Exposure ◽

Population Based Study ◽

Diagnosis Rate ◽

The Impact

40 Background: Prostate cancer (PC) is the most common non-cutaneous cancer in Canadian men and the third most common cause of cancer death in Canada. Several studies have shown that use of commonly prescribed medications, including those used for diabetes and hypercholesterolemia, is associated with improved survival in various malignancies, including PC. There has not been any large population-based study, examining the effects of these and other commonly prescribed medications, on the rate of PC diagnosis, over a 20 years follow-up period. Methods: A retrospective population-based study using data from the institute of clinical evaluative sciences, including all male patients aged 65 and above in Ontario who have had a negative first prostate biopsy between 1994 and 2016. We assessed the impact of commonly prescribed medications on PC diagnosis. The medications included Statins (hydrophilic and hydrophobic), diabetes drugs (metformin, insulins, sulfonylureas, and thizolidinedions), proton pump inhibitors, 5 alpha reductase inhibitors, and alpha blockers. Time dependent Cox regression proportional hazards models were performed determine predictors of PC diagnosis. Medication exposure was time varying and modeled as “ever” vs. “never” use or as cumulative exposure for 6 months of usage. A priori variables included in the model included age, ADG comorbidity score, rurality index, index year, and all medications. Results: A total of 51,415 men were analyzed over a mean (SD) follow-up time of 8.06 (5.44) years. Overall, 10,466 patients (20.4%) were diagnosed with PC, 16,726 (32.5%) had died, and 1,460 (2.8%) patients died of PC. On multivariable analysis increasing age and rurality index were associated with higher PC diagnosis rate, while a more recent index year, and usage of hydrophilic statins was associated with a lower diagnosis rate in both “ever” vs. “never” and cumulative models (HR 0.832, 95% CI 0.732-0.946, p = 0.005, HR 0.973 95% CI 0.951-0.995, p = 0.016, respectively). Conclusions: Hydrophilic statins are associated with a clinically significant lower PC diagnosis. To our knowledge this is the first study demonstrating a clear advantage of one group of statins (hydrophilic) over another (hydrophobic) in PC prevention.

Download Full-text

Endogenous sex hormone levels in men are not associated with risk of venous thromboembolism: the Tromsø study

Acta Endocrinologica ◽

10.1530/eje-08-0888 ◽

2009 ◽

Vol 160 (5) ◽

pp. 833-838 ◽

Cited By ~ 19

Author(s):

Johan Svartberg ◽

Sigrid K Brækkan ◽

Gail A Laughlin ◽

John-Bjarne Hansen

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Free Testosterone ◽

Population Based ◽

Sex Hormone ◽

Population Based Study ◽

Hormone Levels ◽

Increased Risk ◽

The Impact

ObjectivesLow testosterone levels in men have been associated with cardiovascular risk factors and atherosclerosis and lately also an increased risk of both cardiovascular disease (CVD) and all-cause mortality. As arterial CVDs and venous thromboembolism (VTE) have been shown to share common risk factors, the purpose of the present study was to determine the impact of endogenous sex hormone levels on the incidence of VTE in a cohort of men.DesignA prospective, population-based study.MethodsSex hormone measurements were available in 1350 men, aged 50–84, participating in the Tromsø study in 1994–1995. First, lifetime VTE-events during the follow-up were registered up to September 1 2007.ResultsThere were 63 incident VTE-events (4.5 per 1000 person-years) during a mean of 10.4 years of follow-up. Age was significantly associated with increased risk of VTE; men 70 years or older had a 2.5-fold higher risk of VTE (HR 2.47, 95% CI 1.19–5.12), compared with those between 50 and 60 years of age. In age-adjusted analyses, endogenous sex hormones levels were not associated with risk of VTE; for each s.d. increase, hazards ratios (95% CI) were 1.06 (0.83–1.35) for total testosterone, 1.02 (0.79–1.33) for free testosterone, and 1.27 (0.94–1.71) for ln-estradiol. In dichotomized analyses comparing men in the lowest total and free testosterone quartile with men in the higher quartiles, hypoandrogenemia was not associated with risk of VTE.ConclusionsIn this population-based study of middle-aged and older men, endogenous sex hormone levels were not associated with 10-year risk of VTE.

Download Full-text

Children With Appendectomy Have Increased Risk of Future Sepsis: Real-world Data in Taiwan

10.22541/au.161248697.75690035/v1 ◽

2021 ◽

Author(s):

Liao Tzu-Han ◽

Meng Che Wu ◽

Cheng-Li Lin ◽

Chien-Heng Lin ◽

James Cheng-Chung Wei

Keyword(s):

Cox Regression ◽

Propensity Score Analysis ◽

Population Based ◽

Research Database ◽

Real World Data ◽

Parental Occupation ◽

Increased Risk ◽

Future Risk ◽

The Relationship

Backgrounds Appendectomy is one of the most commonly performed surgeries worldwide. Sepsis is an major etiology of morbidity and mortality in children. Our preliminary research revealed a positive correlation among appendectomy and future risk of sepsis in adults. However, to date, the relationship among appendectomy and future risk of sepsis in children remains unknown. The aim of this research was to investigate the relationship among appendectomy and hazard of future sepsis in children. Methods We applied a nationwide population-based cohort to assess whether children who received appendectomy were at increased risk of subsequent sepsis. Overall, 57261 subjects aged below 18 undergoing appendectomy as appendectomy group and 57261 matched controls were identified as non-appendectomy group from the National Health Insurance Research Database in Taiwan. We use propensity score analysis to match age, sex, urbanization level, and parental occupation at the ratio to 1:1. Multiple Cox regression and stratified analyses were used to appraise the adjusted hazard ratio (aHR) for developing sepsis in children. Results Children who received appendectomy had a 2.63 times higher risk of developing sepsis than those who did not, and the risk was even higher in children aged under 6 years. Patients with <1 year follow-up showed a 5.64-fold risk of sepsis in the appendectomy cohort. Patients with 1–4 and ≥5 years’ follow-up showed a 2.41- and 2.02-times risk of sepsis. Conclusion Appendectomy was correlative to a 2.63-fold increased future sepsis risk in children, and the risk in younger patients aged <6 years was even higher. More studies to interpret the possible biological mechanisms of the associations among sepsis and appendectomy are warrant

Download Full-text

Utility of Inferior Vena Cava Filter in the Management of Venous Thromboembolism Among Patients with Brain Metastases: A Population-Based Study

Blood ◽

10.1182/blood-2020-138790 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 47-48

Author(s):

Vaibhav Kumar ◽

Ann M Brunson ◽

Anjlee Mahajan ◽

Nigel S. Key ◽

Ted Wun

Keyword(s):

Brain Metastasis ◽

Brain Metastases ◽

Regression Model ◽

Cox Regression ◽

Vena Cava ◽

Population Based ◽

Population Based Study ◽

Risk Of Death ◽

Icd 10

Background: Brain metastases are a frequently occurring and devastating complication of solid organ malignancies. Individuals with brain metastases are noted to be high risk for venous thromboembolism (VTE) due to hypercoagulability from their malignancy, immobility, and need for cancer directed therapies. The management of VTE in patients with brain metastases is challenging due to the risk of intracranial hemorrhage (ICH) with therapeutic anticoagulation. Inferior vena cava filter (IVCF) are often used to mitigate the risk of ICH, however the utility of this practice and the impact on survival is not clear. Methods: We performed a retrospective cohort study using the linked California Cancer Registry (CCR) and California Patient Discharge Database (PDD) between 2005-2017 with follow up available to 2018. We identified individuals with breast and lung cancer (because they are common), and renal cell carcinoma and melanoma (because of bleeding tendency of brain metastases) who had an incident hospitalization with VTE (either pulmonary embolism, deep vein thrombosis or both). Brain metastasis were identified using the presence of International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) code 198.3 or ICD-10-CM code C79.31 present anytime in PDD and cases were classified as having brain metastases if the code was present prior to or at the time of the index VTE. Cases with multiple malignancies were excluded. ICD-9-CM code 38.7 and ICD-10-CM code 02HV was used to identify patients who received an IVCF. Univariate analysis was used to determine differences in baseline characteristics between those that did and did not receive an IVCF. A logistic regression model that included patient and index VTE hospital characteristics was used to develop a propensity score for IVCF placement. The primary outcomes were 30-day mortality and 180-day intracranial hemorrhage (ICH) determined by ICD codes. A Cox proportional hazards model, inverse propensity weighted for IVCF placement, was used to assess the effect of IVCF placement (as a time-dependent variable) on 30-day mortality. The effect of IVCF on ICH was assessed with a 1:3 propensity matched Fine-Gray model, accounting for the competing risk of death. Results: There were 17,182 patients with a diagnosis of VTE present on admission and an active first primary cancer diagnosis of interest, of these 3,309 (19.3%) had a diagnosis of brain metastasis with median follow-up of 96.8 months. The baseline characteristics of patients are summarized in Table 1. Among patients with brain metastases, 757 of 3309 (22.9%) had an IVCF inserted versus 1801 of 13873 (13.0%) in those without brain metastases (p<0.001). In a multivariable logistic regression model the presence of brain metastasis was an independent predictor for the placement of IVCF (Odds Ratio (OR) 1.84 (95% CI 1.64-2.05). Using balanced (standardized mean difference less than 0.1 for all covariates included in the model) IPW-adjusted Cox regression model, the use of IVCF did not reduce the 30-day risk of death in those with acute VTE (Hazard Ratio (HR) 1.08 (95% CI 0.95-1.23). The presence of brain metastases was associated with a higher 30-day risk of death (HR 1.23 (95% CI 1.13- 1.35). Using IPW-adjusted Cox model restricted to those with brain metastasis, IVCF use was associated with a trend towards reduced 30-day risk of death (HR 0.86 (95% CI 0.73-1.01). In a propensity matched Cox regression competing risk model, the presence of brain metastases was significantly associated with an increased 180-day risk of ICH (HR 6.91 (95% CI 3.54-13.48), with no difference for those that received an IVCF (HR 1.31 (95% CI 0.85-2.01). When compared to breast cancer patients, those with lung cancer had lower risk of ICH (HR 0.28, CI 0.13-0.64), but melanoma and renal cell cancer did not have higher risk. Conclusions: This real-world retrospective population-based study demonstrated the use of IVCF was higher for patients with brain metastases among these four tumor types. There was a suggestion of reduced short-term mortality associated with IVCF placement in VTE patients and brain metastases, but this was not statistically significant. Although limited by the lack of data on anticoagulation use, there was no effect of IVCF placement on the risk of ICH. Randomized clinical trials are needed to determine the effect of IVCF on clinically relevant outcomes for VTE in patients with brain metastasis. Disclosures Key: Takeda: Research Funding; Grifols: Research Funding; Uniqure: Consultancy; Novo Nordisk: Other: Chair of Grants Committee. Wun:Glycomimetics, Inc.: Consultancy.

Download Full-text

The Impact of Prior Malignancies on Second Malignancies and Survival in MM Patients: A Population-Based Study

Blood ◽

10.1182/blood.v128.22.3246.3246 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3246-3246

Author(s):

Gudbjorg Jonsdottir ◽

Sigrún H. Lund ◽

Magnus Björkholm ◽

Ingemar Turesson ◽

Anders Wahlin ◽

...

Keyword(s):

Cancer Diagnosis ◽

Hematological Malignancies ◽

Cox Regression ◽

Population Based ◽

Second Malignancies ◽

Advisory Committees ◽

Population Based Study ◽

Risk Of Death ◽

Increased Risk ◽

Prior Malignancy

Abstract Background Awareness of second malignancies in patients with multiple myeloma (MM) has been increasing during recent years. We have previously shown that second malignancies are associated with a decreased life expectancy in MM patients. Information regarding prior and second malignancies in MM is limited as these patients are often excluded from clinical trials and previously published results from other groups have been conflicting. In the present study we aimed to evaluate two hypotheses. Firstly we hypothesize that prior malignancy is a proxy for genetic instability that could be a risk factor for subsequent malignancy development in MM patients. There is limited data regarding this association in the literature and in two recent registry studies the results were inconclusive. Secondly, to further assess the clinical implication of prior malignancies in MM patients we assessed survival in these patients compared to MM patients without a history of prior malignancy. Patients and Methods All patients diagnosed with MM from January 1, 1973 to December 31, 2013 were identified from the Swedish Cancer Register. All prior and subsequent malignant diagnoses were identified through cross-linkage within the registry. A Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) where prior malignancy was compared in MM patients who developed a subsequent malignancy and MM patients who did not. In another Cox regression model, survival was compared in MM patients with and without a prior malignancy. The same method was used to estimate if there was a dose-dependent relationship, i.e. if an increasing number of prior malignancies was associated with a poorer outcome. Results A total of 22,359 patients were diagnosed with MM during the study period. Of these, 2,620 (12%) patients had one or more prior malignancy diagnosis at the time of MM diagnosis and 1,243 (6%) patients developed subsequent malignancies. Among the MM patients who developed a subsequent malignancy, 148 (12%) had a prior malignancy diagnosis. Hematological malignancies were 7% of prior malignancies and 17% of subsequent malignancies. MM patients with a prior malignancy diagnosis did not have increased risk of developing a subsequent malignancy compared to MM patients without a prior malignancy (HR 1.0, 95% CI 0.9-1.2). MM patients with a prior malignancy diagnosis had a statistically significant 10% increased risk of death (HR=1.1, 95% CI 1.1-1.2, p<0.001) compared to MM patients without a prior malignancy diagnosis. MM patients with 2 or more prior malignancy diagnoses had a 20% increased risk of death (HR=1.2, 95% CI 1.1-1.4, p=0.002) compared to MM patients without a prior malignancy diagnosis (Figure). Summary and Conclusions In our large population-based study we found that prior malignancy negatively impacts survival in MM patients and that more than one prior malignancy decreases survival even further. Interestingly, a prior malignancy did not increase the risk of developing a subsequent malignancy in MM patients. We confirmed prior reports of solid tumors being more common than hematological malignancies, both prior and subsequent to the MM diagnosis. A prior malignancy was associated with a reduced survival in MM patients without being a risk factor for subsequent malignancies. The underlying explanation for this is probably multifactorial, and could include reduced dose intensity of chemotherapy, complications from treatment, or that MM that develops after another malignancy might be biologically different. Given the increase of cancer survivors in general, our findings are of importance both for the individual patients and their families as well as for the treating physician. Figure Survival in MM patients without a prior cancer diagnosis compared to MM patients with one and two or more prior cancer diagnoses Figure. Survival in MM patients without a prior cancer diagnosis compared to MM patients with one and two or more prior cancer diagnoses Disclosures Landgren: Takeda: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Medscape: Employment, Other: Chairman for Medscape Myeloma Program; Amgen: Speakers Bureau; Celgene: Speakers Bureau; BMS: Speakers Bureau.

Download Full-text