Population Based Study of Cytogenetic Abnormalities in Addition to Philadelphia (Ph) Chromosome in Patients with Chronic Myeloid Leukaemia (CML) and Impact on Survival

Abstract Ph chromosome is the hallmark of CML. However there are few reports of additional chromosomal abnormalities at the time of diagnosis and the impact this has on overall survival (OS). [NT1] The Cytogenetic laboratory at this hospital provides a regional service as a single facility. The data from this laboratory was combined with survival information to evaluate the impact of additional chromosomal changes on outcomes in patients with CML. Methods: This is a retrospective population based study, it was not possible to obtain consent from individual patients and details about haematological parameters or treatments delivered were not available. The aim was to evaluate if cytogenetic changes should be considered in addition to established risk scoring systems. Patients were classified as complex-Philadelphia (Ph) if they had t(9;22)(q31;q34) with additional chromosomal abnormalities. Impact of individual additional abnormalities was analysed and then the effect was stratified according to presence of chromosomal gains, deletions or translocations. Few cases who had normal cytogenetics on their first sample as they were initially treated elsewhere. Results: 1129 patients were diagnosed with CML between 1985 and 2013, with 4760 samples analysed. The median age of the patient was 52.4 years (4.3-103, 602 male; 511 female; 16 unknown). Median follow up was 6.4 years [0-26.8 years, 725/1129 (64.2%) had follow-up more than 10 years]. End point for analysis was probability of survival at 10yr. 194/1129 (17.2%) had complex-Ph at diagnosis, 759/1129 (67.2%) had standard Ph, 77/1129 (6.8%) had negative cytogenetics and in 34/1129 (3%) cytogenetic analysis failed at diagnosis. Patients with standard Ph translocation had significantly better chance of achieving cytogenetic CR than those with complex-Ph (23.4% vs. 13.4%, p<0.001). OS was significantly better in patients below the age of 45 (65% vs 25% p <0.0001). OS was also better in patients diagnosed after 2000 (67 % vs 40 %, p<0.0001). In univariate analysis OS was significantly lower with trisomy 8 (10% vs 50%, p<0.0001), del(5q) [NT2] (20% vs 50%, p=0.001), other deletions (12% vs 48%, p=0.0005), del 17( 48% vs. 0%, p<0.0001), add 21 (50% vs. 0%, p<0.0001), any translocations (50% vs. 22%, p<0.0001), der 22 or iso 17 (48% vs. 10%, p<0.0001), any deletions (50% vs. 20%, p<0.0001) and variant Ph translocations (50% vs 22%, p=0.004). In multivariate analysis, excluding year of diagnosis, age group (HR 1.93, 95% CI:1.6-2.4 P=<0.0001), complex t(9;22;v) (HR 1.8, 95% CI:1.0-3.1, P=0.035), del(17q) (HR 3.8, 95% CI:1.1-12.6, P=0.033), translocations (HR:1.6, 95% CI: 1.1-2.25, p=0.013), trisomy 8 (HR: 1.76, 95% CI: 1.19-2.65, p=0.005), add 21 (HR: 3.21, 95% CI: 1.65-6.25, p=0.001) and der 22 or iso17 (HR: 1.57, 95% CI: 1.1-2.25, p=0.013) were independently associated with inferior OS. Number of risk factors in individual patients was used to design a scoring system. Patients with 0 risk factor (70% OS at 10 yr.), 1 risk factor (40% OS at 10 years), 2 risk factors (22% OS at 10 years) or more than 3 risk factors (12% OS at 10 years) had incrementally reduced OS. This was true of patients diagnosed before and after 2000. This analysis suggests that incorporating nature of karyotype at diagnosis can refine established scoring systems. However this data needs to be analysed with larger patient population to include all established risk factors and the effect of therapeutic measures. Disclosures Cavet: Novartis: Research Funding; BMS: Research Funding.

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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.

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Are sleep problems and non-specific health complaints risk factors for chronic pain? A prospective population-based study with 17 year follow-up

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2012.04.001 ◽

2012 ◽

Vol 3 (4) ◽

pp. 210-217 ◽

Cited By ~ 26

Author(s):

Anne K. Nitter ◽

Are H. Pripp ◽

Karin Ø. Forseth

Keyword(s):

Risk Factors ◽

Chronic Pain ◽

Sleep Problems ◽

Population Based ◽

Chronic Widespread Pain ◽

Health Complaints ◽

Widespread Pain ◽

Population Based Study ◽

Specific Health

AbstractIntroductionChronic musculoskeletal pain represents a significant health problem among adults in Norway. The prevalence of chronic pain can be up to 50% in both genders. However, the prevalence of chronic widespread pain is significantly higher in females than in males. Chronic widespread pain is seen as the end of a continuum of pain. There is rather sparse knowledge about the incidence of pain in initially pain free individuals and the course of self-reported pain over time. Moreover, little is known about risk factors for incidence of chronic pain or prognostic factors for the course of self-reported pain. We believe that such knowledge may contribute to develop strategies for treatment at an early stadium of the pain condition and thereby reduce the prevalence of chronic pain included chronic widespread pain.Aims of the studyThe aims of this study were threefold: (1) to calculate the incidence of self-reported musculoskeletal pain in a female cohort, (2) to describe the course of pain and (3) to investigate whether or not health complaints and sleep problems are predictive factors for onset of pain or prognostic factors for the course of pain.MethodsThis is a prospective population-based study of all women between 20 and 50 years who were registered in Arendal, Norway, in 1989 (N = 2498 individuals). A questionnaire about chronic pain (pain >3 months duration in muscles, joints, back or the whole body), modulating factors for pain, sleep problems and seven non-specific health complaints was mailed to all traceable women, in 1990 (N =2498), 1995 (n = 2435) and 2007 (n = 2261). Of these, 1338 responded on all three occasions. Outcome measures were presence and extent of chronic pain.ResultsThe prevalence of chronic pain was 57% in 1990 and 61% in 2007. From 1990 to 2007, 53% of the subjects changed pain category. The incidence of chronic pain in initially pain free individuals during follow-up was 44%, whereas the recovery rate was 25%. Impaired sleep quality predicted onset of chronic pain. There was a linear association between the number of health complaints and the incidence of chronic pain in initially pain free individuals. Equivalent results were found for persistence of pain and worsening of pain.ConclusionThe prevalence of chronic pain was rather stable throughout the follow-up period, but the prevalence of chronic widespread pain increased. Individual changes in pain extent occurred frequently. The presence of sleep disturbances and number of health complaints predicted onset, persistence and worsening of pain.ImplicationsSleep problems must be thoroughly addressed as a possible risk factor for onset or worsening of pain. Elimination of sleep problems in an early phase is an interesting approach in treating chronic pain. More research is needed to illuminate the possible pathogenetic relations between pain, non-specific health complaints, sleep problems and also depression.

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Anti-Psychotic Medication and the Pattern of Cardiovascular Risk Factors: A Population Based Study (The Ayrshire Diabetes Follow-Up Cohort (ADOC) Study)

Journal of Addiction Research & Therapy ◽

10.4172/2155-6105.1000343 ◽

2017 ◽

Vol 08 (05) ◽

Author(s):

Lee E Sit ◽

Mario Hair ◽

Lyall Cameron ◽

Andrew Collier ◽

Ammar Abdeen ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Population Based ◽

Anti Psychotic ◽

Population Based Study

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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.

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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.

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