Calendar Year-matched General Population Research Articles

Antipsychotic Use and Mortality in Persons with Alcohol-Related Dementia or Wernicke-Korsakoff Syndrome: A Nationwide Register Study in Finland.

Research on the use of psychotropic drugs in people with alcohol-related neurocognitive disorders is virtually nonexistent. We examined the prevalence of antipsychotic drug use and its effect on mortality among patients with Wernicke-Korsakoff syndrome (WKS) or alcohol-related dementia (ARD). In this nationwide register study, we collected data on the medication use and mortality of all persons aged ≥40 diagnosed with WKS (n = 1149) or ARD (n = 2432) between 1998 and 2015 in Finland. We calculated the prevalence of antipsychotic use within one year of diagnosis and the adjusted cumulative mortality of antipsychotic users versus non-users in relation to the age-, sex-, and calendar year-matched general population. Of the WKS and ARD patients, 35.9% and 38.5%, respectively, purchased one or more antipsychotic drugs in the year following diagnosis. The adjusted cumulative mortality of the antipsychotic users was significantly lower than that of non-users in both the WKS and ARD groups, where the adjusted hazard ratios (95% CI) were 0.85 (0.72-0.99) and 0.73 (0.65-0.81), respectively. WKS and ARD patients using antipsychotics were less likely to die of alcohol-related causes than antipsychotic non-users, but the difference was significant only in the ARD group. This population-based study shows that antipsychotic use is common in patients with WKS or ARD. In contrast to other dementia studies, our results indicate that the mortality of antipsychotic users is significantly lower than that of non-users. The lower mortality could be explained by decreased alcohol use and better healthcare coverage in antipsychotic users.

Incidence and mortality of alcohol-related dementia and Wernicke-Korsakoff syndrome: A nationwide register study.

BackgroundEpidemiological data on alcohol‐related cognitive disorders are scarce. Up‐to‐date population‐based incidence and mortality rates for Wernicke‐Korsakoff syndrome (WKS) and alcohol‐related dementia (ARD) are necessary to understand the burden of these diseases.MethodsWe collected diagnostic data from the Finnish Hospital Discharge Register and mortality data from Statistics Finland for all persons aged ≥40 years who had received a diagnosis of WKS (n = 1149) or ARD (n = 2432) between 1998 and 2015 in Finland. We calculated the incidences and mortality in relation to the age‐, sex‐ and calendar year‐matched general population. Causes of death were ascertained from death certificates.ResultsFor WKS, the incidence per 100,000 person‐years (95% confidence interval (CI)) was 3.7 (3.4–3.9) in men and 1.2 (1.1–1.3) in women. For ARD, the incidence was 8.2 (7.9–8.6) in men and 2.1 (1.9–2.3) in women. The incidence of WKS peaked in people aged 50–59 years and the incidence of ARD in people aged 70–79 years. The standardized mortality ratio (95% CI) was 5.67 (5.25–6.13) in WKS patients and 5.41 (5.14–5.70) in ARD patients. Most of the excess mortality resulted from alcohol‐related causes.ConclusionsTo our knowledge, this is the first study describing population‐based incidence and mortality rates, sex‐segregated data and causes of death in patients with WKS or ARD. Our results establish a point of reference for the incidence of WKS and ARD and show the high mortality and poor prognosis of these disorders.

Stroke and Risk of Mental Disorders Compared With Matched General Population and Myocardial Infarction Comparators.

Accurate estimates of risks of poststroke outcomes from large population-based studies can provide a basis for public health policy decisions. We examined the absolute and relative risks of a spectrum of incident mental disorders following ischemic stroke and intracerebral hemorrhage. During 2004 to 2018, we used Danish registries to identify patients (≥18 years and with no hospital history of mental disorders), with a first-time ischemic stroke (n=76 767) or intracerebral hemorrhage (n=9344), as well as age-,sex-, and calendar year-matched general population (n=464 840) and myocardial infarction (n=92 968) comparators. We computed risk differences, considering death a competing event, and hazard ratios adjusted for income, occupation, education, and history of cardiovascular and noncardiovascular comorbidity. Compared with the general population, following ischemic stroke, the 1-year risk difference was 7.3% (95% CI, 7.0-7.5) for mood disorders (driven by depression), 1.4% (95% CI, 1.3-1.5) for organic brain disorders (driven by dementia and delirium), 0.8% (95% CI, 0.7-0.8) for substance abuse disorders (driven by alcohol and tobacco abuse), and 0.5% (95% CI, 0.4-0.5) for neurotic disorders (driven by anxiety and stress disorders). For suicide, risk differences were near null. Hazard ratios were particularly elevated in the first year of follow-up, ranging from a 2- to a 4-fold increased hazard, decreasing thereafter. Compared with myocardial infarction patients, the 1-year risk difference was 4.9% (95% CI, 4.6 to 5.3) for mood disorders, 1.0% (95% CI, 0.8 to 1.1) for organic brain disorders, 0.1% (95% CI, 0.0 to 0.2) for substance abuse disorders, but -0.2% (95% CI, -0.2 to -0.1) for neurotic disorders. Hazard ratios during the first year of follow-up were elevated 1.1- to 1.8-fold for mood, organic brain, and neurotic disorders, while decreased 0.8-fold for neurotic disorders. The considerably greater risks of mental disorders following a stroke, particularly mood disorders, underline the importance of mental health evaluation after stroke.

Promyelocytic Leukemia Patients Surviving the Critical Initial Phase Have Survival Equivalent to That of the Calendar Year-, Sex-, and Age-Matched General Population

BackgroundAcute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) frequently presenting with a life-threatening coagulopathy. Fatal bleedings such as intracranial haemorrhage are common initial disease manifestations and contribute to a substantial risk of early death in APL. Patients surviving the critical initial disease phase, however, have excellent outcomes with currently used combinations of all-trans retinoic acid (ATRA) in combination with chemotherapy or arsenic trioxide (ATO). Time-points from which overall survival of cancer patients equalize to that of an age-, sex-, and calendar year-matched general population has become an area of increasing interest in clinical trials as well as for direct patient counselling.AimI) To report crude relative survival for de novo APL patients and for the subset of patients surviving the critical initial disease phase and II) to explore associations between well-established clinical risk factors and normalization of survival.Methods107 de novo APL patients diagnosed between January 2000 and December 2014 (15 years) were identified in the Danish National Acute Leukemia Registry (DNLR), which has coverage of more than 99%. The presence of the PML-RARA fusion gene (t(15;17)(q22;q12)) was documented in all patients. Clinical information was retrieved from DNLR and/or from local medical chart reviews. The survival of an age- sex-, and calendar year-matched background population was constructed using data from the Human Mortality Database. Standardized mortality ratios (SMR) in APL were determined at diagnosis and conditional on reaching progression-free (no death or relapse) survival (PFS) 30 (PFS30), 60 (PFS60), and 90 (PFS90) days after diagnosis. The effect of clinical risk factors (gender, Sanz score, WHO performance status, age ≥/<60 years) on the excess mortality were tested in an excess hazards model. This model focusses on estimating the effect of risk factors on the excess hazards, i.e. the additional hazards on top of the usual hazards rate in a matched population.ResultsMedian age was 50 years and male:female ratio was 1.38. 28% of the patients had a Sanz risk score of 1 (platelet count >40x109/L and leukocyte count ≤10x109/L), 38% had a Sanz risk score of 2 (platelet count ≤40x109/L and leukocyte count ≤10x109/L), and 34% had a Sanz risk score of 3 (leukocyte count >10x109/L). At diagnosis, the standardized mortality ratio for APL patients was 4.76 (95% CI 3.25-6.72), but the SMR rapidly decreased to 2.10 (1.15-3.53) and 1.52 (0.73-2.79) after PFS30 and PFS60, respectively. For the APL patients reaching PFS90, the SMR was 1.22 (0.53-2.41). Subgrouping according to baseline risk factors revealed important differences in SMR at baseline but their prognostic relevance diminished after reaching PFS90 (Figure 1A). The small values of the base-line excess hazards from 90 days onwards (Figure 1B) partially confirm the conclusion from the SMR study. Furthermore, the effect of the risk factors on the excess hazards shows an increased risk for older patients, patients with a Sanz score = 3, and patients with a WHO performance score >= 2 (Table 1).ConclusionsAPL patients with de novo disease surviving the critical initial phase have excellent outcomes and survival equivalent to a matched background population already at PFS90. [Display omitted] DisclosuresSeverinsen:ARIAD: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Oestgaard:Pfizer: Other: Travel expences; The Danish Cancer Society: Research Funding. Schöllkopf:Karyopharm Therapeutics: Research Funding; Pfizer: Other: Travel expences; Teva: Other: Travel expences. El-Galaly:Roche: Other: Travel funding.

Estimated Loss of Lifetime Employment Duration for Patients Undergoing Maintenance Dialysis in Taiwan.

An accurate estimate of the loss of lifetime employment duration resulting from kidney failure can facilitate comprehensive evaluation of societal financial burdens. All patients undergoing incident dialysis in Taiwan during 2000-2017 were identified using the National Health Insurance Research Database. The corresponding age-, sex-, and calendar year-matched general population served as the referents. The survival functions and the employment states of the index cohort (patients on dialysis) and their referents for each age strata were first calculated, and then extrapolated until age 65 years, where the sum of the product of the survival function and the employment states was the lifetime employment duration. The difference in lifetime employment duration between the index and referent cohort was the loss of lifetime employment duration. Extrapolation of survival function and relative employment-to-population ratios were estimated by the restricted cubic spline models and the quadratic/linear models, respectively. A total of 83,358 patients with kidney failure were identified. Men had a higher rate of employment than women in each age strata. The expected loss of lifetime employment duration for men with kidney failure was 11.8, 7.6, 5.7, 3.8, 2.3, 1.0, and 0.2 years for those aged 25-34, 35-40, 41-45, 46-50, 51-55, 56-60, and 61-64 years, respectively; and the corresponding data for women was 10.5, 10.1, 7.9, 5.6, 3.3, 1.5, and 0.3 years, respectively. The values for loss of lifetime employment duration divided by loss of life expectancy were all >70% for women and >88% for men across the different age strata. The sensitivity analyses indicated that the results were robust. The loss of lifetime employment duration in patients undergoing dialysis mainly originates from loss of life expectancy.

Causes that Contribute to the Excess Mortality Risk in Multiple Sclerosis: A Population-Based Study

Background: Lifespan is 6–10 years shorter in multiple sclerosis (MS), but the reasons remain unclear. Using linked clinical- and population-based administrative health databases, we compared cause-specific mortality in an MS cohort to the general population. Methods: MS patients in British Columbia (BC), Canada, were followed from the later of first MS clinic visit or January 1, 1986, to the earlier of death, emigration, or December 31, 2013. Comprehensive mortality information was obtained by linkage to BC’s multiple-cause-of-death mortality data. Causes were grouped using International Classification of Disease codes. Standardized mortality ratios (SMRs) were calculated for underlying cause, and relative mortality ratios (RMRs) for any mention cause, by comparison to mortality rates in the age-, sex-, and calendar year-matched general population. Cause-specific relative mortality was explored by sex and disease course (relapsing onset and primary progressive). Results: Among 6,629 MS patients with 104,236 patient-years of follow-up, 1,416 died. The all-cause mortality risk was increased relative to the general population (SMR 2.71; 95% CI 2.55–2.87). MS was the underlying cause in 50.4%, and a mentioned cause in 77.9%, of deaths. Mortality by underlying cause was higher than expected for genitourinary disorders/infections (SMR 3.55; 95% CI 2.25–5.32), respiratory diseases/infections (SMR 2.69; 95% CI 2.17–3.28), suicide (SMR 2.40; 95% CI 1.61–3.45), cardiovascular disease (SMR 1.57; 95% CI 1.36–1.81), and other infections/septicemia (SMR 1.83; 95% CI 1.15–2.78). Risks of death due to overall cancer, accidents, digestive system disorders, and endocrine/nutritional diseases as underlying causes were similar to the general population. However, mortality with any mention of accidents (RMR 2.71; 95% CI 2.22–3.29) or endocrine/nutritional diseases (RMR 1.75; 95% CI 1.46–2.09) was greater. Bladder cancer mortality was increased in women (SMR 3.87; 95% CI 1.42–8.42) but not men. No notable differences were observed by disease course. Conclusions: MS itself was the most frequent underlying cause of death. Infections (genitourinary, respiratory, and septicemia), suicides, cardiovascular disease, and accidents contributed significantly to the increased risk of death. Some findings differed by sex, but not disease course. Multiple-cause death data offer advantages over “traditional” use of underlying cause only.

Risk of arterial and venous thromboembolism in patients with atrial fibrillation or flutter: A nationwide population-based cohort study

BackgroundPatients with atrial fibrillation or flutter (AFF) are at increased risk of ischemic stroke, but their risk of other thromboembolic events remains less clear. MethodsDuring 2004–2013, we conducted a nationwide population-based cohort study using Danish medical registries. We identified all patients with first-time AFF and sampled a sex-, age-, and calendar year-matched general population comparison cohort without AFF. For myocardial infarction, peripheral embolism, ischemic stroke, hemorrhagic stroke, deep venous thrombosis, and pulmonary embolism, we computed cumulative risks and adjusted incidence rate ratios (aIRRs) adjusted for comorbidity and medication. ResultsThe study population consisted of 103,989 patients with AFF and 519,935 individuals without AFF from the general population. Ten-year cumulative risks in the AFF cohort were 3.5% for myocardial infarction, 0.5% for peripheral embolism, 6.7% for ischemic stroke, 1.3% for hemorrhagic stroke, 1.0% for deep venous thrombosis, and 1.3% for pulmonary embolism. During the first 30days following AFF, aIRRs were markedly (4 to 16-fold) increased for all outcomes and similarly elevated for myocardial infarction (aIRR=8.0, 95% confidence interval (CI): 6.8–9.5) and ischemic stroke (aIRR=9.9, 95% CI: 8.5–11.5). Thereafter, aIRRs decreased gradually, reaching unity after 5years for myocardial infarction, deep venous thrombosis, and pulmonary embolism, but remained 1.6 to 3.5-fold increased for peripheral embolism, ischemic stroke, and hemorrhagic stroke. ConclusionsAFF was a risk factor for all arterial and venous outcomes during the first year of follow-up, but only for peripheral embolism, ischemic stroke, and hemorrhagic stroke thereafter.

Long-Term Follow-up Data Support the Curative Potential of Allogeneic Hematopoietic Cell Transplantation in Patients with Chronic Lymphocytic Leukemia: A Retrospective Analysis from the Chronic Malignancies Working Party of the EBMT

Objectives: In patients with refractory chronic lymphocytic leukemia (CLL), the potential to cure is unique to allogeneic stem cell transplantation (HSCT). Clearance of minimal residual disease by suspected graft-versus-leukemia effects has been described elegantly and documented in several independent patient cohorts. Yet data from large numbers of patients which support the concept of cure by allogeneic transplantation have not been published. With the advent of new targeted therapies for patients with advanced chemo-refractory CLL, this information becomes crucial for clinical decision making and patient counselling. Therefore, we aimed at the description of long-term survival outcomes, and the estimation of excess mortality compared to the age- and sex-matched general population.Patients and Methods: Data from patients with CLL who had received a first allogeneic HSCT from an HLA-identical sibling (SIB) or alternative donor between January 2000 and December 2010, and who were registered with the EBMT database, were analyzed. Patients with Richter’s syndrome and with syngeneic donors were excluded from this analysis. Survival probabilities were calculated by means of the Kaplan-Meier estimator both in the total population, and in patients who passed the 2- and 5-year landmark without previous relapse or progression. Excess mortality of the landmark populations compared to an age-, sex- and calendar year-matched general population was estimated with a Cox regression model for relative survival using the R-package “relsurv”.Results: In total 2589 patients were included into the analysis. The median follow-up of patients alive at the end of follow-up was 4.0 years (range: 1 to 161 months). The median age at HSCT was 55 years (range: 12 to 74 years). One hundred and fifty eight patients (6.1%) were below 40 years of age at the time of transplantation. Seventy-four percent of patients were male. The remission status at the time of transplantation was reported as complete remission in 15%, partial remission in 47%, and stable disease or progressive disease in 32%. Information on the remission status was not available for 6% of the patients. Fifty-one percent of the patients had an HLA-matched sibling donor and seventy-seven percent of patients received reduced-intensity conditioning.For the whole cohort of patients, the 5- and 10-year overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM) were 45%, 35%, 36%, and 35%, 28%, 40%, respectively. The cumulative incidence of relapse (CIR) was 21% at two years, 29% at five years, and 32% at ten years. A total of 1023 patients and 394 patients were alive without relapse or progression, and in follow-up at two and five years after HSCT. Five years after patients had passed the 2- and 5-year landmark, OS, CIR and NRM were 73%, 22%, 16%, and 83%, 11%, 10% respectively.Compared to the general population excess mortality of the 5-year landmark population in the subsequent five years was estimated to be 3% for male patients at an age of 45 years, 10% for male patients at an age of 55 years, and 24% for male patients at an age of 65 years (see Figure 1). For female patients in this 5-year landmark population, the corresponding excess mortality rates were 4%, 11%, and 27%.Patients without progression and with CR at any time from HSCT to the two and five-year landmarks had a slightly better outcome than those who had never had CR. Surprisingly, this was not a result of a lower CIR but of a lower NRM.Conclusion: Long-term follow-up data derived from the EBMT registry show a steady decline in hazard of relapse after allogeneic HSCT, yet relapse continues to be a threat. Moreover, even patients alive and disease-free after 5 years are still confronted with substantial NRM. These results show that there is room for improvement of long-term patient care.By comparing mortality of younger patients who passed the 5-year landmark with the general population, only marginal excess mortality was observed, while elderly patients still had substantial excess mortality beyond this landmark. Nevertheless, the results indicate that a significant fraction of patients can be cured by allogeneic HSCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Association of Pre-Transplant Comorbidities with Long-Term Quality of Life (QOL) Among Survivors After Allogeneic Hematopoietic Cell Transplantation (HCT)

s / Biol Blood Marrow Transplant 19 (2013) S150eS166 S153 increasing population of cancer survivors. Much of our knowledge regarding late effects comes from studies in adult recipients or hospital based studies where duration or reliability of follow-up data is limited. The aim of our study was to examine the risk of second malignancy and late mortality in a population-based cohort of pediatric recipients of allogeneic hematopoietic stem cell transplant (HSCT) in Australia. Methods: Australian pediatric allogeneic HSCT recipients aged less than 15 years and treated for a hematological malignancy from 1982-2007, were identified from pediatric hospitals and the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). Patient records were linked to records held by the Australian Cancer Database (ACD) and National Death Index to determine second cancers and deaths in the cohort. Standardized rates (SIRs & SMRs) and risk factors were characterised for second malignancies following HSCT and late deaths (deaths occurring 2 or more years after HSCT). Results: Second cancers were observed in 17 of the 674 (2.5%) HSCT recipients with a primary cancer diagnosis recorded on the ACD. Thyroid cancer was the most common second cancer observed (n1⁄48) followed by brain tumours (n1⁄44). The rate of second cancers occurring after HSCT was 20 times higher than expected based on rates in the age-, sexand calendar-year matched general population (SIR1⁄420.33, 95% CI1⁄412.64-32). Total body irradiation was associated with a 4-fold increased risk of secondary malignancy, while non-Hodgkin lymphoma patients were 7 times more likely to develop a second malignancy compared to acute lymphoblastic leukaemia patients. While the overall rate of late death was 36 times greater than the rate seen in the age-, sexand calendar-year matched general population (SMR1⁄435.93, 95%CI1⁄426.7448.29), rates of death returned to levels similar to the general population 10 years after HSCT. Conclusions: This is the first study to use population-based registry data to determine the risk of second cancer and late death in pediatric patients with a hematologic cancer treated by allogeneic HSCT. The increased risk of second cancer and late deaths in this population highlights the importance of long-term follow up, surveillance and early detection of second cancer.