Lena Brandt

Mortality and causes of death in schizophrenia in Stockholm County, Sweden

A study of mortality for all patients with a first hospital diagnosis of schizophrenia in Stockholm County, Sweden, during 1973 to 1995 was performed, by linking the in-patient register with the national cause-of-death register. Overall and cause-specific standardized mortality ratios (SMR) were calculated by 5-year age classes and 5-year calendar time periods. The number of excess deaths was calculated by reducing the observed number of deaths by those expected. Our results confirmed a marked increase in mortality in schizophrenia both in males and females. Natural (somatic) causes of death was the main cause of excess deaths, with more than half of the excess deaths in females, and almost half of the excess deaths in males. Suicide was the specific cause of the largest number of excess deaths in males, while in females it was cardiovascular disease. SMRs were increased in both natural and unnatural causes of death, with 2.8 for males and 2.4 for females for all deaths, but were highest in suicide with 15.7 for males and 19.7 for females, and in unspecified violence with 11.7 for males and 9.9 for females. SMRs in suicide were especially high in young patients in the first year after the first diagnosis.

Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists

Background: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear. Objective: To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA. Methods: A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53 067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed. Results: Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas. Conclusion: Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.

Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists

Background: Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s. Objective: To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials. Methods: A population based study of three RA cohorts (one prevalent, admitted to hospital 1990–2003 (n = 53 067), one incident, diagnosed 1995–2003 (n = 3703), and one treated with TNF antagonists 1999–2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003. Results: With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20–50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (−20%) and colorectal cancer (−25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA. Conclusion: The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.

Allogeneic bone marrow transplantation in multiple myeloma

Abstract Background and Methods. In contrast to autologous bone marrow transplants for hematologic cancers, allogeneic transplants contain no tumor cells that might cause a relapse. We report the results of such allogeneic bone marrow transplantation using HLA-compatible sibling donors in 90 patients with multiple myeloma performed in 26 European centers between 1983 and 1989. Results. At the time of the most recent follow-up, 79 months after the start of the study, 47 patients were alive and 43 were dead. The rate of complete remission after bone marrow transplantation was 43 percent for all patients and 58 percent for the patients who had engraftment. The actuarial survival at 76 months was 40 percent. The median duration of relapse-free survival among patients who were in complete remission after bone marrow transplantation was 48 months. The stage of the disease at diagnosis and the number of treatment regimens tried before bone marrow transplantation were predictive of the likelihood of complete remi...

Small-Intestinal Histopathology and Mortality Risk in Celiac Disease

CONTEXT Studies of mortality in celiac disease have not taken small-intestinal pathology into account. OBJECTIVE To examine mortality in celiac disease according to small-intestinal histopathology. DESIGN, SETTING, AND PATIENTS Retrospective cohort study. We collected data from duodenal/jejunal biopsies taken between July 1969 and February 2008 on celiac disease (Marsh stage 3: villous atrophy; n = 29,096 individuals) and inflammation (Marsh stage 1-2; n = 13,306) from all 28 pathology departments in Sweden. A third cohort consisted of individuals with latent celiac disease from 8 university hospitals (n = 3719). Latent celiac disease was defined as positive celiac disease serology in individuals with normal mucosa (Marsh stage 0). Through linkage with the Swedish Total Population Register, we estimated the risk of death through August 31, 2008, compared with age- and sex-matched controls from the general population. MAIN OUTCOME MEASURE All-cause mortality. RESULTS There were 3049 deaths among patients with celiac disease, 2967 with inflammation, and 183 with latent celiac disease. We found an increased hazard ratio (HR) for death in celiac disease (HR, 1.39; 95% confidence interval [CI], 1.33-1.45; median follow-up, 8.8 years), inflammation (HR, 1.72; 95% CI, 1.64-1.79; median follow-up, 7.2 years), and latent celiac disease (HR, 1.35; 95% CI, 1.14-1.58; median follow-up, 6.7 years). The absolute mortality rate was 10.4 (95% CI, 10.0-10.8) per 1000 person-years in celiac disease, 25.9 (95% CI, 25.0-26.8) in inflammation, and 6.7 (95% CI, 5.7-7.6) in latent celiac disease. Excess mortality was 2.9 per 1000 person-years in celiac disease, 10.8 in inflammation, and 1.7 in latent celiac disease. This risk increase was also seen in children. Excluding the first year of follow-up, HRs decreased somewhat. CONCLUSION Risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased.

Excess mortality, causes of death and prognostic factors in anorexia nervosa

BACKGROUND Anorexia nervosa is a mental disorder with high mortality. AIMS To estimate standardised mortality ratios (SMRs) and to investigate potential prognostic factors. METHOD Six thousand and nine women who had in-patient treatment for anorexia nervosa were followed-up retrospectively using Swedish registers. RESULTS The overall SMR for anorexia nervosa was 6.2 (95% CI 5.5-7.0). Anorexia nervosa, psychoactive substance use and suicide had the highest SMR. The SMR was significantly increased for almost all natural and unnatural causes of death. The SMR 20 years or more after the first hospitalisation remained significantly high. Lower mortality was found during the last two decades. Younger age and longer hospital stay at first hospitalisation was associated with better outcome, and psychiatric and somatic comorbidity worsened the outcome. CONCLUSIONS Anorexia nervosa is characterised by high lifetime mortality from both natural and unnatural causes. Assessment and treatment of psychiatric comorbidity, especially alcohol misuse, may be a pathway to better long-term outcome.

Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists

Objectives: The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers. Methods: First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account. Results: Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years. Conclusion: Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.

Allogeneic Bone Marrow Transplantation in Multiple Myeloma

Abstract Background and Methods. In contrast to autologous bone marrow transplants for hematologic cancers, allogeneic transplants contain no tumor cells that might cause a relapse. We report the results of such allogeneic bone marrow transplantation using HLA-compatible sibling donors in 90 patients with multiple myeloma performed in 26 European centers between 1983 and 1989. Results. At the time of the most recent follow-up, 79 months after the start of the study, 47 patients were alive and 43 were dead. The rate of complete remission after bone marrow transplantation was 43 percent for all patients and 58 percent for the patients who had engraftment. The actuarial survival at 76 months was 40 percent. The median duration of relapse-free survival among patients who were in complete remission after bone marrow transplantation was 48 months. The stage of the disease at diagnosis and the number of treatment regimens tried before bone marrow transplantation were predictive of the likelihood of complete remi...

Risk of haematopoietic cancer in patients with inflammatory bowel disease

Background and aims: Several chronic inflammatory conditions are associated with an increased risk of lymphoma. Whether this applies to inflammatory bowel disease (IBD) is still unclear but of paramount interest, particularly in the safety evaluation of newer immunosuppressive drugs. Reports also indicate a possible increase in the risk of leukaemia in IBD. We therefore assessed the risk of haematopoietic cancers in a large cohort of patients with IBD. Subjects and methods: We performed a population based cohort study using prospectively recorded data, including 47 679 Swedish patients with Crohn’s disease (CD) or ulcerative colitis (UC) assembled from regional cohorts of IBD from 1955 to 1990 (n = 8028) and from the Inpatient Register of 1964–2000 (n = 45 060), with follow up until 2001. Relative risks were expressed as standardised incidence ratios (SIR). Results: Overall, we observed 264 haematopoietic cancers during follow up, which corresponded to a borderline significant 20% increased risk in both UC and CD. In UC, lymphomas occurred as expected (SIR 1.0, n = 87) but myeloid leukaemia occurred significantly more often than expected (SIR 1.8, n = 32). In CD, there was a borderline significant increased lymphoma risk (SIR 1.3, n = 65), essentially confined to the first years of follow up. Proxy markers of disease activity had little impact on lymphoma risk. Conclusion: On average, patients with IBD have a marginally increased risk of haematopoietic cancer. In UC, this is accounted for by an excess of myeloid leukaemia. In CD, a modest short term increase in the risk of lymphoma of unknown significance cannot be excluded but any long term risk increase seems unlikely.

Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency

Objectives  Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population.