Risk of fractures and use of bisphosphonates in adult patients with immune thrombocytopenia-A nationwide population-based study.

Corticosteroids remain the first-line treatment of immune thrombocytopenia (ITP), but increase the risk of osteoporosis and fractures. Bisphosphonates are used for the treatment of osteoporosis, but their usage among patients with ITP has not been systemically described. We investigated the risk of fractures and the use of bisphosphonates in adult patients with primary (pITP) and secondary ITP (sITP) compared with matched comparators in a nationwide registry-based cohort study. We identified 4030 patients with pITP (median age 60 years [IQR, 40-74]), 550 with sITP (median age 59 years [IQR, 43-74]) and 182 939 age-sex-matched general population comparators. All individuals were followed for incident fractures. Bisphosphonate use was estimated for calendar-years and in temporal relation to the ITP diagnosis. Adjusted cause-specific hazard ratio (csHR) for any fracture was 1.37 (95% confidence interval [CI] 1.23; 1.54) for pITP and 1.54 (1.17; 2.03) for sITP. The first-year csHR was 1.82 (1.39; 2.40) for pITP and 2.78 (1.58; 4.91) for sITP. Bisphosphonate use over calendar-years and in the early years following ITP diagnosis was higher among patients with ITP diagnosis compared with the general population. In conclusion, the risk of fractures and the use of bisphosphonates are higher in patients with ITP compared with the general population.

Mental health and use of psychotropic prescription drugs in adult patients with primary immune thrombocytopenia: a nationwide population-based cohort study.

Patients with primary immune thrombocytopenia (ITP) suffer from reduced survival and quality of life, but the underlying reasons for this are largely undescribed. Mental health and the use of psychotropic drugs in ITP is unknown. We investigated the risk of hospital registered mental health events including fatigue and the use of psychotropic drugs in adult patients with ITP compared with the general population, using nationwide registry-data. We identified 3,749 patients with ITP and 149,849 age-sex matched general population comparators in the Danish Health Registries in the period 1997-2016. The median age was 60 years (IQR 40-73) and 53% were women. We followed the individuals for incident mental health events and estimated the use of psychotropic drugs over calendar-years and in temporal relation to diagnosis of ITP. The first year cumulative incidence of any mental health event was 2.3% (95% confidence interval, 1.9-2.9) in patients and 0.7% (0.6-0.7) in comparators, yielding an adjusted cause-specific hazard ratio (csHR) of 3.57 (2.84-4.50). The corresponding estimates for depression were 1.2% (0.9-1.6) and 0.3% (0.3-0.4) respectively, with an adjusted csHR of 3.53 (2.56-4.85). We found similar findings for anxiety and fatigue, but risks generally diminished after 1-5 years. The use of opioids, antidepressants, and benzodiazepines increased in temporal relation to diagnosis of ITP. The risk of mental health events and the use of psychotropic drugs is higher in adult patients with ITP compared with the general population, and has a temporal relation to diagnosis of ITP emphasizing that mental health in ITP is a concern.

Survival in adult patients with chronic primary and secondary immune thrombocytopenia: A population-based study.

BACKGROUND: Few studies have investigated long-term survival in patients with primary immune thrombocytopenia (pITP). Further, changes in prognosis over the past decades and prognosis of secondary immune thrombocytopenia (sITP) are largely unstudied. Our objectives were to study comorbidity-adjusted prognostic changes and causes of death in chronic pITP and sITP patients. STUDY DESIGN/METHODS: Using nationwide Danish health registries 1980-2016, we identified 1762 patients with chronic pITP (median age 58 (IQR, 37-73) years) and 128 with chronic sITP (median age 59 (IQR, 40-73) years). Patients were age-sex-matched to 74,781 general population comparators. Comorbidity was assessed using Charlson Comorbidity Index (CCI). RESULTS: Overall median survival was reduced by 5.1 years (95% CI, 0.7-9.4) (p < .001) for pITP and 11.1 years (95% CI, 5.8-16.4) (p < .001) for sITP. 5-year survival increased from 69% (95% CI, 59-78) in 1980-89 to 80% (95% CI, 75-83) in 2010-16 for pITP, and decreased from 100% (95% CI, 89-98) to 64% (95% CI, 87-91) for sITP. However, numbers were small for sITP. 5-year survival for pITP with high CCI was 41% (95% CI, 32-49), and 85% (95% CI, 83-87) for low CCI. Bleeding, infection and hematological cancer were relatively frequent causes of death with adjusted subhazard ratios of 3.25 (95% CI, 2.33-4.52), 1.53 (95% CI, 1.08-2.16) and 2.16 (95% CI, 1.12-4.16) in pITP respectively, and 10.52 (95% CI, 1.43-77.36) for hematological cancer in sITP. CONCLUSIONS: Long-term survival is reduced in chronic ITP but seems to be improving. Comorbidity and sITP are associated with a poor prognosis.

Mental health among patients with non-Hodgkin lymphoma: A Danish nationwide study of psychotropic drug use in 8750 patients and 43 750 matched comparators.

Psychological distress following cancer diagnosis may lead to mental health complications including depression and anxiety. Non-Hodgkin lymphomas (NHLs) include indolent and aggressive subtypes for which treatment and prognosis differ widely. Incident use of psychotropic drugs (PDs-antidepressants, antipsychotics, and anxiolytics) and its correlation to lymphoma types can give insights into the psychological distress these patients endure. In this prospective matched cohort study, we used nationwide population-based registries to investigate the cumulative risk of PD use in NHL patients compared to a sex- and age-matched cohort from the Danish background population. In addition, contact patterns to psychiatric departments and incident intentional self-harm or completed suicide were explored. In total, 8750 NHL patients and 43 750 matched comparators were included (median age 68; male:female ratio 1.6). Median follow-up was 7.1 years. Two-year cumulative risk of PD use was higher in NHL patients (16.4%) as compared to the matched comparators (5.1%, p < .01); patients with aggressive NHL subtypes had the highest incidence. Prescription rates were higher in the first years after diagnosis but approached the rate of the matched population 5 years into survivorship in aggressive NHLs, whereas patients with indolent subtypes continued to be at higher risk. NHL patients had a slightly higher two-year risk of suicide/intentional self-harm (0.3%) as compared to the matched comparators (0.2%, p = .01). These results demonstrate that mental health complications among NHL patients are frequent. Routine assessment for symptoms of depression and anxiety should be consider as part of standard follow-up of NHL patients.

Risk of infection in adult patients with primary immune thrombocytopenia (ITP): a systematic review.

INTRODUCTION: Primary immune thrombocytopenia (ITP) is a bleeding disorder characterized by autoimmune destruction and impaired production of platelets. Immunosuppressive drugs are the main treatment and may increase risk of infection. AREAS COVERED: This systematic review included studies incorporating adult patients with primary ITP and infectious outcomes. Studies comparing risk of infection with the general population were included as primary and studies without this comparison were considered secondary. Three primary and 10 secondary studies were included. The main findings: 1-year adjusted relative-risk of infection was 4.5 (95% CI, 3.3-6.1) fold elevated compared to the general population. When comparing splenectomized with non-splenectomized ITP patients, the +1-year adjusted relative-risk of infection was 4.0 (95% CI, 2.8-5.6). The unadjusted 5-year mortality rate-ratio for infection-related deaths was 6.0 (95% CI, 3.0-11.8) in one study, and the hazard ratio was 2.4 (95% CI, 1.0-5.7) for fatal infections in another. EXPERT OPINION: This review emphasizes that patients with ITP have increased risk of infection. Since ITP is a benign hematologic disease, it is important to assess the extent and causes of infection in the clinical care and considerations before initiating treatment. More homogeneous studies are needed on this topic.

Evans syndrome in children below 13 years of age - A nationwide population-based cohort study.

Evans syndrome is defined by autoimmune haemolytic anaemia and immune thrombocytopenia occurring in the same patient. Although known to be rare the frequency and prognosis of Evans syndrome in children is unknown, and only few registry-based studies are available. The epidemiology and prognosis of Evans syndrome in patients above 13 years of age has recently been investigated. In this age group both incidence and prevalence of Evans syndrome increased during the study period and median survival was just 7.2 years. Using Danish health registries and the same approach, we identified 21 children below 13 years of age with Evans syndrome during 1981-2015. Patients with Evans syndrome were age-and sex matched with children both from the general population, and with patients with either autoimmune haemolytic anaemia or immune thrombocytopenia. The incidence of Evans syndrome ranged between 0.5 and 1.2/1,000,000 person-years. Prevalence was 6.7 and 19.3/1,000,000 in 1990 and 2015 respectively. Hazard ratio for death was 22 fold higher for children with ES compared to matched children from general population, and was also elevated compared to children with autoimmune haemolytic anaemia or immune thrombocytopenia. We conclude that pediatric ES is very rare and associated with elevated mortality. However, despite the nationwide study and a long and complete follow-up, results are imprecise due to the rarity of this disorder.