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Abstract Background Over the last five to ten years there has been an increase in psychosomatic complaints (PSC) in Swedish children. The objective of the study was to examine the relation between PSC and sense of coherence (SOC). Methods A cross-sectional school survey in the county of Västmanland, Sweden. All 16- and 19-year old adolescents present at school on the day of the survey were asked to complete a questionnaire in their classrooms during a one-lesson hour session under the supervision of their teachers. Totally 3,998 students in both private and public schools, studying in ninth grade elementary school or third grade secondary school participated. Results The results from our study show that there is a statistically significant relation between PSC and SOC among adolescents. It also shows that adolescents with a weak SOC score have more symptoms of PSC. Conclusion Our study indicates that SOC can help the adolescents to choose a coping strategy that is appropriate for the situation and thereby may prevent them from developing PSC. However, additional studies are needed to confirm our findings.

Background Psychological well-being is important for individuals, communities and health services throughout the world because of the costs associated with psychological ill-health and the loss of quality of life for those affected and their relatives. Following a salutogenic approach, there is a link between health-promoting resources, such as generalised resistance resources and a positive state of health. Generalised resistance resources have been proposed to relate to an individual's sense of coherence (SOC). The objectives of the present study were (i) to investigate SOC in relation to age and sex, (ii) to investigate psychological well-being in relation to age and sex, and (iii) to investigate the relationship between generalised resistance resources and psychological well-being. Methods A random sample of 43?598 respondents (54% female) aged 18-85-years participated in the present study via a postal survey questionnaire. SOC was measured by the SOC-13 and well-being by the General Health Questionnaire-12 questionnaire. Results Males had both stronger SOC and well-being compared to females. There was a relationship between SOC and age, with stronger SOC in the older age groups. There was a larger proportion of individuals who experienced well-being as a function of age. In addition, an increase in SOC was related to a decrease in psychological well-being, that is, a stronger SOC corresponded to higher well-being. Conclusion Males showed a stronger SOC and more well-being than females. Moreover, SOC and well-being increased with age in both sexes. Our findings suggest that SOC may develop over a entire lifetime. [ABSTRACT FROM AUTHOR]

The article presents clinical recommendations by the European Society for Medical Oncology (ESMO) for the diagnosis, treatment and follow-up of chronic myelogenous leukemia. The disease is linked with splenomegaly and neutrophil leukocytosis, thrombocytosis and basophilia. The first line standard therapy for the disease is the tyrosine kinase inhibitor imatinib.

Chronic myeloid leukemia (CML) stem cells appear resistant to tyrosine kinase inhibitors (TKIs) in vitro, but their impact and drug sensitivity in vivo has not been systematically assessed. We prospectively analyzed the proportion of Philadelphia chromosome-positive leukemic stem cells (LSCs, Ph+CD34+CD38−) and progenitor cells (LPCs, Ph+CD34+CD38+) from 46 newly diagnosed CML patients both at the diagnosis and during imatinib or dasatinib therapy (ClinicalTrials.gov NCT00852566). At diagnosis, the proportion of LSCs varied markedly (1-100%) between individual patients with a significantly lower median value as compared with LPCs (79% vs 96%, respectively, P=0.0001). The LSC burden correlated with leukocyte count, spleen size, hemoglobin and blast percentage. A low initial LSC percentage was associated with less therapy-related hematological toxicity and superior cytogenetic and molecular responses. After initiation of TKI therapy, the LPCs and LSCs rapidly decreased in both therapy groups, but at 3 months time point the median LPC level was significantly lower in dasatinib group compared with imatinib patients (0.05% vs 0.68%, P=0.032). These data detail for the first time the prognostic significance of the LSC burden at diagnosis and show that in contrast to in vitro data, TKI therapy rapidly eradicates the majority of LSCs in patients. [ABSTRACT FROM AUTHOR]

Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile. [ABSTRACT FROM AUTHOR]

Lonafarnib is an orally bio-available farnesyltransferase inhibitor that prevents farnesylation of specific target proteins including Ras. In a multicenter study, 67 patients with advanced myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) were treated with a continuous oral dose of 200-300 mg of lonafarnib and were evaluated for hematologic, pathologic and pharmacodynamic response. The median age of patients was 70 years (range 44-86). There were 32 patients with MDS (RAEB-20 and RAEB-t-12) and 35 with CMML. Overall 16 (24%) of the patients responded with two patients achieving a complete remission and one a partial response. Responses were seen in 6/32 and 10/35 patients with MDS and CMML, respectively. Of the 19 patients who were platelet transfusion-dependent prior to treatment, 5 (26%) became transfusion-free for a median duration of 185 days. A decrease in the farnesylation of the HDJ-2 protein measured in patient-derived cells was observed in the majority of patients during treatment with lonafarnib, but no clear correlation between changes in farnesylation and clinical effect could be made. Gastrointestinal toxicity was significant with 19% of patients discontinuing therapy due to diarrhea, nausea and/or anorexia. Lonafarnib has demonstrable activity in patients with advanced MDS and CMML. [ABSTRACT FROM AUTHOR]

Summary:A phase III, randomized, double-blind, placebo-controlled, multi-center trial was conducted in order to compare the incidence of microbiologically defined infections occurring after high-dose chemotherapy (HDT) and ASCT in 98 patients given lenograstim (Granocyte®) and 94 patients given placebo after transplantation. Hematopoietic recovery, the use of i.v. antibiotics, the numbers of red blood cell and platelet transfusions, the days spent in hospital, and the days on parenteral nutrition were also compared. The incidence of infections until neutrophil recovery was significantly less in patients who received lenograstim after HDT and ASCT as compared to patients who received placebo (66 of 98 vs 86 of 94 patients, P<0.001). Lenograstim also significantly reduced the use of i.v. antibiotics (P<0.001) and the median duration of i.v. antibiotic treatment (8 days vs 10 days, P=0.04), improved neutrophil recovery (absolute neutrophil count>0.5×109/l: 11 days vs 15 days, P<0.001) and reduced the number of days spent in hospital (15 days vs 17 days, P<0.001). The administration of lenograstim after HDT and ASCT significantly reduces the incidence of microbiologically defined infections until neutrophil recovery. It also leads to less use of antibiotics and earlier discharge from hospital.Bone Marrow Transplantation (2004) 34, 955-962. doi:10.1038/sj.bmt.1704724 Published online 18 October 2004 [ABSTRACT FROM AUTHOR]

Summary:We have compared the efficacy of two PBSC mobilisation regimens, mini-ICE+filgrastim (second consolidation) and HiDAC+AMSA+filgrastim (third consolidation), in two consecutive cohorts of patients with AML CR1 receiving treatment according to a joint protocol. Group A: 18 patients, aged 41 (21-65) years, were mobilised with mini-ICE (idarubicin 8?mg/m2+cytarabine 800?mg/m2+etoposide 150?mg/m2 days 1-3) followed by filgrastim 300-480?µg once daily s.c. from day 11 after start of chemotherapy. Only four patients reached >5 CD34+ cells/µl blood (B-CD34+) and were able to undergo leukaphereses. Two out of 18 (11%) reached the defined target of ?2.0 × 106 CD34+ cells/kg after 1-3 leukaphereses. Group B: 20 patients, aged 50 (29-67) years, received HiDAC+AMSA (cytarabine 3?g/m2 b.i.d. days 1, 3, 5+amsacrine 150?mg/m2 q.d. days 2, 4) followed by filgrastim at a similar dose starting on day 7. A total of 18 patients reached B-CD34+ >5/µl and underwent PBSC harvesting, starting on day 23 (14-29) and yielding 4.0 (0.9-21) × 106 CD34+ cells/kg. Of 20 patients, 17 (85%) reached the defined target of ?2.0 × 106 CD34+ cells/kg after 1-3 leukaphereses. We conclude that HiDAC+AMSA+G-CSF - in contrast to mini-ICE+G-CSF - is an efficient regimen for mobilising PBSC in patients with AML CR1.Bone Marrow Transplantation (2003) 32, 1119-1124. doi:10.1038/sj.bmt.1704294 [ABSTRACT FROM AUTHOR]

Abstract: It is still controversial how to treat elderly patients with acute myeloid leukaemia (AML), and results have been poor with most regimens. We report the long-term results of a randomised study performed by the Leukaemia Group of Middle Sweden during 1984–88 comparing two intensive chemotherapeutic drug combinations. Ninety patients ≥60-yr old with untreated AML were randomly allocated to treatment with daunorubicin, cytosine arabinoside (ara-C), and thioguanine (TAD) (43 patients) or a combination in which aclarubicin was substituted for daunorubicin (TAA) (47 patients). Forty-four patients (49%) entered complete remission (CR), 22/43 (51%) in the TAD group and 22/47 (47%) in the TAA group (ns). The CR rate in patients ≤70 yr of age was 30/42 (71%) and in patients >70 yr 14/48 (29%) (P <0.0001). Early death within 30 d after treatment initiation was more often seen in patients >70 yr than in patients ≤70 yr of age, 40% and 12%, respectively ( P <0.005). The median cause-specific survival time was 178 d in the total patient group, and the 2-, 5-, and 10-yr survivals were 22%, 11%, and 8%, respectively. The cause-specific survival was not significantly different between the two treatment arms. At long-term follow-up ≥10 yr after inclusion of the last patient, 5/90 patients (one in the TAD group and four in the TAA group, respectively) were still alive, four in continuous complete remission and one in second complete remission. Thus, both treatment regimens appear to have similar efficacy, with a relatively high complete remission rate, and a reasonable survival as compared to other studies including some long-term survivors. However, early deaths are still numerous, particularly in patients above 70 yr of age, and the relapse rate is substantial. [ABSTRACT FROM AUTHOR]

Unmanipulated autologous bone marrow transplant (ABMT) offers patients with chronic myelogenous leukemia (CML) a long-term survival of 10%, at best. Immunotherapy has a role in the myeloid leukemias, and there is increasing evidence that of all hematopoietic neoplasms, CML may be the most susceptible to immune regulation. Roquinimex is known to enhance T cell, NK cell and macrophage activity. A phase II study was initiated in March 1992 to evaluate the role of roquinimex in Ph chromosome-positive CML post ABMT. Patients were conditioned with busulfan/ cyclophosphamide followed by reinfusion of unmanipulated Ph-positive bone marrow stem cells (>1 × 108 NBC/kg). When engraftment of neutrophils (ANC) reached 100/μl, patients received oral roquinimex twice weekly, escalating to a maximal dose of 0.2 mg/kg in 2 weeks. Seventeen patients have entered the study; 11 in first chronic phase (CP1); two in second chronic phase (CP2) and four in accelerated phase (AP). All required significant myelosuppressive therapy prior to ABMT to maintain stable blood counts and most had also received prior interferon therapy. All patients survived the transplant. Subsequent toxicity consisted mainly of musculoskeletal aches and peripheral edema. Additionally, specific skin changes were observed including graft-versus-host-like disease and eccrine sweat gland necrosis. Eight out of 17 patients are alive 28–60 months post ABMT. Of the nine patients who died, two were in CP2 and three in AP. All patients in CP1 went into a complete hematological remission post ABMT and seven of the 11 patients had at least a major cytogenetic response (greater than 65% Ph-negative metaphases) at 1 year or beyond and four of the 11 patients had a complete cytogenetic response at 2 years or beyond. Cytogenetic response post transplant often developed over time and did not simply represent post ABMT engraftment with Ph-negative cells. The clinical and cytogenetic data in these... [ABSTRACT FROM AUTHOR]

The aims of this study were to assess long-term immunity and reimmunization responses against tetanus toxoid in recipients of autologous stem cell grafts and to compare immune status in patients who underwent ABMT or autologous blood stem cell transplantation (APBSCT). Ninety patients were included in the study; 52 had received ABMT and 38 APBSCT. Thirty of 52 ABMT patients (58%) and 25 of 38 APBSCT patients (66%) had protective antibody levels against tetanus before transplantation (P = NS). The rate of seropositivity had decreased at I year after transplantation; 15 of 52 (29%) ABMT patients and 18 of 38 (47%) APBSCT patients (P = NS) were still positive after 1 year. There were no cases of spontaneous recovery in seronegative patients. Most patients were reimmunized with three doses of tetanus toxoid given at 12, 13, 14 and or 18 months after transplantation. All immunized patients had protective immunity against tetanus at 1 year after vaccination. These results suggest that humoral immunity is defective both after ABMT and after APBSCT and in both cases the loss of immunity seems to be similar. Reimmunization of patients who have undergone ABMT or APBSCT is necessary to obtain protective immunity against tetanus. [ABSTRACT FROM AUTHOR]

Objectives: At-risk drinking of alcohol is increasing in the older population and both at-risk drinking and loneliness have been shown to be risk factors for depression. The aim of this study was therefore to investigate the associations between at-risk drinking, loneliness, and self-reported diagnosed depression in the older population., Methods: The study was based on 10,096 persons aged 70-84 years who answered a survey questionnaire sent to a random population sample in Mid-Sweden in 2017. The overall response rate was 77%. The associations between at-risk drinking, loneliness and depression were analysed using multivariate logistic regression, adjusting for age, educational level, country of birth, economic stress, social support, living alone, physical activity, smoking, BMI, and medication use., Results: The prevalence of at-risk drinking during the last 12 months was 8% among men and 4% among women. In total, 8% of the men and 14% of the women suffered from loneliness at least weekly. Having a current diagnosed depression was more commonly reported among women (9%) than among men (5%). At-risk drinking was associated with a higher prevalence of diagnosed depression in both men (OR:1.76; 95% CI:1.03-3.01) and women (OR:1.83; 95% CI:1.06-3.18), compared to moderate drinking when adjusting for loneliness and potential confounders. Furthermore, persons who suffered from loneliness every week had a higher prevalence of diagnosed depression (OR:5.95; 95% CI:3.72-9.53 in men and OR:4.80; 95% CI:3.44-6.69 in women) than those who did not suffer from loneliness., Conclusion: In this population-based study, both at-risk drinking and loneliness were independently associated with self-reported diagnosed depression among men and women aged 70-84 years. These findings are important for prevention of depression among older people.

Objective: To analyse alcohol consumption and its association with self-rated health among a representative sample of older people in mid-Sweden., Background: Over the past decades, alcohol consumption has increased in the older population in Sweden, but few studies have investigated the association between alcohol consumption and self-rated health in this group. The aim was therefore to investigate alcohol consumption and self-rated health among older Swedes., Methods: The study is based on a cross-sectional study of 11,716 men and women, 65 years and over, answering a survey questionnaire sent to a random population sample in mid-Sweden in 2012. We assessed alcohol consumption with AUDIT-C and its association with self-rated health using logistic regression analysis, adjusting for age, economic situation, educational level, BMI, physical activity, social support and medication use., Results: Men (83%) were more prone to drink alcohol compared to women (71%). The prevalence of risk drinking was about 2% for both genders. Alcohol consumption declined with age. Moderate consumption of alcohol was associated with lower probability of poor self-rated health compared to non-drinking with an adjusted odds ratio 0.64 (95% confidence interval: 0.54-0.76) for men and 0.68 (0.59-0.79) for women., Conclusion: Since the study was cross-sectional the direction of the association could not be determined, and the results should not be interpreted as an argument for promoting alcohol consumption among older people., (© The Author(s) 2019. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Very few population-based studies have investigated self-rated health and related factors in the increasing age group 85 years or older. The aim of this study was to examine self-rated health and its association with living conditions, lifestyle factors, physical and mental health problems and functional ability among the oldest-old in the general population in Sweden., Methods: The study is cross-sectional and based on 1360 persons, 85 years of age or older, who answered a survey questionnaire sent to a random population sample in 2012 (participation rate 47%). Multivariate logistic regression was used as the statistical method., Results: The prevalence of good self-rated health was 39% in men and 30% in women. Physical inactivity, impaired physical mobility, pain, anxiety/depression and longstanding illness were independently associated with poorer than good self-rated health, while factors such as gender, age, educational level, cash margin, living alone, social support, smoking, alcohol use, obesity, accidents and impaired vision/hearing were not., Conclusions: While a considerable part of the oldest-old assess their health as good, not being physically active and having common health problems such as pain and depression as well as impaired physical mobility are associated with poorer than good self-rated health. This should be considered when planning how to improve and maintain health in the growing population of persons 85 years and older., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor (TKI) use and management patterns in patients with chronic phase-chronic myeloid leukemia in the US and Europe in routine clinical practice. Herein we describe interruptions, discontinuations and switching of TKI therapy during the initial 2 years of treatment among 1121 patients prospectively enrolled between October 1, 2010 and March 7, 2017. Patient characteristics were broadly similar between the imatinib (n = 370), dasatinib (n = 376), and nilotinib (n = 375) cohorts. Treatment interruptions occurred in 16.4% (year 1) and 4.0% (year 2) of patients, mainly attributed to hematologic intolerances. Treatment discontinuations occurred in 21.8% (year 1) and 10.2% (year 2) of patients, with the highest rate within the first 3 months for intolerance. Switching of TKI was seen in 17.8% (year 1) and 9.5% (year 2) of patients. Significant associations were found between TKI switching and female gender (year 1), age ≥65 years at diagnosis (year 2) and treatment with imatinib (year 2). Intolerance was the most common reason given for patients discontinuing and for switching TKI therapy; however resistance was also cited. Lack of response monitoring in routine clinical practice may have resulted in lower identification of resistance in this dataset. Data from SIMPLICITY suggest that, in routine clinical practice, intolerance and resistance to TKIs influence decisions to change treatment. Changes in TKI therapy are frequent, with nearly a third of patients discontinuing their first-line TKI., (© 2018 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.)

Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n = 416), dasatinib (n = 418) or nilotinib (n = 408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1242 prospective patients (enrolled October 01 2010-September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib-treated patients enrolled earlier in the study, with subsequent shift toward dasatinib- and nilotinib-treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82%, and 95% of patients by 3, 6, and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P < .001) and at academic versus community practices (P = .001). Age <65 years, patients being followed at sites within Europe, those followed at academic centers and patients no longer on first-line therapy were more likely to be monitored by 12 months. SIMPLICITY demonstrates that the NCCN and ELN recommendations on response monitoring have not been consistently translated into routine clinical practice. In the absence of appropriate monitoring practices, clinical response to TKI therapy cannot be established, any needed changes to treatment strategy will thus not be implemented, and long-term patient outcomes are likely to be impacted., (© 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.)

Background: The total number of cardiovascular (CVD) deaths accounted for almost a third of all deaths globally in 2013. Population based randomised controlled trials, managed within primary care, on CVD risk factor interventions are scarce. The aim of the study was to evaluate the effects of a health dialogue intervention in a primary care setting offered to a population at the age of 55 years, focusing on CVD risk factors., Methods: The study was performed in five primary health care centres in the county of Västmanland, Sweden between April 2011 and December 2012. Men and women were randomly assigned to intervention (n = 440) and control groups (n = 440). At baseline, both groups filled in a health questionnaire and serum cholesterol, fasting plasma glucose, glycated haemoglobin (HbA1c), weight, height, waist (WC) and hip circumference, waist hip ratio (WHR) and systolic/diastolic blood pressure were measured. Intervention group attended a health dialogue, supported by a visualised health profile, with a possibility for further activities. Participation rates at baseline were 53% and 52% respectively. A 1-year follow-up was carried out., Results: The intervention group (n = 165) showed reductions compared to the control group (n = 177) concerning body mass index (BMI) (0.3 kg/m 2 , p = .031), WC (2.1 cm, p ≤ .001) and WHR (.002, p ≤ .001) at the 1-year follow-up. No differences between the intervention and control groups were found in other variables. Intervention group, compared to baseline, had reduced weight, BMI, WC, WHR, HbA1c, and diet, while the men in the control group had reduced their alcohol consumption., Conclusions: A health dialogue intervention at the age of 55 years, conducted in ordinary primary care, showed a moderate effect on CVD risk factor levels, in terms of BMI, WC and WHR., Trial Registration Number: BioMed Central, ISRCTN22586871 , date assigned; 10/12/2015.

Objective: To examine how physical activity and physical mobility are related to obesity in the elderly., Study Design: A cross-sectional study of 2558 men and women aged 65 years and older who participated in a population survey in 2012 was conducted in mid-Sweden with an overall response rate of 67%., Methods: Obesity (body mass index ≥30 kg/m 2 ) was based on self-reported weight and height, and physical activity and physical mobility on questionnaire data. Chi-squared test and multiple logistic regressions were used as statistical analyses., Results: The overall prevalence of obesity was 19% in women and 15% in men and decreased after the age of 75 years. A strong association between both physical activity and obesity, and physical mobility and obesity was found. The odds for obesity were higher for impaired physical mobility (odds ratio [OR] 2.83, 95% confidence interval [CI] 2.14-3.75) than for physical inactivity (OR 1.63, 95% CI 1.28-2.08) when adjusted for gender, age, socio-economic status and fruit and vegetable intake. However, physical activity was associated with obesity only among elderly with physical mobility but not among those with impaired physical mobility., Conclusion: It is important to focus on making it easier for elderly with physical mobility to become or stay physically active, whereas elderly with impaired physical mobility have a higher prevalence of obesity irrespective of physical activity., (Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.

Background and Aims: The simultaneous measurement of many proteins is now possible using multiplex assays. In this pilot study we investigated a total of 124 proteins in plasma from chronic myeloid leukemia (CML) patients with the purpose of identifying proteins that are differently expressed at diagnosis and after tyrosine kinase inhibitor (TKI) treatment initiation., Methods: Samples were taken from 14 CML patients at diagnosis and after three months of TKI treatment (imatinib or dasatinib). Samples were analyzed by Mesoscale Discovery, Myriad RBM MAP technology and Olink Proseek., Results: Multiple plasma proteins were differentially expressed before and after initiation of TKI therapy. Protein patterns demonstrated a possible shift towards Th1-immunity and reduced angiogenic stimuli. Further, some plasma proteins were identified that can be of potential interest to study further for biologic, prognostic or therapeutic significance such as E-selectin, uPAR, growth hormone and carbonic anhydrase IX., Conclusions: Plasma proteomics seems feasible and useful in CML patients, both for studying patterns of protein expression and for identifying single proteins differentially expressed before and after treatment. Plasma proteomics may be useful to map disease activity and biological processes. Hence, plasma proteomics can be used to understand drug mechanisms and treatment responses in CML., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib's price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness ("imatinib-first") would be cost-effective compared with the current standard of care: "physicians' choice" of initiating treatment with any one of the three TKIs., Methods: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician's choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models' clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven's MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study's conduct., Results: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician's choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses., Conclusion: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP., (© The Author 2016. Published by Oxford University Press.)

In patients with chronic myeloid leukemia (CML), first-line imatinib treatment leads to 8-year overall survival (OS) probabilities above 80%. Many patients die of reasons unrelated to CML. This work tackled the reassessment of prognosis under particular consideration of the probabilities of dying of CML. Analyses were based on 2290 patients with chronic phase CML treated with imatinib in six clinical trials. 'Death due to CML' was defined by death after disease progression. At 8 years, OS was 89%. Of 208 deceased patients, 44% died of CML. Higher age, more peripheral blasts, bigger spleen and low platelet counts were significantly associated with increased probabilities of dying of CML and determined a new long-term survival score with three prognostic groups. Compared with the low-risk group, the patients of the intermediate- and the high-risk group had significantly higher probabilities of dying of CML. The score was successfully validated in an independent sample of 1120 patients. In both samples, the new score differentiated probabilities of dying of CML better than the Sokal, Euro and the European Treatment and Outcome Study (EUTOS) score. The new score identified 61% low-risk patients with excellent long-term outcome and 12% high-risk patients. The new score supports the prospective assessment of long-term antileukemic efficacy and risk-adapted treatment.

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.

National and regional population-based registries are, provided diagnostic accuracy and full coverage of the target population, indispensible tools for epidemiological research. Chronic myeloid leukaemia (CML) registries with more comprehensive reporting may also provide complementary data on treatment outcome to those obtained from clinical trials. Reports from several European CML registries consistently show a crude annual incidence of 0.7-1.0/100,000, a median age at diagnosis of 57-60 years and a male/female ratio of 1.2-1.7. The incidence of CML has been stable over time. Worldwide, variations in the reported incidence of CML may be due to methodological issues, but a true difference between different geographical areas and/or ethnical subgroups cannot be excluded. The prevalence of CML is not well known but has been estimated to be 10-12/100,000 inhabitants with a steady increase due to the dramatic improvement in survival of these patients. In recent population-based studies, CML patients have an overall survival that is comparable to that shown in large clinical trials, though relative survival in patients >70 years is still decreased. The importance of socio-economic factors and health-care setting for outcome and the possible increased risk of secondary cancer in CML are areas of ongoing research.

We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100 mg QD or imatinib 400 mg QD and report outcome as an intention-to-treat analysis with 36 months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR(3.0) was reached at 3 months in 36% vs. 8% (P = 0.02), at 12 months in 81% vs. 46% (P = 0.02) and at 18 months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR(4.5) was consistently superior in the dasatinib group at all time points from 6 months onwards, reaching 61% vs. 21% (P < 0.05) at 36 months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation., (© 2014 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.)

Background: The main goal of the health care system in Sweden is good health and health care on equal terms for the entire population. This study investigated the existence of social inequalities in refraining from health care due to financial reasons in Sweden., Methods: The study is based on 38,536 persons who responded to a survey questionnaire sent to a random sample of men and women aged 18-84 years in 2008 (response rate 59%). The proportion of persons who during the past three months due to financial reasons limited or refrained from seeking health care, purchasing medicine or seeking dental care is reported. The groups were defined by gender, age, country of origin, educational level and employment status. The prevalence of longstanding illness was used to describe morbidity in these groups. Differences between groups were tested with chi-squared statistics and multivariate logistic regression models., Results: In total, 3% reported that they had limited or refrained from seeking health care, 4% from purchasing medicine and 10% from seeking dental care. To refrain from seeking health care was much more common among the unemployed (12%) and those on disability pension (10%) than among employees (2%). It was also more common among young adults and persons born outside the Nordic countries. Similar differences also apply to purchasing medicine and dental care. The odds for refraining from seeking health care, purchasing medicine or seeking dental care due to financial reasons were 2-3 times higher among persons with longstanding illness than among persons with no longstanding illness., Conclusions: There are social inequalities in self-reported refraining from health care due to financial reasons in Sweden even though the absolute levels vary between different types of care. Often those in most need refrain from seeking health care which contradicts the national goal of the health care system. The results suggest that the fare systems of health care and dental care should be revised because they contribute to inequalities in health care.

Background: The aims of this study were to determine self-rated oral health and dental attendance habits among Swedish adults, with special reference to the role of social inequalities, after the Swedish dental care reform in 2008., Methods: The study is based on a survey questionnaire, sent to 12,235 residents of a Swedish county, in 2012. The age group was 16-84 years: 5,999 (49%) responded. Using chi-square statistics, differences in prevalence of self-rated oral health and regular dental attendance were analysed with respect to gender, age, educational level, family status, employment status and country of birth. Self-rated poor oral health was analysed by multivarite logistic regression adjusting for the different socio-demographic factors, financial security and having refrained from dental treatment for financial reasons., Results: Three out of four respondents (75%) reported fairly good or very good oral health. Almost 90% claimed to be regular dental attenders. Those who were financially secure reported better oral health. The differences in oral health between those with a cash margin and those without were large whereas the differences between age groups were rather small. About 8% reported that they had refrained from dental treatment for financial reasons during the last three months. Self-rated poor oral health was most common among the unemployed, those on disability pension or on long-term sick leave, those born outside the Nordic countries and those with no cash margin (odds ratios ranging from 2.4 to 4.4). The most important factor contributing to these differences was having refrained from dental treatment for financial reasons., Conclusion: The results are relevant to strategies intended to reduce social inequalities in oral health, affirming the importance of the provision of equitable access to dental care.

Objectives: Previous studies indicate that 40-50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon-alpha (Peg-IFN-α2b) and imatinib may increase the rate of successful discontinuation., Methods: In this pilot study, we prospectively stopped imatinib from patients (n = 12) who had achieved major molecular response (MMR) after ≥12 months of treatment with either imatinib or imatinib+Peg-IFN-α2b. Molecular monitoring was carried out monthly for BCR-ABL1. In addition, analyses of lymphocyte immunophenotype, function, and plasma cytokines were performed., Results: In the monotherapy group, 5/6 patients lost MMR within 4 months. One patient remains to date in MR(4.0) 61 months after discontinuation. In the combination therapy group, 2/6 patients relapsed within 4 months while still receiving Peg-IFN-α2b. Four of six patients were able to discontinue both treatments, but three of these patients relapsed after 3 months. One patient is still in sustained MR(4.0) at 58 months off all treatment. All relapsed patients re-responded to imatinib. The two successfully discontinued patients had either an increased number of NK-cells or functionally active T-cells., Conclusions: A higher frequency of relapsed patients in our study in comparison with other studies may be due to the shorter duration of imatinib treatment prior to discontinuation. However, in selected patients with an active immune system, even a short duration of TKI therapy (<2 yr) may allow for therapy discontinuation but this needs to be confirmed in larger prospective studies., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)