Ixazomib, Lenalidomide, and Dexamethasone (IRD) Treatment with Cytogenetic Risk-Based Maintenance in Transplant-Eligible Myeloma: A Phase 2 Multicenter Study by the Nordic Myeloma Study Group.

Scarce data exist on double maintenance in transplant-eligible high-risk (HR) newly diagnosed multiple myeloma (NDMM) patients. This prospective phase 2 study enrolled 120 transplant-eligible NDMM patients. The treatment consisted of four cycles of ixazomib-lenalidomide-dexamethasone (IRD) induction plus autologous stem cell transplantation followed by IRD consolidation and cytogenetic risk-based maintenance therapy with lenalidomide + ixazomib (IR) for HR patients and lenalidomide (R) alone for NHR patients. The main endpoint of the study was undetectable minimal residual disease (MRD) with sensitivity of <10-5 by flow cytometry at any time, and other endpoints were progression-free survival (PFS) and overall survival (OS). We present the preplanned analysis after the last patient has been two years on maintenance. At any time during protocol treatment, 28% (34/120) had MRD < 10-5 at least once. At two years on maintenance, 66% of the patients in the HR group and 76% in the NHR group were progression-free (p = 0.395) and 36% (43/120) were CR or better, of which 42% (18/43) had undetectable flow MRD <10-5. Altogether 95% of the patients with sustained MRD <10-5, 82% of the patients who turned MRD-positive, and 61% of those with positive MRD had no disease progression at two years on maintenance (p < 0.001). To conclude, prolonged maintenance with all-oral ixazomib plus lenalidomide might improve PFS in HR patients.

Idelalisib (PI3Kδ inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia: A Swedish nation-wide real-world report on consecutively identified patients.

OBJECTIVES: We examined the efficacy and toxicity of the PI3Kδ inhibitor idelalisib in combination with rituximab salvage therapy in consecutively identified Swedish patients with chronic lymphocytic leukemia (CLL). METHODS AND RESULTS: Thirty-seven patients with relapsed/refractory disease were included. The median number of prior lines of therapy was 3 (range 1-11); the median age was 69 years (range 50-89); 22% had Cumulative Illness Rating Scale (CIRS) >6 and 51% had del(17p)/TP53 mutation. The overall response rate was 65% (all but one was partial response [PR]). The median duration of therapy was 9.8 months (range 0.9-44.8). The median progression-free survival was 16.4 months (95% CI: 10.4-26.3) and median overall survival had not been reached (75% remained alive at 24 months of follow-up). The most common reason for cessation of therapy was colitis (n = 8, of which seven patients experienced grade ≥3 colitis). The most common serious adverse event was grade ≥3 infection, which occurred in 24 patients (65%). CONCLUSIONS: Our real-world results suggest that idelalisib is an effective and relatively safe treatment for patients with advanced-stage CLL when no other therapies exist. Alternative dosing regimens and new PI3K inhibitors should be explored, particularly in patients who are double-refractory to inhibitors of BTK and Bcl-2.

Carfilzomib and dexamethasone maintenance following salvage ASCT in multiple myeloma: A randomised phase 2 trial by the Nordic Myeloma Study Group.

OBJECTIVE: We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma. METHODS: This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 â†’ 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86). RESULTS: Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4-21.8) in the control group (HR 0.46, 95% CI 0.30-0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections. CONCLUSION: In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity.

Somatic health in the Indigenous Sami population - a systematic review.

The objective of this systematic review was to survey the current scientific knowledge regarding the state of somatic health among situation of the Indigenous Sami people in Norway, Finland, Sweden and the Kola Peninsula in Russia; and assess the quality of the identified studies. A systematic search in the databases Pubmed, EBSCOhost (AMED, Medline, Cinahl) and Svemed was conducted from January 2000, through December 2017. This systematic search identified 399 articles. After screening abstracts, 93 articles were reviewed in full text, 32 of which met the inclusion criteria. The scientific quality of the evidence was rated according to the Newcastle-Ottawa scale. Based on the studies with moderate to high scientific quality, there is evidence for stating that the majority of the Sami included in this review experience good health. Mortality and life expectancy are similar, with only minor differences, to those of a non-Sami population. The cancer risk rate among Sami was lower than that of the general population of Norway, Sweden and Finland. Self-reported myocardial infarction prevalence was similar between Sami and non-Sami, but Angina pectoris was more prevalent among Sami. In Sweden, cardiovascular disease rates were similar between Sami and non-Sami. Musculoskeletal pain symptoms are common among the Sami population, as are obesity and overweight. To conclude, there are knowledge gaps in regard to the somatic health situation of the Indigenous Sami in the circumpolar area, especially in Russia, Finland and Sweden; as current knowledge is mainly based on publications from the SAMINOR study in Norway. No study obtained the highest quality score, suggesting a need to implement longitudinal prospective studies.

Indigenous and tribal peoples' health (The Lancet-Lowitja Institute Global Collaboration): a population study.

BACKGROUND: International studies of the health of Indigenous and tribal peoples provide important public health insights. Reliable data are required for the development of policy and health services. Previous studies document poorer outcomes for Indigenous peoples compared with benchmark populations, but have been restricted in their coverage of countries or the range of health indicators. Our objective is to describe the health and social status of Indigenous and tribal peoples relative to benchmark populations from a sample of countries. METHODS: Collaborators with expertise in Indigenous health data systems were identified for each country. Data were obtained for population, life expectancy at birth, infant mortality, low and high birthweight, maternal mortality, nutritional status, educational attainment, and economic status. Data sources consisted of governmental data, data from non-governmental organisations such as UNICEF, and other research. Absolute and relative differences were calculated. FINDINGS: Our data (23 countries, 28 populations) provide evidence of poorer health and social outcomes for Indigenous peoples than for non-Indigenous populations. However, this is not uniformly the case, and the size of the rate difference varies. We document poorer outcomes for Indigenous populations for: life expectancy at birth for 16 of 18 populations with a difference greater than 1 year in 15 populations; infant mortality rate for 18 of 19 populations with a rate difference greater than one per 1000 livebirths in 16 populations; maternal mortality in ten populations; low birthweight with the rate difference greater than 2% in three populations; high birthweight with the rate difference greater than 2% in one population; child malnutrition for ten of 16 populations with a difference greater than 10% in five populations; child obesity for eight of 12 populations with a difference greater than 5% in four populations; adult obesity for seven of 13 populations with a difference greater than 10% in four populations; educational attainment for 26 of 27 populations with a difference greater than 1% in 24 populations; and economic status for 15 of 18 populations with a difference greater than 1% in 14 populations. INTERPRETATION: We systematically collated data across a broader sample of countries and indicators than done in previous studies. Taking into account the UN Sustainable Development Goals, we recommend that national governments develop targeted policy responses to Indigenous health, improving access to health services, and Indigenous data within national surveillance systems. FUNDING: The Lowitja Institute.

Infant mortality of Sami and settlers in Northern Sweden: the era of colonization 1750-1900.

UNLABELLED: The study deals with infant mortality (IMR) that is one of the most important aspects of indigenous vulnerability. BACKGROUND: The Sami are one of very few indigenous peoples with an experience of a positive mortality transition. OBJECTIVE: Using unique mortality data from the period 1750-1900 Sami and the colonizers in northern Sweden are compared in order to reveal an eventual infant mortality transition. FINDINGS: The results show ethnic differences with the Sami having higher IMR, although the differences decrease over time. There were also geographical and cultural differences within the Sami, with significantly lower IMR among the South Sami. Generally, parity has high explanatory value, where an increased risk is noted for children born as number five or higher among siblings. CONCLUSION: There is a striking trend of decreasing IMR among the Sami after 1860, which, however, was not the result of professional health care. Other indigenous peoples of the Arctic still have higher mortality rates, and IMR below 100 was achieved only after 1950 in most countries. The decrease in Sami infant mortality was certainly an important factor in their unique health transition, but the most significant change occurred after 1900.

Abandoning "the other": statistical enumeration of Swedish Sami, 1700 to 1945 and beyond.

Sweden has one of the world's most eminent and exhaustive records of statistical information on its population. As early as the eighteenth century, ethnic notations were being made in parish registers throughout the country, and by the early nineteenth century a specific category for the Sami population had been added to the forms used to collect data for the Tabellverket (National Population Statistics). Beginning in 1860, the Sami were also counted in the first official census of the Swedish state. Nonetheless--and in contrast to many other countries--Sweden today lacks separate statistical information not only about its sole recognized indigenous population but also about other ethnic groups. The present paper investigates Sweden's attempts to enumerate its indigenous Sami population prior to World War II and the cessation of ethnic enumeration after the war. How have the Sami been identified and enumerated? How have statistical categories been constructed, and how have they changed over time? The aim of this essay is not to assess the validity of the demographic sources. Instead the paper will explore the historical, social, and cultural factors that have had a bearing on how a dominant administrative structure has dealt with the statistical construct of an indigenous population.

"Do not eat those apples; they've been on the ground!": polio epidemics and preventive measures, Sweden 1880s-1940s.

This article will address how Swedish scientists, physicians and public health officers tried to combat the polio epidemics in the pre-vaccine era. It shows that once polio was considered as an epidemic disease the preventive measures used were based on the hindrance of other infectious diseases. It also illustrates how epidemiological and laboratory studies to some degree affected the thoughts of how polio should be prevented, and that Swedish ideas and experiences differed from those put forward in the USA.

The northern population development; colonization and mortality in Swedish Sápmi, 1776-1895.

OBJECTIVES: The aim of the Consequence of Colonization project is to study population development and mortality in Swedish Sápmi. This article, the first to be drawn from our research, compares these changes between Sami and non-Sami, South and North Sami. Study design. Longitudinal individual based data from computerized records ofthe Glillivare, Undersåker and Frostviken parishes, divided into 2 40-year periods: 1776-1815 and 1856-1895. METHODS: The main source material used for the present study was a set of data files from the Demographic Data Base (DDB) at Umeå University, the largest historical database in Europe. A Sami cohort was created by indicators of ethnicity in the parish registers, and was later extended with automatic linkages to children and parents. RESULTS: Sami mortality rates show great fluctuations during the period 1776-1815, almost always peaking at a higher rate than in the rest of Sweden. The non-Sami group had lower mortality rates compared with both Sweden as a whole and the Sami in the parish. Between 1856 and 1895, the non-Sami experienced a very small reduction in their mortality rates and the Sami experienced overall improvement in their health status. Significant differences in age-specific mortality appear when the South and North Sami are compared, showing that the South Sami had far lower child mortality rates. CONCLUSIONS: The Sami population's health status improved during the nineteenth century. This indicates that they had advanced in the epidemiologic transition model. A corresponding change is not found for the non-Sami group.

Some characteristics of 50/55-year-old individuals with various experience of destructive periodontal disease: a cross-sectional study.

OBJECTIVE: To analyze the association between subject characteristics and degree of destructive periodontal disease in a randomly selected sample of 50/55-year-old individuals. METHODS: A randomized and geographically stratified (urban/rural districts) subject sample composed of dentate 50-year-old (n = 190) and 55-year-old individuals (n = 359) from the county of Varmland, Sweden were examined. Data were collected through full mouth clinical and radiographic examinations and by the use of questionnaires. Based on the cumulative distribution of the individuals with respect to mean probing attachment loss (PAL), subgroups of subjects with the lowest (L20%) and highest (H20%) experience of PAL were identified. Similar classifications were made for never-smokers and current smokers. Correlation analyses and forward stepwise logistic regression models were performed. RESULTS: The subgroup with the most extensive PAL loss (H20%) included a significantly higher proportion of (i) males (60 vs 33%), (ii) subjects with low educational level (65 vs 41%), (iii) smokers (49 vs 15%), and had (iv) less favorable lifestyle characteristics than the subgroup with minimal experience of PAL loss (L20%). The same pattern of differences was observed when the analysis was restricted to never-smokers, with the addition of a significantly lower proportion of subjects living in urban areas (40 vs 69%) in the H20% compared to the L20% subgroup. The stepwise logistic regression analysis revealed that number of teeth and smoking habits were significant factors in the identification of individuals in the L20% subgroup. For the H20% subgroup, number of teeth, gender, number of cigarettes/day and lifestyle index were significant explanatory variables. CONCLUSION: Number of remaining teeth and smoking habits were identified as the main discriminating factors for classification of subjects with regard to degree of destructive periodontal disease.

Intra-oral pattern of tooth and periodontal bone loss between the age of 50 and 60 years. A longitudinal prospective study.

OBJECTIVE: In a 10-year prospective study we analyzed (i) the intra-oral pattern of and (ii) potential risk factors for tooth and periodontal bone loss in 50-year-old individuals. METHODS: A randomized subject sample of 50-year-old inhabitants in the County of Varmland, Sweden, was examined at baseline and after 10 years. Data from full-mouth clinical and radiographic examinations and questionnaire surveys of 309 (72%) of the individuals who were dentate at baseline were available for analysis. Non-parametric tests and binary logistic multiple regression models were used for statistical analysis of the data. RESULTS: 4.1% of the 7,101 teeth present at baseline, distributed among 39% of the subjects, were lost during the 10-year interval. The incidence of tooth loss was highest among mandibular molars (7.5%) and lowest among canines (1.8%). The relative risk (RR) for tooth loss for endodontically compromised teeth was 4.1 and for furcation-involved molars 2.4-6.5, depending on tooth position. Logistic regression analysis identified baseline alveolar bone level (ABL), endodontic conditions, CPITN score (Community Periodontal Index of Treatment Needs), tooth position, caries, and educational level as risk factors for tooth loss. The overall mean 10-year ABL change was -0.54 mm (S.E. 0.01). On a tooth level the ABL change varied between -0.35 mm (mandibular molars) and -0.79 mm (mandibular incisors). Smokers experienced a greater (20-131% depending on tooth type) mean bone loss than non-smokers. The logistic regression model revealed that tooth position, smoking, and probing pocket depth > or =4 mm were risk factors for bone loss of >1 mm. No pertinent differences were observed with respect to risk factors for ABL change in the subgroup of non-smokers compared to the results of the analysis based on the entire subject sample. CONCLUSION: Tooth loss was more common in the molar than in the anterior tooth regions, while periodontal bone loss had a random distribution in the dentition. The predominant risk factors identified with regard to further radiographic bone loss were "probing pocket depth > or =6 mm" and "smoking".

Some risk factors for periodontal bone loss in 50-year-old individuals. A 10-year cohort study.

OBJECTIVE: The aim of this 10-year prospective study of 50-year-old individuals was to analyze the incidence of periodontal bone loss and potential risk factors for periodontal bone loss. METHODS: The subject sample was generated from an epidemiological survey performed in 1988 of subjects living in the County of Värmland, Sweden. A randomized sample of 15% of the 50-year-old inhabitants in the county was drawn. At the 10-year follow-up in 1998, 320 (75%) of the 449 individuals examined at baseline were available for re-examination, out of which 4 had become edentulous. Full-mouth clinical and radiographic examinations and questionnaire surveys were performed in 1988 and 1998. Two hundred and ninety-five individuals (69%) had complete data for inclusion in the analysis of radiographic bone changes over 10 years. Non-parametric tests, correlations and stepwise multiple regression models were used for statistical analysis of the data. RESULTS: The mean alveolar bone level (ABL) in 1988 was 2.2 mm (0.05) and a further 0.4 mm (0.57) (p=0.000) was lost over the 10 years. Eight percent of the subject sample showed no loss, while 5% experienced a mean bone loss of >/=1 mm. Smoking was found to be the strongest individual risk predictor (RR=3.2; 95% CI 2.03-5.15). When including as smokers only those individuals who had continued with the habit during the entire 10-year follow-up period, the relative risk was slightly increased (3.6; 95% CI 2.32-5.57). Subjects who had quit smoking before the baseline examination did not demonstrate a significantly increased risk for disease progression (RR=1.3; 95% CI 0.57-2.96). Stepwise multiple regression analysis revealed that smoking, % approximal sites with probing pocket depth >/=4 mm, number of teeth and systemic disease were significant explanatory factors for 10-year ABL loss (R(2)=0.12). For never smokers, statistically significant predictors were number of teeth, mean ABL, % periodontally healthy approximal sites and educational level (R(2)=0.20). CONCLUSION: The inclusion of smokers in risk analysis for periodontal diseases may obstruct the possibility to detect other true risk factors and risk indicators.

[The history of polio in Sweden - from infantile paralysis to polio vaccine]. / Historien om polio i Sverige: från barnförlamning till poliovaccin.

Although other epidemics declined due to improved hygiene and sanitation, legislation, and vaccination, polio epidemics appeared in Sweden in 1881 and at the turn of the 20th century the disease became and annual feature in the Swedish epidemiological pattern. Due to the vaccination starting in 1957 epidemics ceased to exist in Sweden around 1965. This article deals with the history polio epidemics in Sweden, 1880-1965 and gives a brief description of: the demographical influence of polio, how did the medical authorities investigate and try to combat it, and the different comprehensions of how polio affected its victims.A study of polio incidence in Sweden at the national level during 1905-1962 reveals that the disease caused major epidemics in 1911-1913 and 1953. At the beginning of the 20th century polio primarily attacked children up to 10 years of age, and at the end of the period victims were represented in all age groups, but mainly in the ages 20-39. Due to its enigmatic appearance, polio was not considered as an epidemic infectious disease during the 19th century. Sweden's early epidemics enabled Swedish medical science to act and together with American research institutes it acquired a leading role in international medical research on the disease. In the 1955 Jonas Salk produced the first successful vaccine against polio but also Sweden developed its own vaccine, different in choice of methods and materials from the widely used Salk-vaccine.