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.

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.

Interpersonal Violence Against Indigenous Sámi and Non-Sámi Populations in Arctic Sweden and the Mediating Effect of Historical Losses and Discrimination.

The prevalence of interpersonal violence has been reported at higher levels among Indigenous than non-Indigenous populations worldwide, but has not been thoroughly investigated among the Sámi population in Sweden. The aims of this study were to investigate: (1) the prevalence of emotional, physical, and sexual violence and violence by intimate partners, family members, acquaintances, and strangers among participants identifying as Sámi or Swedish, (2) whether reporting experiences of historical losses and discrimination mediated the anticipated association between identifying as Sámi and reporting experiences of violence, and (3) whether background characteristics were associated with reporting experiences of violence. Cross-sectional questionnaire data collected in 2021 for the "Health and Living conditions in Sápmi" study were used. All adults in an arctic region in Sweden were invited to participate (response rate: 41%). Respondents self-identifying as Sámi (n = 375; 24.7%) or Swedish (n = 1,144; 75.3%) were included in this study. Sámi respondents of both sexes more often reported violence by an acquaintance or stranger. Likewise, more Sámi than Swedish women reported family violence (16.4% vs. 9.2%), but there was no difference concerning intimate partner violence (13.3% vs. 15.4%). Mediation analyses revealed strong positive indirect effects of historical losses and discrimination on the different types of violence. Being female was the strongest predictor of reporting intimate partner violence, and younger age was associated with violence by all perpetrators except family members. In conclusion, interpersonal violence was more often reported by Sámi respondents, but the association was explained in full by experiences of historical losses and discrimination. The results underline the importance of a life-course and even intergenerational and historical perspectives when investigating interpersonal violence.

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.

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.

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.

Measures to prevent portable ladder accidents in the construction industry.

Ladder accidents account for nearly 5% of all reported occupational accidents in the Swedish construction industry. Eighty-five ladder accident victims were interviewed to obtain detailed information about factors contributing to their accidents. Accidents were almost equally divided between straight ladders (N = 39) and step- ladder (N = 33). The majority of accidents occurred while the victim was working from the ladder. Climbing up and, particularly, down straight ladders was associated with numerous accidents. For straight ladders, sliding at the base was the most common event preceding the injury. Low angle of inclination was a common contributing factor. For step-ladders, tipping sideways was the most common preceding event. Misstepping the final step while descending accounted for 10% of all accidents. More than 90% of the victims fell from less than 4 m. The interviews provided detailed information which served as a basis for proposals for alternatives to portable ladders; a step-scaffold adjustable for work at levels up to 3 m and a portable scaffold for work at levels of 1-3 m. These alternatives are under development. In addition, proposals for improving the stability of current portable ladders are made.