Monoclonal gammopathy of undetermined significance : natural course and comorbidities

Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder characterized by an overproduction of monoclonal immunoglobulins. MGUS is asymptomatic but clinically relevant since annually 0.5-1.5% of individuals with MGUS will develop multiple myeloma (MM) or another malignant lymphoproliferative disease. Individuals with MGUS are followed for signs of progression, however, so far this management strategy has never been evaluated. Results from previous studies have shown that individuals with MGUS have inferior survival and increased risk of thrombosis compared to individuals without MGUS, yet all studies to date have been performed on clinically established cohorts of MGUS patients, introducing a high risk of selection bias. Recently, a new entity called light-chain MGUS (LC-MGUS) has been identified. Very little is known about the epidemiology and clinical course of LC-MGUS. In order to establish a clinically informative, correct, and easily applicable definition of LC-MGUS, and describe the prevalence of MGUS and LC-MGUS in the population, we performed a large population-based screening study. We screened more than 11,000 individuals from the Icelandic AGES-Reykjavik Study cohort and the American PLCO Study cohort. The prevalence of MGUS was 4.8-5.2%. Based on findings from the two cohorts and on statistical analysis of normal distributions, we propose a revised definition of LC-MGUS; (1) an abnormal free light-chain ratio (1.65), (2) an elevated involved light chain concentration (40 mg/L or higher), (3) no M-protein on serum protein electrophoresis or immunofixation, and (4) no evidence of end-organ damage that can be attributed to a lymphoproliferative disorder. The prevalence of LC-MGUS in our study using this definition was 0.9-1.0%. The prevalence of LC-MGUS increased with age (p<0.001), was higher in men (p<0.001), and more common among blacks (2.9%) than whites (0.7%) or Asian/Pacific Islanders (0.2%). The revised definition of LC-MGUS captures the condition in fewer but clinically relevant individuals. We conducted three population-based studies with the purpose of studying the natural course and survival of individuals with MGUS and LC-MGUS. We used the Icelandic AGES-Reykjavik Study cohort of 5,764 individuals, including 300 individuals with MGUS and 52 individuals with LC-MGUS, as well as a Swedish cohort of 18,768 MGUS patients. Through the Swedish Cancer Register we identified all patients with MM diagnosed from 1976 to 2013, as well as randomly sampled population-based controls. Individuals with MGUS had a 1.2-fold (95% confidence interval (CI) 1.04-1.4) and individuals with LC-MGUS had a 1.6-fold (1.2-2.3) increased risk of death compared to individuals without MGUS, during a median follow-up time of almost ten years. The risk remained increased after progression to lymphoproliferative disease was taken into account. We found a personal history of autoimmune disease to increase the risk of death significantly in both individuals with MM (hazard ratio (HR) = 1.2, 1.2-1.3) and individuals with MGUS (HR = 1.4, 1.3-1.4). These findings could be due to an underlying genetic susceptibility for both plasma cell disorders and other conditions, such as autoimmune disease, or to the overproduction of light chains causing organ damage. We found that MM patients with prior knowledge of MGUS had a better overall survival (median survival 2.8 years) than MM patients without prior knowledge of MGUS (median survival 2.1 years). Among MM patients with a prior knowledge of MGUS, a low M-protein concentration at MGUS diagnosis was predictive of worse survival in MM (HR = 1.9, 1.1-3.0), possibly due to patients with low M-protein concentration being followed less frequently. Our findings support the recommendations of regular clinical follow-up of individuals with MGUS, regardless of M-protein concentration. In further analysis of the AGES-Reykjavik Study cohort, we assessed the causes of death and risk of thrombosis among individuals with MGUS and LC-MGUS and found an increased risk of death from cancer (HR = 1.8, 1.6-2.3) and from heart disease (HR = 1.4, 1.1-1.8), adjusted for age and sex. We found that a history of thrombosis was more common in individuals with LC-MGUS (25%) than individuals with MGUS (10%) or without MGUS (12%), and that individuals with LC-MGUS had an increased risk of a history of arterial thrombosis especially (crude odds ratio (OR) = 2.5, 95% CI 1.3-4.9), compared to individuals without MGUS. During a median follow-up time of almost nine years, we detected an almost two-fold risk of arterial thrombosis in individuals with LC-MGUS compared to individuals without MGUS (crude HR = 1.9, 1.1-3.2). No increased risk of venous thrombosis was detected in individuals with MGUS or LC-MGUS. Our results suggest that previously detected increased risks of thrombosis in MGUS have been due to confounding factors. Our findings on LC-MGUS point towards an elevated risk of arterial, but not venous, thrombosis. In future investigations, we suggest attention is focused on characterizing the clinical, genetic, and biochemical profiles of LC-MGUS, with the purpose of understanding the connection to cancer, to heart disease, and to thrombosis

Incidence and risk factors for suicide and attempted suicide following a diagnosis of hematological malignancy.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Solid tumors are associated with an increased risk of suicide, however, there is limited detailed information on the risk of suicide in patients with hematological malignancies. Therefore, we conducted a population-based study including 47,220 patients with hematological malignancies (diagnosed 1992-2006) and their 235,868 matched controls to define the incidence and risk factors for suicide and suicide attempt. Information on suicides, suicide attempts, and preexisting psychiatric disorders was obtained from Swedish registers and individual medical records. There was a twofold increased (hazard ratio [HR] = 1.9, 95% confidence interval 1.5-2.3, P < 0.0001) risk of suicide/suicide attempt during the first 3 years after diagnosis in patients with hematological malignancies compared to matched controls. Of all hematological malignancies, multiple myeloma was associated with the highest risk (HR = 3.4; 2.3-5.0, P < 0.0001). Patients with a preexisting psychiatric disorder were at a very high risk of suicide and suicide attempt (HR = 23.3; 16.6-32.6, P < 0.0001), regardless of type of hematological malignancy. Among patients who committed suicide, 19% were in a palliative phase and 44% were in remission with no active treatment. In conclusion, the risk of suicide and suicide attempt is elevated in patients with hematological malignancies. Certain high-risk patients may benefit from early detection and preventive measures.Swedish Cancer Society CAN 2012/483 regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet 20120004 Adolf H Lundin Charitable Foundation Blodcancerfonde

History of autoimmune disease is associated with impaired survival in multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesMultiple myeloma (MM) is a plasma cell disorder preceded by monoclonal gammopathy of undetermined significance (MGUS). Incidence of MM and MGUS is higher among patients with autoimmune disease. The aim of this study was to determine whether a history of autoimmunity has an impact on survival in MM and MGUS. Using high-quality national Swedish registries, we identified 8367 patients with MM, 18,768 patients with MGUS, and 110,251 matched control subjects, and obtained information on previous autoimmune disease in patients and controls. Cox regression was used to calculate hazard ratios (HRs) for overall survival with 95 % confidence intervals (CIs). In patients with MM and a prior autoimmune disease, the risk of death was significantly increased, HR = 1.2 (95 % CI 1.2-1.3) compared to MM patients with no history of autoimmunity. In MGUS patients, a prior autoimmune disease was associated with a significantly 1.4-fold elevated risk of death (95 % CI 1.3-1.4). When analyzing different types of autoimmune diseases, a history of ulcerative colitis had a stronger impact on survival in MM than in controls. Our findings that a history of autoimmune disease has a negative impact on survival in MM and MGUS could be due to shared underlying common genetic factors, or that patients with a history of autoimmunity develop more severe cases of MM and MGUS, or cumulative comorbidity in the individual. Our results suggest that more attention should be paid to comorbidity as a prognostic factor in MGUS and MM, and underlines the need for studies aimed at tailoring therapy according to comorbidity.Swedish Blodcancerfonden Swedish Cancer Society Stockholm County Council Karolinska Institutet Karolinska Institutet Foundations University of Iceland Icelandic Centre for Research (RANNIS) Landspitali University Hospita

Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesAll multiple myeloma (MM) cases are preceded by the premalignant state monoclonal gammopathy of undetermined significance (MGUS). Results from previous studies show a positive association between obesity and MM; however, the association between obesity and MGUS is controversial. The aims were to determine (1) if obesity is associated with an increased risk of MGUS and light-chain MGUS (LC-MGUS) and (2) whether obesity is associated with a higher risk of progression to MM and other lymphoproliferative (LP) diseases. Data from the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (N = 5764) were used. We performed serum protein electrophoresis and serum free light-chain assay on all subjects to identify MGUS and LC-MGUS cases. We included 11 different measures on current and previous obesity in our analysis. Logistic regression and Cox proportional-hazard regression were used to analyze the associations. A total of 300 (5.2%) MGUS and 275 (4.8%) LC-MGUS cases were identified. During a median follow-up of 8 years, 18 had progressed to MM and 11 to other LP diseases. We found no association between the 11 obesity markers and MGUS or LC-MGUS (odds ratios 0.81 to 1.15 for all 11 variables in both conditions). Interestingly, we found that high midlife body mass index increased risk of progression to MM and other LP diseases (hazard ratio, 2.66; 95% confidence interval, 1.17-6.05). To conclude, obesity was not associated with MGUS. However, we found overweight/obesity to be a risk factor for progression from MGUS to MM and other LP diseases, suggesting that obesity plays a role in the transformation of MGUS to MM.National Institutes of Health, National Institute on Aging National Institute on Aging Intramural Research Program, a National Eye Institute Intramural Research Program Award National Institute on Deafness and Other Communication Disorders, Division of Scientific Programs Hjartavernd (the Icelandic Heart Association) Althingi (the Icelandic Parliament) University of Iceland Research Fund Icelandic Centre for Research (RANNIS) Landspitali University Hospital Research Fund Karolinska Instituted Foundations Marie Curie CIG National Cancer Institute, National Institutes of Healt

Bone disease in monoclonal gammopathy of undetermined significance: results from a screened population-based study

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesPrevious studies have shown that individuals with monoclonal gammopathy of undetermined significance (MGUS) have an increased risk of fractures, although the underlying mechanisms remain unknown. Our aim was to analyze bone mineral density (BMD), bone volume, and risk of fractures among individuals with MGUS. We performed a screening using the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study cohort, consisting of 5764 elderly individuals, identifying 300 individuals with MGUS, and 275 with light-chain MGUS. Quantitative computerized tomography was performed in the lumbar spine and hip to evaluate BMD and bone geometry. Analysis of variance and the Tukey honest significance test were used to compare the groups. Hospital records were used to record fractures, with a mean follow-up of 6.9 years. Cox proportional hazard was used to compare fracture risk. No difference was found in BMD between subjects with MGUS and others in the spine (P = .34) or in total hip (P = .30). Individuals with MGUS had a significant increase in bone volume compared with others in the spine (P < .001) and total hip (P < .001). Overall, the risk of fractures was not significantly increased in individuals with MGUS (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.94-1.50). Men with MGUS had a significantly increased fracture risk, compared with other men (HR, 1.46; 95% CI, 1.03-2.08). Our results show that although individuals with MGUS do not have decreased BMD, bone volume is increased, and MGUS men have a 50% increased fracture risk. These results indicate that bone disease and fractures in MGUS differ from processes known from osteoporosis.University of Iceland Research Fund Icelandic Centre for Research (RANNIS) Landspitali University Hospital Research Fund Karolinska Institutet Foundations Marie Curie Career Integration Grants (CIG) National Institutes of Health, National Institute on Aging (NIA) NIA Intramural Research Program National Eye Institute National Institute on Deafness and Other Communication Disorders Division of Scientific Programs, Hjartavernd Althingi (the Icelandic Parliament) National Cancer Institute Memorial Sloan Kettering Cancer Center Icelandic National Bioethics Committe

Dietary intake is associated with risk of multiple myeloma and its precursor disease

Publisher's version (útgefin grein)The etiology of monoclonal gammopathy of undetermined significance (MGUS), the precursor state of multiple myeloma (MM), is mostly unknown and no studies have been conducted on the effect of diet on MGUS or progression from MGUS to MM. We aimed to explore the association between common foods and MGUS and progression to MM. Data from the population-based AGES Study (N = 5,764) were utilized. Food frequency questionnaire was used to assess dietary intake during adolescence, midlife, and late life. Serum protein electrophoresis and serum free light-chain assay was performed to identify MGUS (n = 300) and LC-MGUS cases (n = 275). We cross linked our data with the Icelandic Cancer Registry to find cases of MM in the study group. We found that intake of fruit at least three times per week during adolescence was associated with lower risk of MGUS when compared to lower fruit consumption (OR = 0.62, 95% CI 0.41–0.95). We additionally found that intake of fruit at least three times per week during the late life period was associated with decreased risk of progressing from MGUS to MM (HR = 0.34, 95% CI 0.13–0.89) when compared to lower intake. Adolescent intake of fruit may reduce risk of MGUS, whereas fruit intake after MGUS onset may reduce risk of progressing to MM. Our findings suggest that diet might alter the risk of developing MGUS and progression to MM.The AGES-Reykjavik Study was funded by NIH contract N01-AG-012100, the Intramural Research Program of the National Institute on Aging, by the Icelandic Heart Association, and the Icelandic Parliament. This work was supported by the Icelandic Centre for Research, RANNIS (S.Y. Kristinsson), the Landspitali University Hospital Research Fund (S.Y. Kristinsson), the Karolinska Instituted Foundations (S.Y. Kristinsson), the Marie Curie CIG (S.Y. Kristinsson), and the Memorial Sloan Kettering Core Grant (P30 CA008748) from the National Cancer Institute (O.Landgren). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer Reviewe

Space cooling by district heating : Local absorption chillers in Visby’s district heating system

Behovet av komfortkyla i byggnader förväntas öka till följd av bland annat den globala uppvärmningen och högre krav på behagligt inomhusklimat. Bortsett från fjärrkyla är eldrivna kompressorkylmaskiner idag den vanligaste kyltekniken för komfortkyla. Flera delar av samhället ställs idag om till eldrift, vilket ställer högre krav på elnäten och elproduktionen. Genom att utnyttja fjärrvärmedrivna absorptionskylmaskiner för att möta kylbehovet kan elnäten avlastas och produktionen av marginalel minska. Syftet med detta examensarbete har varit att undersöka möjligheten för Gotlands Energi AB (GEAB) att erbjuda fjärrvärmedriven absorptionskyla genom att installera lokala absorptionskylmaskiner i Visbys fjärrvärmenät. Livscykelkostnaden för absorptionskylanläggningar har beräknats för två referensbyggnader i Visby som har installerade kyleffekter på 170 och 430 kW. Ett kylpris har beräknats för att investeringen ska vara lönsam för GEAB. Hur fjärrvärmenätets returtemperatur påverkas har beräknats utifrån driftdata från GEAB:s fjärrvärmenät i Visby samt specifikationer för absorptionskylmaskinerna. Klimatpåverkan för absorptionskyla och kompressorkyla har beräknats och jämförts med varandra. Resultatet visar att priset för kyla som produceras med absorptionskyla tydligt minskar vid en högre installerad effekt. För en byggnad med en installerad maxeffekt på 170 kW och ett kylbehov på 30 kWh/m2 behöver kylan säljas för 1,79-1,92 SEK/kWh. För en byggnad med en installerad maxeffekt på 430 kW och ett kylbehov på 33 kWh/m2 behöver kylan säljas för 1,21-1,45 SEK/kWh. Lönsamheten för respektive byggnad varierar utifrån vilken värmesänka som används. Det mest ekonomiskt lönsamma är en absorptionskylanläggning där värmesänkan är ett öppet evaporativt kyltorn. En känslighetsanalys visar även att byggnadens kylbehov spelar stor roll för vilket pris som kylan kan säljas för. Ett lågt kylbehov kräver ett högre kylpris för ekonomisk lönsamhet. Om kylan i stället produceras med kompressorkyla behöver den säljas för 1,11 SEK/kWh och 1,24 SEK/kWh för respektive byggnad. Utifrån beräkningarna konstateras att en installerad effekt på 170 kW höjer returtemperaturen med 1,2°C. En installerad effekt på 430 kW höjer returtemperaturen med 2,7°C. Med absorptionskyla i båda byggnaderna och en installerad effekt på 600 kW höjs returtemperaturen med 3,5°C. Beräkningarna har gjorts för maxeffekt. Med miljövärderingen långsiktig marginalel skulle kylproduktion med kompressorkyla ge utsläpp av 190 g CO2-e/kWh. För en byggnad med en installerad maxeffekt på 170 kW skulle en absorptionskylanläggning ge utsläpp av 72–98 g CO2-e/kWh, beroende på valet av värmesänka. För en byggnad med en installerad maxeffekt på 430 kW skulle en absorptionskylanläggning ge utsläpp av 60–86 g CO2-e/kWh, beroende på valet av värmesänka. Att använda absorptionskyla i stället för kompressorkyla ger positiva effekter på klimatet då det minskar produktionen av marginalel

Space cooling by district heating : Local absorption chillers in Visby’s district heating system

Behovet av komfortkyla i byggnader förväntas öka till följd av bland annat den globala uppvärmningen och högre krav på behagligt inomhusklimat. Bortsett från fjärrkyla är eldrivna kompressorkylmaskiner idag den vanligaste kyltekniken för komfortkyla. Flera delar av samhället ställs idag om till eldrift, vilket ställer högre krav på elnäten och elproduktionen. Genom att utnyttja fjärrvärmedrivna absorptionskylmaskiner för att möta kylbehovet kan elnäten avlastas och produktionen av marginalel minska. Syftet med detta examensarbete har varit att undersöka möjligheten för Gotlands Energi AB (GEAB) att erbjuda fjärrvärmedriven absorptionskyla genom att installera lokala absorptionskylmaskiner i Visbys fjärrvärmenät. Livscykelkostnaden för absorptionskylanläggningar har beräknats för två referensbyggnader i Visby som har installerade kyleffekter på 170 och 430 kW. Ett kylpris har beräknats för att investeringen ska vara lönsam för GEAB. Hur fjärrvärmenätets returtemperatur påverkas har beräknats utifrån driftdata från GEAB:s fjärrvärmenät i Visby samt specifikationer för absorptionskylmaskinerna. Klimatpåverkan för absorptionskyla och kompressorkyla har beräknats och jämförts med varandra. Resultatet visar att priset för kyla som produceras med absorptionskyla tydligt minskar vid en högre installerad effekt. För en byggnad med en installerad maxeffekt på 170 kW och ett kylbehov på 30 kWh/m2 behöver kylan säljas för 1,79-1,92 SEK/kWh. För en byggnad med en installerad maxeffekt på 430 kW och ett kylbehov på 33 kWh/m2 behöver kylan säljas för 1,21-1,45 SEK/kWh. Lönsamheten för respektive byggnad varierar utifrån vilken värmesänka som används. Det mest ekonomiskt lönsamma är en absorptionskylanläggning där värmesänkan är ett öppet evaporativt kyltorn. En känslighetsanalys visar även att byggnadens kylbehov spelar stor roll för vilket pris som kylan kan säljas för. Ett lågt kylbehov kräver ett högre kylpris för ekonomisk lönsamhet. Om kylan i stället produceras med kompressorkyla behöver den säljas för 1,11 SEK/kWh och 1,24 SEK/kWh för respektive byggnad. Utifrån beräkningarna konstateras att en installerad effekt på 170 kW höjer returtemperaturen med 1,2°C. En installerad effekt på 430 kW höjer returtemperaturen med 2,7°C. Med absorptionskyla i båda byggnaderna och en installerad effekt på 600 kW höjs returtemperaturen med 3,5°C. Beräkningarna har gjorts för maxeffekt. Med miljövärderingen långsiktig marginalel skulle kylproduktion med kompressorkyla ge utsläpp av 190 g CO2-e/kWh. För en byggnad med en installerad maxeffekt på 170 kW skulle en absorptionskylanläggning ge utsläpp av 72–98 g CO2-e/kWh, beroende på valet av värmesänka. För en byggnad med en installerad maxeffekt på 430 kW skulle en absorptionskylanläggning ge utsläpp av 60–86 g CO2-e/kWh, beroende på valet av värmesänka. Att använda absorptionskyla i stället för kompressorkyla ger positiva effekter på klimatet då det minskar produktionen av marginalel

Self-care strategies for premenstrual syndrome and premenstrual dysphoric syndrome

Bakgrund Premenstruellt syndrom (PMS) och premenstruellt dysforiskt syndrom (PMDS) är tillstånd som innebär en samlad mängd psykiska och/eller fysiska premenstruella besvär hos vissa kvinnor. Dessa tillstånd utgör ett stort lidande och kan leda till psykisk ohälsa, långtidssjukskrivningar, somatiska besvär, drabbade relationer samt svårigheter att klara av sin vardag. Omvårdnadsforskning av dessa kvinnor är dock bristfällig. Forskning på området omvårdnad har dock visat att egenvård stärker patientens känsla av kontroll vid såväl psykiatriska som somatiska sjukdomstillstånd. Syfte Att belysa olika egenvårdsstrategier som kan leda till ett minskat lidande för patienter med premenstruellt syndrom eller premenstruellt dysforiskt syndrom. Metod Studien är en litteraturöversikt och inkluderar 17 vetenskapliga artiklar som söktes fram via systematiska databassökningar i PubMed och Cinahl. Valda artiklar var av kvalitativ och kvantitativ metod för att få en ökad förståelse för både upplevelse av egenvård samt objektiva mått för effektiviteten. Resultat Det fanns en mängd olika egenvårdsstrategier som kvinnor använder sig av och kan använda sig av i olika grad. Tre kategorier i form av livsstil, psykosociala aspekter samt komplementära terapier skapades under analysprocessen. De egenvårdsstrategier som visade det starkaste sambandet med minskat lidande vid PMS eller PMDS var stressreducering, regelbunden fysisk aktivitet och ökad medvetenhet kring sin kropp och sitt eget mående. Slutsats I studierna visade det sig att kvinnor använde egenvårdsstrategier i varierande grad och att de upplevde effektiviteten olika. Egenvård kunde lindra symtomen av PMS/PMDS i olika grad, och främjade känslan av kontroll över den egna situationen. Egenvårdsstrategier kan därmed vara ett redskap för att minska lidandet vid PMS/PMDS.Background Premenstrual syndrome (PMS) and premenstrual dysphoric syndrome (PMDS) are conditions that involve a total amount of mental and / or physical premenstrual disorders for some women. These conditions are a major affliction and can lead to mental illness, long-term sick leave, somatic disorders, affected relationships and difficulties in coping with their everyday lives. However, nursing research of these women is inadequate. Research in the field of nursing has shown that self-care strengthens the patient's sense of control in both psychiatric and somatic disease states. Aim To illuminate different self-care strategies that may lead to reduced suffering for patients with premenstrual syndrome and premenstrual dysphoric syndrome. Method The study is a literature review and includes 17 scientific articles that were searched through systematic database searches in PubMed and Cinahl. Selected articles were of qualitative and quantitative method to gain an increased understanding of both self-care experience and objective measures of efficiency. Results There was a variety of self-care strategies that women use and may use to varying degrees. Three categories in the form of lifestyle, psychosocial aspects and complementary therapies were created during the analysis process. The self-care strategies that has showed the strongest connection with reduced suffering at PMS or PMDS were stress reduction, regular physical activity and increased awareness of their body and their own mood.ConclusionsIn the studies, it was found that women used self-care strategies to varying degrees and that they perceived their effectiveness differently. Self-care was able to relieve the symptoms of PMS / PMDS to varying degrees and promoted the feeling of control over one's own situation. Self-care strategies can thus be a tool for reducing the suffering of PMS / PMDS