Treatment with Daratumumab (Dara), a monoclonal anti-CD38 antibody of IgG1 subtype, is effective in patients with multiple myeloma (MM). However, Dara also impairs the cellular immunity, which in ...turn may lead to higher susceptibility to infections. The exact link between immune impairment and infectious complications is unclear. In this study, we report that nine out of 23 patients (39%) with progressive MM had infectious complications after Dara treatment. Five of these patients had viral infections, two developed with bacterial infections and two with both bacterial and viral infections. Two of the viral infections were exogenous, i.e. acute respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), while five consisted of reactivations, i.e. one herpes simplex (HSV), 1 varicella-zoster (VZV) and three cytomegalovirus (CMV). Infections were solely seen in patients with partial response or worse. Assessment of circulating lymphocytes indicated a selective depletion of NK cells and viral reactivation after Dara treatment, however this finding does not exclude the multiple components of viral immune-surveillance that may get disabled during this monoclonal treatment in this patient cohort. These results suggest that the use of antiviral and antibacterial prophylaxis and screening of the patients should be considered.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Renal impairment is a common feature in multiple myeloma and is considered a poor prognostic factor.
To determine the impact of novel drugs (i.e. bortezomib, lenalidomide and thalidomide) in the ...treatment of myeloma patients with renal impairment. The primary endpoint was overall survival and secondary endpoints were time to next treatment and response.
The study population included all patients diagnosed with treatment-demanding multiple myeloma January 2000 to June 2011 at 15 Swedish hospitals. Renal impairment was defined as an estimated glomerular filtration rate under 60 mL/min/1.73 m2.
The study population consisted of 1538 patients, of which 680 had renal impairment at diagnosis. The median overall survival in patients with renal impairment was 33 months, which was significantly shorter than 52 months in patients with normal renal function (P<0.001). Novel agents in first line improved overall survival (median 60 months) in non-high-dose treated patients with renal impairment (n = 143) as compared to those treated with conventional cytotoxic drugs (n = 411) (median 27 months) (P<0.001). In the multivariate analysis up front treatment with bortezomib was an independent factor for better overall survival in non-high-dose treated renally impaired patients. High-dose treated renally impaired patients had significantly better median overall survival than non-high-dose ones (74 versus 26 months) and novel drugs did not significantly improve survival further in these patients. Patients with renal impairment had both a shorter median time to next treatment and a lower response rate than those with normal renal function. However, novel drugs and high dose treatment lead to a significantly longer time to next treatment and the use of novel agents significantly improved the response rate of these patients.
High dose treatment and novel drugs, especially bortezomib, can effectively overcome the negative impact of renal impairment in patients with multiple myeloma.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This text discusses how the storytelling of the lower classes shaped antagonisms and struggles for agency in the early modern Atlantic. It takes a mutiny carried out by a group of convicts and ...sailors on board a Danish ship, the Merman, in 1683 as its central case study.
Abstract
Introduction
The police register is the main database for monitoring traffic injuries. A study made by Safe Traffic in Norway found that only one of three severe traffic injuries is ...registered in this register. For giving more complete data, a health-based injury monitoring system was established in 2022 for a period of five years, financed by the traffic safety authorities.
Methods
An Injury Minimum Data Set (MDS) is collected from all injuries that are treated in ten hospitals and seven municipality AEDs in the primary health care, a representative sample of all medically treated injuries in Norway. By recording the unique birth number of the patient, double registrations are deleted. When fully developed, this system will register about 50 % of all injuries treated in the hospitals as in- and out-patients, and about 10 % of all injuries in the primary health care system in Norway. Max AIS (Abbreviated Injury Scale) and diagnosis (ICD-10 - hospitals, and ICPC-2 - primary health care) are among the registered variables for each injury. Based on the ICD-10 codes, long term disability weights (DW) can be calculated (Gabbe et al 2014). Then the injury burden of injuries in Norway can be shown by: 1) Threat to life: a) minor (AIS 1), b) moderate (AIS 2) and c) serious, (AIS 3+, including AIS 4-6). 2) Threat of disability: a) low, b) medium and c) high probability of long-term disability.
Results
Data from 2023 seems to be complete enough to enable calculations of the annual injury burden in Norway.
Future work
There is a need to establish internationally agreed disability weights to enable comparisons across countries. And to establish conversions from ICPC-2 codes to ICD-10 codes for enabling calculations of DWs of injuries treated in the primary health system.
It is important to obtain greater insight into health-related quality of life (HRQL) of injury patients in order to document people's pathways to recovery and to quantify the impact of injury on ...population health over time. We performed a systematic review of studies measuring HRQL in general injury populations with a generic health state measure to summarize existing knowledge.
Injury studies (1995-2009) were identified with main inclusion criteria being the use of a generic health status measure and not being restricted to one specific type of injury. Articles were collated by study design, HRQL instrument used, timing of assessment(s), predictive variables and ability to detect change over time.
Forty one studies met inclusion criteria, using 24 different generic HRQL and functional status measures (most used were SF-36, FIM, GOS, EQ-5D). The majority of the studies used a longitudinal design, but with different lengths and timings of follow-up (mostly 6, 12, and 24 months). Different generic health measures were able to discriminate between the health status of subgroups and picked up changes in health status between discharge and 12 month follow-up. Most studies reported high prevalences of health problems within the first year after injury. The twelve studies that reported HRQL utility scores showed considerable but incomplete recovery in the first year after discharge.
This systematic review demonstrates large variation in use of HRQL instruments, study populations, and assessment time points used in studies measuring HRQL of general injury populations. This variability impedes comparison of HRQL summary scores between studies and prevented formal meta-analyses aiming to quantify and improve precision of the impact of injury on population health over time.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Globally, work-related deaths (injuries and diseases) are a major social and public health problem. Register data on fatal occupational injuries in high-income countries may be considered to have ...high quality, especially when reporting is mandatory and regulated by law. We aimed to assess the accuracy of work-related injury death statistics in Norway, with reference to the Labour Inspection Authority and three other on-going registration systems (the cause-specific mortality register, the register for governmental compensations, and the register for insurance companies).
In this register-based study, we used the capture-recapture technique to adjust for undercounting. We investigated whether the capture-recapture method using two or three sources gave a valid estimate of fatal occupational injuries as compared with the number of cases identified in four registers administrated by the Norwegian Labour Inspection Authority, Statistics Norway, the Labour and Welfare Administration, and Finance Norway. The inclusion criteria were fatal unintentional injuries among residents of Norway between 2000 and 2003 that occurred while working for income in private and public land-based industries. We obtained ethical and legal approvals.
In a period of four years (2000−2003), the Labour Inspection Authority registered 171 occupational injury deaths among residents employed in land-based industries. Two combinations of data sources gave capture-recapture estimates of 246 95% CI 216; 279 and 265 95% CI 234; 299 deaths. In total, 246 cases were identified in the four registration systems, which was 44% higher than the number of deaths registered by the Labour Inspection Authority. The Labour Inspection Authority had the most complete register out of the four registration systems.
The capture-recapture method used on two overlapping data sources gave highly valid estimates of the total deaths. We demonstrated the existence of significant weaknesses in the registration systems in a country considered to have high-quality register data.
•Statistics from the Norwegian Labour Inspection Authority under-reported fatal occupational injuries.•The Labour Inspection Authority had the most complete register of the four registration systems.•The actual work injury mortality rate was 27.6 per 1 million employed, which is 44% higher than the official rate of 19.2.•Capture-recapture models gave estimates close to the total number of cases identified in the four registration systems.
Background
The presence of minimal residual disease (MRD+) following autologous stem cell transplantation (ASCT) in multiple myeloma represents a poor prognostic factor for progression‐free survival ...(PFS) and overall survival (OS).
Methods
At our department, we recommend lenalidomide maintenance for patients who are MRD+ after ASCT, while MRD‐negative (MRD−) patients, after information about the national guidelines, were not advised to follow this regimen.
Results
Out of the total 228 patients, 175 received ASCT following first‐line induction (MRD− 92 (53%), MRD+ 83 (47%), at 2 months post‐ASCT), while 53 underwent ASCT after second‐line treatment (MRD− 27 (51%), MRD+ 26 (49%), at the same time point). Comparatively, MRD− patients who did not receive maintenance demonstrated better OS than MRD+ patients who received upfront ASCT and maintenance treatment (96% vs. 86%, p = 0.030, at 3 years). However, nonsignificant difference was found in PFS (76% vs. 62%, at 3 years). Furthermore, second‐line ASCT, MRD− non‐maintained patients exhibited significantly better PFS than MRD+ (71% vs. 27%, p > 0.001, at 3 years). However, OS was better but nonsignificant (96% vs. 76%, at 3 years). Fluorescence in situ hybridization (FISH) analysis was performed on 141 out of the 228 patients. Of these, 85 (60%) patients were deemed standard risk (SR), and 56 (40%) were classified as high risk (HR). In the SR cohort, MRD− patients exhibited better PFS and OS than MRD+ patients (71% vs. 59% and 100% vs. 85%, respectively). In the HR cohort, the MRD− patients showed superior PFS but similar OS compared to MRD+ patients (66% vs. 42% and 81% vs. 80%, respectively).
Conclusions
Our results indicate that being MRD− is a more crucial prognostic factor for the 3‐year PFS and OS than the presence of high‐risk cytogenetic markers or undergoing maintenance treatment. The latter appears insufficient, particularly for MRD+ patients following ASCT in the second‐line setting, suggesting that these patients may require a more intensive treatment approach.
Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM) that undergo autologous stem cell transplantation (ASCT). In this study, we aimed to identify ...the immunological and molecular consequences of del(8)(p21) with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8)(p21) responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8)(p21) to TRAIL/APO2L mediated apoptosis, in cells with del(8)(p21) bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8)(p21) to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8)(p21).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
We wanted to evaluate if health care for multiple myeloma (MM) patients is equal in different regions of Sweden.
Aim
To study differences in survival for MM depending on health care region ...and early use of modern treatment.
Methods and results
Data from the Swedish Myeloma Register from patients diagnosed between 2008 and 2017 was used. Cohorts were defined by the six healthcare regions (labeled A–F) in Sweden and modern initial treatment was defined as including certain drug combinations. To adjust for time to treatment bias, survival analyses were performed also for patients alive 6 months after diagnosis. In all treated MM patients (n = 5326), we observed a superior overall survival (OS) for region A compared to all other regions (p < .01 for all respectively). After adjusting for time to treatment there was also a superior survival in the region with highest use of modern initial treatment (region A) compared to the regions defined in the study as having intermediate and low use (p < .01 for both). In patients receiving autologous stem cell transplantation (ASCT) a superior survival was observed for region A compared to all regions besides region B. Similar results were seen when adjusting for a time to treatment bias. In patients not receiving ASCT, 75 years or older and adjusted for time to treatment bias, a difference was noted only between region A and E (log rank p = .04, HR 1.2, CI 1.00–1.44, p = .06). In multivariate analyses including age, international staging system stage and time period of diagnosis, differences in survival remained for patients receiving ASCT between region A versus C, D, E and F (p = .01, p < .01, p < .01, p = .03).
Conclusion
We observed a superior survival in region A for patients receiving ASCT. Explanations may be higher usage of modern initial treatment or regional residual confounding. For patients not receiving ASCT, 75 years or older, differences in survival could be adjusted for.
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