A Novel Method for Real-Time Quantification of Radioligand Binding to Living Tumor Cells In Vitro.

Background: Real-time quantification of radioligand binding to cells under in vivo-like conditions improves evaluation of clinical potential. Materials and Methods: SKOV-3 tumor cells were grown in a monolayer on a thin glass plate placed in a sealable shallow chamber with a continuous flow of 125I-trastuzumab solution. The time-dependent cell binding was measured using a NaI detector, and the binding parameters were derived by computational analysis. Results: The detection efficiency of 125I was 65 cps/kBq for radioligand bound to the cells. Experiments were analyzed to find the values of kon and koff. The resulting kon was 3.2-7.9 × 104 M-1 s-1 and koff was 0.11-4.2 × 10-5 s-1. Conclusions: Radioligands can be rapidly evaluated by binding to living cells for selection and optimization of radioconjugates for diagnostic and therapeutic purposes.

Sámi traditional medicine and complementary and alternative medicine - a descriptive study of use within the Sámi population of Sweden.

Traditional medicine has been practised for millennia in the Sámi population, based on a Sámi worldview and cosmology, which includes natural remedies, prayers, drums and yoik singing. During the Christianisation of the Sámi during the seventeenth and eighteenth centuries, these practices were condemned. In recent years, however, a revival of Sámi culture has occurred and so has the practice of Sámi traditional medicine (STM) and the use of complementary alternative medicine (CAM). The aim of this study is to map the prevalence and use of STM and CAM among Sámi in Sweden today. The study population consisted of 3641 Sámi from the whole of Sweden, who had participated in the population-based cross-sectional survey Sámi Health on Equal Terms (SámiHET) in 2021. Our results show that women are more prone to use both STM and CAM than men and that younger persons are more likely to use STM and CAM than elderly persons. STM is more often used in the northern parts of Sápmi compared to the southern parts as well as a lower use of CAM in the north. This might be due to the stronger Sámi identity and easier access to traditional Sámi healers/helpers in the north as well as limited access to CAM services.

Estimating the Risk for Secondary Cancer After Targeted α-Therapy with 211At Intraperitoneal Radioimmunotherapy.

Intraperitoneal 211At-based targeted α-therapy (TAT) may hold great promise as an adjuvant therapy after surgery and chemotherapy in epithelial ovarian cancer to eradicate any remaining undetectable disease. This implies that it will also be delivered to patients possibly already cured by the primary treatment. An estimate of long-term risks is therefore sought to determine whether the treatment is justified. Methods: Baseline data for risk estimates of α-particle irradiation were collected from published studies on excess cancer induction and mortality for subjects exposed to either 224Ra treatments or Thorotrast contrast agent (25% ThO2 colloid, containing 232Th). Organ dosimetry for 224Ra and Thorotrast irradiation were taken from the literature. These organ-specific risks were then applied to our previously reported dosimetry for intraperitoneal 211At-TAT patients. Results: Risk could be estimated for 10 different organ or organ groups. The calculated excess relative risk per gray (ERR/Gy) could be sorted into 2 groups. The lower-ERR/Gy group, ranging up to a value of approximately 5, included trachea, bronchus, and lung, at 0.52 (95% CI, 0.21-0.82); stomach, at 1.4 (95% CI, -5.0-7.9); lymphoid and hematopoietic system, at 2.17 (95% CI, 1.7-2.7); bone and articular cartilage, at 2.6 (95% CI, 2.0-3.3); breast, at 3.45 (95% CI, -10-17); and colon, at 4.5 (95% CI, -3.5-13). The higher-ERR/Gy group, ranging from approximately 10 to 15, included urinary bladder, at 10.1 (95% CI, 1.4-23); liver, at 14.2 (95% CI, 13-16); kidney, at 14.9 (95% CI, 3.9-26); and lip, oral cavity, and pharynx, at 15.20 (95% CI, 2.73-27.63). Applying a typical candidate patient (female, age 65 y) and correcting for the reference population mortality rate, the total estimated excess mortality for an intraperitoneal 211At-monoclonal antibody treatment amounted to 1.13 per 100 treated. More than half this excess originated from urinary bladder and kidney, 0.29 and 0.34, respectively. Depending on various adjustments in calculation and assumptions on competing risks, excess mortality could range from 0.11 to 1.84 per 100 treated. Conclusion: Published epidemiologic data on lifelong detriment after α-particle irradiation and its dosimetry allowed calculations to estimate the risk for secondary cancer after 211At-based intraperitoneal TAT. Measures to reduce dose to the urinary organs may further decrease the estimated relative low risk for secondary cancer from 211At-monoclonal antibody-based intraperitoneal TAT.

The Meaning of Sense of Coherence (SOC) in Persons with Late Effects of Polio-A Qualitative Study.

Sense of Coherence (SOC), comprising comprehensibility, manageability and meaningfulness, is important for the sense of living a good life with Late Effects of Polio (LEoP). However, there is a lack of knowledge about the meaning of these three components. The aim of this study was to explore in-depth the meaning of SOC among persons living with LEoP, in terms of comprehensibility, manageability and meaningfulness. A directed content analysis was performed based on individual interviews with 7 men and 7 women with LEoP (mean age 73 years). SOC in persons with LEoP existed in two overarching themes that were closely intertwined: a state of motion and a state of being. The state of motion comprised active approaches, choices and actions, and was a process aimed at achieving a stronger comprehensibility, manageability and meaningfulness. The state of being comprised the comprehensibility, manageability and meaningfulness that the persons currently experienced. A profound understanding of SOC as both a state of motion and state being is essential for rehabilitation professionals when providing self-management support to persons living with LEoP. This understanding can increase their sense of living a good life and also be used in the rehabilitation of other life-long conditions.

Sense of coherence and coping behaviours in persons with late effects of polio.

BACKGROUND: Sense of coherence (SOC), comprising "comprehensibility", "manageability" and "meaningfulness", is important for successful adaptation in persons with late effects of polio (LEoP) and can be used as an estimate of the ability to cope with stressors. Coping behaviours are the actions a person performs to reduce stress and can be divided into problem-focused coping, emotion-focused coping and less useful coping. Our knowledge is very limited of what coping behaviours persons with LEoP use to manage their life situation as well as the association between SOC and coping behaviours. OBJECTIVE: The aims of this cross-sectional study were to assess coping behaviours and to explore the association between SOC and coping behaviours in persons with LEoP. METHODS: In total, 93 ambulant persons (52% women, mean [SD] age 74 [8] years) with clinically and electromyographically verified LEoP responded to a postal survey with the Sense of Coherence Scale 13 items (SOC-13) and the Brief Cope Scale. Three linear regression analyses were used to explore the association between SOC and problem-focused coping, emotion-focused coping and less useful coping, controlling for age and sex. RESULTS: The most-used coping behaviours belonged to the categories problem-focused and emotion-focused coping. We found a significant negative association between SOC and less useful coping; less useful coping explained 34% of the variance of SOC (adj R2 = 0.34, p < 0.001), whereas age and sex were not significant in the analyses. CONCLUSIONS: Persons with LEoP primarily use problem-focused and emotion-focused coping behaviours, which suggests that generally they have adapted well to their disability. Regardless of age and sex, persons with lower SOC scores use less useful coping behaviours, which suggests that they are not as well adapted. These results can facilitate the development of rehabilitation interventions that help persons with LEoP adapt to their situation with a life-long disability.

Work and everyday life in a digitalized time: Experiences of people with subjective cognitive difficulties related to neurological disorders.

INTRODUCTION: Digitalization has changed working life and increased cognitive demands on employees in general. Nevertheless, the consequences for employees with cognitive impairments and subjective cognitive difficulties are to a large extent unexplored. The aim of this study was to explore and describe how employees with subjective cognitive difficulties who are performing digital work tasks experience their vocational situation and how this situation influences their everyday life. METHODS: A qualitative, descriptive, multiple-case study was designed. Self-reports, assessments and qualitative interviews were used to collect data from the seven participants with neurological disorders. The data were analysed using pattern matching. FINDINGS: The analysed data formed four categories conceptualized as "Working to my full potential", "Working, but it is largely up to me", "Working at the expense of everyday life" and "Working without known difficulties", and these categories included one to four subcategories. CONCLUSION: Managing subjective cognitive difficulties in vocational situations and everyday life was challenging in a digitalized working life for participants with neurological disorders. To provide equal access to preventive measures and rehabilitation and a sustainable working life, it is important to investigate the influence of subjective cognitive difficulties systematically on work, everyday life and management strategies in people with neurological disorders in digitalized work.

[Improve the quality of the inpatient psychiatric care]. / Det är hög tid att utveckla den psykiatriska heldygnsvården.

Psychiatric care has changed dramatically from inpatient to outpatient care in the last decades. While a lot of resources have been spent on developing outpatient care, less interest has been invested in inpatient care, which has repeatedly been critisezed for being dominated by control, lack of collaboration between staff and patient and boredom. We suggest that there are three main functions of the psychiatric ward: the asylum function, the intensive care and the observational/diagnostic function. We also present some recent projects aimed at improving the quality of care and we argue for more involvment of the psychiatrists in the internal life and functioning of the psychiatric ward.

From 9 to 91: health promotion through the life-course-illuminating the inner child.

A life-course perspective is according to the World Health Organization about increasing the effectiveness of health promotion interventions at all ages. This targets the needs of human beings throughout their life. Descriptions of the phenomenon of the inner child invite the possibility that it may be of help when promoting health throughout the life-course. The aim was to describe and understand schoolchildren's, adults and older person's experiences of childhood in connection to health and well-being in the present and through the life-course, illuminating the inner child. The research strategy used was a secondary analysis of the original transcribed data from three Swedish studies investigating new questions. In total, 53 individuals aged 9-91, 20 school children, 20 adults and 13 older persons were interviewed about childhood experiences. The schoolchildren were invited to create a drawing, and to narrate about it during the interview. The main question in the secondary analysis was 'How do the participants' narrations about childhood experiences illuminate the inner child, useful for health promotion through the life-course?' The findings showed the importance of a secure atmosphere and trusting relationships, indicating that experiences during childhood can help us to adapt and pass along life lessons across generations. There were narratives about play as an activity where they learned to promote a healthy childhood, struggle for independence and learning how to be responsible when growing up. Dimensions of mental, social and existential well-being can be seen as examples of the inner child's role in health promotion through the life-course.

Evaluation of therapeutic efficacy of 211At-labeled farletuzumab in an intraperitoneal mouse model of disseminated ovarian cancer.

INTRODUCTION: Antibodies labeled with alpha-emitter astatine-211 have previously shown effective in intraperitoneal (i.p.) treatments of ovarian cancer. In the present work we explore the use of investigational farletuzumab, aimed at the folate receptor alpha. The aim was to evaluate the biodistribution and therapeutic effect of 211At-farletuzumab in in-vitro and in-vivo experiments and, using models for radiation dosimetry, to translate the findings to expected clinical result. The activity concentration used for therapy in mice (170 kBq/mL) was chosen to be in agreement with an activity concentration that is anticipated to be clinically relevant in patients (200 MBq/L). METHODS: For biodistribution, using intravenous injections and mice carrying subcutaneous (s.c.) tumors, the animals were administered either 211At-farletuzumab (n = 16); or with a combination of 125I-farletuzumab and 211At-MX35 (n = 12). At 1, 3, 10 and 22 h, mice were euthanized and s.c.-tumors and organs weighted and measured for radioactivity. To evaluate therapeutic efficacy, mice were inoculated i.p. with 2 × 106 NIH:OVCAR-3 cells. Twelve days later, the treatments were initiated by i.p.-administration. Specific treatment was given by 211At-labeled farletuzumab (group A; n = 22, 170 kBq/mL) which is specific for OVCAR-3 cells. Control treatments were given by either 211At-labeled rituximab which is unspecific for OVCAR-3 (group B; n = 22, 170 kBq/mL), non-radiolabeled farletuzumab (group C; n = 11) or PBS only (group D; n = 8). RESULTS: The biodistribution of 211At-farletuzumab was similar to that with 125I as radiolabel, and also to that of 211At-labeled MX35 antibody. The tumor-free fraction (TFF) of the three control groups were all low (PBS 12%, unlabeled specific farletuzumab 9% and unspecific 211At-rituximab 14%). TFF following treatment with 211At-farletuzumab was 91%. CONCLUSION: The current investigation of intraperitoneal therapy with 211At-farletuzumab, delivered at clinically relevant 211At-mAb radioactivity concentrations and specific activities, showed a 6 to 10-fold increase (treated versus controls) in antitumor efficacy. This observation warrants further clinical testing.

Suicide among reindeer herding Sámi in Sweden, 1961-2017.

This study analyses suicides amongst reindeer herding Sámi in Sweden using information from the database of the National Board of Forensic Medicine. Suicides were identified using registers (39 suicides from 1961-2000) and key informants (11 suicides from 2001-2017). A great majority of cases were males (43 males, 7 females), and 50% occurred in the northernmost region. The mean age was 37.4 years with a peak in the group 20-29 years of age. Shooting was the most common (56%) method, followed by hanging. Blood alcohol concentration measures available from 1993 were above 0.2 g/l in 76% of the cases. There was a maximum incidence of suicides between 1981 and 1990. An accumulation of suicides in the months of May (N = 8) and November (N = 7) was seen. The annual suicide rate was estimated to be between 17.5 and 43.9 per 100 000 population. There was a clear gradient in suicide incidence with the highest being in the southernmost region (Jämtland/Härjedalen) and the lowest in the northernmost county (Norrbotten). For strengthened suicide prevention in this group, future research should address sex differences, the role of alcohol use and the general conditions for reindeer herding.

Sense of Coherence and the Association with Sociodemographics and Disability Related Factors in Persons with Late Effects of Polio.

BACKGROUND: Sense of Coherence (SOC) is important for successful adaptation in persons with life-long disabilities. A previous study has shown that persons with Late Effects of Polio (LEoP) have a level of SOC indicating that they generally have the ability to understand, handle, and have the motivation to deal with stressful events and problems arising in their lives. However, no study has explored the associations between SOC, sociodemographics, and disability-related factors in persons with LEoP. OBJECTIVE: To explore the associations between SOC, sociodemographics, and disability-related factors in persons with LEoP. DESIGN: A cross-sectional design. SETTING: University hospital outpatient clinic. STUDY PARTICIPANTS: Ninety-three persons (mean age 74 years, 52% women) with LEoP. MAIN OUTCOME MEASUREMENTS: Swedish versions of the Sense of Coherence scale (SOC-13), Self-reported Impairments in Persons with Late Effects of Polio (SIPP) scale, Reintegration to Normal Living Index (RNL-I) (subscales "Daily Functioning" and "Perceptions of Self"), and Satisfaction With Life Scale (SWLS). METHODS: The participants responded to a postal survey with background information and the four rating scales. To determine factors associated with SOC, a hierarchical regression analysis was performed with SOC as the dependent variable. RESULTS: Higher age, less bothered by symptoms of LEoP, better perceptions of self, and higher life satisfaction were significantly associated with a greater SOC score. The final model explained 60% of the variance in the SOC (R2 Adj = 0.60, P < .001). CONCLUSIONS: The strong association between SOC, higher age, and disability-related factors is important to consider in the rehabilitation of persons with LEoP. This knowledge can assist rehabilitation professionals to plan interventions that enable people with LEoP to develop strategies to better manage their daily life. LEVEL OF EVIDENCE: III.

Functioning and disability from 10 to 16 years after traumatic brain injury.

OBJECTIVES: With increased long-term survival after traumatic brain injury (TBI), there is a need to understand the life situation many years after the injury. In this study, we have assessed persons on average 16 years after their injury and determined changes over 6 years in overall outcome, living condition, marital status and vocational situation, and in their functioning and disability. MATERIALS & METHODS: Individuals (n = 49, mean age 45 years, 28-70 years) who were assessed 6-15 years (average 10 years) post-TBI were reassessed 12-21 years after their injury (average 16 years) using internationally established TBI outcome measures. RESULTS: From the first to the second assessment, overall outcome using the Glasgow Outcome Scale (GOS) was stable for a large majority and no significant changes in marital status or vocational situation were found. There was some significant, but very small, decline regarding cognitive function, home integration and social integration. In the multiple regression analysis, there was a small significant decline in the Mayo-Portland Adaptability Inventory (MPAI-4) Adjustment subscale score for women with a moderate-to-severe injury. CONCLUSIONS: The very small changes over 6 years imply that persons with a TBI can reach and maintain a stable level of functioning many years post-TBI. Women with a moderate-to-severe TBI seem to be more vulnerable and may experience a small decline in some aspects of their functioning related to anxiety, depression, irritability, pain and headache and fatigue. The relatively small sample requires further studies to confirm these findings.

Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations.

Eliminating microscopic residual disease with α-particle radiation is theoretically appealing. After extensive preclinical work with α-particle-emitting 211At, we performed a phase I trial with intraperitoneal α-particle therapy in epithelial ovarian cancer using 211At conjugated to MX35, the antigen-binding fragments-F(ab')2-of a mouse monoclonal antibody. We now present clinical outcome data and toxicity in a long-term follow-up with individual absorbed dose estimations. Methods: Twelve patients with relapsed epithelial ovarian cancer, achieving a second complete or nearly complete response with chemotherapy, received intraperitoneal treatment with escalating (20-215 MBq/L) activity concentrations of 211At-MX35 F(ab')2.Results: The activity concentration was escalated to 215 MBq/L without any dose-limiting toxicities. Most toxicities were low-grade and likely related to the treatment procedure, not clearly linked to the α-particle irradiation, with no observed hematologic toxicity. One grade 3 fatigue and 1 grade 4 intestinal perforation during catheter implantation were observed. Four patients had a survival of more than 6 y, one of whom did not relapse. At progression, chemotherapy was given without signs of reduced tolerability. Overall median survival was 35 mo, with a 1-, 2-, 5-, and 10-y survival of 100%, 83%, 50%, and 25%, respectively. Calculations of the absorbed doses showed that a lower specific activity is associated with a lower single-cell dose, whereas a high specific activity may result in a lower central dose in microtumors. Individual differences in absorbed dose to possible microtumors were due to variations in administered activity and the specific activity. Conclusion: No apparent signs of radiation-induced toxicity or decreased tolerance to relapse therapy were observed. The dosimetric calculations show that further optimization is advisable to increase the efficacy and reduce possible long-term toxicity.

Sense of Coherence in persons with late effects of polio.

BACKGROUND: Sense of Coherence (SOC) is important for successful adaptation and mental well-being in people with life-long medical conditions. Late effects of polio (LEoP) often lead to a life-long disability, but no study has assessed SOC in this population. OBJECTIVE: To assess SOC in persons with LEoP and to explore the association between SOC, demographics (age, gender, marital status and level of education) and variables related to LEoP (age at polio onset, number of years from polio until onset of LEoP and self-rated disability). METHOD: Ninety-three community-dwelling persons with clinically verified LEoP responded to a postal survey with the Sense of Coherence Scale (SOC-13). A hierarchical multiple regression analysis was performed to explore the associations with SOC. RESULTS: SOC varied considerably among the participants. The mean and median SOC-13 total sum score was 71.8 and 76 points, which is similar to age-matched non-disabled people. The number of years before onset of LEoP and self-rated disability together with the participants' marital status and level of education explained 37% (p < 0.001) of the variance in SOC. CONCLUSION: Persons with LEoP have a level of SOC indicating that they generally have the ability to understand, handle and being motivated when dealing with stressful events and problems arising in their lives as a result of their disability. Being married and having a higher education, living many years before onset of LEoP and perceiving a mild to moderate disability contributed to a strong SOC.

Model of Intraperitoneal Targeted α-Particle Therapy Shows That Posttherapy Cold-Antibody Boost Enhances Microtumor Radiation Dose and Treatable Tumor Sizes.

Intraperitoneally administered radiolabeled monoclonal antibodies (mAbs) have been tested in several clinical trials, often with promising results, but have never proven curative. Methods: We have previously presented simulations of clinically relevant amounts of intraperitoneal 90Y-mAbs for treatment of minimal disease and shown that such treatments are unlikely to eradicate microtumors. Our previous model simulated the kinetics of intraperitoneally infused radiolabeled mAbs in humans and showed the benefit of instead using α-emitters such as 211At. In the current work, we introduce penetration of mAbs into microtumors with radii of up to 400 µm. Calculations were performed using dynamic simulation software. To determine the radiation dose distribution in nonvascularized microtumors of various sizes after intraperitoneal 211At-radioimmunotherapy, we used an in-house-developed Monte Carlo program for microdosimetry. Our aim was to find methods that optimize the therapy for as wide a tumor size range as possible. Results: Our results show that high-specific-activity radiolabeled mAbs that are bound to a tumor surface will penetrate slowly compared with the half-lives of 211At and shorter-lived radionuclides. The inner-core cells of tumors with radii exceeding 100 µm may therefore not be sufficiently irradiated. For lower specific activities, the penetration rate and dose distribution will be more favorable for such tumors, but the dose to smaller microtumors and single cells will be low. Conclusion: Our calculations show that the addition of a boost with unlabeled mAb 1-5 h after therapy results in sufficient absorbed doses both to single cells and throughout microtumors up to approximately 300 µm in radius. This finding should also hold for other high-affinity mAbs and short-lived α-emitters.

Therapeutic efficacy of α-radioimmunotherapy with different activity levels of the 213Bi-labeled monoclonal antibody MX35 in an ovarian cancer model.

BACKGROUND: The aim of this study was to compare the therapeutic efficacy of two different activity levels of the 213Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of 213Bi-MX35, 3 MBq/mL (n = 20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy. Body weight and white blood cell counts were monitored after treatment for possible signs of toxicity. RESULTS: The tumor-free fraction of the animals treated with 3 MBq/mL of 213Bi-MX35 was 0.55, whereas that of animals treated with 9 MBq/mL of 213Bi-MX35 was 0.78. The control group treated with unlabeled MX35 had a tumor-free fraction of 0.15. No significant reduction in white blood cell counts or weight loss was observed. CONCLUSIONS: Tumor growth after i.p. treatment with 213Bi-MX35 was significantly reduced compared to treatment with unlabeled MX35. Treatment with 9 MBq/mL of 213Bi-MX35 resulted in higher tumor-free fraction compared with 3 MBq/mL of 213Bi-MX35, but this difference was not statistically significant. No signs of toxicity were observed in the treated animals.

Life satisfaction and associated factors in persons with mild to moderate Parkinson's disease.

BACKGROUND: Life satisfaction (LS) is an overall goal in the long-term management and rehabilitation of persons with Parkinson's disease (PD). However, very little is known about LS in persons with PD and no study has examined factors associated with their LS. OBJECTIVE: To describe LS in persons with mild to moderate PD and to evaluate the association with gender, age, years since diagnosis, and sense of coherence, perceived participation, and mental and emotional status. METHODS: Eighty persons with mild to moderate PD (46 men and 34 women, mean age 70.1 years, mean time since diagnosis 7.4 years) responded to a postal survey with the Swedish versions of the Satisfaction With Life Scale (SWLS), the Sense of Coherence scale (SOC-13), the Reintegration to Normal Living Index (RNLI) and the Geriatric Depression Scale (GDS-20). Hierarchical multiple regression analyses were used to evaluate the association with LS. RESULTS: The mean SWLS total score was 21.8 points, and 45% rated themselves as satisfied to highly satisfied with their lives. SOC and years since diagnosis explained 36% of the variance, where a strong SOC, indicating a person's capacity to adapt to the overall strains of the disease, showed the strongest association with a high LS. CONCLUSIONS: Persons with mild to moderate PD seem to be generally satisfied with their lives but LS may decrease as the disease progresses. The strong association with SOC implies that LS may increase through rehabilitation that support persons with PD to understand and confront the nature of problems arising in their lives as a result of their PD.

Biokinetic Modeling and Dosimetry for Optimizing Intraperitoneal Radioimmunotherapy of Ovarian Cancer Microtumors.

UNLABELLED: A biokinetic model was constructed to evaluate and optimize various intraperitoneal radioimmunotherapies for micrometastatic tumors. The model was used to calculate the absorbed dose to both anticipated microtumors and critical healthy organs and demonstrated how intraperitoneal targeted radiotherapy can be optimized to maximize the ratio between them. METHODS: The various transport mechanisms responsible for the biokinetics of intraperitoneally infused radiolabeled monoclonal antibodies (mAbs) were modeled using a software package. Data from the literature were complemented by pharmacokinetic data derived from our clinical phase I study to set parameter values. Results using the ß-emitters (188)Re, (177)Lu, and (90)Y and the α-emitters (211)At, (213)Bi, and (212)Pb were compared. The effects of improving the specific activity, prolonging residence time by introducing an osmotic agent, and varying the activity concentration of the infused agent were investigated. RESULTS: According to the model, a 1.7-L infused saline volume will decrease by 0.3 mL/min because of lymphatic drainage and by 0.7 mL/min because of the transcapillary convective component. The addition of an osmotic agent serves to lower the radiation dose to the bone marrow. Clinically relevant radioactivity concentrations of α- and ß-emitters bound to mAbs were compared. For α-emitters, microtumors receive high doses (>20 Gy or 100 Sv [relative biological effect = 5]). Since most of the tumor dose originates from cell-bound radionuclides, an increase in the specific activity would further increase the tumor dose without affecting the dose to peritoneal fluid or bone marrow. For ß-emitters, tumors will receive almost entirely nonspecific irradiation. The dose from cell-bound radiolabeled mAbs will be negligible by comparison. For the long-lived (90)Y, tumor doses are expected to be low at the maximum activity concentration delivered in clinical studies. CONCLUSION: According to the presented model, α-emitters are needed to achieve radiation doses high enough to eradicate microscopic tumors.

Life satisfaction after traumatic brain injury: comparison of ratings with the Life Satisfaction Questionnaire (LiSat-11) and the Satisfaction With Life Scale (SWLS).

BACKGROUND: An optimal life satisfaction (LS) is considered an important long-term outcome after a traumatic brain injury (TBI). It is, however, not clear to what extent a single instrument captures all aspects of LS, and different instruments may be needed to comprehensively describe LS. The aim of this study was to compare self-ratings of life satisfaction after a TBI with two commonly used instruments. METHODS: Life Satisfaction Questionnaire (LiSat-11), comprising eleven items and Satisfaction With Life Scale (SWLS), comprising five items, were administered to 67 individuals (51 men and 16 women). Secondary analysis of data collected as part of a survey of individuals with TBI 6 to 15 years post TBI. RESULTS: Item 1 in LiSat-11 ('Life as a whole') and the total SWLS score was strongly correlated (Spearman's rho = 0.66; p < 0.001). The total score in SWLS had the strongest correlation with items in LiSat-11. All items in LiSat-11, except 'Family life' and 'Partner relationship', were moderately to strongly correlated with items in SWLS. The item 'Partner relationship' in LiSat-11 did not correlate with any of the items in SWLS or the total score. The item 'If I could live my life over, I would change nothing' in SWLS had the weakest correlations with items in LiSat-11. Items 'Vocation' and 'Leisure' in LISat-11 were most strongly correlated with items in SWLS, whereas the item 'ADL' in LiSat-11 was more weakly correlated with items in SWLS. CONCLUSIONS: The strength of the relationships implies that the two instruments assess similar but not identical aspects of LS and therefore complement each other when it is rated.