Eight-Week Supplementation With Bifidobacterium lactis HN019 and Functional Constipation: A Randomized Clinical Trial.

Importance: Probiotic supplementation may improve bowel movements. However, large, properly designed studies are lacking. Objective: To evaluate the potential benefit of Bifidobacterium animalis subsp lactis HN019 on constipation, expressed as complete spontaneous bowel movements (CSBMs). Design, Setting, and Participants: This randomized triple-blind placebo-controlled clinical trial with 2 weeks of run-in and 8 weeks of intervention was conducted from December 25, 2020, to February 28, 2022, at 5 hospitals in Shanghai, China. Participants included healthy volunteers with functional constipation according to Rome III criteria, 18 to 70 years of age, and a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of less than 30.0. Eligibility after the run-in phase required the randomized participants to have 3 or fewer CSBMs/wk. Data were analyzed from September 29, 2022, to March 23, 2023, and reported as intention to treat. Intervention: Participants were randomized to receive probiotic (B lactis HN019, 7.0 × 109 colony forming units (CFU)/d in maltodextrin at the start of the study and 4.69 × 109 CFU/d at the end of the study or maltodextrin placebo once a day for 8 weeks. Main Outcomes and Measures: Primary outcome was change in CSBMs. Secondary outcomes included use of rescue medication, stool consistency, degree of straining for each bowel movement, abdominal pain, and bloating. Further, dietary habits and physical activity were recorded. Fecal samples were analyzed for moisture content, short-chain fatty acids, branched-chain fatty acids, microbiota composition, and calprotectin. Results: Of the 283 individuals assessed for eligibility, 229 were randomized to either the placebo (n = 117) or the HN019 (n = 112) group. One participant in the placebo group discontinued due to COVID-19 restrictions. The 229 participants (194 [84.7% female) had a median age of 45 (38-52) years, mean (SD) BMI of 22.8 (2.5), and a mean (SD) of 0.77 (1.0) CSBM/wk. There was no difference in the change of weekly CSBMs from baseline to the end of study between the HN019 (least-square mean change, 0.80 [95% CI, 0.54-1.05]) and placebo (least-square mean change, 0.66 [95% CI, 0.41-0.90]) groups. Conclusions and Relevance: Although probiotics have been reported to improve bowel function, this large, well-conducted randomized clinical trial did not confirm such results. Daily consumption of B lactis HN019 at the tested dose of 4.69 × 109 CFU did not outperform placebo to increase CSBMs. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000029215.

Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial.

OBJECTIVE: To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS: In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean ± SD 16.4 ± 4.1) with a diabetes duration of 7-193 days (88.8 ± 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 µg GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS: Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA1c ≤9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION: Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.

A multicentre, international, observational study on transarterial chemoembolisation in colorectal cancer liver metastases: Design and rationale of CIREL.

BACKGROUND: About 70-80% of patients with colorectal liver metastases appear as ineligible for a curative treatment approach. Transarterial chemoembolisation (TACE) using irinotecan-eluting beads has emerged as a promising treatment option in cases with irresectable liver metastases. Despite being in clinical practice for years, little is known about the treatment characteristics and outcomes when used as per routine hospital practice. METHODS: Patients with hepatic metastases from colorectal cancer origin, admitted to contributing centres to receive TACE with drug-eluting LifePearl® Microspheres loaded with irinotecan, as part of their standard care, will be consecutively added to the registry. Data will be collected until the end of study, loss to follow-up or death. Primary endpoint is the characterisation of the treatment usage at the selected sites in Europe. Secondary endpoints include outcome parameters, safety and toxicity, as well as quality of life. CONCLUSION AND AIMS: This multicentre, international, prospective observational study conducted in European centres plans to collect real-life data. This data will form an evidence-base from which conclusions can be drawn on how to improve patient selection and optimise treatment protocols when treating with TACE using irinotecan-eluting microspheres. Trial registration NCT03086096.

Clinical Application of Radioembolization in Hepatic Malignancies: Protocol for a Prospective Multicenter Observational Study.

BACKGROUND: Radioembolization, also known as transarterial radioembolization or selective internal radiation therapy with yttrium-90 (90Y) resin microspheres, is an established treatment modality for patients with primary and secondary liver tumors. However, large-scale prospective observational data on the application of this treatment in a real-life clinical setting is lacking. OBJECTIVE: The main objective is to collect data on the clinical application of radioembolization with 90Y resin microspheres to improve the understanding of the impact of this treatment modality in its routine practice setting. METHODS: Eligible patients are 18 years or older and receiving radioembolization for primary and secondary liver tumors as part of routine practice, as well as have signed informed consent. Data is collected at baseline, directly after treatment, and at every 3-month follow-up until 24 months or study exit. The primary objective of the Cardiovascular and Interventional Radiological Society of Europe Registry for SIR-Spheres Therapy (CIRT) is to observe the clinical application of radioembolization. Secondary objectives include safety, effectiveness in terms of overall survival, progression-free survival (PFS), liver-specific PFS, imaging response, and change in quality of life. RESULTS: Between January 2015 and December 2017, 1047 patients were included in the study. The 24-month follow-up period ended in December 2019. The first results are expected in the third quarter of 2020. CONCLUSIONS: The CIRT is the largest observational study on radioembolization to date and will provide valuable insights to the clinical application of this treatment modality and its real-life outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02305459; https://clinicaltrials.gov/ct2/show/NCT02305459. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16296.

COMPARISON OF COMPUTATIONAL PHANTOMS AND INVESTIGATION OF THE EFFECT OF BIODISTRIBUTION ON ACTIVITY ESTIMATIONS.

A comparison was made between two computational phantoms, modelled from the unified phantom UPh-08 T, for whole-body counting applications. One of these was further compared with the International Commission on Radiological Protection reference adult male computational phantom. The simulations that were performed for the comparison of all three voxel phantoms use various distributions of 60Co. The two voxel phantoms of the UPh-08 T showed good agreement, despite different methods of phantom modelling. Also, effects on efficiency of the inhomogeneous distribution of a radionuclide in the computational UPh-08 T phantom were studied, using the realistic biodistribution of 140La. The results show that the activity estimation of radionuclides, which are inhomogeneously distributed in the human body, will be in error if a homogeneous distribution is assumed for the calibration of whole-body counting systems.

Characterization of strong (241)Am sources.

Gamma ray spectra of strong (241)Am sources may reveal information about the source composition as there may be other radioactive nuclides such as progeny and radioactive impurities present. In this work the possibility to use gamma spectrometry to identify inherent signatures in (241)Am sources in order to differentiate sources from each other, is investigated. The studied signatures are age, i.e. time passed since last chemical separation, and presence of impurities. The spectra of some sources show a number of Doppler broadened peaks in the spectrum which indicate the presence of nuclear reactions on light elements within the sources. The results show that the investigated sources can be differentiated between by age and/or presence of impurities. These spectral features would be useful information in a national nuclear forensics library (NNFL) in cases when the visual information on the source, e.g. the source number, is unavailable.

Physical effects of trauma and the psychological consequences of preexisting diseases account for a significant portion of the health-related quality of life patterns of former trauma patients.

BACKGROUND: Health-related quality of life (HRQoL) is known to be significantly affected in former trauma patients. However, the underlying factors that lead to this outcome are largely unknown. In former intensive care unit (ICU) patients, it has been recognized that preexisting disease is the most important factor for the long-term HRQoL. The aim of this study was to investigate HRQoL up to2 years after trauma and to examine the contribution of the trauma-specific, ICU-related, sociodemographic factors together with the effects of preexisting disease, and further to make a comparison with a large general population. METHODS: A prospective 2-year multicenter study in Sweden of 108 injured patients. By mailed questionnaires, HRQoL was assessed at 6 months,12 months, and 24 months after the stay in ICU by Short Form (SF)-36, and information of preexisting disease was collected from the national hospital database. ICU-related factors were obtained from the local ICU database. Comorbidity and HRQoL (SF-36) was also examined in the reference group, a random sample of 10,000 inhabitants in the uptake area of the hospitals. RESULTS: For the trauma patients, there was a marked and early decrease in the physical dimensions of the SF-36 (role limitations due to physical problems and bodily pain). This decrease improved rapidly and was almost normalized after 24 months. In parallel, there were extensive decreases in the psychologic dimensions (vitality, social functioning, role limitations due to emotional problems,and mental health) of the SF-36 when comparisons were made with the general reference population. CONCLUSIONS: The new and important finding in this study is that the trauma population seems to have a trauma-specific HRQoL outcome pattern.First, there is a large and significant decrease in the physical dimensions of the SF-36, which is due to musculoskeletal effects and pain secondary to the trauma. This normalizes within 2 years, whereas the overall decrease in HRQoL remains and most importantly it is seen mainly in the psychologic dimensions and it is due to preexisting diseases.

Incidence and seasonality of falls amongst old people receiving home help services in a municipality in northern Sweden.

OBJECTIVES: Falls among old people is a well-documented phenomenon; however, falls among people living in the community and receiving home help services have been under-researched. The aim of this study was to investigate the incidence, including possible seasonal variation, circumstances and injuries related to falls among community living home help receivers, and to investigate whether fall incidence is associated with the type and amount of home help services received. STUDY DESIGN: Prospective cohort study. METHODS: All 614 persons aged 65 and over who were living in a particular northern Swedish community and receiving municipality home help were included. Data on age, sex and home help service use were collected from home help service records, and falls were reported by staff on report forms specifically designed for the study. Results. A total number of 264 falls were recorded among 122 participants. The overall fall incidence was 626 per 1,000 PY, and incidence rate ratios were significantly correlated to the total amount of services used (p<0.001), as well as to the degree of help for I-ADL needs (p<0.001), P-ADL needs (p<0.001) and escort service (p=0.007). The proportion of falls reported as resulting in injury was 33%. The monthly fall incidence was significantly associated to daylight photoperiod, however it was not associated to temperature. CONCLUSIONS: Fall incidence among home help receivers aged 65 and over seems correlated to the amount of services they receive. This is probably explained by the fact that impairments connected to ADL limitations and home help needs also are connected to an increased risk of falls. This implies that fall prevention should be considered when planning home help care for old people with ADL limitations. Further research on the connection between daylight photoperiod and fall incidence in populations at different latitudes is needed.

Pre-existing disease: the most important factor for health related quality of life long-term after critical illness: a prospective, longitudinal, multicentre trial.

INTRODUCTION: The aim of the present multicenter study was to assess long term (36 months) health related quality of life in patients after critical illness, compare ICU survivors health related quality of life to that of the general population and examine the impact of pre-existing disease and factors related to ICU care on health related quality of life. METHODS: Prospective, longitudinal, multicentre trial in three combined medical and surgical intensive care units of one university and two general hospitals in Sweden. By mailed questionnaires, health related quality of life was assessed at 6, 12, 24 and 36 months after the stay in ICU by EQ-5D and SF-36, and information of pre-existing disease was collected at the 6 months measure. ICU related factors were obtained from the local ICU database. Comorbidity and health related quality of life (EQ-5D; SF-36) was examined in the reference group. Among the 5306 patients admitted, 1663 were considered eligible (>24 hrs in the intensive care unit, and age >or= 18 yrs, and alive 6 months after discharge). At the 6 month measure 980 (59%) patients answered the questionnaire. Of these 739 (75%) also answered at 12 month, 595 (61%) at 24 month, and 478 (47%) answered at the 36 month measure. As reference group, a random sample (n = 6093) of people from the uptake area of the hospitals were used in which concurrent disease was assessed and adjusted for. RESULTS: Only small improvements were recorded in health related quality of life up to 36 months after ICU admission. The majority of the reduction in health related quality of life after care in the ICU was related to the health related quality of life effects of pre-existing diseases. No significant effect on the long-term health related quality of life by any of the ICU-related factors was discernible. CONCLUSIONS: A large proportion of the reduction in the health related quality of life after being in the ICU is attributable to pre-existing disease. The importance of the effect of pre-existing disease is further supported by the small, long term increment in the health related quality of life after treatment in the ICU. The reliability of the conclusions is supported by the size of the study populations and the long follow-up period.

Prevalence of sleep disturbances and long-term reduced health-related quality of life after critical care: a prospective multicenter cohort study.

INTRODUCTION: The aim of the present prospective multicenter cohort study was to examine the prevalence of sleep disturbance and its relation to the patient's reported health-related quality of life after intensive care. We also assessed the possible underlying causes of sleep disturbance, including factors related to the critical illness. METHODS: Between August 2000 and November 2003 we included 1,625 consecutive patients older than 17 years of age admitted for more than 24 hours to combined medical and surgical intensive care units (ICUs) at three hospitals in Sweden. Conventional intensive care variables were prospectively recorded in the unit database. Six months and 12 months after discharge from hospital, sleep disturbances and the health-related quality of life were evaluated using the Basic Nordic Sleep Questionnaire and the Medical Outcomes Study 36-item Short-form Health Survey, respectively. As a nonvalidated single-item assessment, the quality of sleep prior to the ICU period was measured. As a reference group, a random sample (n = 10,000) of the main intake area of the hospitals was used. RESULTS: The prevalence of self-reported quality of sleep did not change from the pre-ICU period to the post-ICU period. Intensive care patients reported significantly more sleep disturbances than the reference group (P < 0.01). At both 6 and 12 months, the main factor that affected sleep in the former hospitalised patients with an ICU stay was concurrent disease. No effects were related to the ICU period, such as the Acute Physiology and Chronic Health Evaluation score, the length of stay or the treatment diagnosis. There were minor correlations between the rate and extent of sleep disturbance and the health-related quality of life. CONCLUSION: There is little change in the long-term quality of sleep patterns among hospitalised patients with an ICU stay. This applies both to the comparison before and after critical care as well as between 6 and 12 months after the ICU stay. Furthermore, sleep disturbances for this group are common. Concurrent disease was found to be most important as an underlying cause, which emphasises that it is essential to include assessment of concurrent disease in sleep-related research in this group of patients.

Psychometric evaluation and further validation of the Hagedoorn et al. modified EVLN measure.

The aim of the present study was to evaluate and further validate a modified Exit, Voice, Loyalty and Neglect (EVLN) instrument (Hagedoorn, Van Yperen, Van de Vliert & Buunk, 1999), in a Swedish sample (n= 792). To test the underlying scaling assumptions, the convergent and divergent validity, a multitrait/multi-item analysis was conducted and factor analyses were used to evaluate the factor structure. The concurrent validity was tested by using the modified EVLN instrument as predictor and three different forms of justice as criteria in the analysis. The criterion-related validity was tested and an association between exit behavioral response and actual exit behavior was found (predictive validity). The results showed that the instrument may be considered to be a valid measure with the exception of the aggressive voice scale.

Organisational change, job strain and increased risk of stroke? A pilot study.

AIMS: The objective of this pilot study was to explore whether organisational change and work-related stress, as measured by the Job Content Questionnaire, were associated with first-ever stroke among working people aged 30-65. METHODS: In a case-control study a total of 65 consecutive cases, aged 30-65 years of age, with first-ever stroke were recruited from four hospitals in Sweden during 2000-2002. During the same period, 103 random population controls in the same age interval were recruited. Data on job-related stress and traditional medical risk factors were collected by a questionnaire. RESULTS: In the multivariate analyses, organisational change (OR 3.38) increased the likelihood of stroke, while experiencing an active job (OR 0.37) decreased the likelihood of stroke. Regarding risk factors outside work, age (OR 1.11), low physical activity (OR 5.21), low education (OR 2.48) and family history of stroke (OR 2.59) were associated with increased likelihood of stroke. CONCLUSION: This study suggests an association between organisational change, work-related stress and stroke. The likelihood of stroke was lower for people in active job situations.

Perceived participation and problems in participation are determinants of life satisfaction in people with spinal cord injury.

PURPOSE: To determine the relationships between perceived participation and problems in participation, and life satisfaction in people with spinal cord injury (SCI). METHOD: A total of 157 men and women with SCI completed the Swedish versions of the Impact on Participation and Autonomy Questionnaire (IPA) and the Life Satisfaction Questionnaire (LiSat-9). RESULTS: The respondents' perceived participation in the five domains of the IPA was significantly correlated with their satisfaction with life as a whole (P < 0.01) and in most of the eight other domains of life satisfaction (P < 0.05 to P < 0.01) in the LiSat-9. The respondents' life satisfaction decreased gradually with increasing frequency of severe problems in participation and significant differences within groups of increasingly severe problems were found. The level of life satisfaction in respondents that perceived no severe problems with participation was similar to those of a normal population. CONCLUSIONS: Perceived participation and problems in participation are determinants of life satisfaction in people with SCI. The results emphasize the importance to focus on severe problems with participation in order to optimize life satisfaction during the rehabilitation after SCI.

Sick leave, disability pension and health-care-seeking behaviour prior to stroke, among people aged 30-65: a case-control study.

PRIMARY OBJECTIVE: To explore sick leave, disability pension and health-care-seeking behaviour among people 30-65 years of age prior to their stroke in 2001 in the county of Ostergötland, Sweden. RESEARCH DESIGN: A register-based, retrospective case-control study for the period 1 January 1998-31 December 2000. Cases (n=212): patients aged 30-65 with first-ever stroke in 2001. Controls (n=4606): people aged 30-65, randomly selected from the same base population. MAIN OUTCOMES AND RESULTS: More than 91 days of accumulated sick leave among women was associated with increased likelihood of developing stroke (OR=1.89). Among men, 29-90 days and more than 91 days on sick leave increased the likelihood of stroke (OR=2.34 and OR=3.43, respectively). CONCLUSION: Frequent health-care-seeking behaviour is not a tool for identifying women who develop stroke, while it may be an indicator for men. Accumulated sick leave may be a tool for identifying men and women with higher risk of stroke.

Health, quality of life, social network and use of health care: a comparison between those granted and those not granted disability pensions.

PURPOSE: The aim was to compare self-rated health, health-related quality of life (HRQoL), social networks and health care utilisation of those granted disability pension (DP) and those not granted disability pension (nDP). METHOD: Demographic data and medical diagnoses were obtained from the records of the social insurance office. Data concerning self-reported health, HRQoL social networks, and use of health care were collected by a postal questionnaire. The nDP group included all those not granted full DPs between 1999 and 2000 (n = 99). The DP group were a random sample of those granted full DPs, during the same period (n = 197). RESULTS: The nDP group had more often multiple diagnoses, and lower self-reported health and HRQoL compared to those granted DP. In particular, their average scores were lower on the SF-36 scales social functioning, role limitations due to physical problems and mental health. The nDP group also had significantly smaller social networks. CONCLUSIONS: Contrary to expectations, those not granted a disability pension do not seem to have better health, but rather to suffer from more sickness than those who were granted a disability pension.

Role of preexisting disease in patients' perceptions of health-related quality of life after intensive care.

OBJECTIVES: To find out how patients perceive their health-related quality of life after they have been treated in an intensive care unit and whether preexisting disease influenced their perception. DESIGN: : Follow-up, quantitative, dual-site study. SETTING: Combined medical and surgical intensive care units of one university and one general hospital in Sweden. PATIENTS: Among the 1,938 patients admitted, 562 were considered eligible (>24 hrs in the intensive care unit, and age >18 yrs). The effect of preexisting disease was assessed by use of a large reference group, a random sample (n = 10,000) of the main intake area of the hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During 2000-2002, data were collected from the intensive care unit register and from a questionnaire mailed to the patients 6 months after their discharge from hospital. Subjects in the reference group were sent postal questionnaires during 1999. Of the patients in the intensive care unit group, 74% had preexisting diseases compared with 51% in the reference group. Six months after discharge, health-related quality of life was significantly lower among patients than in the reference group. When comparisons were restricted to the previously healthy people in both groups, the observed differences were about halved, and when we compared the patients in the intensive care unit who had preexisting diseases with subjects in the reference group who had similar diseases, we found little difference in perceived health-related quality of life. In some dimensions of health-related quality of life, we found no differences between patients in the intensive care unit and the subjects in the reference population. CONCLUSIONS: Preexisting diseases significantly affect the extent of the decline of health-related quality of life after critical care, and this effect may have been underestimated in the past. As most patients who are admitted to an intensive care unit have at least one preexisting disease, it is important to account for these effects when examining outcome.