Incidence of invasive infections with Group B streptococcus in adults in Norway 1996-2019: a nationwide registry-based case-control study.

PURPOSE: Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy adults, but has also become an increasing cause of invasive infection. The aims of this study were to describe the incidence and factors associated with the occurrence of invasive GBS disease in adults in Norway. METHODS: We performed a nationwide retrospective case-control study of invasive GBS infections during 1996-2019, with two control groups; invasive Group A streptococcal disease (GAS) to control for changes in surveillance and diagnostics, and a second representing the general population. RESULTS: A total of 3710 GBS episodes were identified. The age-standardized incidence rate increased steadily from 1.10 (95% CI 0.80-1.50) in 1996 to 6.70 (95% CI 5.90-7.50) per 100,000 person-years in 2019. The incidence rate had an average annual increase of 6.44% (95% CI 5.12-7.78). Incidence rates of GAS varied considerably, and there was no evidence of a consistent change over the study period. GBS incidence was highest among adults > 60 years of age. Cardiovascular disease, cancer, and diabetes were the most common comorbid conditions. There was a shift in the distribution of capsular serotypes from three dominant types to more equal distribution among the six most common serotypes. CONCLUSIONS: The incidence of invasive GBS disease in adults increased significantly from 1996 to 2019. The increasing age of the population with accompanying underlying comorbid conditions might contribute to the increasing burden of invasive GBS disease. Interestingly, type 1 diabetes was also associated with the occurrence of invasive GBS disease.

The effect of parental pain, disability benefits and education on risk of long-term sick leave due to musculoskeletal disorders and the modifying effect of sleep and physical activity: the HUNT study.

BACKGROUND: Family factors, sleep, and physical activity have previously been associated with risk of sick leave and disability benefits due to musculoskeletal disorders. However, how these factors act during adolescence and young adulthood is unclear. The aim of this study was to (i) examine if chronic pain, disability benefits and education in parents influence the risk of long-term sick leave due to musculoskeletal disorders in young adulthood, and (ii) to explore if offspring sleep problems and physical activity modify these effects. METHODS: A population-based prospective study of 18,552 adolescents and young adults (≤ 30 years) in the Norwegian HUNT Study. Survey data was linked to national registry data on sick leave, disability benefits, family relations and educational attainment. We used Cox regression to estimate hazard ratio (HR) with 95% confidence interval (CI) for long-term (≥ 31 days) sick leave due to a musculoskeletal disorder in offspring associated with parental factors and the joint effect of parental factors and offspring lifestyle factors. RESULTS: Parental chronic pain (HR 1.36, 95% CI 1.27-1.45), disability benefits (HR 1.41, 95% CI 1.33-1.48) and low educational attainment (HR 1.78, 95% CI 1.67-1.90) increased the risk of long-term sick leave due to musculoskeletal disorders among offspring. There was no strong evidence that sleep and physical activity modified these effects. CONCLUSION: Chronic pain, disability benefit and low education in parents increased the risk of long-term sick leave due to musculoskeletal disorders among offspring, but these effects were not modified by offspring sleep problems or physical activity level. The findings suggest that efforts beyond individual lifestyle factors might be important as preventive measures.

Incidence of sick leave and disability pension in adults with musculoskeletal pain and co-occurring long-term conditions: data from the Norwegian HUNT study and national registries.

BACKGROUND: Musculoskeletal pain is one of the leading causes of work productivity loss. Long-term conditions (LTCs) commonly occur alongside musculoskeletal pain. However, the incidence of sick leave and disability pension according to LTC status in people with musculoskeletal pain has not been previously described. METHODS: Working-age participants (20-65 years) with persistent musculoskeletal pain who participated in the HUNT3 Study (1995-97) were included. Twenty-five LTCs were classified into 8 LTC groups according to the International Classification of Diseases version 11. Data on sickness and disability benefits were obtained from the National Insurance Database and linked to the HUNT3 data using participants' personal identification number. Age-adjusted incidence rates (IRs) (per 10,000 person-years) and hazard ratios (HRs) of sick leave during 5-year follow-up and disability pension during ~ 25-year follow-up were estimated with 95% confidence intervals (CIs) and presented according to LTC status. RESULTS: Overall, 11,080 participants with musculoskeletal pain were included. Of those, 32% reported one LTC and 45% reported ≥ 2 LTCs. During the follow up period, 1,312 participants (12%) received disability pension due to musculoskeletal conditions. The IR of sick leave and disability pension due to musculoskeletal conditions increased with number of LTCs. Specifically, the IR of sick leave was 720 (95% CI 672 to 768) in participants without any LTCs and 968 (95% CI 927 to 1,009) if they had ≥ 2 LTCs. The IRs of disability pension were 87 (95% CI 75 to 98) and 167 (95% CI 154 to 179) among those with no LTCs and ≥ 2 LTCs, respectively. The incidence of sick leave and disability pension due to musculoskeletal conditions was largely similar across LTCs, although the incidence of disability pension was somewhat higher among people with sleep disorders (IR: 223, 95% CI 194 to 252). CONCLUSIONS: Among people with persistent musculoskeletal pain, the incidence of prematurely leaving the work force due to musculoskeletal conditions was twice as high for those with multiple LTCs compared to those without any LTCs. This was largely irrespective of the type of LTC, indicating that the number of LTCs are an important feature when evaluating work participation among people with musculoskeletal pain.

Intergenerational and genetic influences on physical activity: family data from the HUNT study, Norway.

OBJECTIVES: The objectives of this study are to examine the association of physical activity in parents with physical activity in their adult offspring and explore if the offspring's genetic liability (ie, polygenic risk score) to physical activity influences this association. METHODS: The Trøndelag Health Study cohort is a population-based longitudinal study with data collected in 1984-1986, 1995-1997, 2006-2008 and 2017-2019. We calculated the odds ratio for being physically active and mean difference in physical activity levels according to parental physical activity (device-measured and self-reported) and own polygenic risk score. RESULTS: Compared with offspring with mothers in the lowest third of metabolic equivalent of task (MET)-min/day accumulated by vigorous physical activities, offspring with mothers in the upper third had an OR of 1.93 (95% CI 1.65 to 2.27) for accumulating ≥900 MET-min/week of vigorous physical activity. The OR for the corresponding father-offspring association was 1.78 (95% CI 1.48 to 2.14). Compared with offspring of parents not accumulating ≥900 MET-min/week, we found an OR of 1.89 (95% CI 1.45 to 2.44) for offspring to meet the same threshold if both parents accumulated ≥900 MET-min/week. Offspring with higher polygenic risk score to bephysically active and having physically active parents did more weekly physical activity, but we found no strong evidence of multiplicative synergistic effects between these two factors (all p values ≥0.01). CONCLUSION: Both parental physical activity and offspring's polygenic risk score were positively associated with physical activity levels in the adult offspring, but there was no evidence of effect modification between these factors. A family-based approach to promote physical activity may be effective from a public health perspective.

Coding practice for sepsis 2008-21. / Kodepraksis ved sepsis 2008­21.

Background: Sepsis has a high incidence and mortality rate. Accurate data are needed for health service planning and for research, and there is a need to identify coding practices in Norway. Material and method: All patients over 17 years of age who had been admitted to Norwegian hospitals with sepsis in the period 2008-21 were identified using diagnostic codes for infection plus organ failure, and specific codes for sepsis, from the Norwegian Patient Registry. Results: There were 317 705 admissions with diagnostic codes for sepsis, of which 210 391 (66.2 %) were sepsis with a known focus, 77 627 (24.4 %) were of unknown focus and 29 687 (9.3 %) were codes for both a known and unknown focus. The percentage of sepsis episodes coded with a known focus varied between the health regions. The highest percentage was in the Western Norway Regional Health Authority (72.1 %, 95 % confidence interval (CI): 71.8 to 72.5), and the lowest was in the Central Norway Regional Health Authority (59.2 %, 95 %, CI 58.7 to 59.7). The use of codes with a known focus increased each year on average by 3.2 % (95 % CI 2.7 to 3.6, from 47.5 % in 2008 to 82.3 % in 2021), while the use of codes with an unknown focus decreased by 2.3 % (95 % CI -2.7 to -1.9) from 37.8 % in 2008 to 13.0 % in 2021. Known and unknown focus combined also decreased by 0.9 % per year on average (95 % CI -1.0 to -0.8) from 14.3 % in 2008 to 4.1 % in 2021. Interpretation: The coding of sepsis in Norwegian hospitals has become more uniform.

The Epidemiology of Moderate and Severe Traumatic Brain Injury in Central Norway.

INTRODUCTION: Few studies account for prehospital deaths when estimating incidence and mortality rates of moderate and severe traumatic brain injury (msTBI). In a population-based study, covering both urban and rural areas, including also prehospital deaths, the aim was to estimate incidence and mortality rates of msTBI. Further, we studied the 30-day and 6-month case-fatality proportion of severe TBI in relation to age. METHODS: All patients aged ≥17 years who sustained an msTBI in Central Norway were identified by three sources: (1) the regional trauma center, (2) the general hospitals, and (3) the Norwegian Cause of Death Registry. Incidence and mortality rates were standardized according to the World Health Organization's world standard population. Case-fatality proportions were calculated by the number of deaths from severe TBI at 30 days and 6 months, divided by all patients with severe TBI. RESULTS: The overall incidence rates of moderate and severe TBI were 4.9 and 6.7 per 100,000 person-years, respectively, increasing from age 70 years. The overall mortality rate was 3.4 per 100,000 person-years, also increasing from age 70 years. Incidence and mortality rates were highest in men. The case-fatality proportion in people with severe TBI was 49% in people aged 60-69 years and 81% in people aged 70-79 years. CONCLUSION: The overall incidence and mortality rates for msTBI in Central Norway were low but increased from age 70 years, and among those ≥80 years of age with severe TBI, nearly all died. Overall estimates are strongly influenced by high incidence and mortality rates in the elderly, and studies should therefore report age-specific estimates, for better comparison of incidence and mortality rates.

Insomnia symptoms and risk of bloodstream infections: prospective data from the prospective population-based Nord-Trøndelag Health Study (HUNT), Norway.

Previous research suggests decreased immune function and increased risk of infections in individuals with insomnia. We examined the effect of insomnia symptoms on risk of bloodstream infections (BSIs) and BSI-related mortality in a population-based prospective study. A total of 53,536 participants in the second Norwegian Nord-Trøndelag Health Study (HUNT2) (1995-97) were linked to prospective data on clinically relevant BSIs until 2011. In Cox regression, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for a first-time BSI and for BSI-related mortality (BSI registered ≤30 days prior to death) associated with insomnia symptoms. Compared with participants who reported "no symptoms", participants reporting having "difficulty initiating sleep" (DIS) often/almost every night had a HR for a first-time BSI of 1.14 (95% CI 0.96-1.34). Participants reporting "difficulties maintaining sleep" (DMS) often/almost every night had a HR of 1.19 (95% CI 1.01-1.40), whereas those having a feeling of "non-restorative sleep" once a week or more had a HR of 1.23 (95% CI 1.04-1.46). Participants frequently experiencing all three of the above symptoms had a HR of 1.39 (1.04-1.87), whilst those who had both DIS and DMS had a HR of 1.15 (0.93-1.41) and being troubled by insomnia symptoms to a degree that affected work performance was associated with a HR of 1.41 (95% CI 1.08-1.84). The HRs for BSI-related mortality suggest an increased risk with increasing insomnia symptoms, but the CIs are wide and inconclusive. We found that frequent insomnia symptoms and insomnia symptoms that affected work performance were associated with a weak positive increased risk of BSI.

Can the bias of self-reported sitting time be corrected? A statistical model validation study based on data from 23 993 adults in the Norwegian HUNT study.

BACKGROUND: Despite apparent shortcomings such as measurement error and low precision, self-reported sedentary time is still widely used in surveillance and research. The aim of this study was threefold; (i) to examine the agreement between self-reported and device-measured sitting time in a general adult population; (ii), to examine to what extent demographics, lifestyle factors, long-term health conditions, physical work demands, and educational level is associated with measurement bias; and (iii), to explore whether correcting for factors associated with bias improves the prediction of device-measured sitting time based on self-reported sitting time. METHODS: A statistical validation model study based on data from 23 993 adults in the Trøndelag Health Study (HUNT4), Norway. Participants reported usual sitting time on weekdays using a single-item questionnaire and wore two AX3 tri-axial accelerometers on the thigh and low back for an average of 3.8 (standard deviation [SD] 0.7, range 1-5) weekdays to determine their sitting time. Statistical validation was performed by iteratively adding all possible combinations of factors associated with bias between self-reported and device-measured sitting time in a multivariate linear regression. We randomly selected 2/3 of the data (n = 15 995) for model development and used the remaining 1/3 (n = 7 998) to evaluate the model. RESULTS: Mean (SD) self-reported and device-measured sitting time were 6.8 (2.9) h/day and 8.6 (2.2) h/day, respectively, corresponding to a mean difference of 1.8 (3.1) h/day. Limits of agreement ranged from - 8.0 h/day to 4.4 h/day. The discrepancy between the measurements was characterized by a proportional bias with participants device-measured to sit less overestimating their sitting time and participants device-measured to sit more underestimating their sitting time. The crude explained variance of device-measured sitting time based on self-reported sitting time was 10%. This improved to 24% when adding age, body mass index and physical work demands to the model. Adding sex, lifestyle factors, educational level, and long-term health conditions to the model did not improve the explained variance. CONCLUSIONS: Self-reported sitting time had low validity and including a range of factors associated with bias in self-reported sitting time only marginally improved the prediction of device-measured sitting time.

Trends in mortality after a sepsis hospitalization: a nationwide prospective registry study from 2008 to 2021.

BACKGROUND: Few studies have reported on mortality beyond one year after sepsis. We aim to describe trends in short- and long-term mortality among patients admitted with sepsis, and to describe the association between clinical characteristics and mortality for improved monitoring, treatment and prognosis. METHODS: Patients ≥ 18 years admitted to all Norwegian hospitals (2008-2021) with a first sepsis episode were identified using Norwegian Patient Registry and International Classification of Diseases 10th Revision codes. Sepsis was classified as implicit (known infection site plus organ dysfunction), explicit (unknown infection site), or COVID-19-related sepsis. The outcome was all-cause mortality. We describe age-standardized 30-day, 90-day, 1-, 5- and 10-year mortality for each admission year and estimated the annual percentage change with 95% confidence interval (CI). The association between clinical characteristics and all-cause mortality is reported as hazard ratios (HRs) adjusted for age, sex and calendar year in Cox regression. RESULTS: The study included 222,832 patients, of whom 127,059 (57.1%) had implicit, 92,928 (41.7%) had explicit, and 2,845 (1.3%) had COVID-19-related sepsis (data from 2020 and 2021). Trends in overall age-standardized 30-day, 90-day, 1- and 5-year mortality decreased by 0.29 (95% CI - 0.39 to - 0.19), 0.43 (95% CI - 0.56 to - 0.29), 0.61 (95% CI - 0.73 to - 0.49) and 0.66 (95% CI - 0.84 to - 0.48) percent per year, respectively. The decrease was observed for all infections sites but was largest among patients with respiratory tract infections. Implicit, explicit and COVID-19-related sepsis had largely similar overall mortality, with explicit sepsis having an adjusted HR of 0.980 (95% CI 0.969 to 0.991) and COVID-19-related sepsis an adjusted HR of 0.916 (95% CI 0.836 to 1.003) compared to implicit sepsis. Patients with respiratory tract infections have somewhat higher mortality than those with other infection sites. Number of comorbidities was positively associated with mortality, but mortality varied considerably between different comorbidities. Similarly, number of acute organ dysfunctions was strongly associated with mortality, whereas the risk varied for each type of organ dysfunction. CONCLUSION: Overall mortality has declined over the past 14 years among patients with a first sepsis admission. Comorbidity, site of infection, and acute organ dysfunction are patient characteristics that are associated with mortality. This could inform health care workers and raise the awareness toward subgroups of patients that needs particular attention to improve long-term mortality.

Return to work after hospitalization for sepsis: a nationwide, registry-based cohort study.

BACKGROUND: Sepsis survivors commonly experience functional impairment, which may limit return to work. We investigated return to work (RTW) of patients hospitalized with sepsis and the associations with patient and clinical characteristics. METHODS: Working-age patients (18-60 years) admitted to a Norwegian hospital with sepsis between 2010 and 2021 were identified using the Norwegian Patient Registry and linked to sick-leave data from the Norwegian National Social Security System Registry. The main outcome was proportion of RTW in patients hospitalized with sepsis at 6 months, 1 year, and 2 years after discharge. Secondary outcomes were time trends in age-standardized proportions of RTW and probability of sustainable RTW (31 days of consecutive work). The time trends were calculated for each admission year, reported as percentage change with 95% confidence interval (CI). Time-to-event analysis, including crude and adjusted hazard risk (HRs), was used to explore the association between sustainable RTW, characteristics and subgroups of sepsis patients (intensive care unit (ICU) vs. non-ICU and COVID-19 vs. non-COVID-19). RESULTS: Among 35.839 hospitalizations for sepsis among patients aged 18-60 years, 12.260 (34.2%) were working prior to hospitalization and included in this study. The mean age was 43.7 years. At 6 months, 1 year, and 2 years post-discharge, overall estimates showed that 58.6%, 67.5%, and 63.4%, respectively, were working. The time trends in age-standardized RTW for ICU and non-ICU sepsis patients remained stable over the study period, except the 2-year age-standardized RTW for non-ICU patients that declined by 1.51% (95% CI - 2.22 to - 0.79) per year, from 70.01% (95% CI 67.21 to 74.80) in 2010 to 57.04% (95% CI 53.81-60.28) in 2019. Characteristics associated with sustainable RTW were younger age, fewer comorbidities, and fewer acute organ dysfunctions. The probability of sustainable RTW was lower in ICU patients compared to non-ICU patients (HR 0.56; 95% CI 0.52-0.61) and higher in patients with COVID-19-related sepsis than in sepsis patients (HR 1.31; 95% CI 1.15-1.49). CONCLUSION: Absence of improvement in RTW proportions over time and the low probability of sustainable RTW in sepsis patients need attention, and further research to enhance outcomes for sepsis patients is required.

Changes of inflammation in patients with psoriatic arthritis after high intensity interval training assessed by ultrasound and MRI, a randomized controlled trial.

BACKGROUND: In psoriatic arthritis (PsA) there is a theoretical risk of increased disease activity related to strenuous physical activity, including exercise. We evaluated the effect of high intensity interval training (HIIT) on objective measures of inflammation in PsA assessed by ultrasound (US) of peripheral joints and entheses, and by bone marrow edema (BME) on MRI of the sacroiliac joints (SIJ) and spine. METHODS: We randomly assigned 67 PsA patients to an intervention group that performed structured HIIT for 11 weeks, or to a control group instructed not to change their physical exercise habits. Outcome measures included US evaluation of the total cohort and MRI in a subgroup of 41; both assessed at 3 months. We calculated the proportions with an increased US B-mode and power-doppler (PD) signal of joints and entheses and Spondyloarthritis-Research-Consortium-of-Canada (SPARCC)-BME score of the SIJ and spine for both groups. RESULTS: Proportions with an increased US B-mode score of the joints were 32% and 28% in HIIT and control groups, respectively. Corresponding proportions of PD scores of the joints were 7% and 10% and PD scores of entheses were 32% and 31%. The proportions with increased MRI BME of the SIJ were 6% in the HIIT group and 10% in the control group. Corresponding proportions were 6% and 5% for the MRI BME of the spine. CONCLUSION: In PsA patients with a low to moderate disease activity, there was no clear evidence of objectively measured increased inflammation after HIIT, as evaluated by US and MRI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02995460 (16/12/2016).

Multimorbidity and co-occurring musculoskeletal pain do not modify the effect of the SELFBACK app on low back pain-related disability.

BACKGROUND: SELFBACK, an artificial intelligence (AI)-based app delivering evidence-based tailored self-management support to people with low back pain (LBP), has been shown to reduce LBP-related disability when added to usual care. LBP commonly co-occurs with multimorbidity (≥ 2 long-term conditions) or pain at other musculoskeletal sites, so this study explores if these factors modify the effect of the SELFBACK app or influence outcome trajectories over time. METHODS: Secondary analysis of a randomized controlled trial with 9-month follow-up. Primary outcome is as follows: LBP-related disability (Roland Morris Disability Questionnaire, RMDQ). Secondary outcomes are as follows: stress/depression/illness perception/self-efficacy/general health/quality of life/physical activity/global perceived effect. We used linear mixed models for continuous outcomes and logistic generalized estimating equation for binary outcomes. Analyses were stratified to assess effect modification, whereas control (n = 229) and intervention (n = 232) groups were pooled in analyses of outcome trajectories. RESULTS: Baseline multimorbidity and co-occurring musculoskeletal pain sites did not modify the effect of the SELFBACK app. The effect was somewhat stronger in people with multimorbidity than among those with LBP only (difference in RMDQ due to interaction, - 0.9[95 % CI - 2.5 to 0.6]). Participants with a greater number of long-term conditions and more co-occurring musculoskeletal pain had higher levels of baseline disability (RMDQ 11.3 for ≥ 2 long-term conditions vs 9.5 for LBP only; 11.3 for ≥ 4 musculoskeletal pain sites vs 10.2 for ≤ 1 additional musculoskeletal pain site); along with higher baseline scores for stress/depression/illness perception and poorer pain self-efficacy/general health ratings. In the pooled sample, LBP-related disability improved slightly less over time for people with ≥ 2 long-term conditions additional to LBP compared to no multimorbidity and for those with ≥4 co-occurring musculoskeletal pain sites compared to ≤ 1 additional musculoskeletal pain site (difference in mean change at 9 months = 1.5 and 2.2, respectively). All groups reported little improvement in secondary outcomes over time. CONCLUSIONS: Multimorbidity or co-occurring musculoskeletal pain does not modify the effect of the selfBACK app on LBP-related disability or other secondary outcomes. Although people with these health problems have worse scores both at baseline and 9 months, the AI-based selfBACK app appears to be helpful for those with multimorbidity or co-occurring musculoskeletal pain. TRIAL REGISTRATION: NCT03798288 . Date of registration: 9 January 2019.

Thyroid function and risk of bloodstream infections: Results from the Norwegian prospective population-based HUNT Study.

OBJECTIVE: Previous studies on thyroid function and risk of infection is conflicting and often stem from intensive care cohorts were nonthyroidal illness syndrome (NTIS) may be present. The objective of this study was to identify the risk of bloodstream infections (BSI) and BSI-related mortality with thyroid-stimulating hormone (TSH) levels within the reference range in a general population. DESIGN: Prospective follow-up. PARTICIPANTS: The HUNT2 (1995-97) included 34,619 participants with information on TSH levels. MEASUREMENTS: Hazard ratios (HRs) with 95% confidence interval (CI) confirmed BSIs and BSI-related mortality until 2011. RESULTS: During a median follow-up of 14.5 years, 1179 experienced at least one episode of BSI and 208 died within 30 days after a BSI. TSH levels within the reference range of 0.5-4.5 mU/L were not associated with the risk of first-time BSI, with an HR of 0.97 (95% CI: 0.90-1.04) per mU/L. Stratified by baseline age < or ≥65 years, TSH was inversely associated with the risk of BSI (HR: 0.88; 95% CI: 0.78-1.00 per mU/L) in the youngest age group only. Persons with any baseline thyroid disease had a 30% risk and the hyperthyroid subgroup a 57%, and hypothyroidism a 20% increased risk of BSI. TSH levels were not clearly associated with BSI mortality, but the HRs were imprecise due to few BSI-related deaths. CONCLUSION: There was some evidence of a weak inverse association between TSH levels and the risk of BSI in persons below 65 years of age. The increased risk seen in persons with thyroid illness is probably explained by confounding by concurrent ill health.

The interplay between multisite pain and insomnia on the risk of anxiety and depression: the HUNT study.

BACKGROUND: Chronic musculoskeletal pain and insomnia frequently co-occur and are known independent risk factors for anxiety and depression. However, the interplay between these two conditions on the risk of anxiety and depression has not been explored. METHODS: A population-based prospective study of 18,301 adults in the Norwegian HUNT Study without anxiety or depression at baseline (2006-2008). We calculated adjusted risk ratios (RRs) with 95% confidence intervals (CIs) for anxiety and/or depression at follow-up (2017-2019), associated with i) number of chronic pain sites, and ii) chronic pain and insomnia symptoms jointly. RESULTS: At follow-up, 2155 (11.8%) participants reported anxiety and/or depression. The number of pain sites was positively associated with risk of anxiety and/or depression (Ptrend, < 0.001). Compared to people without chronic pain and insomnia symptoms, people with ≥5 pain sites and no insomnia symptoms had a RR of 1.52 (95% CI: 1.28 to 1.81) for anxiety and/or depression, those with no chronic pain but with insomnia had a RR of 1.78 (95% CI: 1.33 to 2.38), whereas the RR among people with both ≥5 pain sites and insomnia was 2.42 (95% CI: 1.85 to 3.16). We observed no synergistic effect above additivity for the combination of ≥5 pain sites and insomnia on risk of anxiety and/or depression. CONCLUSIONS: This study shows that people with multisite chronic pain who also suffer from insomnia are at a particularly high risk for anxiety and/or depression, suggesting that insomnia symptoms are important contributors to the association between multisite pain and common mental health problems.

Acute kidney injury in intensive care patients: Incidence, time course, and risk factors.

BACKGROUND: Acute kidney injury (AKI) is frequent and influences the prognosis of intensive care unit (ICU) patients. The aim of this study was to estimate the incidence, time-course, risk factors, and mortality of AKI among unselected ICU patients. METHODS: All adult ICU patients admitted to the ICU at the University Hospital in Central Norway from 2010 to 2015 with a stay of 24 h or more were included in the study. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. All patients were followed with respect to reversal of AKI. Risk factors for AKI were analyzed using Cox regression. RESULTS: Among 2325 ICU patients, 1245 developed AKI during the ICU stay, corresponding to an incidence of 53.5 % (CI, 51.5-55.5). The incidence according to KDIGO AKI stages 1, 2, and 3 was 26.2, 11.7, and 15.7%, respectively. The median duration of AKI was 24 (CI 19-24), 32 (CI 26-39), and 101 (CI 75-164) hours for AKI KDIGO stage 1, 2, and 3, respectively. AKI was transient, persistent, or AKD in 73.4, 16.5, and 10.0% of the patients with a known outcome. AKI reversal was observed in 72.9% of all AKI patients. Independent risk factors for AKI in a multivariate analysis were hypertension, diabetes, heart disease, and higher body weight. Episodes of mean arterial pressure below 73 mmHg were associated with a higher risk of AKI. CONCLUSIONS: In our material, the incidence of AKI was comparable to what has been reported previously. Risk factors for the development of AKI were a MAP below 73, hypertension, diabetes, heart disease, chronic kidney disease, and higher body weight. Most AKI patients regain their kidney function during the ICU stay, particularly in the KDIGO AKI stages 1 and 2.

Changes in circulating insulin-like growth factor-1 and its binding proteins in yearling rainbow trout during spring under natural and manipulated photoperiods and their relationships with gill Na+, K+-ATPase and body size.

Smoltification in salmonids occurs during spring in response to increasing photoperiod to prepare for marine life. Smoltification is associated with increased hypo-osmoregulatory ability and enhanced growth potential, mediated by growth hormone and insulin-like growth factor (IGF)-1. Rainbow trout is uniquely insensitive to the induction of smoltification-associated changes by photoperiod, such as the activation of gill Na+,K+-ATPase (NKA). We measured the circulating IGF-1 and IGF-binding protein (IGFBP)-2b levels in yearling rainbow trout exposed to natural and manipulated photoperiods during spring and correlated these with gill NKA activity and body size. Although the effect of photoperiod manipulation on body size and circulating IGF-1 and IGFBP-2b was negligible, they were positively correlated with gill NKA activity in fish under simulated natural photoperiod. We next pit-tagged yearling rainbow trout and fed them a restricted ration or to satiation under a natural photoperiod. In April, gill NKA activity was higher in the satiation group than in the restricted group and positively correlated with body size and growth rate. In addition, circulating IGFBP-2b was positively correlated with gill NKA, size and growth, whereas circulating IGF-1 was correlated only with size and growth. The relationship between circulating IGF-1 and growth intensified from May to June, suggesting that the IGF-1-growth relationship was disrupted in April when gill NKA was activated. Two additional IGFBPs were related to growth parameters but not to gill NKA activity. The present study suggests that circulating IGFBP-2b and IGF-1 mediate the size-dependent activation of gill NKA in yearling rainbow trout during spring.

Plasma Calprotectin Levels Associate with Suspected Metabolic-Associated Fatty Liver Disease and All-Cause Mortality in the General Population.

Metabolic-associated fatty liver disease (MAFLD) is characterized by hepatic steatosis, metabolic dysregulation, and neutrophilic inflammation. In this study, we hypothesized that systemic levels of plasma calprotectin, as a biomarker of neutrophilic inflammation, may be associated with suspected MAFLD. Plasma calprotectin levels were measured in subjects (n = 5446) participating in the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort study. Suspected MAFLD was defined by the fatty liver index (FLI ≥ 60) and hepatic steatosis index (HSI ≥ 36) as proxies. Plasma calprotectin levels were significantly higher in subjects with FLI ≥ 60 (0.57 [IQR: 0.42−0.79] mg/L, n = 1592) (p < 0.001) compared to subjects with FLI < 60 (0.46 [0.34−0.65] mg/L, n = 3854). Multivariable logistic regression analyses revealed that plasma calprotectin levels were significantly associated with suspected MAFLD (FLI ≥ 60), even after adjustment for potential confounding factors, including current smoking, alcohol consumption, hypertension, diabetes, cardiovascular diseases, insulin resistance (HOMA-IR), hs-CRP, eGFR, and total cholesterol levels (OR 1.19 [95% CI: 1.06−1.33], p = 0.003). Interaction analyses revealed significant effect modifications for the association between plasma calprotectin and suspected MAFLD by BMI (p < 0.001) and hypertension (p = 0.003), with the strongest associations in subjects with normal BMI and without hypertension. Prospectively, plasma calprotectin levels were significantly associated with all-cause mortality after adjustment for potential confounding factors, particularly in subjects without suspected MAFLD (FLI < 60) (hazard ratio (HR) per doubling: 1.34 (1.05−1.72), p < 0.05). In conclusion, higher plasma calprotectin levels are associated with suspected MAFLD and with the risk of all-cause mortality, the latter especially in subjects without suspected MAFLD.

Long-term changes in self-reported sleep quality and risk of chronic musculoskeletal pain: The HUNT Study.

We examined the association between long-term (~10 years) changes in self-reported sleep quality and risk of any chronic musculoskeletal pain and chronic widespread pain. The study comprised data on 6,033 people who participated in three consecutive surveys in the Norwegian HUNT Study (1995-1997, 2006-2008 and 2017-2019) and who were without chronic musculoskeletal pain at the first two surveys. We used a modified Poisson regression model to calculate adjusted risk ratios for chronic pain at follow-up (2017-2019) associated with categories of poor and good sleep quality reported in 1995-1997 and 2006-2008. Compared with people who reported good sleep at both surveys (crude absolute risk: 32.4%), the risk ratios of any chronic pain were 1.20 (95% confidence interval: 1.02-1.41) for those who changed from poor to good sleep; 1.25 (95% confidence interval: 1.12-1.39) for those who changed from good to poor sleep; and 1.41 (95% confidence interval: 1.21-1.63) for those who reported long-term poor sleep. The corresponding risk ratios for chronic widespread pain were 1.35 (95% confidence interval: 0.82-2.23), 1.55 (95% confidence interval: 1.14-2.12) and 2.09 (95% confidence interval: 1.38-3.17), respectively. In conclusion, these findings indicate that people with long-term poor sleep quality have a markedly higher risk of chronic musculoskeletal pain and chronic widespread pain, compared with people who remain good sleep quality.

Genetic variants related to physical activity or sedentary behaviour: a systematic review.

BACKGROUND: Research shows that part of the variation in physical activity and sedentary behaviour may be explained by genetic factors. Identifying genetic variants associated with physical activity and sedentary behaviour can improve causal inference in physical activity research. The aim of this systematic review was to provide an updated overview of the evidence of genetic variants associated with physical activity or sedentary behaviour. METHODS: We performed systematic literature searches in PubMed and Embase for studies published from 1990 to April 2020 using keywords relating to "physical activity", "exercise", "sedentariness" and "genetics". Physical activity phenotypes were either based on self-report (e.g., questionnaires, diaries) or objective measures (e.g., accelerometry, pedometer). We considered original studies aiming to i) identify new genetic variants associated with physical activity or sedentary behaviour (i.e., genome wide association studies [GWAS]), or ii) assess the association between known genetic variants and physical activity or sedentary behaviour (i.e., candidate gene studies). Study selection, data extraction, and critical appraisal were carried out by independent researchers, and risk of bias and methodological quality was assessed for all included studies. RESULTS: Fifty-four out of 5420 identified records met the inclusion criteria. Six of the included studies were GWAS, whereas 48 used a candidate gene approach. Only one GWAS and three candidate gene studies were considered high-quality. The six GWAS discovered up to 10 single nucleotide polymorphisms (SNPs) associated with physical activity or sedentariness that reached genome-wide significance. In total, the candidate gene studies reported 30 different genes that were associated (p < 0.05) with physical activity or sedentary behaviour. SNPs in or close to nine candidate genes were associated with physical activity or sedentary behaviour in more than one study. CONCLUSION: GWAS have reported up to 10 loci associated with physical activity or sedentary behaviour. Candidate gene studies have pointed to some interesting genetic variants, but few have been replicated. Our review highlights the need for high-quality GWAS in large population-based samples, and with objectively assessed phenotypes, in order to establish robust genetic instruments for physical activity and sedentary behaviour. Furthermore, consistent replications in GWAS are needed to improve credibility of genetic variants. TRIAL REGISTRATION: Prospero CRD42019119456 .

Intact rather than total circulating insulin-like growth factor binding protein-1a is a negative indicator of growth in masu salmon.

Insulin-like growth factor binding protein (IGFBP)-1a is one of three major circulating forms in salmon and induced under catabolic conditions. However, there is currently no immunoassay available for this form because of a lack of standard and specific antibodies. We developed a time-resolved fluoroimmunoassay (TR-FIA) for salmon IGFBP-1a using recombinant protein for labeling, an assay standard, and production of antiserum. The TR-FIA had a low cross-reactivity (3.6%) with IGFBP-1b, another major form in the circulation. Fasting for 4 wk had no effect on serum immunoreactive (total) IGFBP-1a levels in yearling masu salmon, whereas 6-wk fasting significantly increased it. There was a significant, but weak, negative relationship between serum total IGFBP-1a level and individual growth rate (r2 = 0.12, P = 0.01). We next developed a ligand immuno-functional assay (LIFA) using europium-labeled IGF-I to quantify intact IGFBP-1a. In contrast to total IGFBP-1a, serum intact IGFBP-1a levels increased after 4 wk of fasting, and refeeding for 2 wk restored it to levels similar to those of the fed control. Serum intact IGFBP-1a levels showed a significant negative correlation with individual growth rate (r2 = 0.52, P < 0.001), which was as good as that of IGFBP-1b. Our findings using newly developed TR-FIA and LIFA suggest that regulation of intact IGFBP-1a levels has an important effect on growth in salmon and that intact IGFBP-1a is a negative index of salmon growth.