Unveiling sex bias and adverse neonatal outcomes in ultrasound estimation of gestational age: A population-based cohort study.

BACKGROUND: Gestational age estimation by second-trimester ultrasound biometry introduces systematic errors due to sex differences in early foetal growth, consequently increasing the risk of adverse neonatal outcomes. Ultrasound estimation earlier in pregnancy may reduce this bias. OBJECTIVES: To investigate the distribution of sex ratio by gestational age and estimate the risk of adverse outcomes in male foetuses born early-term and female foetuses born post-term by first- and second-trimester ultrasound estimations. METHODS: This population-based study compared two cohorts of births with gestational age based on first- and second-trimester ultrasound in the Medical Birth Registry of Norway between 2016 and 2020. We used a log-binomial regression model to estimate adjusted relative risk (RR) with 95% confidence interval (CI) for Apgar score <7 at 5 min, umbilical artery pH <7.05, neonatal intensive care unit (NICU) admission and respiratory morbidity in relation to foetal sex. RESULTS: The sex ratio at birth in gestational weeks 36-43 showed less male predominance in pregnancies estimated in first compared to second trimester. Any adverse outcome was registered in 627 of 4470 male infants born in gestational weeks 37-38 and 618 of 6406 females born ≥41 weeks. Male infants born in weeks 37-38 had lower risk of NICU admission (RR 0.76, 95% CI 0.58, 0.99), Apgar score <7 at 5 min (RR 0.63, 95% CI 0.28, 1.41) and respiratory morbidity (RR 0.68, 95% CI 0.37, 1.25) in first- compared to second-trimester estimations. Female infants estimated in first trimester born ≥41 weeks had lower risk of umbilical artery pH <7.05, NICU admissions and respiratory morbidity; however, CIs were wide. CONCLUSIONS: Early ultrasound estimation of gestational age may reduce the excess risk of adverse neonatal outcomes and highlight the role of foetal sex and the timing of ultrasound assessment in the clinical evaluation of preterm and post-term pregnancies.

Women's negative childbirth experiences and socioeconomic factors: Results from the Babies Born Better survey.

OBJECTIVE: To investigate the association between women's socioeconomic status and overall childbirth experience and to explore how women reporting an overall negative birth experience describe their experiences of intrapartum care. METHODS: We used both quantitative and qualitative data from the Babies Born Better (B3) survey version 2, including a total of 8317 women. First, we performed regression analyses to explore the association between women's socioeconomic status and labour and birth experience, and then a thematic analysis of three open-ended questions from women reporting a negative childbirth experience (n = 917). RESULTS: In total 11.7% reported an overall negative labour and birth experience. The adjusted odds ratio (OR) of a negative childbirth experience was elevated for women with non-tertiary education, for unemployed, students and not married or cohabiting. Women with lower subjective living standard had an adjusted OR of 1.70 (95% CI 1.44-2.00) for a negative birth experience, compared with those with average subjective living standard. The qualitative analysis generated three themes: 1) Uncompassionate care: lack of sensitivity and empathy, 2) Impersonal care: feeling objectified, and 3) Critical situations: feeling unsafe and loss of control. CONCLUSION: Important socioeconomic disparities in women's childbirth experiences exist even in the Norwegian setting. Women reporting a negative childbirth experience described disrespect and mistreatment as well as experiences of insufficient attention and lack of awareness of individual and emotional needs during childbirth. The study shows that women with lower socioeconomic status are more exposed to these types of experiences during labour and birth. TWEETABLE ABSTRACT: Women with lower socioeconomic status are more exposed to negative experiences during labour and birth.

Seasonal variation in gestational diabetes mellitus among women in Norway: a national population-based study.

OBJECTIVES: Previous research on seasonal variation in the incidence of gestational diabetes mellitus (GDM) has shown inconclusive results. Furthermore, little is known about whether a seasonal variation in GDM might be associated with the maternal country of birth. We examined whether there was seasonal variation in GDM incidence by the maternal country background. DESIGN: National population-based registry study. SETTING AND PARTICIPANTS: We used national population-based data from the Medical Birth Registry of Norway (MBRN), n=1 443 857 (1990-2016) and data from four merged community-based studies (4GDM) with universal screening for GDM, n=2 978 (2002-2013). OUTCOME MEASURES: The association between season of pregnancy onset with incidence of GDM was examined separately in both datasets using logistic regression analyses, stratified by the mother's country background using two broad geographical categories (MBRN: Norwegian and immigrant; 4GDM: European and African/Asian ethnicity). Winter season was used as reference category. RESULTS: The incidence of GDM in MBRN was highest when the pregnancy started during the winter (Norwegian-born: 1.21%; immigrants: 3.32%) and lowest when pregnancy started during the summer for both Norwegian and immigrant women (Norwegian-born: 1.03% (OR 0.85, 95% CI 0.81 to 0.98); immigrants: 2.99% (OR 0.90, 95% CI 0.84 to 0.96)). The 4GDM data showed that women with European ancestry had the highest incidence of GDM when pregnancy started during autumn (10.7%, OR 1.01, 95% CI 0.69 to 1.46) and winter (10.6%), while ethnic African and Asian women had the highest incidence when pregnancy onset was during the summer (15.3%, OR 1.17, 95% CI 0.54 to 2.53). CONCLUSIONS: Based on national population-based data, this study suggests that GDM incidence varies by season in both Norwegian-born and immigrant women. The 4GDM dataset did not show a clear seasonal variation in GDM incidence, possibly due to the relatively small sample. Causes for the seasonal variation in GDM should be explored further.

Adjusting for outcome risk factors in immigrant datasets: total or direct effects?

BACKGROUND: When quantifying differences in health outcomes between immigrants and non-immigrants, it is common practice to adjust for observed differences in outcome risk factors between the groups being compared. However, as some of these outcome risk factors may act as mediators on the causal path between the exposure and outcome, adjusting for these may remove effects of factors that characterize the immigrants rather than removing a bias between immigrants and non-immigrants. METHODS: This study investigates the underlying conditions for which adjusting for outcome risk factors in regression models can lead to the estimation of either total or direct effect for the difference in health outcomes between immigrants and non-immigrants. For this investigation, we use modern tools in causal inference to construct causal models that we believe are highly relevant in an immigrant dataset. In these models, the outcome risk factor is modeled either as a mediator, a selection factor, or a combined mediator/selection factor. Unlike mediators, selection factors are variables that affect the probability of being in the immigrant dataset and may contribute to a bias when comparing immigrants and non-immigrants. RESULTS: When the outcome risk factor acts both as a mediator and selection factor, the adjustment for the risk factor in regression models leads to the estimation of what is known as a "controlled" direct effect. When the outcome risk factor is either a selection factor or a mediator alone, the adjustment for the risk factor in regression models leads to the estimation of a total effect or a controlled direct effect, respectively. In all regression analyses, also adjusting for various confounding paths, including mediator-outcome confounding, may be necessary to obtain valid controlled direct effects or total effects. CONCLUSIONS: Depending on the causal role of the outcome risk factors in immigrant datasets, regression adjustment for these may result in the estimation of either total effects or controlled direct effects for the difference in outcomes between immigrants and non-immigrants. Because total and controlled direct effects are interpreted differently, we advise researchers to clarify to the readers which types of effects are presented when adjusting for outcome risk factors in immigrant datasets.

Systemic Activation of the Kynurenine Pathway in Graves Disease With and Without Ophthalmopathy.

CONTEXT: Graves disease (GD) is one of the most common autoimmune disorders. Recent literature has shown an immune response involving several different inflammatory related proteins in these patients. OBJECTIVE: This work aimed to characterize the kynurenine pathway, activated during interferon-γ (IFN-γ)-mediated inflammation and cellular (T-helper type 1 [Th1] type) immunity, in GD patients with and without thyroid eye disease (TED). METHODS: We analyzed 34 biomarkers by mass spectrometry in serum samples from 100 patients with GD (36 with TED) and 100 matched healthy controls. The analytes included 10 metabolites and 3 indices from the kynurenine pathway, 6 microbiota-derived metabolites, 10 B-vitamers, and 5 serum proteins reflecting inflammation and kidney function. RESULTS: GD patients showed significantly elevated levels of 7 biomarkers compared with healthy controls (omega squared [ω2] > 0.06; P < .01). Of these 7, the 6 biomarkers with the strongest effect size were all components of the kynurenine pathway. Factor analysis showed that biomarkers related to cellular immunity and the Th1 responses (3-hydroxykynurenine, kynurenine, and quinolinic acid with the highest loading) were most strongly associated with GD. Further, a factor mainly reflecting acute phase response (C-reactive protein and serum amyloid A) showed weaker association with GD by factor analysis. There were no differences in biomarker levels between GD patients with and without TED. CONCLUSION: This study supports activation of IFN-γ inflammation and Th1 cellular immunity in GD, but also a contribution of acute-phase reactants. Our finding of no difference in systemic activation of the kynurenine pathway in GD patients with and without TED implies that the local Th1 immune response in the orbit is not reflected systemically.

Hearing threshold and physical performance in older people: a cross-sectional study from the HUNT4 cohort.

PURPOSE: To evaluate the association between increased hearing loss and reduced physical performance in older people. METHODS: Cross-sectional population-based study using data from the fourth wave of the Trøndelag Health Survey (HUNT4) in Norway. Data were obtained from the subproject HUNT4 Hearing which collected audiometric data of people > 70 years (N = 13,197). Analyses were performed on all participants who had completed audiometry and measured balance using the Short Physical Performance Battery (SPPB), which was scored from 0 (worst score) to 12. The hearing threshold was expressed as a pure tone average (PTA). Associations between the hearing threshold for the best and worst ear and physical performance were analyzed by linear regression models adjusted for age, sex, education, diabetes, and cardiovascular disease. Hearing threshold was indicated with steps of 10 dB. RESULTS: Of 13,197 eligible participants, 4101 who completed audiometry and SPPB (52.3% women. mean age 76.3 years) were included. The analyses revealed an association between reduced SPPB and increased hearing threshold in the best ear (b = - 0.296; 95% CI - 0.343 to - 0. 249; P < 0.001) and the worst ear (b = - 0.229; 95% CI - 0.270 to - 0.189; P < 0.001). CONCLUSIONS: In this population study, we found that the increased hearing threshold was associated to reduced physical performance as measured by SPPB. The association seemed to be strongest for the best ear. The association between hearing threshold and physical performance illustrates the importance of assessing physical performance in people with hearing loss to prevent the risk of falls and disability. The underlying causes of the associations between hearing loss and poorer physical performance are not fully understood and should be further investigated. LEVEL OF EVIDENCE: Level 3.

The ability of the Ages and Stages Questionnaire (ASQ) to indicate motor difficulties in infants in primary care.

INTRODUCTION: Delayed achievement of motor milestones may be an early indicator of motor difficulties. Parent-reported questionnaires may serve as an efficient, low-cost screening to identify infants in need of further clinical assessment, and thus be a helpful tool in busy health care centers. PURPOSE: To examine the ability of the Ages and Stages Questionnaire, second edition (ASQ-2) to indicate motor difficulties in infants using the Infant Motor Profile (IMP) as the reference standard. METHODS: A cross-sectional design was applied to examine the correlation between parent-reported data of the ASQ-2 and data from physiotherapist assessment using IMP. Included were 432 mainly low-risk infants aged 3-12 months from primary care. RESULTS: Overall, ASQ-2 gross and fine motor scores did not correlate well with the IMP total or domain scores. The ASQ-2 gross motor cut point (> 2SD below the mean), showed 34.3% sensitivity and 96.7% specificity using the 15th percentile from IMP performance domain as reference standard. The positive predictive value to indicate motor difficulties was 48%. CONCLUSION: The motor domains of ASQ-2 have poor ability to identify infants with motor difficulties as indicated by their IMP scores in low-risk infants.

Cohort profile: Outcomes & Multi-morbidity In Type 2 diabetes (OMIT) - a national registry-based observational cohort with focus on care and treatment of key high-risk groups in Norway.

PURPOSE: The 'Outcomes & Multi-morbidity in Type 2 Diabetes' (OMIT) is an observational registry-based cohort of Norwegian patients with type 2 diabetes (T2D) established to study high-risk groups often omitted from randomised clinical trials. PARTICIPANTS: The OMIT cohort includes 57 572 patients with T2D identified via linkage of Norwegian Diabetes Register for Adults and the Rogaland-Oslo-Salten-Akershus-Hordaland study, both offering data on clinical patient characteristics and drug prescriptions. Subsequently these data are further linked to the Norwegian Prescription Database for dispensed medications, the Norwegian Population Register for data on death and migration, Statistics Norway for data on socioeconomic factors and ethnicity and the Norwegian Directorate of Health for data on the general practices and clinical procedures involved in the care of cohort patients. OMIT offers large samples for key high-risk patient groups: (1) young-onset diabetes (T2D at age <40 years) (n=6510), (2) elderly (age >75 years) (n=15 540), (3) non-Western ethnic minorities (n=9000) and (4) low socioeconomic status (n=20 500). FINDINGS TO DATE: On average, patient age and diabetes duration is 67.4±13.2 and 12.3±8.3 years, respectively, and mean HbA1c for the whole cohort through the study period is 7.6%±1.5% (59.4±16.3 mmol/mol), mean body mass index (BMI) and blood pressure is 30.2±5.9 kg/m2 and 135±16.1/78±9.8 mm Hg, respectively. Prevalence of retinopathy, coronary heart disease and stroke is 10.1%, 21% and 6.7%, respectively. FUTURE PLANS: The OMIT cohort features 5784 subjects with T2D in 2006, a number that has grown to 57 527 in 2019 and is expected to grow further via repeated linkages performed every third to fifth year. At the next wave of data collection, additional linkages to Norwegian Patient Registry and Norwegian Cause of Death Registry for data on registered diagnoses and causes of death, respectively, will be performed.

Antibiotic use in children before, during and after hospitalisation.

PURPOSE: To investigate ambulatory antibiotic use in children during 1 year before and 1 year after in-hospital antibiotic exposure compared to children from the general population that had not received antibiotics in-hospital. METHODS: Explorative data-linkage cohort study from Norway of children aged 3 months to 17 years. One group had received antibiotics in-Hospital (H+), and one group had not received antibiotics in-hospital (H-). The H+ group was recruited during admission in 2017. Using the Norwegian Population Registry, 10 children from the H- group were matched with one child from the H+ group according to county of residence, age and sex. We used the Norwegian Prescription Database to register antibiotic use 1 year before and 1 year after the month of hospitalisation. RESULTS: Of 187 children in the H+ group, 83 (44%) received antibiotics before hospitalisation compared to 288/1870 (15%) in the H- group, relative risk (RR) 2.88 (95% confidence interval 2.38-3.49). After hospitalisation, 86 (46%) received antibiotics in the H+ group compared to 311 (17%) in the H- group, RR 2.77 (2.30-3.33). Comorbidity-adjusted RR was 2.30 (1.84-2.86) before and 2.25 (1.81-2.79) after hospitalisation. RR after hospitalisation was 2.55 (1.99-3.26) in children 3 months-2 years, 4.03 (2.84-5.71) in children 3-12 years and 2.07 (1.33-3.20) in children 13-17 years. CONCLUSIONS: Children exposed to antibiotics in-hospital had two to three times higher risk of receiving antibiotics in ambulatory care both before and after hospitalisation. The link between in-hospital and ambulatory antibiotic exposure should be emphasised in future antibiotic stewardship programs.

Are infants exposed to antimicrobials during the first 3 months of life at increased risk of recurrent use? An explorative data-linkage study.

OBJECTIVES: To investigate whether infants exposed to antimicrobials in hospital during the first 3 months of life had an increased risk of ambulatory antimicrobial use during the following year compared with infants not exposed to antimicrobials during the first 3 months of life. METHODS: Norwegian cohort study of infants less than 3 months consisting of one group exposed to antimicrobials recruited during hospitalization and one group not exposed to antimicrobials. Ten unexposed infants were matched with one exposed infant according to county of residence, birth year and month, and sex. The Norwegian Prescription Database was applied to register antimicrobial use from the month after discharge and 1 year onward. We defined comorbidity based on antimicrobials prescribed as reimbursable prescriptions due to underlying diseases. RESULTS: Of 95 infants exposed to antimicrobials during the first 3 months of life, 23% had recurrent use compared with 14% use in 950 unexposed infants [relative risk (RR) = 1.7 (95% CI = 1.1-2.5) and comorbidity-adjusted RR = 1.4 (95% CI = 0.9-2.2)]. The recurrence use rate in exposed term infants (≥37 weeks, n = 70) was 27% compared with 12% in their unexposed matches [RR 2.3 = (95% CI = 1.4-3.7) and comorbidity-adjusted RR = 1.9 (95% CI = 1.2-3.2). Of 25 exposed preterm infants, 3 (12%) had recurrent use. The total antimicrobial prescription rate was 674/1000 in the exposed group and 244/1000 in the unexposed group [incidence rate ratio = 2.8 (95% CI = 1.6-4.9)]. CONCLUSIONS: Infants exposed to antimicrobials during the first 3 months of life had an increased risk of recurrent use during the following year. This increased risk also appeared in term infants without infection-related comorbidity.

A randomized controlled trial on the effect of blue-blocking glasses compared to partial blue-blockers on melatonin profile among nulliparous women in third trimester of the pregnancy.

OBJECTIVE: In pregnancy melatonin regulates circadian rhythms, induce sleep, and has a neuroprotective positive effect on fetal development. Artificial blue light in the evening delays and suppresses melatonin production. Thus, we investigated the effect of blocking blue light on the melatonin profile. METHODS: A randomized controlled trial (n=30 blue-blocking glasses vs. n=30 control glasses with partial blue-blocking effect) including healthy nulliparous pregnant women in the beginning of the third trimester. Salivary melatonin and subjective sleep were measured before and after two weeks of intervention/control condition. Saliva was sampled at 30-min intervals from 3 h before normal bedtime. Melatonin onset was set at 4.0 pg/ml. RESULTS: Due to missing data melatonin onset was estimated for 47 participants. At posttreatment, melatonin onset advanced by 28 min in the blue-blocking group compared with the control condition (p=.019). Melatonin levels were significantly higher, favoring the blue-blocking glass condition, at clock time 20:00, 21:00 and 22:00 h, and for sample number 3 and 4. The phase angle (time interval) between melatonin onset and sleep bedtime and sleep onset time increased within the blue blocking group (+45 min and +41 min, respectively), but did not reach statistical significance compared to control condition (+13 min and +26 min, respectively). CONCLUSION: Blocking blue light in the evening had a positive effect on the circadian system with an earlier onset and rise of melatonin levels in healthy nulliparous pregnant women. This demonstrated the effectiveness and feasibility of a simple non-pharmacological chronobiological intervention during pregnancy.

The Relationship Between Perceived Social Support and PTSD Symptoms After Exposure to Physical Assault: An 8 Years Longitudinal Study.

Consequences of nondomestic violence are known to be multifaceted with high rates of emotional and psychological problems in addition to physical injuries, and victims report many trauma related symptoms. This study explore if perceived social support (PSS) (Social Provisions Scale [SPS]) and post-traumatic stress disorder (PTSD) symptoms (Impact of Event Scale [IES-22]) are interrelated among adult victims at four assessment points up until eight years after the exposure to physical assault; soon after the event (T1), three months after T1 (T2), one year after T1 (T3), and eight years after T1 (T4). One hundred and forty-three subjects participated at T1, 94 at T2, 73 at T3, and 47 accepted a follow-up at T4. At T1, 138 of 143 completed the questionnaires within 16 weeks after the incident. PTSD symptoms were highly correlated across time (p < .001); PSS were significantly correlated only between T1 and T2 (p < .001), T1 and T3 (p < .05), and between T2 and T3 (p < .05). Cross-lagged analyses showed an inverse relationship between prior PSS and later PTSD symptoms across all time points (ps < .05); not proved between prior PTSD symptoms and later PSS (ps > .1). PSS at T1 was an independent predictor of PSS one year and eight years after the incident. We conclude that higher perception of social support protects against the development of PTSD symptoms; diminished perception of social support increases the risk of developing PTSD symptoms. These findings suggest that PSS after experiencing a violent assault should be considered as an important factor in natural recovery in the long run, as well as essential alongside psychiatric treatment. Establishing psychosocial interventions for victims of physical violence in the acute phase may prevent prolonged trauma reactions.

Dizziness and physical health are associated with pain in dizzy patients-A cross-sectional study.

BACKGROUND AND PURPOSE: Associations between dizziness, health-related quality of life, and musculoskeletal pain have not been systematically explored in patients with vestibular disorders. Such knowledge may be important for choice of treatments. The study objectives were to examine the extent and localization of musculoskeletal pain and explore whether pain was associated with dizziness and health-related quality of life. METHODS: The cross-sectional study investigated anonymized data from an earlier survey on patients with long-lasting dizziness (>3 months) examined in an oto-rhino-laryngological department. The sample includes patient between 18 and 70 years with Ménière's disease, vestibular schwannoma, benign positional paroxysmal vertigo, vestibular neuritis, non-otogenic dizziness, and cervicogenic dizziness. General musculoskeletal, that is, pain in muscles, tendons, and joints was registered by a yes/no question. A pain drawing registered localization of pain. Multiple binary logistic regression models were used to determine the association between pain and vertigo-balance and autonomic-anxiety related dizziness by the short Vertigo Symptom Scale (VSS) and sub-scales (VSS-V, VSS-A), and between pain and health-related quality of life by the SF-36, mental and physical component summary scale (SF-36 MCS, SF-36 PCS). RESULTS: The sample consisted of 503 patients, 60.2% were women, the median age was 50 years. General musculoskeletal pain was reported by 72.8% of patients, neck pain by 59.2% and widespread pain by 21.9%. Multiple binary logistic regression models demonstrated that all the pain measures were significantly associated with VSS-V and VSS-A and SF-36 PCS, but not SF-36 MCS. DISCUSSIONS: Musculoskeletal pain is prevalent in patients with long-lasting dizziness. The strong associations between pain, VSS, and SF-36 PCS could result in a self-sustaining complex condition. The findings imply that in addition to assessing and treating the vestibular symptoms, musculoskeletal symptoms and physical health should be addressed.

Use of patient-reported outcome measures (PROMs) in clinical diabetes consultations: the DiaPROM randomised controlled pilot trial.

OBJECTIVE: To pilot test the proposed DiaPROM trial components and address uncertainties associated with conducting a full-scale randomised controlled trial (RCT) to evaluate whether such a trial is feasible. DESIGN: Two-arm pilot RCT. PARTICIPANTS: Adults aged ≥18-39 years, with minimum 1 year type 1 diabetes duration, attending outpatient follow-up. Exclusion criteria were pregnancy, severe cognitive, somatic or psychiatric conditions and impaired vision. RANDOMISATION AND INTERVENTION: All participants completed electronic Patient-Reported Outcome Measures (PROMs) prior to the annual diabetes consultation. Using computer-generated block-randomisation without blinding, we assigned participants in a 1:1 ratio stratified by sex to receive standard care or an intervention. Physicians reviewed diabetes distress scores (Problem Areas In Diabetes scale) and referred individuals with scores ≥30 or single item(s) ≥3 to minimum two diabetes nurse consultations where reported problems were reviewed and discussed. OUTCOMES: Recruitment and retention rates; participants perceptions about intervention components. Variance and estimated between-group differences in follow-up scores (Diabetes Distress Scale (DDS), WHO 5-Well-being Index, Perceived Competence for Diabetes Scale and glycaemic control) and DDS correlation with baseline scores, to assist sample size calculations. RESULTS: We randomised 80 participants to the control or intervention arm (one participant was later excluded). 23/39 intervention arm participants qualified for additional consultations and 17 attended. 67/79 attended the 12-month follow-up (15.2% attrition); 5/17 referred to additional consultations were lost to follow-up (29.4% attrition). Participants reported PROMs as relevant (84.6%) and acceptable (97.4%) but rated the usefulness of consultations as moderate to low. Baseline mean±SD DDS score was 2.1±0.69; DDS SD was 0.71 (95% CI: 0.60 to 0.86) at follow-up; correlation between baseline and follow-up DDS scores was 0.8 (95% CI: 0.7 to 0.9). CONCLUSIONS: The pilot trial revealed need for intervention modifications ahead of a full-scale trial to evaluate use of PROMs in diabetes consultations. Specifically, participant acceptability and intervention implementation need further investigation.

Norwegian Psychomotor Physiotherapy versus Cognitive Patient Education and active physiotherapy-A randomized controlled trial.

BACKGROUND AND PURPOSE: Norwegian Psychomotor Physiotherapy (NPMP) has been an established treatment approach for more than 50 years, mostly in the Scandinavian countries, usually applied to patients with widespread and long-lasting musculoskeletal pain and/or psychosomatic disorders. Few studies have investigated the outcomes of NPMP, and no randomized clinical trials (RCT) with a comparing treatment group have systematically been tried out on individuals. METHODS: This is a pragmatic, single-blinded RCT where 128 participants with long-lasting widespread musculoskeletal pain and/or pain located to the neck and shoulders were block randomized to NPMP or Cognitive Patient Education combined with active individualized physiotherapy (COPE-PT). Intention-to-treat with linear mixed models were used to estimate the group differences in treatment effects. The outcomes at 3, 6, and 12 months follow-up were pain intensity, function, anxiety and depression, quality of life, sleep, fear of movement, and subjective health complaints. Risk profile (Örebro) was examined at 3 and 6 months. All participants underwent physical tests at baseline and 6 months. RESULTS: One-year data were available for 66.4% of the original participants. Calculated with intention-to-treat analysis, at 3 months statistically significant differences were found in favor of COPE-PT for pain, anxiety and depression, quality of life-physical dimension, risk profile and fear of movement. At 6 months, statistically significant differences in favor of COPE-PT were found for anxiety and depression, and sleep. At 12 months, the improvements were still statistically significant for anxiety, depression and sleep. Both groups improved, but no statistically significant differences were found between the groups on the physical tests at 6 months. CONCLUSIONS: COPE-PT, which is targeted towards pain-coping and increasing activity, contribute to more improvements than NPMP.

One Year Change in 6-Minute Walk Test Outcomes is Associated with COPD Prognosis.

Six-minute walk test (6MWT) measures walking distance (6MWD) and desaturation status in chronic obstructive pulmonary disease (COPD) patients. This study aimed to examine whether change in 6MWD and desaturation in 1 year were risk factors for later mortality, lung function decline and number of exacerbations. A total of 295 COPD patients performed 6MWT at baseline and 1 year later in the Bergen COPD cohort study 2006-2011. They were clinically examined and interviewed at annual visits. Mortality information was collected from the Norwegian Cause of Death Registry in 2015. We performed cox regression for mortality outcomes, linear mixed effect models for lung function, and negative binomial regression for exacerbations. Patients who desaturated in both 6MWTs had increased risk of all-cause and respiratory mortality, hazard ratio (HR) 2.7 (95% confidence interval [CI] 1.5-5.0) and 3.6 (95% CI 1.7-7.6), respectively, compared to non-desaturators. Patients who desaturated only at second 6MWT were at risk for all-cause mortality (HR 2.0, 95% CI 1.0-3.8). There were no apparent association between 6MWD and mortality. Desaturation in second 6MWT was associated with later increased rate of decline in forced vital capacity (FVC) % predicted (after 1 year predicted mean 4.2% above non-desaturators, after 5 years 0.7% below). Decline in 6MWD ≥ 30m was borderline (p = 0.06) associated with later decline in forced expiratory volume in 1 second % predicted, and with exacerbations (p = 0.07). Repeated desaturation in the 6MWT over time in COPD patients is a risk factor for all-cause and respiratory mortality, while onset of desaturation is associated with future FVC decline.

Effects of external inspections on sepsis detection and treatment: a stepped-wedge study with cluster-level randomisation.

OBJECTIVE: To evaluate the effects of external inspections on (1) hospital emergency departments' clinical processes for detecting and treating sepsis and (2) length of hospital stay and 30-day mortality. DESIGN: Incomplete cluster-randomised stepped-wedge design using data from patient records and patient registries. We compared care processes and patient outcomes before and after the intervention using regression analysis. SETTING: Nationwide inspections of sepsis care in emergency departments in Norwegian hospitals. PARTICIPANTS: 7407 patients presenting to hospital emergency departments with sepsis. INTERVENTION: External inspections of sepsis detection and treatment led by a public supervisory institution. MAIN OUTCOME MEASURES: Process measures for sepsis diagnostics and treatment, length of hospital stay and 30-day all-cause mortality. RESULTS: After the inspections, there were significant improvements in the proportions of patients examined by a physician within the time frame set in triage (OR 1.28, 95% CI 1.07 to 1.53), undergoing a complete set of vital measurements within 1 hour (OR 1.78, 95% CI 1.10 to 2.87), having lactate measured within 1 hour (OR 2.75, 95% CI 1.83 to 4.15), having an adequate observation regimen (OR 2.20, 95% CI 1.51 to 3.20) and receiving antibiotics within 1 hour (OR 2.16, 95% CI 1.83 to 2.55). There was also significant reduction in mortality and length of stay, but these findings were no longer significant when controlling for time. CONCLUSIONS: External inspections were associated with improvement of sepsis detection and treatment. These findings suggest that policy-makers and regulatory agencies should prioritise assessing the effects of their inspections and pay attention to the mechanisms by which the inspections might contribute to improve care for patients. TRIAL REGISTRATION: NCT02747121.

Use of Antidepressants in Older People during a 10-Year Period: An Observational Study on Prescribed Doses and Serum Levels.

BACKGROUND: According to previous studies, older patients frequently have serum concentrations of antidepressant medication above the recommended reference range. OBJECTIVE: The aim of this study was to investigate whether prescribed doses of antidepressants and the proportion of individuals with serum concentrations above the recommended reference range in older individuals (≥ 65 years) have changed over a 10-year period in Norway. METHODS: Serum concentration measurements and prescribed daily doses of antidepressants in 2007 and 2017 were extracted from a therapeutic drug monitoring (TDM) database at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. The database contains routine follow-up serum concentration measurements of psychotropic drugs for patients from all parts of the country. For citalopram, escitalopram, sertraline, mirtazapine and venlafaxine, the differences between 2007 and 2017 in mean prescribed doses and the proportion of patients with at least one serum concentration above the reference range, according to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guidelines, were compared. For the proportion of patients with serum concentrations above the recommended reference range, differences between individuals aged 65-79 and ≥ 80 years were also examined. RESULTS: The analyses of prescribed doses included 806 patients from 2007 and 1932 patients from 2017, with 972 and 2441 TDM samples, respectively. Between 2007 and 2017, modest reductions in prescribed daily doses were observed for citalopram (20 vs. 17 mg/day) and escitalopram (11 vs. 10 mg/day), but the proportion of patients with serum concentrations above the recommended reference range was unchanged for both drugs, i.e. 11.5% vs. 12.4% for citalopram and 3.6% vs. 2.9% for escitalopram. For mirtazapine and venlafaxine, prescribed doses were reduced from 28 to 25 mg/day and 150 to 125 mg/day, respectively. A significant reduction in the proportion of individuals with serum concentrations above the recommended reference range was observed for mirtazapine (27.1% vs. 11.5%) and for individuals aged ≥ 80 years using venlafaxine (60.0% vs. 30.0%). For sertraline, no differences in prescribed doses or serum concentrations above the recommended reference range were observed. CONCLUSIONS: Over a 10-year period, prescribed doses of antidepressants have been slightly reduced in older Norwegian patients, but a considerable proportion is still exposed to high serum concentrations of antidepressants.

Being overweight in childhood, puberty, or early adulthood: Changing asthma risk in the next generation?

BACKGROUND: Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation. OBJECTIVE: We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. METHODS: We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status. RESULTS: We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found. CONCLUSION: Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health.

Examining boys' and girls' health-related quality of life from the first to the third year of upper secondary school: A prospective longitudinal study.

AIM: To examine differences in health-related quality of life between boys and girls in the first and third years of upper secondary school. DESIGN: Prospective longitudinal study. METHODS: The KIDSCREEN-10 was used to assess health-related quality of life. Differences in health-related quality of life over time were estimated using a linear mixed-effects model for correlated measurements. RESULTS: In the first-year boys (N = 168) and girls (N = 228) reported a mean health-related quality of life score of 76.3 (SD 10.7) and 69.8 (SD 11.5), respectively. In the third year, the mean health-related quality of life score for boys and girls was 73.5 (SD 12.4) and 65.7 (SD 13.3), respectively. Boys had a significant decrease in health-related quality of life mean score of -2.6 and girls a significant decrease of -3.8 (p < .001) over the 3-year period. There was no significant difference between boys' and girls' health-related quality of life changes (p = .39).