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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.

Background: In order to change antibiotic prescribing behaviour, we need to understand the prescribing process. The aim of this study was to identify targets for antibiotic stewardship interventions in hospitals through analysis of the antibiotic prescribing process from admission to discharge across five groups of infectious diseases., Methods: We conducted a multi-centre, observational cohort study, including patients with lower respiratory tract infections, exacerbation of chronic obstructive pulmonary disease, skin- and soft tissue infections, urinary tract infections or sepsis, admitted to wards of infectious diseases, pulmonary medicine and gastroenterology at three teaching hospitals in Western Norway. Data was collected over a 5-month period and included antibiotics prescribed and administered during admission, antibiotics prescribed at discharge, length of antibiotic therapy, indication for treatment and discharge diagnoses, estimated glomerular filtration rate (eGFR) on admission, antibiotic allergies, place of initiation of therapy, admittance from an institution, patient demographics and outcome data. Primary outcome measure was antibiotic use throughout the hospital stay, analysed by WHO AWaRe-categories and adherence to guideline. Secondary outcome measures were a) antibiotic prescribing patterns by groups of diagnoses, which were analysed using descriptive statistics and b) non-adherence to the national antibiotic guidelines, analysed using multivariate logistic regression., Results: Through analysis of 1235 patient admissions, we identified five key targets for antibiotic stewardship interventions in our population of hospital inpatients; 1) adherence to guideline on initiation of treatment, as this increases the use of WHO Access-group antibiotics, 2) antibiotic prescribing in the emergency room (ER), as 83.6% of antibiotic therapy was initiated there, 3) understanding prescribing for patients admitted from other institutions, as this was significantly associated with non-adherence to guideline (OR = 1.44 95% CI 1.04, 2.00), 4) understanding cultural and contextual drives of antibiotic prescribing, as non-adherent prescribing differed significantly between the sites of initiation of therapy (between hospitals and ER versus ward) and 5) length of therapy, as days of antibiotic therapy was similar across a wide range of diagnoses and with prolonged therapy after discharge., Conclusions: Analysing the process of antibiotic prescribing in hospitals with patient-level data identified important targets for antibiotic stewardship interventions in hospitals.

Background: This study compares subsequent birth outcomes in migrant women who had already had a child before arriving in Norway with those in migrant women whose first birth occurred in Norway. The aim of this study was to investigate the associations between country of first birth and adverse neonatal outcomes (very preterm birth, moderately preterm birth, post-term birth, small for gestational age, large for gestational age, low Apgar score, stillbirth and neonatal death) in parous migrant and Norwegian-born women., Methods: National population-based study including second and subsequent singleton births in Norway from 1990 to 2016. Data were retrieved from the Medical Birth Registry of Norway and Statistics Norway. Neonatal outcomes were compared between births to: 1) migrant women with a first birth before immigration to Norway (n = 30,062) versus those with a first birth after immigration (n = 66,006), and 2) Norwegian-born women with a first birth outside Norway (n = 6205) versus those with a first birth in Norway (n = 514,799). Associations were estimated as crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) using multiple logistic regression., Results: Migrant women with a first birth before immigrating to Norway had increased odds of adverse outcomes in subsequent births relative to those with a first birth after immigration: very preterm birth (22-31 gestational weeks; aOR = 1.27; CI 1.09-1.48), moderately preterm birth (32-36 gestational weeks; aOR = 1.10; CI 1.02-1.18), post-term birth (≥42 gestational weeks; aOR = 1.19; CI 1.11-1.27), low Apgar score (< 7 at 5 min; aOR = 1.27; CI 1.16-1.39) and stillbirth (aOR = 1.29; CI 1.05-1.58). Similar results were found in the sample of births to Norwegian-born women., Conclusions: The increased odds of adverse neonatal outcomes for migrant and Norwegian-born women who had their first births outside Norway should serve as a reminder of the importance of taking a careful obstetric history in these parous women to ensure appropriate care for their subsequent pregnancies and births in Norway.

Objective: To investigate voice characteristics and exercise related respiratory symptoms in extremely preterm born 11-year-old children, focusing particularly on associations with management of a patent ductus arteriosus (PDA). Study design: Prospective follow-up of all children born in Norway during 1999-2000 at gestational age <28 weeks or with birthweight <1,000 g. Neonatal data were obtained prospectively on custom-made registration forms completed by neonatologists. Voice characteristics and exercise related respiratory symptoms were obtained at 11 years by parental questionnaires. Result: Questionnaires were returned for 228/372 (61%) eligible children, of whom 137 had no history of PDA. PDA had been noted in 91 participants, of whom 36 had been treated conservatively, 21 with indomethacin, and 34 with surgery. Compared to the children treated with indomethacin or conservatively, the odds ratio (95% confidence interval) for the surgically treated children were 3.4 (1.3; 9.2) for having breathing problems during exercise, 16.9 (2.0; 143.0) for having a hoarse voice, 4.7 (1.3; 16.7) for a voice that breaks when shouting, 4.6 (1.1; 19.1) for a voice that disturbs singing, and 3.7 (1.1; 12.3) for problems shouting or speaking loudly. The significance of surgery per se was uncertain since the duration of mechanical ventilation was associated with the same outcomes. Conclusion: Extremely preterm born children with a neonatal history of PDA surgery had more problems with voice and breathing during exercise in mid-childhood than those whose PDA had been handled otherwise. The study underlines the causal heterogeneity of exercise related respiratory symptoms in preterm born children., (Copyright © 2020 Engeseth, Engan, Clemm, Vollsæter, Nilsen, Markestad, Halvorsen and Røksund.)

Purpose: Since evidence of an association between vitamin B12 (B12) deficiency and anemia in older people is limited and inconclusive, we wanted to investigate this association in old, frail nursing home patients., Methods: The study includes patients admitted to short-term, post-acute care (n = 765) and residents in long-term care (LTC) (n = 1665), in the municipality of Bergen. Anemia was defined according to the WHO criteria: Hb < 13 g/dL in men and < 12 g/dL in women, and as Hb < 11 g/dL, in both sex (moderate/severe anemia). The presence of anemia was analyzed in patients with subnormal (< 250 pmol/L), normal (250-650 pmol/L) and high (> 650 pmol/L) B12, and the association between anemia and clinical parameters, and including B12, was analyzed using logistic regression models. The use of B12 supplementation was investigated in the LTC patients., Results: Mean age of the 2430 patients was 86 ± 7 years. WHO-defined anemia was seen in 1023 (42%), and moderate/severe anemia in 384 (16%) of the patients. In multiple logistic regression analyses, we found no statistically significant associations of subnormal B12 with WHO-defined anemia or moderate/severe anemia. Renal insufficiency, iron deficiency and CRP > 10 mg/L were significantly associated with both types of anemia, (p < 0.001). Among the LTC residents, 405 (24%) received B12 supplements, 112 (7%) of them had elevated B12 > 650 pmol/L., Conclusion: In older nursing home patients, no association was observed between subnormal B12 and anemia. Older patients in Western societies with mild/moderate anemia should not be treated with B12 supplements without further investigation.

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., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Early recognition of sepsis is critical for timely initiation of treatment. The first objective of this study was to assess the timeliness of diagnostic procedures for recognizing sepsis in emergency departments. We define diagnostic procedures as tests used to help diagnose the condition of patients. The second objective was to estimate associations between diagnostic procedures and time to antibiotic treatment, and to estimate associations between time to antibiotic treatment and mortality., Methods: This observational study from 24 emergency departments in Norway included 1559 patients with infection and at least two systemic inflammatory response syndrome criteria. We estimated associations using linear and logistic regression analyses., Results: Of the study patients, 72.9% (CI 70.7-75.1) had documented triage within 15 minutes of presentation to the emergency departments, 44.9% (42.4-47.4) were examined by a physician in accordance with the triage priority, 44.4% (41.4-46.9) were adequately observed through continual monitoring of signs while in the emergency department, and 25.4% (23.2-27.7) received antibiotics within 1 hour. Delay or non-completion of these key diagnostic procedures predicted a delay of more than 2.5 hours to antibiotic treatment. Patients who received antibiotics within 1 hour had an observed 30-day all-cause mortality of 13.6% (10.1-17.1), in the timespan 2 to 3 hours after admission 5.9% (2.8-9.1), and 4 hours or later after admission 10.5% (5.7-15.3)., Conclusions: Key procedures for recognizing sepsis were delayed or not completed in a substantial proportion of patients admitted to the emergency department with sepsis. Delay or non-completion of key diagnostic procedures was associated with prolonged time to treatment with antibiotics. This suggests a need for systematic improvement in the initial management of patients admitted to emergency departments with sepsis., Competing Interests: The authors have declared that no competing interests exist.

The original article [1] contains errors in Tables 1 and 3: Table 1 erroneously mentions use of a treadmill which should instead state 'bicycle', and Table 3 has a minor typesetting mistake.

Background: Discharge conversation is an essential part of preparing patients for the period after hospitalisation. Successful communication during such conversations is associated with improved health outcomes for patients., Objective: To investigate the association between discharge conversation and discharge quality assessed by measuring elderly patients' experiences., Methods: In this cross-sectional study, we surveyed all patients ≥65 years who had been discharged from two medical units in two hospitals in Western Norway 30 days prior. We measured patient experiences using two previously validated instruments: The Discharge Care Experiences Survey Modified (DICARES-M) and The Nordic Patient Experiences Questionnaire (NORPEQ). We examined differences in characteristics between patients who reported having a discharge conversation with those who did not, and used regression analyses to examine the associations of the DICARES-M and NORPEQ with the usefulness of discharge conversation., Results: Of the 1418 invited patients, 487 (34%) returned the survey. Their mean age was 78.5 years (SD=8.3) and 52% were women. The total sample mean scores for the DICARES-M and NORPEQ were 3.9 (SD=0.7, range: 1.5-5.0) and 4.0 (SD=0.7, range: 2.2-5.0), respectively. Higher DICARES-M and NORPEQ scores were found for patients who reported having a discharge conversation (74%) compared with those who did not (15%), or were unsure (11%) whether they had a conversation (p<0.001). Patients who considered the conversation more useful had significantly higher scores on both the DICARES-M and NORPEQ (p<0.001)., Conclusions: Reported discharge conversation at the hospital was correlated with positive patient experiences measurements indicating the increased quality of hospital discharge care. The reported usefulness of the conversation had a significant association with discharge care quality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Knowledge of the effect of marine protein hydrolysate (MPH) supplementation to promote recovery after high intensity performance training is scarce. The aim of this study was to examine the effect of MPH supplementation to whey protein (WP) and carbohydrate (CHO): (CHO-WP-MPH), on short-term recovery following high intensity performance, compared to an isoenergetic and isonitrogenous supplement of WP and CHO: (CHO-WP), in male cyclists., Methods: This was a double-blinded crossover study divided into three phases. Fourteen healthy men participated. In phase I, an incremental bicycle exercise test was performed for establishment of intensities used in phase II and III. In phase II (9-16 days after phase 1), the participants performed first one high intensity performance cycling session, followed by nutrition supplementation (CHO-WP-MPH or CHO-WP) and 4 hours of recovery, before a subsequent high intensity performance cycling session. Phase III (1 week after phase II), was similar to phase II except for the nutrition supplementation, where the participants received the opposite supplementation compared to phase II. Primary outcome was difference in time to exhaustion between the cycling sessions, after nutrition supplementations containing MPH or without MPH. Secondary outcomes were differences in heart rate (HR), respiratory exchange ratio (RER), blood lactate concentration and glucose., Results: The mean age of the participants was 45.6 years (range 40-58). The maximal oxygen uptake (mean ± SD) measured at baseline was 54.7 ± 4.1 ml∙min - 1 ∙kg - 1 . There were no significant differences between the two nutrition supplementations measured by time to exhaustion at the cycling sessions (mean diff  = 0.85 min, p = 0.156, 95% confidence interval (CI), - 0.37, 2.06), HR (mean diff  = 0.8 beats pr.min, p = 0.331, 95% CI, - 0.9, 2.5), RER (mean diff  = - 0.05, p = 0.361, 95% CI -0.07 - 0.17), blood lactate concentration (mean diff  = - 0.24, p = 0.511, 95% CI, - 1.00, 0.53) and glucose (mean diff  = 0.23, p = 0.094, 95% CI, - 0.05, 0.51)., Conclusions: A protein supplement with MPH showed no effects on short-term recovery in middle-aged healthy male cyclists compared to a protein supplement without MPH., Trial Registration: The study was registered 02.05.2017 at ClinicalTrials.gov (Protein Supplements to Cyclists, NCT03136133 , https://clinicaltrials.gov/ct2/show/NCT03136133?cond=marine+peptides&rank=1 .

Self-selection into prospective cohort studies and loss to follow-up can cause biased exposure-outcome association estimates. Previous investigations illustrated that such biases can be small in large prospective cohort studies. The structural approach to selection bias shows that general statements about bias are not possible for studies that investigate multiple exposures and outcomes, and that inverse probability of participation weighting (IPPW) but not adjustment for participation predictors generally reduces bias from self-selection and loss to follow-up. We propose to substantiate assumptions in structural models of selection bias through calculation of genetic correlations coefficients between participation predictors, outcome, and exposure, and to estimate a lower bound for bias due to self-selection and loss to follow-up by comparing effect estimates from IPP weighted and unweighted analyses. This study used data from the Norwegian Mother and Child Cohort Study and the Medical Birth Registry of Norway. Using the example of risk factors for ADHD, we find that genetic correlations between participation predictors, exposures, and outcome suggest the presence of bias. The comparison of exposure-outcome associations from regressions with and without IPPW revealed meaningful deviations. Assessment of selection bias for entire multi-exposure multi-outcome cohort studies is not possible. Instead, it has to be assessed and controlled on a case-by-case basis.

Objective: Metabolic syndrome (MetS) includes hyperglycaemia, hypertension, central adiposity, elevated triglyceride levels and low levels of high-density lipoprotein cholesterol. All factors are identified as risk factors for cardiovascular disease and mortality. This longitudinal study examined whether loneliness, which has been shown to predict a range of negative health outcomes, increases the risk for MetS., Methods: We used data from 'the Nord-Trøndelag Health Study' (HUNT) which is a large longitudinal health study based on a Mid-Norway county population (n=26 990). Self-reports, physical examinations and blood samples were analysed to evaluate the associations between loneliness and incidents of MetS after 10 years (follow-up survey conducted during 2006-2008). We also investigated the role of depression as a potential mediating factor., Results: Individuals who reported higher levels of loneliness had a higher odds for MetS (adjusted OR 1.09 (95% CI 1.02 to 1.16); p=0.007). This effect was mediated through depression., Conclusions: Findings suggest that loneliness may be an important factor that increases the risk for MetS. The effect of loneliness on MetS is mediated through depressive symptoms. Reducing loneliness may help prevent the incidence of MetS and related diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

This study examines how preconception folic acid supplement use varied in immigrant women compared with non-immigrant women. We analyzed national population-based data from Norway from 1999-2016, including 1,055,886 pregnancies, of which 202,234 and 7,965 were to 1st and 2nd generation immigrant women, respectively. Folic acid supplement use was examined in relation to generational immigrant category, maternal country of birth, and length of residence. Folic acid supplement use was lower overall in 1st and 2nd generation immigrant women (21% and 26%, respectively) compared with Norwegian-born women (29%). The lowest use among 1st generation immigrant women was seen in those from Eritrea, Ethiopia, Morocco, and Somalia (around 10%). The highest use was seen in immigrant women from the United States, the Netherlands, Denmark, and Iceland (>30%). Folic acid supplement use increased with increasing length of residence in immigrant women from most countries, but the overall prevalence was lower compared with Norwegian-born women even after 20 years of residence (adjusted odds ratio: 0.63; 95% confidence interval: 0.60-0.67). This study suggests that immigrant women from a number of countries are less likely to use preconception folic acid supplements than non-immigrant women, even many years after settlement.

Background: The Discharge Care Experiences Survey (DICARES) was previously developed to measure quality of discharge care in elderly patients (≥ 65 years). The objective of this study was to test the factorial validity of responses of the DICARES, and to investigate its association with existing quality indicators., Methods: We conducted a cross-sectional study at two hospitals in Bergen, Western Norway. A survey, including DICARES, was sent by postal mail to 1,418 patients 30 days after discharge from hospital. To test the previously identified three-factor structure of the DICARES we applied a first order confirmatory factor analysis with corresponding fit indices and reliability measures. Spearman's correlation coefficients, and linear regression, was used to investigate the association of DICARES scores with the quality indicators Nordic Patient Experiences Questionnaire and emergency readmission within 30 days., Results: A total of 493 (35%) patients completed the survey. The mean age of the respondents was 79 years (SD = 8) and 52% were women. The confirmatory factor analysis showed acceptable fit. Cronbach's α between items within factors was 0.82 (Coping after discharge), 0.71 (Adherence to treatment), and 0.66 (Participation in discharge planning). DICARES was moderately correlated with the Nordic Patient Experiences Questionnaire (rho = 0.49, P < 0.001). DICARES overall score was higher in patients with no readmissions compared to those who were emergency readmitted within 30 days (P < 0.001), indicating that more positive experiences were associated with fewer readmissions., Conclusions: DICARES appears to be a feasible instrument for measuring quality of discharge care in elderly patients (≥ 65 years). This brief questionnaire seems to be sensitive with regard to readmission, and independent of comorbidity. Further studies of patients' experiences are warranted to identify elements that impact on discharge care in other patient groups., Competing Interests: The authors have declared that no competing interests exist.

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)., Competing Interests: The authors declare that they have no conflict of interest., (© 2019 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Purpose: To compare injections of hyaluronic acid (HA) and autologous fat (AF) for the treatment of unsightly temporal hollowing after lateral orbital wall decompression in thyroid eye disease., Methods: In this nonblinded prospective comparative interventional study, patients received injections of HA in the right temple and AF in the left temple. Additional injections were given when needed at follow-up after 6, 12, 18, and 24 months. Follow-up included an interview; clinical examination with an evaluation of symmetry, contour, and skin surface; and ultrasound measurements. From photographs, the temporal hollowing was graded 1-3. The main endpoints were grading of temporal hollowing and temporal soft tissue thickness., Results: Seventeen patients were treated bilaterally and 12 unilaterally (five received HA and seven AF). Injection(s) of HA and AF administered at each site were a median (range) of 1 (1-4) and 2 (1-5), respectively. The total combined volume of HA injected per site was 0.9 (0.2-2.0) ml and that of AF was 3.1 (0.5-9.6) ml. At the final examination, a statistically significant difference in mean (SD) grading scores of temporal hollowing due to HA (1.18 (0.26)) compared to those of AF (1.85 (0.44)) was observed (p < 0.001). Six months after administering an injection of HA, the temporal soft tissue thickness was 2.35 (0.24) cm compared to 2.19 (0.28) cm obtained with an injection of AF (p < 0.001). By using a linear mixed-effect model and adjusting for baseline values, age, sex, and refill, the difference in favor of HA persisted at all later follow-ups. Increased fibrosis of the subcutaneous tissue developed at 5/24 sites that received AF., Conclusion: Injection of HA is superior to that of AF for treating temporal hollowing after lateral orbital wall decompression., (Copyright © 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Clinical antibiotic prescribing guidelines are essential in defining responsible use in the local context. Our objective was to investigate the association between adherence to national antibiotic prescribing guidelines and patient outcomes across a wide range of infectious diseases in hospital inpatients., Methods: Over five months in 2014, inpatients receiving antibiotics under the care of pulmonary medicine, infectious diseases and gastroenterology specialties across three university hospitals in Western Norway were included in this observational cohort study. Patient and antibiotic prescribing data gathered from electronic medical records included indication for antibiotics, microbiology test results, discharge diagnoses, length of stay (LOS), comorbidity, estimated glomerular filtration rate (eGFR) on admission and patient outcomes (primary: 30-day mortality; secondary: in-hospital mortality, 30-day readmission and LOS). Antibiotic prescriptions were classified as adherent or non-adherent to national guidelines according to documented indication for treatment. Patient outcomes were analysed according to status for adherence to guidelines using multivariate logistic, linear and competing risk regression analysis with adjustments made for comorbidity, age, sex, indication for treatment, seasonality and whether the patient was admitted from an institution or not., Results: In total, 1756 patients were included in the study. 30-day-mortality and in-hospital mortality were lower (OR = 0.48, p  = 0.003 and OR = 0.46, p  = 0.001) in the guideline adherent group, compared to the non-adherent group. Adherence to guideline did not affect 30-day readmission. In linear regression analysis there was a trend towards shorter LOS when LOS was analysed for patients discharged alive (predicted mean difference - 0.47, 95% CI (- 1.02, 0.07), p  = 0.081). In competing risk analysis of LOS, the adherent group had a subdistribution hazard ratio (SHR) of 1.17 95% CI (1.02, 1.34), p  = 0.025 for discharge compared to the non-adherent group., Conclusions: Adhering to antibiotic guidelines when treating infections in hospital inpatients was associated with favourable patient outcomes in terms of mortality and LOS., Competing Interests: The study was conducted in accordance with the Declaration of Helsinki, national and institutional standards [28]. The study was approved by the local data protection officer (2013/9352) and the regional ethical committee approved the waiver of informed consent (2013/1305). All patients were informed in writing about the study taking place and given the opportunity to withdraw.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Living with type 1 diabetes (T1D) is demanding, and emotional problems may impair ability for diabetes self-management. Thus, diabetes guidelines recommend regular assessment of such problems. Using patient-reported outcome measures (PROMs) to assess diabetes-related distress and psychological well-being is considered useful. It has been proposed that future work should examine the use of PROMs to support the care of individual patients and improve the quality of health services. To our knowledge, the use of PROMs has not been systematically evaluated in diabetes care services in Norway. Electronically captured PROMs can be directly incorporated into electronic patient records. Thus, the study's overall aim was to examine the feasibility and acceptability of capturing PROMs electronically on a touchscreen computer in clinical diabetes practice., Methods: Adults with T1D age ≥ 40 years completed PROMs on a touchscreen computer at Haukeland University Hospital's diabetes outpatient clinic. We included 46 items related to diabetes-related distress, self-perceived diabetes competence, awareness of hypoglycaemia, occurrence of hyperglycaemia, hypoglycaemia and fluctuating glucose levels, routines for glucose monitoring, general well-being and health-related quality of life. Participants subsequently completed a paper-based questionnaire regarding comprehension and relevance of the PROMs, acceptance of the number of items and willingness to complete electronic PROMs annually. We wrote field notes in the outpatient clinic based on observations and comments from the invited participants., Results: During spring 2017, 69 participants (50.7% men), age 40 to 74 years, were recruited. Generally, the touchscreen computer functioned well technically. Median time spent completing the PROMs was 8 min 19 s. Twenty-nine (42.0%) participants completed the PROMs without missing items, with an 81.4% average instrument completion rate. Participants reported that the PROMs were comprehensible ( n  = 62) and relevant ( n  = 46) to a large or very large degree, with an acceptable number of items ( n  = 51). Moreover, 54 were willing to complete PROMs annually. Participants commented that the focus on living with diabetes was valued., Conclusions: Capturing PROMs on a touchscreen computer in an outpatient clinic was technically and practically feasible. The participants found the PROMs to be relevant and acceptable with a manageable number of items, and reported willingness to complete PROMs annually., Competing Interests: The study was approved by the Regional Committee for Medical and Health Research Ethics (reference number 2016/2200) and was performed according to the Declaration of Helsinki. Participants provided informed written consent and were free to withdraw their consent at any time without explanation and without any consequence for further follow-up at the outpatient clinic.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Effective use of microbiology test results may positively influence patient outcomes and limit the use of broad-spectrum antibiotics. However, studies indicate that their potential is not fully utilized. We investigated microbiology test ordering practices and the use of test results for antibiotic decision-making in hospitals., Methods: A multicentre cohort study was conducted during five months in 2014 in Medical departments across three hospitals in Western Norway. Patients treated with antibiotics for sepsis, urinary tract infections, skin and soft tissue infections, lower respiratory tract infections or acute exacerbations of chronic obstructive pulmonary disease were included in the analysis. Primary outcome measures were degree of microbiology test ordering, compliance with microbiology testing recommendations in the national antibiotic guideline and proportion of microbiology test results used to inform antibiotic treatment. Data was obtained from electronic- and paper medical records and charts and laboratory information systems., Results: Of the 1731 patient admissions during the study period, mean compliance with microbiology testing recommendations in the antibiotic guideline was 89%, ranging from 81% in patients with acute exacerbations of chronic obstructive pulmonary disease to 95% in patients with sepsis. Substantial additional testing was performed beyond the recommendations with 298/606 (49%) of patients with lower respiratory tract infections having urine cultures and 42/194 (22%) of patients with urinary tract infections having respiratory tests. Microbiology test results from one of the hospitals showed that 18% (120/672) of patient admissions had applicable test results, but only half of them were used for therapy guidance, i.e. in total, 9% (63/672) of patient admissions had test results informing prescription of antibiotic therapy., Conclusions: This study showed that despite a large number of microbiology test orders, only a limited number of tests informed antibiotic treatment. To ensure that microbiology tests are used optimally, there is a need to review the utility of existing microbiology tests, test ordering practices and use of test results through a more targeted and overarching approach., Competing Interests: The Western Regional Committee for Medical and Health Research Ethics in Norway assessed the study, and concluded that no ethical approval was needed. The Committee approved the waiver of informed consent on the condition that all patients received written information about the study, with opportunity to withdraw from it (2013/1305). Data collection was also approved by The Data Protection Officer at all three hospitals (2013/9352).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Introduction: Although diabetes distress is found to be associated with decreased glycaemic control among adults with type 1 diabetes, the psychological and emotional impact of living with the condition is often not recognised and often under-reported in diabetes care. Therefore, regular assessment of diabetes distress is recommended. Assessment of diabetes distress using patient-reported outcome measures (PROMs) in clinical practice has the potential to enhance care for people with diabetes by identifying problems and improving patient-clinician communication. In this study protocol, we describe a pilot randomised controlled trial (RCT) aiming to test the feasibility of all components of an empowerment-based intervention using PROMs as dialogue support in clinical diabetes consultations, and to address the uncertainties associated with running a fully powered evaluation study., Methods and Analysis: We will undertake a two-arm pilot RCT of an intervention using the Problem Areas In Diabetes (PAID) scale in clinical diabetes consultations in order to conclude whether a fully powered trial is appropriate and/or feasible. The study will also include qualitative indepth interviews with participants and healthcare providers. Our objectives are to (1) evaluate the recruitment procedures and attrition rates; (2) evaluate the performance of the randomisation procedure; (3) evaluate the participants' mean scores on the outcome measures before and after the intervention; (4) evaluate if the intervention consultations are acceptable and feasible; and (5) explore patients' and healthcare providers' experiences with the use of PAID as dialogue support and empowerment-based communication skills in clinical diabetes consultations. The quantitative data analysis includes descriptive statistics (frequencies, percentages, means, SD and CI). For the qualitative data, we will perform thematic analysis., Ethics and Dissemination: Ethical approval has been obtained from the Western Norway Regional Committee for Medical and Health Research Ethics (2017/1506/REC west). We will present the findings from the study phases at national and international conferences and submit manuscripts to peer-reviewed journals and popular science journals., Trial Registration Number: NCT03471104; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Severe Respiratory Insufficiency (SRI) questionnaire is a specific measure of health-related quality of life (HRQoL) in patients treated with long-term mechanical ventilation (LTMV). The aim of the present study was to examine whether SRI sum scores and related subscales are associated with mortality in LTMV patients., Methods: The study included 112 LTMV patients (non-invasive and invasive) from the Norwegian LTMV registry in Western Norway from 2008 with follow-up in August 2014. SRI data were obtained through a postal questionnaire, whereas mortality data were obtained from the Norwegian Cause of Death Registry. The SRI questionnaire contains 49 items and seven subscales added into a summary score (range 0-100) with higher scores indicating a better HRQoL. The association between the SRI score and mortality was estimated as hazard ratios (HRs) with 95% confidence intervals (95% CI) using Cox regression models and HRs were estimated per one unit change in the SRI score., Results: Of the 112 participating patients in 2008, 52 (46%) had died by August 2014. The mortality rate was the highest in patients with chronic obstructive pulmonary disease (75%), followed by patients with neuromuscular disease (46%), obesity hypoventilation syndrome (31%) and chest wall disease (25%) (p < 0.001). Higher SRI sum scores in 2008 were associated with a lower mortality risk after adjustment for age, education, hours a day on LTMV, time since initiation of LTMV, disease category and comorbidity (HR 0.98, 95% CI: 0.96-0.99). In addition, SRI-Physical Functioning (HR 0.98, 95% CI: 0.96-0.99), SRI-Psychological Well-Being (HR 0.98, 95% CI: 0.97-0.99), and SRI-Social Functioning (HR 0.98, 95% CI: 0.97-0.99) remained significant risk factors for mortality after covariate adjustment. In the subgroup analyses of patient with neuromuscular diseases we found significant inverse associations between some of the SRI subscales and mortality., Conclusions: SRI score is associated with mortality in LTMV-treated patients. We propose the use of SRI in the daily clinic with repeated measurements as part of individual follow-up. Randomized clinical trials with interventions aimed to improve HRQoL in LTMV patients should consider the SRI questionnaire as the standard HRQoL measurement.

Background: Migrant women's overall increased risk of adverse pregnancy outcomes is well known. The aim of this study was to investigate possible associations between stillbirth and maternal country of birth and other migration related factors (paternal origin, reason for immigration, length of residence and birthplace of firstborn child) in migrant women in Norway., Methods: Nationwide population-based study including births to primiparous and multiparous migrant women (n = 198,520) and non-migrant women (n = 1,156,444) in Norway between 1990 and 2013. Data from the Medical Birth Registry of Norway and Statistics Norway. Associations were investigated by multiple logistic regression and reported as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: Primiparous women from Sri-Lanka and Pakistan, and multiparous women from Pakistan, Somalia, the Philippines and Former Yugoslavia had higher odds of stillbirth when compared to non-migrant women (adjusted OR ranged from 1.58 to 1.79 in primiparous and 1.50 to 1.71 in multiparous women). Primiparous migrant women whose babies were registered with Norwegian-born fathers had decreased odds of stillbirth compared to migrant women whose babies were registered with foreign-born fathers (aOR = 0.73; CI 0.58-0.93). Primiparous women migrating for work or education had decreased odds of stillbirth compared to Nordic migrants (aOR = 0.58; CI 0.39-0.88). Multiparous migrant women who had given birth to their first child before arriving in Norway had higher odds of stillbirth in later births in Norway compared with multiparous migrant women who had their first child after arrival (aOR = 1.28; CI 1.06-1.55). Stillbirth was not associated with length of residence in Norway., Conclusions: This study identifies sub-groups of migrant women who are at an increased risk of stillbirth, and highlights the need to improve care for them. More attention should be paid to women from certain countries, multiparous women who had their first baby before arrival and primiparous women whose babies have foreign-born fathers.

Background: A review of the literature reveals a lack of validated instruments that particularly measure quality in the hospital discharge process. This study aims to develop and validate a survey instrument feasible for measuring quality (≥65 years) related to the discharge process based on elderly patients' experiences., Methods: Construction of the Discharge Care Patient Experience Survey (DICARES) was based on 16 items identified by literature reviews. Intraclass correlation for test-retest was applied to assess consistency of the survey. Explorative factors analysis was applied to identify and validate the factor structures of the DICARES. Cronbach's α was used to assess internal reliability. To evaluate the external validity of the final DICARES questionnaire the patients' scores were correlated with scores obtained from the three other questionnaires; the Nordic Patient Experiences Questionnaire, the 12-Item Short-Form Health Survey and Subjective Health Complaints. The DICARES association with readmissions was examined., Results: A total of 270 patients responded (64.4%). The mean age of participants was 77.1 years and 57.8% were men. The exploratory factor analysis resulted in a 10-item instrument consisting of three factors explaining 63.5% of the total variance. The Cronbach's α were satisfactory (≥70). Overall intraclass correlation was 0.76. A moderate Spearman correlation (rho = 0.54, p <0.01) was found between the total mean DICARES score and total mean score of the Nordic Patient Experiences Questionnaire. The total mean DICARES score was inversely associated with the quality indicator based on readmissions (OR 0.62, CI 95: 0.41-0.95, p = 0.028)., Conclusion: We have developed a 10-item questionnaire consisting of three factors which may be a feasible instrument for measuring quality of the discharge process in elderly patients. Further testing in a wider population should be carried out before implementation in health care settings., Competing Interests: The authors have declared that no competing interests exist.

Background: To investigate whether the occurrence of preeclampsia varied by maternal reasons for immigration., Methods: We included 1,287,270 singleton pregnancies (163,508 to immigrant women) in Norway during 1990-2013. Individual data were obtained through record linkage between the Medical Birth Registry of Norway and Statistics Norway. Analyses were performed for preeclampsia overall and in combination with preterm birth < 37 and < 34 weeks of gestation, referred to as preterm and very preterm preeclampsia. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression with robust standard errors, adjusted for relevant covariates, including maternal income and education., Results: Preeclampsia was reported in 3.5% of Norwegian women and 2.5% of immigrants. Compared with Norwegian women, the adjusted OR for preeclampsia was lowest in labour immigrants (adjusted OR 0.55 [95% CI 0.49-0.62]), followed by family immigrants (0.62 [0.59-0.65]), immigrant students (0.75 [0.65-0.86]), refugees (0.81 [0.75-0.88]), and immigrants from other Nordic countries (0.87 [0.80-0.94]). Compared with Norwegian women, labour immigrants also had lower adjusted odds of preterm and very preterm preeclampsia, whereas refugees had increased adjusted odds of preterm and very preterm preeclampsia (< 37 weeks: 1.18 [1.02-1.36], and < 34 weeks: 1.41 [1.15-1.72])., Conclusions: The occurrence of preeclampsia was lower overall in immigrants than in non-immigrants, but associations varied by maternal reasons for immigration. Maternity caregivers should pay increased attention to pregnant women with refugee backgrounds due to their excess odds of preterm preeclampsia.

Background: Patients with celiac disease (CD), including adults with subclinical disease, have low bone mineral density (BMD), deteriorated bone microarchitecture and meta-analysis show an increased risk of fracture. Immunoglobulin A (IgA) against transglutaminase 2 (IgA TG2) is a highly reliable marker to detect CD., Main Objective: To explore the prevalence of positive IgA TG2 and CD in patients with distal radius and ankle fracture compared to community-based controls., Methods: Four hundred patients aged 40 years or above with distal fractures were included in a case-control study. About 197 controls were identified from the National Population Registry, those included had never suffered a fracture. BMD was measured, and comorbidities, medications, physical activity, smoking habits, body mass index (BMI) and nutritional factors were registered. Blood analysis to detect common causes of secondary osteoporosis was performed., Results: About 2.5% of the fracture patients had positive IgA TG2, compared to 1% in the control group. The odds ratio, adjusted for sex and age, of having positive IgA TG2 was 2.50 (95% CI 0.54-11.56)., Conclusions: There were no significantly increased odds of CD in adult patients with fractures compared to controls; however, results imply that positive IgA TG2 is more prevalent in fracture patients than in controls. This study indicates that universal screening for CD in fracture patients is not warranted, but supports current clinical practice in Norway to suspect and investigate for CD in patients with fracture, osteoporosis and other risk factors for CD.

Background: There is limited evidence from multicenter, randomized controlled studies to inform planning and implementation of antibiotic stewardship interventions in hospitals., Methods: A cluster randomized, controlled, intervention study was performed in selected specialities (infectious diseases, pulmonary medicine and gastroenterology) at three emergency care hospitals in Western Norway. Interventions applied were audit with feedback and academic detailing. Implementation strategies included co-design of interventions with stakeholders in local intervention teams and prescribers setting local targets for change in antibiotic prescribing behaviour. Primary outcome measures were adherence to national guidelines, use of broad-spectrum antibiotics and change in locally defined targets of change in prescribing behaviour. Secondary outcome measures were length of stay, 30-day readmission, in-hospital- and 30-day mortality., Results: One thousand eight hundred two patients receiving antibiotic treatment were included. Adherence to guidelines had an absolute increase from 60 to 66% for all intervention wards ( p  = 0.04). Effects differed across specialties and pulmonary intervention wards achieved a 14% absolute increase in adherence ( p  = 0.003), while no change was observed for other specialties. A pulmonary ward targeting increased use of penicillin G 2 mill IU × 4 for pneumonia and COPD exacerbations had an intended increase of 30% for this prescribing behaviour ( p  < 0.001)., Conclusions: Pulmonary wards had a higher increase in adherence, independent of applied intervention. The effect of antibiotic stewardship interventions is dependent on how and in which context they are implemented. Additional effects of interventions are seen when stakeholders discuss ward prescribing behaviour and agree on specific targets for changes in prescribing practice., Competing Interests: The study was conducted in accordance with the Declaration of Helsinki, national and institutional standards [27]. The study was approved by the Data Protection Officer (2013/9352) and the Western Regional Committee for Medical and Health Research Ethics approved the waiver of informed consent (2013/1305). All patients received written information about the study, with opportunity to withdraw from the study. The study was not registered in a clinical trial database as randomization was conducted at cluster level only, with primary aim of investigating the effect of interventions on ward prescribing behaviour. Individual patient treatment was at the discretion of the treating physician.Not applicableJ.S.W received a 3-month grant in patient safety research for preparation of the manuscript, but the funder has not played any role in the design, execution, analysis or reporting of the research. Competing interests for other authors: None to declare.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Despite extensive knowledge of smoking effects on respiratory disease, there is no study including all age windows of exposure among ever smokers. The objective of this study was to assess the effects from smoking exposure in utero, early childhood, adolescence and adulthood on respiratory health outcomes in adult male and female ever smokers., Methods: Respiratory health outcomes were assessed in 10,610 participants of the European Community Respiratory Health Survey (ECRHS) I who reported a history of ever smoking by questionnaire. The associations of maternal smoking in utero, maternal smoking during childhood, age of smoking debut and pack-years of smoking with respiratory symptoms, obstructive diseases and bronchial hyperreactivity were analysed using generalized linear regression, non-linearity between age of smoking debut and outcomes were assessed by Generalized additive mixed models., Results: Respiratory symptoms and asthma were more frequent in adults if their mother smoked during pregnancy, and, in men, also if mother smoked in childhood. Wheeze and ≥3 respiratory symptoms declined with later smoking debut among women [≤10 years: OR = 3.51, 95% CI 1.26, 9.73; 11-12 years: 1.57[1.01-2.44]; 13-15 years: 1.11[0.94-1.32] and ≤10 years: 3.74[1.56-8.83]; 11-12 years: 1.76[1.19-2.56]; 13-15 years: 1.12[0.94-1.35], respectively]. Effects of increasing number of packyears were pronounced in women (Chronic Obstructive Pulmonary Disease (COPD): OR/10 packyears women: 1.33 [1.18, 1.50], men: 1.14 [1.04, 1.26] p interaction = 0.01)., Conclusions: Among ever smokers, smoking exposure in each stage of the lifespan show persistent harmful effects for adult respiratory health, while women appeared to be more vulnerable to an early age of smoking debut and amount of smoking in adulthood., (Copyright © 2018. Published by Elsevier Inc.)

Background: Maternal predictors of folic acid (FA) supplementation use to reduce offspring risk of neural tube defects are well known, while paternal determinants for maternal FA use are less known. Such knowledge is important to increase women's compliance to recommended periconceptional FA use., Methods: In a nation-wide study of 683,785 births registered in the Medical Birth Registry of Norway during 1999-2010, the associations between paternal characteristics (age, education, occupation, country of origin) and maternal FA use were estimated by relative risks (RR) with 95% confidence intervals (CI), using log-binomial regression., Results: Maternal FA use before and during pregnancy (adequate FA use) was found in 16% of the births. The association between paternal age and adequate FA use was inversely U-shaped; adjusted RRs for adequate FA use were 0.35 (95% CI 0.28-0.43) and 0.72 (95% CI 0.71-0.74) for paternal age < 20 and ≥ 40 years, respectively, comparing age 30-34 years. Compulsory education (1-9 years) among fathers was compared to tertiary education; the RR was 0.69 (95% CI 0.68-0.71) for adequate FA use. The lower risk of adequate FA use for paternal compulsory education was present in all categories of maternal education. Occupation classes other than "Higher professionals" were associated with decreased risk of adequate FA use, compared with the reference "Lower professionals". RR for adequate FA use was 0.58 (95% CI 0.56-0.60) comparing fathers from "Low/middle-income countries" with fathers born in Norway., Conclusion: Adequate FA use in the periconceptional period was lower when fathers were younger or older than 30-34 years, had shorter education, had manual or self-employed occupations, or originated from low/middle-income countries. Partners may contribute to increase women's use of periconceptional FA supplementation.

Surgical site infections (SSI) are amongst the most common health care-associated infections and have adverse effects for patient health and for hospital resources. Although surgery guidelines recognize poor nutritional status to be a risk factor for SSI, they do not tell how to identify this condition. The screening tool Nutritional Risk Screening 2002 is commonly used at hospitals to identify patients at nutritional risk. We investigated the association between nutritional risk and the incidence of SSI among 1194 surgical patients at Haukeland University Hospital (Bergen, Norway). This current study combines data from two mandatory hospital-based registers: a) the incidence of SSI within 30 days after surgery, and b) the point-prevalence of patients at nutritional risk. Patients with more than 30 days between surgery and nutritional risk screening were excluded. Associations were assessed using logistic regression, and the adjusted odds ratio included age (continuous), gender (male/female), type of surgery (acute/elective) and score from The American Society of Anesthesiologists Physical Status Classification System. There was a significant higher incidence of SSI among patients at nutritional risk (11.8%), as compared to those who were not (7.0%) (p = 0.047). Moreover, the incidence of SSI was positively associated with the prevalence of nutritional risk in both simple (OR 1.76 (95% CI: 1.04, 2.98)) and adjusted (OR 1.81 (95% CI: 1.04, 3.16)) models. Answering "yes" to the screening questions regarding reduced dietary intake and weight loss was significantly associated with the incidence of SSI (respectively OR 2.66 (95% CI: 1.59, 4.45) and OR 2.15 (95% CI: 1.23, 3.76)). In conclusion, we demonstrate SSI to occur more often among patients at nutritional risk as compared to those who are not at nutritional risk. Future studies should investigate interventions to prevent both SSI and nutritional risk among surgical patients.

Background: Respiratory complications represent the major cause of death in amyotrophic lateral sclerosis (ALS). Noninvasive respiratory support is the mainstay therapy, but treatment becomes challenging as the disease progresses, possibly due to a malfunctioning larynx, which is the entrance to the airways. We studied laryngeal response patterns to mechanically assisted cough (mechanical insufflation-exsufflation) as ALS progresses., Methods: This prospective longitudinal study of 13 consecutively included subjects with ALS were followed up during 2011-2016 with repeated tests of lung function, neurological status, and laryngeal responses to mechanical insufflation-exsufflation using video-recorded flexible transnasal fiberoptic laryngoscopy., Results: Follow-up time was median 17 (range 6-59) months. In total, 751 laryngoscopy recordings from 67 individual examinations (median 4 per subject, range 2-11 per subject) were analyzed. Adverse laryngeal events that developed with disease progression during insufflation included adduction of true vocal folds in 8 of 9 spinal-onset subjects and adduction of aryepiglottic folds in all subjects, initially at the highest positive pressure and prior to onset of other bulbar symptoms in spinal-onset subjects. As cough became less expulsive with disease progression, laryngeal adduction occurred at lower insufflation pressures. Retroflex movement of the epiglottis was observed in 7 of 13 subjects regardless of insufflation pressures and independent of bulbar involvements. Backward movement of the tongue base occurred regardless of insufflation pressures in all but 1 subject. During exsufflation, constriction of the hypopharynx was observed in all subjects regardless of the presence of bulbar symptoms, after the adverse events that occurred during insufflation., Conclusions: Applying high insufflation pressures during mechanically assisted cough in ALS can become counterproductive as the disease progresses as well as prior to the onset of bulbar symptoms. The application of positive inspiratory pressures should be tailored to the individual patient, and laryngoscopy during ongoing treatment appears to be a feasible tool., (Copyright © 2018 by Daedalus Enterprises.)

The authors found errors in Table 1 after publication of the original article [1].The correct values for medical history of coronary artery disease (CAD) at baseline are 110 (40%) of all patients, 54 (35.5%) of patients categorized as having normoglycaemia, 42 (46.7%) of patients categorized as having intermediate hyperglycaemia, and 14 (42.4%) of patients categorized as having DM.All presented numbers and calculations in Table 1 are checked. No other errors were found. The presented errors did not affect results, scientific content or conclusions.The corrected Table 1 is presented in this erratum.The authors apologize for having presented this error in the original article.

Aims: To examine changes and explanatory variables for changes in health-related quality of life in patients treated with long-term mechanical ventilation over a 6-year period., Background: Long-term mechanical ventilation is a treatment for individuals with chronic hypercapnic respiratory failure, primarily caused by neuromuscular diseases, obesity hypoventilation syndrome, chronic obstructive pulmonary and restrictive thoracic diseases. Studies on long-term outcome on health-related quality of life and factors influencing it are lacking., Design: Prospective cohort study., Methods: Data were collected from the Norwegian Long-Term-Mechanical-Ventilation Registry and from patient-reported questionnaire in 2008 and 2014. Health-related quality of life was measured by the Severe Respiratory Insufficiency questionnaire, containing 49 items and seven subdomains. Linear mixed effects models were used to measure changes and identify factors for changes., Results: After 6 years, 60 patients were still participating, out of 127 at baseline. Health-related quality of life improved significantly in the total score and in four subdomains of the questionnaire. Satisfaction with training in long-term mechanical ventilation was an explanatory variable for improved 'psychological well-being' and follow-up for improvement of 'anxiety'. Side effects of the treatment like facial soreness were associated with the total score. High age and high forced vital capacity were related to lower 'physical function' and improved 'social functioning', respectively., Conclusion: Long-term mechanical ventilation over 6 years improved health-related quality of life in most patients. Patient training, follow-up and reduction of side effects, largely delivered by trained nurses, contribute to achieve the main goal of the treatment-improved health-related quality of life., (© 2017 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.)

Introduction: Inspections are widely used in health care as a means to improve the health services delivered to patients. Despite their widespread use, there is little evidence of their effect. The mechanisms for how inspections can promote change are poorly understood. In this study, we use a national inspection campaign of sepsis detection and initial treatment in hospitals as case to: (1) Explore how inspections affect the involved organizations. (2) Evaluate what effect external inspections have on the process of delivering care to patients, measured by change in indicators reflecting how sepsis detection and treatment is carried out. (3) Evaluate whether external inspections affect patient outcomes, measured as change in the 30-day mortality rate and length of hospital stay., Methods and Analysis: The intervention that we study is inspections of sepsis detection and treatment in hospitals. The intervention will be rolled out sequentially during 12 months to 24 hospitals. Our effect measures are change on indicators related to the detection and treatment of sepsis, the 30-day mortality rate and length of hospital stay. We collect data from patient records at baseline, before the inspections, and at 8 and 14 months after the inspections. We use logistic regression models and linear regression models to compare the various effect measurements between the intervention and control periods. All the models will include time as a covariate to adjust for potential secular changes in the effect measurements during the study period. We collect qualitative data before and after the inspections, and we will conduct a thematic content analysis to explore how inspections affect the involved organisations., Ethics and Dissemination: The study has obtained ethical approval by the Regional Ethics Committee of Norway Nord and the Norwegian Data Protection Authority. It is registered at www.clinicaltrials.gov (Identifier: NCT02747121). Results will be reported in international peer-reviewed journals., Trial Registration: NCT02747121; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Acute hepatic porphyria (AHP) is considered to be a risk factor for primary liver cancer (PLC), but varying risk estimates have been published., Objectives: Our aim was to investigate the risk of PLC and other cancers in persons with AHP using a nationwide cohort design. Given that greater numbers of women than men tend to have manifest and more severe AHP, a further aim was to investigate sex differences in this risk., Methods: The study sample consisted of all Norwegian residents aged 18 years or older during the period 2000-2011. Persons with AHP (n = 251) were identified through the Norwegian Porphyria Centre, and patients with a cancer diagnosis were identified by linkage to the Cancer Registry of Norway., Results: For persons with AHP, the annual incidence rate of PLC was 0.35%. PLC risk was substantially higher for individuals with an AHP diagnosis compared to the reference population [adjusted hazard ratio (aHR) 108, 95% confidence interval (CI) 56-207]. In a meta-analysis of published studies on PLC and AHP, including ours, women had a higher risk than men. In addition, our results suggested that persons with AHP may have increased risks of kidney (aHR 7.4, 95% CI 2.4-23.1) and endometrial cancers (aHR 6.2, 95% CI 2.0-19.3)., Conclusions: Our findings confirmed a substantially higher risk of PLC associated with AHP compared to the general population. In a meta-analysis, the risk was shown to be greater for women than men. The novel findings of a moderate to substantial association between AHP and kidney and endometrial cancers should be investigated further., (© 2017 The Association for the Publication of the Journal of Internal Medicine.)

Objectives: Patients with posterior circulation infarction (PCI) have more subtle symptoms than anterior circulation infarction (ACI) and could come too late for acute intervention. This study aimed to describe the clinical presentation, management, and outcome of PCI in the NORSTROKE registry., Methods: All patients with PCI admitted to the Department of Neurology at Haukeland University Hospital and registered in the NORSTROKE database 2006-2013 were included (n=686). Patients with ACI (n=1758) were used for comparison., Results: Patients with PCI were younger (68.2 vs 71.8, P<.001), had longer median time from symptom onset to admission (3.8 hours vs 2.2 hours, P<.001), and were less likely to arrive at hospital within 4.5 hours from symptom onset (56.2% vs 72.5%, P<.001, ictus known). Patients with PCI scored lower on baseline National Institute of Health Stroke Scale (NIHSS) total score (3.2 vs 6.3, P<.001), and lower or equally on all items of NIHSS, except for ataxia in two limbs. Patients with PCI were less likely to receive i.v. thrombolytic treatment (9.9% vs 21.5%, OR 0.66, CI 0.47-0.94). On day 7, patients with PCI scored lower on NIHSS (2.8 vs 4.9, P<.001), modified Rankin Scale (2.0 vs 2.3, P<.001), and higher on Barthel Index (84.5 vs 76.0, P<.001)., Conclusions: Our study is, to our knowledge, the largest series reporting comprehensively on PCI verified by diffusion-weighted imaging. PCI patients are younger than ACI and have better outcome. PCI and ACI are equally investigated in the acute setting, but thrombolysis rates remain 50% lower in PCI., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Maternal smoking during pregnancy, especially when sustained, leads to numerous adverse health outcomes in offspring. Pregnant women disproportionately underreport smoking and smokers tend to have lower follow-up rates to repeat questionnaires. Missing, incomplete, or inaccurate data on presence and duration of smoking in pregnancy impairs identification of novel health effects and limits adjustment for smoking in studies of other pregnancy exposures. An objective biomarker in newborns of maternal smoking during pregnancy would be valuable., Objectives: We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms., Methods: Using a dimension reduction method, we developed and tested a numeric score in newborns to reflect sustained maternal smoking in pregnancy from data on cotinine, a short-term smoking biomarker measured mid-pregnancy, and Illumina450K cord blood DNA methylation from newborns in the Norwegian Mother and Child Cohort Study (MoBa)., Results: This score reliably predicted smoking status in the training set ( n = 1,057; accuracy = 96%, sensitivity = 80%, specificity = 98%). Sensitivity (58%) was predictably lower in the much smaller test set ( n = 221), but accuracy (91%) and specificity (97%) remained high. Reduced birth weight, a well-known effect of maternal smoking, was as strongly related to the score as to cotinine. A three-site score had lower, but acceptable, performance (accuracy train = 82%, accuracy test = 83%)., Conclusions: Our smoking methylation score represents a promising novel biomarker of sustained maternal smoking during pregnancy easily calculated with Illumina450K or IlluminaEPIC data. It may help identify novel health impacts and improve adjustment for smoking when studying other risk factors with more subtle effects.

Background: Preterm delivery increases the risk of neonatal morbidity and mortality. Studies suggest that maternal diet may affect the prevalence of preterm delivery. The aim of this study was to assess whether maternal intakes of seafood and marine long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) from supplements were associated with preterm delivery., Methods: The study population included 67,007 women from the Norwegian Mother and Child Cohort Study. Maternal food and supplement intakes were assessed by a validated self-reported food frequency questionnaire in mid-pregnancy. Information about gestational duration was obtained from the Medical Birth Registry of Norway. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between total seafood, lean fish, fatty fish, and LCn-3PUFA intakes and preterm delivery. Preterm was defined as any onset of delivery before gestational week 37, and as spontaneous or iatrogenic deliveries and as preterm delivery at early, moderate, and late preterm gestations., Results: Lean fish constituted 56%, fatty fish 34% and shellfish 10% of seafood intake. Any intake of seafood above no/rare intake (>5 g/d) was associated with lower prevalence of preterm delivery. Adjusted HRs were 0.76 (CI: 0.66, 0.88) for 1-2 servings/week (20-40 g/d), 0.72 (CI: 0.62, 0.83) for 2-3 servings/week (40-60 g/d), and 0.72 (CI: 0.61, 0.85) for ≥3 servings/week (>60 g/d), p-trend <0.001. The association was seen for lean fish (p-trend: 0.005) but not for fatty fish (p-trend: 0.411). The intake of supplementary LCn-3PUFA was associated only with lower prevalence of early preterm delivery (before 32 gestational weeks), while increasing intake of LCn-3PUFA from food was associated with lower prevalence of overall preterm delivery (p-trend: 0.002). Any seafood intake above no/rare was associated with lower prevalence of both spontaneous and iatrogenic preterm delivery, and with lower prevalence of late preterm delivery., Conclusions: Any intake of seafood above no/rare consumption was associated with lower prevalence of preterm delivery. The association was stronger for lean than for fatty fish. Intake of supplementary LCn-3PUFA was associated only with early preterm delivery. The findings corroborate the current advice to include fish and seafood as part of a balanced diet during pregnancy.

Maternal nutrition and inflammation have been suggested as mediators in the development of various adverse pregnancy outcomes associated with maternal obesity. We have investigated the relation between pre-pregnancy BMI, B vitamin status, and inflammatory markers in a group of healthy pregnant women. Cobalamin, folate, pyridoxal 5'-phosphate, and riboflavin; and the metabolic markers homocysteine, methylmalonic acid, and 3-hydroxykynurenine/xanthurenic acid ratio (HK/XA); and markers of cellular inflammation, neopterin and kynurenine/tryptophan ratio (KTR) were determined in pregnancy week 18 and related to pre-pregnancy body mass index (BMI), in 2797 women from the Norwegian Mother and Child Cohort Study (MoBa). Pre-pregnancy BMI was inversely related to folate, cobalamin, pyridoxal 5'-phosphate (PLP), and riboflavin ( p < 0.001), and associated with increased neopterin and KTR levels ( p < 0.001). Inflammation seemed to be an independent predictor of low vitamin B6 status, as verified by low PLP and high HK/XA ratio. A high pre-pregnancy BMI is a risk factor for low B vitamin status and increased cellular inflammation. As an optimal micronutrient status is vital for normal fetal development, the observed lower B vitamin levels may contribute to adverse pregnancy outcomes associated with maternal obesity and B vitamin status should be assessed in women with high BMI before they get pregnant., Competing Interests: The authors declare no conflict of interest.

Background: Children exposed to maternal smoking during pregnancy exhibit increased risk for many adverse health effects. Maternal smoking influences methylation in newborns at specific CpG sites (CpGs). Here, we extend evaluation of individual CpGs to gene-level and pathway-level analyses among 1062 participants in the Norwegian Mother and Child Cohort Study (MoBa) using the Illumina 450 K platform to measure methylation in newborn DNA and maternal smoking in pregnancy, assessed using the biomarker, plasma cotinine. We used novel implementations of bioinformatics tools to collapse epigenome-wide methylation data into gene- and pathway-level effects to test whether exposure to maternal smoking in utero differentially methylated CpGs in genes enriched in biologic pathways. Unlike most pathway analysis applications, our approach allows replication in an independent cohort., Results: Data on 485,577 CpGs, mapping to a total of 20,199 genes, were used to create gene scores that were tested for association with maternal plasma cotinine levels using Sequence Kernel Association Test (SKAT), and 15 genes were found to be associated (q < 0.25). Six of these 15 genes (GFI1, MYO1G, CYP1A1, RUNX1, LCTL, and AHRR) contained individual CpGs that were differentially methylated with regards to cotinine levels (p < 1.06 × 10 -7 ). Nine of the 15 genes (FCRLA, MIR641, SLC25A24, TRAK1, C1orf180, ITLN2, GLIS1, LRFN1, and MIR451) were associated with cotinine at the gene-level (q < 0.25) but had no genome-wide significant individual CpGs (p > 1.06 × 10 -7 ). Pathway analyses using gene scores resulted in 51 significantly associated pathways, which we tested for replication in an independent cohort (q < 0.05). Of those 32 replicated in an independent cohort, which clustered into six groups. The largest cluster consisted of pathways related to cancer, cell cycle, ERα receptor signaling, and angiogenesis. The second cluster, organized into five smaller pathway groups, related to immune system function, such as T-cell regulation and other white blood cell related pathways., Conclusions: Here we use novel implementations of bioinformatics tools to determine biological pathways impacted through epigenetic changes in utero by maternal smoking in 1062 participants in the MoBa, and successfully replicate these findings in an independent cohort. The results provide new insight into biological mechanisms that may contribute to adverse health effects from exposure to tobacco smoke in utero.

Background: Neopterin levels and kynurenine/tryptophan ratios (KTRs) increase with IFN-γ stimulation, indicating T H 1 immunity, and thus might be inversely associated with asthma., Objective: We sought to examine the association of maternal neopterin levels and KTRs during pregnancy with asthma in the offspring., Methods: We analyzed the associations of maternal plasma total neopterin levels and KTRs in midpregnancy with asthma at age 7 years among 2883 children in the Norwegian Mother and Child Cohort Study. Asthma was classified either based on registered dispensed asthma medications in the Norwegian Prescription Database or maternal report. We calculated adjusted relative risks using log-binomial regression., Results: The median gestational week of blood sampling was 18 weeks (interquartile range, 17-19 weeks). The risk of dispensed asthma medications at age 7 years was highest among children of mothers in the highest quartile of neopterin levels, whereas the risk was similar in the 3 lowest quartiles. The adjusted relative risk of dispensed asthma medications was 1.66 (95% CI, 1.16-2.38) when comparing children of mothers in the highest quartile with those in the 3 lowest quartiles. A similar association was observed for maternal report of asthma at age 7 years. When we evaluated allergic versus nonallergic asthma, neopterin levels tended to be associated with nonallergic asthma. Maternal KTR was not associated with asthma development., Conclusions: Our findings indicate that high maternal levels of neopterin, a marker of cellular immune activation, during pregnancy were positively associated with asthma in offspring. Experimental studies would be needed to further elucidate underlying mechanisms., Competing Interests: Dr. Ueland is a member of the steering board of the nonprofit Foundation to Promote Research into Functional Vitamin B12 Deficiency, which owns Bevital, the company that carried out biochemical analyses. None of the other authors had any conflicts of interest., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Aims: Like most European countries, Norway has refrained from mandatory food fortification with folic acid to reduce the number of neural tube defects. We explored the role of folic acid and multivitamin supplements in the prevention of neural tube defects among newborn infants., Methods: We used data from the Medical Birth Registry of Norway, 1999-2013. A total of 528,220 women had 880,568 pregnancies resulting in 896,674 live- and stillborn infants, of whom 270 had neural tube defects. Relative risks were estimated with log-binomial regression., Results: From 1999 to 2013, intake of folic acid supplements increased from 4.8% to 27.4%. Vitamin supplement use was more frequent in older, married or cohabiting women and those with lower parity, as well as women who did not smoke during pregnancy. The overall adjusted relative risk of infant neural tube defects associated with maternal vitamin intake before pregnancy relative to no intake was 0.76 (95% confidence interval: 0.53-1.10). When we divided our study period in two (1999-2005 and 2006-2013), we found a significantly reduced risk of neural tube defects overall by vitamin use in the second time period, but not in the first: adjusted relative risk 0.54 (95% confidence interval: 0.31-0.91) and 1.02 (95% confidence interval: 0.63-1.65), respectively., Conclusions: OVER THE FULL STUDY PERIOD, WE FOUND NO STATISTICALLY SIGNIFICANT ASSOCIATION BETWEEN VITAMIN USE AND NEURAL TUBE DEFECTS OVERALL HOWEVER, VITAMIN USE WAS ASSOCIATED WITH A SIGNIFICANTLY LOWER RISK OF NEURAL TUBE DEFECTS IN THE SECOND HALF OF THE STUDY PERIOD, 2006-2013., (© 2016 the Nordic Societies of Public Health.)

Background: Women in many countries are advised to use folic acid supplements before and early during pregnancy to reduce the risk of neural tube defects in their infants. This study aimed to update the prevalence and to identify possible determinants of preconception folic acid supplement use in Italian women., Methods: The study was based on cross-sectional data from seven maternity clinics located in six Italian regions from January to June, 2012. Data on maternal characteristics and supplement use were collected for 2,189 women using a self-administered questionnaire., Results: Preconception folic acid use was reported by 23.5 % (n = 515) of the participants. Of these, 479 (93 %) women had taken folic acid supplements on a daily basis as recommended by the health authorities. Women who both had intended their pregnancy and had requested a preconception health visit to a doctor/gynecologist were substantially more likely than the reference group to initiate folic acid supplementation before their pregnancy (48.6 versus 4.8 %). Preconception folic acid use was also associated with higher maternal age, higher education, marriage/cohabitation, lower parity, infertility treatments, and chronic disease., Conclusions: Data from seven maternity clinics located in six Italian regions indicate that preconception folic acid supplement use in many Italian women is low. Women who do not plan their pregnancy or do not request a preconception health visit to their doctor have among the lowest prevalence of preconception folic acid use. Improving folate status in these and other supplemental non-users may have important disease preventive effects.

Objectives: The majority of patients experience moderate-to-intense pain following ankle surgery. Early, adequate treatment of postoperative pain is desirable for optimal pain relief, which in turn may facilitate optimal pulmonary function, normal respiration pattern, rehabilitation and prevention of a chronic pain condition. In this retrospective study, we aimed to identify possible predictors of moderate-to-intense postoperative pain while in the Post Anaesthesia Care Unit (PACU) in patients operated for ankle fractures., Materials and Methods: Social demographics and clinical characteristics from admission throughout the stay in the PACU were collected from the hospital patient record system in retrospect. Pain was assessed using a Visual Analogue Scale (VAS) or a verbal Numeric Rating Scale (vNRS). A VAS/vNRS score 4-6 was classified as moderate and 7-10 as intense pain. Other factors which were investigated were time from ankle fracture to surgery, anaesthetic procedure, pre-, per- and postoperative medical treatment, radiological classification, complexity of fracture, operative technique, and time using tourniquet procedure., Results: Data from 336 patients who underwent surgery to repair an ankle fracture between January 2009 and December 2010 were analysed. None of the following variables had a statistically significant effect on pain; age, weight, smoking, timeframe from fracture to operation, type of anaesthesia, opioids given peroperatively, complexity of the fracture, operation technique or tourniquet inflation procedure. Female sex predicted moderate-to-intense postoperative pain in the PACU with odds ratio 2.31 (95% confidence interval 1.39-3.86), P=0.001. As far as we know, this is the first study to show a sex difference in reporting pain in the first hours after surgery for ankle fracture., Conclusion: Female patients operated for ankle fracture report higher pain-intensity-score than male patients while in the PACU., Implications: Our findings suggest that treatment strategies to prevent high peaks of pain should particularly target women operated for an ankle fracture., (Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Few studies have examined whether specific subtypes of anemia in older persons are more related to adverse outcomes such as hospital readmissions and death after acute hospitalization and post-acute care., Methods: An observational prospective cohort study was conducted between 2011 and 2014. A total of 884 community-dwelling patients, ≥70 years of age were transferred from acute medical and orthopaedic hospital departments to a skilled nursing home where they were examined by comprehensive geriatric assessment and had laboratory tests taken for the investigation of anemia. They were divided into three major groups and compared; 1) no anemia (reference group), 2) explained anemia (renal insufficiency, iron deficiency, vitaminB12/folate deficiency or multifactorial anemia) and 3) unexplained anemia. The groups were compared, and association of anemia with hospital readmission and death was estimated by logistic regression analyses., Results: Compared to the patients with unexplained anemia (n=135), patients with explained anemia (n=275) had more often died (22 % vs. 14 %, p=0.05) and had more frequenlty been readmitted to hospital (39 % vs. 27 %, p=0.03). Compared to the patients without anemia (n=474), the patients with explained anemia had increased odds of hospital readmissions (OR = 1.54 (95 % CI: 1.05-2.25), p=0.03), while patients with unexplained anemia, (n=135), had neither increased odds of hospital readmissions, (OR=0.83, 95 % CI: 0.51-1.34, p=0.44) nor death (OR = 0.74, 95 % CI: 0.41-1.31, p=0.30), in adjusted regression analysis., Conclusion: Since no increased risk of hospital readmissions or death was seen in older patients with unexplained anemia in the first year after acute hospitalization, no further invasive investigations might be necessary to investigate the cause of anemia in these patients. A close clinical follow up might be the best way to care for older patients with a mild and unexplained anemia.

Background: Decreased diffusing capacity of the lung for carbon monoxide (DLCO) is associated with emphysema. DLCO is also related to decreased arterial oxygen tension (PaO2), but there are limited data on associations between PaO2 and computed tomography (CT) derived measures of emphysema and airway wall thickness., Objective: To examine whether CT measures of emphysema and airway wall thickness are associated with level of arterial oxygen tension beyond that provided by measurements of diffusion capacity and spirometry., Methods: The study sample consisted of 271 smoking or ex-smoking COPD patients from the Bergen COPD Cohort Study examined in 2007-2008. Emphysema was assessed as percent of low-attenuation areas<-950 Hounsfield units (%LAA), and airway wall thickness as standardised measure at an internal perimeter of 10 mm (AWT-Pi10). Multiple linear regression models were fitted with PaO2 as the outcome variable, and %LAA, AWT-Pi10, DLCO and carbon monoxide transfer coefficient (KCO) as main explanatory variables. The models were adjusted for sex, age, smoking status, and haemoglobin concentration, as well as forced expiratory volume in one second (FEV1)., Results: Sixty two per cent of the subjects were men, mean (SD) age was 64 (7) years, mean (SD) FEV1 in percent predicted was 50 (15)%, and mean PaO2 (SD) was 9.3 (1.1) kPa. The adjusted regression coefficient (CI) for PaO2 was -0.32 (-0.04-(-0.019)) per 10% increase in %LAA (p<0.01). When diffusion capacity and FEV1 were added to the model, respectively, the association lost its statistical significance. No relationship between airway wall thickness and PaO2 was found., Conclusion: CT assessment of airway wall thickness is not associated with arterial oxygen tension in COPD patients. Emphysema score measured by chest CT, is related to decreased PaO2, but cannot replace measurements of diffusion capacity in the clinical evaluation of hypoxaemia.

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure., (Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the recovery and outcome of older communitydwelling patients admitted to intermediate care (IC) in nursing homes after acute hospitalization, and to compare patients who were able and unable to return directly to their own homes., Design: Prospective, observational, cohort study conducted between June 2011 and 2014., Setting: A 19- bed IC unit in a nursing home with increased multidisciplinary staffing., Participants: A total of 961 community-dwelling patients, ≥70 years of age, considered to have a rehabilitation potential and no major cognitive impairment or delirium, transferred from internal medicine, cardiac, pulmonary and orthopaedic hospital departments., Measurements: Demographic data, clinical information, comprehensive geriatric assessment (CGA), discharge destination and length of stay. Residence status and mortality 1 month, 2 months, 3 months, and 6 months after discharge from the hospital., Results: The trajectory of recovery was divided into 3 groups: 1) Rapid recovery, able to return home after median 14 days in IC (n=785, 82%); 2) Slow recovery, requiring additional transfer to other nursing home after IC, but still able to return home within 2 months (n=106, 11%). 3) Poor recovery, requiring transfer to other nursing home after IC and still in a nursing home or dead at 2 months (n=66, 7%). Significant different clinical characteristics were demonstrated between the patients in the 3 groups. After 6 months, the recovery of patients with rapid or slow recovery was similar, 87% were living at home, compared to only 20% of the patients with poor recovery. In multiple logistic regression analysis, slow or poor recovery was significantly associated with low scores on the Barthel index and orthopaedic admission diagnosis., Conclusions: Although the majority of patients selected for treatment in the IC unit were able to recover and return home, a group of patients needed extra time, up to 2 months, to recover and another group had a poor chance of recovering and returning home. Different caring pathways for different patient groups may be considered in the PAC setting.

Aims: The prevalence of diabetes mellitus (DM) and mortality with respect to glycaemic status in patients with abdominal aortic aneurysms (AAA) was evaluated. Glycaemic status was assessed by an oral glucose tolerance test (OGTT) and by HbA1c., Methods: Sixty-six patients with AAA admitted to the vascular surgery unit for elective surgery between October 2006 and September 2007 were included. Seven patients had previously known DM. OGTT and HbA1c results were available from 58 patients. The patients were categorized as having DM, prediabetes and normoglycaemia according to the WHO's and American Diabetes Association's criteria., Results: The prevalence of newly diagnosed DM according to the OGTT and HbA1c results were 12% and 14% respectively. Mean follow-up time was 68 months and all-cause mortality 43%. HbA1c was an independent predictor for mortality in the DM category. Hazard ratio of all-cause mortality in the DM category defined by the HbA1c values was 6.35, 95% [CI 1.49-27.1]; p = 0.01., Conclusions: DM defined by HbA1c ≥ 6.5% is an important determinant of mortality following surgical treatment for AAA. Half the patients with AAA and DM were unaware of their DM diagnosis. All patients with AAA should be tested for DM using HbA1c. The results should be confirmed in a larger prospective study., (Copyright © 2016 Elsevier Inc. All rights reserved.)