Linda Leivseth

Natural course of acute neck and low back pain in the general population: The HUNT study

&NA; In subjects who largely refrained from health care treatment, neck and low back pain declined rapidly after a new pain episode, with the exception of some important subgroups. &NA; In this prospective cohort study we aimed to describe the natural course of acute neck and low back pain in a general population of Norway. We screened 9056 subjects aged 20–67 years who participated in a general health survey for a new episode of neck or low back pain the previous month. The screening identified 219 subjects who formed the cohort for this study. Pain intensity was reported on a numeric rating scale (0–10) at 1, 2, 3, 6, and 12 months after start of the new pain episode. The course of pain was described for neck and low back pain, different baseline pain levels, age groups, and number of pain sites at baseline. Use of medication and health care was described and associations between pain intensity and seeking health care were estimated. Pain declined rapidly within 1 month after a new pain episode, with a reduction of 0.91 (95% confidence interval [CI] 0.50–1.32) for neck pain and 1.40 (95% CI 0.82–1.99) for low back pain with little change thereafter. However, pain remained unchanged over the follow‐up year for those with equal pain in the neck and low back areas at baseline and for those reporting 4 or more pain sites at baseline. Only 1 in 5 sought health care for their complaints. Still, the course of pain was comparable to effect sizes reported in interventional studies. This study thus contributes natural course reference data for comparisons of pain outcome in clinical trials and practice.

Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2007 and 2011 staging systems: a pooled analysis of individual patient data

BACKGROUND There is no universal consensus on the best staging system for chronic obstructive pulmonary disease (COPD). Although documents (eg, the Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2007) have traditionally used forced expiratory volume in 1 s (FEV1) for staging, clinical parameters have been added to some guidelines (eg, GOLD 2011) to improve patient management. As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aimed to investigate how individual patients were categorised by GOLD 2007 and 2011, and compare the prognostic accuracy of the staging documents for mortality. METHODS We searched reports published from Jan 1, 2008, to Dec 31, 2014. Using data from cohorts that agreed to participate and had a minimum amount of information needed for GOLD 2007 and 2011, we did a patient-based pooled analysis of existing data. With use of raw data, we recalculated all participant assignments to GOLD 2007 I-IV classes, and GOLD 2011 A-D stages. We used survival analysis, C statistics, and non-parametric regression to model time-to-death data and compare GOLD 2007 and GOLD 2011 staging systems to predict mortality. FINDINGS We collected individual data for 15 632 patients from 22 COPD cohorts from seven countries, totalling 70 184 person-years. Mean age of the patients was 63·9 years (SD 10·1); 10 751 (69%) were men. Based on FEV1 alone (GOLD 2007), 2424 (16%) patients had mild (I), 7142 (46%) moderate (II), 4346 (28%) severe (III), and 1670 (11%) very severe (IV) disease. We compared staging with the GOLD 2007 document with that of the new GOLD 2011 system in 14 660 patients: 5548 (38%) were grade A, 2733 (19%) were grade B, 1835 (13%) were grade C, and 4544 (31%) were grade D. GOLD 2011 shifted the overall COPD severity distribution to more severe categories. There were nearly three times more COPD patients in stage D than in former stage IV (p<0·05). The predictive capacity for survival up to 10 years was significant for both systems (p<0·01) but area under the curves were only 0·623 (GOLD 2007) and 0·634 (GOLD 2011), and GOLD 2007 and 2011 did not differ significantly. We identified the percent predicted FEV1 thresholds of 85%, 55% and 35% as better to stage COPD severity for mortality, which are similar to the ones used previously. INTERPRETATION Neither GOLD COPD classification schemes have sufficient discriminatory power to be used clinically for risk classification at the individual level to predict total mortality for 3 years of follow-up and onwards. Increasing intensity of treatment of patients with COPD due to their GOLD 2011 reclassification is not known to improve health outcomes. Evidence-based thresholds should be searched when exploring the prognostic ability of current and new COPD multicomponent indices. FUNDING None.

GOLD classifications and mortality in chronic obstructive pulmonary disease: the HUNT Study, Norway

Background How different Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications of chronic obstructive pulmonary disease (COPD) predict mortality is unclear. Objective To examine the association of spirometric GOLD grades and the new ABCD groups with mortality, and to compare their informativeness in relation to mortality. Methods We studied 1540 people with post-bronchodilator COPD who participated in the Norwegian Nord-Trøndelag Health Study 1995–1997 and were followed up on all-cause mortality until May 2012. The associations of spirometric GOLD grades and ABCD groups with mortality were estimated by sex specific adjusted HRs from Cox regression and standardised mortality ratios. To assess the informativeness of spirometric GOLD grades and ABCD groups at predicting mortality we used the difference in twice the log-likelihood of a Cox regression model with and without each COPD classification. Results The distribution of participants was 28% in GOLD 1, 57% in GOLD 2, 13% in GOLD 3 and 2% in GOLD 4, in contrast to 61% in group A, 18% in group B, 12% in group C and 10% in group D. During a median of 14.6 years of follow-up, 837 people (54%) died. Mortality increased gradually from GOLD 1 to 4, while it was generally similar in groups A and B, and in groups C and D. Spirometric GOLD grades were substantially more informative than ABCD groups at predicting mortality. Conclusions Spirometric GOLD grades predicted mortality better than the new ABCD groups among people with COPD from a Norwegian general population.

The joint association of anxiety, depression and obesity with incident asthma in adults: the HUNT Study

BACKGROUND Anxiety or depression symptoms may increase the risk of developing asthma, and their interaction with obesity is not known. We aimed to assess the association of anxiety or depression symptoms and the joint association of these symptoms and obesity with incident asthma. METHODS We conducted a prospective cohort study of 23 599 adults who were 19-55 years old and free from asthma at baseline in the Norwegian Nord-Trøndelag Health Study. The Hospital Anxiety and Depression Scale was used to measure anxiety or depression symptoms. Obesity was defined as a body mass index≥30.0 kg/m2. Incident asthma was self-reported new cases of asthma during the 11-year follow-up. RESULTS Having anxiety or depression symptoms was associated with incident asthma [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.09-1.78). Obese participants with anxiety or depression symptoms had a substantially higher risk of incident asthma (OR 2.93, 95% CI 2.20-3.91) than any other group (non-obese participants without anxiety or depression symptoms [reference], non-obese participants with anxiety or depression symptoms (OR 1.20, 95% CI 1.00-1.45) and obese participants without anxiety or depression symptoms (OR 1.47, 95% CI 1.19-1.82)]. The relative excess risk for incident asthma due to interaction between anxiety or depression symptoms and obesity was 1.26 (95% CI 0.39-2.12). CONCLUSIONS This study suggests that having anxiety or depression symptoms contributes to the development of asthma in adults. The risk of asthma may be further increased by the interaction between anxiety or depression symptoms and obesity.

Lung function and anxiety in association with dyspnoea: The HUNT study

BACKGROUND Few studies from the general population have investigated the role of anxiety in reporting dyspnoea. We examined the independent and combined association of lung function and anxiety symptoms with the prevalence of dyspnoea in different situations. METHODS The study included 5627 women and 5066 men who participated in the Lung study of the Nord-Trøndelag Health Study second survey in 1995-97. In a cross-sectional design we used logistic regression to calculate adjusted odds ratios (ORs) for reporting dyspnoea associated with levels of percent predicted FEV(1) (ppFEV(1)) and anxiety (Hospital Anxiety and Depression Scale). RESULTS Overall, there was a linear inverse association between ppFEV(1) and dyspnoea (all P(trend) < 0.001), and a positive association between anxiety symptoms and dyspnoea (all P(trend) < 0.001). In combined analysis, using people with ppFEV(1) ≥100 without anxiety as reference, the OR (95% confidence interval) for reporting dyspnoea when walking on flat ground was 6.23 (3.45-11.28) in women with ppFEV(1) <80 without anxiety and 15.14 (7.13-32.12) in women with ppFEV(1) <80 with anxiety. The corresponding ORs among men were 5.75 (2.23-14.18) and 15.19 (4.74-48.64), respectively. Similar patterns were seen for dyspnoea when sitting still and woken at night by dyspnoea. CONCLUSION Impaired lung function and anxiety symptoms were independently associated with reporting dyspnoea. Within lung function levels, reporting dyspnoea was more common among people with anxiety symptoms than among people without. This suggests that, in addition to its relation to reduced lung function, the subjective experience of breathing discomfort may also influence or be influenced by anxiety.

Lung Function and Respiratory Symptoms in Association with Mortality: The HUNT Study

Whether respiratory symptoms are associated with mortality independent of lung function is unclear. The authors explored the association of the exposures i) lung function, ii) respiratory symptoms, and iii) lung function and respiratory symptoms combined, with the outcomes all-cause and cardiovascular mortality. The study included 10,491 adults who participated in the Nord-Trøndelag Health Study (HUNT) Lung Study in 1995-1997 and were followed through 2009. Cox regression was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals for all-cause and cardiovascular mortality associated with pre-bronchodilator% predicted forced expiratory volume in 1 second (ppFEV1), chronic obstructive pulmonary disease (COPD) grades, and respiratory symptoms (chronic bronchitis, wheeze, and levels of dyspnoea). Lung function was inversely associated with all-cause mortality. Compared to ppFEV1 ≥100, ppFEV1 <50 increased the HR to 6.85 (4.46-10.52) in women and 3.88 (2.60-5.79) in men. Correspondingly, compared to normal airflow, COPD grade 3 or 4 increased the HR to 6.50 (4.33-9.75) in women and 3.57 (2.60-4.91) in men. Of the respiratory symptoms, only dyspnoea when walking remained associated with all-cause mortality after controlling for lung function (HR 1.73 [1.04-2.89] in women and 1.57 [1.04-2.36] in men). Analyses of lung function and dyspnoea when walking as a combined exposure further supported this finding. Overall, associations between lung function and cardiovascular mortality were weaker, and respiratory symptoms were not associated with cardiovascular mortality. In conclusion, lung function was inversely associated with all-cause and cardiovascular mortality, and dyspnoea when walking was associated with all-cause mortality independent of lung function.

A simple algorithm for the identification of clinical COPD phenotypes

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses. Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative. Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respiratory disease (FEV1, dyspnoea grade) and those with multi-morbidity (dyspnoea grade, age, FEV1 and body mass index). Application of this algorithm to the 3CIA cohorts confirmed that it identified subgroups of patients with different clinical characteristics, mortality rates (median, from 4% to 27%) and age at death (median, from 68 to 76 years). A simple algorithm, integrating respiratory characteristics and comorbidities, allowed the identification of clinically relevant COPD phenotypes. An algorithm integrating respiratory characteristics and comorbidities identifies clinical COPD phenotypes http://ow.ly/eSRp30fJPG5

Regional variation in hospitalizations and outpatient appointments for diverticular disease in Norway: a nationwide cross-sectional study

Abstract Objective: To investigate the use of specialized health care services for diverticular disease in different hospital referral regions in Norway. Materials and methods: Nationwide cross-sectional study with data from the Norwegian Patient Registry and Statistics Norway. All Norwegian inhabitants aged 40 years and older in the years 2012–16 (2,517,938) were included. We obtained the rates (n/100,000 population) for hospitalizations, outpatient appointments, and surgery for diverticular disease for the population in each hospital referral region. We also quantified the use of lower gastrointestinal (LGI) endoscopy in hospitalizations and outpatient appointments for diverticular disease and the use of LGI endoscopy performed on any indication. Results: There were 131 hospitalizations and 381 outpatient appointments for diverticular disease per 100,000 population annually. Hospitalization rates varied 1.9-fold across regions from 94 to 175. Outpatient appointment rates varied 2.5-fold across regions from 258 to 655. Outpatient appointments were strongly correlated to hospitalizations (rs=0.75, p < .001) and outpatient LGI endoscopy for any indication (rs=0.67, p < .001). Hospitalization and surgery rates remained stable over the study period, while outpatient appointment rates increased by 37%. Concurrently, rates of outpatient LGI endoscopy performed on any indication increased by 35%. Conclusion: There was considerable regional variation in both hospitalizations and outpatient appointments for diverticular disease. The extent of variation and the correlation with diagnostic intensity of LGI endoscopy indicate that the regional variation in health care utilization for diverticular disease to a large extent can be explained by regional differences in clinical practice rather than disease burden.

Prevalence and trend of COPD from 1995–1997 to 2006–2008: The HUNT study, Norway

BACKGROUND COPD is a major cause of morbidity and mortality across the world and new estimates of prevalence and trend are of great importance. We aimed to estimate the prevalence and trend of COPD from 1995-1997 to 2006-2008 in Norwegian adults ≥40 years from the Nord-Trøndelag Health Study. MATERIAL AND METHODS COPD was assessed using a fixed-ratio and lower limit of normal (LLN) criteria. Pre-bronchodilator spirometry was performed during 1995-1997 (n = 7158) and 2006-2008 (n = 8788). The prevalence of COPD was weighted using the inverse probability of selection and predicted probability of response. RESULTS The prevalence of pre-bronchodilator COPD was 16.7% in 1995-1997 and 14.8% in 2006-2008 using fixed-ratio criteria, and 10.4% in 1995-1997 and 7.3% in 2006-2008 using LLN criteria. The prevalence of LLN COPD was higher among men (13.0% in 1995-1997, 7.7% in 2006-2008) than women (8.0% in 1995-1997, 6.9% in 2006-2008). From 1995-1997 to 2006-2008, the prevalence decreased among men but remained relatively stable among women. Over the 11-year period, the cumulative incidence of pre-bronchodilator COPD using LLN criteria was 3.3% and 2.7% among men and women respectively. The prevalence of self-reported asthma and respiratory symptoms increased. CONCLUSIONS The prevalence declined in men but not in women from 1995-1997 to 2006-2008, and was consistently higher among men than women.

Large-scale external validation and comparison of prognostic models: an application to chronic obstructive pulmonary disease

BackgroundExternal validations and comparisons of prognostic models or scores are a prerequisite for their use in routine clinical care but are lacking in most medical fields including chronic obstructive pulmonary disease (COPD). Our aim was to externally validate and concurrently compare prognostic scores for 3-year all-cause mortality in mostly multimorbid patients with COPD.MethodsWe relied on 24 cohort studies of the COPD Cohorts Collaborative International Assessment consortium, corresponding to primary, secondary, and tertiary care in Europe, the Americas, and Japan. These studies include globally 15,762 patients with COPD (1871 deaths and 42,203 person years of follow-up). We used network meta-analysis adapted to multiple score comparison (MSC), following a frequentist two-stage approach; thus, we were able to compare all scores in a single analytical framework accounting for correlations among scores within cohorts. We assessed transitivity, heterogeneity, and inconsistency and provided a performance ranking of the prognostic scores.ResultsDepending on data availability, between two and nine prognostic scores could be calculated for each cohort. The BODE score (body mass index, airflow obstruction, dyspnea, and exercise capacity) had a median area under the curve (AUC) of 0.679 [1st quartile–3rd quartile = 0.655–0.733] across cohorts. The ADO score (age, dyspnea, and airflow obstruction) showed the best performance for predicting mortality (difference AUCADO – AUCBODE = 0.015 [95% confidence interval (CI) = −0.002 to 0.032]; p = 0.08) followed by the updated BODE (AUCBODE updated – AUCBODE = 0.008 [95% CI = −0.005 to +0.022]; p = 0.23). The assumption of transitivity was not violated. Heterogeneity across direct comparisons was small, and we did not identify any local or global inconsistency.ConclusionsOur analyses showed best discriminatory performance for the ADO and updated BODE scores in patients with COPD. A limitation to be addressed in future studies is the extension of MSC network meta-analysis to measures of calibration. MSC network meta-analysis can be applied to prognostic scores in any medical field to identify the best scores, possibly paving the way for stratified medicine, public health, and research.