Hanne Thorsen

The Danish Randomized Lung Cancer CT Screening Trial—Overall Design and Results of the Prevalence Round

Introduction: Lung cancer screening with low dose computed tomography (CT) has not yet been evaluated in randomized clinical trials, although several are underway. Methods: In The Danish Lung Cancer Screening Trial, 4104 smokers and previous smokers from 2004 to 2006 were randomized to either screening with annual low dose CT scans for 5 years or no screening. A history of cigarette smoking of at least 20 pack years was required. All participants have annual lung function tests, and questionnaires regarding health status, psychosocial consequences of screening, smoking habits, and smoking cessation. Baseline CT scans were performed in 2052 participants. Pulmonary nodules were classified according to size and morphology: (1) Nodules smaller than 5 mm and calcified (benign) nodules were tabulated, (2) Noncalcified nodules between 5 and 15 mm were rescanned after 3 months. If the nodule increased in size or was larger than 15 mm the participant was referred for diagnostic workup. Results: At baseline 179 persons showed noncalcified nodules larger than 5 mm, and most were rescanned after 3 months: The rate of false-positive diagnoses was 7.9%, and 17 individuals (0.8%) turned out to have lung cancer. Ten of these had stage I disease. Eleven of 17 lung cancers at baseline were treated surgically, eight of these by video assisted thoracic surgery resection. Conclusions: Screening may facilitate minimal invasive treatment and can be performed with a relatively low rate of false-positive screen results compared with previous studies on lung cancer screening.

CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT

Background The effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial. Methods 4104 men and women, healthy heavy smokers/former smokers were randomised to five annual low-dose CT screenings or no screening. Two experienced chest radiologists read all CT scans and registered the location, size and morphology of nodules. Nodules between 5 and 15 mm without benign characteristics were rescanned after 3 months. Growing nodules (>25% volume increase and/or volume doubling time<400 days) and nodules >15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice. Results Participation rates were high in both groups (screening: 95.5%; control: 93.0%; p<0.001). Lung cancer detection rate was 0.83% at baseline and mean annual detection rate was 0.67% at incidence rounds (p=0.535). More lung cancers were diagnosed in the screening group (69 vs 24, p<0.001), and more were low stage (48 vs 21 stage I–IIB non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC), p=0.002), whereas frequencies of high-stage lung cancer were the same (21 vs 16 stage IIIA–IV NSCLC and extensive stage SCLC, p=0.509). At the end of screening, 61 patients died in the screening group and 42 in the control group (p=0.059). 15 and 11 died of lung cancer, respectively (p=0.428). Conclusion CT screening for lung cancer brings forward early disease, and at this point no stage shift or reduction in mortality was observed. More lung cancers were diagnosed in the screening group, indicating some degree of overdiagnosis and need for longer follow-up.

The effect of low-level laser therapy on musculoskeletal pain: A meta-analysis

&NA; A meta‐analysis was undertaken of low‐level laser therapy (LLLT) on musculoskeletal pain. A literature search revealed 23 LLLT trials and of these 17 were controlled trials. Ten were double blind and 7 were insufficiently blinded. Within the studies identified pain was assessed by visual analogue scale or by “some other indices of pain”. Nine double‐blind trials and 4 controlled trials presented results in a form which allowed pooling of data. In the double‐blind trials, the mean difference in pain between LLLT and placebo was 0.3% (S.E.(d) 4.6%, confidence limits −10.3–10.9%). In the insufficiently blinded trials the mean difference in pain was 9.5% (S.E.(d) 4.5%, confidence limits −2.9–21.8%). We conclude that LLLT has no effect on pain in musculoskeletal syndromes.

Effect of CT screening on smoking habits at 1-year follow-up in the Danish Lung Cancer Screening Trial (DLCST)

Background: The effect of low-dose CT screening for lung cancer on smoking habits has not been reported in large randomised controlled trials. Methods: This study evaluated the effect on smoking habits of screening with low-dose CT at 1-year follow up in the Danish Lung Cancer Screening Trial (DLCST), a 5-year randomised controlled trial comprising 4104 subjects; 2052 subjects received annual low-dose CT scan (CT group) and 2052 received no intervention (control group). Participants were healthy current and former smokers (>4 weeks since smoking cessation) with a tobacco consumption of >20 pack years. Smoking habits were determined at baseline and at annual screening. Smoking status was verified using exhaled carbon monoxide levels. Lung function tests, nicotine dependency and motivation to quit smoking were assessed. Quit rates and relapse rates were determined at 1-year follow-up for all subjects. Results: At 1 year the quit rates among smokers were 11.9% in the CT group and 11.8% in the control group (p = 0.95). Relapse rates for former smokers were 10.0% and 10.5% in the CT and control groups, respectively (p = 0.81). Significant predictors (p<0.05) for smoking cessation were: high motivation to quit, low dependency, low ratio of forced expiratory volume in 1 s to forced vital capacity, low pack years, higher age, longer period of abstinence and CT findings necessitating 3-month repeat CT scans. Conclusions: Overall, quit rates were similar in the CT and control group at 1-year follow-up, with a net quit rate of 6.0%. Quit rates were higher and relapse rate lower among subjects with initial CT findings that necessitated a repeat scan 3 months later.

Adaptation into Danish of the Stanford Health Assessment Questionnaire (HAQ) and the Rheumatoid Arthritis Quality of Life Scale (RAQoL).

OBJECTIVES The study was designed to adapt the Stanford Health Assessment Questionnaire (HAQ) and the Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) for use in Denmark. METHOD The instruments were translated into Danish and then field-tested with 10 RA patients for relevance, and face and content validity. Reliability and validity were assessed by administering the new measures and a comparator instrument (the Danish Nottingham Health Profile) to 80 RA patients on two occasions. RESULTS Patients found both measures acceptable and easy to complete. They had good test-retest reliability (>0.90) and internal consistency and were both able to discriminate between groups with different levels of functional status and self-perceived severity. When compared with the NHP sections, both measures showed expected convergence and divergence. CONCLUSION Given the excellent psychometric properties of the Danish versions of the RAQoL and HAQ, both are recommended for inclusion in clinical trials and studies.Objectives: The study was designed to adapt the Stanford Health Assessment Questionnaire (HAQ) and the Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) for use in Denmark. Method: The instruments were translated into Danish and then field-tested with 10 RA patients for relevance, and face and content validity. Reliability and validity were assessed by administering the new measures and a comparator instrument (the Danish Nottingham Health Profile) to 80 RA patients on two occasions. Results: Patients found both measures acceptable and easy to complete. They had good test-retest reliability (>0.90) and internal consistency and were both able to discriminate between groups with different levels of functional status and self-perceived severity. When compared with the NHP sections, both measures showed expected convergence and divergence. Conclusion: Given the excellent psychometric properties of the Danish versions of the RAQoL and HAQ, both are recommended for inclusion in clinical trials and studies.

Low level laser therapy for myofascial pain in the neck and shoulder girdle. A double-blind, cross-over study

In a controlled, cross-over study the effect of low level laser therapy (LLLT) was evaluated. During a five weeks period forty-seven female laboratory technicians received six laser and six placebo treatments to tender points in the neck and shoulder girdle. Subjects rated the placebo treatment significantly more beneficial than LLLT (p = .04). There was no reduction in consumption of analgesics associated with either laser or placebo treatment. The results indicate no beneficial effect of LLLT for myofascial pain.

Inter-tester reliability of a new diagnostic classification system for patients with non-specific low back pain

Most patients referred to physiotherapy with low back pain are without a precise medical diagnosis. Identification of subgroups of non-specific low back pain patients may improve clinical outcomes and research efficiency. A pathoanatomic classification system has been developed, classifying patients with non-specific low back pain into 12 different syndromes and three subcategories based on history and physical examination. The purpose of this study was to estimate the inter-tester reliability of clinical tests used as criteria for classifying patients. Ninety patients with chronic low back pain were each examined by two physiotherapists. A total of four physiotherapists conducted the assessments. Examination findings were recorded independently by the two examiners. Percentage of agreement and kappa coefficients were calculated for each category. The overall rate of agreement was 72% and the kappa coefficient was 0.62 for the mutually exclusive syndromes in the classification system. Agreement rates for each of the syndromes ranged from 74% to 100% and kappa coefficients ranged from 0.44 to 1.00. The findings suggest the inter-tester reliability of the system is acceptable. The relatively modest level of total agreement (39%) for the system as a whole might indicate that the utility of the system for general screening purposes is limited, compared with the utility in identification of particular syndromes. Due to low prevalence of positive findings in some of the syndromes, future work should focus on testing reliability on a larger sample of patients, and testing of validity and feasibility of the system.

Diagnostic classification of non-specific low back pain. A new system integrating patho-anatomic and clinical categories

Identifying relevant subgroups of nonspecific low back pain patients may improve research efficiency and clinical outcomes. This article presents available data supporting the rationale behind a new pathoanatomic oriented classification system for low back pain. A systematic framework was used to assess issues of validity, reliability, feasibility, and generalizability. Results from studies examining elements of the 12 categories of the classification system are presented to allow the assessment to be made. Particular emphasis has been given to the evidence of diagnostic accuracy of the criteria based on data from history taking and clinical tests. The classification system was found to be potentially useful for research purposes. Further testing of the classification system is required.

The Adequacy of Measurement of Short and Long-Term Consequences of False-Positive Screening Mammography

Objectives: The aim of this study is to review quantitative studies on womens experiences of consequences of false-positive screening mammography to assess the adequacy of the most frequently used instruments for measuring short-term and long-term psychological consequences. Methods: Relevant papers reporting quantitative studies on consequences of false-positive screening mammography were identified using MEDLlNE, CINAHL, EMBASE and PsycInfo databases. Articles citing development and psychometric properties of the most frequently used measures were also retrieved. Finally, the review focused on studies that had used at least one of the most frequently used measures. Results: Twenty-three relevant studies were identified. The most commonly used measures were the General Health Questionnaire (GHQ), the Hospital Anxiety and Depression Scale (HADS), the Psychological Consequences Questionnaire (PCQ) and the State-Trait Anxiety Inventory (STAI). One or more of these was used in 17 of the 23 studies. Conclusions: The GHQ, the HADS and the STAI have problems with language, content relevance, and content coverage in studies of false-positive screening mammography. These instruments should not be used to measure psychological consequences of any kind of cancer screening. The PCQ is an adequate questionnaire for measuring short-term consequences, and the PCQ is preferable to other measures because of its higher sensitivity. However, there is little evidence that the PCQ is able to adequately detect all long-term consequences of screening mammography. Given the inadequacy of the measurement instruments used, any current conclusions about the long-term consequences of false-positive results of screening mammography must remain tentative.

Methodological aspects of differential item functioning in the Rasch model

Summary Items do not always function equally in different groups (e.g. across genders, languages and cultures). Consequently, where patient-reported outcomes are used and different groups are compared, data should be checked for differential item functioning (DIF). An item that functions with the same constant magnitude of difference across a construct measured possesses uniform DIF. In contrast, non-uniform DIF is characterised by an uneven difference in item function across the latent variable measured. The aims of this paper are to report on the methodological aspects of DIF using Rasch analysis and to demonstrate how the mean scores in a scale can be adjusted due to uniform DIF. Different examples of DIF are reported including examples of differences between the mean scores before and after adjusting for an identified uniform DIF. In conclusion, the difference between subpopulations and, therefore, other outcomes such as economic impact could be under or overestimated if one or more items in a dimension possess DIF.