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1.  Comparing clinical attachment level and pocket depth for predicting periodontal disease progression in healthy sites of patients with chronic periodontitis using multi-state Markov models 
To understand degeneration of healthy sites and identify factors associated with disease progression in patients with chronic periodontitis.
Material and Methods
Data on healthy sites from 163 American and Swedish subjects were analysed using two-three-state (health, gingivitis, chronic periodontitis) Markov models based on bleeding on probing (BOP), and either clinical attachment level (CAL) + BOP or pocket depth (PD) + BOP.
In 2 years, 10% (CAL + BOP) and 3% (PD + BOP) of healthy sites developed chronic periodontitis. On average, healthy sites remained healthy for 32 months before transiting in both models. Most transitions (87–97%) from health were to the gingivitis state. The expected duration of the gingivitis lesion was 4–5 months and sites recovered with a high probability (96–98%). Disease severity as measured by number of sites with CAL/PD > 4 mm at baseline and smoking, were associated with fast progression from health to chronic periodontitis within 6 months as were gingival redness in the PD + BOP model only. With age, the rate of disease progression to gingivitis decreased.
Transition probabilities for gingivitis and chronic periodontitis were higher with CAL + BOP than with PD + BOP. Smoking and disease severity were significant predictors for fast progression.
PMCID: PMC4139458  PMID: 24888705
antibiotics; chronic periodontitis; multi-state Markov models; periodontal therapy
2.  Multilevel analysis of bacterial counts from chronic periodontitis after root planing/scaling, surgery, and systemic and local antibiotics: 2-year results 
Journal of Oral Microbiology  2013;5:10.3402/jom.v5i0.20939.
To follow changes (over 2 years) in subgingival bacterial counts of five microbial complexes including health-related Actinomyces spp. in deeper pockets (≥5 mm) after periodontal treatments.
Eight different treatments were studied: (1) scaling+root planing (SRP); (2) periodontal surgery (SURG)+systemic amoxicillin (AMOX)+systemic metronidazole (MET); (3) SURG+locally delivered tetracycline (TET); (4) SURG; (5) AMOX+MET+TET; (6) AMOX+MET; (7) TET; and (8) SURG+AMOX+MET+TET. Antibiotics were given immediately following SRP. Subgingival plaque was collected mesiobuccally from each tooth, except third molars, from 176 subjects, completing the study, at baseline, 3, 6, 12, 18, and 24 months post-treatment and analysed for 40 different bacteria using checkerboard hybridization. A negative binomial (NB) generalized estimating equation (NB GEE) model was used to analyze count data and a logistic GEE was used for proportions.
We observed short-term beneficial changes in the composition of the red complex of up to 3 months by treating subjects with AMOX+MET+TET. Similar short-term improvements with the same treatment were observed for Tannerella forsythia and Treponema denticola of the red complex. SURG had also short-term beneficial effect on Porphyromonas gingivalis. No periodontal treatments applied to severely affected sites promoted the growth of Actinomyces. Smoking elevated counts of both the red and orange complex while bleeding on probing (BOP) and gingival redness were also predictors of more red complex counts. Comparatively similar findings were obtained by analyzing counts and by analyzing proportions.
Although short-term reductions in the counts of the red complex were observed in sites that were treated with AMOX+MET+TET, long-term significant effects were not observed with any of the eight treatments. Poor oral hygiene in patients with severe chronic periodontitis diminished the beneficial effects of treatment.
PMCID: PMC3708352  PMID: 23853701
microbiota; chronic periodontitis; periodontal therapy; antibiotics; multilevel analysis; NB GEE; fractional response methods
3.  Stress associated gene expression in blood cells is related to outcome in radiotherapy treated head and neck cancer patients 
BMC Cancer  2012;12:426.
We previously observed that a radiotherapy-induced biochemical response in plasma was associated with favourable outcome in head and neck squamous carcinoma cancer (HNSCC) patients. The aim of the present study was to compare stress associated blood cell gene expression between two sub-groups of HNSCC patients with different biochemical responses to radiotherapy.
Out of 87 patients (histologically verified), 10 biochemical ‘responders’ having a high relative increase in plasma oxidative damage and a concomitant decrease in plasma antioxidants during radiotherapy and 10 ‘poor-responders’ were selected for gene-expression analysis and compared using gene set enrichment analysis.
There was a significant induction of stress-relevant gene-sets in the responders following radiotherapy compared to the poor-responders. The relevance of the involvement of similar stress associated gene expression for HNSCC cancer and radioresistance was verified using two publicly available data sets of 42 HNSCC cases and 14 controls (GEO GSE6791), and radiation resistant and radiation sensitive HNSCC xenografts (E-GEOD-9716).
Radiotherapy induces a systemic stress response, as revealed by induction of stress relevant gene expression in blood cells, which is associated to favourable outcome in a cohort of 87 HNSCC patients. Whether these changes in gene expression reflects a systemic effect or are biomarkers of the tumour micro-environmental status needs further study.
Trial registration
Raw data are available at ArrayExpress under accession number E-MEXP-2460.
PMCID: PMC3517770  PMID: 23009663
Radiotherapy; HNSCC; Antioxidants; Microarray; GSEA; Cancer
4.  Multilevel analysis of clinical parameters in chronic periodontitis after root planing/scaling, surgery, and systemic and local antibiotics: 2-year results 
Journal of Oral Microbiology  2012;4:10.3402/jom.v4i0.17535.
Find the periodontal treatment that best maintained clinical results over time evaluated by changes in pocket depth (PD) and clinical attachment level (CAL).
229 patients with chronic periodontitis from USA (n=134) and Sweden (n=95) were randomly assigned to eight groups receiving (1) scaling+root planing (SRP) alone or combined with (2) surgery (SURG)+systemic amoxicillin (AMOX)+systemic metronidazole (MET); (3) SURG+local tetracycline (TET); (4) SURG; (5) AMOX+MET+TET; (6) AMOX+MET; (7) TET; and (8) SURG+AMOX+MET+TET. Antibiotics were given immediately after SRP. Plaque, gingival redness, bleeding on probing, suppuration, PD, and CAL were recorded at baseline and after 3, 6, 12, 18, and 24 months. Treatment effects were evaluated by linear multilevel regression and logistic multilevel regression models. We considered only data from sites with a baseline PD of at least 5 mm of 187 patients completing the study.
Surgically treated patients experienced most CAL loss. Adjunctive therapy including SURG was most effective in reducing PD. Combining SURG with AMOX, MET, and TET gave significant clinical benefits. Past and current smoking habits were significant predictors of deeper PD. Only current smoking was a significant predictor of CAL loss. Bleeding, accumulation of plaque, gingival redness, and suppuration were significant predictors of further CAL loss and deeper PD.
Both surgical and non-surgical therapies can be used to arrest chronic periodontitis. SURG+AMOX+MET+TET gave best maintenance of clinical results.
PMCID: PMC3337750  PMID: 22545190
modeling; chronic periodontitis; periodontal therapy; antibiotics; surgery
5.  Changes in somatic disease incidents during opioid maintenance treatment: results from a Norwegian cohort study 
BMJ Open  2011;1(1):e000130.
To examine the effect of opioid maintenance treatment (OMT) on somatic morbidity in a cohort of OMT patients.
Retrospective cohort study.
OMT programme in two Norwegian counties.
200 OMT patients, participation rate 71.2%.
Main outcome measures
Incidence rates (IR) before, during and after OMT for acute/subacute hospital-treated somatic disease incidents (drug-related, non-drug-related, injuries) and rates for inpatient days and outpatient treatment contacts.
IR for drug-related hospital treatment episodes were 76% lower during compared to before OMT (before versus during incidence rate ratio (IRR) 4.2 (95% CI 2.9 to 6.2), p<0.001) and 11 times higher after compared to during OMT (after versus during IRR 11.1 (6.6 to 18.5), p<0.001). For non-drug-related treatment episodes, IR were 35% higher during than before OMT (before versus during IRR 0.7 (0.6 to 1.0), p=0.02) and 32% higher after compared to during OMT (IRR 1.4 (0.9 to 2.2), p=0.15), while injuries showed little change according to OMT status. Although patients with on-going drug-taking during OMT showed less reduction in drug-related hospital-treated incidents during treatment than patients not using illicit drugs, the quartile with most drug-taking showed a significant reduction (before versus during IRR 3.6 (2.4 to 5.3)). Patients who had experienced cessation of OMT showed a significant reduction in drug-related treatment episodes during OMT (before versus during IRR 1.7 (1.0 to 2.9)), although less than patients without OMT interruptions (before versus during IRR 6.1 (3.6 to 10.6)), and a significant increase after OMT cessation compared with during OMT (IRR 5.4 (3.0 to 9.7)).
Acute/subacute drug-related somatic morbidity is reduced during compared to before OMT. This was also found for patients with on-going drug-taking during OMT. However, acute drug-related health problems show an increase after OMT cessation, and this is a matter of concern. Further studies on somatic morbidity after OMT cessation should be carried out.
Article summary
Article focus
Opioid maintenance treatment (OMT) is the most widely used treatment for opioid dependence, but the effects of OMT on physical health problems have received relatively little attention.
This study investigates how acute somatic morbidity (drug-related, non-drug-related, injuries) varies according to OMT status (before, during, after OMT) in a cohort of 200 OMT patients.
The research questions were: Is somatic morbidity reduced during OMT compared to before and after treatment? If so, what types of disease incidents are reduced? How is the effect of OMT status on somatic morbidity influenced by various patient characteristics?
Key messages
Acute drug-related somatic morbidity (overdoses, injecting-related, other) is substantially reduced during compared to before OMT.
This was also found for ‘problem patients’ with on-going drug-taking during OMT, but to a lesser degree than for patients not using illicit drugs.
Strengths and limitations of this study
Participation rate was high, selection bias limited, observation period long and the evaluation of morbidity changes was based on assessment of full-text hospital records.
The study focused on acute health problems treated in hospital, but elective hospital contact due to chronic health problems and primary healthcare contacts were not included.
PMCID: PMC3191421  PMID: 22021771
6.  Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers 
BMC Medicine  2010;8:54.
Plant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases. However, the mechanisms behind this protective effect are not elucidated. We have tested the hypothesis that intake of antioxidant-rich foods can affect groups of genes associated with cellular stress defence in human blood cells. Trial registration number: NCT00520819
In an 8-week dietary intervention study, 102 healthy male smokers were randomised to either a diet rich in various antioxidant-rich foods, a kiwifruit diet (three kiwifruits/d added to the regular diet) or a control group. Blood cell gene expression profiles were obtained from 10 randomly selected individuals of each group. Diet-induced changes on gene expression were compared to controls using a novel application of the gene set enrichment analysis (GSEA) on transcription profiles obtained using Affymetrix HG-U133-Plus 2.0 whole genome arrays.
Changes were observed in the blood cell gene expression profiles in both intervention groups when compared to the control group. Groups of genes involved in regulation of cellular stress defence, such as DNA repair, apoptosis and hypoxia, were significantly upregulated (GSEA, FDR q-values < 5%) by both diets compared to the control group. Genes with common regulatory motifs for aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (AhR/ARNT) were upregulated by both interventions (FDR q-values < 5%). Plasma antioxidant biomarkers (polyphenols/carotenoids) increased in both groups.
The observed changes in the blood cell gene expression profiles suggest that the beneficial effects of a plant-based diet on human health may be mediated through optimization of defence processes.
PMCID: PMC2955589  PMID: 20846424
7.  Dairy consumption and calcium intake and risk of breast cancer in a prospective cohort: The Norwegian Women and Cancer study 
Cancer Causes & Control  2010;21(11):1875-1885.
To study the association between consumption of dairy products and calcium intake and risk of breast cancer risk according to menopausal status.
In a population-based prospective cohort study of 64,904 Norwegian women followed from 1996/1999 through 2006, we examined total dairy consumption and consumption of various dairy products in relation to pre- and postmenopausal breast cancer risk. We also examined breast cancer in relation to calcium intake and to milk consumption during childhood and performed additional analyses corrected for measurement errors in the dietary data. In total, 218 premenopausal and 1,189 postmenopausal incident breast cancer cases were diagnosed during follow-up.
Total dairy, adult, and childhood milk consumption was not associated with either pre- or postmenopausal breast cancer risk. Premenopausal women with the highest consumption of white cheese had half the risk of breast cancer compared to those with the lowest consumption (hazard rate ratio in the 4th quartile vs. the 1st quartile 0.50, 95% confidence interval 0.29–0.87). Total calcium intake tended to be inversely related to premenopausal (hazard rate ratio in the 4th quartile vs. the 1st quartile 0.65, 95% confidence interval 0.39–1.08) and postmenopausal breast cancer (hazard rate ratio in the 4th quartile vs. the 1st quartile 0.85, 95% confidence interval 0.70–1.04). Correcting for measurement errors did not alter the results substantially, nor did exclusion of early cancer cases.
Dairy consumption is not strongly related to breast cancer risk in this prospective study. A non-significant negative association between calcium intake and breast cancer risk was seen, particularly among premenopausal women.
PMCID: PMC2959158  PMID: 20658314
Milk; Calcium; Food frequency questionnaire; Measurement errors; Norway
8.  Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study 
BMC Cancer  2009;9:458.
The purpose of this study was to compare plasma levels of antioxidants and oxidative stress biomarkers in head and neck squamous cell carcinoma (HNSCC) patients with healthy controls. Furthermore, the effect of radiotherapy on these biomarkers and their association with survival in HNSCC patients were investigated.
Seventy-eight HNSCC patients and 100 healthy controls were included in this study. Follow-up samples at the end of radiotherapy were obtained in 60 patients. Fifteen antioxidant biomarkers (6 carotenoids, 4 tocopherols, ascorbic acid, total antioxidant capacity, glutathione redox potential, total glutathione and total cysteine) and four oxidative stress biomarkers (total hydroperoxides, γ-glutamyl transpeptidase, 8-isoprostagladin F2α and ratio of oxidized/total ascorbic acid) were measured in plasma samples. Analysis of Covariance was used to compare biomarkers between patients and healthy controls. Kaplan-Meier plots and Cox' proportional hazards models were used to study survival among patients.
Dietary antioxidants (carotenoids, tocopherols and ascorbic acid), ferric reducing antioxidant power (FRAP) and modified FRAP were lower in HNSCC patients compared to controls and dietary antioxidants decreased during radiotherapy. Total hydroperoxides (d-ROMs), a marker for oxidative stress, were higher in HNSCC patients compared to controls and increased during radiotherapy. Among the biomarkers analyzed, high levels of plasma carotenoids before radiotherapy are associated with a prolonged progression-free survival (hazard rate ratio: 0.42, 95% CI: 0.20-0.91, p = 0.03). Additionally, high relative increase in plasma levels of d-ROMs (hazard rate ratio: 0.31, 95% CI: 0.13-0.76, p = 0.01) and high relative decrease in FRAP (hazard rate ratio: 0.42, 95% CI: 0.17-0.998, p = 0.05) during radiotherapy are also positively associated with survival.
Biomarkers of antioxidants and oxidative stress are unfavourable in HNSCC patients compared to healthy controls, and radiotherapy affects many of these biomarkers. Increasing levels of antioxidant biomarkers before radiotherapy and increasing oxidative stress during radiotherapy may improve survival indicating that different factors/mechanisms may be important for survival before and during radiotherapy in HNSCC patients. Thus, the therapeutic potential of optimizing antioxidant status and oxidative stress should be explored further in these patients.
PMCID: PMC2813240  PMID: 20025747
9.  Is the association between acne and mental distress influenced by diet? Results from a cross-sectional population study among 3775 late adolescents in Oslo, Norway 
BMC Public Health  2009;9:340.
Several studies with conflicting findings have investigated the association between acne and mental health problems. Acne usually starts in adolescents, as does an increase in the prevalence of depression and anxiety. Recently, there has been more focus on the link between diet and acne and diet and mental health problems. The objective of this study is to investigate the association between acne and mental distress and to explore a possible influence of dietary factors on the relation.
A population-based cross-sectional study in Oslo of 18 or 19 year old adolescents. The participation rate was 80%. Acne was self-reported. To measure mental distress, the Hopkins Symptom Checklist 10 was used. Diet and lifestyle variables were also collected by questionnaire and socio-demographic variables were obtained from Statistics Norway.
The prevalence of acne was 14.4% among the males and 12.8% among the females. The mean score of mental distress increased when the severity of acne increased. In the crude analyses, the significant associations with acne among the males were: mental distress OR = 1.63, frequent consumption of chocolate/sweets OR = 1.40, frequent consumption of potato chips OR = 1.54. The significant crude associations with acne among the females were: mental distress OR = 2.16, infrequent consumption of raw vegetables OR = 1.41, non-Western background OR = 1.77 and low family income OR = 2.14. No crude associations with acne were identified in either gender for the consumption of sugary soft drinks, fatty fish, cigarette smoking or alcohol. In adjusted models which included diet and socio-demographic variables, the association between acne and mental distress was unchanged for both males (OR = 1.68) and females (OR = 2.04), and between acne and infrequent consumption of raw vegetables among the females (OR = 1.38).
Among late adolescents in Oslo, self-reported acne is significantly associated with mental distress and, among girls, with infrequent consumption of raw vegetables. Our finding does not support the hypothesis that dietary factors alter the relationship between acne and mental distress.
PMCID: PMC2751780  PMID: 19758425
10.  Three-year follow-up of physical activity in Norwegian youth from two ethnic groups: associations with socio-demographic factors 
BMC Public Health  2008;8:419.
More research on factors associated with physical activity and the decline in participation during adolescence is needed. In this paper, we investigate the levels, change, and stability of physical activity during the late teens among ethnic Norwegians and ethnic minorities, and we examine the associations between physical activity and socio-demographic factors.
The baseline (T1) of this longitudinal study included 10th graders who participated in the youth part of the Oslo Health Study, which was carried out in schools in 2000–2001. The follow-up (T2) in 2003–2004 was conducted partly at school and partly by mail. A total of 2489 (1112 boys and 1377 girls) participated both at baseline and at follow-up. Physical activity level was measured by a question on weekly hours of physical activity outside of school. Socio-demographic variables were collected by questionnaire and from data obtained from Statistics Norway. Analysis of variance was used to study the level of and changes (T1 to T2) in physical activity, and the associations between physical activity and socio-demographic factors. Stability in physical activity was defined as the percentage of students reporting the same physical activity both times.
Boys were more active than girls at age 15 and 18 years, independent of ethnic background. Among girls, ethnic Norwegians were more active than ethnic minorities. Hours per week spent on physical activity declined in all groups during the follow-up period. Few associations were found between physical activity and socio-demographic factors in both cross-sectional and longitudinal data. Among the ethnic minority girls, 65% reported being physically active 0–2 hours per week at baseline, and 82% of these girls reported the same level at follow up.
The association between physical activity and ethnicity at age 15 years remained the same during the follow-up. Few associations were found between physical activity and socio-demographic variables. A large proportion of ethnic minority girls reported a persistently low physical activity level, and this low participation rate may need special attention.
PMCID: PMC2640384  PMID: 19102770
11.  Own and parental war experience as a risk factor for mental health problems among adolescents with an immigrant background: results from a cross sectional study in Oslo, Norway 
An increasing proportion of immigrants to Western countries in the past decade are from war affected countries. The aim of this study was to estimate the prevalence of war experience among adolescents and their parents and to investigate possible differences in internalizing and externalizing mental health problems between adolescents exposed and unexposed to own and parental war experience.
The study is based on a cross-sectional population-based survey of all 10th grade pupils in Oslo for two consecutive years. A total of 1,758 aadolescents were included, all with both parents born outside of Norway. Internalizing and externalizing mental health problems were measured by Hopkins Symptom Checklist-10 and subscales of the Strengths and Difficulties Questionnaire, respectively. Own and parental war experience is based on adolescent self-report.
The proportion of adolescents with own war experience was 14% with the highest prevalence in immigrants from Eastern Europe and Sub-Saharan Africa. The proportion of parental war experience was 33% with Sub-Saharan Africa being highest. Adolescents reporting own war experience had higher scores for both internalizing and externalizing mental health problems compared to immigrants without war experience, but only externalizing problems reached statistically significant differences. For parental war experience there was a statistically significant relationship between parental war experience and internalizing mental health problems. The association remained significant after adjustment for parental educational level and adolescents' own war experience.
War exposure is highly prevalent among immigrants living in Oslo, Norway, both among adolescents themselves and their parents. Among immigrants to Norway, parental war experience appears to be stronger associated with mental health problems than adolescents own exposure to war experience.
PMCID: PMC1635694  PMID: 17081315
12.  Regression analysis with categorized regression calibrated exposure: some interesting findings 
Regression calibration as a method for handling measurement error is becoming increasingly well-known and used in epidemiologic research. However, the standard version of the method is not appropriate for exposure analyzed on a categorical (e.g. quintile) scale, an approach commonly used in epidemiologic studies. A tempting solution could then be to use the predicted continuous exposure obtained through the regression calibration method and treat it as an approximation to the true exposure, that is, include the categorized calibrated exposure in the main regression analysis.
We use semi-analytical calculations and simulations to evaluate the performance of the proposed approach compared to the naive approach of not correcting for measurement error, in situations where analyses are performed on quintile scale and when incorporating the original scale into the categorical variables, respectively. We also present analyses of real data, containing measures of folate intake and depression, from the Norwegian Women and Cancer study (NOWAC).
In cases where extra information is available through replicated measurements and not validation data, regression calibration does not maintain important qualities of the true exposure distribution, thus estimates of variance and percentiles can be severely biased. We show that the outlined approach maintains much, in some cases all, of the misclassification found in the observed exposure. For that reason, regression analysis with the corrected variable included on a categorical scale is still biased. In some cases the corrected estimates are analytically equal to those obtained by the naive approach. Regression calibration is however vastly superior to the naive method when applying the medians of each category in the analysis.
Regression calibration in its most well-known form is not appropriate for measurement error correction when the exposure is analyzed on a percentile scale. Relating back to the original scale of the exposure solves the problem. The conclusion regards all regression models.
PMCID: PMC1559617  PMID: 16820052

Results 1-12 (12)