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author:("Sandvik, liv")
1.  Association between moderate to severe psoriasis and periodontitis in a Scandinavian population 
BMC Oral Health  2014;14(1):139.
The aim of the present study was to compare the prevalence of periodontitis and alveolar bone loss among individuals with psoriasis and a group of randomly selected controls.
Fifty individuals with psoriasis and 121 controls completed a structured questionnaire, and were examined clinically and radiographically. Oral examination included numbers of missing teeth, probing pocket depth (PPD), clinical attachment level (CAL), presence of dental plaque and bleeding on probing, as well as alveolar bone loss from radiographs. Questionnaires requested information on age, gender, education, dental care, smoking habits, general diseases and medicament use. For adjustment for baseline differences between psoriasis individuals and controls the propensity score based on gender, age and education was computed using multivariate logistic regression. A subsample analysis for propensity score matched psoriasis individuals (n = 50) and controls (n = 50) was performed.
When compared with controls, psoriasis individuals had significantly more missing teeth and more sites with plaque and bleeding on probing. The prevalence of moderate and severe periodontitis was significantly higher among psoriasis individuals (24%) compared to healthy controls (10%). Similarly, 36% of psoriasis cases had one or more sites with radiographic bone loss ≥3 mm, compared to 13% of controls. Logistic regression analysis showed that the association between moderate/severe periodontitis and psoriasis remained statistically significant when adjusted for propensity score, but was attenuated when smoking was entered into the model. The association between psoriasis and one or more sites with bone loss ≥3 mm remained statistically significant when adjusted for propensity score and smoking and regularity of dental visits. In the propensity score (age, gender and education) matched sample (n = 100) psoriasis remained significantly associated with moderate/severe periodontitis and radiographic bone loss.
Within the limits of the present study, periodontitis and radiographic bone loss is more common among patients with moderate/severe psoriasis compared with the general population. This association remained significant after controlling for confounders.
PMCID: PMC4280688  PMID: 25427764
Alveolar bone loss; Comorbidity; Periodontitis; Psoriasis
2.  Risk Factors for Aggressive Recurrent Respiratory Papillomatosis in Adults and Juveniles 
PLoS ONE  2014;9(11):e113584.
In this cohort study we examined whether gender, age at onset, observation time or human papillomavirus (HPV) genotype are risk factors for an aggressive clinical course in Recurrent Respiratory Papillomatosis (RRP). Clinical data from patient records comprised gender, age at onset, date of first endolaryngeal procedure with biopsy, date of last follow-up, total number of endolaryngeal procedures, and complications during the observation period. Disease was defined as juvenile (JoRRP) or adult onset (AoRRP) according to whether the disease was acquired before or after the age of 18. Aggressive disease was defined as distal spread, tracheostomy, four surgical operations annually or >10 surgeries in total. DNA was extracted from formalin-fixed paraffin-embedded tissue. HPV genotyping was performed by quantitative PCR assay identifying 15 HPV genotypes. The study included 224 patients. The majority were males (141/174 in AoRRPs and 31/50 in JoRRPs; p = 0.005). The median follow-up from initial diagnosis was 12.0 years (IQR 3.7–32.9) for JoRRPs and 4.0 years (IQR 0.8–11.7) for AoRRPs. The disease was more aggressive in juveniles than adults (p<0.001), a difference that disappeared after 10 years' observation. JoRRPs with aggressive disease were younger at onset (mean difference 4.6 years, 95%CI [2.4, 6.8], p = 0.009). HPV6 or −11 was present in all HPV-positive papillomas. HPV11 was more prevalent in aggressive disease, and HPV6 in non-aggressive disease (p<0.001). Multiple logistic regression revealed that only age at onset (OR = 0.69, 95% CI [0.53, 0.88], p = 0.003) was associated with aggressive disease in juveniles, while HPV11 (OR = 3.74, 95% CI [1.40, 9.97], p = 0.008) and observation time >10 years (OR = 13.41, 95% CI [5.46, 32.99[, p<001) were risk factors in adults. In conclusion, the only significant risk factor for developing aggressive disease in JoRRPs was age at onset, but both HPV11 and observation time >10 years were risk factors for an aggressive disease course in AoRRPs.
PMCID: PMC4242649  PMID: 25419846
3.  Environmental exposures and the risk of multiple sclerosis investigated in a Norwegian case–control study 
BMC Neurology  2014;14(1):196.
Several environmental exposures, including infection with Epstein-Barr virus, low levels of vitamin D and smoking are established risk factors for multiple sclerosis (MS). Also, high hygienic standard and infection with parasites have been proposed to influence MS risk. The aim of this study was to investigate the influence of various environmental exposures on MS risk in a Norwegian cohort, focusing on factors during childhood related to the hygiene hypothesis.
A questionnaire concerning environmental exposures, lifestyle, demographics and comorbidity was administrated to 756 Norwegian MS patients and 1090 healthy controls. Logistic regression was used to calculate odds ratio (OR) with 95% confidence interval (CI) for the risk of MS associated with the variables infectious mononucleosis, severe infection during childhood, vaccination and animals in the household during childhood. Age, gender, HLA-DRB1*15:01, smoking and infectious mononucleosis were included as covariates. General environmental exposures, including tobacco use, were also evaluated.
Infectious mononucleosis was confirmed to be significantly associated with increased MS risk, also after adjusting for the covariates (OR = 1.79, 95% CI: 1.12-2.87, p = 0.016). The controls more often reported growing up with a cat and/or a dog in the household, and this was significant for ownership of cat also after adjusting for the covariates (OR = 0.56, 95% CI: 0.40-0.78, p = 0.001). More patients than controls reported smoking and fewer patients reported snuff use.
In this Norwegian MS case–control study of environmental exposures, we replicate that infectious mononucleosis and smoking are associated with increased MS risk. Our data also indicate a protective effect on MS of exposure to cats during childhood, in accordance with the hypothesis that risk of autoimmune diseases like MS may increase with high hygienic standard.
PMCID: PMC4186947  PMID: 25274070
Multiple sclerosis; Environmental risk factors; Mononucleosis; Tobacco use; Hygiene hypothesis; HLA-DRB1*15:01
4.  Recurrent Respiratory Papillomatosis: HPV Genotypes and Risk of High-Grade Laryngeal Neoplasia 
PLoS ONE  2014;9(6):e99114.
Patients with recurrent respiratory papillomatosis (RRP) in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV) genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma). High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR = 2.35, 95% CI 1.1, 4.99), as well as respiratory tract carcinomas (RR = 48, 95% CI 10.72, 214.91). In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.
PMCID: PMC4053369  PMID: 24918765
5.  Perceived competence and attitudes towards patients with suicidal behaviour: a survey of general practitioners, psychiatrists and internists 
Competence and attitudes to suicidal behaviour among physicians are important to provide high-quality care for a large patient group. The aim was to study different physicians’ attitudes towards suicidal behaviour and their perceived competence to care for suicidal patients.
A random selection (n = 750) of all registered General Practitioners, Psychiatrists and Internists in Norway received a questionnaire. The response rate was 40%. The Understanding of Suicidal Patients Scale (USP; scores < 23 = positive attitude) and items about suicide in case of incurable illness from the Attitudes Towards Suicide Questionnaire were used. Five-point Likert scales were used to measure self-perceived competence, level of commitment, empathy and irritation felt towards patients with somatic and psychiatric diagnoses. Questions about training were included.
The physicians held positive attitudes towards suicide attempters (USP = 20.3, 95% CI: 19.6–20.9). Internists and males were significantly less positive. There were no significant differences in the physicians in their attitudes toward suicide in case of incurable illness according to specialty. The physicians were most irritated and less committed to substance misuse patients. Self perceived competence was relatively high. Forty-three percent had participated in courses about suicide assessment and treatment.
The physicians reported positive attitudes and relatively high competence. They were least committed to treat patients with substance misuse. None of the professional groups thought that patients with incurable illness should be given help to commit suicide.
Further customized education with focus on substance misuse might be useful.
PMCID: PMC4048050  PMID: 24886154
Attitudes; Incurable illness; Substance misuse; Suicide attempt; Physicians
6.  Global miRNA expression analysis of serous and clear cell ovarian carcinomas identifies differentially expressed miRNAs including miR-200c-3p as a prognostic marker 
BMC Cancer  2014;14:80.
Improved insight into the molecular characteristics of the different ovarian cancer subgroups is needed for developing a more individualized and optimized treatment regimen. The aim of this study was to a) identify differentially expressed miRNAs in high-grade serous ovarian carcinoma (HGSC), clear cell ovarian carcinoma (CCC) and ovarian surface epithelium (OSE), b) evaluate selected miRNAs for association with clinical parameters including survival and c) map miRNA-mRNA interactions.
Differences in miRNA expression between HGSC, CCC and OSE were analyzed by global miRNA expression profiling (Affymetrix GeneChip miRNA 2.0 Arrays, n = 12, 9 and 9, respectively), validated by RT-qPCR (n = 35, 19 and 9, respectively), and evaluated for associations with clinical parameters. For HGSC, differentially expressed miRNAs were linked to differentially expressed mRNAs identified previously.
Differentially expressed miRNAs (n = 78) between HGSC, CCC and OSE were identified (FDR < 0.01%), of which 18 were validated (p < 0.01) using RT-qPCR in an extended cohort. Compared with OSE, miR-205-5p was the most overexpressed miRNA in HGSC. miR-200 family members and miR-182-5p were the most overexpressed in HGSC and CCC compared with OSE, whereas miR-383 was the most underexpressed. miR-205-5p and miR-200 members target epithelial-mesenchymal transition (EMT) regulators, apparently being important in tumor progression. miR-509-3-5p, miR-509-5p, miR-509-3p and miR-510 were among the strongest differentiators between HGSC and CCC, all being significantly overexpressed in CCC compared with HGSC. High miR-200c-3p expression was associated with poor progression-free (p = 0.031) and overall (p = 0.026) survival in HGSC patients. Interacting miRNA and mRNA targets, including those of a TP53-related pathway presented previously, were identified in HGSC.
Several miRNAs differentially expressed between HGSC, CCC and OSE have been identified, suggesting a carcinogenetic role for these miRNAs. miR-200 family members, targeting EMT drivers, were mostly overexpressed in both subgroups, among which miR-200c-3p was associated with survival in HGSC patients. A set of miRNAs differentiates CCC from HGSC, of which miR-509-3-5p and miR-509-5p are the strongest classifiers. Several interactions between miRNAs and mRNAs in HGSC were mapped.
PMCID: PMC3928323  PMID: 24512620
Ovarian carcinoma; MicroRNA; Microarray; Quantitative PCR; Survival
7.  Predicting the clinical outcome of stimulant medication in pediatric attention-deficit/hyperactivity disorder: data from quantitative electroencephalography, event-related potentials, and a go/no-go test 
We searched for predictors of the clinical outcome of stimulant medication in pediatric attention-deficit/hyperactivity disorder (ADHD), emphasizing variables from quantitative electroencephalography, event-related potentials (ERPs), and behavioral data from a visual go/no-go test.
Nineteen-channel electroencephalography (EEG) was recorded during the resting state in eyes-open and eyes-closed conditions and during performance of the cued go/no-go task in 98 medication-naïve ADHD patients aged 7–17 years and in 90 controls with the same age and sex distribution as the patients. For patients, the recording was followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the electrophysiological results independently rated the patients as responders (REs) (N=74) or non-responders (non-REs) (N=24). Using a logistic regression model, comparisons were made between REs and non-REs on the EEG spectra, ERPs (cue P3, contingent negative variation, and P3 no-go of the ERP waves and independent components [ICs] extracted from these waves), reaction time, reaction time variability, number of commission and omission errors, intelligence quotient, age, sex, ADHD subtype, and comorbidities.
The two groups differed significantly on eight of the variables, with effect sizes (Cohen’s d) ranging from 0.49 to 0.76. In the multivariate logistic regression analysis, only three of these variables were significantly associated with clinical outcome. The amplitude of the IC cue P3, which has a parietal–occipital distribution, was normal in REs but significantly smaller in non-REs, whereas the centrally distributed IC P3 no-go early was smaller in REs than in non-REs and controls. In addition, the REs had more power in the EEG theta band. A quartile-based index was calculated using these three variables. The group with the lowest scores comprised only 36% REs; response rates in the three other groups were 83%, 86%, and 89%.
The clinical outcome of stimulant medication was best predicted by electrophysiological parameters. The brain dysfunctions of the REs appear to be primarily associated with prefrontal lobe hypoactivation. The non-REs were deviant from the controls in parietal–occipital functions.
PMCID: PMC3921081  PMID: 24523588
ADHD; stimulants; predictions; clinical outcome; QEEG; ERP; go; no-go test
8.  Fear–avoidance beliefs associated with perceived psychological and social factors at work among patients with neck and back pain: a cross-sectional multicentre study 
Neck and back pain are common and often account for absenteeism at work. Factors at work as well as fear–avoidance beliefs may influence sick-leave in these patients. The aims of this study were to assess: (1) how sick-listed patients in specialised care perceive demand, control, support, effort, reward, and overcommitment at work compared to a general reference group of workers; (2) if women and men report demand, control, support, effort, reward, and overcommitment differently; and (3) the association between psychological and social factors at work and fear–avoidance beliefs about work.
A cross-sectional multicentre study was carried out in 373 patients on sick leave due to neck and back pain. Psychosocial work factors were measured by demand, control, and support, (Nordic Questionnaire for Psychological and Social Factors at Work), and effort, reward and overcommitment (Effort Reward Imbalance Questionnaire). Fear avoidance beliefs about work were measured by the Fear–Avoidance Belief Questionnaire Work subscale (FABQ-W).
Although the patients differed significantly from a reference working group regarding several subscales of demand, control, support, effort, reward, and overcommitment, the magnitude of these differences were small. The study population also reported significantly higher scores for ‘demand for physical endurance’ than the reference population, and Cohen’s d = 0.55 here indicated a medium degree of difference. Female patients reported significantly higher on support, whereas male patients reported significantly higher demand for physical endurance, quantitative demand, effort, and overcommitment. Demand for physical endurance, job control, job support, high reward, and overcommitment were significantly associated with FABQ-W.
Perceived psychological and social factors at work were strongly associated with fear–avoidance beliefs about work in sick-listed neck and back patients. The demand for physical endurance, control, support, high reward, as well as overcommittment at work outweighed pain and added to the burden of emotional distress and disability regarding fear–avoidance beliefs.
PMCID: PMC4222809  PMID: 24261336
Fear–avoidance beliefs; Neck pain; Back pain; Psychosocial work factors; Disability
9.  Life style and longevity among initially healthy middle-aged men: prospective cohort study 
BMC Public Health  2013;13:831.
Few studies have examined how various lifestyle factors in midlife predict longevity, and none of these studies have examined the impact of physical fitness. The present study aimed to examine longevity in relation to smoking, overweight and physical fitness.
We prospectively studied longevity (defined as reaching at least 85 years of age) in relation to smoking status, body mass index and physical fitness in 821 healthy men between 51 and 59 years of age. Of these, 369 were smokers, 320 were overweight, and 31 were obese. The associations were adjusted for age, systolic blood pressure and cholesterol level, using multivariate logistic regression analysis. Deaths were registered until the 31st of December, 2006. Physical fitness was measured as the total work performed in a maximal exercise tolerance bicycle test.
252 men survived to the age of 85 years (30.7%). Smoking status was significantly and independently related to longevity; 37.2% of the non-smokers survived to the age of 85, and 22.8% of the smokers. Among non-smokers, overweight and physical fitness were significantly and independently related to longevity after adjustment for age, blood pressure and cholesterol level, but not among smokers. Among non-smokers with high physical fitness, 48.8% reached the age of 85 years, compared to 27.9% among non-smokers with low physical fitness.
Lifestyle variables appear to be strong and independent predictors of longevity in initially healthy middle-aged men. The probability of longevity may be a useful concept when informing the general public about the benefits of a healthy lifestyle.
PMCID: PMC3846763  PMID: 24025031
Prospective; Healthy men; Smoking; Overweight; Fitness; Longevity
10.  Five-year mortality after acute poisoning treated in ambulances, an Emergency outpatient clinic and hospitals in Oslo 
The long-term mortality after prehospital treatment for acute poisoning has not been studied previously. Thus, we aimed to estimate the five-year mortality and examine the causes of death and predictors of death for all acutely poisoned patients treated in ambulances, the emergency outpatient clinic, and hospitals in Oslo during 2003–2004.
A prospective cohort study included all adults (≥16 years; n=2045, median age=35 years, male=58%) who were discharged after treatment for acute poisoning in ambulances, the emergency outpatient clinic, and the four hospitals in Oslo during one year. The patients were observed until the end of 2008. Standardized mortality rates (SMRs) were calculated and multivariate Cox regression analysis was applied.
The study comprised 2045 patients; 686 treated in ambulances, 646 treated in the outpatient clinic, and 713 treated in hospitals. After five years, 285 (14%) patients had died (four within one week). The SMRs after ambulance, outpatient, and hospital treatment were 12 (CI 9–14), 10 (CI 8–12), and 6 (CI 5–7), respectively. The overall SMR was 9 (CI 8–10), while the SMR after opioid poisoning was 27 (CI 21–32). The most frequent cause of death was accidents (38%). In the regression analysis, opioids as the main toxic agents (HR 2.3, CI 1.6–3.0), older age (HR 1.6, CI 1.5–1.7), and male sex (HR 1.4, CI 1.1–1.9) predicted death, whereas the treatment level did not predict death.
The patients had high mortality compared with the general population. Those treated in hospital had the lowest mortality. Opioids were the major predictor of death.
PMCID: PMC3846782  PMID: 23965589
Emergency medical services; Mortality; Opioids; Treatment level
11.  Prevalence and Risk Indicators for Anal Incontinence among Pregnant Women 
ISRN Obstetrics and Gynecology  2013;2013:947572.
The aim of this study was to assess the prevalence and risk factors of anal incontinence in an unselected pregnant population at second trimester. A survey of pregnant women attending a routine ultrasound examination was conducted in a university hospital in Oslo, Norway. A questionnaire consisting of 105 items concerning anal incontinence (including St. Mark's score), urinary incontinence, medication use, and comorbidity was posted to women when invited to the ultrasound examination. Results. Prevalence of self-reported anal incontinence (St. Mark's score ≥ 3) was the lowest in the group of women with a previous cesarean section only (6.4%) and the highest among women with a previous delivery complicated by obstetric anal sphincter injury (24.4%). Among nulliparous women the prevalence of anal incontinence was 7.7% and was associated to low educational level and comorbidity. Prevalence of anal incontinence increased with increasing parity. Urinary incontinence was associated with anal incontinence in all parity groups. Conclusions. Anal incontinence was most frequent among women with a history of obstetric anal sphincter injury. Other obstetrical events had a minor effect on prevalence of anal incontinence among parous women. Prevention of obstetrical sphincter injury is likely the most important factor for reducing bothersome anal incontinence among fertile women.
PMCID: PMC3681258  PMID: 23819058
12.  Incidence of obstetric anal sphincter injuries after training to protect the perineum: cohort study 
BMJ Open  2012;2(5):e001649.
To compare the incidence of obstetric anal sphincter injuries (OASIS) in two time periods, before and after implementing a training programme for improved perineal support aimed at reducing the incidence of obstetric anal sphincter injuries. The secondary aim was to study incidence of obstetric anal sphincter injuries in subgroups defined by risk factors for OASIS.
Population-based cohort study.
University hospital setting in Oslo, Norway.
Two cohorts of all delivering women in the largest hospital in Norway during two time periods (2003–2005 and 2008–2010) were studied. After excluding caesarean sections and preterm deliveries (< week 32), the study population consisted of 31 709 deliveries, among which 907 women were identified with obstetric anal sphincter injury.
Primary and secondary outcome measures
Incidence of OASIS in two time periods. Maternal, obstetrical and foetal risk factors for OASIS were collected from the hospital obstetric database. Univariate analyses and multivariate logistic regression analyses, presenting adjusted ODs for OASIS, were performed.
The OASIS incidence was significantly reduced by 50%, from 4% (591/14787) in the first time period to 1.9% (316/16 922) in the second. This reduction could not be explained by changes in population characteristics or OASIS risk factors during the study years. The reduction of incidence of OASIS between the two study periods was consistent across subgroups of women; regardless of parity, delivery method and infant birth weight.
A marked reduction in the incidence of OASIS was observed in all studied subgroups of women after implementing the training programme for perineal protection. Further, this reduction could not be explained by the differences in patient characteristics across the study period. These findings indicate that the training programme with improved perineal protection markedly reduced the risk of OASIS.
PMCID: PMC3488722  PMID: 23075573
Education & Training (see Medical Education & Training); Medical Education & Training; obstetric anal sphincter injury; delivery
13.  ZNF385B and VEGFA Are Strongly Differentially Expressed in Serous Ovarian Carcinomas and Correlate with Survival 
PLoS ONE  2012;7(9):e46317.
The oncogenesis of ovarian cancer is poorly understood. The aim of this study was to identify mRNAs differentially expressed between moderately and poorly differentiated (MD/PD) serous ovarian carcinomas (SC), serous ovarian borderline tumours (SBOT) and superficial scrapings from normal ovaries (SNO), and to correlate these mRNAs with clinical parameters including survival.
Differences in mRNA expression between MD/PD SC, SBOT and SNO were analyzed by global gene expression profiling (n = 23), validated by RT-qPCR (n = 41) and correlated with clinical parameters.
Thirty mRNAs differentially expressed between MD/PD SC, SBOT and SNO were selected from the global gene expression analyses, and 21 were verified (p<0.01) by RT-qPCR. Of these, 13 mRNAs were differentially expressed in MD/PD SC compared with SNO (p<0.01) and were correlated with clinical parameters. ZNF385B was downregulated (FC = −130.5, p = 1.2×10−7) and correlated with overall survival (p = 0.03). VEGFA was upregulated (FC = 6.1, p = 6.0×10−6) and correlated with progression-free survival (p = 0.037). Increased levels of TPX2 and FOXM1 mRNAs (FC = 28.5, p = 2.7×10−10 and FC = 46.2, p = 5.6×10−4, respectively) correlated with normalization of CA125 (p = 0.03 and p = 0.044, respectively). Furthermore, we present a molecular pathway for MD/PD SC, including VEGFA, FOXM1, TPX2, BIRC5 and TOP2A, all significantly upregulated and directly interacting with TP53.
We have identified 21 mRNAs differentially expressed (p<0.01) between MD/PD SC, SBOT and SNO. Thirteen were differentially expressed in MD/PD SC, including ZNF385B and VEGFA correlating with survival, and FOXM1 and TPX2 with normalization of CA125. We also present a molecular pathway for MD/PD SC.
PMCID: PMC3460818  PMID: 23029477
14.  Bone Turnover and Metabolism in Patients with Early Multiple Sclerosis and Prevalent Bone Mass Deficit: A Population-Based Case-Control Study 
PLoS ONE  2012;7(9):e45703.
Low bone mass is prevalent in ambulatory multiple sclerosis (MS) patients even shortly after clinical onset. The mechanism is not known, but could involve shared etiological risk factors between MS and low bone mass such as hypovitaminosis D operating before disease onset, or increased bone loss after disease onset. The aim of this study was to explore the mechanism of the low bone mass in early-stage MS patients.
Methodology/Principal Findings
We performed a population-based case-control study comparing bone turnover (cross-linked N-terminal telopeptide of type 1 collagen; NTX, bone alkaline phosphatase; bALP), metabolism (25-hydroxy- and 1, 25-dihydroxyvitamin D, calcium, phosphate, and parathyroid hormone), and relevant lifestyle factors in 99 patients newly diagnosed with clinically isolated syndrome (CIS) or MS, and in 159 age, sex, and ethnicity matched controls. After adjustment for possible confounders, there were no significant differences in NTX (mean 3.3; 95% CI −6.9, 13.5; p = 0.519), bALP (mean 1.6; 95% CI −0.2, 3.5; p = 0.081), or in any of the parameters related to bone metabolism in patients compared to controls. The markers of bone turnover and metabolism were not significantly correlated with bone mass density, or associated with the presence of osteoporosis or osteopenia within or between the patient and control groups. Intake of vitamin D and calcium, reported UV exposure, and physical activity did not differ significantly.
Bone turnover and metabolism did not differ significantly in CIS and MS patients with prevalent low bone mass compared to controls. These findings indicate that the bone deficit in patients newly diagnosed with MS and CIS is not caused by recent acceleration of bone loss, and are compatible with shared etiological factors between MS and low bone mass.
PMCID: PMC3446908  PMID: 23029191
15.  Oral health and mortality risk in the institutionalised elderly 
Objective: Examining oral health and oral hygiene as predictors of subsequent one-year survival in the institutionalized elderly. Design: It was hypothesized that oral health would be related to mortality in an institutionalized geriatric population. A 12-month prospective study of 292 elderly residing in nine geriatric institutions in Granada, Spain, was thus carried out to evaluate the association between oral health and mortality. Independent samples, T-test, chi-square test and Cox regression analysis were used to analyze the data. Sixty-three participants died during the 12-month follow-up. Results: Mortality was increased in denture users (RR = 2.18, p= 0.007) and in people suffering severe cognitive impairment (RR = 2. 24, p= 0.003). One-year mortality was 50% in participants having both these characteristics. Conclusions: Oral hygiene was not significantly associated with mortality. Cognitive impairment and wearing dentures increased the risk of death. One-year mortality was 50% in cognitively impaired residents wearing dentures as opposed to 10% in patients without dentures and cognitive impairment.
Key words:Oral health, mortality risk, institutionalised elderly.
PMCID: PMC3476025  PMID: 22322487
16.  Severe tooth wear in Prader-Willi syndrome. A case–control study 
BMC Oral Health  2012;12:12.
Prader-Willi syndrome (PWS) is a rare complex multsystemic genetic disorder characterized by severe neonatal hypotonia, endocrine disturbances, hyperphagia and obesity, mild mental retardation, learning disabilities, facial dysmorphology and oral abnormalities. The purpose of the present study was to explore the prevalence of tooth wear and possible risk factors in individuals with Prader-Willi syndrome.
Forty-nine individuals (6-40 years) with PWS and an age- and sex-matched control group were included. Tooth wear was evaluated from dental casts and intraoral photographs and rated by four examiners using the Visual Erosion Dental Examination (VEDE) scoring system and the individual tooth wear index IA. In accordance with the VEDE scoring system, tooth wear was also evaluated clinically. Whole saliva was collected.
Mean VEDE score was 1.70 ± 1.44 in the PWS group and 0.46 ± 0.36 in the control group (p < 0.001). Median IA was 7.50 (2.60-30.70) in the PWS group and 2.60 (0.90-4.70) among controls (p < 0.001). In the PWS group tooth wear correlated significantly with age (VEDE; r = 0.79, p < 0.001, IA; r = 0.82, p < 0.001) and saliva secretion (VEDE; r = 0.46, p = 0.001, IA; r = 0.43, p = 0.002). Tooth grinding was also associated with tooth wear in the PWS group, as indicated by the mean VEDE 2.67 ± 1.62 in grinders and 1.14 ± 0.97 in non-grinders (p = 0.001) and median IA values 25.70 (5.48-68.55) in grinders and 5.70 (1.60-9.10) in non-grinders (p = 0.003). Multivariate linear regression analysis was performed with tooth wear as the dependent variable and PWS (yes/no), age, tooth grinding and saliva secretion as independent variables. PWS (yes/no), age and tooth grinding retained a significant association with tooth wear, VEDE (p < 0.001) and log IA (p < 0.001). The only factor significantly associated with tooth wear in the control group was age.
Our study provides evidence that tooth wear, in terms of both erosion and attrition, is a severe problem in Prader-Willi syndrome. There is therefore considerable need for prosthodontic rehabilitation in young adults with PWS.
PMCID: PMC3437195  PMID: 22639910
Prader-Willi syndrome; Tooth wear; Tooth grinding; Saliva secretion; Rehabilitation
17.  Mortality and health-related quality of life in prevalent dialysis patients: Comparison between 12-items and 36-items short-form health survey 
To assess health- related quality of life (HRQOL) with SF-12 and SF-36 and compare their abilities to predict mortality in chronic dialysis patients, after adjusting for traditional risk factors.
The Short-Form Health Survey (SF-36) with the embedded SF-12 was applied in 301 dialysis patients cross-sectionally. Physical and mental component summary (PCS-36, MCS-36, PCS-12, and MCS-12) scores were calculated. Clinical and demographic data were collected. Mortality (followed for up to 4.5 years) was analyzed with Kaplan Meier plots and Cox proportional hazards, after censoring for renal transplantation. Exclusion factors were observation time <2 months (n = 21) and missing component summary scores (n = 10 for SF-36; n = 28 for SF-12), thus 252 patient were included in the analyses.
In 252 patients (60.2 ± 15.5 years, 65.9% males, dialysis vintage 9.0, IQR 5.0-23.0 months), mortality during follow-up was 33.7%.(85 deaths). Significant correlations were observed between PCS-36 and PCS-12 (ρ = 0.93, p < 0.001) and between MCS-36 and MCS-12 (ρ = 0.95, p < 0.001). Mortality rate was highest in patients in the lowest quartile of PCS-12 (χ2 = 15.3, p = 0.002) and PCS-36 (χ2 = 16.7, p = 0.001). MCS was not associated with mortality. Adjusted hazard ratios for mortality were 2.5 (95% CI 1.0-6.3, PCS-12) and 2.7 (1.1 – 6.4, PCS-36) for the lowest compared with the highest (“best perceived”) quartile of PCS.
Compromised HRQOL is an independent predictor of poor outcome in dialysis patients. The SF-12 provided similar predictions of mortality as SF-36, and may serve as an applicable clinical tool because it requires less time to complete.
PMCID: PMC3464967  PMID: 22559816
Chronic kidney disease; Dialysis; Health-related quality of life; Mortality; Physical component summary score; SF-12 and SF-36
18.  The Impact of Oral Health on Taste Ability in Acutely Hospitalized Elderly 
PLoS ONE  2012;7(5):e36557.
To investigate to what extent various oral health variables are associated with taste ability in acutely hospitalized elderly.
Impaired taste may contribute to weight loss in elderly. Many frail elderly have poor oral health characterized by caries, poor oral hygiene, and dry mouth. However, the possible influence of such factors on taste ability in acutely hospitalized elderly has not been investigated.
Materials and Methods
The study was cross-sectional. A total of 174 (55 men) acutely hospitalized elderly, coming from their own homes and with adequate cognitive function, were included. Dental status, decayed teeth, oral bacteria, oral hygiene, dry mouth and tongue changes were recorded. Growth of oral bacteria was assessed with CRT® Bacteria Kit. Taste ability was evaluated with 16 taste strips impregnated with sweet, sour, salty and bitter taste solutions in 4 concentrations each. Correct identification was given score 1, and maximum total taste score was 16.
Mean age was 84 yrs. (range 70–103 yrs.). Total taste score was significantly and markedly reduced in patients with decayed teeth, poor oral hygiene, high growth of oral bacteria and dry mouth. Sweet and salty taste were particularly impaired in patients with dry mouth. Sour taste was impaired in patients with high growth of oral bacteria.
This study shows that taste ability was reduced in acutely hospitalized elderly with caries activity, high growth of oral bacteria, poor oral hygiene, and dry mouth. Our findings indicate that good oral health is important for adequate gustatory function. Maintaining proper oral hygiene in hospitalized elderly should therefore get high priority among hospital staff.
PMCID: PMC3343000  PMID: 22570725
20.  Surgery with disc prosthesis versus rehabilitation in patients with low back pain and degenerative disc: two year follow-up of randomised study 
Objective To compare the efficacy of surgery with disc prosthesis versus non-surgical treatment for patients with chronic low back pain.
Design A prospective randomised multicentre study.
Setting Five university hospitals in Norway.
Participants 173 patients with a history of low back pain for at least one year, Oswestry disability index of at least 30 points, and degenerative changes in one or two lower lumbar spine levels (86 patients randomised to surgery). Patients were treated from April 2004 to September 2007.
Interventions Surgery with disc prosthesis or outpatient multidisciplinary rehabilitation for 12-15 days.
Main outcome measures The primary outcome measure was the score on the Oswestry disability index after two years. Secondary outcome measures were low back pain, satisfaction with life (SF-36 and EuroQol EQ-5D), Hopkins symptom check list (HSCL-25), fear avoidance beliefs (FABQ), self efficacy beliefs for pain, work status, and patients’ satisfaction and drug use. A blinded independent observer evaluated scores on the back performance scale and Prolo scale at two year follow-up.
Results The study was powered to detect a difference of 10 points on the Oswestry disability index between the groups at two years. At two years there was a mean difference of −8.4 points (95% confidence interval −13.2 to −3.6) in favour of surgery. In the analysis of prespecified secondary outcomes, there were significant differences in favour of surgery for low back pain (mean difference −12.2, −21.3 to −3.1), patients’ satisfaction (63% (n=46) v 39% (n=26)), SF-36 physical component score (mean difference 5.8, 2.5 to 9.1), self efficacy for pain (mean difference 1.0, 0.2 to 1.9), and the Prolo scale (mean difference 0.9, 0.1 to 1.6). There were no significant differences in return to work, SF-36 mental component score, EQ-5D, fear avoidance beliefs, Hopkins symptom check list, drug use, and the back performance scale. One serious complication of leg amputation occurred during surgical revision of a polyethylene dislodgement. The drop-out rate was 20% (34) and the crossover rate was 6% (5).
Conclusions Surgical intervention with disc prosthesis for chronic low back pain resulted in a significantly greater improvement in the Oswestry score compared with rehabilitation, but this improvement did not clearly exceed the prespecified minimally important clinical difference between groups of 10 points, and the data are consistent with a wide range of differences between the groups, including values well below 10 points. The potential risks of surgery and the substantial amount of improvement experienced by a sizeable proportion of the rehabilitation group also have to be incorporated into overall decision making.
Trial registration NCT 00394732.
PMCID: PMC3100911  PMID: 21596740
21.  The casualty chain inventory: a new scale for measuring peritraumatic responses: a cross-sectional study 
Peritraumatic psychological- and sensory impressions in victims of civilian accidents are only partly understood. This study scrutinizes the level and duration of perceived psychological threat at scene of injury as well as in hospital (the casualty chain) measured by the Casualty Chain Inventory (CCI). The purpose of the study was to assess and validate the CCI, and to examine the correlations between the new instrument and stress responses measured by the Impact of Event Scale (IES) and the Post-traumatic Stress Scale-10 (PTSS-10)
Three hundred and fifteen injured, conscious, hospitalised patients were assessed with a self-report questionnaire. The CCI consists of eight items including sensory impressions and well-known psychological responses to trauma.
The internal consistency of the CCI was solid (Cronbach's alpha: .83-.85). A factor analysis revealed two components, "perception" and "dissociation". The instrument correlates significantly with the Impact of Event Scale (r = 0.47 - 0.54) and the Posttraumatic Stress Scale-10 (r = 0.32 - 0.50). The explained variance is high both at the scene of injury (61%) and in the hospital (65%). Dissociation and perception either used as a two-factor solution or as a sum score measured in the hospital, gave the strongest prediction for later psychological distress.
The CCI appears to be a useful screening instrument for, at an early state, identifying patients hospitalized after a physical incident at risk for subsequent psychological distress.
PMCID: PMC3124412  PMID: 21592327
22.  Parametric methods outperformed non-parametric methods in comparisons of discrete numerical variables 
The number of events per individual is a widely reported variable in medical research papers. Such variables are the most common representation of the general variable type called discrete numerical. There is currently no consensus on how to compare and present such variables, and recommendations are lacking. The objective of this paper is to present recommendations for analysis and presentation of results for discrete numerical variables.
Two simulation studies were used to investigate the performance of hypothesis tests and confidence interval methods for variables with outcomes {0, 1, 2}, {0, 1, 2, 3}, {0, 1, 2, 3, 4}, and {0, 1, 2, 3, 4, 5}, using the difference between the means as an effect measure.
The Welch U test (the T test with adjustment for unequal variances) and its associated confidence interval performed well for almost all situations considered. The Brunner-Munzel test also performed well, except for small sample sizes (10 in each group). The ordinary T test, the Wilcoxon-Mann-Whitney test, the percentile bootstrap interval, and the bootstrap-t interval did not perform satisfactorily.
The difference between the means is an appropriate effect measure for comparing two independent discrete numerical variables that has both lower and upper bounds. To analyze this problem, we encourage more frequent use of parametric hypothesis tests and confidence intervals.
PMCID: PMC3097007  PMID: 21489231
23.  Serum cytokine and glucose levels as predictors of poststroke fatigue in acute ischemic stroke patients 
Journal of Neurology  2011;258(4):670-676.
Fatigue is a common but often overlooked symptom after stroke. This study investigated whether stroke type, infarct volume, and laterality, as well as the levels of various cytokines and other blood components in the acute phase of acute ischemic stroke (AIS), can predict the level of fatigue at 6, 12, and 18 months after its onset. In 45 patients with acute stroke, serum levels of C-reactive protein, hemoglobin, glucose, and 13 cytokines were measured within 72 h of stroke onset. The cytokine measurements were performed using BioPlex XMap technology (Luminex). The acute serum levels of interleukin (IL)-1β and glucose were positively correlated with the score on the Fatigue Severity Scale (FSS) at 6 months after the stroke (r = 0.37, p = 0.015, and r = 0.37, p = 0.017, respectively). The acute serum levels of IL-ra and IL-9 were negatively correlated with FSS score at 12 months after the stroke (r = −0.38, p = 0.013, and r = −0.36, p = 0.019, respectively). The FSS score at 12 months after stroke was significantly lower in patients with radiologically confirmed infarction than in those without such confirmation (p = 0.048). The FSS score at 18 months was not correlated with any of the measured variables. High acute serum levels of glucose and IL-1β, and low IL1-ra and IL-9 may predict fatigue after AIS, indicating that the development of poststroke fatigue can be accounted for by the proinflammatory response associated with AIS. These novel findings support a new cytokine theory of fatigue after stroke. However, more research is needed to validate the results of this study.
PMCID: PMC3065647  PMID: 21365457
Acute ischemic stroke; Inflammation; Cytokines; Proinflammatory; Anti-inflammatory
24.  Cardiac magnetic resonance visualizes acute and chronic myocardial injuries in myocarditis 
Our objective was to evaluate the ability of CMR to visualize myocardial injuries over the course of myocarditis. We studied 42 patients (39 males, 3 females; age 37 ± 14 years) with myocarditis during the acute phase and after 12 ± 9 months. CMR included function analyses, T2-weighted imaging (T2 ratio), T1-weighted imaging before and after i.v. gadolinium injection (global relative enhancement; gRE), and late gadolinium enhancement (LGE). In the acute phase, the T2 ratio was elevated in 57%, gRE in 31%, and LGE was present in 64% of the patients. In 32 patients (76%) were any two (or more) out of three sequences abnormal. At follow-up, there was an increase in ejection fraction (57.4 ± 11.9% vs. 61.4 ± 7.6; P < 0.05) while both T2 ratio (2.04 ± 0.32 vs. 1.70 ± 0.28; P < 0.001) and gRE (4.07 ± 1.63 vs. 3.11 ± 1.22; P < 0.05) significantly decreased. The LGE persisted in 10 patients. Dilated cardiomyopathy was present in 3 patients and 4 patients received a defibrillator or a pacemaker. A comprehensive CMR approach is a useful tool to visualize myocardial tissue injuries over the course of myocarditis. CMR may help to differentiate acute from healed myocarditis, and add information for the differential diagnoses.
PMCID: PMC3288366  PMID: 21347598
Myocarditis; Coronary angiography; Cardiac magnetic resonance; Myocardial injury; Differential diagnosis
25.  Effects of acute substance use and pre-injury substance abuse on traumatic brain injury severity in adults admitted to a trauma centre 
The aims of this study were to describe the occurrence of substance use at the time of injury and pre-injury substance abuse in patients with moderate-to-severe traumatic brain injury (TBI). Effects of acute substance use and pre-injury substance abuse on TBI severity were also investigated.
A prospective study of 111 patients, aged 16-55 years, injured from May 2005 to May 2007 and hospitalised at the Trauma Referral Centre in Eastern Norway with acute TBI (Glasgow Coma Scale 3-12). Based on structural brain damages shown on a computed tomography (CT) scan, TBI severity was defined by modified Marshall classification as less severe (score <3) and more severe (score ≥3). Clinical definition of substance use (alcohol and/or other psychoactive substances) was applied when hospital admission records reflected blood alcohol levels or a positive drug screen, or when a physician verified influence by examining the patient. Pre-injury substance abuse (alcohol and drug problems) was screened by using the CAGE questionnaire.
Forty-seven percent of patients were positive for substance use on admission to hospital. Significant pre-injury substance abuse was reported by 26% of patients. Substance use at the time of injury was more frequent in the less severe group (p = 0.01). The frequency of pre-injury substance abuse was higher in the more severe group (30% vs. 23%). In a logistic regression model, acute substance use at time of injury tended to decrease the probability of more severe intracranial injury, but the effect was not statistically significant after adjusting for age, gender, education, cause of injury and substance abuse, OR = 0.39; 95% CI 0.11-1.35, p = 0.14. Patients with positive screens for pre-injury substance abuse (CAGE ≥2) were more likely to have more severe TBI in the adjusted regression analyses, OR = 4.05; 95% CI 1.10-15.64, p = 0.04.
Acute substance use was more frequent in patients with less severe TBI caused by low-energy events such as falls, violence and sport accidents. Pre-injury substance abuse increased the probability of more severe TBI caused by high-energy trauma such as motor vehicle accidents and falls from higher levels. Preventive efforts to reduce substance consumption and abuse in at-risk populations are needed.
PMCID: PMC2890596  PMID: 20504353

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