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Ingvild Dalen

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Universidade do Porto

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The University of Georgia

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Papers by Ingvild Dalen

Complement activation correlates to disease severity and contribute to cytokine response in falciparum malaria

by Mauro Prato and Ingvild Dalen

Journal of Infectious Diseases, 2015

The impact of complement activation and its possible relation to cytokine responses in malaria pa... more The impact of complement activation and its possible relation to cytokine responses in malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria, and in human whole blood stimulated with malaria relevant agents ex vivo. Complement was significantly activated in the malaria cohort as compared to healthy controls, positively correlated to disease severity, and with certain cytokines, in particular IL-8/CXCL8. This was confirmed in ex vivo-stimulated blood where complement inhibition significantly reduced IL-8/CXCL8 release. Plasmodium falciparum malaria is associated with a systemic complement activation and complement-dependent release of inflammatory cytokines, of which IL-8/CXCL8 is particularly prominent. by guest on September 16, 2016 http://jid.oxfordjournals.org/ Downloaded from by guest on September 16, 2016 http://jid.oxfordjournals.org/ Downloaded from

Loss of Dopamine Transporter Binding and Clinical Symptoms in Dementia With Lewy Bodies

Movement Disorders, 2015

Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies... more Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies. The aim of this study was to explore the association between loss of striatal dopamine transporter binding and symptoms in dementia with Lewy bodies. Thirty-five patients with dementia with Lewy bodies underwent single-photon emission computerized tomography brain imaging with N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([(123) I]FP-CIT). Associations between striatal binding ratios and motor (UPDRS), psychiatric (Neuropsychiatric Inventory; [NPI]), and cognitive (Mini-Mental State Examination [MMSE] and neuropsychological tests) symptoms were assessed by linear regression analysis. The explorative analysis showed that the motor UPDRS was negatively associated with putamen dopamine transporter binding, whereas no association with striatal dopamine transporter binding was found for total NPI, hallucinations, apathy, depression, anxiety, and MMSE scores. However, in post-hoc analysis, executive impairment was positively associated with dopamine transporter loss after adjustment of age and gender. Dopamine deficiency in patients with dementia with Lewy bodies was associated with severity of motor symptoms, but did not correlate significantly with ratings of neurobehavioral disturbances or overall cognition. © 2015 International Parkinson and Movement Disorder Society.

Encouraging adolescents to contact their GP: a community-based trial

by Ingvild Dalen and Ole Haavet

British Journal of General Practice

Adolescents, especially males, often fail to see their GP. To determine whether an informative le... more Adolescents, especially males, often fail to see their GP. To determine whether an informative letter could enhance the accessibility and utilisation of healthcare facilities and services. A community-based trial in one town in Oslo, using a retrospective control group. GPs in one town in Oslo sent a personal, informative letter at the beginning of 2008 and 2009 to individuals in their practice population who were turning 16 years of age that year. The pooled data for the same year for each surgery were collected. Retrospective data from 1990 and 1991 served as controls for the intervention groups of data collected in 2006 and 2007 respectively. An International Classification of Primary Care-2 diagnosis was given for each contact. The proportion of adolescents in contact with a GP increased from 59% in the control group to 69% in the intervention group (P<0.001). For the males, the increase was from 54% to 72% (P<0.001). This reduced sex differences in healthcare seeking. For...

Improving antibiotic prescribing in acute respiratory tract infections: cluster randomised trial from Norwegian general practice (prescription peer academic detailing (Rx-PAD) study)

by Ingvild Dalen and Jørund Straand

BMJ (online)

To assess the effects of a multifaceted educational intervention in Norwegian general practice ai... more To assess the effects of a multifaceted educational intervention in Norwegian general practice aiming to reduce antibiotic prescription rates for acute respiratory tract infections and to reduce the use of broad spectrum antibiotics. Cluster randomised controlled study. Existing continuing medical education groups were recruited and randomised to intervention or control. 79 groups, comprising 382 general practitioners, completed the interventions and data extractions. The intervention groups had two visits by peer academic detailers, the first presenting the national clinical guidelines for antibiotic use and recent research evidence on acute respiratory tract infections, the second based on feedback reports on each general practitioner's antibiotic prescribing profile from the preceding year. Regional one day seminars were arranged as a supplement. The control arm received a different intervention targeting prescribing practice for older patients. Prescription rates and proport...

Pelvic girdle pain 3-6 months after delivery in an unselected cohort of Norwegian women

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, Jan 22, 2015

Persistent pelvic girdle pain (PGP) after delivery is considered uncommon. The aim of this study ... more Persistent pelvic girdle pain (PGP) after delivery is considered uncommon. The aim of this study was to assess the frequency of persistent PGP after delivery in an unselected population, its influence on the women's daily life, and potential risk factors. The study population was drawn from a previous retrospective study of pelvic pain (PP) during pregnancy. The women were followed until 3-6 months after delivery in a prospective cohort study. All women were contacted by telephone and those with persistent PP were invited to fill in questionnaires and undergo a clinical examination. 68 of 330 women reported persistent pain in the pelvic area 3-6 months after delivery. 47 underwent a clinical examination, after which 36 women were diagnosed with either PGP alone (n = 25), or PGP combined with low back pain (LBP) (n = 11). Affected women reported a poor subjective health status, but the pain did not have a major impact on their daily life activities. Women with 3 independent risk ...

A cluster-randomized educational intervention to reduce inappropriate prescription patterns for elderly patients in general practice--The Prescription Peer Academic Detailing (Rx-PAD) study [NCT00281450]

by Ingvild Dalen, Jørund Straand, and Mette Brekke

BMC health services research, 2006

Age-related alterations in metabolism and excretion of medications increase the risk of adverse d... more Age-related alterations in metabolism and excretion of medications increase the risk of adverse drug events in the elderly. Inappropriate polypharmacy and prescription practice entails increased burdens of impaired quality of life and drug related morbidity and mortality. The main objective of this trial is to evaluate effects of a tailored educational intervention towards general practitioners (GPs) aimed at supporting the implementation of a safer drug prescribing practice for elderly patients > or = 70 years. Approximately 80 peer continuing medical education (CME) groups (about 600 GPs) in southern Norway will be recruited to a cluster randomized trial. Participating groups will be randomized either to an intervention- or a control group. The control group will not receive any intervention towards prescription patterns in elderly, but will be the target of an educational intervention for prescription of antibiotics for respiratory tract infections. A multifaceted intervention...

Persistence and Prognostic Implications of Orthostatic Hypotension in Older Individuals with Mild-to-Moderate Dementia

Dementia and geriatric cognitive disorders extra

To study the course and prognostic implications of orthostatic hypotension (OH) in older individu... more To study the course and prognostic implications of orthostatic hypotension (OH) in older individuals with mild-to-moderate dementia. Referrals to outpatient clinics specialising in old age psychiatry and geriatric medicine in the counties of Rogaland and Hordaland in western Norway with a first-time diagnosis of mild dementia were consecutively asked for inclusion. A total of 211 participants underwent a comprehensive baseline assessment with annual follow-ups. Patients with OH at both baseline and the 1-year follow-up were classified as having persistent OH. Outcome measures were the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating sum of boxes (CDR-SB), and time to death. From baseline to the 4-year follow-up, 30-45% of the participants had OH at each follow-up. In multivariable analysis, persistent OH was not significantly associated with either the longitudinal course of MMSE or CDR-SB scores or survival. OH was moderately prevalent over 4 years in older indivi...

Vitamin D status in recently arrived immigrants from Africa and Asia: a cross-sectional study from Norway of children, adolescents and adults

BMJ open, 2013

To estimate the prevalence of vitamin D deficiency (25(OH)D) <50 nmol/L among recently arrived... more To estimate the prevalence of vitamin D deficiency (25(OH)D) <50 nmol/L among recently arrived immigrants from Africa and Asia in Oslo, and to explore 25(OH)D levels according to origin, gender and age. A cross-sectional study. Primary healthcare unit in Oslo, Norway, offering family immigrants, asylum seekers, United Nations (UN) refugees or individuals granted asylum a free medical examination on arrival. All individuals from African and Asian countries (n=591) referred to the Centre of Migrant Health, Health Agency, Oslo, Norway in 2010, estimated to cover 60% of the targeted population. 25(OH)D <50 nmol/L was very prevalent in immigrants from the Middle East (81% (95% CI 75.4% to 86.6%)), South Sahara Africa (73% (CI 67.5% to 78.5%)) and South Asia (75% (CI 64.0% to 86.0%)), in contrast to East Asians (24% (CI 12.6% to 35.4%)), p<0.001 for differences. The prevalence of 25(OH)D<25 nmol/L was lower but followed the same pattern (Middle East: 38% (CI 31.1% to 45.0%), S...

Are children carrying the burden of broad-spectrum antibiotics in general practice? Prescription pattern for paediatric outpatients with respiratory tract infections in Norway

BMJ open, 2013

To investigate the antibiotic prescription pattern and factors that influence the physicians'... more To investigate the antibiotic prescription pattern and factors that influence the physicians' choice of antibiotic. Observational study. Primary healthcare in Norway, December 2004 through November 2005. 426 general practitioners, GPs, in Norway, giving 24 888 respiratory tract infection episodes with 19 938 children aged 0-6 years. Assess antibiotic prescription details and patient and GP characteristics associated with broad-spectrum and narrow-spectrum antibiotic use. Of the 24 888 episodes in the study, 26.2% (95% CI 25.7% to 26.8%) included an antibiotic prescription. Penicillin V accounted for 42% and macrolide antibiotics for 30%. The prescription rate varied among the physicians, with a mean of 25.5% (95% CI 24.2% to 26.7%). Acute tonsillitis gave the highest odds for a prescription, OR 33.6 (95% CI 25.7% to 43.9%), compared to 'acute respiratory tract infections and symptoms' as a reference group. GPs with a prescription rate of 33.3% or higher had the larger pr...

Symptom reporting in a general population in Norway: results from the Ullensaker study

by Ingvild Dalen and Jørund Straand

Scandinavian journal of primary health care, 2013

To determine the number of symptoms experienced in an adult population and their relationship wit... more To determine the number of symptoms experienced in an adult population and their relationship with self- reported health, demographic, and lifestyle factors. A postal questionnaire addressing 23 different symptoms, health, demographic, and lifestyle factors. The community of Ullensaker, Norway, in 2004. Subjects. 3325 subjects (participation rate = 54.4%). Number of self-reported symptoms. At least one symptom was reported by 91.9% of the participants, 46.7% reported six or more, and 17.3% reported 10 or more symptoms. Symptom reporting was frequent in all age groups, also among young people. Women reported a greater mean number of symptoms than men (6.7 vs. 5.1). Those reporting poor health, receipt of social security benefit, unemployment, low education, or obesity had most symptoms. The proportion of respondents with these characteristics increased almost linearly with increasing number of symptoms. According to an adjusted multivariate model, self-reported overall health explain...

Can antibiotic prescriptions in respiratory tract infections be improved? A cluster-randomized educational intervention in general practice--the Prescription Peer Academic Detailing (Rx-PAD) Study [NCT00272155]

by Ingvild Dalen and Jørund Straand

BMC health services research, 2006

More than half of all antibiotic prescriptions in general practice are issued for respiratory tra... more More than half of all antibiotic prescriptions in general practice are issued for respiratory tract infections (RTIs), despite convincing evidence that many of these infections are caused by viruses. Frequent misuse of antimicrobial agents is of great global health concern, as we face an emerging worldwide threat of bacterial antibiotic resistance. There is an increasing need to identify determinants and patterns of antibiotic prescribing, in order to identify where clinical practice can be improved. Approximately 80 peer continuing medical education (CME) groups in southern Norway will be recruited to a cluster randomized trial. Participating groups will be randomized either to an intervention- or a control group. A multifaceted intervention has been tailored, where key components are educational outreach visits to the CME-groups, work-shops, audit and feedback. Prescription Peer Academic Detailers (Rx-PADs), who are trained GPs, will conduct the educational outreach visits. During...

Ethnic differences in obesity among immigrants from developing countries, in Oslo, Norway

International journal of obesity (2005), 2006

To compare ethnic and gender differences in generalized and central obesity and to investigate wh... more To compare ethnic and gender differences in generalized and central obesity and to investigate whether these differences persisted after adjusting for socio-demographic and lifestyle factors. In 2002, the population-based cross-sectional, Oslo Immigrant Health study was conducted. A total of 7890 Oslo residents, born between 1942 and 1971 in Turkey, Iran, Pakistan, Sri Lanka and Vietnam, were invited and 3019 attended. Participants completed a health questionnaire and attended a clinical screening that included height, weight, waist and hip measurements. Generalized obesity (BMI> or =30 kg/m2) was greatest among women from Turkey (51.0%) and least among men from Vietnam (2.7%). The highest proportions of central obesity (waist hip ratio (WHR)>or =0.85) were observed among women from Sri Lanka (54.3%) and Pakistan (52.4%). For any given value of BMI, Sri Lankans and Pakistanis had higher WHR compared to the other groups. Despite a high mean BMI, Turkish men (27.9 kg/m2) and wom...

C2 monitoring in maintenance renal transplant recipients: is it worthwhile?

Transplantation, Jan 27, 2003

Presently, there is little knowledge regarding cyclosporine (CsA) concentration at 2 hr post-dose... more Presently, there is little knowledge regarding cyclosporine (CsA) concentration at 2 hr post-dose (C2) monitoring in maintenance patients. This study evaluates the actual C2 range in stable renal transplant recipients (who underwent transplantation >12 months ago). In addition, we investigated whether underexposure or overexposure to CsA (assessed by C2) affects graft function (as measured by serum [S]-creatinine). All renal transplant recipients in Norway receiving CsA were asked to participate; 1447 fulfilled the criteria. Valid C2 and CsA trough concentration (C0) measurements were performed in 1032 renal transplant recipients (71%) monitored by C0. Target C0 level was 75 to 125 mumol/L. CsA levels were measured using a Cloned Enzyme Donor Immunoassay method, and all analyses were performed in the same laboratory (overall mean [+/-standard deviation] CsA C0=112+/-31 mug/L, CsA C2=697+/-211 mug/L [range 81-1580 mug/L], CsA dose [mg/day]=208+/-61, CsA dose [mg/kg/day]=2.8+/-1.1,...

The long-term development of non-motor problems after STN-DBS

Acta Neurologica Scandinavica, 2015

Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term benef... more Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term beneficial effects on motor symptoms in patients with Parkinson&amp;amp;#39;s disease (PD). The long-term development of non-motor problems after STN-DBS is not fully understood. In this study, we have studied how non-motor problems develop in patients with and without STN-DBS. We collected data from a prospectively followed cohort of patients that had been operated with STN-DBS 6-9 years before final examination and compared our findings to the longitudinal development of non-motor problems in a non-operated, comparable reference population. In general, the non-motor problems of advanced PD seem to develop independently of treatment with STN-DBS. We found that depressions do not worsen after STN-DBS, and the Montgomery and Aasberg Depression Rating Scale score in operated patients was substantially reduced from pre-operatively to post-operatively. Further, fatigue may represent an important unrecognized side effect of long-term stimulation, as fatigue was found to increase rapidly in operated patients already a year after surgery and continued to increase trough the 6- to 9-year follow-up. The non-motor problems of advanced PD seem to develop independently of treatment with STN-DBS. This may influence the strategy for choice of when to perform this therapy for eligible patients.

Motor symptoms after deep brain stimulation of the subthalamic nucleus

Acta Neurologica Scandinavica, 2014

Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term benef... more Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term beneficial effects on motor symptoms in patients with Parkinson&amp;amp;#39;s disease (PD). The efficacy of STN-DBS on non-dopaminergic motor symptoms remains less elucidated. In this study, we have examined short- and long-term impacts of STN-DBS on the development of the postural instability and gait difficulties (PIGD) phenotype, freezing of gait (FOG), and falls. We collected data from a prospectively followed cohort of patients that had been operated with STN-DBS 6-9 years before final examination and compared our findings to the longitudinal development of the same symptoms in a non-operated, historical reference population. During short-term follow-up after surgery, we observed a marked improvement in mean UPDRS-motor score from 27 to 18. We also found clear improvements in tremor, bradykinesia, rigidity, and PIGD scores. However, 6-9 years after surgery, all patients had a dominating PIGD pattern of parkinsonism and 50% of the patients had developed FOG and/or had become recurrent fallers. The disease development in a group of patients with PD from the presurgery period had a similar trajectory as among the operated patients. In addition, mean annual change of both bradykinesia and PIGD scores was nearly identical in both study groups while tremor and rigidity had a significant better development in the operated patients. We found that STN-DBS induces an acute improvement of PIGD symptoms. The following long-term development was however characterized by a marked progression of non-dopaminergic symptoms.

Psychosocial factors and distress: a comparison between ethnic Norwegians and ethnic Pakistanis in Oslo, Norway

BMC public health, 2006

In the Norwegian context, higher mental distress has been reported for the non-Western immigrants... more In the Norwegian context, higher mental distress has been reported for the non-Western immigrants compared to the ethnic Norwegians and Western immigrants. This high level of distress is often related to different socio-economic conditions in this group. No efforts have been made earlier to observe the impact of changed psychosocial conditions on the state of mental distress of these immigrant communities due to the migration process. Therefore, the objective of the study was to investigate the association between psychological distress and psychosocial factors among Pakistani immigrants and ethnic Norwegians in Oslo, and to investigate to what extent differences in mental health could be explained by psychosocial and socioeconomic conditions. Data was collected from questionnaires as a part of the Oslo Health Study 2000-2001. 13581 Norwegian born (attendance rate 46%) and 339 ethnic Pakistanis (attendance rate 38%) in the selected age groups participated. A 10-item version of Hopki...

Regression analysis with categorized regression calibrated exposure: some interesting findings

by Ingvild Dalen and Anette Hjartåker

Emerging themes in epidemiology, 2006

Regression calibration as a method for handling measurement error is becoming increasingly well-k... more 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 depressio...

Sensitivity of regression calibration to non-perfect validation data with application to the Norwegian Women and Cancer Study

by Ingvild Dalen and Anette Hjartåker

Statistics in medicine, Jan 15, 2015

Measurement error occurs when we observe error-prone surrogates, rather than true values. It is c... more Measurement error occurs when we observe error-prone surrogates, rather than true values. It is common in observational studies and especially so in epidemiology, in nutritional epidemiology in particular. Correcting for measurement error has become common, and regression calibration is the most popular way to account for measurement error in continuous covariates. We consider its use in the context where there are validation data, which are used to calibrate the true values given the observed covariates. We allow for the case that the true value itself may not be observed in the validation data, but instead, a so-called reference measure is observed. The regression calibration method relies on certain assumptions.This paper examines possible biases in regression calibration estimators when some of these assumptions are violated. More specifically, we allow for the fact that (i) the reference measure may not necessarily be an 'alloyed gold standard' (i.e., unbiased) for the ...

Cytokine Network in Adults with Falciparum Malaria and HIV-1: Increased IL-8 and IP-10 Levels Are Associated with Disease Severity

by Ingvild Dalen and Nina Langeland

PLoS ONE, 2014

Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the ... more Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection. This was a prospective cross-sectional study. Clinical data and blood samples were collected from adults in Mozambique. Plasma was analysed for 21 classical pro- and anti-inflammatory cytokines, including interleukins, interferons, and chemokines. We included 212 in-patients with fever and/or suspected malaria and 56 healthy controls. Falciparum malaria was diagnosed in 131 patients, of whom 70 were co-infected with HIV-1. The malaria patients had marked increases in their cytokine responses compared with the healthy controls. Some of these changes, particularly interleukin 8 (IL-8) and interferon-γ-inducing protein 10 (IP-10) were strongly associated with falciparum malaria and disease severity. Both these chemokines were markedly increased in patients with falciparum malaria as compared with healthy controls, and raised levels of IL-8 and IP-10 were associated with increased disease severity, even after adjusting for relevant confounders. For IL-8, particularly high levels were found in malaria patients that were co-infected with HIV and in those who died during hospitalization. Our findings underscore the complex role of inflammation during infection with P. falciparum, and suggest a potential pathogenic role for IL-8 and IP-10. However, the correlations do not necessarily mean any causal relationship, and further both clinical and mechanistic research is necessary to elucidate the role of cytokines in pathogenesis and protection during falciparum malaria.

Correction for misclassification of a categorized exposure in binary regression using replication data

Statistics in Medicine, 2009

Continuous epidemiologic exposure data are often categorized according to one or more cut points ... more Continuous epidemiologic exposure data are often categorized according to one or more cut points before inclusion in a regression analysis involving some outcome variable. If the original data are subject to measurement error, the categorized data will be afflicted with misclassification, which is differential, and which induces biases in naïve methods that ignore the misclassification. We propose a method for measurement error adjustment in these settings, when there are replicate data available on the original measurements, and when the outcome variable is dichotomous. Working on the continuous measurements, conditional densities of the exposure given the outcome are estimated and used to obtain odds ratios. The estimation of densities is done either parametrically or nonparametrically. The method is compared with the naïve approach of simply categorizing the erroneous mean measurements in simulation studies, and although the nonparametric method is more variable, it has the best overall performance, the greatest differences being observed in settings where the effects and/or the measurement errors are large. The performance of the parametric method is highly dependent on the model fit. Applying the methods to a real-life data set from the Framingham Heart Study produced larger estimated odds ratios for coronary heart disease as a result of elevated systolic blood pressure, as compared with naïve odds ratios. We provide some discussion of alternative procedures that might be considered including regression calibration, SIMEX and the use of estimated misclassification probabilities.

Complement activation correlates to disease severity and contribute to cytokine response in falciparum malaria

by Mauro Prato and Ingvild Dalen

Journal of Infectious Diseases, 2015

The impact of complement activation and its possible relation to cytokine responses in malaria pa... more The impact of complement activation and its possible relation to cytokine responses in malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria, and in human whole blood stimulated with malaria relevant agents ex vivo. Complement was significantly activated in the malaria cohort as compared to healthy controls, positively correlated to disease severity, and with certain cytokines, in particular IL-8/CXCL8. This was confirmed in ex vivo-stimulated blood where complement inhibition significantly reduced IL-8/CXCL8 release. Plasmodium falciparum malaria is associated with a systemic complement activation and complement-dependent release of inflammatory cytokines, of which IL-8/CXCL8 is particularly prominent. by guest on September 16, 2016 http://jid.oxfordjournals.org/ Downloaded from by guest on September 16, 2016 http://jid.oxfordjournals.org/ Downloaded from

Loss of Dopamine Transporter Binding and Clinical Symptoms in Dementia With Lewy Bodies

Movement Disorders, 2015

Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies... more Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies. The aim of this study was to explore the association between loss of striatal dopamine transporter binding and symptoms in dementia with Lewy bodies. Thirty-five patients with dementia with Lewy bodies underwent single-photon emission computerized tomography brain imaging with N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([(123) I]FP-CIT). Associations between striatal binding ratios and motor (UPDRS), psychiatric (Neuropsychiatric Inventory; [NPI]), and cognitive (Mini-Mental State Examination [MMSE] and neuropsychological tests) symptoms were assessed by linear regression analysis. The explorative analysis showed that the motor UPDRS was negatively associated with putamen dopamine transporter binding, whereas no association with striatal dopamine transporter binding was found for total NPI, hallucinations, apathy, depression, anxiety, and MMSE scores. However, in post-hoc analysis, executive impairment was positively associated with dopamine transporter loss after adjustment of age and gender. Dopamine deficiency in patients with dementia with Lewy bodies was associated with severity of motor symptoms, but did not correlate significantly with ratings of neurobehavioral disturbances or overall cognition. © 2015 International Parkinson and Movement Disorder Society.

Encouraging adolescents to contact their GP: a community-based trial

by Ingvild Dalen and Ole Haavet

British Journal of General Practice

Adolescents, especially males, often fail to see their GP. To determine whether an informative le... more Adolescents, especially males, often fail to see their GP. To determine whether an informative letter could enhance the accessibility and utilisation of healthcare facilities and services. A community-based trial in one town in Oslo, using a retrospective control group. GPs in one town in Oslo sent a personal, informative letter at the beginning of 2008 and 2009 to individuals in their practice population who were turning 16 years of age that year. The pooled data for the same year for each surgery were collected. Retrospective data from 1990 and 1991 served as controls for the intervention groups of data collected in 2006 and 2007 respectively. An International Classification of Primary Care-2 diagnosis was given for each contact. The proportion of adolescents in contact with a GP increased from 59% in the control group to 69% in the intervention group (P<0.001). For the males, the increase was from 54% to 72% (P<0.001). This reduced sex differences in healthcare seeking. For...

Improving antibiotic prescribing in acute respiratory tract infections: cluster randomised trial from Norwegian general practice (prescription peer academic detailing (Rx-PAD) study)

by Ingvild Dalen and Jørund Straand

BMJ (online)

To assess the effects of a multifaceted educational intervention in Norwegian general practice ai... more To assess the effects of a multifaceted educational intervention in Norwegian general practice aiming to reduce antibiotic prescription rates for acute respiratory tract infections and to reduce the use of broad spectrum antibiotics. Cluster randomised controlled study. Existing continuing medical education groups were recruited and randomised to intervention or control. 79 groups, comprising 382 general practitioners, completed the interventions and data extractions. The intervention groups had two visits by peer academic detailers, the first presenting the national clinical guidelines for antibiotic use and recent research evidence on acute respiratory tract infections, the second based on feedback reports on each general practitioner's antibiotic prescribing profile from the preceding year. Regional one day seminars were arranged as a supplement. The control arm received a different intervention targeting prescribing practice for older patients. Prescription rates and proport...

Pelvic girdle pain 3-6 months after delivery in an unselected cohort of Norwegian women

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, Jan 22, 2015

Persistent pelvic girdle pain (PGP) after delivery is considered uncommon. The aim of this study ... more Persistent pelvic girdle pain (PGP) after delivery is considered uncommon. The aim of this study was to assess the frequency of persistent PGP after delivery in an unselected population, its influence on the women's daily life, and potential risk factors. The study population was drawn from a previous retrospective study of pelvic pain (PP) during pregnancy. The women were followed until 3-6 months after delivery in a prospective cohort study. All women were contacted by telephone and those with persistent PP were invited to fill in questionnaires and undergo a clinical examination. 68 of 330 women reported persistent pain in the pelvic area 3-6 months after delivery. 47 underwent a clinical examination, after which 36 women were diagnosed with either PGP alone (n = 25), or PGP combined with low back pain (LBP) (n = 11). Affected women reported a poor subjective health status, but the pain did not have a major impact on their daily life activities. Women with 3 independent risk ...

A cluster-randomized educational intervention to reduce inappropriate prescription patterns for elderly patients in general practice--The Prescription Peer Academic Detailing (Rx-PAD) study [NCT00281450]

by Ingvild Dalen, Jørund Straand, and Mette Brekke

BMC health services research, 2006

Age-related alterations in metabolism and excretion of medications increase the risk of adverse d... more Age-related alterations in metabolism and excretion of medications increase the risk of adverse drug events in the elderly. Inappropriate polypharmacy and prescription practice entails increased burdens of impaired quality of life and drug related morbidity and mortality. The main objective of this trial is to evaluate effects of a tailored educational intervention towards general practitioners (GPs) aimed at supporting the implementation of a safer drug prescribing practice for elderly patients > or = 70 years. Approximately 80 peer continuing medical education (CME) groups (about 600 GPs) in southern Norway will be recruited to a cluster randomized trial. Participating groups will be randomized either to an intervention- or a control group. The control group will not receive any intervention towards prescription patterns in elderly, but will be the target of an educational intervention for prescription of antibiotics for respiratory tract infections. A multifaceted intervention...

Persistence and Prognostic Implications of Orthostatic Hypotension in Older Individuals with Mild-to-Moderate Dementia

Dementia and geriatric cognitive disorders extra

To study the course and prognostic implications of orthostatic hypotension (OH) in older individu... more To study the course and prognostic implications of orthostatic hypotension (OH) in older individuals with mild-to-moderate dementia. Referrals to outpatient clinics specialising in old age psychiatry and geriatric medicine in the counties of Rogaland and Hordaland in western Norway with a first-time diagnosis of mild dementia were consecutively asked for inclusion. A total of 211 participants underwent a comprehensive baseline assessment with annual follow-ups. Patients with OH at both baseline and the 1-year follow-up were classified as having persistent OH. Outcome measures were the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating sum of boxes (CDR-SB), and time to death. From baseline to the 4-year follow-up, 30-45% of the participants had OH at each follow-up. In multivariable analysis, persistent OH was not significantly associated with either the longitudinal course of MMSE or CDR-SB scores or survival. OH was moderately prevalent over 4 years in older indivi...

Vitamin D status in recently arrived immigrants from Africa and Asia: a cross-sectional study from Norway of children, adolescents and adults

BMJ open, 2013

To estimate the prevalence of vitamin D deficiency (25(OH)D) <50 nmol/L among recently arrived... more To estimate the prevalence of vitamin D deficiency (25(OH)D) <50 nmol/L among recently arrived immigrants from Africa and Asia in Oslo, and to explore 25(OH)D levels according to origin, gender and age. A cross-sectional study. Primary healthcare unit in Oslo, Norway, offering family immigrants, asylum seekers, United Nations (UN) refugees or individuals granted asylum a free medical examination on arrival. All individuals from African and Asian countries (n=591) referred to the Centre of Migrant Health, Health Agency, Oslo, Norway in 2010, estimated to cover 60% of the targeted population. 25(OH)D <50 nmol/L was very prevalent in immigrants from the Middle East (81% (95% CI 75.4% to 86.6%)), South Sahara Africa (73% (CI 67.5% to 78.5%)) and South Asia (75% (CI 64.0% to 86.0%)), in contrast to East Asians (24% (CI 12.6% to 35.4%)), p<0.001 for differences. The prevalence of 25(OH)D<25 nmol/L was lower but followed the same pattern (Middle East: 38% (CI 31.1% to 45.0%), S...

Are children carrying the burden of broad-spectrum antibiotics in general practice? Prescription pattern for paediatric outpatients with respiratory tract infections in Norway

BMJ open, 2013

To investigate the antibiotic prescription pattern and factors that influence the physicians'... more To investigate the antibiotic prescription pattern and factors that influence the physicians' choice of antibiotic. Observational study. Primary healthcare in Norway, December 2004 through November 2005. 426 general practitioners, GPs, in Norway, giving 24 888 respiratory tract infection episodes with 19 938 children aged 0-6 years. Assess antibiotic prescription details and patient and GP characteristics associated with broad-spectrum and narrow-spectrum antibiotic use. Of the 24 888 episodes in the study, 26.2% (95% CI 25.7% to 26.8%) included an antibiotic prescription. Penicillin V accounted for 42% and macrolide antibiotics for 30%. The prescription rate varied among the physicians, with a mean of 25.5% (95% CI 24.2% to 26.7%). Acute tonsillitis gave the highest odds for a prescription, OR 33.6 (95% CI 25.7% to 43.9%), compared to 'acute respiratory tract infections and symptoms' as a reference group. GPs with a prescription rate of 33.3% or higher had the larger pr...

Symptom reporting in a general population in Norway: results from the Ullensaker study

by Ingvild Dalen and Jørund Straand

Scandinavian journal of primary health care, 2013

To determine the number of symptoms experienced in an adult population and their relationship wit... more To determine the number of symptoms experienced in an adult population and their relationship with self- reported health, demographic, and lifestyle factors. A postal questionnaire addressing 23 different symptoms, health, demographic, and lifestyle factors. The community of Ullensaker, Norway, in 2004. Subjects. 3325 subjects (participation rate = 54.4%). Number of self-reported symptoms. At least one symptom was reported by 91.9% of the participants, 46.7% reported six or more, and 17.3% reported 10 or more symptoms. Symptom reporting was frequent in all age groups, also among young people. Women reported a greater mean number of symptoms than men (6.7 vs. 5.1). Those reporting poor health, receipt of social security benefit, unemployment, low education, or obesity had most symptoms. The proportion of respondents with these characteristics increased almost linearly with increasing number of symptoms. According to an adjusted multivariate model, self-reported overall health explain...

Can antibiotic prescriptions in respiratory tract infections be improved? A cluster-randomized educational intervention in general practice--the Prescription Peer Academic Detailing (Rx-PAD) Study [NCT00272155]

by Ingvild Dalen and Jørund Straand

BMC health services research, 2006

More than half of all antibiotic prescriptions in general practice are issued for respiratory tra... more More than half of all antibiotic prescriptions in general practice are issued for respiratory tract infections (RTIs), despite convincing evidence that many of these infections are caused by viruses. Frequent misuse of antimicrobial agents is of great global health concern, as we face an emerging worldwide threat of bacterial antibiotic resistance. There is an increasing need to identify determinants and patterns of antibiotic prescribing, in order to identify where clinical practice can be improved. Approximately 80 peer continuing medical education (CME) groups in southern Norway will be recruited to a cluster randomized trial. Participating groups will be randomized either to an intervention- or a control group. A multifaceted intervention has been tailored, where key components are educational outreach visits to the CME-groups, work-shops, audit and feedback. Prescription Peer Academic Detailers (Rx-PADs), who are trained GPs, will conduct the educational outreach visits. During...

Ethnic differences in obesity among immigrants from developing countries, in Oslo, Norway

International journal of obesity (2005), 2006

To compare ethnic and gender differences in generalized and central obesity and to investigate wh... more To compare ethnic and gender differences in generalized and central obesity and to investigate whether these differences persisted after adjusting for socio-demographic and lifestyle factors. In 2002, the population-based cross-sectional, Oslo Immigrant Health study was conducted. A total of 7890 Oslo residents, born between 1942 and 1971 in Turkey, Iran, Pakistan, Sri Lanka and Vietnam, were invited and 3019 attended. Participants completed a health questionnaire and attended a clinical screening that included height, weight, waist and hip measurements. Generalized obesity (BMI> or =30 kg/m2) was greatest among women from Turkey (51.0%) and least among men from Vietnam (2.7%). The highest proportions of central obesity (waist hip ratio (WHR)>or =0.85) were observed among women from Sri Lanka (54.3%) and Pakistan (52.4%). For any given value of BMI, Sri Lankans and Pakistanis had higher WHR compared to the other groups. Despite a high mean BMI, Turkish men (27.9 kg/m2) and wom...

C2 monitoring in maintenance renal transplant recipients: is it worthwhile?

Transplantation, Jan 27, 2003

Presently, there is little knowledge regarding cyclosporine (CsA) concentration at 2 hr post-dose... more Presently, there is little knowledge regarding cyclosporine (CsA) concentration at 2 hr post-dose (C2) monitoring in maintenance patients. This study evaluates the actual C2 range in stable renal transplant recipients (who underwent transplantation >12 months ago). In addition, we investigated whether underexposure or overexposure to CsA (assessed by C2) affects graft function (as measured by serum [S]-creatinine). All renal transplant recipients in Norway receiving CsA were asked to participate; 1447 fulfilled the criteria. Valid C2 and CsA trough concentration (C0) measurements were performed in 1032 renal transplant recipients (71%) monitored by C0. Target C0 level was 75 to 125 mumol/L. CsA levels were measured using a Cloned Enzyme Donor Immunoassay method, and all analyses were performed in the same laboratory (overall mean [+/-standard deviation] CsA C0=112+/-31 mug/L, CsA C2=697+/-211 mug/L [range 81-1580 mug/L], CsA dose [mg/day]=208+/-61, CsA dose [mg/kg/day]=2.8+/-1.1,...

The long-term development of non-motor problems after STN-DBS

Acta Neurologica Scandinavica, 2015

Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term benef... more Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term beneficial effects on motor symptoms in patients with Parkinson&amp;amp;#39;s disease (PD). The long-term development of non-motor problems after STN-DBS is not fully understood. In this study, we have studied how non-motor problems develop in patients with and without STN-DBS. We collected data from a prospectively followed cohort of patients that had been operated with STN-DBS 6-9 years before final examination and compared our findings to the longitudinal development of non-motor problems in a non-operated, comparable reference population. In general, the non-motor problems of advanced PD seem to develop independently of treatment with STN-DBS. We found that depressions do not worsen after STN-DBS, and the Montgomery and Aasberg Depression Rating Scale score in operated patients was substantially reduced from pre-operatively to post-operatively. Further, fatigue may represent an important unrecognized side effect of long-term stimulation, as fatigue was found to increase rapidly in operated patients already a year after surgery and continued to increase trough the 6- to 9-year follow-up. The non-motor problems of advanced PD seem to develop independently of treatment with STN-DBS. This may influence the strategy for choice of when to perform this therapy for eligible patients.

Motor symptoms after deep brain stimulation of the subthalamic nucleus

Acta Neurologica Scandinavica, 2014

Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term benef... more Stimulation of the subthalamic nucleus (STN-DBS) is an established treatment with long-term beneficial effects on motor symptoms in patients with Parkinson&amp;amp;#39;s disease (PD). The efficacy of STN-DBS on non-dopaminergic motor symptoms remains less elucidated. In this study, we have examined short- and long-term impacts of STN-DBS on the development of the postural instability and gait difficulties (PIGD) phenotype, freezing of gait (FOG), and falls. We collected data from a prospectively followed cohort of patients that had been operated with STN-DBS 6-9 years before final examination and compared our findings to the longitudinal development of the same symptoms in a non-operated, historical reference population. During short-term follow-up after surgery, we observed a marked improvement in mean UPDRS-motor score from 27 to 18. We also found clear improvements in tremor, bradykinesia, rigidity, and PIGD scores. However, 6-9 years after surgery, all patients had a dominating PIGD pattern of parkinsonism and 50% of the patients had developed FOG and/or had become recurrent fallers. The disease development in a group of patients with PD from the presurgery period had a similar trajectory as among the operated patients. In addition, mean annual change of both bradykinesia and PIGD scores was nearly identical in both study groups while tremor and rigidity had a significant better development in the operated patients. We found that STN-DBS induces an acute improvement of PIGD symptoms. The following long-term development was however characterized by a marked progression of non-dopaminergic symptoms.

Psychosocial factors and distress: a comparison between ethnic Norwegians and ethnic Pakistanis in Oslo, Norway

BMC public health, 2006

In the Norwegian context, higher mental distress has been reported for the non-Western immigrants... more In the Norwegian context, higher mental distress has been reported for the non-Western immigrants compared to the ethnic Norwegians and Western immigrants. This high level of distress is often related to different socio-economic conditions in this group. No efforts have been made earlier to observe the impact of changed psychosocial conditions on the state of mental distress of these immigrant communities due to the migration process. Therefore, the objective of the study was to investigate the association between psychological distress and psychosocial factors among Pakistani immigrants and ethnic Norwegians in Oslo, and to investigate to what extent differences in mental health could be explained by psychosocial and socioeconomic conditions. Data was collected from questionnaires as a part of the Oslo Health Study 2000-2001. 13581 Norwegian born (attendance rate 46%) and 339 ethnic Pakistanis (attendance rate 38%) in the selected age groups participated. A 10-item version of Hopki...

Regression analysis with categorized regression calibrated exposure: some interesting findings

by Ingvild Dalen and Anette Hjartåker

Emerging themes in epidemiology, 2006

Regression calibration as a method for handling measurement error is becoming increasingly well-k... more 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 depressio...

Sensitivity of regression calibration to non-perfect validation data with application to the Norwegian Women and Cancer Study

by Ingvild Dalen and Anette Hjartåker

Statistics in medicine, Jan 15, 2015

Measurement error occurs when we observe error-prone surrogates, rather than true values. It is c... more Measurement error occurs when we observe error-prone surrogates, rather than true values. It is common in observational studies and especially so in epidemiology, in nutritional epidemiology in particular. Correcting for measurement error has become common, and regression calibration is the most popular way to account for measurement error in continuous covariates. We consider its use in the context where there are validation data, which are used to calibrate the true values given the observed covariates. We allow for the case that the true value itself may not be observed in the validation data, but instead, a so-called reference measure is observed. The regression calibration method relies on certain assumptions.This paper examines possible biases in regression calibration estimators when some of these assumptions are violated. More specifically, we allow for the fact that (i) the reference measure may not necessarily be an 'alloyed gold standard' (i.e., unbiased) for the ...

Cytokine Network in Adults with Falciparum Malaria and HIV-1: Increased IL-8 and IP-10 Levels Are Associated with Disease Severity

by Ingvild Dalen and Nina Langeland

PLoS ONE, 2014

Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the ... more Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection. This was a prospective cross-sectional study. Clinical data and blood samples were collected from adults in Mozambique. Plasma was analysed for 21 classical pro- and anti-inflammatory cytokines, including interleukins, interferons, and chemokines. We included 212 in-patients with fever and/or suspected malaria and 56 healthy controls. Falciparum malaria was diagnosed in 131 patients, of whom 70 were co-infected with HIV-1. The malaria patients had marked increases in their cytokine responses compared with the healthy controls. Some of these changes, particularly interleukin 8 (IL-8) and interferon-γ-inducing protein 10 (IP-10) were strongly associated with falciparum malaria and disease severity. Both these chemokines were markedly increased in patients with falciparum malaria as compared with healthy controls, and raised levels of IL-8 and IP-10 were associated with increased disease severity, even after adjusting for relevant confounders. For IL-8, particularly high levels were found in malaria patients that were co-infected with HIV and in those who died during hospitalization. Our findings underscore the complex role of inflammation during infection with P. falciparum, and suggest a potential pathogenic role for IL-8 and IP-10. However, the correlations do not necessarily mean any causal relationship, and further both clinical and mechanistic research is necessary to elucidate the role of cytokines in pathogenesis and protection during falciparum malaria.

Correction for misclassification of a categorized exposure in binary regression using replication data

Statistics in Medicine, 2009

Continuous epidemiologic exposure data are often categorized according to one or more cut points ... more Continuous epidemiologic exposure data are often categorized according to one or more cut points before inclusion in a regression analysis involving some outcome variable. If the original data are subject to measurement error, the categorized data will be afflicted with misclassification, which is differential, and which induces biases in naïve methods that ignore the misclassification. We propose a method for measurement error adjustment in these settings, when there are replicate data available on the original measurements, and when the outcome variable is dichotomous. Working on the continuous measurements, conditional densities of the exposure given the outcome are estimated and used to obtain odds ratios. The estimation of densities is done either parametrically or nonparametrically. The method is compared with the naïve approach of simply categorizing the erroneous mean measurements in simulation studies, and although the nonparametric method is more variable, it has the best overall performance, the greatest differences being observed in settings where the effects and/or the measurement errors are large. The performance of the parametric method is highly dependent on the model fit. Applying the methods to a real-life data set from the Framingham Heart Study produced larger estimated odds ratios for coronary heart disease as a result of elevated systolic blood pressure, as compared with naïve odds ratios. We provide some discussion of alternative procedures that might be considered including regression calibration, SIMEX and the use of estimated misclassification probabilities.