Publications by authors named "Christofer Lundqvist"

70 Publications

Cognitive Impairment 13 Months After Hospitalization for COVID-19.

Open Forum Infect Dis 2022 Jul 26;9(7):ofac355. Epub 2022 Jul 26.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

This study assessed cognitive function 13 months after hospital discharge for coronavirus disease 2019 (COVID-19), using computer-based cognitive tests. Compared to population norms, 14%-25% of patients were impaired in each dimension, and 53% had cognitive impairment in 1 or more of 4 tests. There was some association with acute COVID-19 disease severity.
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http://dx.doi.org/10.1093/ofid/ofac355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330249PMC
July 2022

Correction to: Patterns and predictors of analgesic use in pregnancy: a longitudinal drug utilization study with special focus on women with migraine.

BMC Pregnancy Childbirth 2022 Apr 8;22(1):300. Epub 2022 Apr 8.

Pharmacoepidemiology & Drug Safety Research Group, Department of Pharmacy, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, P.O. Box. 1068, Blindern, 0316, Oslo, Norway.

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http://dx.doi.org/10.1186/s12884-022-04525-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991970PMC
April 2022

The effect of cognitive function and central nervous system depressant use on mortality-A prospective observational study of previously hospitalised older patients.

PLoS One 2022 3;17(3):e0263024. Epub 2022 Mar 3.

Health Services Research Unit (HØKH), Akershus University Hospital, Lørenskog, Norway.

Background: Older patients are often users of prolonged Central Nervous System Depressants (CNSD) (Z-hypnotics, benzodiazepines and opioids), which may be associated with reduced cognition. The long-term effects of CNSD use and reduced cognitive function in older patients are unclear. The aim of this study was to examine whether cognitive function and CNSD use at baseline hospitalisation were associated with all-cause mortality two years after discharge.

Methods: We conducted a prospective observational study, including baseline data (2017-2018) from previously hospitalised older patients (65-90 years), assessing all-cause mortality two years after discharge. We used logistic regression to assess the primary outcome, all-cause mortality two years after baseline hospitalisation. The primary predictors were cognitive function measured by The Mini Mental State Examination (MMSE) and prolonged CNSD use (continuous use ≥ 4 weeks). Adjustment variables: age, gender, education, the Hospital Anxiety and Depression Scale (HADS) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), using receiver operating characteristics (ROC) to compare the predictive power of the models. In a sub-analysis we used, the Neurobehavioural Cognitive State Examination (Cognistat) and the Clock Drawing Test.

Results: Two years after discharge, out of 246 baseline patients, 43 were deceased at follow-up, among these 27 (63%) were CNSD users, and 16 (36%) were non-users at baseline, (p = 0.002). In the multivariable models cognitive function (MMSE score) was a predictor of mortality (OR 0.81 (95% CI 0.69; 0.96), p = 0.014). CNSD use was associated with mortality (OR 2.71 (95% CI 1.06; 6.95), p = 0.038), with ROC AUC: 0.74-0.77 for these models. Results using Cognistat supported the findings. The Clock Drawing Test was not significant predictor of mortality.

Conclusion: Two years after discharge from the hospital, older patients with reduced cognitive function and CNSD use during hospital stay had higher mortality. This underlines that inappropriate (prolonged and concurrent) use of CNSDs should be avoided by older patients, particularly in patients with reduced cognitive function.

Trial Registration: NCT03162081, 22 May 2017.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263024PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893618PMC
March 2022

The association between pain and central nervous system depressing medication among hospitalised Norwegian older adults.

Scand J Pain 2022 Jul 16;22(3):483-493. Epub 2021 Dec 16.

Health Services Research Unit, Akershus University Hospital, Lorenskog, Norway.

Objectives: Central nervous system depressant medications (CNSD) including benzodiazepines, z-hypnotics and opioids are regularly prescribed for the older patient. These medications are linked to dependence and associated with severe side effects in some older patients. Consensus recommendations for this group suggest limiting their use. We have recently described a high proportion of long-term CNSD use and dependence among older in-hospital patients. In this study, we aim to investigate factors associated with pain intensity and presentation of pain among older adults with long-term use of CNSDs compared to non-users.

Methods: Two hundred and forty six elderly hospitalised patients were recruited consecutively in a cross-sectional study. Data was collected from patients and electronic health records (EHR). Independent variables were sex, age, education, emotional symptoms (hospital anxiety and depression scale [HADS]), cognitive function (Mini-mental State Examination test [MMSE]), comorbidity (cumulative illness rating score - geriatrics [CIRS-G]), loneliness (the six-item De Jong Gierveld Loneliness Scale) and prolonged (≥4 weeks) use of any CNSDs or prolonged use of opioids (≥4 weeks). All variables, including pain intensity, were collected at one time point consistent with the cross-sectional study design. Statistical analyses included descriptive statistics and linear regression models using the above mentioned variables and pain intensity (visual analogue scale for pain intensity [VAS] pain 0-100) as outcome. Additional information regarding pain presentation was extracted from the patients' EHR.

Results: Mean pain intensity VAS (SD) was 35.2 (30.4) and 18.1 (24.2) respectively, for patients with vs. without prolonged use of CNSDs. In the multivariable linear regression analysis, prolonged use of CNSDs and opioids were positively associated with pain intensity (VAS) (regression coefficient (95% CI) 20.7 (11.0; 30.3), p<0.001, and 19.8 (5.7; 33.8), p=0.006, respectively), while sex, age, education, MMSE, HADS, CIRS-G and loneliness scores were not. Pain related to back (23.2%) and lower extremities (23.2%) were most common pain sites, and those with one or more pain sites reported overall higher pain intensity compared to those with no reported pain sites (p<0.006).

Conclusions: Prolonged use of CNSD medications as well as prolonged use of opioids are both positively associated with pain intensity. The results may have implications for treatment and long-term pain management for older patients.
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http://dx.doi.org/10.1515/sjpain-2021-0120DOI Listing
July 2022

Complement ratios C3bc/C3 and sC5b-9/C5 do not increase the sensitivity of detecting acute complement activation systemically.

Mol Immunol 2022 01 11;141:273-279. Epub 2021 Dec 11.

Department of Immunology, Oslo University Hospital and University of Oslo, Norway; Division of Emergencies and Critical Care, Oslo University Hospital, Norway. Electronic address:

Background: Complement activation plays an important pathogenic role in numerous diseases. The ratio between an activation product and its parent protein is suggested to be more sensitive to detect complement activation than the activation product itself. In the present study we explored whether the ratio between the activation product and the parent protein for C3 (C3bc/C3) and for C5 (sC5b-9/C5) increased the sensitivity to detect complement activation in acute clinical settings compared to the activation product alone.

Materials And Methods: Samples from patients with acute heart failure following ST-elevated myocardial infarction (STEMI) and from patients with out-of-hospital cardiac arrest (OHCA) were used. C3, C3bc and C5, sC5b-9 were analysed in 629 and 672 patient samples, respectively. Healthy controls (n = 20) served to determine reference cut-off values for activation products and ratios, defined as two SD above the mean.

Results: Increased C3bc/C3- and sC5b-9/C5 ratios were vastly dependent on C3bc and sC5b-9. Thus, 99.5 % and 98.1 % of the increased C3bc/C3- and sC5b-9/C5 ratios were solely dependent on increased C3bc and sC5b-9, respectively. Significantly decreased C3 and C5 caused increased ratios in only 3/600 (0.5 %) and 4/319 (1.3 %) samples, respectively. Strong correlations between C3bc and C3bc/C3-ratio and between sC5b-9 and sC5b-9/C5-ratio were found in the STEMI- (r = 0.926 and r = 0.786, respectively) and the OHCA-population (r = 0.908 and r = 0.843, respectively; p < 0.0001 for all). Importantly, sC5b-9 identified worse outcome groups better than sC5b-9/C5-ratio.

Conclusion: C3bc and sC5b-9 were sensitive markers of complement activation. The ratios of C3bc/C3 and sC5b-9/C5 did not improve detection of complement activation systemically.
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http://dx.doi.org/10.1016/j.molimm.2021.11.016DOI Listing
January 2022

The management and clinical knowledge of headache disorders among general practitioners in Norway: a questionnaire survey.

J Headache Pain 2021 Nov 11;22(1):136. Epub 2021 Nov 11.

Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.

Background: General practitioners (GPs) diagnose and manage a majority of headache patients seeking health care. With the aim to understand the potential for clinical improvement and educational needs, we performed a study to investigate Norwegian GPs knowledge about headache and its clinical management.

Methods: We invited GPs from a random sample of 130 Norwegian continuous medical education (CME) groups to respond to an anonymous questionnaire survey.

Results: 367 GPs responded to the survey (73% of invited CME groups, 7.6% of all GPs in Norway). Mean age was 46 (SD 11) years, with an average of 18 (SD 10) years of clinical experience. In general the national treatment recommendations were followed, while the International Classification of Headache Disorders and other international guidelines were rarely used. Overall, 80% (n = 292) of the GPs suggested adequate prophylactic medication for frequent episodic migraine, while 28% (n = 101) suggested adequate prophylactic medication for chronic tension-type headache (CTTH). Half (52%, n = 191)) of the respondents were aware that different types of acute headache medication can lead to medication-overuse headache (MOH), and 59% (n = 217) knew that prophylactic headache medication does not lead to MOH. GPs often used MRI in the diagnostic work-up. GPs reported that lack of good treatment options was a main barrier to more optimized treatment of headache patients.

Conclusion: The knowledge of management of CTTH and MOH was moderate compared to migraine among Norwegian GPs.
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http://dx.doi.org/10.1186/s10194-021-01350-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582095PMC
November 2021

Complement activation is associated with poor outcome after out-of-hospital cardiac arrest.

Resuscitation 2021 09 11;166:129-136. Epub 2021 Jun 11.

Dept. of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway; Dept. of Anaesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Dept. of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway. Electronic address:

Background: Cardiopulmonary resuscitation after cardiac arrest initiates a whole-body ischemia-reperfusion injury, which may activate the innate immune system, including the complement system. We hypothesized that complement activation and subsequent release of soluble endothelial activation markers were associated with cerebral outcome including death.

Methods: Outcome was assessed at six months and defined by cerebral performance category scale (1-2; good outcome, 3-5; poor outcome including death) in 232 resuscitated out-of-hospital cardiac arrest patients. Plasma samples obtained at admission and day three were analysed for complement activation products C3bc, the soluble terminal complement complex (sC5b-9), and soluble CD14. Endothelial cell activation was measured by soluble markers syndecan-1, sE-selectin, thrombomodulin, and vascular cell adhesion molecule.

Results: Forty-nine percent of the patients had good outcome. C3bc and sC5b-9 were significantly higher at admission compared to day three (p < 0.001 for both) and in patients with poor compared to good outcome (p = 0.03 and p < 0.001, respectively). Unadjusted, higher sC5b-9 at admission was associated with poor outcome (odds ratio 1.08 (95% CI 1.01-1.14), p = 0.024). Adjusted, sC5b-9 was still associated with outcome, but the association became non-significant when time to return-of-spontaneous-circulation above 25 min was included as a covariate. Endothelial cell activation markers increased from admission to day three, but only sE-selectin and thrombomodulin were significantly higher in patients with poor versus good outcome (p = 0.004 and p = 0.03, respectively) and correlated to sCD14 and sC5b-9/C3bc, respectively.

Conclusion: Complement system activation, reflected by sC5b-9 at admission, leading to subsequent endothelial cell activation, was associated with poor outcome in out-of-hospital cardiac arrest patients.
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http://dx.doi.org/10.1016/j.resuscitation.2021.05.038DOI Listing
September 2021

The patterns and burden of multimorbidity in geriatric patients with prolonged use of addictive medications.

Aging Clin Exp Res 2021 Oct 18;33(10):2857-2864. Epub 2021 Feb 18.

Health Services Research Unit (HØKH), Akershus University Hospital, Lørenskog, Norway.

Background: Multimorbidity and prolonged use of addictive medications are prevalent among older patients, and known to increase the risk of adverse drug events. Yet, the relationship between these two entities has remained understudied.

Aims: This study explored the association between multimorbidity burden and prolonged use of addictive medications in geriatric patients, adjusted for clinically important covariates. Furthermore, we identified comorbidity patterns in prolonged users.

Methods: We conducted a cross-sectional study on a consecutive sample of 246 patients, aged 65-90 years, admitted to a large public university hospital in Norway. We defined prolonged use of addictive medications as using benzodiazepines, opioids and/or z-hypnotics beyond the duration recommended by clinical guidelines (≥ 4 weeks). Multimorbidity was assessed with the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), based on diagnoses made by independent physicians.

Results: Compared to non-prolonged use, prolonged use was significantly more common among patients who had psychiatric (19/27, 70%), liver (19/22, 86%), upper gastrointestinal tract (21/32, 66%), musculoskeletal (52/96, 54%), or nervous system disorders (46/92, 50%). Patients with prolonged use had a higher multimorbidity burden than those without such use (CIRS-G score, mean = 7.7, SD = 2.7 versus mean = 4.6, SD = 2.2, p < 0.001). Multivariable logistic regression indicated a significant association between multimorbidity burden and prolonged addictive medication use (OR = 1.72, 95% CI 1.42-2.08). Predictive margins postestimation showed a systematic increase in the predicted CIRS-G scores when the number of addictive drug used increases.

Conclusions: Multimorbidity is strongly associated with prolonged use of addictive medications. Multiple substance use may aggravate disease burden of older patients.
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http://dx.doi.org/10.1007/s40520-021-01791-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531043PMC
October 2021

Health-related quality of life after out-of-hospital cardiac arrest - a five-year follow-up studyJūratė Šaltytė Benth.

Resuscitation 2021 05 8;162:372-380. Epub 2021 Feb 8.

Department of Acute Medicine, Oslo University Hospital, Ullevål, Norway.

Background: Health-related quality of life (HRQoL) is affected after out-of-hospital cardiac arrest (OHCA), but data several years after the arrest are lacking. We assessed long-term HRQoL in OHCA survivors and how known outcome predictors impact HRQoL.

Methods: In adult OHCA survivors, HRQoL was assessed five years post arrest using Short-form 36 (SF-36), EQ-5D-3 L (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) among others. Results were compared to the next of kins' estimates and to a Norwegian reference population.

Results: Altogether 96 survivors were included mean 5.3 (range 3.6-7.2) years after OHCA. HRQoL compared well to the reference population, except for lower score for general health with 67.2 (95%CI (62.1; 72.3) vs. 72.9 (71.9; 74.0)), p = 0.03. Younger (≤58 years) vs. older survivors scored lower for general health with mean (SD) of 62.1 (27.5) vs. 73.0 (19.5), p = 0.03, vitality (55.2 (20.5) vs. 64.6 (17.3), p = 0.02, social functioning (75.3 (28.7) vs. 94.1 (13.5), p < 0.001 and mental component summary (49.0 (9.9) vs. 55.8 (6.7), p < 0.001. They scored higher for HADS-anxiety (4.8 (3.6 vs. 2.7 (2.5), p = 0.001, and had lower EQ-5D index (0.72 (0.34) vs. 0.84 (0.19), p = 0.04. Early vs. late awakeners had higher EQ-5D index (0.82 (0.23) vs. 0.71 (0.35), p = 0.04 and lower HADS-depression scores (2.5 (2.9) vs. 3.8 (2.3), p = 0.04. Next of kin estimated HRQoL similar to the survivors' own estimates.

Conclusions: HRQoL five years after OHCA was good and mainly comparable to a matched reference population. Stratified analyses revealed impaired HRQoL among younger survivors and those awakening late, mainly for mental domains.
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http://dx.doi.org/10.1016/j.resuscitation.2021.01.036DOI Listing
May 2021

"What should I do when I get home?" treatment plan discussion at discharge between specialist physicians and older in-patients: mixed method study.

BMC Health Serv Res 2020 Nov 3;20(1):1002. Epub 2020 Nov 3.

Health Services Research Unit, Akershus University Hospital, Lørenskog, Norway.

Background: During discharge from hospital, older patients and physicians discuss the plan for managing patients' health at home. If not followed at home, it can result in poor medication management, readmissions, or other adverse events. Comorbidities, polypharmacy and cognitive impairment may create challenges for older patients. We assessed discharge conversations between older in-patients and physicians for treatment plan activities and medication information, with emphasis on the role of cognitive function in the ongoing conversation.

Methods: We collected 11 videos of discharge consultations, medication lists, and self-reported demographic information from hospitalised patients ≥65 years at the Geriatric department in a general hospital. Mini Mental State Examination score < 25 was classified as low cognitive function. We used microanalysis of face-to-face dialogue to identify and characterise sequences of interaction focused on and distinguishing the treatment plan activities discussed. In addition to descriptive statistics, we used a paired-sample t-test and Mann-Whitney U test for non-parametric data.

Results: Patients' median age was 85 (range: 71-90);7 were females and 4 males. Median of 17 (range: 7 to 23) treatment plan activities were discussed. The proportions of the activities, grouped from a patient perspective, were: 0.40 my medications, 0.21 something the hospital will do for me, 0.18 someone I visit away from home, 0.12 daily routine and 0.09 someone coming to my home. Patients spoke less (mean 190.9 words, SD 133.9) during treatment plan activities compared to other topics (mean 759 words, SD 480.4), (p = .001). Patients used on average 9.2 (SD 3.1) medications; during the conversations, an average of 4.5 (SD 3.3) were discussed, and side effects discussed on average 1.2 (SD 2.1) times. During treatment plan discussions, patients with lower cognitive function were less responsive and spoke less (mean 116.5 words, SD 40.9), compared to patients with normal cognition (mean 233.4 words, SD 152.4), (p = .089).

Conclusion: Physicians and geriatric patients discuss many activities during discharge conversations, mostly focusing on medication use without stating side effects. Cognitive function might play a role in how older patients respond. These results may be useful for an intervention to improve communication between physicians and older hospitalised patients.
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http://dx.doi.org/10.1186/s12913-020-05860-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607876PMC
November 2020

Health-related quality of life in hospitalized older patients with versus without prolonged use of opioid analgesics, benzodiazepines, and z-hypnotics: a cross-sectional study.

BMC Geriatr 2020 10 23;20(1):425. Epub 2020 Oct 23.

Health Services Research Unit (HØKH), Akershus University Hospital, PO Box 1000, 1478, Lørenskog, Norway.

Background: Central nervous system depressant medications (CNSDs) such as opioid analgesics and sedative-hypnotics are commonly prescribed to older patients for the treatment of chronic pain, anxiety and insomnia. Yet, while many studies reported potential harms, it remains unknown whether persistent use of these medications is beneficial for older patients' self-reported health-related quality of life (HRQoL). The present study clarified this knowledge gap through comparing HRQoL of hospitalized older patients with versus without using CNSD drugs for ≥4 weeks. Moreover, we explored the relationship between such use and HRQoL, adjusting for the effects of polypharmacy, comorbidity burden and other clinically relevant covariates.

Methods: The study was cross-sectional and included 246 older patients recruited consecutively from somatic departments of a large regional university hospital in Norway. We defined prolonged CNSD use as using opioids, benzodiazepines and/or z-hypnotics for ≥4 weeks. Patients' self-reported HRQoL were measured with scales of the EuroQol EQ-5D-3L instrument. Data analyses were mainly descriptive statistics and regression models.

Results: Patients with prolonged use of CNSDs reported lower scores on both EQ-5D index and EQ VAS compared with those without such use (p < 0.001). They had higher odds of having more problems performing usual activities (OR = 3.37, 95% CI: 1.40 to 8.13), pain/discomfort (OR = 2.06, 95% CI: 1.05 to 4.04), and anxiety/depression (OR = 3.77, 95% CI: 1.82 to 7.82). In multivariable regression models, there was no significant association between prolonged CNSD use and HRQoL when including pain as a predictor variable. In models not including pain, CNSD use was strongly associated with HRQoL (adjusted for sociodemographic background, polypharmacy, comorbidity, anxiety and depressive symptoms, regression coefficient - 0.19 (95% CI, - 0.31 to - 0.06).

Conclusions: Older patients with prolonged CNSD use reported poorer HRQoL. They also had more pain and higher depression scores. Prolonged use of CNSDs was not independently associated with higher HRQoL.
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http://dx.doi.org/10.1186/s12877-020-01838-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585301PMC
October 2020

Association between prescribed central nervous system depressant drugs, comorbidity and cognition among hospitalised older patients: a cross-sectional study.

BMJ Open 2020 07 27;10(7):e038432. Epub 2020 Jul 27.

Health Services Research Unit (HØKH), Akershus University Hospital, Lorenskog, Norway.

Objectives: Central nervous system depressants (CNSDs) such as opioids, benzodiazepine and Z-hypnotics are commonly used. However, CNSDs may influence cognitive function, especially in older hospitalised patients with comorbidities. The aim was to examine the association between CNSD use and cognitive function in older patients. We assessed global and domain specific cognitive function, among hospitalised older patients, including covariates for comorbidity, anxiety and depression.

Design: Cross-sectional hospital-based study.

Settings: Data was collected consecutively from inpatients at somatic wards of a general university hospital.

Participants: Older patients between 65 and 90 years with/without CNSD use for ≥4 weeks.

Outcome Measures: The main outcome was cognitive function assessed by Cognistat. Secondary outcomes were routine clinical tests in the wards (mini-mental state examination (MMSE), trail making test (TMT) A and B, and clock drawing tests). Analyses were bivariate and multiple linear regression, adjusted for age, gender, and education. Covariates were comorbidity, depression and anxiety scores.

Results: The main result indicated that CNSD users (n=100) had (β=-3.4, 95% CI 6.27 to -0.58, p=0.017) lower Cognistat score than non-users (n=146), adjusted for age, gender, education, anxiety and depression, but not significant when including covariate for comorbidity (β= -2.50 - 5.45; -0.46, p=0.097). Comorbidity was associated with cognitive function (β=-0.77, 95% CI -1.22 to -0.14, p=0.014). Cognistat subdimensions associated with CNSD use were language (p=0.017) and calculation (p=0.003). In clock drawing test, users had lower scores than non-users (β=-0.80, 95% CI 1.24 to -0.36, p=0.004), but no significant difference was found with MMSE and TMT A or B. Z-hypnotics were associated with reduced cognitive function.

Conclusion: Among older hospitalised patients, global cognition and specific cognitive functions were associated with long-term use of CNSD medication as well as with somatic comorbidity.

Trial Registration Number: NCT03162081, 22 May 2017.
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http://dx.doi.org/10.1136/bmjopen-2020-038432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389767PMC
July 2020

Cerebrospinal fluid opening pressure in clinical practice - a prospective study.

J Neurol 2020 Dec 17;267(12):3696-3701. Epub 2020 Jul 17.

Department Neurology, Akershus University Hospital, Lørenskog, Norway.

Background: Measurement of CSF opening pressure (CSFOP) is valuable and much used in the investigation of several neurological conditions. However, there are different opinions regarding reference values and influence of age, gender and body mass index (BMI). We have, in a previous study, noted possible differences in CSFOP between gender and age groups. Here the aim was to collect information regarding normal distribution of CSFOP in an out-patient sample and also include BMI.

Methods: We collected CSFOP from a lumbar puncture, following a standardized procedure, performed in an ordinary neurological out-patient sample. Age, gender and BMI was also registered. Descriptive statistics and linear regression was used.

Results: 339 patients with a normal distribution of age and BMI were included consecutively (60% females). We found a mean CSFOP of 17.5 HO (range 4.0-30.0). In multivariable linear regression, age, gender and BMI all independently affected CSFOP. Male gender (β = 1.5, p = 0.002), lower age (β =  - 0.095, p < 0.001) and higher BMI (β = 0.42, p < 0.001) were all associated with higher CSFOP.

Conclusion: Using two standard deviations, we provide suggestions for CSFOP limits with respect to gender, age and BMI. Our results suggest that CSFOP cut-offs for pathological intracranial hypertension should be raised with these factors taken into consideration. As a "rule-of-thumb" we suggest the following cut-offs: for males < 30 cm HO (< 25 if over age 70), and for females < 25 cm HO (27.5 if over 30 BMI). A diagnosis of intracranial hypertension should not be given without such considerations.
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http://dx.doi.org/10.1007/s00415-020-10075-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674322PMC
December 2020

Late awakening, prognostic factors and long-term outcome in out-of-hospital cardiac arrest - results of the prospective Norwegian Cardio-Respiratory Arrest Study (NORCAST).

Resuscitation 2020 04 8;149:170-179. Epub 2020 Jan 8.

Department of Anaesthesiology, Oslo University Hospital, Ullevål, Postboks 4956 Nydalen, N-0424 Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Institute of Clinical Medicine, PB 1171 Blindern, N-0318 Oslo, Norway.

Background: Outcome prediction after out-of-hospital cardiac arrest (OHCA) may lead to withdrawal of life-sustaining therapy if the prognosis is perceived negative. Single use of uncertain prognostic tools may lead to self-fulfilling prophecies and death. We evaluated prognostic tests, blinded to clinicians and without calls for hasty outcome prediction, in a prospective study.

Methods: Comatose, sedated TTM 33-treated OHCA patients of all causes were included. Clinical-neurological/-neurophysiological/-biochemical predictors were registered. Patients were dichotomized into good/poor outcome using cerebral performance category (CPC) six months and > four years post-arrest. Prognostic tools were evaluated using false positive rates (FPR).

Results: We included 259 patients; 49 % and 42 % had good outcome (CPC 1-2) after median six months and 5.1 years. Unwitnessed arrest, non-shockable rhythms, and no-bystander-CPR predicted poor outcome with FPR (CI) 0.05 (0.02-0.10), 0.13 (0.08-0.21), and 0.13 (0.07-0.20), respectively. Time to awakening was median 6 (0-25) days in good outcome patients. Among patients alive with sedation withdrawal >72 h, 49 % were unconscious, of whom 32 % still obtained good outcome. Only absence of pupillary light reflexes (PLR) -and N20-responses in somato-sensory evoked potentials (SSEP), as well as increased neuron-specific enolase (NSE) later than 24 h to >80 μg/L, had FPR 0. Malignant EEG (burst suppression/epileptic activity/flat) differentiated poor/good outcome with FPR 0.05 (0.01-0.15).

Conclusion: Time to awakening was over six days in good outcome patients. Most clinical parameters had too high FPRs for prognostication, except for absent PLR and SSEP-responses >72 h after sedation withdrawal, and increased NSE later than 24 h to >80 μg/L.
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http://dx.doi.org/10.1016/j.resuscitation.2019.12.031DOI Listing
April 2020

Effect of Clinical Geriatric Assessments and Collaborative Medication Reviews by Geriatrician and Family Physician for Improving Health-Related Quality of Life in Home-Dwelling Older Patients Receiving Polypharmacy: A Cluster Randomized Clinical Trial.

JAMA Intern Med 2020 02;180(2):181-189

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Importance: Polypharmacy and inappropriate drug regimens are major health concerns among older adults. Various interventions focused on medication optimization strategies have been carried out, but the effect on patient-relevant outcomes remains uncertain.

Objective: To investigate the effect of clinical geriatric assessments and collaborative medication reviews by geriatrician and family physician (FP) on health-related quality of life and other patient-relevant outcomes in home-dwelling older patients receiving polypharmacy.

Design, Setting, And Participants: Cluster randomized, single-blind, clinical trial. Norwegian FPs were recruited from March 17, 2015, to March 16, 2017, to participate in the trial with their eligible patients. Participants were home-dwelling patients 70 years or older, using at least 7 medications regularly, and having their medications administered by the home nursing service. Patients in the control group received usual care. Randomization occurred at the FP level. A modified intent-to-treat analysis was used.

Intervention: The intervention consisted of 3 main parts: (1) clinical geriatric assessment of the patients combined with a thorough review of their medications; (2) a meeting between the geriatrician and the FP; and (3) clinical follow-up.

Main Outcomes And Measures: The primary outcome was health-related quality of life as assessed by the 15D instrument (score range, 0-1; higher scores indicate better quality of life, with a minimum clinically important change of ±0.015) at week 16. Secondary outcomes included changes in medication appropriateness, physical and cognitive functioning, use of health services, and mortality.

Results: Among 174 patients (mean [SD] age, 83.3 [7.3] years; 67.8% women; 87 randomized to the intervention group and 87 randomized to the control [usual care] group) in 70 FP clusters (36 intervention and 34 control), 158 (90.8%) completed the trial. The mean (SD) 15D instrument score at baseline was 0.708 (0.121) in the intervention group and 0.714 (0.113) in the control group. At week 16, the mean (SD) 15D instrument score was 0.698 (0.164) in the intervention group and 0.655 (0.184) in the control group, with an estimated between-group difference of 0.045 (95% CI, 0.004-0.086; P = .03). Several secondary outcomes were also in favor of the intervention. There were more drug withdrawals, reduced dosages, and new drug regimens started in the intervention group.

Conclusions And Relevance: This study's findings indicate that, among older patients exposed to polypharmacy, clinical geriatric assessments and collaborative medication reviews carried out by a geriatrician in cooperation with the patient's FP can result in positive effects on health-related quality of life.

Trial Registration: ClinicalTrials.gov identifier: NCT02379455.
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http://dx.doi.org/10.1001/jamainternmed.2019.5096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802420PMC
February 2020

Sociodemographic, clinical and pharmacological profiles of medication misuse and dependence in hospitalised older patients in Norway: a prospective cross-sectional study.

BMJ Open 2019 09 5;9(9):e031483. Epub 2019 Sep 5.

Health Services Research Unit (HØKH), Akershus University Hospital, Lørenskog, Norway.

Objectives: Timely recognition of medication misuse and dependence is crucial to avoid both adverse drug events and increasing health expenditure. Yet the detection of these disorders in older people remains challenging due to the paucity of evidence on characteristics of patients at risk. This study investigates sociodemographic, pharmacological and clinical characteristics and factors associated with prolonged medication use, misuse and dependence in hospitalised older patients, focusing on three commonly prescribed central nervous system depressants (CNSDs): opioid analgesics, benzodiazepines and z-hypnotics.

Design: A prospective, cross-sectional study complying with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.

Setting: Somatic departments of the Akershus University Hospital, Norway.

Participants: 246 patients aged 65-90 were included.

Outcome Measures: Prolonged use was defined as using CNSDs for ≥4 weeks. Misuse and dependence were assessed with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for substance abuse and dependence. We used descriptive statistics to report patients' characteristics and logistic regression to demonstrate factors associated with prolonged use, and misuse or dependence.

Results: Forty per cent of participants reported using CNSDs for ≥4 weeks. The odds of prolonged use were higher for patients aged 75-84 (OR=2.32, 95% CI 1.16 to 4.65) and ≥85 (OR=3.33, 95% CI 1.25 to 8.87) vs <75 years, for pain intensity (OR=1.02, 95% CI 1.01 to 1.04), and polypharmacy versus no polypharmacy (OR=5.16, 95% CI 2.13 to 12.55). The odds were lower for patients who completed secondary education (OR=0.33, 95% CI 0.13 to 0.83) compared with those with only basic education. Factors associated with misuse or dependence were pain intensity (OR=1.02, 95% CI 1.01 to 1.04) and concurrent use of ≥2 CNSDs (OR=3.99, 95% CI 1.34 to 11.88).

Conclusion: CNSD overuse is prevalent among hospitalised older patients, despite clear guidelines and recommendations. Our findings underline a need for stronger focus on responsible prescribing, timely detection and prevention of this issue, with special attention towards older patients, those with enhanced pain, polypharmacy and/or concurrent use of several CNSDs.

Trial Registration Number: NCT03162081.
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http://dx.doi.org/10.1136/bmjopen-2019-031483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731874PMC
September 2019

The Severity of Dependence Scale detects medication misuse and dependence among hospitalized older patients.

BMC Geriatr 2019 06 24;19(1):174. Epub 2019 Jun 24.

Health Services Research Unit (HØKH), Akershus Univeristy Hospital, PO Box 1000, 1478, Lorenskog, Norway.

Background: In older patients, timely recognition and treatment of medication misuse and dependence are crucial to secure medication safety and to avoid increasing health expenditure. Nonetheless, the detection of this condition remains challenging due to the paucity of screening instruments validated for older people. This study assesses diagnostic accuracy, reliability, validity and the factor structure of the Severity of Dependence Scale (SDS) in detecting medication misuse and dependence among hospitalized older patients, focusing on prescribed central nervous system depressants (CNSDs): opioid analgesics, benzodiazepines and z-hypnotics.

Methods: 246 adults aged 65-90 were recruited consecutively from somatic departments of the Akershus University Hospital, Norway. Among these, 100 patients were identified as prolonged users of CNSDs. Diagnostic accuracy and validity of the SDS were assessed using DSM-IV criteria for substance abuse and dependence as the reference standard. We also performed an exploratory factor analysis and assessment of internal consistency using Cronbach's alpha.

Results: The area under the ROC curve was 0.86 (95%CI = 0.79-0.93; p < 0.001). A score of 5.5 was determined as the optimal cutoff for detecting CNSD misuse and dependence among older patients. Cronbach's alpha obtained was satisfactory (α = 0.73). There was a significant positive correlation between the SDS score and DSM-IV criteria for substance abuse and dependence (Pearson's correlation coefficient = 0.61, p < 0.001). The uni-dimensionality of the SDS was documented.

Conclusions: The SDS is reliable, valid and capable of detecting medication misuse and dependence among hospitalized older patients, with good diagnostic performance. The scale thus holds promise for use in both clinical and research contexts.

Trial Registration: ClinicalTrials.gov Identifier: NCT03162081 . Registered 3 May 2017.
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http://dx.doi.org/10.1186/s12877-019-1182-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591833PMC
June 2019

Urine -2-Microglobulin, Osteopontin, and Trefoil Factor 3 May Early Predict Acute Kidney Injury and Outcome after Cardiac Arrest.

Crit Care Res Pract 2019 7;2019:4384796. Epub 2019 May 7.

Institute of Clinical Medicine, University of Oslo, P.O.Box 1072 Blindern, 0316 Oslo, Norway.

Purpose: Acute kidney injury (AKI) is a common complication after out-of-hospital cardiac arrest (OHCA), leading to increased mortality and challenging prognostication. Our aim was to examine if urine biomarkers could early predict postarrest AKI and patient outcome.

Methods: A prospective observational study of resuscitated, comatose OHCA patients admitted to Oslo University Hospital in Norway. Urine samples were collected at admission and day three postarrest and analysed for -2-microglobulin (2M), osteopontin, and trefoil factor 3 (TFF3). Outcome variables were AKI within three days according to the Kidney Disease Improving Global Outcome criteria, in addition to six-month mortality and poor neurological outcome (PNO) (cerebral performance category 3-5).

Results: Among 195 included patients (85% males, mean age 60 years), 88 (45%) developed AKI, 88 (45%) died, and 96 (49%) had PNO. In univariate analyses, increased urine 2M, osteopontin, and TFF3 levels sampled at admission and day three were independent risk factors for AKI, mortality, and PNO. Exceptions were that 2M measured at day three did not predict any of the outcomes, and TFF3 at admission did not predict AKI. In multivariate analyses, combining clinical parameters and biomarker levels, the area under the receiver operating characteristics curves (95% CI) were 0.729 (0.658-0.800), 0.797 (0.733-0.861), and 0.812 (CI 0.750-0.874) for AKI, mortality, and PNO, respectively.

Conclusions: Urine levels of 2M, osteopontin, and TFF3 at admission and day three were associated with increased risk for AKI, mortality, and PNO in comatose OHCA patients. This trail is registered with NCT01239420.
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http://dx.doi.org/10.1155/2019/4384796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530154PMC
May 2019

Validity of self-reported assessment of Severity of Dependence Scale in Medication-Overuse Headache.

Scand J Pain 2019 Oct 12;19(4):837-841. Epub 2019 Jun 12.

Research Centre, Akershus University Hospital, Lørenskog, Norway.

The interview-based Severity of Dependence Scale (SDS) predicts the outcome of withdrawal therapy in Medication-Overuse Headache (MOH). We aimed to compare the interview-based SDS with a self-administrated written version. Fifty-three MOH patients, 19 chronic headache patients without medication overuse and 25 population controls were recruited from a previous randomized controlled trial. The SDS was scored in a telephone interview by headache experts, further, the participants filled in the SDS as a part of a self-administered questionnaire. The SDS assesses scores dependence through five questions, each scored from 0 to 3. A score of ≥5 is associated with MOH. Mean SDS scores were 2.8 (SD 3.0) vs. 3.1 (SD 2.9),  = 0.12, for the interview vs. the self-reported questionnaire, with a correlation 0.78. There was a non-significant bias of 0.32 (95% limits of agreement of -3.6; 4.2) between the two methods in the Bland-Altman analysis. A self-reported SDS questionnaire can be used, and may yield valuable information as a screening tool prior to headache consultations or studies. The possibilities of designing web-based self-treatment tools based on SDS self-assessment and brief intervention may be a future approach for a large group of patients.
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http://dx.doi.org/10.1515/sjpain-2019-0022DOI Listing
October 2019

Severity of Analgesic Dependence and Medication-overuse Headache.

J Addict Med 2019 Sep/Oct;13(5):346-353

Research Centre, Akershus University Hospital, Lørenskog (CL, ESK); Department of Neurology, Akershus University Hospital, Nordbyhagen (CL, ESK); Institute of Clinical Medicine, Campus Akershus University Hospital, University of Oslo, Nordbyhagen, Norway (CL, MBR); National Addiction Centre, King's College, London, UK (MG); Head and Neck Research Group, Research Centre, Akershus University Hospital, Lørenskog (MBR); Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway (JS, ESK).

Background And Aims: Medication-overuse headache (MOH) is a common chronic headache caused by overuse of headache analgesics. It has similarities with substance dependence disorders. The treatment of choice for MOH is withdrawal of the offending analgesics. Behavioral brief intervention treatment using methods adapted from substance misuse settings is effective. Here we investigate the severity of analgesics dependence in MOH using the Severity of Dependence Scale (SDS), validate the SDS score against formal substance dependence diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and examine whether the SDS predicts successful withdrawal.

Methods: Representative recruitment from the general population; 60 MOH patients, 15 chronic headache patients without medication overuse and 25 population controls. Headaches were diagnosed using the International Classification of Headache Disorders, medication use was assessed and substance dependence classified according to the DSM-IV. The SDS was scored by interviewers blinded to patient group. Descriptive statistics were used and validity of the SDS score assessed against a substance dependence diagnosis using ROC analysis.

Results: Sixty-two percent of MOH patients overused simple analgesics, 38% centrally acting analgesics (codeine, opiates, triptans). Fifty percent of MOH patients were classified as DSM-IV substance dependent. Centrally active medication and high SDS scores were associated with higher proportions of dependence. ROC analysis showed SDS scores accurately identified dependence (area under curve 88%). Lower SDS scores were associated with successful withdrawal (P = 0.004).

Conclusions: MOH has characteristics of substance dependence which should be taken into account when choosing treatment strategy.

Trial Registration: Based on data collected in previously reported randomized BIMOH trial (; in the present manuscript, Clinical trials registration number: NCT01314768). The present part, however, represents observational data and is not a treatment trial.
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http://dx.doi.org/10.1097/ADM.0000000000000504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791494PMC
July 2020

Impact of chronic headache on workdays, unemployment and disutility in the general population.

J Epidemiol Community Health 2019 04 25;73(4):360-367. Epub 2019 Jan 25.

Head and Neck Research Group, Research Centre, Akershus Universitetssykehus HF, Lorenskog, Norway.

Background: Data on the socioeconomic burden of chronic headache (≥15 days/last month or 180 days/year) is lacking. This study investigated the impact of chronic headache on sickness absence, unemployment and disutility in the general population in Norway.

Methods: 30 000 persons aged 30-44 from the general population were screened for chronic headache by a screening questionnaire. The responder rate was 71%. The International Classification of Headache Disorders was used. We analysed the association of chronic headache with lost workdays, days with ≥50% reduced productivity, sick leave, unemployment and disutility, as assessed with the Short-Form Six-Dimension (SF-6D) in separate regression analyses.

Results: Eighty-three per cent (427/516, 79% women) of the eligible participants completed the data on workdays and utility. They reported a mean of 9.7 (SD 24.8) workdays lost over the last 3 months, because of headache. The mean disutility score (1-SF-6D score) was 0.41. Thirty-three per cent were on long-term (>1 year) sick leave. The OR for being on sick leave was 1.9 (95% CI 1.1 to 3.2, p=0.017) for those with secondary compared with primary chronic headache. Similarly, the OR for increased number of workdays lost to headache was 3.5 (95% CI 1.8 to 6.5, p<0.001) and for unemployment 1.7 (95% CI 1.0 to 2.9, p=0.07), for those with secondary compared with primary chronic headache. Secondary chronic headache, high headache frequency and high psychological distress were significantly associated with higher disutility score.

Conclusions: The burden of chronic headache in the general population is substantial with high rates of lost workdays and disutility.
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http://dx.doi.org/10.1136/jech-2018-211127DOI Listing
April 2019

Illness perception in people with primary and secondary chronic headache in the general population.

J Psychosom Res 2019 01 5;116:83-92. Epub 2018 Dec 5.

Head and Neck Research Group, Research Centre, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Campus Akershus University Hospital, University of Oslo, Nordbyhagen, Norway.

Background: Chronic headache (headache ≥15 days/month) is a leading cause of disability. Illness perception, beliefs and cognitive models are likely central for patient understanding of their chronic pain condition and are associated with treatment outcome. However, these factors are insufficiently described in chronic headache.

Objective: To describe illness perception, and to explore the effect of background variables and headache characteristics on illness perceptions in primary and secondary chronic headaches in the general population.

Methods: 30,000 persons aged 3044 from the general population were screened for chronic headache by a mailed questionnaire. Those with self-reported chronic headache were interviewed by headache specialists. The questionnaire response rate was 71%, and the interview participation rate was 74%. The International Classification of Headache Disorders III was applied. Illness perception was assessed by the Revised Illness Perception Questionnaire (IPQ-R). The statistical approach was exploratory.

Results: 405 of the 516 eligible participants (78%) completed the IPQ-R. Confirmatory factor analysis showed good internal validity in chronic headache. People believed their chronic headache to be long-lasting, with negative life consequences including emotional distress. Severe headache-related disability was associated with more perception of chronicity, more perceived consequences, emotional load and illness identity and less illness coherence. People with secondary chronic headache scored significantly higher on chronicity and life consequences, and had less personal control than those with primary chronic headache.

Conclusion: Chronic primary and secondary headache is associated with a high symptom burden and chronicity with large perceived negative consequences for daily living, suggesting multidisciplinary management may be necessary.
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http://dx.doi.org/10.1016/j.jpsychores.2018.12.001DOI Listing
January 2019

Symptoms of premenstrual syndrome in female migraineurs with and without menstrual migraine.

J Headache Pain 2018 Oct 17;19(1):97. Epub 2018 Oct 17.

Head and Neck Research Group, Research Centre, Akershus University hospital, Lørenskog, Norway.

Background: Menstrual migraine (MM) and premenstrual syndrome (PMS) are two conditions linked to specific phases of the menstrual cycle. The exact pathophysiological mechanisms are not fully understood, but both conditions are hypothesized to be triggered by female sex hormones. Co-occurrence of MM and PMS is controversial. The objective of this population-based study was to compare self-assessed symptoms of PMS in female migraineurs with and without MM. A total of 237 women from the general population who self-reported migraine in at least50% of their menstruations in a screening questionnaire were invited to a clinical interview and diagnosed by a neurologist according to the International Classification of Headache Disorders II (ICHD II), including the appendix criteria for MM. All women were asked to complete a self-administered form containing 11 questions about PMS-symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. The number of PMS symptoms was compared among migraineurs with and without MM. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS).

Findings: A total of 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n = 61) or because they did not fulfil the ICHD-criteria for migraine (n = 6). Among the remaining 126 migraineurs, 78 had MM and 48 non-menstrually related migraine. PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs. 5.9, p = 0.84). Women with MM reported more migraine days/month, longer lasting migraine attacks and higher HIT-6 scores than those without MM, but MIDAS scores were similar.

Conclusion: We did not find any difference in number of self-reported PMS-symptoms between migraineurs with and without MM.
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http://dx.doi.org/10.1186/s10194-018-0931-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755584PMC
October 2018

Psychological distress, neuroticism and disability associated with secondary chronic headache in the general population - the Akershus study of chronic headache.

J Headache Pain 2018 Aug 3;19(1):62. Epub 2018 Aug 3.

Head and Neck Research Group, Research Centre, Akershus University Hospital, Lørenskog, Norway.

Background: Primary headaches are associated with psychological distress, neuroticism and disability. However, little is known about headache-related disability and psychological distress among people with secondary chronic headaches.

Methods: 30,000 persons aged 30-44 from the general population was screened for headache by a questionnaire. The responder rate was 71%. The International Classification of Headache Disorders with supplementary definitions for chronic rhinosinusitis and cervicogenic headache were used. The Hopkins Symptom Checklist-25 assessed high psychological distress, the Migraine Disability Assessment questionnaire assessed disability, and Eysenck Personality Questionnaire assessed neuroticism.

Results: Ninety-five of the 113 eligible participants (84%) completed the self-reported questionnaire. A total of 38 people had chronic post-traumatic headache, 21 had cervicogenic headache, and 39 had headache attributed to chronic rhinosinusitis, while 9 had co-occurrence of chronic post-traumatic and cervicogenic headache. Six persons had miscellaneous secondary chronic headaches. Overall, 49% of those with secondary chronic headache reported high psychological distress, which is significantly higher than in the general population. A high level of neuroticism was significantly more common in those with secondary chronic headache than in the general population. Severe headache-related disability was reported by 69%. 92 persons were followed up after 3 years. A low headache frequency was the only significant predictor of improvement of ≥ 25% in headache days. Having post-traumatic or cervicogenic headache and not headache attributed to chronic rhinosinusitis predicted an increased risk > 25% worsening of headache days or having a severe disability at 3 years follow-up.

Conclusion: Psychological distress and neuroticism were more common among people with secondary chronic headache than in the general population. Only a high headache frequency was significantly associated with increased headache disability at baseline and a poor prognosis in the long term.
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http://dx.doi.org/10.1186/s10194-018-0894-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095768PMC
August 2018

Characteristics of menstrual versus non-menstrual migraine during pregnancy: a longitudinal population-based study.

J Headache Pain 2018 Apr 2;19(1):27. Epub 2018 Apr 2.

Health Services Research Centre, Akershus University Hospital, Post Box 1000, 1478, Lørenskog, Oslo, Norway.

Background: Migraine is a common headache disorder that affects mostly women. In half of these, migraine is menstrually associated, and ranges from completely asymptomatic to frequent pain throughout pregnancy.

Methods: The aim of the study was to define the pattern (frequency, intensity, analgesics use) of migrainous headaches among women with and without menstural migraine (MM) during pregnancy, and define how hormonally-related factors affect its intensity.

Results: The analysis was based upon data from 280 women, 18.6% of them having a self-reported MM. Women with MM described a higher headache intensity during early pregnancy and postpartum compared those without MM, but both groups showed improvement during the second half of pregnancy and directly after delivery. Hormonal factors and pre-menstrual syndrome had no effect upon headache frequency, but may affect headache intensity.

Conclusions: Individual treatment plan is necessary for women with migrainous headaches during pregnancy, especially for those suffering highest symptoms load.
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http://dx.doi.org/10.1186/s10194-018-0853-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880793PMC
April 2018

Reply to the letter by Min et al.

Cephalalgia 2018 09 3;38(10):1701-1702. Epub 2017 Dec 3.

1 Head and Neck Research Group, Research Centre, Akershus University Hospital, Lørenskog, Norway.

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http://dx.doi.org/10.1177/0333102417747213DOI Listing
September 2018

The association between adolescent and parental use of non-prescription analgesics for headache and other somatic pain - A cross-sectional study.

Scand J Pain 2017 07 25;16:114-121. Epub 2017 May 25.

Health Services Research Centre, Akershus University Hospital, Lørenskog, Norway; Department Neurology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Campus Akershus University Hospital, University of Oslo, Norway. Electronic address:

Background And Purpose: Over the last years, concern has been expressed about adolescents' possible liberal attitude towards - and use of - non-prescription analgesics. A high consumption of analgesics is unfortunate as it may lead to various harmful effects and worsening of headache. In order to address this challenge, it is necessary to achieve a more extensive knowledge about adolescent consumption. The main aim of this study was to examine the association between adolescent and parental use of non-prescription analgesics, taking into account headache as well as other somatic pain. The effects of parental prescription analgesics use was a secondary aim.

Methods: The study is based on data from two cross-sectional health studies conducted in 2005 and 2012 in Norway, including 646 adolescents and an accompanying parent. By using sample weights, the final weighted sample used in the analysis was 1326. Data was collected through postal questionnaires to parents and adolescents as well as parental telephone interviews. Questionnaires included questions on different pain locations and the pain for each location was graded according to how troubling the pain was. Medication data on prescription and non-prescription analgesics was from telephone interviews and was quantified based on the pattern over the past 4 weeks. Multivariate logistic regression models and complex samples analyses were used.

Results: 20% of adolescents were reported as using non-prescription analgesics during the previous 4 weeks. Girls were more often reported to use non-prescription analgesics than boys. Headache and all other somatic pain locations except back pain were reported more frequently among girls while boys more frequently reported back pain. There was a clear association between the use of non-prescription analgesics and headache with 34% of adolescents with headache using non-prescription analgesics versus 19% of adolescents with other somatic pain and 14% of adolescents not reporting pain. Among adolescents reporting headache, 9% were reported to use non-prescription analgesics daily or almost daily versus 3% and 2% among those reporting other somatic pain and reporting no pain respectively. In addition, parental use of non-prescription analgesics was a strong independent predictor of adolescent use (adjusted OR 1.69 for boys, 1.54 for girls). This relationship increased when the adolescents were less bothered by headache themselves.

Conclusion: Headache is the dominant medication-driving pain for non-prescription analgesics among adolescents but parental medication use of non-prescription analgesics also strongly influences adolescent use.

Implications: There is a need for health services to improve information to parents and adolescents about risks associated with use of analgesics and also to work on prophylactic strategies focusing on adolescents. Parents should be made aware that their medicine use strongly influences that of their children.
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http://dx.doi.org/10.1016/j.sjpain.2017.04.069DOI Listing
July 2017

Excessive daytime sleepiness in secondary chronic headache from the general population.

J Headache Pain 2017 Aug 16;18(1):85. Epub 2017 Aug 16.

Head and Neck Research Group, Research Centre, Akershus University Hospital, PO Box 95, 1478, Lørenskog, Norway.

Background: Excessive daytime sleepiness (EDS, defined as Epworth sleepiness scale score > 10) is a common symptom, with a prevalence of 10-20% in the general population. It is associated with headache and other chronic pain disorders. However, little is known about the prevalence of EDS among people with secondary chronic headaches.

Findings: A total of 30,000 persons aged 30-44 from the general population was screened for headache by a questionnaire. The 633 eligible participants with self-reported chronic headache were interviewed and examined by a headache specialist who applied the International Classification of Headache Disorders with supplementary definitions for chronic rhinosinusitis and cervicogenic headache. A total of 93 participants had secondary chronic headache and completed the ESS. A total of 47 participants had chronic post-traumatic headache (CPTH) and/or cervicogenic headache (CEH), 39 participants had headache attributed to chronic rhinosinusitis (HACRS), while 7 had other secondary headaches. 23.3% of those with CPTH, CEH or HACRS reported EDS. In multivariable logistic regression analysis the odds ratios of EDS were not significantly different in people with CPTH/CEH or HACRS.

Conclusion: Almost one out of four subjects with secondary chronic headache reported EDS with no differences between the various secondary chronic headaches.
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http://dx.doi.org/10.1186/s10194-017-0794-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559413PMC
August 2017

Patterns and predictors of analgesic use in pregnancy: a longitudinal drug utilization study with special focus on women with migraine.

BMC Pregnancy Childbirth 2017 Jul 14;17(1):224. Epub 2017 Jul 14.

Pharmacoepidemiology & Drug Safety Research Group, School of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, P.O. Box. 1068, Blindern, 0316, Oslo, Norway.

Background: Few studies have investigated the drug utilization patterns and factors predicting drug use in pregnant women with migraine. This longitudinal drug utilization study aimed to describe patterns of analgesic use in a sample of Norwegian pregnant women according to their migraine history, and to identify predictors for analgesic use among these women.

Methods: Pregnant women giving birth at Akershus University Hospital between 2008 and 2010 were recruited at ultrasound examination in gestational week 17. Data were collected by questionnaires in gestational weeks 17 and 32, and at 8 weeks postpartum, and linked to birth records. Women were grouped into four categories according to migraine history: no migraine history, previous migraine history, recent migraine history (within 1 year prior to pregnancy) and migraine in pregnancy. Patterns of use of analgesics were analyzed descriptively. Multivariable logistic regression was used to identify factors predicting analgesic use.

Results: Out of 1981 women, 5.0% reported having migraine in pregnancy, 13.2% had a recent history of migraine, 11.5% had a previous history of migraine, and 68.8% reported no history of migraine. Analgesic use declined during pregnancy. Many women switched from triptans and non-steroidal anti-inflammatory drugs to paracetamol, which constituted most of the analgesic use. Factors associated with analgesic use included recent migraine history (OR 1.6, 95% CI 1.2-2.2), more severe headache intensity (OR 1.3, 95% CI 1.3-1.4), smoking (OR 1.9, 95% CI 1.1-3.3) and multiparity (OR 1.4, 95% CI 1.1-1.7).

Conclusions: Women with migraine stop or switch medications during pregnancy. Analgesic use in pregnancy is affected by migraine characteristics and intensity, and also by socio-demographic factors. Clinicians should bear this in mind when giving advice on adequate management of migraine in pregnancy and safe analgesic use.
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http://dx.doi.org/10.1186/s12884-017-1399-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512742PMC
July 2017
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