Publications by authors named "Per Liv"

27 Publications

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A tactile resonance sensor for prostate cancer detection - evaluation on human prostate tissue.

Biomed Phys Eng Express 2021 Feb 15. Epub 2021 Feb 15.

Umeå Universitet Medicinska fakulteten, Medical Bioscience, Pathology, Umea, 90185, SWEDEN.

Prostate cancer surgery risks erectile problems and incontinence for the patient. An instrument for guiding surgeons to avoid nerve bundle damage and ensure complete cancer removal is desirable. We present a tactile resonance sensor made of PZT ceramics, mounted in a 3D motorized translation stage for scanning and measuring tissue stiffness for detecting cancer in human prostate. The sensor may be used during surgery for guidance, scanning the prostate surface for the presence of cancer, indicating migration of cancer cells into surrounding tissue. Ten fresh prostates, obtained from patients undergoing prostate cancer surgery, were cut into 0.5 cm thick slices. Each slice was measured for tissue stiffness at about 25 different sites and compared to histology for validation cancer prediction by stiffness. The statistical analysis was based on a total of 148 sites with non-cancer and 40 sites with cancer. Using a generalized linear mixed model (GLMM), the stiffness data predicted cancer with an area under the curve of 0.74, after correcting for overfitting using bootstrap validation. Mean prostate stiffness on the logarithmic scale (p = 0.015) and standardized Z-scores (p = 0.025) were both significant predictors of cancer. This study concludes that stiffness measured by the tactile resonance sensor is a significant predictor of prostate cancer with potential for future development towards a clinical instrument for surgical guidance.
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http://dx.doi.org/10.1088/2057-1976/abe681DOI Listing
February 2021

Prevalence of temporomandibular disorder in adult patients with chronic pain.

Scand J Pain 2021 01 24;21(1):41-47. Epub 2020 Sep 24.

Umea Universitet Medicinska fakulteten, Spiralvägen 27, Umeå, Sverige, 901 85, Sweden.

Objectives: Chronic pain patients often suffer in multiple locations. In health care, examinations of bodily pain usually do not include questions about temporomandibular disorders (TMD); hence TMD symptoms and potential comorbidities are not regularly assessed. Therefore, the primary aim was to evaluate the prevalence of TMD in patients referred to a pain rehabilitation clinic, and the secondary aim was to evaluate possible factors associated with TMD symptoms.

Methods: Consecutive chronic pain patients referred to the Pain Rehabilitation Clinic at the Umeå University Hospital in Sweden were included. TMD symptoms were assessed using three valid screening questions - 3Q/TMD. Pain sites, emotional distress, kinesiophobia, and demographics were obtained from the Swedish Quality Registry for Pain Rehabilitation.

Results: In total, 188 (144 women) chronic pain patients (mean age 41.8 years) were included. Of these, 123 (96 women) answered affirmatively to at least one of the 3Q/TMD. The relative risk of TMD symptoms among the patients with chronic pain, in comparison to the general population, was 7.1 (95% CI 5.9-8.4). Age was the only independent variable associated with TMD among the patients (p = 0.018).

Conclusions: The prevalence of TMD symptoms was higher in a chronic pain population compared to the general population. The 3Q/TMD questionnaire could be a suitable screening tool at pain rehabilitation clinics to identify patients for further examination of involvement of pain in the trigeminal region. Our results reinforce the clinical importance of paying attention to concurrent widespread pain and local TMD symptoms.
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http://dx.doi.org/10.1515/sjpain-2020-0077DOI Listing
January 2021

Location matters: highly divergent protein levels in samples from different CNS compartments in a clinical trial of rituximab for progressive MS.

Fluids Barriers CNS 2020 Jul 29;17(1):49. Epub 2020 Jul 29.

Department of Neurosciences, Uppsala University, Uppsala, Sweden.

Background: The relationship between proteins in different CNS extracellular compartments is unknown. In this study the levels of selected proteins in three compartments in people with progressive multiple sclerosis (PMS) were compared.

Methods: During an open label, phase 1b study on intraventricular administration of rituximab for PMS, samples were collected from the interstitial space (ISS) of the brain through microdialysis. Samples were also obtained from ventricular and lumbar cerebrospinal fluid (CSF). These samples were analyzed with a multiplexed proximity extension assay, measuring the levels of 180 proteins split equally between two panels, detecting proteins associated with immunology and neurology, respectively.

Results: Considerable differences in concentrations were observed between the three analyzed compartments. Compared to ventricular CSF, ISS fluid contained statistically significant higher levels of 25 proteins (84% immunology panel and 16% neurology panel). Ventricular CSF contained significantly higher levels of 54 proteins (31% immunology panel and 69% neurology panel) compared to ISS fluid, and 17 proteins (76% immunology panel and 24% neurology panel) compared to lumbar CSF. Lumbar CSF showed significantly higher levels of 115 proteins (32% immunology panel and 68% neurology panel) compared to ventricular CSF. The three compartments displayed poor correlation with a median Spearman's rho of -0.1 (IQR 0.4) between ISS and ventricular CSF and 0.3 (IQR 0.4) between ventricular and lumbar CSF.

Conclusion: A substantial heterogeneity in the protein levels of samples obtained from different CNS compartments was seen. Therefore, data obtained from analysis of lumbar CSF should be interpreted with caution when making conclusions about pathophysiological processes in brain tissue.
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http://dx.doi.org/10.1186/s12987-020-00205-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390226PMC
July 2020

Increasing gender differences in the prevalence and chronification of orofacial pain in the population.

Pain 2020 08 16;161(8):1768-1775. Epub 2020 Mar 16.

Department of Odontology/Clinical Oral Physiology, Faculty of Medicine, University of Umeå , Umeå , Sweden.

Although a fluctuating pattern of orofacial pain across the life span has been proposed, data on its natural course are lacking. The longitudinal course of orofacial pain in the general population was evaluated using data from routine dental check-ups at all Public Dental Health services in Västerbotten, Sweden. In a large population sample, 2 screening questions were used to identify individuals with pain once a week or more in the orofacial area. Incidence and longitudinal course of orofacial pain were evaluated using annual data for 2010 to 2017. To evaluate predictors for orofacial pain remaining over time, individuals who reported pain on at least 2 consecutive dental check-ups were considered persistent. A generalized estimating equation model was used to analyze the prevalence, accounting for repeated observations on the same individuals. In total, 180,308 individuals (equal gender distribution) were examined in 525,707 dental check-ups. More women than men reported orofacial pain (odds ratio 2.58, 95% confidence interval [CI] 2.48-2.68), and there was a significant increase in the prevalence of reported pain from 2010 to 2017 in both women and men. Longitudinal data for 135,800 individuals were available for incidence analysis. Women were at higher risk of both developing orofacial pain (incidence rate ratio 2.37; 95% CI 2.25-2.50) and reporting pain in consecutive check-ups (incidence rate ratio 2.56; 95% CI 2.29-2.87). In the northern Swedish population studied, the prevalence of orofacial pain increases over time and more so in women, thus indicating increasing differences in gender for orofacial pain.
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http://dx.doi.org/10.1097/j.pain.0000000000001872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365674PMC
August 2020

Effectiveness of a self-managed digital exercise programme to prevent falls in older community-dwelling adults: study protocol for the Safe Step randomised controlled trial.

BMJ Open 2020 05 17;10(5):e036194. Epub 2020 May 17.

Department of Community Medicine and Rehabilitation, Physiotherapy, Umeå University, Umeå, Sweden.

Introduction: Exercise interventions have a strong evidence base for falls prevention. However, exercise can be challenging to implement and often has limited reach and poor adherence. Digital technology provides opportunities for both increased access to the intervention and support over time. Further knowledge needs to be gained regarding the effectiveness of completely self-managed digital exercise interventions. The main objective of this study is to compare the effectiveness of a self-managed digital exercise programme, Safe Step, in combination with monthly educational videos with educational videos alone, on falls over 1 year in older community-dwelling adults.

Methods And Analysis: A two-arm parallel randomised controlled trial will be conducted with at least 1400 community-living older adults (70+ years) who experience impaired balance. Participants will be recruited throughout Sweden with enrolment through the project website. They will be randomly allocated to either the Safe Step exercise programme with additional monthly educational videos about healthy ageing and fall prevention, or the monthly education videos alone. Participants receiving the exercise intervention will be asked to exercise at home for at least 30 min, 3 times/week with support of the Safe Step application. The primary outcome will be rate of falls (fall per person year). Participants will keep a fall calendar and report falls at the end of each month through a digital questionnaire. Further assessments of secondary outcomes will be made through self-reported questionnaires and a self-test of 30 s chair stand test at baseline and 3, 6, 9 and 12 months after study start. Data will be analysed according to the intention-to-treat principle.

Ethics And Dissemination: Ethical approval was obtained by The Regional Ethical Review Board in Umeå (Dnr 2018/433-31). Findings will be disseminated through the project web-site, peer-reviewed journals, national and international conferences and through senior citizen organisations' newsletters.

Trial Registration Number: NCT03963570.
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http://dx.doi.org/10.1136/bmjopen-2019-036194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239551PMC
May 2020

Vitamin D status and cardiometabolic risk markers in young Swedish children: a double-blind randomized clinical trial comparing different doses of vitamin D supplements.

Am J Clin Nutr 2020 04;111(4):779-786

Department of Clinical Sciences, Pediatrics, Lund University, Lund, Sweden.

Background: Observational studies have linked low vitamin D status to unfavorable cardiometabolic risk markers, but double-blinded vitamin D intervention studies in children are scarce.

Objectives: The aim was to evaluate the effect of different doses of a vitamin D supplement on cardiometabolic risk markers in young healthy Swedish children with fair and dark skin.

Methods: Cardiometabolic risk markers were analyzed as secondary outcomes of a double-blind, randomized, milk-based vitamin D intervention trial conducted during late fall and winter in 2 areas of Sweden (latitude 63°N and 55°N, respectively) in both fair- and dark-skinned 5- to 7-y-old children. During the 3-mo intervention, 206 children were randomly assigned to a daily milk-based vitamin D3 supplement of either 10 or 25 µg or placebo (2 µg; only at 55°N). Anthropometric measures, blood pressure, serum 25-hydroxyvitamin D [25(OH)D], total cholesterol, HDL cholesterol, apoA-I, apoB, and C-reactive protein (CRP) were analyzed and non-HDL cholesterol calculated at baseline and after the intervention.

Results: At baseline, serum 25(OH)D was negatively associated with systolic and diastolic blood pressure (β = -0.194; 95% CI: -0.153, -0.013; and β = -0.187; 95% CI: -0.150, -0.011, respectively). At follow-up, there was no statistically significant difference in any of the cardiometabolic markers between groups.

Conclusions: We could not confirm any effect of vitamin D supplementation on serum lipids, blood pressure, or CRP in healthy 5- to 7-y-old children. The study was registered at clinicaltrials.gov (NCT01741324).
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http://dx.doi.org/10.1093/ajcn/nqaa031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138658PMC
April 2020

Reply.

J Cataract Refract Surg 2019 11;45(11):1692-1693

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http://dx.doi.org/10.1016/j.jcrs.2019.08.049DOI Listing
November 2019

The impact of corneal guttata on the results of cataract surgery.

J Cataract Refract Surg 2019 06 6;45(6):803-809. Epub 2019 Apr 6.

Department of Clinical Science/Ophthalmology, Umeå University, Umeå, Sweden. Electronic address:

Purpose: To study the impact of corneal guttata on postoperative visual acuity and patients' self-assessed visual function after cataract surgery.

Setting: Patient data from 49 Swedish cataract surgery units.

Design: Retrospective cross-sectional register-based study.

Methods: Data from patients who had cataract surgery from 2010 to 2017 and completed the Catquest-9SF questionnaire were obtained from the Swedish National Cataract Register. Logistic proportional odds regression was used to model the impact of corneal guttata on the visual acuity and self-assessed visual function. Adjustments were made for age, sex, ocular comorbidities, days to follow-up, preoperative corrected distance visual acuity (CDVA) and preoperative Rasch person score. The main outcome measures were postoperative CDVA and Rasch person score calculated from the Catquest-9SF questionnaire.

Results: The study comprised data from 33 741 patients. Cataract surgery greatly improved CDVA and self-assessed visual function in patients both with and without corneal guttata. Still, corneal guttata was significantly associated with a poorer visual acuity and a worse self-assessed visual function after cataract surgery. The negative effect of corneal guttata on visual acuity was most prominent during the first 3 weeks postoperatively, but it persisted at least 3 months postoperatively.

Conclusions: Patients with corneal guttata benefit substantially from cataract surgery but have an additional risk for inferior results compared with patients without corneal guttata. These findings could serve as valuable tools in clinical practice, in particular, when deciding to perform cataract surgery and how to inform the patient about surgical benefits and risks.
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http://dx.doi.org/10.1016/j.jcrs.2018.12.023DOI Listing
June 2019

Living with a pacemaker: patient-reported outcome of a pacemaker system.

BMC Cardiovasc Disord 2018 06 4;18(1):110. Epub 2018 Jun 4.

Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.

Background: The aim of this study was to assess among pacemaker patients their overall satisfaction with the pacemaker system, pain, soreness/discomfort, cosmetic results, restrictions due to impaired movement of the shoulder/arm/chest, related sleep disturbances, and concern about possible device malfunction.

Methods: The seven-item questionnaire was mailed to patients from a single center who had a pacemaker implant or replacement between 2006 and 2016. A higher score indicated worse outcome on a visual analog scale (VAS) of 0-100 mm.

Results: The response rate was 75.5% and 342 questionniares were analyzed. Median age of respondents was 77.6 years and 57.0% were males. In total, 65 complications requiring surgery (10 pocket corrections (2.9%), 5 in females) occurred during a median follow-up of 5.6 years.The distribution of the primary outcome had a median score of 5 while the 75th percentile was 13. Cosmetic appearance was significantly associated with reoperation (but not other variables). Overall scores for men and women were 5 vs. 6, respectively, which achieved significance (p = 0.042). Median ratings of pain, soreness/discomfort, cosmetic appearance, range of motion, sleep, and concern about device malfunction were all ≤5. Females reported worse outcomes for all questions, except for cosmetic results and concern about malfunction.

Conclusions: The vast majority of patients report excellent overall satisfaction with the pacemaker system, and are not affected by pain, soreness/discomfort, or concern about device malfunction. They also reported favourable outcomes with respect to cosmetic results, shoulder movement, and sleep. However, some patients underwent a surgical correction of the pacemaker pocket.
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http://dx.doi.org/10.1186/s12872-018-0849-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987385PMC
June 2018

Placement Of Cardiac PacemaKEr Trial (POCKET) - rationale and design: a randomized controlled trial.

Heart Int 2017 Jan-Dec;12(1):e8-e11. Epub 2017 Apr 14.

Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle - Sweden.

Background: A pacemaker system consists of one or two leads connected to a device that is implanted into a pocket formed just below the collarbone. This pocket is typically subcutaneous, that is, located just above the pectoral fascia. Even though the size of pacemakers has decreased markedly, complications due to superficial implants do occur. An alternative technique would be intramuscular placement of the pacemaker device, but there are no randomized controlled trials (RCTs) to support this approach, which is the rationale for the Placement Of Cardiac PacemaKEr Trial (POCKET). The aim is to study if intramuscular is superior to subcutaneous placement of a pacemaker pocket.

Methods: In October 2016, we started to enroll 200 consecutive patients with an indication for bradycardia pacemaker implantation. Patients are randomized to random block sizes, stratified by age group (cut-off: 65 years) and sex, and then randomized to either subcutaneous or intramuscular implant. A concealed allocation procedure is employed, using sequentially numbered, sealed envelopes. Pocket site is blinded to the patient and in all subsequent care. The primary endpoint is patient overall satisfaction with the pocket location at 24 months as measured using a visual analog scale (VAS) 0-10. Secondary endpoints are: complications, patient-reported satisfaction at 1, 12, and 24 months (overall satisfaction, pain, discomfort, degree of unsightly appearance, movement problems, and sleep problems due to device).

Conclusions: POCKET is a prospective interventional RCT designed to evaluate if intramuscular is superior to subcutaneous placement of a bradycardia pacemaker during a two-year follow-up.
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http://dx.doi.org/10.5301/heartint.5000235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421194PMC
April 2017

A novel method for superimposition and measurements on maxillary digital 3D models-studies on validity and reliability.

Eur J Orthod 2018 01;40(1):45-51

Department of Orthodontics, Faculty of Odontology, Malmö University, Malmö, Sweden.

Background: Serial 3D models can be used to analyze changes, but correct superimposition is crucial before measurements can be assessed. Earlier studies show that every palatal structure changes due to growth or treatment. Here, we describe a new method that uses an algorithm-based analysis to perform superimpositions and measurements in maxillary 3D models. This method can be used to identify deformations. In a second step, only unchanged areas are used for superimposition.

Objectives: This study investigates the validity and reliability of this novel method.

Methods: Digital 3D models from 16 cases were modified by an independent 3D engineer to simulate space closure and growth. True values for tooth movements were available as reference. Measurements and repeated measurements were performed by four observers.

Results: The total tooth movement had an absolute mean error of 0.0225 mm (SD 0.03). The intraclass correlation coefficient (ICC) was 0.9996. Rotational measurements had an absolute mean error of 0.0291 degrees (SD 0.04 degrees) and an ICC of 0.9999.

Limitations: Serial models need to be taken with a moderate interval (1 to 2 years). Obvious changed areas in the palate need to be cropped before processing the models.

Conclusion: The tested method is valid and reliable with excellent accuracy and precision even when changes through growth or orthodontic treatment occur.
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http://dx.doi.org/10.1093/ejo/cjx029DOI Listing
January 2018

Non-small Cell Lung Cancer (NSCLC) in Octogenarians in Clinical Practice.

Anticancer Res 2016 10;36(10):5397-5402

Department of Respiratory Medicine, Gävle Hospital, Gävle, Sweden.

Background/aim: Globally, an increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue. We performed a retrospective study of our patients to demonstrate how octogenarians with non-small cell lung cancer (NSCLC) are treated in real-life clinical practice.

Patients And Methods: This was a retrospective observational study of all elderly (≥80 years) patients with NSCLC referred to the Department of Respiratory Medicine and Allergy, Karolinska Hospital, Sweden, 2003-2010, and followed until June, 2016.

Results: In total, 452 patients, 216 (47.8%) men and 236 (52.2%) women, were included. The mean and median age was 83 years; 28 (6.2%) were aged 90 years or more. Current or former smokers constituted 91.1%, with men having smoked more (p<0.001). There was no difference in performance status (PS) between genders with PS 0-1 in 45.4%, PS 2 in 25.6% and PS3-4 in 29%. About a third each was diagnosed in stages 1-II, III and IV. Adenocarcinoma was most common (45.6%), 18.1% had squamous cell carcinoma, while histological diagnosis was unavailable in 23.2%. Best supportive care (BSC) was given only to 209 patients (46.2%). Potentially curative therapy was administered to 16.5% of men and 20.3% of the women with surgery performed in 35 patients (7.8%) and stereotactic body radiation therapy (SBRT) in 48 patients (10.6%). Chemotherapy was given to 51 patients (11.2%) and palliative radiotherapy to 77 (17.0%). Second-line chemotherapy was given in 4% and third-line in 1.5%. Only one patient received fourth-line. Male patients who received chemotherapy survived a mean of 281 days and for female patients it was 332 days (not significant). Median overall survival (OS) was 115 days in patients receiving BSC and 362 days in patients given any therapy. Patients who underwent surgery for stage I-II had a median OS of 5.6 years compared to 3.5 years for patients given SBRT.

Conclusion: Treatment of NSCLC patients 80 years and older with any modality is feasible with a good PS. Survival is fairly good with surgery or SBRT.
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http://dx.doi.org/10.21873/anticanres.11115DOI Listing
October 2016

Observer performance in estimating upper arm elevation angles under ideal viewing conditions when assisted by posture matching software.

Appl Ergon 2016 Jul 8;55:208-215. Epub 2016 Mar 8.

Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, University of Gävle, Gävle SE-801 76, Sweden; Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle SE-801 88, Sweden. Electronic address:

Selecting a suitable body posture measurement method requires performance indices of candidate tools. Such data are lacking for observational assessments made at a high degree of resolution. The aim of this study was to determine the performance (bias and between- and within-observer variance) of novice observers estimating upper arm elevation postures assisted by posture matching software to the nearest degree from still images taken under ideal conditions. Estimates were minimally biased from true angles: the mean error across observers was less than 2°. Variance between observers was minimal. Considerable variance within observers, however, underlined the risk of relying on single observations. Observers were more proficient at estimating 0° and 90° postures, and less proficient at 60°. Thus, under ideal visual conditions observers, on average, proved proficient at high resolution posture estimates; further investigation is required to determine how non-optimal image conditions, as would be expected from occupational data, impact proficiency.
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http://dx.doi.org/10.1016/j.apergo.2016.01.012DOI Listing
July 2016

Causes of death and mortality in hypertrophic cardiomyopathy patients with implantable defibrillators in Sweden.

J Cardiovasc Med (Hagerstown) 2016 Jul;17(7):478-84

aDepartment of Medicine, Cardiology Research Unit, Karolinska Institutet, Stockholm bCentre for Research and Development, Uppsala University/Region Gävleborg, Gävle cHeart Center and Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

Aims: Implantable defibrillators (ICDs) successfully terminate ventricular arrhythmias in hypertrophic cardiomyopathy (HCM), protect against bradycardia, and monitor atrial arrhythmias. This may alter the natural history and causes of death.

Methods: This nationwide observational longitudinal retrospective study of all HCM patients implanted during 1995-2012 obtained data from the Swedish ICD Registry, the National Patient Register, the Cause of Death Register, and were validated by review of medical records.

Results: Of 342 patients (mean age 51.8 years, 70.8% males), 45 died during a total follow-up of 1847 years (mean 5.4 years). Mean age at death was 68.2 years (range 21-83 years; 12 were ≥75 years). Mean follow-up time among the deceased was 4.9 years (quartiles 1.4-7.4 years). All-cause mortality was higher in HCM patients compared with the age and sex-matched Swedish general population (standardized mortality ratio 3.4; 95% confidence interval 2.4-4.5; P < 0.001). Main cause of death was heart failure (n = 27), stroke (n = 5), cancer (n = 3), myocardial infarction (n = 2), sepsis (n = 2), and others (n = 4). Two patients died suddenly, one after the ICD was turned off because of inappropriate shocks, and one patient whose device system was removed after infection. HCM was the main cause of death in 76% of the cases, mainly because of progressive heart failure.

Conclusion: For HCM patients, ICDs almost eliminate premature arrhythmic death and result in a shift to heart failure as the cause of death in the majority of cases. Still, mortality in HCM patients remains elevated and management of heart failure and comorbidities must be improved to increase survival.
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http://dx.doi.org/10.2459/JCM.0000000000000359DOI Listing
July 2016

Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy.

Pacing Clin Electrophysiol 2016 Mar 21;39(3):291-301. Epub 2016 Jan 21.

Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

Background: Risk stratification of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is mainly based on evaluations from patients at highly specialized centers.

Aim: To evaluate risk markers for appropriate implantable cardioverter defibrillator (ICD) therapy in an unselected, nationwide cohort of HCM.

Methods: Patients with an ICD due to HCM were identified from the Swedish ICD Registry since its start in 1995, merged with Patient Register data, and medical records were retrieved. Risk markers for ventricular arrhythmias leading to appropriate ICD therapy were analyzed using Cox proportional hazard ratio (HR).

Results: Of 321 patients (70.1% males), at least one appropriate therapy occurred in 77 (24.0%) during a mean follow-up of 5.4 years (5.3% per year; primary prevention 4.5%, secondary prevention 7.0%). Cumulative incidences at 1 year, 3 years, and 5 years were 8.1%, 15.3%, and 21.3%, respectively. Cardioversion effectively restored rhythm in 52% of the first episode and antitachycardia pacing was sufficient in the remaining. For the whole cohort, ejection fraction (EF) <50% (HR 2.63; P < 0.001) was associated with appropriate ICD therapy. In primary prevention, patients with established risk markers experienced appropriate therapy; atrial fibrillation (AF; HR 2.54; P = 0.010), EF < 50% (HR 2.78; P = 0.004), and nonsustained ventricular tachycardia (HR 1.80; P = 0.109) had the highest HR, and wall thickness ≥ 30 mm, syncope, exercise blood pressure response, or family history of SCD had weaker associations.

Conclusion: ICD therapy successfully terminates ventricular arrhythmias in HCM. In addition to conventional risk markers, a history of AF or EF < 50% may be considered in risk stratification.
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http://dx.doi.org/10.1111/pace.12801DOI Listing
March 2016

A Comparison of Two Strategies for Building an Exposure Prediction Model.

Ann Occup Hyg 2016 Jan 30;60(1):74-89. Epub 2015 Sep 30.

4.Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, Umeå University, 901 87 Umeå, Sweden.

Cost-efficient assessments of job exposures in large populations may be obtained from models in which 'true' exposures assessed by expensive measurement methods are estimated from easily accessible and cheap predictors. Typically, the models are built on the basis of a validation study comprising 'true' exposure data as well as an extensive collection of candidate predictors from questionnaires or company data, which cannot all be included in the models due to restrictions in the degrees of freedom available for modeling. In these situations, predictors need to be selected using procedures that can identify the best possible subset of predictors among the candidates. The present study compares two strategies for selecting a set of predictor variables. One strategy relies on stepwise hypothesis testing of associations between predictors and exposure, while the other uses cluster analysis to reduce the number of predictors without relying on empirical information about the measured exposure. Both strategies were applied to the same dataset on biomechanical exposure and candidate predictors among computer users, and they were compared in terms of identified predictors of exposure as well as the resulting model fit using bootstrapped resamples of the original data. The identified predictors were, to a large part, different between the two strategies, and the initial model fit was better for the stepwise testing strategy than for the clustering approach. Internal validation of the models using bootstrap resampling with fixed predictors revealed an equally reduced model fit in resampled datasets for both strategies. However, when predictor selection was incorporated in the validation procedure for the stepwise testing strategy, the model fit was reduced to the extent that both strategies showed similar model fit. Thus, the two strategies would both be expected to perform poorly with respect to predicting biomechanical exposure in other samples of computer users.
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http://dx.doi.org/10.1093/annhyg/mev072DOI Listing
January 2016

Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy.

Anticancer Res 2015 Oct;35(10):5491-7

Center for Research and Development, Uppsala University, Gävle Hospital, Gävle, Sweden Department of Oncology, Gävle Hospital, Gävle, Sweden Department of Radiation Sciences and Oncology, Umeå University Hospital, Umeå, Sweden.

Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC).

Patients And Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (≥50 Gy) in Sweden during the time period 1990 to 2000.

Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical- and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17).

Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.
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October 2015

Chemotherapy Treatment of Elderly Patients (≥70 Years) with Non-Small Cell Lung Cancer: A Seven-Year Retrospective Study of Real-Life Clinical Practice at Karolinska University Hospital, Sweden.

Lung Cancer Int 2015 14;2015:317868. Epub 2015 Jul 14.

Department of Respiratory Medicine, Gävle Hospital, 80187 Gävle, Sweden ; Karolinska Institutet, Stockholm, Sweden ; Centre for Research and Development, Uppsala University, County Council of Gävleborg, Gävle, Sweden.

An increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue; so we performed a retrospective study of our patients to demonstrate how elderly patients with NSCLC are treated in real-life, clinical practice. All patients aged ≥70 years with NSCLC at our department were reviewed retrospectively. In total, 1059 patients (50.8% of all NSCLC patients). Of these patients, 243 (22.9%) received chemotherapy, 164 (70.4%) of whom were treated with a platinum doublet using carboplatin. Second- and third-line chemotherapy were given to 31.4% and 13.9% of patients, respectively. Median overall survival was 289 and 320 days for male and female patients, respectively. Patients with performance status (PS) 0 experienced significantly better survival than patients with PS1 or PS 2: 410, 314, and 204 days, respectively. Age was of less importance, with patients aged 70-79 years versus those aged ≥80 years. Treatment of elderly NSCLC patients with chemotherapy is feasible if they have a good PS and appears to prolong survival. In this study, we found no significant differences in survival either between age groups or genders.
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http://dx.doi.org/10.1155/2015/317868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517544PMC
August 2015

Hypertrophic Cardiomyopathy and Implantable Defibrillators in Sweden: Inappropriate Shocks and Complications Requiring Surgery.

J Cardiovasc Electrophysiol 2015 Oct 2;26(10):1088-94. Epub 2015 Sep 2.

Cardiology, Heart Center and Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

Introduction: The expanded use of implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) based on risk stratification in individuals without known previous ventricular arrhythmia is justified by an acceptable risk of device-related adverse events. Such complications, leading to surgical procedures or inappropriate electrical shocks, may impact mortality, morbidity, quality of life, and cost-effectiveness.

Methods And Results: From the Swedish ICD Registry, implants due to HCM since 1995 until November 2012 in patients aged ≥18 years were identified and medical records reviewed. Inappropriate ICD shock occurred in 14.3% (46 of 321 patients; mean follow-up 5.4 years) with a recurrent episode in 28.2% of them. In multivariable analysis, hazard ratio (HR) for atrial fibrillation was 3.5 (95% confidence interval 1.8-6.8; P < 0.001) but showed no significant association to male sex (HR = 0.77), age (HR = 0.99), secondary indication (HR = 1.02) or device, ICD-DR/CRTD vs. ICD-VR (HR 1.07). Inappropriate shocks were triggered by atrial fibrillation/flutter or ectopic tachycardia (56.5%), sinus tachycardia (14.5%), lead dysfunction (14.5%), and T-wave oversensing (13.0%). A reintervention, besides elective device replacement, occurred in 92 patients (totally 150 procedures). The majority were lead-related (70.0%) procedures, especially of the ICD lead. Reintervention was associated with female sex (HR = 1.6 P = 0.04).

Conclusion: Inappropriate ICD shock triggered by atrial arrhythmias, lead dysfunction, or complications requiring surgical interventions, is a concern in HCM patients who will be eligible for long-term prevention of sudden death. Efforts to avoid adverse events and provide balanced risk-benefit information are important, especially in primary prevention.
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http://dx.doi.org/10.1111/jce.12750DOI Listing
October 2015

Digging deeper into the assessment of upper arm elevation angles using standard inclinometry.

Appl Ergon 2015 Nov 19;51:102-3. Epub 2015 May 19.

Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, University of Gävle, SE-80176 Gävle, Sweden; Institute of Environmental Medicine, Karolinska Institutet, SE-171 77, Stockholm, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.apergo.2015.04.012DOI Listing
November 2015

Is what you see what you get? Standard inclinometry of set upper arm elevation angles.

Appl Ergon 2015 Mar 27;47:242-52. Epub 2014 Oct 27.

Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, University of Gävle, SE-80176 Gävle, Sweden; Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address:

Previous research suggests inclinometers (INC) underestimate upper arm elevation. This study was designed to quantify possible bias in occupationally relevant postures, and test whether INC performance could be improved using calibration. Participants were meticulously positioned in set arm flexion and abduction angles between 0° and 150°. Different subject-specific and group-level regression models comprising linear and quadratic components describing the relationship between set and INC-registered elevation were developed using subsets of data, and validated using additional data. INC measured arm elevation showed a downward bias, particularly above 60°. INC data adjusted using the regression models were superior to unadjusted data; a subject-specific, two-point calibration based on measurements at 0° and 90° gave results closest to the 'true' set angles. Thus, inclinometer measured arm elevation data required calibration to arrive at 'true' elevation angles. Calibration to a common measurement scale should be considered when comparing arm elevation data collected using different methods.
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http://dx.doi.org/10.1016/j.apergo.2014.08.014DOI Listing
March 2015

Cost-efficient measurement strategies for posture observations based on video recordings.

Appl Ergon 2013 Jul 18;44(4):609-17. Epub 2013 Jan 18.

Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, University of Gävle, Gävle, Sweden.

Assessment of working postures by observation is a common practice in ergonomics. The present study investigated whether monetary resources invested in a video-based posture observation study should preferably be spent in collecting many video recordings of the work and have them observed once by one observer, or in having multiple observers rate postures repeatedly from fewer videos. The study addressed this question from a practitioner's perspective by focusing two plausible scenarios: documenting the mean exposure of one individual, and of a specific occupational group. Using a data set of observed working postures among hairdressers, empirical values of posture variability, observer variability, and costs for recording and observing one video were entered into equations expressing the total cost of data collection and the information (defined as 1/SD) provided by the resulting estimates of two variables: percentage time with the arm elevated <15° and >90°. Sixteen measurement strategies involving 1-4 observers repeating their posture ratings 1-4 times were examined for budgets up to €2000. For both posture variables and in both the individual and group scenario, the most cost-efficient strategy at any specific budget was to engage 3-4 observers and/or having observer(s) rate postures multiple times each. Between 17% and 34% less information was produced when using the commonly practiced approach of having one observer rate a number of video recordings one time each. We therefore recommend observational posture assessment to be based on video recordings of work, since this allows for multiple observations; and to allocate monetary resources to repeated observations rather than many video recordings.
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http://dx.doi.org/10.1016/j.apergo.2012.12.003DOI Listing
July 2013

Accuracy and precision of variance components in occupational posture recordings: a simulation study of different data collection strategies.

BMC Med Res Methodol 2012 Jun 18;12:58. Epub 2012 Jun 18.

Centre for Musculoskeletal Research, University of Gävle, Gävle, Sweden.

Background: Information on exposure variability, expressed as exposure variance components, is of vital use in occupational epidemiology, including informed risk control and efficient study design. While accurate and precise estimates of the variance components are desirable in such cases, very little research has been devoted to understanding the performance of data sampling strategies designed specifically to determine the size and structure of exposure variability. The aim of this study was to investigate the accuracy and precision of estimators of between-subjects, between-days and within-day variance components obtained by sampling strategies differing with respect to number of subjects, total sampling time per subject, number of days per subject and the size of individual sampling periods.

Methods: Minute-by-minute values of average elevation, percentage time above 90° and percentage time below 15° were calculated in a data set consisting of measurements of right upper arm elevation during four full shifts from each of 23 car mechanics. Based on this parent data, bootstrapping was used to simulate sampling with 80 different combinations of the number of subjects (10, 20), total sampling time per subject (60, 120, 240, 480 minutes), number of days per subject (2, 4), and size of sampling periods (blocks) within days (1, 15, 60, 240 minutes). Accuracy (absence of bias) and precision (prediction intervals) of the variance component estimators were assessed for each simulated sampling strategy.

Results: Sampling in small blocks within days resulted in essentially unbiased variance components. For a specific total sampling time per subject, and in particular if this time was small, increasing the block size resulted in an increasing bias, primarily of the between-days and the within-days variance components. Prediction intervals were in general wide, and even more so at larger block sizes. Distributing sampling time across more days gave in general more precise variance component estimates, but also reduced accuracy in some cases.

Conclusions: Variance components estimated from small samples of exposure data within working days may be both inaccurate and imprecise, in particular if sampling is laid out in large consecutive time blocks. In order to estimate variance components with a satisfying accuracy and precision, for instance for arriving at trustworthy power calculations in a planned intervention study, larger samples of data will be required than for estimating an exposure mean value with a corresponding certainty.
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http://dx.doi.org/10.1186/1471-2288-12-58DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377541PMC
June 2012

Cost efficiency comparison of four video-based techniques for assessing upper arm postures.

Ergonomics 2012 ;55(3):350-60

Department of Occupational and Public Health Sciences, Centre for Musculoskeletal Research, University of Gävle, Gävle, Sweden.

Unlabelled: Many video-based techniques for assessing postures at work have been developed. Choosing the most appropriate technique should be based on an evaluation of different alternatives in terms of their ability to produce posture information at low input costs, i.e. their cost efficiency. This study compared four video-based techniques for assessing upper arm postures, using cost and error data from an investigation on hairdressers. Labour costs associated with the posture assessments from the video recordings were the dominant factor in the cost efficiency comparison. Thus, a work sampling technique associated with relatively large errors appeared, in general, to be the most cost-efficient because it was labour-saving. Measurement bias and other costs than labour cost for posture assessment influenced the ranking and economic evaluation of techniques, as did the applied measurement strategy, i.e. the numbers of video recordings and repeated assessments of them.

Practitioner Summary: The cost efficiency of four video-based techniques for assessing upper arm postures was compared. Work sampling techniques were in general more cost efficient than continuous observations since they were labour-saving. Whilst a labour cost dominated the comparison, 'hidden costs', bias and measurement strategy also influenced this dominance.
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http://dx.doi.org/10.1080/00140139.2011.642007DOI Listing
July 2012

Cost-efficient observation of working postures from video recordings--more videos, more observers or more views per observer?

Work 2012 ;41 Suppl 1:2302-6

Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, University of Gävle, SE-80176 Gävle, Sweden.

In ergonomics, assessing the working postures of an individual by observation is a very common practice. The present study investigated whether monetary resources devoted to an observational study should preferably be invested in collecting many video recordings of the work, or in having several observers estimate postures from available videos multiple times. On the basis of a data set of observed working postures among hairdressers, necessary information in terms of posture variability, observer variability, and costs for recording and observing videos was entered into equations providing the total cost of data collection and the precision (informative value) of the resulting estimates of two variables: percentages time with the arm elevated <15 degrees and >90 degrees. In all 160 data collection strategies, differing with respect to the number of video recordings and the number of repeated observations of each recording, were simulated and compared for cost and precision. For both posture variables, the most cost-efficient strategy for a given budget was to engage 4 observers to look at available video recordings, rather than to have one observer look at more recordings. Since the latter strategy is the more common in ergonomics practice, we recommend reconsidering standard practice in observational posture assessment.
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http://dx.doi.org/10.3233/WOR-2012-0456-2302DOI Listing
February 2014

Theoretical and empirical efficiency of sampling strategies for estimating upper arm elevation.

Ann Occup Hyg 2011 May;55(4):436-49

Department of Occupational and Public Health Sciences, Centre for Musculoskeletal Research, University of Gävle, Gävle, Sweden.

Objectives: To investigate the statistical efficiency of strategies for sampling upper arm elevation data, which differed with respect to sample sizes and sample allocations within and across measurement days. The study was also designed to compare standard theoretical predictions of sampling efficiency, which rely on several assumptions about the data structure, with 'true' efficiency as determined by bootstrap simulations.

Methods: Sixty-five sampling strategies were investigated using a data set containing minute-by-minute values of average right upper arm elevation, percentage of time with an arm elevated <15°, and percentage of time with an arm elevated >90° in a population of 23 house painters, 23 car mechanics, and 26 machinists, all followed for four full working days. Total sample times per subject between 30 and 240 min were subdivided into continuous time blocks between 1 and 240 min long, allocated to 1 or 4 days per subject. Within day(s), blocks were distributed using either a random or a fixed-interval principle. Sampling efficiency was expressed in terms of the variance of estimated mean exposure values of 20 subjects and assessed using standard theoretical models assuming independence between variables and homoscedasticity. Theoretical performance was compared to empirical efficiencies obtained by a nonparametric bootstrapping procedure.

Results: We found the assumptions of independence and homoscedasticity in the theoretical model to be violated, most notably expressed through an autocorrelation between measurement units within working days. The empirical variance of the mean exposure estimates decreased, i.e. sampling efficiency increased, for sampling strategies where measurements were distributed widely across time. Thus, the most efficient allocation strategy was to organize a sample into 1-min block collected at fixed time intervals across 4 days. Theoretical estimates of efficiency generally agreed with empirical variances if the sample was allocated into small blocks, while for larger block sizes, the empirical 'true' variance was considerably larger than predicted by theory. Theory overestimated efficiency in particular for strategies with short total sample times per subject.

Conclusions: This study demonstrates that when exposure data are autocorrelated within days-which we argue is the major reason why theory overestimates sampling performance-sampling efficiency can be improved by distributing the sample widely across the day or across days, preferably using a fixed-interval strategy. While this guidance is particularly valid when small proportions of working days are assessed, we generally recommend collecting more data than suggested by theory if a certain precision of the resulting exposure estimate is needed. More data per se give a better precision and sampling larger proportion(s) of the working day(s) also alleviate the negative effects of possible autocorrelation in data.
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http://dx.doi.org/10.1093/annhyg/meq095DOI Listing
May 2011

Upper arm postures and movements in female hairdressers across four full working days.

Ann Occup Hyg 2010 Jul 12;54(5):584-94. Epub 2010 Apr 12.

Department of Occupational and Environmental Medicine, Umeå University Hospital, SE-901 85 Umeå, Sweden.

Objectives: To describe upper arm postures and movements among female hairdressers, including the variability between hairdressers, between days within hairdresser, and between tasks, as a basis for understanding the characteristics of exposures in the job, considering possible sources of variation and recovery, and discussing appropriate exposure assessment strategies.

Methods: Data on upper arm postures were collected using inclinometers during four working days the same week from 28 female hairdressers working in 13 salons. Twenty of the hairdressers noted customer on and off times in a diary, to allow separate analyses of customer tasks (CT) and auxiliary non-customer tasks (AT), including breaks. For a number of posture and movement variables, mean values and variance components between subjects (BS) and within subjects between days (BD) were estimated using restricted maximum likelihood algorithms in one-way random effect models.

Results: For the 20 hairdressers with diaries, CT accounted for 279 min (58%) (SD(BS) = 39 min and SD(BD) = 85 min) of the working day and AT and breaks for 207 min (42%) (SD(BS) = 46 min and SD(BD) = 88 min). The hairdressers worked with the right arm elevated >60 degrees for 6.8% of the whole job (SD(BS) = 2.8% and SD(BD) = 2.0%). On average, the hairdressers worked with the right arm elevated >60 degrees for 9.0% of the time during CT, compared to 3.7% during AT, resulting in a contrast between tasks of 0.35.

Conclusions: Hairdressers may be at risk for developing musculoskeletal disorders in the neck and shoulders due to a considerable occurrence of highly elevated arms, especially during CT. On the other hand, we do not find reasons to classify hairdressing as a job with too little variation. Posture variability between days within hairdressers was in the same order of magnitude as that between hairdressers, suggesting that 'typical' workdays do not exist. The exposure contrast between CT and AT for variables describing elevated arm postures indicates that for these variables a simple task-based approach for estimating job exposure could be successful.
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http://dx.doi.org/10.1093/annhyg/meq028DOI Listing
July 2010
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