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  • 1.
    Ali, Muhanned
    et al.
    Kristianstad & Hässleholm Hosp, Dept Orthoped, Hässleholm, Sweden.
    Brogren, Elisabeth
    Skåne Univ Hosp, Dept Hand Surg, Malmö, Sweden;Kristianstad & Hässleholm Hosp, Dept Orthoped, Hässleholm, Sweden.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Atroshi, Isam
    Lund Univ, Dept Clin Sci Orthoped, Lund, Sweden;Kristianstad & Hässleholm Hosp, Dept Orthoped, Hässleholm, Sweden.
    Association Between Distal Radial Fracture Malunion and Patient-Reported Activity Limitations: A Long-Term Follow-up2018In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 100, no 8, p. 633-639Article in journal (Refereed)
    Abstract [en]

    Background: The long-term effect of distal radial fracture malunion on activity limitations is unknown. Between 2001 and 2002, we conducted a prospective cohort study of all patients with distal radial fracture treated with casting or percutaneous fixation in northeast Scania in Sweden. In that original study, the patients completed the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at baseline and at 2 years. We performed a long-term follow-up study of patients who were 18 to 65 years of age at the time of the fracture to investigate the association between fracture malunion and activity limitations. Methods: In this long-term follow-up, patients who had participated in the original study completed the DASH questionnaire and a visual analog scale (VAS) for pain and for satisfaction (scored, 0 [best] to 100) and underwent radiographic and physical examinations at 12 to 14 years after the fracture. We defined malunion as dorsal angulation of >= 10 degrees, ulnar variance of >= 3 mm, and/or radial inclination of <= 15 degrees. We also assessed the presence of radiocarpal osteoarthritis and ulnar styloid nonunion. The primary outcome was the change in DASH score from baseline. Secondary outcomes were DASH, pain, and satisfaction scores, wrist range of motion, and grip strength at the time of the follow-up. Results: Of 85 eligible patients, 63 (74%) responded to the questionnaires and underwent examinations. Mal union was found in 25 patients, osteoarthritis was found in 38 patients, and styloid nonunion was found in 9 patients. Compared with patients without malunion, those with malunion had significantly worse DASH scores from baseline to 12 to 14 years (p = 0.002); the adjusted mean difference was 11 points (95% confidence interval [CI], 4 to 17 points). Similarly, follow-up scores were significantly worse among patients with malunion; the adjusted mean difference was 14 points (95% CI, 7 to 22 points; p < 0.001) for DASH scores, 10 points (95% CI, 0 to 20 points; p = 0.049) for VAS pain scores, and 26 points (95% CI, 11 to 41 points; p = 0.001) for VAS satisfaction scores. No differences were found in range of motion or grip strength. Osteoarthritis (mostly mild) and styloid nonunion had no significant association (p > 0.05) with DASH scores, VAS pain or satisfaction scores, or grip strength. Conclusions: Patients who sustain a distal radial fracture at the age of 18 to 65 years and develop malunion are more likely to have worse long-term outcomes including activity limitations and pain.

  • 2.
    Austin, Peter C.
    et al.
    Inst Clin Evaluat Sci, G106,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada.;Univ Toronto, Inst Hlth Management Policy & Evaluat, Toronto, ON, Canada.;Sunnybrook Res Inst, Schulich Heart Res Program, Toronto, ON, Canada..
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Lund Univ, Unit Social Epidemiol, Fac Med, Malmo, Sweden..
    Merlo, Juan
    Lund Univ, Unit Social Epidemiol, Fac Med, Malmo, Sweden.;Region Skane, Ctr Primary Hlth Care Res, Malmo, Sweden..
    The median hazard ratio: a useful measure of variance and general contextual effects in multilevel survival analysis2017In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 36, no 6, p. 928-938Article in journal (Refereed)
    Abstract [en]

    Multilevel data occurs frequently in many research areas like health services research and epidemiology. A suitable way to analyze such data is through the use of multilevel regression models (MLRM). MLRM incorporate cluster-specific random effects which allow one to partition the total individual variance into between-cluster variation and between-individual variation. Statistically, MLRM account for the dependency of the data within clusters and provide correct estimates of uncertainty around regression coefficients. Substantively, the magnitude of the effect of clustering provides a measure of the General Contextual Effect (GCE). When outcomes are binary, the GCE can also be quantified by measures of heterogeneity like the Median Odds Ratio (MOR) calculated from a multilevel logistic regression model. Time-to-event outcomes within a multilevel structure occur commonly in epidemiological and medical research. However, the Median Hazard Ratio (MHR) that corresponds to the MOR in multilevel (i.e., 'frailty') Cox proportional hazards regression is rarely used. Analogously to the MOR, the MHR is the median relative change in the hazard of the occurrence of the outcome when comparing identical subjects from two randomly selected different clusters that are ordered by risk. We illustrate the application and interpretation of the MHR in a case study analyzing the hazard of mortality in patients hospitalized for acute myocardial infarction at hospitals in Ontario, Canada. We provide R code for computing the MHR. The MHR is a useful and intuitive measure for expressing cluster heterogeneity in the outcome and, thereby, estimating general contextual effects in multilevel survival analysis.

  • 3.
    Carlander, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Karolinska Inst, Dept Med Huddinge, Unit Infect Dis, SE-17177 Stockholm, Sweden.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    van Beirs, Astrid
    Linkoping Univ, Fac Med & Hlth Sci, Linkoping, Sweden.
    Yilmaz, Aylin
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Infect Dis, Gothenburg, Sweden.
    Elfgren, Kristina
    Karolinska Univ Hosp Huddinge, Dept Obstet & Gynaecol, CLINTEC, Stockholm, Sweden.
    Dillner, Joakim
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.
    Sönnerborg, Anders
    Karolinska Inst, Dept Med Huddinge, Unit Infect Dis, SE-17177 Stockholm, Sweden.
    Sparen, Pär
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Suppressive antiretroviral therapy associates with effective treatment of high-grade cervical intraepithelial neoplasia2018In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 32, no 11, p. 1475-1484Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess if women living with HIV (WLWH) have poorer outcome after treatment of cervical intraepithelial neoplasia grade 2, grade 3, adenocarcinoma in situ or cervical cancer (CIN2+) than HIV-negative women (HNW) and to identify predictors of CIN2+ treatment failure and recurrence in WLWH. Design: Population-based cohort study with follow-up between 1983 and 2015. Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ (n = 179) sometime between 1983 and 2014. For each WLWH, two HNW resident in the same counties and matched for country of birth, diagnosed with CIN2+, were chosen as controls. Treatment failure was defined as the presence of CIN2+ at initial follow-up. Recurrence was defined as the presence of CIN1+ subsequent to an initial normal follow-up. Results: WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% confidence interval (CI) 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0 [95% CI 2.1-11.6]) than HNW. Suppressive antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced OR of treatment failure (OR 0.3 [95% CI 0.1-0.8]). Immunosuppression (CD4(+) cell count < 200 cells/mu l) associated strongly with treatment failure (OR compared with CD4 (+) cell count >= 500: 8.5 [95% CI 2.3-30.7]). Conclusion: Suppressive ART is associated with effective treatment of CIN2+. Early HIV diagnosis and ART are essential for successful CIN2+ treatment.

  • 4.
    Condén, Emelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Malardalen Univ, Sch Hlth Care & Social Welf, Vasteras, Sweden..
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Is type D personality an independent risk factor for recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients?2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 5, p. 522-533Article in journal (Refereed)
    Abstract [en]

    Background: Type D personality refers to a combination of simultaneously high levels of negative affectivity and social inhibition. The present study aimed to examine whether type D personality was independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality. Design: This was a prospective cohort study. Methods: Utilising data from the Vastmanland Myocardial Infarction Study, 946 post-acute myocardial infarction patients having data on the DS14 instrument used to measure type D personality were followed-up for recurrent myocardial infarction and all-cause mortality until 9 December 2015. Data were analysed using Cox regression, adjusted for established risk factors. Results: In total, 133 (14.1%) patients suffered from type D personality. During a mean follow-up time for recurrent myocardial infarction of 5.7 (3.2) years, 166 (17.5%) patients were affected by recurrent myocardial infarction, of which 26 (15.7%) had type D personality, while during a mean follow-up time for all-cause mortality of 6.3 (2.9) years, 321 (33.9%) patients died, of which 42 (13.1%) had type D personality. After adjusting for established risk factors, type D personality was not significantly associated with recurrent myocardial infarction or all-cause mortality using any of the previously proposed methods for measuring type D personality. A weak association was found between the social inhibition part of type D personality and a decreased risk of all-cause mortality, but this association was not significant after taking missing data into account in a multiple imputation analysis. Conclusions: No support was found for type D personality being independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality.

  • 5.
    Granstam, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Westborg, Inger
    Umea Univ, Dept Clin Sci Ophthalmol, Umea, Sweden..
    Barkander, Anna
    Ostersund Cty Hosp, Dept Ophthalmol, Ostersund, Sweden..
    Börjesson, Malin
    Skelleftea Cty Hosp, Dept Ophthalmol, Skelleftea, Sweden..
    Lindahl, Sara
    Umea Univ Hosp, Dept Ophthalmol, Umea, Sweden..
    Meszaros, Eva
    Gavleborg Cty Hosp Gavle, Dept Ophthalmol, Gavle, Sweden..
    Wojciechowska-Zajac, Anna
    Sunderby Cty Hosp, Dept Ophthalmol, Sunderbyn, Sweden..
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Albrecht, Susanne
    RC Syd, Swedish Macula Register, Karlskrona, Sweden..
    Karlsson, Niklas
    RC Syd, Swedish Macula Register, Karlskrona, Sweden..
    Bjarnhall, Gunilla
    RC Syd, Swedish Macula Register, Karlskrona, Sweden..
    Lovestam-Adrian, Monica
    Lund Univ, IKVL Inst Clin Sci, Ophthalmol, Lund, Sweden..
    Reduced occurrence of severe visual impairment after introduction of anti-Vascular Endothelial Growth Factor in wet age-related macular degeneration: a population- and register-based study from northern Sweden2016In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 7, p. 646-651Article in journal (Refereed)
    Abstract [en]

    PurposeTo study the occurrence of severe visual impairment (SVI) and treatment outcome at 12months in patients treated for wet age-related macular degeneration (AMD) by use of data from the Swedish Macula Register (SMR) and referrals to the regional low vision clinics in five northern counties. MethodsReferrals to low vision clinics during 2005, 2009 and 2013 and treatment outcome at 12months from the SMR database from 2008 until 2013 in patients >65years of age in five northern counties were included in the survey. ResultsThe rate of referral due to AMD was significantly reduced during the time period (-48%; p<0.001). At 12months, a significant slight mean improvement in logMAR visual acuity (VA) was observed (-0.01, SD 0.37; p<0.001) after a mean of 5.02.3 anti-vascular endothelial growth factor (VEGF)-injections were administered. Age and low baseline VA was associated with less favourable visual outcome (p<0.001). ConclusionReferral rate to low vision clinic is a valuable tool for estimating occurrence of SVI and fell between the years 2005 until 2013. Data from the SMR showed improvement in visual acuity on the whole, but also identified patients at high risk for developing SVI during anti-VEGF-treatment.

  • 6.
    Hellström, Charlotta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. School of Health, Care and Social Welfare, Mälardalen University.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nillson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Aslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Gambling frequency and symptoms of attention-deficit hyperactivity disorder in relation to problem gambling among Swedish adolescents: A population-based study2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 22, no 2, p. 119-126Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate the associations between gambling frequency, attention-deficit hyperactivity disorder (ADHD) symptoms, and problem gambling among adolescent boys and girls. One hypothesis was that adolescents with increased ADHD symptoms have a higher frequency of gambling compared to adolescents with fewer ADHD symptoms.

    Method: A population-based sample of adolescents (aged 15–18 years) completed a questionnaire on demographics, gambling habits, ADHD symptoms, and problematic gambling; 1412 adolescents (from 4440 sampled) with gambling experience were included in the final sample.

    Results: A zero-inflated negative binomial regression analysis revealed that increased ADHD symptoms, higher gambling frequency, and higher age were associated with lower odds for being non-susceptible to gambling problems. Moreover, gambling frequency interacted with ADHD symptoms in predicting probability of being non-susceptible to gambling problems. However, when analysing those already susceptible to problem gambling, ADHD symptoms did not modify the effect of gambling frequency on the expected magnitude of gambling problems. In susceptible individuals, problem gambling increased with both increased ADHD symptoms and increased gambling frequency, but the level of problems due to gambling frequency did not change depending on the ADHD symptom level. There was an interaction effect between sex and gambling frequency in relation to gambling problems.

    Conclusions: Adolescents with ADHD symptoms seem to be more sensitive to gambling, in terms of being susceptible to developing gambling problems. However, once susceptible, adolescents with ADHD symptoms are affected by gambling frequency similarly to other susceptible participants.

  • 7. Hermanson, Maria
    et al.
    Hägglund, Gunnar
    Riad, Jacques
    Wagner, Philippe
    d epartment of Clinical s cience, o rthopedic s urgery, s kåne u niversity Hospital, Lund.
    Head-shaft angle is a risk factor for hip displacement in children with cerebral palsy2015In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, no 2, p. 229-232Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Hip dislocation in children with cerebral palsy (CP) is a common and severe problem. The Swedish follow-up program for CP (CPUP) includes standardized monitoring of the hips. Migration percentage (MP) is a widely accepted measure of hip displacement. Coxa valga and valgus of the femoral head in relation to the femoral neck can be measured as the head-shaft angle (HSA). We assessed HSA as a risk factor for hip displacement in CP.

    PATIENTS AND METHODS: We analyzed radiographs of children within CPUP from selected regions of Sweden. Inclusion criteria were children with Gross Motor Function Classification System (GMFCS) levels III-V, MP of < 40% in both hips at the first radiograph, and a follow-up period of 5 years or until development of MP > 40% of either hip within 5 years. Risk ratio between children who differed in HSA by 1 degree was calculated and corrected for age, MP, and GMFCS level using multiple Poisson regression.

    RESULTS: 145 children (73 boys) with a mean age of 3.5 (0.6-9.7) years at the initial radiograph were included. 51 children developed hip displacement whereas 94 children maintained a MP of < 40%. The risk ratio for hip displacement was 1.05 (p < 0.001; 95% CI 1.02-1.08). When comparing 2 children of the same age, GMFCS level, and MP, a 10-degree difference in HSA results in a 1.6-times higher risk of hip displacement in the child with the higher HSA.

    INTERPRETATION: A high HSA appears to be a risk factor for hip displacement in children with CP.

  • 8.
    Linden, Olof
    et al.
    Lund Univ, Dept Clin Sci, Orthoped, Lund, Sweden.
    Hagglund, Gunnar
    Lund Univ, Dept Clin Sci, Orthoped, Lund, Sweden.
    Rodby-Bousquet, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Lund Univ, Dept Clin Sci, Orthoped, Lund, Sweden.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    The development of spasticity with age in 4,162 children with cerebral palsy: a register-based prospective cohort study2019In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 90, no 3, p. 286-291Article in journal (Refereed)
    Abstract [en]

    Background and purpose

    Spasticity is often regarded as a major cause of functional limitation in children with cerebral palsy (CP). We analyzed the spasticity development with age in the gastrosoleus muscle in children with CP.

    Children and methods

    This is a longitudinal cohort study of 4,162 children (57% boys) with CP born in 1990-2015, monitored using standardized follow-up examinations in the Swedish surveillance program for CP. The study is based on 57,953 measurements of spasticity of the gastrosoleus muscle assessed using the Ashworth scale (AS) in participants between 0 and 15 years of age. The spasticity was analyzed in relation to age, sex, and Gross Motor Function Classification System (GMFCS) levels using a linear mixed model. Development of spasticity with age was modeled as a linear spline.

    Results

    The degree of spasticity increased in most children over the first 5 years of life. At 5 years of age, 38% had an AS level of 2. The spasticity then decreased for 65% of the children during the remaining study period. At 15 years of age only 22% had AS 2. The level of spasticity and the rate of increase and decrease before and after 5.5 years of age were higher in children at GMFCS IV-V.

    Interpretation

    The degree of spasticity of the gastrosoleus muscle often decreases after 5 years of age, which is important for long-term treatment planning and should be considered in spasticity management.

  • 9.
    Merlo, Juan
    et al.
    Lund Univ, Fac Med, Dept Clin Sci, Unit Social Epidemiol,CRC, Jan Waldenstroms St 35, SE-21421 Malmo, Sweden.;Ctr Primary Hlth Care Res, Malmo, Sweden..
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Lund Univ, Fac Med, Dept Clin Sci, Unit Social Epidemiol,CRC, Jan Waldenstroms St 35, SE-21421 Malmo, Sweden..
    Austin, Peter C.
    Inst Clin Evaluat Sci, Toronto, ON, Canada..
    Subramanian, S. , V
    Leckie, George
    Lund Univ, Fac Med, Dept Clin Sci, Unit Social Epidemiol,CRC, Jan Waldenstroms St 35, SE-21421 Malmo, Sweden.;Univ Bristol, Ctr Multilevel Modelling, Bristol, Avon, England..
    General and specific contextual effects in multilevel regression analyses and their paradoxical relationship: A conceptual tutorial2018In: SSM - Population Health, ISSN 2352-8273, Vol. 5, p. 33-37Article in journal (Refereed)
    Abstract [en]

    To be relevant for public health, a context (e.g., neighborhood, school, hospital) should influence or affect the health status of the individuals included in it. The greater the influence of the shared context, the higher the correlation of subject outcomes within that context is likely to be. This intra-context or intra-class correlation is of substantive interest and has been used to quantify the magnitude of the general contextual effect (GCE). Furthermore, ignoring the intra-class correlation in a regression analysis results in spuriously narrow 95% confidence intervals around the estimated regression coefficients of the specific contextual variables entered as covariates and, thereby, overestimates the precision of the estimated specific contextual effects (SCEs). Multilevel regression analysis is an appropriate methodology for investigating both GCEs and SCEs. However, frequently researchers only report SCEs and disregard the study of the GCE, unaware that small GCEs lead to more precise estimates of SCEs so, paradoxically, the less relevant the context is, the easier it is to detect (and publish) small but "statistically significant" SCEs. We describe this paradoxical situation and encourage researchers performing multilevel regression analysis to consider simultaneously both the GCE and SCEs when interpreting contextual influences on individual health.

  • 10.
    Merlo, Juan
    et al.
    Lund Univ, Fac Med, Unit Social Epidemiol, Malmo, Sweden..
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Lund Univ, Fac Med, Unit Social Epidemiol, Malmo, Sweden..
    Ghith, Nermin
    Lund Univ, Fac Med, Unit Social Epidemiol, Malmo, Sweden.;Bispebjerg Hosp, Res Unit Chron Condit, Copenhagen, Denmark..
    Leckie, George
    Univ Bristol, Ctr Multilevel Modelling, Bristol, Avon, England..
    An Original Stepwise Multilevel Logistic Regression Analysis of Discriminatory Accuracy: The Case of Neighbourhoods and Health2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 4, article id e0153778Article in journal (Refereed)
    Abstract [en]

    Background and Aim Many multilevel logistic regression analyses of "neighbourhood and health" focus on interpreting measures of associations (e.g., odds ratio, OR). In contrast, multilevel analysis of variance is rarely considered. We propose an original stepwise analytical approach that distinguishes between "specific" (measures of association) and "general" (measures of variance) contextual effects. Performing two empirical examples we illustrate the methodology, interpret the results and discuss the implications of this kind of analysis in public health. Methods We analyse 43,291 individuals residing in 218 neighbourhoods in the city of Malm, Sweden in 2006. We study two individual outcomes (psychotropic drug use and choice of private vs. public general practitioner, GP) for which the relative importance of neighbourhood as a source of individual variation differs substantially. In Step 1 of the analysis, we evaluate the OR and the area under the receiver operating characteristic (AUC) curve for individual-level covariates (i.e., age, sex and individual low income). In Step 2, we assess general contextual effects using the AUC. Finally, in Step 3 the OR for a specific neighbourhood characteristic (i.e., neighbourhood income) is interpreted jointly with the proportional change in variance (i.e., PCV) and the proportion of ORs in the opposite direction (POOR) statistics. Results For both outcomes, information on individual characteristics (Step 1) provide a low discriminatory accuracy (AUC = 0.616 for psychotropic drugs; = 0.600 for choosing a private GP). Accounting for neighbourhood of residence (Step 2) only improved the AUC for choosing a private GP (+0.295 units). High neighbourhood income (Step 3) was strongly associated to choosing a private GP (OR = 3.50) but the PCV was only 11% and the POOR 33%. Conclusion Applying an innovative stepwise multilevel analysis, we observed that, in Malmo, the neighbourhood context per se had a negligible influence on individual use of psychotropic drugs, but appears to strongly condition individual choice of a private GP. However, the latter was only modestly explained by the socioeconomic circumstances of the neighbourhoods. Our analyses are based on real data and provide useful information for understanding neighbourhood level influences in general and on individual use of psychotropic drugs and choice of GP in particular. However, our primary aim is to illustrate how to perform and interpret a multilevel analysis of individual heterogeneity in social epidemiology and public health. Our study shows that neighbourhood "effects" are not properly quantified by reporting differences between neighbourhood averages but rather by measuring the share of the individual heterogeneity that exists at the neighbourhood level.

  • 11.
    Merlo, Juan
    et al.
    Lund Univ, Fac Med, Res Unit Social Epidemiol, Jan Waldenstroms St 35, SE-20502 Malmo, Sweden.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Lund Univ, Fac Med, Res Unit Social Epidemiol, Jan Waldenstroms St 35, SE-20502 Malmo, Sweden;.
    Leckie, George
    Lund Univ, Fac Med, Res Unit Social Epidemiol, Jan Waldenstroms St 35, SE-20502 Malmo, Sweden;Univ Bristol, Ctr Multilevel Modelling, 35 Berkeley Sq, Bristol BS8 1JA, Avon, England.
    A simple multilevel approach for analysing geographical inequalities in public health reports: The case of municipality differences in obesity2019In: Health and Place, ISSN 1353-8292, E-ISSN 1873-2054, Vol. 58, article id UNSP 102145Article in journal (Refereed)
    Abstract [en]

    The epidemiological analysis of geographical inequalities in individual outcomes is a fundamental theme in public health research. However, many traditional studies focus on analysing area differences in averages outcomes, disregarding individual variation around such averages. In doing so, these studies may produce misleading information and lead researchers to draw incorrect conclusions. Analysing individual and municipality differences in body mass index (BMI) and overweight/obesity status, we apply an analytical approach based on the multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA). This analytical approach may be viewed as a reorganization of existing multilevel modelling concepts in order to provide a systematic approach to simultaneously considering both differences between area averages and individual heterogeneity around those averages. In doing so, MAIHDA provides an improved approach to the quantification and understanding of geographical inequalities as compared with traditional approaches.

  • 12. Mulinari, Shai
    et al.
    Juárez, Sol Pia
    Wagner, Philippe
    Unit of Social Epidemiology, Faculty of Medicine, Lund University, Malmö, Sweden.
    Merlo, Juan
    Does Maternal Country of Birth Matter for Understanding Offspring's Birthweight?: A Multilevel Analysis of Individual Heterogeneity in Sweden2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0129362Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Many public health and epidemiological studies have found differences between populations (e.g. maternal countries of birth) in average values of a health indicator (e.g. mean offspring birthweight). However, the approach based solely on population-level averages compromises our understanding of variability in individuals' health around the averages. If this variability is high, the exclusive study of averages may give misleading information. This idea is relevant when investigating country of birth differences in health.

    METHODS AND RESULTS: To exemplify this concept, we use information from the Swedish Medical Birth Register (2002-2010) and apply multilevel regression analysis of birthweight, with babies (n = 811,329) at the first, mothers (n = 571,876) at the second, and maternal countries of birth (n = 109) at the third level. We disentangle offspring, maternal and maternal country of birth components of the total offspring heterogeneity in birthweight for babies born within the normal timespan (37-42 weeks). We found that of such birthweight variation about 50% was at the baby level, 47% at the maternal level and only 3% at the maternal countries of birth level.

    CONCLUSION: In spite of seemingly large differences in average birthweight among maternal countries of birth (range 3290-3677 g), knowledge of the maternal country of birth does not provide accurate information for ascertaining individual offspring birthweight because of the high inter-offspring heterogeneity around country averages. Our study exemplifies the need for a better understanding of individual health diversity for which group averages may provide insufficient and even misleading information. The analytical approach we outline is therefore relevant to investigations of country of birth (and ethnic) differences in health in general.

  • 13.
    Skau, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Hosp Vastmanland, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Hosp Vastmanland, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Wagner, Philippe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Hosp Vastmanland, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    GDF-15 and TRAIL-R2 are powerful predictors of long-term mortality in patients with acute myocardial infarction2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 15, p. 1576-1583Article in journal (Refereed)
    Abstract [en]

    Background The Proximity Extension Assay proteomics chip provides a large-scale analysis of 92 biomarkers linked to cardiovascular disease or inflammation. We aimed to identify the biomarkers that best predicted long-term all-cause mortality in patients with acute myocardial infarction. Methods In this prospective cohort study, 92 biomarkers were analysed in 847 consecutive patients from the Vastmanland Myocardial Infarction Study with a median follow-up of 6.9 years. Results The mean ( standard deviation) age of the patients was 70 (11.8) years and 32.7% were female. Two hundred and seven patients had died after follow-up. The biomarkers most strongly linked to all-cause mortality were growth differentiation factor 15 (GDF-15) and tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2). Cox regression analysis showed that GDF-15 (hazard ratio 1.25 per unit change, 95% confidence interval, 1.02-1.53, p=0.031) and TRAIL-R2 (hazard ratio 1.37 per unit change, 95% confidence interval 1.12-1.67, p=0.002) were independent predictors of long-term all-cause mortality after adjusting for age, gender, diabetes, previous myocardial infarction, stroke, heart failure, hypertension, smoking, hypercholesterolaemia, body mass index, ST-elevation myocardial infarction, left ventricular ejection fraction, troponin I, estimated glomerular filtration rate, N-terminal pro-brain natriuretic peptide and C-reactive protein. The combination of GDF-15 and TRAIL-R2 with established risk factors and biomarkers showed a discriminating accuracy of separating survivors from non-survivors with a cross-validated area under the receiving operating characteristics curve of 0.88 within five years. Conclusion GDF-15 and TRAIL-R2 were the most powerful Proximity Extension Assay chip biomarkers in predicting long-term all-cause mortality in patients with acute myocardial infarction.

  • 14.
    Wagner, Philippe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Alvegård, Thor
    Ranstam, Jonas
    Rydholm, Anders
    Vult von Steyern, Fredrik
    Olsson, Håkan
    Oral contraceptive use, parity, and constitutional characteristics in soft tissue sarcoma: a Swedish population-based case-control study 1988-20092014In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, no 9, p. 1167-1177Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The study was designed to investigate the influence of surrogate factors associated with sex (SH) and growth hormones (GH) on the risk of developing soft tissue sarcomas (STS).

    BACKGROUND AND METHODS: The etiology of soft tissue sarcoma is largely unknown. We have studied the effect of hormone related factors on STS in the Swedish population between 1988 and 2009 using a population-based matched case-control design.

    RESULTS: Our study is the largest on this topic to date, including 634 cases in a primary matched analysis and 855 cases in an unmatched sensitivity analysis. We identified protective effects connected to constitutional characteristics, hormonal and reproductive factors. Being shorter than your peers at age 11 was associated with an odds ratio (OR) of 0.51 (0.36-0.74). Having used oral contraceptives (OC), OR 0.75 (0.49-1.15), and high parity, OR 0.16 (0.04-0.63), comparing three or more children to two or less, also appeared to reduce the risk of STS. The risk was further reduced with the duration of OC use (p = 0.01), comparing use for 11 years or more to use for 3 years or less yielded an OR of 0.10 (0.02-0.41). No effect was observed for ever having had perimenopausal hormone therapy OR 1.02 (0.70-1.47). The effect of BMI varied significantly with subtype (p = 0.03) and tumor location (p < 0.001).

    CONCLUSIONS: We observed surrogates of SH, GH, and insulin-like growth factor 1 to be associated with STS development. These findings are important as they may connect STSs to the group of hormone-dependent tumors, potentially revealing common treatment and prevention targets.

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